Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride

Abstract

Background

In spite of more than 100 years of investigations the question of whether a reduced sodium intake improves health is still unsolved.

Objectives

To estimate the effects of low sodium intake versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL) and triglycerides.

Search methods

The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to March 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the reference lists of relevant articles.

Selection criteria

Studies randomising persons to low‐sodium and high‐sodium diets were included if they evaluated at least one of the above outcome parameters.

Data collection and analysis

Two review authors independently collected data, which were analysed with Review Manager 5.3.

Main results

A total of 185 studies were included. The average sodium intake was reduced from 201 mmol/day (corresponding to high usual level) to 66 mmol/day (corresponding to the recommended level).

The effect of sodium reduction on blood pressure (BP) was as follows: white people with normotension: SBP: mean difference (MD) ‐1.09 mmHg (95% confidence interval (CI): ‐1.63 to ‐0.56; P = 0.0001); 89 studies, 8569 participants; DBP: + 0.03 mmHg (MD 95% CI: ‐0.37 to 0.43; P = 0.89); 90 studies, 8833 participants. High‐quality evidence.

Black people with normotension: SBP: MD ‐4.02 mmHg (95% CI:‐7.37 to ‐0.68; P = 0.002); seven studies, 506 participants; DBP: MD ‐2.01 mmHg (95% CI:‐4.37 to 0.35; P = 0.09); seven studies, 506 participants. Moderate‐quality evidence.

Asian people with normotension: SBP: MD ‐0.72 mmHg (95% CI: ‐3.86 to 2.41; P = 0.65); DBP: MD ‐1.63 mmHg (95% CI:‐3.35 to 0.08; P =0.06); three studies, 393 participants. Moderate‐quality evidence.

White people with hypertension: SBP: MD ‐5.51 mmHg (95% CI: ‐6.45 to ‐4.57; P < 0.00001); 84 studies, 5925 participants; DBP: MD ‐2.88 mmHg (95% CI: ‐3.44 to ‐2.32; P < 0.00001); 85 studies, 6001 participants. High‐quality evidence.

Black people with hypertension: SBP MD ‐6.64 mmHg (95% CI:‐9.00 to ‐4.27; P = 0.00001); eight studies, 619 participants; DBP ‐2.91 mmHg (95% CI:‐4.52, ‐1.30; P = 0.0004); eight studies, 619 participants. Moderate‐quality evidence.

Asian people with hypertension: SBP: MD ‐7.75 mmHg (95% CI:‐11,44 to ‐4.07; P < 0.0001) nine studies, 501 participants; DBP: MD ‐2.68 mmHg (95% CI: ‐4.21 to ‐1.15; P = 0.0006). Moderate‐quality evidence.

In plasma or serum, there was a significant increase in renin (P < 0.00001), aldosterone (P < 0.00001), noradrenaline (P < 0.00001), adrenaline (P < 0.03), cholesterol (P < 0.0005) and triglyceride (P < 0.0006) with low sodium intake as compared with high sodium intake. All effects were stable in 125 study populations with a sodium intake below 250 mmol/day and a sodium reduction intervention of at least one week.

Authors' conclusions

Sodium reduction from an average high usual sodium intake level (201 mmol/day) to an average level of 66 mmol/day, which is below the recommended upper level of 100 mmol/day (5.8 g salt), resulted in a decrease in SBP/DBP of 1/0 mmHg in white participants with normotension and a decrease in SBP/DBP of 5.5/2.9 mmHg in white participants with hypertension. A few studies showed that these effects in black and Asian populations were greater. The effects on hormones and lipids were similar in people with normotension and hypertension. Renin increased 1.60 ng/mL/hour (55%); aldosterone increased 97.81 pg/mL (127%); adrenalin increased 7.55 pg/mL (14%); noradrenalin increased 63.56 pg/mL: (27%); cholesterol increased 5.59 mg/dL (2.9%); triglyceride increased 7.04 mg/dL (6.3%).

Plain language summary

The effect of a low salt diet on blood pressure and some hormones and lipids in people with normal and elevated blood pressure

Review question

Studies in which participants were distributed by chance into groups with high and low salt intake were analysed to investigate the effect of reduced salt intake on blood pressure (BP) and potential side effects of sodium reduction on some hormones and lipids.

Background

As a reduction in salt intake decreases blood pressure (BP) in individuals with elevated BP, we are commonly advised to cut down on salt. However, the effect of salt reduction on BP in people with a normal BP has been questioned. Furthermore, several studies have shown that salt reduction activates the salt conserving hormonal system (renin and aldosterone), the stress hormones (adrenalin and noradrenalin) and increases fatty substances (cholesterol and triglyceride) in the blood.

Search date

The present evidence is current to April 2016.

Study characteristics

One hundred and eighty‐five intervention studies of 12,210 individuals lasting four to 1100 days were included, which evaluated at least one of the effect measures. Participants were healthy or had elevated blood pressure. Longitudinal studies have shown that the effect of reduced salt intake on BP is stable after at maximum seven days and population studies have shown that very few people eat more than 14.5 g salt per day. Therefore, we also perfomed subgroup sub‐analyses of 125 studies with a duration of at least seven days and a salt intake of maximum 14.5 g.

Study funding sources

Forty‐four studies did not mention support. One hundred and twenty‐two studies were supported by public foundations. Twelve studies were supported by the pharmaceutical industry and one study by an electronic company. Six studies were supported by food industry organisations.

Key results

The mean dietary sodium intake was reduced from 11.5 g per day to 3.8 g per day. The reduction in SBP/DBP in people with normotension was about 1/0 mmHg, and in people with hypertension about 5.5/2.9 mmHg. In contrast, the effect on hormones and lipids were similar in people with normotension and hypertension. Renin increased 1.60 ng/mL/hour (55%); aldosterone increased 97.81 pg/mL (127%); adrenalin increased 7.55 pg/mL (14%); noradrenalin increased 63.56 pg/mL (27%); cholesterol increased 5.59 mg/dL (2.9%); triglyceride increased 7.04 mg/dL (6.3%).

Quality of evidence

Only randomised controlled trials were included and the basic grade of evidence was therefore considered to be high, although the grade of evidence was downgraded in some of the smaller analyses. In general, the description of the randomisation procedure was insufficient, introducing a bias which could exaggerate the effects, but many of the studies were published in a period where it was not customary to report such descriptions. The majority of studies were open, but the outcomes of these did not differ from the outcomes of the double‐blind studies. Almost all individual studies of participants with normal blood pressure (BP) show no significant effect of sodium reduction on BP, whereas a large number of studies in people with hypertension did show significant effect of sodium reduction on BP. Thus, there was a high grade of consistency between the outcomes of the individual studies and the outcomes of the meta‐analyses. Sensitivity analyses of studies lasting at least one week (the time of maximal efficacy) confirmed the primary analyses. Finally, the impact of commercial interests on the outcomes was negligible.

Background

Description of the condition

Some health institutions (WHO 2012), and dietary recommendations (ADG 2015), assume that reduction in salt intake from "high" to "low" levels is associated with reduction in systolic and diastolic blood pressure (SBP and DBP), which might result in a decrease in mortality. However, the definitions of “high”, “normal” and “low” sodium intake are unclear. The present usual sodium intake indicates that an intake in the interval 109 mmol/day to 209 mmol/day (McCarron 2013; Powles 2013, Table 15) would be “normal”, a high sodium intake would be above 209 mmol/day and a low sodium intake would be below 109 mmol/day, but according to the health institutions a “normal” sodium intake is below 100 mmol/day (ADG 2015), or below 87 mmol/day (WHO 2012), and a sodium intake above 100 mmol/day is “high”, whereas a “low” sodium intake is not defined. The confusion is strengthened by the use of different terms to describe salt (salt (sodium chloride) and sodium) and different units for salt/sodium intake (mg/day or mmol/day). To reduce the confusion we have shown the different definitions and units for salt and sodium intake in Table 15. In the present review, which represents a third update of the first meta‐analysis that includes an analysis of hormones and lipids in addition to blood pressure (Graudal 1998), updated in 2003 (Jürgens 2003) and 2011 (Graudal 2011), we use the term "sodium" and the unit "mmol".

1. Sodium intake.

Reference	Recommended upper level*	World, lower range*	World, lower 2.5%*	World, mean*	World, Upper 97.5%*	World, upper range*
ADG 2015	100 (2300) (5800)
WHO 2012	87 (2000) (5046)
McCarron 2013		90 (2070) (5220)	109 (2500) (6320)	159 (3660) (9220)	209 (4810) (12120)	248 (5700) (14400)
Powles 2013		95 (2200) (5510)		172 (3950) (10000)		240 (5520) (13920)

1. number: mmol; 2. number: mg sodium; 3. number: mg sodium chloride

Blood pressure is associated with mortality (Collins 1990).The hypothesis that a reduced sodium intake (sodium reduction) will reduce blood pressure (BP) and subsequently reduce morbidity and mortality was raised in 1904 on the basis of individual patient cases (Ambard 1904). Subsequently in 1907, these results were opposed (Löwenstein 1907). The clinical and physiological effects of salt published in studies during the first half of the 20th century were reviewed in 1949 (Chapman 1949). Consequently, scientific studies have been performed for almost 70 years before modern standard scientific randomised controlled trials (RCTs) (1000 Parijs 1973) and observational studies (Kagan 1985) were performed in humans. However, these scientific studies are interpreted differently (Taubes 1998, Graudal 2005, Bayer 2012). While health institutions (ADG 2015, WHO 2012) support sodium reduction below 100 mmol/day sceptics have claimed that this recommended upper limit (UL) for sodium intake is based on a biased selection of evidence (Folkow 2011), and is inconsistent with Institute of Medicine’s definition of an adequate nutrient intake, which is “the approximate intake found in apparently healthy populations" (IOM 2006; Heaney 2013). For sodium "the approximate intake in apparently healthy populations" is between 90 mmol/day and 248 mmol/day (Table 15).

The present Cochrane review is based on a meta‐analysis published in 1998 (Graudal 1998). In 1998, the usual sodium intake was known in some populations, but it was not well‐defined worldwide until recently (Table 15). The present upper level of 100 mmol/day was defined in 2005 (IOM 2005). Furthermore, the significance of the duration of sodium reduction was not established. In 1998, we therefore included all available randomised studies, irrespective of sodium intake and duration of intervention, assuming that the average values of multiple studies would be relevant for the general population. We separated study populations in a group of populations with normal BP to investigate the potential effect of sodium reduction in the general population and in a group of hypertensive populations to investigate the potential effect of sodium reduction as a treatment for hypertensive individuals. In a cross‐sectional multiple regression analysis including many covariates we found that the duration of the sodium reduction intervention had no impact on the effect of sodium reduction on BP (Graudal 1998). In addition to this cross‐sectional meta‐regression analysis, a recent meta‐analysis of longitudinal studies measuring the BP‐effect of sodium reduction several times during the observation period showed that there was no difference in SBP effect or DBP effect between week one and week six, thus estimating the time point for maximal efficacy to be at maximum at one week (Graudal 2015). These results are shown in Table 16. In the Graudal 1998 analysis, the average sodium intake in the non‐reduced group was 203 mmol/day and in the reduced group it was 62 mmol/day. In the two following updates of the review, the corresponding sodium reductions were from 205 mmol/day to 64 mmol/day (Jürgens 2003) and from 202 mmol/day to 67 mmol/day (Graudal 2011). We now know (McCarron 2013; Powles 2013) that this reduction corresponds to a reduction from a high usual level to the present recommended levels (defined in 2005 (IOM 2005) and in 2012 (WHO 2012) i.e. the present review is relevant in the context of evaluating the consequences of the present recommendations to reduce sodium intake to a level below 100 mmol/day.

2. Differences in BP effects of reduced sodium intake at different time points in longitudinal studies.

Comparison	References	SBP diff. (95% CI)	P	DBP diff. (95% CI)	P
Week 1 vs.2	1070 Parker 1990;1180 Palacios 2004;1183 Gates 2004;1188 Swift 2005	‐0.18 (‐3.03 to 2.67)	0.90	0.12 (‐2.53 to 2.77)	0.93
Week 1 vs.4	1070 Parker 1990;1088 Ruppert 1993;1128 Schorr 1996;1180 Palacios 2004;1183 Gates 2004;1186 Forrester 2005 N	‐0.50 (‐3.20 to 2.20)	0.72	0.35 (‐2.02 to 2.72)	0.77
Week 2 vs.4	1011 MacGregor 1982;1039 ANHMRCDS 1986;1055 ANHMRCDS 1989;1070 Parker 1990;1075 Mascioli 1991;1082 Cobiac 1992 1097 Nestel 1993;1100 Fotherby 1993;1080 Huggins 1992;1183 Gates 2004;1186 Forrester 2005 N;1201 Nowson 2009	‐0.10 (‐1.88 to 1.68)	0.91	‐0.20 (‐1.12 to 0.72)	0.67
Week 2 vs.6	1039 ANHMRCDS 1986;1055 ANHMRCDS 1989;1085 Sciarrone 1992;1097 Nestel 1993;1201 Nowson 2009	‐0.50 (‐2.66 to 1.66)	0.65	‐0.42 (‐1.69 to 0.85)	0.52
Week 4 vs.6	1039 ANHMRCDS 1986;1055 ANHMRCDS 1989;1085 Sciarrone 1992;1097 Nestel 1993;1201 Nowson 2009	0.39 (‐1.77 to 2.55)	0.72	‐0.22 (‐1.50 to 1.06)	0.74

Data from Graudal 2015

Description of the intervention

As in the previous meta‐analyses, RCTs are included, which allocate participants to two diets with a different content of salt (sodium chloride) or to either salt tablets or placebo tablets. The compliance in the RCTs is ensured by measurement of sodium excretion in the urine, which is accepted to be a reliable surrogate for the measuring of sodium intake. The sodium content of the “high” and “low” sodium diets were not defined according to the recommendations or the usual sodium intake, but just to describe the relative content of the two randomised study populations.

How the intervention might work

Extracellular fluid volume (ECFV) is determined by the balance between sodium intake and renal excretion of sodium. A steady state exists whereby sodium intake equals output, while ECFV is expanded during salt loads and shrunken during salt restriction (Palmer 2008). Thus, the idea behind sodium reduction is to shrink ECFV in order to decrease BP. The precondition for this idea is that the smaller ECFV associated with the decrease in BP has no counteracting effects on health outcomes that could outweigh the BP‐effect.

Why it is important to do this review

A verification of the hypothetical sodium‐BP relationship would support continuous attempts to lower sodium intake in order to reduce mortality. In this context it is important to define the correct UL for a healthy sodium intake, which would have a significant impact on the strategy to lower sodium intake. For instance if 100 mmol/day is the correct UL, more than 95% of the World’s populations should reduce sodium intake, but if the UL is 250 mmol/day, only about 5% should reduce sodium intake. In the latter case, a strategy to lower sodium intake in the general population would not be necessary, which would save significant efforts and costs. The same would be the case if the sodium‐BP relationship could be denied, as indicated by many RCTs of participants with normal BP (Graudal 2011). Worst case scenario is that sodium reduction could lead to side effects, which might trump the potential BP effect and result in increased mortality, as indicated by longitudinal observational studies (Alderman 2010, Pfister 2014, O'Donnell 2014, Graudal 2014; Mente 2016). Consequently, it is important to investigate the effect of sodium reduction not only on BP, but also on potential surrogate markers for clinical side effects.

Objectives

The purpose of the present review was to estimate the influence of low‐ versus high‐dietary sodium intake on systolic blood pressure (SBP) and diastolic blood pressure (DBP), and blood concentrations of renin, aldosterone, catecholamines, cholesterol, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL) and triglyceride to contribute to the evaluation of the possible suitability of sodium reduction as a prophylaxis initiative and treatment of hypertension.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs) allocating participants to diets with different sodium contents, the lowest defined as “low” and the highest defined as “high”, and in which the sodium intake was estimated by the 24‐hour urinary sodium excretion (either measured on the basis of a 24‐hour urine collection, or estimated from a sample of at least eight hours).

Types of participants

Persons with normal or elevated blood pressure irrespective of race and age were included. Studies systematically investigating unhealthy patients with other diseases than elevated blood pressure, for instance diabetes or heart failure, were excluded.

Types of interventions

The intervention was a change in sodium intake, the study populations randomly being divided into a group eating a “low” sodium diet or a "high" sodium diet. As "low" and "high" were not specifically defined in relation to the usual intake or the definitions of the health institutions (Table 15), both diets could contain any amount of sodium, the assumption being that in most studies a "low" sodium diet would contain sodium within the low range (< 100 mmol)/day or usual range (100 mmol to 250 mmol/day) and the “high” sodium diet would contain sodium within the usual range (100 mmol to 250 mmol/day) or above the usual range (≥ 250 mmol/day). Confounding was not allowed, i.e. studies treating persons with a concomitant intervention such as an antihypertensive medication, potassium supplementation or weight reduction were only included if the concomitant intervention was identical during the low and the high‐sodium diet.

Types of outcome measures

Outcome measures were effects on SBP, DBP, renin, aldosterone, adrenaline, noradrenaline, triglyceride, cholesterol, LDL and HDL. In studies reporting BP only as mean arterial pressure (MAP), SBP was estimated from SBP = 1.3 MAP + 1.4, and DBP was estimated from DBP = 0.83 MAP – 0.7 (Tozawa 2002). Separate meta‐analyses were performed for each outcome measure. Concerning blood pressure, participants were stratified according to ethnicity (Whites, Blacks and Asians) and according to level of blood pressure (hypertension or normotension). Hypertension was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg. Study populations in which participants were treated with antihypertensive treatment were defined as hypertensive irrespective of baseline BP. In studies that investigated different ethnicities and different BP levels, the first priority was to separate these subgroups. If separate data were not given, the study data would be analysed according to the biggest subgroup. Concerning all other outcome variables, no stratifications were performed.

Primary outcomes

All outcomes were considered primary outcomes.

Secondary outcomes

None.

Search methods for identification of studies

Electronic searches

The Cochrane Hypertension Information Specialist conducted systematic searches in the following databases for randomised controlled trials without language, publication year or publication status restrictions:

• the Cochrane Hypertension Specialised Register via the Cochrane Register of Studies (searched 7 March 2016);

• the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3) via the Cochrane Register of Studies Online (CRSO) (searched 7 March 2016);

• MEDLINE Ovid (from 1946 onwards), and MEDLINE Ovid In‐Process & Other Non‐Indexed Citations (searched 7 March 2016);

• Embase Ovid (searched 7 March 2016);

• ClinicalTrials.gov (www.clinicaltrials.gov) searched 7 March 2016).

