Table 1.

Included Studies (N=11)

Author	Country	Outcome	Population	Intervention/Follow‐Up	Measurement Method	Results	Comments
Surrogate markers (2 randomized controlled trials [RCTs], 1 systematic review, 2 cohort [total of 5 studies])
Dickinson and colleagues30	Australia	Endothelial function, endothelin‐1	25 overweight or obese normotensive participants	6 weeks of “low” sodium 6 g salt (sodium 2400 mg)/24 h and 6 weeks of “usual” sodium 9 g salt (sodium 3600 mg)/24 h. 12‐week crossover	24‐h urinary sodium excretion; flow‐mediated dilatation (FMD)	Endothelin‐1 decreased by 14% after 6 weeks (P<.05) and this was associated with 45% increase in FMD (from 3.5 to 5.6; P<.001)	No changes to blood pressure (BP) between RCC cases and subcohort members. FMD not a hard outcome
Jablonkski (2013)	United States	Systolic BP (SBP), urinary marinobufagenin (MBG), and arterial stiffness	11 participants with SBP within 130–159 mm Hg and diastolic BP (DBP) <99 mm Hg	5 weeks on a low‐sodium diet with 4.4±0.5 g salt (sodium 1760±200 mg)/24 h and 5 weeks on a normal‐sodium diet with 8.2±0.5 g salt (sodium 3280±200 mg)/24 h. 10‐week intervention	24‐h urinary sodium excretion; urine and plasma MBG excretion; aortic pulse wave velocity	urinary MBG excretion, SBP, DBP, and aortic pulse wave velocity were lower during the low‐ vs normal‐sodium intake (25.4 vs 30.7 pmol/kg per day; 127 mm Hg vs 138 mm Hg and 77 mm Hg vs 81 mm Hg; and 700 cm/s vs 843 cm/s; P<.05)
Aburto and colleagues32	Australia, Belgium, Finland, France, Germany, the Netherlands, Norway, New Zealand, Sweden, United Kingdom, United States, Japan, Scotland, Taiwan. One cohort study included participants from 40 countries.	Cholesterol: total, low‐ and high‐density lipoprotein; triglycerides; urinary nor/adrenaline; plasma nor/adrenaline; urinary protein excretion protein:creatinine ratio; creatinine clearance; serum creatinine; glomerular filtration rate	5508 participants	Decreased sodium intake	Sodium intake was estimated to equal 24‐h urinary sodium excretion	Reduced sodium intake had no significant adverse effect on total cholesterol, low‐ and high‐density lipoprotein cholesterol, or triglyceride levels (mean difference 0.02 mmol/L, 0.03 mmol/L, −0.01 mmol/L, and 0.04 mmol/L, respectively). No effect of reduced sodium intake on urinary nor/adrenaline (mean difference −13.10 pg/mL and 17.13 pg/mL, respectively). No effect of reduced sodium on catecholamine levels (adrenaline 6.90 pg/mL, noradrenaline 8.23 pg/mL); nonsignificantly lower urinary protein excretion with reduced sodium intake (−76.61 μmol/L); lower urinary protein excretion with lower sodium intake; beneficial effect of lower sodium intake on renal function
Larsen and colleagues26	Denmark	Body weight, waist circumference, body fat, and fat free mass (FFM)	215 participants	Changes in body weight, waist circumference, body fat, and FFM were calculated after 6 years of follow‐up	24‐h urinary sodium excretion	Increase in body fat of 0.24 kg (P=.015, confidence interval, 0.05–0.43) per 6 g of salt (sodium 2400 mg)/24 h; decrease in FFM of −0.21 kg (P=.041, confidence interval, −0.40 to −0.001) per 6 g of salt (sodium 2400 mg)/24 h. No significant associations between 24‐h urinary sodium and change in body weight or waist circumference
Jain and colleagues25	United States	Total‐body percentage fat (TBPF)	2782 participants	Association of urinary sodium‐to‐potassium ratio with obesity; multiethnic cohort Dallas Heart study: race classified into African American (49.8%), white (30.8%), and Hispanic (17.2%) and other (2.2%); 12% diabetes mellitus and 36% hypertension	Ratio of sodium‐to‐potassium intake estimated from spot urine; TBPF measured by dual‐energy x‐ray absorptiometry; fasting venous blood	TBFP was 32%±10%; urinary sodium to potassium was 4.2±2.6; TBPF increased by 0.75% (95% confidence interval, 0.25–1.25; P=.003) and 0.43%(95% confidence interval, 0.15–0.72; P=.003) in unadjusted and adjusted models, respectively, for every 3‐unit increase in urinary sodium to potassium ratio
Blood pressure (1 RCT, 2 COCHRANE, and 1 systematic review [total of 4 studies])