The Hypertension Group Specialised Register includes controlled trials from searches of CAB Abstracts & Global Health, CINAHL, Cochrane Central Register of Controlled Trials, Embase, MEDLINE, ProQuest Dissertations & Theses, PsycINFO, Web of Science and the WHO International Clinical Trials Registry Platform (ICTRP).

The Information Specialist modelled subject strategies for databases on the search strategy designed for MEDLINE. Where appropriate, they were combined with subject strategy adaptations of the sensitivity and precision‐maximising search strategy designed by Cochrane for identifying randomised controlled (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.d. (Handbook 2011)). Search strategies for major databases are provided in Appendix 1.

Searching other resources

• The Cochrane Hypertension Information Specialist searched the Hypertension Specialised Register segment (which includes searches of MEDLINE for systematic reviews) to retrieve existing systematic reviews relevant to this systematic review, so that we could scan their reference lists for additional trials.

• We checked the bibliographies of included studies and any relevant systematic reviews identified for further references to relevant trials.

• Where necessary, we contacted authors of key papers and abstracts to request additional information about their trials.

Searches carried out for previous versions of this review

Trial search: Parijs and colleagues published the first RCT of the effect of sodium reduction on BP in 1973 (1000 Parijs 1973). In our first meta‐analysis (Graudal 1998), a literature search in MEDLINE (1966‐through December 1997) was performed using the following combinations of search terms: 1) salt or sodium, 2) restriction or dietary, 3) blood pressure or hypertension, 4) randomized or random. We combined 1, 2, 3 and 4 and found 291 references. Of these, 76 randomised trials from 60 references met the inclusion criteria. From the reference lists of these articles and from four previous meta‐analyses (Grobbee 1986, Law 1991, Cutler 1991, Midgley 1996), an additional 23 references reporting on 39 trials were identified, resulting in a total of 83 references.

Similar searches were made for hormones and lipids changing the third search term (blood pressure or hypertension) with the hormone or lipid term resulting in additional five sub‐studies dealing with hormones and lipids (Jula‐Karanko 1992, Jula‐Mäki 19921026 Koolen 1984(2), 1104 Overlack 1993, Ruppert 1994). Of these 88 references, three dealing exclusively with diabetes patients were excluded in the 2003 update (Dodson 1989, Mühlhauser 1996, Miller 1997).

In January 2002, a repeated search was performed through December 2001, revealing an additional 12 references, of which one was excluded because it only included patients with diabetes (Imanishi 2001). Accordingly, the 2004 updated review included a total of 96 references.

In December 2009, a literature search for the 2011 update was performed from 1950 through December 2009. This search revealed a total of 511 references in Ovid MEDLINE, 282 in Ovid EMBASE and 1428 in Cochrane CENTRAL. Headlines and abstracts were read and 44 articles from MEDLINE (26 included), eight from Embase (one included) and 129 from CENTRAL (45 included) were retrieved as full‐text papers for further review. A total of 72 new references investigating at least one of the effect variables met the inclusion criteria for this review. The search was not limited to English language studies. Two studies in Italian were identified and included. During the present revision, we discovered that in a few of the previously included studies, some subgroup data were published in two papers. To avoid duplication due to including subgroup data from several papers, we included them from the main paper only. As a result, three previously included references were excluded (Steegers 1991, Ruppert 1991, Ruppert 1994). The most recent search was performed on July 21, 2011, revealing 293 additional references. After screening of titles and abstracts, four full‐text papers were retrieved, of which two contained data to be included. Consequently a total of 167 studies were supposed to be included in the 2011 updated version of this systematic review. However, in connection with the present update, a recount revealed a counting error, as the number of references in reality was 166.

Data collection and analysis

Selection of studies

See Search methods for identification of studies.

Review author NG performed the study selection for the 1998 version (Graudal 1998) and the 2003 version (Jürgens 2003). Review authors NG and GJ independently performed the supplementary study selection for the 2011 version (Graudal 2011. NG and THG independently performed the supplementary study selection for the current 2016 version. Discrepancies were resolved by agreement.

Data extraction and management

Two authors independently recorded the following data from each trial:

1. the sample size (N);

2. the mean age of participants;

3. the fraction of females, males; Whites, Blacks and Asians;

4. the duration of the intervention;

5. the sodium reduction measured as the difference between 24‐hour urinary sodium excretion during low‐sodium and high‐sodium diets and standard deviation (SD);

6. SBP (SD) and DBP (SD) before and after intervention;

7. difference between changes in SBP and DBP obtained during low‐sodium and high‐sodium diets and the SD of these differences;

8. for cross‐over studies, when possible, the overall effect estimate and standard error (SE);

9. levels of hormones and lipids in the blood and their standard deviations during low‐sodium and high‐sodium diets. Concerning lipids, cholesterol units of mmol/L were transformed to mg/dL by means of the factor 38.6 and triglyceride units of mmol/L were transformed to mg/dL by means of the factor 88.4. Other renin units than ng/mL/hour were when possible transformed to ng/mL/hour, and units of aldosterone, noradrenalin and adrenalin other than pg/mL were transformed to pg/mL by means of the molecular weights.

If there were discrepancies between review authors they looked at the data together and came to an agreement.

Assessment of risk of bias in included studies

This was performed using the Cochrane 'Risk of bias' tool, including recording of allocation, blinding, incomplete outcome data and selective reporting. Subgroup analyses of the primary analysis of SBP were performed for contrasting sources of bias appearing from the 'Risk of bias' analysis.

Measures of treatment effect

This was defined as the mean difference (MD) between the changes from baseline to end of treatment during low‐ and high‐sodium diets. When units within an analysis were different the standardised mean difference (SMD) was used.

Unit of analysis issues

Blood pressure (BP) 

Combined analyses were performed including both parallel and cross‐over studies. The generic inverse variance data type was used to analyse the effect in order to ensure that the weight of the cross‐over studies was not underestimated compared with the parallel studies. For parallel studies, the SE was calculated in the usual way as follows: SE (diff) = sqrt SE₁² + SE₂². For cross‐over studies the given SE (difference) was used. A linear regression equation linking the given SE to the calculated SE (sqrt SE₁² + SE₂²) was calculated by means of the studies which reported both SE (difference) and SE on BP during both intervention periods. This equation was used to transform all calculated SEs to estimated “true” SEs (difference) in cross‐over studies that did not report SE (difference). In this way, it was ensured that cross‐over studies were attributed proper weight compared with the parallel studies. There were not enough studies to calculate separate equations for Black and Asian populations and therefore the equations calculated in the white populations were used to transform these SEs when necessary.

Hormones and lipids

The very few parallel studies were excluded and the large fraction of cross‐over studies were analysed separately. As the large majority of cross‐over studies reported separate data for each intervention period instead of overall estimates of effect, the continuous data type was used in the separate analyses of the cross‐over studies.

Dealing with missing data

If the SD was not reported it was calculated from a given SE, 95% confidence interval (CI), P value or t value, estimated from a figure or imputed from the formula SD (change) = sq root (SD1sq + SD2sq), SD1 is SD on blood pressure before intervention and SD2 is SD on blood pressure after intervention.

Assessment of heterogeneity

A Chi² test included in the forest plot was used to assess whether observed differences in results are compatible with chance alone. A low P value (or a large Chi² statistic relative to its degree of freedom) provides evidence of heterogeneity of intervention effects (variation in effect estimates beyond chance).

Assessment of reporting biases

Funnel plots were assessed for asymmetry. Selective reporting of SBP and DBP was recorded

Data synthesis

Individual study subgroup data defined before randomisation based on ethnicity and state of hypertension were included in the meta‐analysis as subgroups, whereas sodium sensitivity subgroups, which were defined by the authors of the individual studies after they had analysed the data, were combined by the present authors and subsequently the combined data were included in the meta‐analyses.

The mean difference (MD) was calculated for outcome measures with identical units in the included studies (BP without transformation of data (all measured as mmHg), adrenaline, aldosterone, noradrenalin and lipids, after transformation). The standardised mean difference (SMD) was calculated for outcome measures with different units (renin), but a separate calculation of MD for the majority of renin studies with identical unit (ng/mL/hour) was also performed. With the MD method, the difference in effect between two treatments is divided by the SD of the measurements. By that transformation, the effect measures become dimensionless and the outcomes from trials, which have used different units, can consequently be combined. As we accumulated data from a series of studies that had been performed by researchers operating independently, and as the goal of the analysis was to extrapolate to other populations, we used a random‐effects model in our primary analysis to estimate the summary measure as the mean of a distribution of effects.

Level of significance: In case of multiple independent comparisons, it is important to avoid coincidental significance. Ten meta‐analyses were performed. However, the SBP and DBP comparisons are not independent of each other and BP depends on renin and aldosterone as well as catecholamines. Concerning lipids, these are mutually dependent, whereas the dependency on BP and hormones is not obvious. Consequently, the 10 meta‐analyses could be sub‐classified into a group of meta‐analyses of mutually dependent BP and hormones and an independent group of meta‐analyses of mutually dependent lipid fractions. Consequently, the level of significance was reduced by means of the formula 1‐0.95 x 1/N = 1‐0.95 x 1/2 = 0.025, (N = number of independent investigations = 2).

Subgroup analysis and investigation of heterogeneity

Since the previous version of this review, we now have reasonable evidence to determine the time of maximal efficacy to be one week (Table 16). Therfore, there is a risk that studies lasting for less than one week may underestimate the effect of sodium reduction. Furthermore, evidence has appeared to indicate that all of the world’s populations have a mean sodium intake below 250 mmol/day (Table 15), and as dose‐response studies have indicated that sodium reductions from very high levels have bigger effects than reductions from usual levels (Graudal 2015), such studies may contribute to overestimate the effect. We therefore performed a subgroup analysis intending to eliminate these potential biases on SBP and DBP (stratified according to normal BP or hypertension) and renin, aldosterone, noradrenalin, adrenalin, cholesterol triglyceride, HDL and LDL by exclusion of studies with a duration of less than seven days and sodium intake above 250 mmol/day.

Sources of bias: subgroup analyses were performed for contrasting sources of bias appearing from the 'Risk of bias' analysis.

Sensitivity analysis

Sensitivity analyses were performed excluding studies giving rise to asymmetry in the funnel plots.

Results

Description of studies

Results of the search

During this 2016 update, we identified two studies with duplicate data, which were subsequently excluded (Jula‐Karanko 1992;Jula‐Mäki 1992), as all data could be extracted from a later paper (1110 Jula 1994).

In September 2014, a literature search for the present update was performed as described in "Search methods for identification of studies". The de‐duplicated results from the searches revealed 626 articles. On the basis of titles, 549 were excluded. Seventy‐seven abstracts were read and 27 full‐text articles obtained, of which, nine fulfilled the inclusion criteria. In a supplementary search in April 15 2015, an additional 102 references were identified. Six articles were obtained, of which three fulfilled the inclusion criteria.The last updated search was performed on 7 March 2016. The de‐duplicated results from the searches revealed 994 articles. During the primary screening, 687 were excluded and on the basis of titles and abstracts, a further 236 articles were eliminated. Seventy‐one abstracts were read in detail and 29 full‐text articles obtained, of which, seven fulfilled the inclusion criteria. Additionally, two articles were identified from a reference list of a review article. A WHO International Clinical Trials Registry Platform search using the search term “diet and sodium” revealed 141 trials, but none were included.

A total of 185 references (164 from the 2011 review plus 9 + 3 + 9 new references) were thus included in the present updated 2016 version.

Included studies

See Characteristics of included studies.

One hundred and eighty‐five references were included in the review. Eight included only data on hormones and lipids, whereas 177 included BP data, as well as hormone and lipid data in a significant number of these. The total number of study populations with BP outcomes included in the primary analysis was 206. The median of the mean ages was 44 years (range: 12 to 73), which is a little higher than the median age of most populations (typically 35 years) and the mean sodium intake in the high‐sodium group was 201 mmol/day (SD: 69) and in the low‐sodium group was 66 mmol/day (SD: 47), corresponding to a mean sodium reduction of 135 mmol/day.The median of the mean ages of the study's 125 white populations included in the subgroup analysis (duration of at least seven days, a sodium intake of less than 250 mmol/day) was 45.4 years (range: 13 to 73) the mean sodium intake in the high‐sodium group was 177 mmol/day (SD: 35) and in the low‐sodium group was 68 mmol/day (SD: 36), corresponding to a mean sodium reduction of 109 mmol/day. The mean BP in the normotensive study populations was 119/71 mmHg, which is close to the population mean of the USA population (119/71 mmHg) (Wright 2011), and a little higher than the mean of the normotensive fraction of the USA population (115/70 mmHg) (Wright 2011). The mean BP in the untreated hypertensive study populations was 151/93 mmHg and in the treated hypertensive study populations was 144/88 mmHg, both of which are higher than corresponding pressures in the USA population (146/84 mmHg and 131/72 mmHg) (Wright 2011).

In 83 studies including 7729 participants, there was information of the baseline 24‐hour sodium excretion, not influenced by diets. This was 159 mmol/24‐hour (range: 90‐274 mmol) (10‐90 percentiles: 123‐194 mmol).

Excluded studies

See Characteristics of excluded studies.

Risk of bias in included studies

See Characteristics of included studies and Figure 1

1.

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

The obligatory trial quality criterion was randomisation. Double‐blind, single‐blind or open studies with a parallel or a cross‐over design were accepted. A study was defined as single‐blind if an investigator measured BP without knowledge of the diet or by a computerised manometer, and as open if precautions to decrease observer bias were not mentioned.

We found two important contrasts: general blinding and blinding of outcome detection (Figure 1). We performed subgroup analyses of BP in both normotensive and hypertensive white populations, but not in the black and Asian populations due to the small numbers of trials. We did not perform subgroup analyses on the biochemical outcomes (hormones and lipids) as they are supposed to be performed blindly in 100% of cases.

Allocation

Only 14 studies (1034 Watt 1985; 1078 Egan 1991; 1081 TOHP I 1992; 1107 MacFadyen 1994;1135 TOHP II 1997; 1136 van Buul 1997;1142 Knuist 1998; 1195 Jessani 2008; 1197 Dickinson 2009; 1198 He 2009; 1206 Graffe 2012; 1208 Todd 2012; 1217 Markota 2015; 1225 Gijsbers 2015), either partly or sufficiently explained the allocation sequence generation and concealment. Consequently, there is a general significant risk that allocation was not unbiased.

Blinding

Fifty‐six studies were reported to be double‐blind and in 115 studies, the risk of detection bias was estimated to be low (Figure 1). Separate analyses were performed on studies with low and high risks of general blinding and outcome detection.

Incomplete outcome data

Based on the information given in the individual articles, incomplete outcome data generally was a small problem (Figure 1). However, only a few studies showed flow charts of the fate of the participants. Therefore, this bias may be significant.

Selective reporting

Based on the information given in the individual articles, reporting bias was small (Figure 1). However, as protocols did not exist for the vast majority of studies, this evaluation may be imprecise.

Other potential sources of bias

The effect of an intervention on BP may depend on factors such as baseline BP and ethnicity. Therefore, a biased distribution of such factors in the included study populations compared with the general population may bias the effect of the intervention found in the meta‐analysis to be different from the potential effect in the general population. We therefore performed separate analyses for hypertensive and normotensive individuals and for different ethnicities.

Effects of interventions

See: Table 1; Table 2; Table 3; Table 4; Table 5

for the main comparison.

Low sodium intake compared with high sodium intake for blood pressure
Patient or population: White population with normal or elevated blood pressure, but otherwise healthy Settings: Hospitals units in Europe and North America Intervention: Low sodium intake Comparison: High sodium intake
Outcomes	Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
White population, normotensive, SBP mmHg	‐1.09 (‐1.63 to ‐0.56)	8569 (89)	⊕⊕⊕⊕ high
White population, normotensive, DBP mmHg	0.03 (‐0.37 to 0.43)	8833 (90)	⊕⊕⊕⊕ high
White population, hypertensive, SBP mmHg	‐5.51 (‐6.45 to ‐4.57)	5925 (84)	⊕⊕⊕⊕ high
White population, hypertensive, DBP mmHg	‐2.88 (‐3.44 to ‐2.32)	6001 (85)	⊕⊕⊕⊕ high
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. DBP: diastolic blood pressure; SBP: systolic blood pressure

2.

Low sodium intake compared with high sodium intake for blood pressure
Patient or population: Black population with normal or elevated blood pressure, but otherwise healthy Settings: Hospital units in North America, UK and Africa Intervention: Low sodium intake Comparison: High sodium intake
Outcomes	Mean difference (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
Black population, normotensive, SBP mmHg	‐4.02 (‐7.37 to ‐0.68)	506 (7)	⊕⊕⊕⊝ moderate1
Black population, normotensive, DBP mmHg	‐2.01 (‐4.37 to 0.35)	506 (7)	⊕⊕⊕⊝ moderate1
Black population, hypertensive, SBP mmHg	‐6.64 (‐9.00 to ‐4.27)	619 (8)	⊕⊕⊕⊝ moderate1
Black population, hypertensive, DBP mmHg	‐2.91 (‐4.52 to ‐1.30)	619 (8)	⊕⊕⊕⊝ moderate1
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. DBP: diastolic blood pressure; SBP: systolic blood pressure

1. Downgraded due to the wide confidence intervals

3.

Low sodium intake compared with high sodium intake for blood pressure
Patient or population: Asian population with normal or elevated blood pressure, but otherwise healthy Settings: Hospital units in Japan and China Intervention: Low sodium intake Comparison: High sodium intake
Outcomes	Mean difference (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
Asian population, normotensive, SBP mmHg	‐0.72 (‐3.86 to 2.41)	393 (3)	⊕⊕⊕⊝ moderate1
Asian population, normotensive, DBP mmHg	‐1.63 (‐3.35 to 0.08)	393 (3)	⊕⊕⊕⊝ moderate1
Asian population, hypertensive, SBP mmHg	‐7.75 (‐11.44 to ‐4.07)	501 (8)	⊕⊕⊕⊝ moderate1
Asian population, hypertensive, DBP mmHg	‐2.68 (‐4.21 to ‐1.15)	501 (8)	⊕⊕⊕⊝ moderate1
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. DBP: diastolic blood pressure; SBP: systolic blood pressure

1. Downgraded due to the wide confidence intervals

4.

Low sodium intake compared with high sodium intake for hormones
Patient or population: Participants with normal or elevated blood pressure, but otherwise healthy Settings: Hospital units Intervention: Low sodium intake Comparison: High sodium intake
Outcomes	Mean difference (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
Renin SMD	1.22 (1.07 to 1.37) N*: 1.44 (1.24 to 1.65) H*: 0.91 (0.71 to 1.10)	5498 (88)	⊕⊕⊕⊕ high
Aldosterone pg/mL	97.81 (82.56 to 113.05) N*: 115.83 (91.74 to 139.91) H*: 73.02 (55.94 to 90.09)	4884 (65)	⊕⊕⊕⊕ high
Noradrenaline pg/mL	63.56 (42.66 to 84.46) N*: 66.50 (41.72 to 91.29) H*: 57.36 (14.10 to 100.61)	1736 (36)	⊕⊕⊕⊕ high
Adrenaline pg/mL	7.55 (0.85 to 14.26) N*:4.45 (3.43 to 12.33) H*:13.45 (1.25 to 25.66)	662 (16)	⊕⊕⊕⊝ moderate1
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. SMD: standardised mean difference

N*: Study populations with mean SBP < 140 mmHg

H*:Study populations with mean SBP > 140 mmHg

1. Downgraded due to the wide confidence interval

5.

Low sodium intake compared with high sodium intake for lipids
Patient or population: Participants with normal or elevated blood pressure, but otherwise healthy Settings: Hospital units Intervention: Low sodium intake Comparison: High sodium intake
Outcomes	Mean difference (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
Cholesterol mg/dL	5.64 (2.46, 8.82) N*:7.46 (3.65, 11.28) H*:2.55 (‐2.69, 7.80)	1800 (27)	⊕⊕⊕⊝ moderate1
Trigyceride mg/dL	7.04 (3.04, 11.05) N*: 6.88 (1.18, 12.59) H*: 7.19 (1.57, 12.81)	1390 (19)	⊕⊕⊕⊝ moderate1
High‐density lipoprotein (HDL) mg/dL	‐0.29 (‐1.66, 1.08)	1442 (19)	⊕⊕⊕⊝ moderate1
Low‐density lipoprotein (LDL) mg/dL	3.12 (‐0.41, 6.64)	1358 (17)	⊕⊕⊕⊝ moderate1
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Downgraded due to the wide confidence intervals.

See Data and analyses.

Blood pressure in white participants

See Table 1

In the meta‐analyses of trials of white participants with normal blood pressure (BP), the mean difference (MD) was a change in systolic blood pressure (SBP) of ‐1.09 mmHg (95% CI: ‐1.63 to ‐0.56) (P = 0.0001) (89 trials, 8569 trials) (Analysis 1.1; Figure 2), and in diastolic blood pressure (DBP) of + 0.03 mmHg (95% CI: ‐0.37 to 0.43) (P = 0.89) (90 trials, (8833 participants) (Analysis 1.2; Figure 3) (high‐quality evidence).

1.1. Analysis.

Comparison 1 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites, Outcome 1 White population, normotensive, SBP.

2.

Forest plot of comparison: 1 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in whites, outcome: 1.2 Whites, normotensive, SBP.

1.2. Analysis.

Comparison 1 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites, Outcome 2 White population, normotensive, DBP.

3.

Forest plot of comparison: 1 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in whites, outcome: 1.2 Whites, normotensive, DBP.

In subgroup meta‐analyses of trials with a duration of at least one week and a sodium intake of a maximal 250 mmol/day, the MD showed a decrease in SBP of ‐1.31 mmHg (‐1.83 to ‐0.80) (P = 0.00001) (59 trials, 7125 participants) (Analysis 4.1) and in DBP of ‐0.36 mmHg (95% CI: ‐0.79, 0.07) (P = 0.10) (61 trials) (Analysis 4.2). A further elimination of five studies, which, although the mean BP was normal, did include individuals with hypertension, reduced the SBP/DBP effect to ‐1.08/‐0.24 mmHg.

4.1. Analysis.

Comparison 4 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites, subgroup analysis, Outcome 1 White population, normotensive, SBP.

4.2. Analysis.

Comparison 4 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites, subgroup analysis, Outcome 2 White population, normotensive, DBP.

In the trials of white people with elevated BP, MD showed a decrease in SBP of ‐5.51 mmHg (95% CI: ‐6.45 to ‐4.57) (P < 0.00001) (84 trials, 5925 participants) (Analysis 1.3), and in DBP of ‐2.88 mmHg (95% CI: ‐3.44 to ‐2.32) (P < 0.00001) (85 trials, 6001 participants) (Analysis 1.4) (high‐quality evidence).

1.3. Analysis.

Comparison 1 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites, Outcome 3 White population, hypertensive, SBP.

1.4. Analysis.

Comparison 1 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites, Outcome 4 White population, hypertensive, DBP.

In subgroup meta‐analyses of trials with a duration of at least one week and a sodium intake of a maximal 250 mmol/day, MD showed a decrease in SBP of ‐5.02 mmHg (‐6.00 to ‐4.05) (P < 0.00001) (63 trials) ( Analysis 4.3) and in DBP of ‐2.78 mmHg (95% CI: ‐3.42 to ‐2.14) (P < 0.00001) (64 trials ) (Analysis 4.4).

4.3. Analysis.

Comparison 4 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites, subgroup analysis, Outcome 3 White population, hypertensive, SBP.

4.4. Analysis.

Comparison 4 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites, subgroup analysis, Outcome 4 White population, hypertensive, DBP.

Blood pressure in black participants

See Table 2

In the meta‐analyses of seven trials involving 506 black participants with normal BP, MD showed a decrease in SBP of ‐4.02 mmHg (95% CI:‐7.37 to ‐0.68) (P = 0.02) (Analysis 2.1) and in DBP of ‐2.01 mmHg (95% CI:‐4.37, 0.35) (P = 0.09) (Analysis 2.2) (moderate‐quality evidence).

2.1. Analysis.

Comparison 2 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Blacks, Outcome 1 Black population, normotensive, SBP.

2.2. Analysis.

Comparison 2 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Blacks, Outcome 2 Black population, normotensive, DBP.

In the meta‐analyses of eight trials of 619 black participants with elevated BP, MD showed a decrease in SBP of ‐6.64 mmHg (95% CI:‐9.00, ‐4.27)

(P = 0.00001) (Analysis 2.3) and in DBP of ‐2.91 mmHg (95% CI:‐4.52, ‐1.30) (P = 0.0004) (Analysis 2.4) (moderate‐quality evidence).

2.3. Analysis.

Comparison 2 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Blacks, Outcome 3 Black population, hypertensive, SBP.

2.4. Analysis.

Comparison 2 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Blacks, Outcome 4 Black population, hypertensive, DBP.

Blood pressure in Asian participants

See Table 3

In the meta‐analyses of three trials involving 393 Asian participants with normal BP, MD showed a decrease in SBP of ‐0.72 mmHg (95% CI: ‐3.86, 2.41) (P = 0.65) (Analysis 3.1) and in DBP of ‐1.63 mmHg (95% CI:‐3.35 to 0.08) (P= 0.06) (Analysis 3.2) (moderate‐quality evidence).

3.1. Analysis.

Comparison 3 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Asians, Outcome 1 Asians population normotensive, SBP.

3.2. Analysis.

Comparison 3 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Asians, Outcome 2 Asian population, normotensive, DBP.

In the meta‐analyses of nine trials involving 501 Asian participants with elevated BP, MD showed a decrease in SBP of of ‐7.75 mmHg (95% CI:‐11.44, ‐4.07) (P < 0.0001) (Analysis 3.3) and in DBP of ‐2.68 mmHg (95% CI: ‐4.21 to ‐1.15)(P = 0.0006) (Analysis 3.4) (moderate‐quality evidence).

3.3. Analysis.

Comparison 3 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Asians, Outcome 3 Asian population, hypertensive, SBP.

3.4. Analysis.

Comparison 3 Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Asians, Outcome 4 Asian population, hypertensive, DBP.

Renin

See Table 4

Two parallel trials were excluded (1110 Jula 1994; 1155 Heer 2000).

In the remaining 82 cross‐over trials (5498 participants) of measurement of renin (including 88 comparisons reported in the Data & analyses), the standardised mean difference (SMD) of sodium reduction was 1.22 standardized units (95% CI: 1.07 to 1.37) (Z= 15.68, P < 0.00001) (Analysis 5.1) (high‐quality evidence). In 73 comparisons, which all had the same unit (ng/mL/hour), either directly or after transformation, the MD was 1.60 ng/mL/hour (95% CI: 1.40 to 1.79) (Z= 16.04, P < 0.00001).

5.1. Analysis.

Comparison 5 Effect of salt reduction on hormones, Outcome 1 Renin (ng/mL/hour).

In comparisons with a duration of at least seven days and a sodium intake of less than 250 mmol/day (44 trials, 3470 participants), the SMD was 1.05 standardized units (95% CI: 0.85 to 1.24), (Z= 10.35, P < 0.00001) (Analysis 6.1) In 39 comparisons using ng/mL/hour as the unit, the corresponding MD was 1.30 ng/mL/hour (95% CI: 1.06 to 1.53), (Z= 10.65, P < 0.00001). The effect in normotensive participants was significantly higher than in hypertensive participants (Table 4).

6.1. Analysis.

Comparison 6 Effect of salt reduction on hormones, subgroup analysis, Outcome 1 Renin (ng/mL/hour).

Aldosterone

See Table 4

Three parallel trials were excluded (1110 Jula 1994; 1111 Howe 1994; 1155 Heer 2000).

In the remaining 65 cross‐over trials (4884 participants) of measurement of aldosterone, MD was 97.81 pg/mL (95% CI: 82.56 to 113.05) (Z = 12.58, P < 0.00001) (Figure 4, Analysis 5.2) (high‐quality evidence). In comparisons with duration of at least one week and sodium intake of less than 250 mmol/day (34 trials, 3128 participants), MD was 95.59 pg/mL (95% CI: 74.12 to 117.05), P = 0.00001 (Analysis 6.2).The effect in normotensive participants was significantly higher than in hypertensive participants (Table 4).

4.

Forest plot of comparison: 5 Effect of salt reduction on hormones, outcome: 5.2 Aldosterone (pg/mL).

5.2. Analysis.

Comparison 5 Effect of salt reduction on hormones, Outcome 2 Aldosterone (pg/mL).

6.2. Analysis.

Comparison 6 Effect of salt reduction on hormones, subgroup analysis, Outcome 2 Aldosterone (pg/mL).

Noradrenaline

See Table 4

One parallel trial was excluded (1110 Jula 1994).

In the remaining 34 cross‐over trials (1736 participants) of measurement of noradrenaline (including 36 comparisons reported in the Data & analyses), MD was 63.56 pg/mL (95% CI: 42.66 to 84.46), (z = 5.96, P = 0.00001) (Figure 5, Analysis 5.3) (high‐quality evidence). In comparisons with duration of at least one week and a sodium intake of less than 250 mmol/day (23 studies, 964 participants) MD was 48.66 pg/mL (95% CI: 28.88 to 68.44), P = 0.00001 (Analysis 6.3). There was no difference between normotensive participants and hypertensive participants (Table 4).

5.

Forest plot of comparison: 5 Effect of salt reduction on hormones, outcome: 5.3 Noradrenaline (pg/mL).

5.3. Analysis.

Comparison 5 Effect of salt reduction on hormones, Outcome 3 Noradrenaline (pg/mL).

6.3. Analysis.

Comparison 6 Effect of salt reduction on hormones, subgroup analysis, Outcome 3 Noradrenaline (pg/mL).

Adrenaline

See Table 4

One parallel trial was excluded (1110 Jula 1994).

In the remaining 15 cross‐over trials (662 participants) of measurement of adrenaline (including 16 comparisons reported in the Data & analyses), MD was 7.55 pg/mL (95% CI: 0.85 to 14.26), (z = 2.21, P = 0.03) (Analysis 5.4) (moderate‐quality evidence). In comparisons with duration of at least one week and sodium intake of less than 250 mmol/day (12 studies, 486 participants) MD was 7.79 pg/mL (95% CI: 0.31 to 15.28), P = 0.04 (Analysis 6.4). There was no difference between normotensive participants and hypertensive participants (Table 4).

5.4. Analysis.

Comparison 5 Effect of salt reduction on hormones, Outcome 4 Adrenaline (pg/mL).

6.4. Analysis.

Comparison 6 Effect of salt reduction on hormones, subgroup analysis, Outcome 4 Adrenaline (pg/mL).

Cholesterol

See Table 5

Three parallel trials were excluded (1015 Bulpitt 1984; 1085 Sciarrone 1992; 1199 Meland 2009). In the remaining 26 cross‐over trials (1800 participants) of measurement of cholesterol (including 27 comparisons reported in the Data & analyses), MD showed an increase of 5.64 mg/dL (95% CI: 2.46 to 8.82), P = 0.0005 (Figure 6, Analysis 7.1) (moderate‐quality evidence). In comparisons with duration of at least one week and sodium intake of less than 250 mmol/day (20 trials, 1180 participants) MD was 4.88 mg/dL (95% CI: 1.19 to 8.56), P = 0.01 (Analysis 8.1). The effect in normotensive participants was significantly higher than in hypertensive participants (Table 5)

6.

Forest plot of comparison: 6 Effect of salt reduction on lipids, outcome: 6.1 Cholesterol.

7.1. Analysis.

Comparison 7 Effect of salt reduction on lipids, Outcome 1 Cholesterol (mg/dL).

8.1. Analysis.

Comparison 8 Effect of salt reduction on lipids, subgroup analysis, Outcome 1 Cholesterol (mg/dL).

Triglyceride

See Table 5

Two parallel trials were excluded (1085 Sciarrone 1992; 1199 Meland 2009) .

In the remaining 19 cross‐over trials (1390 participants) of measurement of triglyceride, MD showed an increase of 7.04 mg/dL (95% CI: 3.04 to 11.05), P = 0.0006 (Analysis 7.2) (moderate‐quality evidence). In comparisons with duration of at least one week and sodium intake of less than 250 mmol/day (12 trials, 770 participants) the effect was 6.92 (mg/dL [95% CI: 1.82 to 12.02), P = 0.008 (Analysis 8.2). There was no difference between normotensive participants and hypertensive participants (Table 5)

7.2. Analysis.

Comparison 7 Effect of salt reduction on lipids, Outcome 2 Trigyceride (mg/dL).

8.2. Analysis.

Comparison 8 Effect of salt reduction on lipids, subgroup analysis, Outcome 2 Trigyceride (mg/dL).

High‐density lipoprotein (HDL)

See Table 5

Two parallel trials were excluded (1085 Sciarrone 1992; 1199 Meland 2009).

In the remaining 19 cross‐over trials (1442 participants) of measurement of HDL, there was no effect of sodium reduction on serum HDL: MD: ‐0.29 mg/dL (95% CI: ‐1.66 to 1.08) P = 0.68 (Analysis 7.3) (moderate‐quality evidence). This result did not change in comparisons with duration of at least one week and sodium intake of less than 250 mmol/day (‐0.67 mg/dL (‐2.18 to 0.83), P = 0.38 (14 trials, 948 participants)) (Analysis 8.3).

7.3. Analysis.

Comparison 7 Effect of salt reduction on lipids, Outcome 3 High density lipoprotein, HDL (mg/dL).

8.3. Analysis.

Comparison 8 Effect of salt reduction on lipids, subgroup analysis, Outcome 3 High density lipoprotein, HDL (mg/dL).

Low‐density lipoprotein (LDL)

See Table 5

One parallel trial was excluded (1085 Sciarrone 1992).

In the remaining 17 cross‐over trials (1358 participants) of measurement of LDL, MD showed a non‐significant increase of 3.12 mgdL (95% CI: ‐0.41, to, 6.64), P = 0.08 (Analysis 7.4). In comparisons with duration of at least one week and sodium intake of less than 250 mmol/day (12 trials, 864 participants), MD was 3.63 mgdL (95% CI: ‐0.44 to 7.69), P = 0.08 (Analysis 8.4).

7.4. Analysis.

Comparison 7 Effect of salt reduction on lipids, Outcome 4 Low density lipoprotein, LDL (mg/dL).

8.4. Analysis.

Comparison 8 Effect of salt reduction on lipids, subgroup analysis, Outcome 4 Low density lipoprotein, LDL (mg/dL).

Bias analyses

Bias analysis: Comparing low bias risk versus high bias risk of general blinding and blinding of outcome detection for SBP‐outcomes in white people with normotension and hypertension showed no important differences. See Data and analyses: 9 Bias analyses.

Additional subgroup analyses

Hormones and lipids

Inclusion of the few parallel studies did not change any of the results (data not shown).

Sensitivity analyses

The funnel plots of all analyses were investigated. For each funnel plot, all studies giving rise to asymmetry were eliminated. The resulting effect was compared with the original analysis. All these analyses showed only marginal effects without significance (not shown).

Discussion

Summary of main results

The effect of sodium reduction from an average high usual intake (201 mmol/day) to the recommended level (66 mmol/day) was small in study populations with normal blood pressure (BP) (‐1.09/+0.03 mmHg) corresponding to a mean arterial pressure effect of only ‐0.3 mmHg . In hypertensive study populations the effect was (‐5.51/‐2.88 mmHg). In a subgroup analysis intending to eliminate the potential bias of a very short intervention duration (< seven days) and very high sodium intake (> 250 mmol/day), the decrease in BP in study populations with a normal BP (‐1.31/‐0.36 mmHg) and hypertension (‐5.02/‐2.78 mmHg) was also small. The effect of sodium reduction on hormones and on lipids showed statistically significant increases in renin, aldosterone, noradrenalin, cholesterol and triglyceride in the primary analysis, as well as in the subgroup analysis, whereas the increase in adrenalin was borderline significant (P < 0.03). The increase in cholesterol in the low‐salt group seemed mainly to be due to an increase in low‐density lipoprotein (LDL), which was borderline significant. The slight decrease in high‐density lipoprotein (HDL) in the low‐salt group was not significant.

The analysis of black populations showed that the effect of sodium reduction in black people with normotension corresponded to the one found in black people with hypertension. This was in contrast to the analyses of white and Asian populations in whom the effect was smaller in those who were normotensive than in those who were hypertensive. However, compared with previous analyses (Graudal 1998; Jürgens 2003), the diverging results within the black populations and between the black and white populations are smaller. In a recent detailed analysis, we found that a significant fraction of the differences between the three ethnicity groups could be ascribed to differences in baseline BP, age, and amount of sodium reduction. Furthermore there was no difference in BP outcome between ethnicity groups investigated in the same study (Graudal 2015b) indicating that the differences found in the present meta‐analysis mainly may be due to confounders rather than ethnical differences.

Overall completeness and applicability of evidence

In the primary analysis, population samples from the whole BP distribution of the populations were included. In this analysis, the intake of sodium in the “high” sodium group was in the interval 100 mmol/day to 795 mmol/day in 205 comparisons (99%), and below 100 mmol/day in one comparison, the mean level being 201 mmol/day. The intake of sodium in the low‐sodium group was below 100 mmol/day in 168 comparisons (82%) and above 100 mmol/day in 38 comparisons, the mean level being 66 mmol/day. In the subgroup analysis, the intake of sodium in the “high” sodium group was in the interval 109 mmol/day to 248 mmol/day in 143 comparisons (99%), and below 100 mmol/day in one comparison, the mean level being 167 mmol/day. The intake of sodium in the low‐sodium group was below 100 mmol/day in 114 comparisons (80%) and above 100 mmol/day in 30 comparisons, the mean level being 60 mmol/day. Consequently, this meta‐analysis in general compares the effects of a dietary sodium intake, which is lower than usual and in accordance with the recommendations to reduce sodium below 100 mmol/day with a sodium intake, which is within the present world‐wide usual range of sodium intake, the level in the primary analysis being in the high end of the usual intake and the level in the subgroup analysis being close to the world mean of 159 mmol/day (Table 15). The mean and the range of the baseline 24‐hour sodium excretion of the included populations before diet manipulation (159 mmol/24 hours (10 to 90 percentile: 123 to 194)) were almost identical with the usual range of sodium intake in the world's populations (McCarron 2013; Powles 2013). Thus, the present review shows the consequences of the recommendations of the health institutions, which is to reduce the usual sodium intake of the world's populations (90 mmol/day to 250 mmol/day) to a level below 87 mmol/day to 100 mmol/day.

Quality of the evidence

The study populations included in the present meta‐analysis were in general very heterogeneous with large variations in baseline BP, age, sodium intake and degree of sodium reduction. The analyses of BP and hormones were generally very heterogeneous. Especially, the I² values for renin and aldosterone were very high, but as renin and aldosterone rise sharply with sodium reduction below 2.3 g sodium, but only moderately above 2.3 g sodium (Brunner 1972; Graudal 1998), the extreme heterogeneity of the outcomes of these variables is not surprising. In spite of the clinical heterogeneity, no heterogeneity was detected in the meta‐analyses of lipid outcomes implying that these outcomes are robust. The number of studies included in the BP analyses (n = 206) is substantial as is the number of participants (more than 6000). This should allow robust conclusions. The fundamental quality criterion was randomisation, but a weakness is that very few of the studies described the sequence generation and the random allocation procedures leaving a substantial bias risk of insufficient randomisation, which could not be explored in a meaningful way due to the lack of contrasts between the number of studies with low and high risk of these biases (Figure 1). Another weakness was that a large number of studies were not double‐blind. However, concerning this source of bias, there were no obvious trends towards different effects in the low‐risk blinded groups compared with the high‐risk open groups (Analysis 9.1; Analysis 9.2; Analysis 9.3; Analysis 9.4; Analysis 9.5; Analysis 9.6; Analysis 9.7; Analysis 9.8).

9.1. Analysis.

Comparison 9 Bias analyses, Outcome 1 White population, normotensive, SBP blinding‐high.

9.2. Analysis.

Comparison 9 Bias analyses, Outcome 2 White population, normotensive, SBP blinding‐low.

9.3. Analysis.

Comparison 9 Bias analyses, Outcome 3 White population, normotensive, SBP outcome‐assesed‐high.

9.4. Analysis.

Comparison 9 Bias analyses, Outcome 4 White population, normotensive, SBP outcome‐assesed‐low.

9.5. Analysis.

Comparison 9 Bias analyses, Outcome 5 White population, hypertensive, SBP blinding‐high.

9.6. Analysis.

Comparison 9 Bias analyses, Outcome 6 White population, hypertensive, SBP blinding‐low.

9.7. Analysis.

Comparison 9 Bias analyses, Outcome 7 White population, hypertensive, SBP outcome‐assesed‐high.

9.8. Analysis.

Comparison 9 Bias analyses, Outcome 8 White population, hypertensive, SBP outcome‐assesed‐low.

Potential biases in the review process

The present review is the largest of the many existing meta‐analyses on sodium reduction, and other meta‐analyses have not identified studies, which were not identified by our search. Our analysis is the largest partly because our selection criteria were less restrict. Therefore, a fraction of the included studies had an experimental character investigating a sodium intake far beyond the sodium intake in the general population for only four to six days, which may not be relevant for the general population on long‐term sodium reduction. The fact that the subgroup analysis eliminating the potential short‐term intervention bias and very high sodium intake bias showed similar results as the primary analysis indicates that the inclusion of extreme studies had a minor impact on the mean of the outcome effects. Other meta‐analyses have extracted almost identical data in the individual studies indicating that our data extraction is unbiased. Finally, elimination of studies giving rise to asymmetry in the funnel plots did not change the results indicating a low risk of publication bias.

Agreements and disagreements with other studies or reviews

The scientific evidence behind the sodium reduction recommendations is a series of studies and meta‐analyses, which are biased by high baseline blood pressure, high age and overweight (Graudal (3) 2016). The most prominent of these studies (DASH 2001), was additionally biased by a control group diet, which was designed to contain only half of the normal amount of potassium. Despite these studies are irrelevant as evidence for pubic health recommendations, the Food and Drug Administration (FDA) has released draft proposed voluntary guideline to encourage companies to steadily reduce sodium in processed foods (Frieden TR 2016), the main argument being a dose‐response meta‐regression analysis of mixed normotensive and hypertensive study populations, which was biased because it included mainly studies with high blood pressure and inappropriately forced the dose‐response relationship through zero and thereby further doubled the postulated effect. In contrast, previous meta‐analyses of randomised controlled trials (RCTs) have shown similar results of sodium reduction on BP. In 1986, Grobbee and Hofman combined 13 studies of persons with normal and elevated BP in a meta‐analysis and found a significant hypotensive effect of reduced sodium intake on SBP of ‐3.6 mmHg and a non‐significant effect on DBP of ‐2.0 mmHg (Grobbee 1986). In 1991, a second meta‐analysis of 24 RCTs showed an effect of ‐4.0/‐2.5 mmHg for persons with elevated BP and ‐1.0/‐0.2 for persons with normal BP (Cutler 1991). This was verified in an update from 1997 (Cutler 1997). In 1996, a meta‐analysis of 53 RCTs showed an effect of ‐3.7/‐0.9 mmHg in persons with elevated BP and ‐1.0/‐0.1 in persons with normal BP (Midgley 1996). In an analysis of eight RCTs lasting for at least six months, the effect was ‐2.9/‐2.1 mmHg for persons with elevated BP and ‐1.3/‐ 0.8 mmHg for persons with normal BP (Ebrahim 1998). These results were confirmed in an update (Hooper 2002). All these similar results confirm that selection of RCTs based on magnitude of sodium difference or duration of the intervention does not significantly change the overall effect size estimate. These meta‐analyses indicate that major disagreements about this effect size no longer seem to exist. However, there is still significant disagreement regarding the relevance of the effect size and the relevance of potential side effects (Taubes 1998).

The effect of sodium reduction on BP in hypertensive and normotensive study populations in the present review matches the effects found in most of these previous reviews, although the effect of sodium reduction on BP in normotensives is marginally lower than in the meta‐analysis, which supports the WHO recommendations (Aburto 2013). In hypertensive study populations, there was no differences between the WHO review and our review. In normotensive study populations, the difference was small, the BP effect in the WHO review being ‐1.38/‐0.58 mmHg and in ours being ‐1.09/0.03 (‐1.31/‐0.36 in the subgroup analysis).This study differed from ours as it only included studies lasting at least four weeks. However, as duration has no impact on the BP effect (Table 16), a more reliable explanation for the difference between the WHO review and our review is that the study populations with normal BP in the WHO review generally have a high baseline BP in the upper 50% percentile of the population.

According to WHO, the small effect in normotensive study populations is sufficient to recommend sodium reduction for the whole population, the assumption being that the association between BP and mortality is consistent. This, however, may not be the case. For instance, beta‐blockers reduce BP in hypertensive individuals, but not mortality (Wiysonge 2012), and a recent meta‐analysis of patients with diabetes showed that antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in diabetes patients with SBP higher than 140 mm Hg, but if SBP is less than140 mm Hg further treatment is associated with an increased risk of cardiovascular death, with no observed benefit (Brunström 2016). Such studies indicate that it is not possible to extend the general association of BP with mortality (Collins 1990) to the effect of a BP‐reducing intervention on mortality. The reason for this inconsistency may be side effects of the intervention. However, while short duration has been suggested to underestimate the BP effect, it has concomitantly been suggested to overestimate possible adverse effects on hormones and lipids. This idea that the duration of the intervention tends to underestimate some physiological outcomes and overestimate others has not been documented, but still has been used to disregard side effects shown in studies lasting less than four weeks. Very few studies lasting more than for weeks have investigated side effects, and further more these studies do not reduce sodium to the recommended level, but to levels above 87 mmol/day, and therefore the side effects in these few studies may not be fully disclosed. In contrast, the present analysis shows that the adverse effects on hormones and lipids are significant, when the sodium intake is lowered from a high usual sodium intake to a level in accordance with the recommendations of the health institutions. In addition, we have just shown that sodium reduction results in an increase in heart rate of 2.4% (Graudal (2) 2016). This may be an important side effect as resting heart rate is directly associated with mortality (Ho 2014; Jensen 2012). The assumption that at least some of these effects may be persistent and not just temporary has been indicated in observational studies. Yanomamo Indians, who persistently ingest very small amounts of sodium, have a three times higher level of renin in the blood and a 10 times higher excretion of aldosterone in the urine than normal controls (Oliver 1975). Furthermore, renin and aldosterone rise slowly as long as the intake is above 100 mmol/day, but exponentially, when sodium intake is reduced to levels below 100 mmol/day (Brunner 1972). Thus, the present meta‐analysis provides a possible explanation for the small effect of reduced sodium intake on blood pressure: compensatory activation of the renin‐aldosterone system is proportional to the degree of sodium reduction. Furthermore, the increases in noradrenaline and adrenaline may contribute to this counter‐regulation (Warren 1980) and contribute to an increase in heart rate.

The very small effect of sodium reduction on BP in healthy individuals shown in the present review and other reviews including the WHO review, the risk of significant side effects shown in this review, and the possibility that an intervention to reduce BP may not reduce mortality (Wiysonge 2012), and even may increase mortality in some population groups with a normal BP (Brunström 2016) indicate that the BP‐effect is not sufficient as a basis for recommendations in the general population, but should be verified in studies directly relating sodium intake with morbidity and mortality. Unfortunately, RCTs of the effect of sodium reduction below 100 mmol/day on mortality in healthy individuals do not exist (Graudal (1) 2016). A recently updated meta‐analysis of eight RCTs with follow‐up data on morbidity and mortality found a non‐significant trend versus reduced cardiovascular (CV) morbidity, but could not demonstrate reduced all‐cause mortality in the low‐sodium group (Adler 2014). These trials were performed in overweight pre‐hypertensive or hypertensive individuals and the sodium reduction was not below 100 mmol/day, but down to 100 mmol/day.

The sodium‐mortality relationship has also been estimated by means of 27 observational studies (Alderman 2010; Mente 2016; O'Donnell 2014; Pfister 2014), which directly asses the relationship between sodium intake in the individual and mortality. Most of these studies were evaluated in an IOM report (IOM 2013). This IOM report did not confirm the 100 mmol/day upper level for sodium intake, which was defined in a previous IOM report (IOM 2005), but concluded that “Science was insufficient and inadequate to establish whether reducing sodium intake below 2300 mg/d (100 mmol) either decreases or increases CVD risk in the general population”. A later meta‐analysis of these population studies found that a sodium intake below 114 mmol/day was associated with increased mortality, as was a sodium intake above 214 mmol/day (Graudal 2014). Increased mortality with high sodium intake has also been shown in another meta‐analysis, which, however, did not investigate the effect of a low sodium intake (Strazzulo 2009). This U‐shaped relation between sodium intake and mortality has been identified in several individual population studies (O'Donnell 2011; O'Donnell 2014; Pfister 2014; Thomas 2011). The health institutions, however, generally do not accept this evidence from the observational studies (Gunn 2013; Whelton 2012; WHO 2012). In a recent paper, which discusses methodological issues of observational studies, representatives of the American Heart Association state that the association of low sodium intake with increased mortality observed in observational studies may reflect that sick people have a low sodium intake (reverse causality: sick people with a high mortality have a low sodium intake, it is not the low sodium intake, which increases the mortality) (Cobb 2014). This hypothesis is not directly supported by the observational studies, as the outcomes generally are adjusted for confounders such as cardiovascular and renal diseases and diabetes and show that the mortality associated with a low sodium intake is higher in healthy populations than in populations including sick individuals (Graudal 2014; O'Donnell 2014). Table 17 shows a meta‐analysis of the risk of all‐cause mortality in Study populations within the usual sodium intake range versus a low sodium intake below 114 mmol/day (Graudal 2014) or below 130 mmol/day (O'Donnell 2014). The analysis is confined to include samples of individuals representative of the general populations and all individual study analyses are adjusted for multiple confounders such as cardiovascular disease, hypertension and diabetes. To further reduce the risk of reverse causality, the most healthy subgroup was included in the analysis, when results were given for subgroups, The possibility of reverse causality can never be completely excluded, but as a minimum there is no indication in population studies that sodium intake below 100 mmol/day has beneficial health effects in healthy individuals. In the NHANES I and III studies this was demonstrated by independent groups (Alderman 1998; Cohen 2008; He 1999; Yang 2011).

3. Association of low sodium intake with mortality in prospective observational studies.

Study	Multiple adjustment*	Exclusion	N (LS)	N (US)	RR/OR (95% CI)
Alderman 1998 (NHANES I)	Yes	None	2837	8509	0.88 (0.80, to, 0.97)
He 1999 (NHANES I)	Yes	Overweight (BMI > 27.3)	1699	5098	0.98 (0.88 to 1.09)
Tuomilehto 2001	Yes	Males**	634	311	0.91 (0.56 to 1.48)
Cohen 2006 (NHANES II)	Yes	None	3711	3443	0.78 (0.67 to 0.91)
Gelijnse 2007	Yes	CVD and HT	392	392	1.12 (0.86 to 1.46)
Cohen 2008 (NHANES III)	Yes	None	2175	4350	0.83 (0.73 to 0.94)
Yang 2011 (NHANES III)	Yes	Overweight (BMI > 25)	3067	6133	0.93 (0.73 to 1.18)
Stolarz‐Skrzypek 2011	Yes	None	1250	1220	0.82 (0.62 to 1.08)
Gardener 2012	Yes	None	1138	961	0.89 (0.74 to 1.07)
Pfister 2014 (Norfolk)	Yes	0‐2 year events	3070	9249	0.92 (0.82 to 1.02)
O'Donnell 2014 (PURE)	Yes	CVD, Cancer, DM, smokers	6162	38643	0.62 (0.54 to 0.71)]
Total (95% CI)#			21369	67078	0.84 (0.76 to 0.93)
Total (95% CI)##			21123	65450	0.87 (0.76 to 0.98)

Only studies, which were representative for the general population and which adjusted for confounders were included.

If subgroup results were given, the results of the most healthy subgroup was used in the analysis to reduce

the possibility of reverse causation

#With primary NHANES analyses (Alderman 1998, Cohen 2008)

## With NHANES re‐analyses (He 1999, Yang 2011)

* Studies were generally adjusted for at least sex, age and CVD risk factors

** In the male group a low salt intake group could not be identified, as the salt intake

in the lowest salt intake quartile was up to 159 mmol.

BMI: body mass index; CVD: cardiovascular disease; DM: diabetes mellitus; HT: hypertension

The BP effect of reduced sodium intake has been related to age. Freedman and Petitti analysed data from Intersalt (Intersalt 1988) and found the paradox that along with the significant association between increase in blood pressure with age and the salt excretion in urine, there was an inverse relationship between estimated BP and salt excretion in urine at age 20. Freedman stated that unless you preferred to conclude that salt should be eaten in high doses by youngsters and in reduced amounts by the elderly, the findings were probably due to uncontrolled confounding, not to variation in salt intake (Freedman 2001). Furthermore, it is now clear that the BP of different age cohorts in a cross‐sectional study like Intersalt is not representative of each other, verified by a study showing that recent birth cohorts attained lower BP than did earlier birth cohorts in the period 1887 to 1994 (Goff 2001). According to this study, based on data from more than 50,000 persons, it can be estimated that the median BP is about 15 mmHg lower in a 50‐year old person from a recent birth cohort compared with a 50‐year old from a birth cohort from the late 19th century. Consequently, there has been a dramatic fall in BP during the 20th century. In this context, the possible mean arterial pressure effect of sodium reduction of ‐0.3 mmHg in normotensive persons seems negligible. Finally, it has been difficult to maintain a significant sodium reduction in longer‐term studies, which should be taken into consideration, when recommending sodium reduction. One reason for this could be that the sodium intake is regulated by neuro‐physiological and hormonal mechanisms (Geerling 2008), and therefore difficult to diverge from.

The hypothetical consequences of the present findings are that people with normotension would have no benefit from sodium reduction, but may suffer from harms, because sodium reduction has a negligible effect on BP, but results in significant side effects. People with hypertension may benefit due to the effect on BP, but may also suffer from harms due to the side effects. This is exactly what was found in the most recent meta‐analysis of four population studies (133,000 individuals) in which the authors had access to individual participant data (Mente 2016). The conclusion was "Compared with moderate sodium intake, high sodium intake is associated with an increased risk of cardiovascular events and death in hypertensive populations (no association in normotensive population), while the association of low sodium intake with increased risk of cardiovascular events and death is observed in those with or without hypertension. These data suggest that lowering sodium intake is best targeted at populations with hypertension who consume high sodium diets", a conclusion, which matches perfectly with the results of the present meta‐analysis.

Authors' conclusions

Implications for practice.

The present meta‐analysis shows that a low‐ versus high‐sodium diet in white people with normal blood pressure (BP) decreases BP less than 1%. A significant concomitant increase in plasma renin, plasma aldosterone, plasma noradrenalin, and to a lesser degree of plasma adrenaline may contribute to the small effect of sodium reduction on BP. Furthermore, sodium reduction resulted in a significant increase in plasma cholesterol and plasma triglyceride, which expressed in percentage, was numerically larger than the decrease in BP. Due to the relatively small effects and due to the antagonistic nature of the effects (decrease in BP, increase in hormones and lipids), these results do not support that sodium reduction may have net beneficial effects in a population of  white people with normal BP.

In white people with elevated BP, sodium reduction decreases BP by about 3.5%, indicating that sodium reduction may be used as a supplementary treatment for hypertension. In Asian and black people the effect of sodium reduction was a little larger than in white people, but at present too few studies have been carried out to conclude different from that above.

Implications for research.

The data suggesting that black and Asian populations are more sensitive to sodium reduction than white people requires further studies. In future studies of mixed populations, it is important that the effects on white, black and Asian populations are reported separately. Population studies have shown a U‐shaped association between sodium intake and mortality indicating that the beneficial effect of sodium reduction on BP outweigh the harmful effect on hormones and lipids at sodium intake above the usual sodium intake, but that the harms of sodium reduction outweigh the benefits at sodium intake below the usual sodium intake. Long‐term randomised controlled trials (RCTs) with mortality and morbidity outcomes would be desirable to confirm or reject these findings. However, such studies may not be practicable. After 185 RCTs and 27 population studies without an obvious signal in favour of sodium reduction below 100 mmol/day, another position could be to accept that the present usual sodium intake may be the optimal intake for the general population.

What's new

Date	Event	Description
4 January 2017	New citation required but conclusions have not changed	updated version of the review with up‐to‐date search and methodology
4 January 2017	New search has been performed	Twenty‐one new references were included. One erroneously double‐counted and two previously included duplicate references were excluded. Separate analyses of mean blood pressure (MBP) in white participants were excluded. Instead MBP effects were transformed to SBP and DBP effects by means of regression analyses and included in the SBP and DBP analyses. Previous subgroup analyses of studies with a duration of at least four weeks (BP), two to four weeks (hormones and lipids) and lipid studies with sodium reduction to moderate levels were eliminated. Instead, a subgroup analysis of studies lasting at least seven days and with a sodium intake of maximum 250 mmol/day in the high sodium group was performed on all outcomes. The text of the review includes new subheadings available in Rev Man.

History

Protocol first published: Issue 1, 2003
 Review first published: Issue 1, 2003

Date	Event	Description
17 November 2002	New search has been performed	Substantive amendment

Appendices

Appendix 1. Search strategies

Database: Ovid MEDLINE(R) 1946 to Present with Daily Update
 Search Date: 7 March 2016
 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
 1 sodium chloride, dietary/ (5340)
 2 sodium, dietary/ (7840)
 3 sodium/ (101026)
 4 (sodium or salt).tw. (346998)
 5 or/1‐4 (400932)
 6 diet, sodium‐restricted/ (5815)
 7 ((salt or sodium) adj5 (chang$ or curb$ or diet$ or free or intake or limit$ or load$ or low$ or minimi$ or reduc$ or restrict$ or supplement$)).tw. (50878)
 8 or/6‐7 (53160)
 9 hypertension/ (207011)
 10 hypertens$.tw. (322915)
 11 exp blood pressure/ (260732)
 12 (blood pressure or bloodpressure or bp).tw. (317168)
 13 or/9‐12 (707443)
 14 renin/ (27614)
 15 renin.tw. (43610)
 16 aldosterone/ (22706)
 17 aldosterone.tw. (28823)
 18 exp catecholamines/ (242929)
 19 (catecholamine$ or sympathin$ or dopamine$ or hydroxytyramine$ or dihydroxyphenethylamine or intropin or epinephrine or adrenaline or epitrate or vaponefrin or medihaler‐epi or micronefrin or micronephrine or racepinephrine or epifrin or lyophrin or norepinephrin$ or noradrenaline or levarterenol or levonorepinephrine or levophed or arterenol or levonor or orciprenaline or metaproterenol or alupent or metaprel or alotec or astmopent).tw. (246296)
 20 exp cholesterol/ (142389)
 21 (cholesterol$ or epicholesterol$ or azacosterol$ or diazacholesterol$ or hydroxycholesterol$ or 19‐iodocholesterol$ or iodocholesterol$ or ketocholesterol$ or oxocholesterol$ or lipid$ or glyceride$ or triglyceride$ or glycolipid$ or lipoprotein$ or ldl or hdl).tw. (533921)
 22 or/14‐21 (953557)
 23 randomized controlled trial.pt. (407656)
 24 controlled clinical trial.pt. (90132)
 25 randomized.ab. (304936)
 26 placebo.ab. (155515)
 27 clinical trials as topic/ (175120)
 28 randomly.ab. (215798)
 29 trial.ti. (132445)
 30 or/23‐29 (931053)
 31 animals/ not (humans/ and animals/) (4161827)
 32 30 not 31 (852135)
 33 5 and 8 and (13 or 22) and 32 (1933)
 34 remove duplicates from 33 (1925)
 
 ***************************
 
 Database: Cochrane Central Register of Controlled Trials <2016, Issue 3> via Cochrane Register of Studies Online
 Search Date: 7 March 2016
 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
 #1 MESH DESCRIPTOR Sodium Chloride, Dietary 211
 #2 MESH DESCRIPTOR Sodium, Dietary 328
 #3 MESH DESCRIPTOR Sodium 1917
 #4 (salt or sodium):TI,AB 18678
 #5 #1 OR #2 OR #3 OR #4 19256
 #6 MESH DESCRIPTOR Diet, Sodium‐Restricted 518
 #7 (salt or sodium) near5 (chang* or curb* or diet* or free or intake or limit* or load* or low* or minimi* or reduc* or restrict* or supplement*) 3206
 #8 #6 OR #7 3206
 #9 MESH DESCRIPTOR Hypertension 13753
 #10 (antihypertens* or hypertens*):TI,AB 32980
 #11 MESH DESCRIPTOR Blood Pressure EXPLODE ALL TREES 24184
 #12 (blood pressure or bloodpressure or bp) 55509
 #13 #9 OR #10 OR #11 OR #12 71017
 #14 renin 4518
 #15 aldosterone 3221
 #16 MESH DESCRIPTOR Catecholamines EXPLODE ALL TREES 8599
 #17 (catecholamine* or sympathin* or dopamine* or hydroxytyramine* or dihydroxyphenethylamine or intropin or epinephrine or adrenaline or epitrate or vaponefrin or medihaler‐epi or micronefrin or micronephrine or racepinephrine or epifrin or lyophrin or norepinephrin* or noradrenaline or levarterenol or levonorepinephrine or levophed or arterenol or levonor or orciprenaline or metaproterenol or alupent or metaprel or alotec or astmopent) 16533
 #18 MESH DESCRIPTOR Cholesterol EXPLODE ALL TREES 8755
 #19 (cholesterol* or epicholesterol* or azacosterol* or diazacholesterol* or hydroxycholesterol* or 19‐iodocholesterol* or iodocholesterol* or ketocholesterol* or oxocholesterol* or lipid* or glyceride* or triglyceride* or glycolipid* or lipoprotein* or ldl or hdl) 37244
 #20 #14 OR #15 OR #16 OR #17 OR #18 OR #19 59594
 #21 #5 AND #8 AND #13 OR #20 1820
 
 ***************************
 
 Database: Embase <1980 to 2016 March 04>
 Search Date: 7 March 2016
 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
 1 sodium chloride, dietary/ (7530)
 2 sodium, dietary/ (6109)
 3 sodium/ (91427)
 4 (sodium or salt).tw. (424462)
 5 or/1‐4 (472096)
 6 diet, sodium‐restricted/ (8257)
 7 ((salt or sodium) adj5 (chang$ or curb$ or diet$ or free or intake or limit$ or load$ or low$ or minimi$ or reduc$ or restrict$ or supplement$)).tw. (61099)
 8 or/6‐7 (64792)
 9 exp hypertension/ (545880)
 10 hypertens$.tw. (476727)
 11 exp blood pressure/ (434877)
 12 (blood pressure or bloodpressure or bp).tw. (428835)
 13 or/9‐12 (1125448)
 14 renin/ (25693)
 15 renin.tw. (51567)
 16 aldosterone/ (30390)
 17 aldosterone.tw. (34355)
 18 exp catecholamine/ (324747)
 19 (catecholamine$ or sympathin$ or dopamine$ or hydroxytyramine$ or dihydroxyphenethylamine or intropin or epinephrine or adrenaline or epitrate or vaponefrin or medihaler‐epi or micronefrin or micronephrine or racepinephrine or epifrin or lyophrin or norepinephrin$ or noradrenaline or levarterenol or levonorepinephrine or levophed or arterenol or levonor or orciprenaline or metaproterenol or alupent or metaprel or alotec or astmopent).tw. (288546)
 20 exp cholesterol/ (239050)
 21 (cholesterol$ or epicholesterol$ or azacosterol$ or diazacholesterol$ or hydroxycholesterol$ or 19‐iodocholesterol$ or iodocholesterol$ or ketocholesterol$ or oxocholesterol$ or lipid$ or glyceride$ or triglyceride$ or glycolipid$ or lipoprotein$ or ldl or hdl).tw. (688622)
 22 or/14‐21 (1238526)
 23 randomized controlled trial/ (394072)
 24 crossover procedure/ (46238)
 25 double‐blind procedure/ (126561)
 26 (randomi?ed or randomly).tw. (845561)
 27 (crossover$ or cross‐over$).tw. (78158)
 28 placebo.ab. (219858)
 29 (doubl$ adj blind$).tw. (159441)
 30 assign$.ab. (271379)
 31 allocat$.ab. (97448)
 32 or/23‐31 (1264495)
 33 (exp animal/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans).ti.) (5457724)
 34 32 not 33 (1101675)
 35 5 and 8 and (13 or 22) and 34 (2193)
 36 remove duplicates from 35 (2167)
 
 ***************************
 
 Database: Hypertension Group Specialised Register via Cochrane Register of Studies
 Search Date: 7 March 2016
 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
 #1 ((salt or sodium):TI)
 #2 ((chang* or curb* or diet* or free or intake or limit* or load* or low* or minimi* or reduc* or restrict* or supplement*))
 #3 RCT:DE
 #4 (Meta‐Analysis OR Review):MISC2
 #5 #1 AND (#2) AND ((#3 OR #4)) (708)
 
 ***************************
 
 Database: ClinicalTrials.gov
 Search Date: 7 March 2016
 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
 Search terms: (salt OR sodium) AND randomized
 Study type: Interventional Studies
 Interventions: diet
 Outcome Measures: blood pressure (113)
 
 ***************************
 
 Medline In‐Process: 98

Total: 1925 + 1820 + 2167 + 708 + 113 + 98 = 6831
 
 After de‐duplication: 3269

Data and analyses

Comparison 1. Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 White population, normotensive, SBP	89	8569	Mean Difference (Random, 95% CI)	‐1.09 [‐1.63, ‐0.56]
2 White population, normotensive, DBP	90	8833	Mean Difference (Random, 95% CI)	0.03 [‐0.37, 0.43]
3 White population, hypertensive, SBP	84	5925	Mean Difference (Random, 95% CI)	‐5.51 [‐6.45, ‐4.57]
4 White population, hypertensive, DBP	85	6001	Mean Difference (Random, 95% CI)	‐2.88 [‐3.44, ‐2.32]

Comparison 2. Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Blacks.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Black population, normotensive, SBP	7	506	Mean Difference (Random, 95% CI)	‐4.02 [‐7.37, ‐0.68]
2 Black population, normotensive, DBP	7	506	Mean Difference (Random, 95% CI)	‐2.01 [‐4.37, 0.35]
3 Black population, hypertensive, SBP	8	619	Mean Difference (Random, 95% CI)	‐6.64 [‐9.00, ‐4.27]
4 Black population, hypertensive, DBP	8	619	Mean Difference (Random, 95% CI)	‐2.91 [‐4.52, ‐1.30]

Comparison 3. Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Asians.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Asians population normotensive, SBP	3	393	Mean Difference (Random, 95% CI)	‐0.72 [‐3.86, 2.41]
2 Asian population, normotensive, DBP	3	393	Mean Difference (Random, 95% CI)	‐1.63 [‐3.35, 0.08]
3 Asian population, hypertensive, SBP	8	501	Mean Difference (Random, 95% CI)	‐7.75 [‐11.44, ‐4.07]
4 Asian population, hypertensive, DBP	8	501	Mean Difference (Random, 95% CI)	‐2.68 [‐4.21, ‐1.15]

Comparison 4. Effect of salt reduction on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Whites, subgroup analysis.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 White population, normotensive, SBP	59	7125	Mean Difference (Random, 95% CI)	‐1.31 [‐1.83, ‐0.80]
2 White population, normotensive, DBP	61		Mean Difference (Random, 95% CI)	‐0.36 [‐0.79, 0.07]
3 White population, hypertensive, SBP	63		Mean Difference (Random, 95% CI)	‐5.02 [‐4.00, ‐4.05]
4 White population, hypertensive, DBP	64		Mean Difference (Random, 95% CI)	‐2.78 [‐3.42, ‐2.14]

Comparison 5. Effect of salt reduction on hormones.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Renin (ng/mL/hour)	88	5498	Std. Mean Difference (IV, Random, 95% CI)	1.22 [1.07, 1.37]
2 Aldosterone (pg/mL)	65	4884	Mean Difference (IV, Random, 95% CI)	97.81 [82.56, 113.05]
3 Noradrenaline (pg/mL)	36	1736	Mean Difference (IV, Random, 95% CI)	63.56 [42.66, 84.46]
4 Adrenaline (pg/mL)	16	662	Mean Difference (IV, Random, 95% CI)	7.55 [0.85, 14.26]

Comparison 6. Effect of salt reduction on hormones, subgroup analysis.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Renin (ng/mL/hour)	44	3470	Std. Mean Difference (IV, Random, 95% CI)	1.05 [0.85, 1.24]
2 Aldosterone (pg/mL)	34	3128	Mean Difference (IV, Random, 95% CI)	95.59 [74.12, 117.05]
3 Noradrenaline (pg/mL)	23	964	Mean Difference (IV, Random, 95% CI)	48.66 [28.88, 68.44]
4 Adrenaline (pg/mL)	12	486	Mean Difference (IV, Random, 95% CI)	7.79 [0.31, 15.28]

Comparison 7. Effect of salt reduction on lipids.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Cholesterol (mg/dL)	27	1800	Mean Difference (IV, Random, 95% CI)	5.64 [2.46, 8.82]
2 Trigyceride (mg/dL)	19	1390	Mean Difference (IV, Random, 95% CI)	7.04 [3.04, 11.05]
3 High density lipoprotein, HDL (mg/dL)	19	1442	Mean Difference (IV, Random, 95% CI)	‐0.29 [‐1.66, 1.08]
4 Low density lipoprotein, LDL (mg/dL)	17	1358	Mean Difference (IV, Fixed, 95% CI)	3.12 [‐0.41, 6.64]

Comparison 8. Effect of salt reduction on lipids, subgroup analysis.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Cholesterol (mg/dL)	20	1180	Mean Difference (IV, Random, 95% CI)	4.88 [1.19, 8.56]
2 Trigyceride (mg/dL)	12	770	Mean Difference (IV, Fixed, 95% CI)	6.92 [1.82, 12.02]
3 High density lipoprotein, HDL (mg/dL)	14	948	Mean Difference (IV, Fixed, 95% CI)	‐0.67 [‐2.18, 0.83]
4 Low density lipoprotein, LDL (mg/dL)	12	864	Mean Difference (IV, Fixed, 95% CI)	3.63 [‐0.44, 7.69]

Comparison 9. Bias analyses.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 White population, normotensive, SBP blinding‐high	66	7100	Mean Difference (Fixed, 95% CI)	‐0.91 [‐1.19, ‐0.63]
2 White population, normotensive, SBP blinding‐low	24	1193	Mean Difference (Fixed, 95% CI)	‐1.05 [‐1.61, ‐0.50]
3 White population, normotensive, SBP outcome‐assesed‐high	36	2771	Mean Difference (Fixed, 95% CI)	‐1.12 [‐1.60, ‐0.65]
4 White population, normotensive, SBP outcome‐assesed‐low	56	5768	Mean Difference (Fixed, 95% CI)	‐0.89 [‐1.18, ‐0.60]
5 White population, hypertensive, SBP blinding‐high	45	3814	Mean Difference (Fixed, 95% CI)	‐6.03 [‐6.64, ‐5.41]
6 White population, hypertensive, SBP blinding‐low	36	1911	Mean Difference (Fixed, 95% CI)	‐5.78 [‐6.39, ‐5.17]
7 White population, hypertensive, SBP outcome‐assesed‐high	27	2470	Mean Difference (Fixed, 95% CI)	‐6.07 [‐6.95, ‐5.19]
8 White population, hypertensive, SBP outcome‐assesed‐low	55	3433	Mean Difference (Fixed, 95% CI)	‐5.71 [‐6.23, ‐5.19]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

1000 Parijs 1973.

Methods	Op CO
Participants	N 17 (22) Hyp Age 41
Interventions	SR 98 Dur 28
Outcomes	SBP DBP
Notes	LoFo: 5 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Each patient received a number
Allocation concealment (selection bias)	High risk	Those with uneven numbers were instructed to take a low‐sodium diet during the first period and a high‐sodium diet during the second period and vice versa for those with even numbers
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Immediate attrition: 5 participants. 17 completed regular sodium period, 15 completed low sodium period. The outcome measurement was based on the 15 participants, who completed both periods. Total attrition 7 participants, i.e. there was no difference in attrition between the two treatment periods, but the total attrition was significant (32%).
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1001 Mark 1975.

Methods	Op CO
Participants	N 6 Hyp Age 28
Interventions	SR 305 Dur 10
Outcomes	SBP DBP Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.

1002 Morgan 1978.

Methods	SB P
Participants	N 62, M/F:62/0 Hyp Age 60
Interventions	SR 23 Dur 90
Outcomes	SBP DBP
Notes	LoFO: 3 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 3/62
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1003 Sullivan 1980.

Methods	S CO
Participants	N 27 Norm Age 29
Interventions	SR 146 Dur 4
Outcomes	SBP DBP Aldo Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	High risk	Only the 10 first participants received the high and low salt diets in random order until it was established that the order of administration did not appear to make a difference in the results
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Measurements were mad by 2 observers who were not aware of the participant's dietary state

1004 Sullivan 1980 H.

Methods	Op CO
Participants	N 19 Hyp Age27
Interventions	SR153 Dur4
Outcomes	SBP DBP Aldo Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	High risk	Only the 10 first participants received the high‐ and low‐salt diets in random order until it was established that the order of administration did not appear to make a difference in the results
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Measurements were mad by 2 observers who were not aware of the participant 's dietary state

1005 Rankin 1981.

Methods	Op CO
Participants	N 8 (M/F:8/0) Normotension Age 30
Interventions	SR 776 (796‐20) Dur 6
Outcomes	MAP, NE
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1006 Skrabal 1981.

Methods	Op CO
Participants	N 20 Norm Age 23
Interventions	SR 150 Dur 14
Outcomes	SBP DBP Aldo Renin NA A
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1007 Morgan 1981.

Methods	SB P
Participants	N 12 Hyp Age 38
Interventions	SR 67 Dur 56
Outcomes	DBP
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	High risk	SBP effect not reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1009 Ambrosioni 1982.

Methods	SB CO
Participants	N 25 Hyp Age 23
Interventions	SR 60 Dur 42
Outcomes	SBP DBP
Notes	LoFo:1 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 1
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1010 Myers 1982.

Methods	Op CO
Participants	N 136 Norm Age 39
Interventions	SR 130 Dur 14
Outcomes	SBP DBP
Notes	Included 182 LoFo: 46 IT: yes (results not shown, but reported to be "similar")
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow‐up 46/182
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1011 MacGregor 1982.

Methods	DB CO
Participants	N19 Hyp Age 49
Interventions	SR 76 Dur 28
Outcomes	SBP DBP Aldo Renin
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind study

1012 Beard 1982.

Methods	Op P
Participants	N90 Hyp Age48
Interventions	SR124 Dur 84
Outcomes	SBP DBP
Notes	Included 113 LoFo:23 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up LS: 11/56; US: 12/57
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1013 Puska 1983.

Methods	SB P
Participants	N38 Norm Age40
Interventions	SR90 Dur72
Outcomes	SBP DBP
Notes	LoFo: 4 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Lost to follow up normotensive, LS: 2/19; US: 0/19; Lost to follow up hypertensive, LS: 2/15; US: 0/19
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	outcome detection blinded

1015 Bulpitt 1984.

Methods	Op P
Participants	N 65 (M/F29/36)(B/W/A.0/65/0) Hypertension Age 54.6
Interventions	SR 59 (161‐102) Dur 90
Outcomes	SBP, DBP, Chol
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	The low sodium group received dietary advice, the reference group did not
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1016 Silman 1983.

Methods	Op P
Participants	N28 Hyp Age55
Interventions	SR 63 Dur 90
Outcomes	SBP DBP
Notes	LoFo: 7 IT: No Weighted average of BP effects obtained ar 1,2,3,6 and 12 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up LS: 0/12; US: 7/16
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1017 Sowers 1983.

Methods	Op CO
Participants	N 9 (M/F:9/0) Normotension Age 23
Interventions	SR 154 (196‐42) Dur 5
Outcomes	renin, Aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1018 Watt 1983.

Methods	DB CO
Participants	N18 Hyp Age52
Interventions	SR 56 Dur 28
Outcomes	SBP DBP Renin
Notes	Included 20 LoFo:2 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information
Selective reporting (reporting bias)	Low risk	Lost to follow up 2/20
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1019 Cooper 1984.

Methods	SB CO
Participants	N59 Norm Age16
Interventions	SR55 Dur 24
Outcomes	SBP DBP
Notes	Included 124(1984+1984b) LoFo: 11 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up: 11/24
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1021 Skrabal 1984.

Methods	Op CO
Participants	N30 Norm Age23
Interventions	SR137 Dur14
Outcomes	SBP DBP Aldo Renin NA A
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1023 Gillies 1984.

Methods	Op CO
Participants	N 24 (M/F:14/10)(B/W/A.0/24/0) Hypertension Age 56.7
Interventions	SR 77 (169‐92) Dur 42
Outcomes	SBP, DBP
Notes	LoFo:4. 24 of 28 completed the study. IT:No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up: 4/28
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1024 Erwteman 1984.

Methods	S BP
Participants	N94 (22 blacks) Hyp Age46
Interventions	SR58 Dur28
Outcomes	SBP DBP
Notes	Included 107 LoFo: 13 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 13/107. " No apparent relation between treatment and discontinuing the trial"
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1025 Koolen 1984.

Methods	Op CO
Participants	N20 Hyp Age41
Interventions	SR213 Dur14
Outcomes	SBP DBP Aldo Renin NA
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1026 Koolen 1984(2).

Methods	S CO
Participants	N25 Caucasians Hyp Age41
Interventions	SR 208 Dur 14
Outcomes	NA
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1027 Fagerberg 1984.

Methods	Op P
Participants	N30 Hyp Age51
Interventions	SR99 Dur63
Outcomes	SBP DBP
Notes	Included 34 LoFo: 4 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Lost to follow up 4/34. Group association unclear
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1028 Maxwell 1984.

Methods	Op P
Participants	N30 Hyp Age 46
Interventions	SR161 Dur 84
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1029 Richards 1984.

Methods	SB CO
Participants	N12 Hyp Age36
Interventions	SR100 Dur28
Outcomes	SBP DBP Aldo Renin NA
Notes	Included 16 LoFo: 4 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 4/16
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1030 Resnick 1985.

Methods	Op CO
Participants	N12 Hyp Age
Interventions	SR190 Dur5
Outcomes	SBP DBP Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1031 Tuthill 1985.

Methods	DB P
Participants	N 191 (M/F:0/191) Normotension Age 17
Interventions	SR 14 (600 mg) Dur 56
Outcomes	SBP, DBP
Notes	LoFo: 13. 191 of 204 completed the study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 13/204. Group association unclear
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1032 Skrabal 1985.

Methods	SB CO
Participants	N34 Norm Age23
Interventions	SR144 Dur14
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1034 Watt 1985.

Methods	DB CO
Participants	N31 Norm Age23
Interventions	SR60 Dur28
Outcomes	SBP DBP
Notes	Included 75 (1985+1985b) LoFo: 9 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Low risk	The statistician randomised and labelled the containers of the tablets without calling on the research team
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 9/75
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1036 Richards 1986.

Methods	SB CO
Participants	N 8 males Norm Age36
Interventions	SR181 Dur4
Outcomes	SBP DBP Aldo Renin
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1037 Teow 1986.

Methods	Op CO
Participants	N9 Norm Age25
Interventions	SR 200 Dur 14
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1038 Logan 1986.

Methods	Op P
Participants	N86 Hyp Age47
Interventions	SR43 Dur180
Outcomes	SBP DBP
Notes	LoFo: ?
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1039 ANHMRCDS 1986.

Methods	SB P
Participants	N100 Hyp Age53
Interventions	SR70 Dur 84
Outcomes	SBP DBP
Notes	Included 107 LoFo:19 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS: 10/52; US: 9/55
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1040 El Ashry 1987.

Methods	SB CO
Participants	N13 Norm Age24
Interventions	SR222 Dur14
Outcomes	SBP DBP Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1042 Fuchs 1987.

Methods	Op CO
Participants	N6 Norm Age20
Interventions	SR99 Dur9
Outcomes	SBP DBP
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1044 Morgan 1987.

Methods	SB P
Participants	N20 Hyp Age58
Interventions	SR57 Dur60
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1045 Kurtz 1987.

Methods	DB CO
Participants	N5 Hyp Age58
Interventions	SR217 Dur7
Outcomes	SBP DBP
Notes	Included 7 LoFo: 2 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 2/7
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1046 Grobbee 1987.

Methods	DB CO
Participants	N40 Hyp Age24
Interventions	SR72 (129‐57) Dur42
Outcomes	SBP DBP Renin NA A Chol
Notes	Included 42 LoFo: 2 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 2/42
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1047 MacGregor 1987.

Methods	DB CO
Participants	N15 Hyp Age52
Interventions	SR100 Dur30
Outcomes	SBP DBP
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1048 Lawton 1988.

Methods	Op CO
Participants	N13 Norm Age24
Interventions	SR313 Dur6
Outcomes	SBP DBP Renin NA
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1049 Lawton 1988 H.

Methods	Op CO
Participants	N9 Hyp Age25
Interventions	SR328 Dur6
Outcomes	SBP DBP Renin NA
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1050 Morgan 1988.

Methods	SB CO
Participants	N16 Hyp Age63
Interventions	SR50 Dur14
Outcomes	SBP DBP Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors
Blinding of outcome assessment (detection bias) All outcomes	Low risk	outcome detection blinded

1051 Morgan 1988,2.

Methods	DB CO
Participants	N 8 Hypertension Age 63
Interventions	SR 67 (135‐68) Dur 14
Outcomes	SBP, DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1052 Shore 1988.

Methods	SB CO
Participants	N6 Hyp Age
Interventions	SR 97 Dur5
Outcomes	SBP DBP Aldo Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors
Blinding of outcome assessment (detection bias) All outcomes	Low risk	outcome detection blinded

1053 Sudhir 1989.

Methods	Op CO
Participants	N 6 (M/F:6/0)(B/W/A.0/6/0) Normotension Age 35
Interventions	SR 134 (163‐29) Dur 12
Outcomes	SBP, DBP, renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1054 Hargreaves 1989.

Methods	DB CO
Participants	N8 Norm Age23
Interventions	SR106 Dur14
Outcomes	SBP DBP Aldo Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1055 ANHMRCDS 1989.

Methods	Op P
Participants	N103 Hyp Age58
Interventions	SR63 Dur 48
Outcomes	SBP DBP
Notes	Included 111 LoFo:8 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS: 4/54; US: 4/57
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1056 MacGregor 1989.

Methods	DB CO
Participants	N20 Hyp Age57
Interventions	SR150 Dur30
Outcomes	SBP DBP Aldo Renin NA
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1057 Dimsdale 1990 W.

Methods	Op CO
Participants	N19 (White) Norm Age34
Interventions	SR183 Dur5
Outcomes	SBP DBP Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1058 Dimsdale 1990 WH.

Methods	Op CO
Participants	N17 (White) Hyp Age34
Interventions	SR 198 Dur 5
Outcomes	SBP DBP Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1059 Dimsdale 1990 B.

Methods	Op CO
Participants	N23 (Black) Norm Age34
Interventions	SR178 Dur5
Outcomes	SBP DBP Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1060 Dimsdale 1990 BH.

Methods	Op CO
Participants	N16 (Black) Hyp Age34
Interventions	SR178 Dur5
Outcomes	SBP DBP Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1061 Schmid 1990.

Methods	SB CO
Participants	N9 Norm Age32
Interventions	SR190 Dur7
Outcomes	SBP DBP
Notes	Allocation: random numbers LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1062 Schmid 1990 H.

Methods	SB CO
Participants	N9 Hyp Age36
Interventions	SR Dur
Outcomes	SBP DBP
Notes	Allocation: random numbers LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information: "with the help of random numbers"
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1063 HPTRG 1990.

Methods	SB P
Participants	N 579 Norm Age40
Interventions	SR23 Dur 1100
Outcomes	SBP DBP
Notes	Included 634 LoFo: 65 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS: 30/312; US: 35/322
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1064 Bruun 1990.

Methods	Op CO
Participants	N10 Norm Age46
Interventions	SR341 Dur4
Outcomes	SBP DBP Aldo Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1065 Bruun 1990 H.

Methods	Op CO
Participants	N12 Hyp Age47
Interventions	SR331 Dur4
Outcomes	SBP DBP Aldo Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1066 Sharma 1990.

Methods	SB CO
Participants	N15 Norm Age24
Interventions	SR192 (210.7‐18.7) Dur 7
Outcomes	SBP DBP Chol HDL LDL TG
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1067 Sharma 1990,2.

Methods	SB CO
Participants	N 40 (M/F:40/0)(B/W/A.0/40/0) Normotension Age 25
Interventions	SR 214 (239‐25) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 5. 40 of 45 completed the study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1068 Friberg 1990.

Methods	Op CO
Participants	N10 Norm Age33
Interventions	SR117 Dur 13
Outcomes	SBP DBP Renin NA
Notes	LoFo:4 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 4/10
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1069 Del Rio 1990.

Methods	DB CO
Participants	N 15 (B/W/A 0/15/0) Hypertension, Age 49
Interventions	SR 100 (190‐90) Dur 14
Outcomes	SBP, DBP, chol, trig
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1070 Parker 1990.

Methods	DB P
Participants	N31 Hyp Age50
Interventions	SR73 Dur28
Outcomes	SBP DBP
Notes	1990 + 1990 b Included 63 LoFo: 4 before randomization IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0 after randomization
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1072 Mtabaji 1990.

Methods	Op P
Participants	N30 (Black) Norm Age
Interventions	SR272 Dur7
Outcomes	SBP (MBP +1/3MBP) DBP (MBP‐1/3MBP)
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1073 Sharma 1991.

Methods	SB CO
Participants	N23 Norm Age25
Interventions	SR 246 Dur6
Outcomes	SBP DBP Aldo
Notes	1991 + 1991b included 25 LoFo. 2 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 2/23
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1074 Howe 1991.

Methods	Op CO
Participants	N 100 (M/F:52/48)(B/W/A.0/100/0) Normotension Age 13
Interventions	SR 81 (179‐98) Dur 28
Outcomes	SBP, DBP
Notes	LoFo:10. 90 of 100 completed the study. IT:No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 10/100
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1075 Mascioli 1991.

Methods	DB CO
Participants	N 48 (M/F:38/10) Norm Age52
Interventions	SR70 Dur28
Outcomes	SBP DBP
Notes	included 50 LoFo. 2 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 2/50
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1076 Carney 1991.

Methods	DB CO
Participants	N11 Hyp Age54
Interventions	SR102 Dur 42
Outcomes	SBP DBP Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1077 Singer 1991.

Methods	DB CO
Participants	N21(6 blacks) Hyp Age54
Interventions	SR91 Dur30
Outcomes	SBP DBP Aldo Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1078 Egan 1991.

Methods	DB CO
Participants	N27 Hyp Age39
Interventions	SR194 (214‐21) Dur7
Outcomes	SBP (MBP+1/3MBP) DBP (MBP‐1/3MBP) Renin NA l Chol LDL
Notes	Eandomisation schedule LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Low risk
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0/27
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1079 Gow 1992.

Methods	Op CO
Participants	N 9 Norm Age not given
Interventions	SR 94 (111‐17) Dur7
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1080 Huggins 1992.

Methods	DB CO
Participants	N 9 (M/F:7/2)(B/W/A.0/9/0) Normotension Age 25
Interventions	SR 97 (170‐73) Dur 14
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1081 TOHP I 1992.

Methods	SB P
Participants	N744 (131 blacks) Norm Age43
Interventions	SR 47 Dur 550
Outcomes	SBP DBP
Notes	LoFo: 0 IT: yes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Low risk	Randomization assignments were received from the coordinating center by telephone or sealed opaque envelopes were used to convey the treatment assignment.
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1082 Cobiac 1992.

Methods	DB P
Participants	N52 Norm Age66
Interventions	SR75 Dur28
Outcomes	SBP DBP
Notes	Included 114(1992+1992b) LoFo: 7 before randomization, 1 after IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 1/107
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1084 Benetos 1992.

Methods	DB CO
Participants	N20 Hyp Age42
Interventions	SR78 Dur 28
Outcomes	SBP DBP Aldo Renin NA A
Notes	Included 22 LoFo: 2 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 2/22
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1085 Sciarrone 1992.

Methods	DB P
Participants	N91 Hyp Age54
Interventions	SR82 Dur 56
Outcomes	SBP DBP Chol HDL LDL TG
Notes	95 included LoFO: 4 IT: No Lipid values were estimated on the basis of initial values(table 2) and changes (figure 4)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 4/95. Group association unclear
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1088 Ruppert 1993.

Methods	SB CO
Participants	N30 Norm Age46 salt sensitive
Interventions	SR270 Dur7
Outcomes	SBP DBP Aldo Renin NA
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1091 Burnier 1993.

Methods	Op CO
Participants	N16 Norm Age29
Interventions	SR186 Dur6
Outcomes	SBP DBP Aldo Renin
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1093 Sharma 1993.

Methods	SB CO
Participants	N16 Norm Age24
Interventions	SR 224 Dur7
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1094 Sharma 1993,2.

Methods	Op CO
Participants	N 15 (M/F:15/0)(B/W/A.0/15/0) Normotension Age 25
Interventions	SR 198 (219‐21) Dur 6
Outcomes	Renin, aldo, NE
Notes	LoFo: 5. 15 of 20 completed the study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Randomisation according to a Latin‐Square design
Blinding (performance bias and detection bias) All outcomes	High risk	Open
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 5/20
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1095 Fliser 1993.

Methods	SB CO
Participants	N8 Norm Age25 +Doxazosin
Interventions	SR190 (211‐21) Dur8
Outcomes	SBP (MBP+1/3MBP) DBP (MBP‐1/3MBP) NA Chol HDL LDL TG
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1097 Nestel 1993.

Methods	DB P
Participants	N36 Norm Age66
Interventions	SR56 Dur42
Outcomes	SBP DBP
Notes	Included 70 (1993+1993b) LoFo: 4 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 4/70. Group association unclear
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1099 Donovan 1993.

Methods	SB CO
Participants	N8 Norm Age36
Interventions	SR152 Dur5
Outcomes	SBP DBP Aldo Renin
Notes	LoFo. 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1100 Fotherby 1993.

Methods	DB CO
Participants	N17 Hyp Age73
Interventions	SR79 Dur 35
Outcomes	SBP DBP Aldo Renin
Notes	Included 18 LoFo. 1 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 1/18
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1101 Redon‐Mas 1993.

Methods	Op P
Participants	N418 Hyp Age55
Interventions	SR104 Dur28
Outcomes	SBP DBP
Notes	574 included LoFo: 156 IT: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up LS: 57/287; US: 99/287
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1102 Ruilope 1993.

Methods	DB P
Participants	N19 Hyp Age
Interventions	SR69 Dur21
Outcomes	SBP DBP
Notes	LoFo. 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1103 Del Rio 1993.

Methods	DB CO
Participants	N30 Hyp Age49
Interventions	SR151 (198‐47) Dur 14
Outcomes	SBP DBP Renin Chol HDL TG
Notes	Included 47 LoFo. 17 IT: no
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 17/47
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1104 Overlack 1993.

Methods	SB CO
Participants	N30 salt sensitive Norm Age46
Interventions	SR270 Dur7
Outcomes	Aldo Renin NA
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1107 MacFadyen 1994.

Methods	DB CO
Participants	N 12 (M/F:12/0)(B/W/A.0/12/0) Normotension Age 24
Interventions	SR 40 (165‐115) Dur 4
Outcomes	SBP, DBP, renin
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Low risk	Independently prepared schedule by Department of Pharmacy
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1108 Buckley 1994.

Methods	SB CO
Participants	N12 (3 blacks) Hyp Age49
Interventions	SR 296 Dur 5
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1109 Zoccali 1994.

Methods	SB CO
Participants	N 15 Hyp Age 45
Interventions	SR 163 Dur 7
Outcomes	SBP DBP Aldo Renin
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1110 Jula 1994.

Methods	Op P
Participants	N76 Hyp Age44
Interventions	SR57 Dur365
Outcomes	SBP DBP Aldo Renin NA A
Notes	Included 91 LoFo: 15 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1111 Howe 1994.

Methods	DB P
Participants	N 56 (M/F:31/25)(B/W/A.0/56/0) Hypertension Age 55
Interventions	SR 80 (158‐78) Dur 42
Outcomes	SBP, DBP, aldo
Notes	LoFo:5. 56 of 61 completed the study. IT:No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 5/61. Group association unclear
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1112 Iwaoka 1994.

Methods	Op CO
Participants	N 31 (M/F:17/14)(B/W/A.0/0/31) Hypertension Age 48
Interventions	SR 266 (298‐32) Dur 7
Outcomes	SBP, DBP
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1113 Miller 1995.

Methods	DB CO
Participants	N 36 (M/F:36/0)(B/W/A.0/36/0) Normotension Age 23
Interventions	SR 58 (191‐133) Dur 14
Outcomes	SBP, DBP, NE
Notes	LoFo: 4. 36 of 40 completed the study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 4/40
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1114 Fliser 1995.

Methods	Op CO
Participants	N 14 (M/F:14/0)(B/W/A.0/14/0) Normotension Age 26
Interventions	SR 180 (203‐23) Dur 7
Outcomes	MAP, renin, NE
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1115 Doig 1995.

Methods	DB CO
Participants	N 81(M/F 81/0 (B/W/A 0/81/0) Normotension, Age 25
Interventions	SR 112 (130‐18) Dur 4
Outcomes	SBP, DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1116 Stein 1995.

Methods	Op CO
Participants	N 7 (M/F:7/0)(B/W/A.0/7/0) Normotension Age 33.7
Interventions	SR 183 (201‐18) Dur 5
Outcomes	SBP, DBP, renin, NE
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1117 Arrol 1995.

Methods	Op P
Participants	N 181 (M/F:95/86)(B/W/A.0/181/0) Hypertension Age 55
Interventions	SR 16 (122‐106) Dur 182
Outcomes	SBP, DBP
Notes	LoFo: 27. 181 of 208 completed study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 27/208. group association unclear
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1118 Draaijer 1995.

Methods	Op CO
Participants	N 10 (M/F:10/0)(B/W/A.0/10/0) Hypertension Age 41
Interventions	SR 131 (283‐24) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1119 Overlack 1995.

Methods	DB CO
Participants	N11 Hyp Age61
Interventions	SR240 Dur7
Outcomes	SBP (MBP+1/3MBP) DBP (MBP‐1/3MBP) Aldo Renin NA
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1122 Dubbert 1995.

Methods	P SB
Participants	N 122 (B/W/A.67/55/0) Hypertension Age 62
Interventions	SR 45 (187‐142) Dur 90
Outcomes	SBP, DBP
Notes	LoFo: 36. 122 of 158 completed the study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	random number table, randomisation procedure stratified by race
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up LS:24/106; US: 12/52
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1124 Weir 1995.

Methods	SB CO
Participants	N11 (8 black) Hyp Age60 sodium sensitive
Interventions	SR146 Dur14
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1125 Grey 1996.

Methods	DB CO
Participants	N34 Norm Age23
Interventions	SR133 (185‐52) Dur7
Outcomes	SBP DBP Chol HDL LDL TG
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1126 Feldman 1996.

Methods	DB CO
Participants	N5 Norm Age27
Interventions	SR176 Dur7
Outcomes	SBP (MBP+1/3MBP) DBP (MBP‐1/3MBP) NA A Chol
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1127 Feldman 1996 H.

Methods	DB CO
Participants	N8 Hyp Age27
Interventions	SR178 Dur7
Outcomes	SBP (MBP+1/3MBP) DBP (MBP‐1/3MBP) NA A Chol
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1128 Schorr 1996.

Methods	DB CO
Participants	N16 Norm Age 64
Interventions	SR 74 (175.2‐104.8) Dur28
Outcomes	SBP DBP Aldo Renin Chol HDL LDL TG
Notes	Included 21 LoFo: 5 IT: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 5/21
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1129 Bellini 1996.

Methods	DB CO
Participants	N 43 (M/F:43/0)(B/W/A.0/43/0) Hypertension Age 46
Interventions	SR 121 (233‐112) Dur 14
Outcomes	SBP, DBP, renin, aldo, NE
Notes	LoFo: 12. 43 of 55 completed study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 12/55
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1130 Inoue 1996.

Methods	DB CO
Participants	N 14 (M/F:8/6)(B/W/A.4/7/3) Hypertension Age 46
Interventions	SR 293 (329‐36) Dur 7
Outcomes	SBP, DBP
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1131 Ferri 1996.

Methods	DB CO
Participants	N61 Hyp Age47
Interventions	SR264 Dur14
Outcomes	SBP DBP Aldo Renin
Notes	79 were included. 65 were randomised. LoFo: 4 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 4/65
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1132 Ishimitsu 1996 A.

Methods	Op CO
Participants	N HT: 23 (M/F:11/12) NT 7 (M/F:3/4)(B/W/A.0/0/30) Hypertension and normotension Age 54
Interventions	SR 194 (217‐23) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1133 Ishimitsu 1996 AH.

Methods	Op CO
Participants	N HT: 23 (M/F:11/12) NT 7 (M/F:3/4)(B/W/A.0/0/30) Hypertension and normotension Age 54
Interventions	SR 194 (217‐23) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1134 Cappuccio 1997.

Methods	DB CO
Participants	N47 Hyp Age67
Interventions	SR83 Dur 30
Outcomes	SBP DBP
Notes	Included 52 randomised 48 LoFo: 1 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 1
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1135 TOHP II 1997.

Methods	SB P
Participants	N1190 (203 blacks) High norm Age 42
Interventions	SR40 Dur 1100
Outcomes	SBP DBP
Notes	LoFo:161 IT: yes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Low risk	Randomization was performed by telephone contact with the TOHP coordinating center or by opening a sealed opaque envelope
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS: 79/596; US: 82/594
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1136 van Buul 1997.

Methods	Op CO
Participants	N 232 (M/F:0/232)(B/W/A.0/232/0) Normotension Age 28
Interventions	SR 65 (140‐75(week 28)) Dur 196
Outcomes	SBP, DBP
Notes	LoFo: 28. 242 of 270 completed the study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Low risk	Randomisation by a closed envelope system
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 28/270
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1137 Schorr 1997.

Methods	SB CO
Participants	N27 Norm Age25 sodium sensitive
Interventions	SR208 Dur7
Outcomes	SBP (MBP+1/3MBP) DBP (MBP‐1/3MBP)
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1138 McCarron 1997.

Methods	DB CO
Participants	N99 (24 blacks) Hyp Age52
Interventions	SR 55.4 (175.9‐120.5) Dur28
Outcomes	SBP DBP Chol HDL LDL TG
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1139 Meland 1997.

Methods	DB CO
Participants	N 16 (M/F:13/3)(B/W/A.0/16/0) Hypertension Age 50
Interventions	SR 66 (191‐125) Dur 56
Outcomes	SBP, DBP, chol, HDL
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1140 Fotherby 1997.

Methods	DB CO
Participants	N 17 (M/F:4/13)(B/W/A.0/17/0) Hypertension Age 73
Interventions	SR 79 (174‐95) Dur 35
Outcomes	Chol, HDL, LDL, Trig
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1141 Ferri 1998.

Methods	DB CO
Participants	N, HT: 39; NT 8 (B/W/A.0/47/0) Hypertension and normotension Age 45
Interventions	SR 170 (200‐30) Dur 14
Outcomes	Chol, HDL, LDL, trig
Notes	30/76 were eliminated/lost before randomization. 39 of 46 randomised hypertensives + 8 controls completed the study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Lost to follow up 7/46 HT
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1142 Knuist 1998.

Methods	Op P
Participants	N 361 (80% Caucasian) Pregnant women, Normotension Age 27.5
Interventions	SR 40 (124‐84) Dur 35 (mean duration)
Outcomes	DBP
Notes	LoFo: 67. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Low risk	Block randomisation. Treatment allocation in opaque sealed envelopes.
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up LS: 35/184; US: 32/177
Selective reporting (reporting bias)	High risk	SBP effect not reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1143 Bech 1998.

Methods	Op CO
Participants	N 12 (M/F:6/6)(B/W/A.0/12/0) Normotension Age 23.8
Interventions	SR 235 (273‐38) Dur 5
Outcomes	MAP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1144 Foo 1998.

Methods	DB CO
Participants	N 18, (8 males, 10 females) Normotensive Mean age 51
Interventions	SR 149 (227‐78) Dur 6
Outcomes	SBP DBP Renin Aldosterone
Notes	LoFo: 0 SDs estimated on the basis of p‐values
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1145 Wing 1998.

Methods	DB CO
Participants	N17 Hyp Age61
Interventions	SR59 Dur42
Outcomes	SBP DBP
Notes	39 included 19 randomised LoFo: 2 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 2/19
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1146 Herlitz 1998.

Methods	DB CO
Participants	N 6 (M/F 6/0)(B/W/A 0/6/0) treated hypertension (from150/106 to 124/82) Age 46
Interventions	SR 98 (325‐227) Dur 6
Outcomes	SBP DBP Renin
Notes	Included 8 LoFO: 2 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 2/8
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1147 Feldman 1999.

Methods	Op CO
Participants	N 8 (M/F:8/0)(B/W/A.0/8/0) Normotension Age 33
Interventions	SR 159 (207‐48) Dur 7
Outcomes	SBP, DBP, chol, NE
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1148 Damasceno 1999.

Methods	DB CO
Participants	N 39 (19HT and 20NT) (M/F:19/20)(B/W/A 39/0/0) Hypertension and normotension Age HT 43; NT 38
Interventions	SR HT: 81 (114‐33); NT: 180 (210‐30) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1149 Davrath 1999.

Methods	SB CO
Participants	N 8 Norm Age 25
Interventions	SR 95 Dur 5
Outcomes	SBP DBP Renin NA A
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1150 Schorr 1999.

Methods	SB CO
Participants	N 187 (M/F:187/0)(B/W/A.0/187/0) Normotension Age 25
Interventions	SR 206 (225‐19) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 13. 187 of 200 completed study. IT: No.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 13/200
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1151 Uzu 1999.

Methods	SB CO
Participants	N70 (Japanese) Hyp Age50
Interventions	SR173 (204‐31) Dur7
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1152 Chiolero 2000.

Methods	Op CO
Participants	N Hyp: 38 (M/F:21/17); Norm: 12 (M/F:6/6) (B/W/A.0/50/0) Hypertension and normotension Age 43 and 40
Interventions	SR 183 (255‐72) and 201 (265‐64) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 5. 38 of 43 and 12 of 12 completed study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 5/43 (Hyp) and 0/12 (Norm)
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1153 Bruun 2000.

Methods	Op CO
Participants	N 42 (M/F:34/8)(B/W/A.0/42/0) Normotension Age 26
Interventions	SR 237 (273‐36) Dur 4
Outcomes	SBP, DBP, renin, aldo, NE, E, chol, HDL, LDL, Trig
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1154 Burnier 2000.

Methods	Op CO
Participants	N 15 (M/F:15/0)(B/W/A.0/15/0) Hypertension and normotension Age 22.7
Interventions	SR 131 (144‐13) Dur 7
Outcomes	SBP, DBP, renin, aldo, NE, E
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1155 Heer 2000.

Methods	Op CO
Participants	N 32 (M/F:32/0)(B/W/A.0/32/0) Normotension Age 25
Interventions	SR139 (226‐87) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1156 Barba 2000.

Methods	DB CO
Participants	N 7 (M/F:7/0)(B/W/A.0/7/0) Normotension Age 32
Interventions	SR 154 (177‐23) Dur 7
Outcomes	MAP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1157 Boero 2000.

Methods	Op CO
Participants	N 13 (M/F:10/3)(B/W/A.0/13/0) Hypertension Age 51
Interventions	SR 209 (270‐61) Dur 14
Outcomes	SBP, DBP, Chol, HDL, LDL, Trig,
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information

1158 Suzuki 2000.

Methods	Op CO
Participants	N 20 (M/F:9/11)(B/W/A.0/0/20) Hypertension Age 59
Interventions	SR 116 (167‐51) Dur 7
Outcomes	nocturnal MAP, NE and E
Notes	LoFo:0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1159 Ames 2001.

Methods	SB CO
Participants	13 (M/F: 6/7) Hyp Age 60
Interventions	SR 133 (265‐132) Dur 28
Outcomes	SBP DBP NA A TG: Chol: HDL: LDL:
Notes	21 patients included 8 diabetes patients excluded LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Single blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1160 DASH 2001 W.

Methods	DB CO
Participants	N54 Norm Non‐black Age 48
Interventions	SR55 Dur30
Outcomes	SBP DBP not mentioned, see DASH 2
Notes	LoFo: 5% IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 5%
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The personnel involved in the collection of the outcome data were unaware of participants diet assignment

1161 DASH 2001 WH.

Methods	DB CO
Participants	N37 Hyp Non‐black Age 48
Interventions	SR 55 Dur 30
Outcomes	SBP DBP not mentioned, see DASH 2b
Notes	LoFo: 5% IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 5%
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The personnel involved in the collection of the outcome data were unaware of participants diet assignment

1162 DASH 2001 B.

Methods	DB CO
Participants	N68 Norm Black Age 48
Interventions	SR55 Dur30
Outcomes	SBP DBP not mentioned, see DASH 2c
Notes	LoFo: 5% IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 5%
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The personnel involved in the collection of the outcome data were unaware of participants diet assignment

1163 DASH 2001 BH.

Methods	DB CO
Participants	N46 Hyp Black Age 48
Interventions	SR 55 Dur 30
Outcomes	SBP DBP not mentioned, see DASH 2d
Notes	LoFo: 5% IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 5%
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The personnel involved in the collection of the outcome data were unaware of participants diet assignment

1168 Cuzzola 2001.

Methods	DB CO
Participants	N 19 Hyp Age 47
Interventions	SR 161 Dur: 14
Outcomes	SBP DBP Aldo Renin
Notes	Data available in patients in upper tertile of sodium excretion (19 of 55 patients)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	High risk	Data available in patients in upper tertile of sodium excretion (19 of 55 patients)
Selective reporting (reporting bias)	High risk	Only BP data for the upper sodium reduction tertile was reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1169 Seals 2001.

Methods	Op P
Participants	N 35 (M/F:0/35)(B/W/A.0/34/1) Hypertension Age 64
Interventions	SR 46 (132‐86) Dur 90
Outcomes	SBP, DBP, Chol, HDL, LDL, Trig
Notes	LoFo: 4. 35 of 39 completed the study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS: 1/18; US: 3/21
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1170 TONE 2001 W.

Methods	SB P
Participants	N 471 (non‐blacks) Hyp Age 66
Interventions	SR 40 DUR: 105
Outcomes	SBP DBP
Notes	2001 + 2001b included 681 (LS: 340; US: 341) Attended last visit: LS 310; US: 314 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 57/681. Group association unclear
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1171 TONE 2001 B.

Methods	SB P
Participants	N 142 (blacks) Hyp Age 66
Interventions	SR 40 DUR: 105
Outcomes	SBP DBP
Notes	2001 + 2001b included 681 (LS: 340; US: 341) Attended last visit: LS 310; US: 314 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 57/681. Group association unclear
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1172 Johnson 2001.

Methods	DB CO
Participants	N 40 Hypertension Age 69
Interventions	SR 73 (185‐112) Dur 14
Outcomes	SBP, DBP
Notes	LoFo:6; 40 of 46 completed the study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Sequenced treatments in Latin square design
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 6/46
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1173 Manunta 2001.

Methods	SB CO
Participants	N20 (M/F: 16/4) Hyp Age 48
Interventions	SR 110 Dur 14
Outcomes	Renin Aldosteron
Notes	138 included in acute study. 20 with SR> 100 mmol included in 14 day study. LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1174 Kleij 2002.

Methods	Op CO
Participants	N 27 (M/F:20/7)(B/W/A.0/27/0) Norm Age 24.8
Interventions	SR 186 (236‐50) Dur 7
Outcomes	MAP Ren, Aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1175 Kerstens 2003.

Methods	Op CO
Participants	N 28 (M/F:21/7)(B/W/A.0/28/0) Norm Age 24
Interventions	SR 202 (248‐42) Dur 7
Outcomes	MAP Ren, Aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1176 Dishy 2003.

Methods	Op CO
Participants	N 25 (2 blacks, 23 whites) Norm Mean age 34 (18‐50)
Interventions	SR 300 (321‐21) Dur 6
Outcomes	SBP DBP Renin A
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1177 Nowson 2003.

Methods	Op CO
Participants	N 108 (M/F:44/64/20 dropouts)(B/W/A.0/108/0) normotension Age 47
Interventions	SR 90 (140‐50) Dur 28
Outcomes	SBP, DBP, renin
Notes	LoFo: 20. 108 completed study
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 20/128
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1178 Perry 2003.

Methods	Op CO
Participants	N 15 (M/F:15/0)(B/W/A.0/15/0) Normotension Age 26
Interventions	SR 105 (175‐70) Dur 5
Outcomes	SBP, DBP, renin, aldo, NE, Chol, trig
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1179 Nakamura 2003 A.

Methods	DB P
Participants	N 65 (M/F:41/24)(B/W/A.0/0/65) Hypertension and normotension Age 46.6
Interventions	SR 20 (1.4g) Dur 42
Outcomes	SBP, DBP,
Notes	LoFo 1
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS: 1/33; US: 0/32
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1180 Palacios 2004.

Methods	Op CO
Participants	N 40 (M/F:0/23/17 dropouts) (B/W/A.15/8/0) Normotension Age 13
Interventions	SR 86 (120‐34) Dur 21
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 17. 23 completed study
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 17/40
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1181 Beeks 2004.

Methods	OP CO
Participants	N 117 (M/F:67/50)(B/W/A.0/117/0) Hyp Age 54
Interventions	SR 99 (171‐72) Dur 7
Outcomes	SBP DBP Aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1182 Berge‐Landry 2004.

Methods	Op CO
Participants	N 48 (M/F:38/10)(B/W/A.12/34/2) Hyp Age 51
Interventions	SR 285 (309‐24) Dur 28
Outcomes	SBP DBP Cho Trig
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1183 Gates 2004.

Methods	DB CO
Participants	N 12 (M/F:6/6)(B/W/A.0/12/0) Hyper Age 64
Interventions	SR 95 (155‐60) Dur 28
Outcomes	SBP DBP Chol, HDL, LDL, Trig, Renin, NE, E
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1184 Harsha 2004.

Methods	DB CO
Participants	N 193 (M/F:89/104)(B/W/A.57/136/0) Mixed Hyper/Norm Age 49
Interventions	SR 77 (141‐64) Dur 30
Outcomes	Chol, HDL, LDL, Trig, Renin, NE, E
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1185 Zanchi 2004.

Methods	DB CO
Participants	N 10 (M/F:10/0)(B/W/A.0/10/0) Normotension Age 25
Interventions	SR 250 (270‐20) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1186 Forrester 2005 N.

Methods	Op CO
Participants	58 Nigerians (M/F: 34/24) Norm (114.6/72.9) Mean age 46.6 (25‐55)
Interventions	SR 72.2 Dur 21
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Block randomisation
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1187 Forrester 2005 J.

Methods	Op CO
Participants	56 Jamaicans (M/F: 34/22) Norm (125.9/76.3) Mean age 40.8 (25‐55)
Interventions	SR 78.8 Dur 21
Outcomes	SBP DBP
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Block randomisation
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1188 Swift 2005.

Methods	DB CO
Participants	N 40 (M/F:17/23)(B/W/A 40/0/0) Hypertension Age 50
Interventions	SR 78 (167‐89) Dur 28
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 7. 40 of 47 completed study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 7/47
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1189 Damgaard 2006.

Methods	Op CO
Participants	N 14 (M/F:14/0)(B/W/A.0/14/0) Norm Age 57
Interventions	SR 129 (188‐59) Dur 7
Outcomes	SBP DBP NE and E
Notes	LoFo: 2 excluded because of side effects
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 2/14
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1190 Takahashi 2006.

Methods	Op CO
Participants	N 448 (M/F:145/303)(B/W/A.0/0/448) Hypertension (107) and normotension (341) Age 56.4
Interventions	SR 38 (237‐199) Dur 365
Outcomes	SBP, DBP
Notes	LoFo: 102. 448 of 550 completed study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation: computer generated random number
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 102/550
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1191 Melander 2007.

Methods	DB CO
Participants	N 39 (M/F: 20/19) Mixed hypertensive and normotensive (144/90.6) Age 53
Interventions	SR 89 (140‐51) Dur 28
Outcomes	SBP DBP renin
Notes	LoFo: 7. 39 completed. IT: No Diet + salt capsules/placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 7/46
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1192 Townsend 2007.

Methods	Op CO
Participants	N 20 (M/F:12/8)(B/W/A.10/9/1) Norm Age 30
Interventions	SR 171 (194‐23) Dur 6
Outcomes	SBP DBP Aldo Renin
Notes	Randomized 21. LoFo: 3 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Prespecified randomised blocked table
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 3/21
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1193 Dengel 2007.

Methods	DB CO
Participants	N 28, 10 males, 18 females, 5 blacks, 23 whites Hypertension Mean age 63
Interventions	SR 155 (191‐36) Dur 8
Outcomes	SBP ‐10 DBP ‐4 Renin 1.64 ng/s Aldo 334.2
Notes	LoFo: 0 Blood pressure effects estimated from figure 1. The effects of two genotype groups were added to one group and calculated as simple means.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1194 Tzemos 2008.

Methods	DB CO
Participants	N 16 (M/F:16/0)(B/W/A.0/16/0) Normotension Age 27
Interventions	SR 149 (225‐76) Dur 5
Outcomes	SBP, DBP, renin, aldo, chol, HDL, LDL, Trig,
Notes	LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1195 Jessani 2008.

Methods	Op CO
Participants	N 184 (M/F:87/97)(B/W/A.0/184/0) Normotension Age 50
Interventions	SR 81 (138‐57) Dur 7
Outcomes	SBP, DBP
Notes	LoFo:16; 184 of 200 completed the study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation by computer generated numbers
Allocation concealment (selection bias)	Low risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 16/200
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1196 Paulsen 2009.

Methods	DB CO
Participants	N 22 (M/F:12/10)(B/W/A.0/22/0) Normotension Age 47
Interventions	SR 47 (357‐310) Dur 4
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 5. 22 of 27 completed study. IT: No.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 5/27
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1197 Dickinson 2009.

Methods	Op CO
Participants	N 29 (M/F: 7/22) Normotension (116/73) Mean age 63
Interventions	SR 92 (156‐64) Dur 14
Outcomes	SBP DBP
Notes	32 included. LoFo: 3 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	computer generated
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 3/32
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1198 He 2009.

Methods	DB CO
Participants	Whites: 77; Blacks: 75; Asians: 35 Hypertension (Baseline BP 147/91) Mean Age 50
Interventions	SR 55 (165‐110) Dur 42
Outcomes	SBP DBP Renin Aldosterone
Notes	LoFO: W/B/A: 6/6/6 IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated, ethnic stratification
Allocation concealment (selection bias)	Low risk	Tablets supplied by independent company
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 18/187
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1199 Meland 2009.

Methods	Op P
Participants	N 46 (M/F:34/12)(B/W/A.0/46/0) Hypertension Age 56
Interventions	SR 43 (126‐83) Dur 56
Outcomes	SBP, DBP, Aldo, Chol, Trig
Notes	LoFo: 0. 71 tested, 46 included.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0/46
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1200 Pimenta 2009.

Methods	Op CO
Participants	N 12 (M/F:4/8)(B/W/A.6/6) Hypertension Age 55.5
Interventions	SR 206 (252‐46) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	LoFo: 1. 12 of 13 completed study. IT: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 1/13
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1201 Nowson 2009.

Methods	Op P
Participants	N 111 women 59 normotensives and 35 hypertensives completed Mean age 59
Interventions	SR 42 (108‐66) Dur 98
Outcomes	SBP DBP
Notes	LoFo: 16 IT: No. Two different diets were compared and there was other differences between the diets than sodium intake. These differences were assumed not to influence blood pressure.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information. Randomisation stratified by BMI
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS: 7/53; US: 9/58
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1202 Weir 2010.

Methods	CO, SB
Participants	N 132 (M/F: 73/59, W/B/A: 115/15/2) Hypertension Mean age: 51.5
Interventions	SR 123 (208‐85) 28 days
Outcomes	SBP DBP
Notes	LoFo 17
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Single blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 17/132
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1203 Starmans‐Kool 2011.

Methods	CO DB
Participants	10 males Normotension Mean age 32
Interventions	SR 97 (191‐94) 14 days
Outcomes	SBP DBP
Notes	LoFo 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1204 Carey 2012.

Methods	Op CO
Participants	N 185 (M/F:72/113)(B/W/A.0/183/0) Norm Age 47
Interventions	SR 204 (188‐59) Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	No report of excluded participants. LoFo of those reported 0.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No report of screening of participants. LoFo of those reported 0.
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1205 Carey 2012 Hyperpath.

Methods	Op CO
Participants	N 211 (M/F:129/82)(B/W/A.Mixed) Hypertension Age 49.2
Interventions	SR 211 Dur 7
Outcomes	SBP, DBP, renin, aldo
Notes	No report of excluded participants. LoFo of those reported 0.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No report of excluded participants. LoFo of those reported 0.
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1206 Graffe 2012.

Methods	DB CO
Participants	N 21 (M/F:10/11)(B/W/A.0/11/0) Norm Age 26
Interventions	SR 172 Dur 4
Outcomes	SBP, DBP, renin, aldo
Notes	Included 25 LoFo: 4
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A computer‐generated randomization list was drawn up by an independent colleague.
Allocation concealment (selection bias)	Low risk	A copy of the list was given to the hospital kitchen, and the original was kept in a sealed envelope at the department. The code was revealed when the study was finished.
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 4/25
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1207 Krikken 2012.

Methods	Op, CO
Participants	N 65 (M/F:65/0)(B/W/A.0/65/0)
Interventions	SR 192 Dur 7
Outcomes	SBP, DBP, Ren, Aldo, Chol, HDL, LDL
Notes	No report of excluded participants. LoFo of those reported 0.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No report of excluded participants. LoFo of those reported 0.
Selective reporting (reporting bias)	Unclear risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1208 Todd 2012.

Methods	SB, Co
Participants	N 23 (M/F:5/18)(B/W/A.0/23/0) Normotension Age 43.7
Interventions	SR 140 Dur 28
Outcomes	SBP, DBP
Notes	28 screened, 25 included, 23 randomized. LoFo. 4
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization was carried out by a third party using http:// www.randomization.com to generate the randomization sequence for the tomato juice interventions.
Allocation concealment (selection bias)	Low risk	The sequence was given to the Dunedin hospital pharmacy, where a study dedicated pharmacist added the allocated amount of salt to the tomato juice.
Blinding (performance bias and detection bias) All outcomes	Low risk	Single blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 4/23
Selective reporting (reporting bias)	Unclear risk	No distinct selective reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The investigators remained blind to the randomization sequence throughout the study. Participants were initially blind to the randomization sequence, but once they began each phase of the intervention they were aware of the presence or absence of added salt. They were asked not to tell the investigator which tomato juice they had received.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1209 Bonfils 2013.

Methods	Op, CO
Participants	12 obese with treated hypertension, N 12 (M/F:5/7)(B/W/A.0/12/0), Age 43 12 obese with normal BP, N 12 (M/F:5/7)(B/W/A.0/12/0), Age 39 12 non‐obese controls with normal BP, N 12 (M/F:5/7)(B/W/A.0/12/0), Age 39
Interventions	SR 131 Dur 5
Outcomes	SBP, DBP
Notes	LoFo no information
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Simple randomization, that is tossing a coin to decide whether patients should have low‐salt diet followed by high‐salt diet or vice versa.
Allocation concealment (selection bias)	High risk	The primary investigator assigned participants to the interventions according to the randomization sequence. The patients were not blinded for treatment assignment.
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No report of excluded participants. LoFo of those reported 0.
Selective reporting (reporting bias)	Unclear risk	No distinct reporting bias
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1212 Mak 2013.

Methods	Op, CO
Participants	N 13 (M/F:12/1)(B/W/A.0/13/0) Normotension Age 24
Interventions	SR: 190 Dur: 7
Outcomes	SBP, DBP
Notes	No report of excluded participants. LoFo of those reported 0.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No report of excluded participants. Lost to follow up of those reported 0.
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information

1213 Mallamaci 2013.

Methods	Op, CO
Participants	N 32 (M/F:23/9)(B/W/A.0/32/0) Hypertension Age 48
Interventions	SR 165 Dur 14
Outcomes	SBP, DBP, renin, aldo
Notes	32 of 102 screened were randomized. LoFo: 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0/32
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1214 Dickinson 2014.

Methods	SB, CO
Participants	N 25 (M/F:/)(B/W/A.0/25/0) Normotension Age 35.1
Interventions	SR 42 Dur 42
Outcomes	SBP, DBP, renin, aldo,
Notes	Screened 87, Randomized 50, allocated to diet 34, received diet 25
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Single blind
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 9/34
Selective reporting (reporting bias)	Unclear risk	No distinct selective reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1215 Allen 2014.

Methods	Op, CO
Participants	N 70 (M/F:26/44)(B/W/A.0/70/0) Normotension Age 24
Interventions	SR 83 Dur 5
Outcomes	SBP, DBP
Notes	No report of excluded participants. LoFo of those reported 0.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No report of excluded participants. lost to follow up of those reported 0/70.
Selective reporting (reporting bias)	Unclear risk	No distinct selective reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1216 Barros 2015.

Methods	Op, P
Participants	N 35 (M/F:12/24) (B/W/A. ? Brazilians) Hypertension Age 55.5
Interventions	SR: 48 Dur: 28
Outcomes	SBP, DBP
Notes	38 of 56 screened were randomized. LoFo 3
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Participants were randomized "according to the order of visit"
Allocation concealment (selection bias)	High risk	"Participants received plastic bags containing the daily amount of salt." "Participants were not aware of the type of salt they were receiving" (but the researcher was.
Blinding (performance bias and detection bias) All outcomes	High risk	Single blind (participant)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS: 3/19; US: 0/19
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1217 Markota 2015.

Methods	Op, P
Participants	N 150 (M/F:77/73) (B/W/A. 0/150/0) Hypertension Age 59.4
Interventions	SR: 28 Dur: 60
Outcomes	SBP, DBP
Notes	150 of 171 fulfilling inclusion criteria were randomized. LoFo 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Low risk	instructions in sealed envelopes
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0/150
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1218 Visser 2008.

Methods	Op, CO
Participants	N 34 (M/F:34/0)(B/W/A.0/34/0) Normotension Age 26.5
Interventions	SR 181 Dur 7
Outcomes	SBP, DBP, renin, aldo, cholesterol
Notes	No report of excluded participants. Lost to follow up of those reported 0.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No report of excluded participants. Lost to follow up of those reported 0.
Selective reporting (reporting bias)	Unclear risk	No distinct selective reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open study: Detection bias due to knowledge of the allocated interventions by outcome assessors

1219 Sharma 3 1993.

Methods	SB, CO
Participants	N 18 (M/F:18/0)(B/W/A.0/18/0) Normotension Age 24
Interventions	SR 218 Dur 7
Outcomes	SBP, DBP
Notes	No report of excluded participants. Lost to follow up 0.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0/18
Selective reporting (reporting bias)	Low risk	No distinct selective reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1220 Gomi 1998.

Methods	Op, CO
Participants	N 12 (M/F:8/4)(B/W/A.0/0/12) Hypertension Age 51.8
Interventions	SR 70 Dur 7
Outcomes	SBP, DBP, renin, aldosterone, noradrenalin
Notes	LoFo 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0.
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1221 Facchini 1999.

Methods	Op, CO
Participants	N 19 (M/F:17/2)(B/W/A.0/19/0) Normotension Age 43
Interventions	SR 168.7 Dur 5
Outcomes	SBP, DBP, renin, aldosterone
Notes	LoFo 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1222 Pechere‐Bertschi 2000.

Methods	Op, CO
Participants	N 35 (M/F:0/35)(B/W/A.0/35/0) Normotension Age 28.9
Interventions	SR 177.8 Dur 7
Outcomes	SBP, DBP, renin, aldosterone, noradrenalin
Notes	LoFo 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0/35
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1223 Pechère‐Bertschi 2003.

Methods	Op, CO
Participants	N 27 (M/F:0/27)(B/W/A.0/27/0) Normotension Age 26
Interventions	SR 192.8 Dur 7
Outcomes	SBP, DBP, renin, aldosterone, noradrenalin, adrenalin
Notes	LoFo 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0/27
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1224 Ho 2007.

Methods	Op, CO
Participants	N 25 (M/F:8/17)(B/W/A.0/25/0) Normotension Age 48.8
Interventions	SR 206.9 Dur 14
Outcomes	SBP, DBP, renin, aldosterone
Notes	101 screened, 44 included, LoFo 19
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	Lost to follow up 19/44
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1225 Gijsbers 2015.

Methods	DB, CO
Participants	N 36 (M/F:24/12)(B/W/A.0/36/0) Hypertension Age 65.8
Interventions	SR 206.9 Dur 28
Outcomes	SBP, DBP, cholesterol, triglyceride, HDL, LDL
Notes	83 screened, 37 randomized, lost to follow up 1
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	computer‐generated table
Allocation concealment (selection bias)	Low risk	independent person
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	lost to follow up 1/37
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind study

1226 Cavka 2015.

Methods	SB, P
Participants	N 54 (M/F:0/54)(B/W/A.0/54/0) Normotension Age 20
Interventions	SR 149.4 Dur 7
Outcomes	SBP, DBP, renin, aldosterone
Notes	LoFo 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Single blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up LS: 0/24; US: 0/30
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

1227 McManus 2015.

Methods	Op, CO
Participants	N 60 (M/F:27/33)(B/W/A.0/60/0) Normotension Age 50.1
Interventions	SR 102.7 Dur 5
Outcomes	Aldosterone
Notes	LoFo 0
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow up 0/60
Selective reporting (reporting bias)	Low risk	No distinct selective outcome reporting
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open study: Performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome detection blinded

A: adrenaline; Age: mean age of persons in trial; Chol: cholesterol; CO: cross‐over; DB: double blind; DBP: net change of diastolic blood pressure, mmHg; Dur: duration of intervention, days; HDL: high‐density lipoprotein; Hyp: hypertensive; LDL: low‐density lipoprotein; TG: triglyceride; LoFo: number lost to follow‐up; IT: "intention‐to‐treat" of those lost to follow‐up; N: number of persons in trial; NA: noradrenaline; Norm: normotensive; Op: open; P: parallel; SB: single‐blind; SBP: net change of systolic blood pressure, mmHg; SR: sodium reduction, mmol/24hours

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Anderson 1990	No data on urine sodium excretion
Dodson 1989	Includes only patients with diabetes mellitus
Imanishi 2001	Includes only patients with diabetes mellitus
Jula‐Karanko 1992	Duplicate: all data could be extracted from a later paper (1110 Jula 1994)
Jula‐Mäki 1992	Duplicate: all data could be extracted from a later paper (1110 Jula 1994)
Miller 1997	Includes only patients with diabetes mellitus
Mühlhauser 1996	Includes only patients with diabetes mellitus
Palmer 1989	No data on urine sodium excretion
Parfrey 1981	Withdrawal of paper by the authors due to erroneous form
Ruppert 1991	Sub‐study of 1088 Ruppert 1993
Ruppert 1994	Sub‐study of 1088 Ruppert 1993
Steegers 1991	Sub‐study of 1136 van Buul 1997

Differences between protocol and review

This review was invited on the basis of the first published version in JAMA in 1998 and therefore a formal protocol was not performed.

The purpose and the methods of the present update are essentially identical with the 1998 JAMA version and the previous Cochrane versions.

Contributions of authors

Graudal NA: Study design and definition of selection criteria; Data collection and analysis; Formulation of manuscript

Hubeck‐Graudal T: Data collection and analysis; Revision of manuscript.

Jürgens G: Data collection and analysis; Revision of manuscript.

Sources of support

Internal sources

• No sources of support supplied

External sources

• The A.P. Møller Foundation for the Advancement of Medical Science , Denmark.

  The A.P.M. foundation is a non‐profit funding source, which donated a grant for the pay of Niels Graudal

Declarations of interest

None.
 All authors are employed at public institutions. None of the authors has any connection with or receives funds from the food and salt industries or has commercial interests that might bear on this article.

New search for studies and content updated (no change to conclusions)