Diaz and colleagues33	United States	Visit‐to‐visit (VVV) BP variability	1820 overweight participants with high‐normal DBP	TOHP II: Education and counselling on (1) weight loss, (2) sodium reduction, (3) combined weight loss, and sodium reduction vs (4) usual care. 36‐month follow‐up	24‐h urinary sodium excretion	VVV of SBP was not significantly different among the 3 intervention groups vs usual care (7.2, 7.1, 6.9, and 6.9 mm Hg respectively). Similarly, maintained sodium reduction throughout follow‐up did not have an effect on VVV	The aim of the TOPH II trial was not to test VVV, rather the adherence to and effects of the sodium reduction intervention among overweight adults
He and colleagues34	Multinational	BP	3230 participants (34 RCTs)	Decreased sodium intake in participants with normal and elevated BP	24‐h urinary sodium excretion	Elevated BP: sodium reduction 4.4 g of salt (sodium 1760 mg)/24 h and reduction of 5.39 mm Hg SBP and 2.82 mm Hg DBP. Normal BP: sodium reduction 4.4 g salt (sodium 1760 mg)/24 h and BP reduction of 2.42 mm Hg SBP and 1.00 mm Hg DBP
Aburto and colleagues32	Australia, Belgium, Finland, France, Germany, the Netherlands, Norway, New Zealand, Sweden, United Kingdom, United States, Japan, Scotland, and Taiwan. One cohort study included participants from 40 countries	BP	5508 participants	Decreased sodium intake	Sodium intake was estimated to equal 24‐h urinary sodium excretion	Sodium intake of <5 g of salt (sodium <2000 mg) vs >5 g of salt (sodium >2000 mg)/24 h reduced SBP by 3.39 mm Hg and DBP by 1.54 mm Hg
Rees and colleagues35	Multinational	Cardiovascular disease risk	18,175 participants/clusters in 44 RCTs (11 on BP and sodium: 6406 participants)	Dietary advice vs no advice or minimal advice	24‐h urinary sodium excretion	BP reduced by 2.61 mm Hg SBP and 1.45 mm Hg DBP. 24‐h urinary sodium excretion reduced by 2.3 g salt (sodium 940 mg) after 3–36 months. Serum cholesterol reduced; mean high‐density lipoprotein cholesterol and triglyceride unchanged
Substantive patient outcomes (3 cohort and 1 systematic review [total of 4 studies])
Deckers (2014)	The Netherlands	Renal cell cancer (RCC)	120,852 participants 55–69 years from The Netherlands Cohort Study (485 RCC cases included in case‐cohort analysis)	Follow‐up of 17.3 years	Food frequency questionnaire to assess sodium, potassium, and fluid intake; observed incidence of RCC cases	Sodium intake increased RCC risk (P trend=0.03). High‐sodium and low‐fluid intake increase RCC risk (P interaction=.02). Potassium intake and RCC risk was not associated	Exposure was only assessed at baseline. Food frequency questionnaire shows weak estimate of sodium intake
Cook and colleagues27	United States	Cardiovascular disease or cardiovascular disease death	2275 participants (30–54 years) from the Trials of Hypertension Prevention (TOHP) I and II who were not in sodium‐reduction intervention arm	Follow‐up of 10 years after end of TOHP I and 5 years after the end of TOHP II	24‐h urinary sodium excretion; review of medical records on notification of primary end point	There was a 17% increase in risk of cardiovascular disease per 2.5 g of salt (sodium 1000 mg)/24 h (P<.054)	Residual confounding of other healthy lifestyle behaviors
He and colleagues28	United Kingdom	BP, stroke, and ischemic heart disease	31,672 participants from the Health Survey for England from 2003 to 2011	Follow‐up of 9 years during the implementation of United Kingdom's National Salt Reduction Program	24‐h urinary sodium excretion in a random sample of 1589 participants 19–64 years; review of national statistics on deaths from ischemic heart disease and cardiovascular disease	Stroke mortality decreased by 42% (P<.001); ischemic heart disease decreased by 40% (P<.001); BP decreased by 3.0±0.33/1.4±0.20 mm Hg (P<.001); salt intake decreased by 1.4 g of salt (sodium 560 mg)/24 h (P<.001)	Does not quantify salt reduction contribution to stroke, and ischemic heart disease mortality “likely to play and important role”
Aburto and colleagues32	Australia, Belgium, Finland, France, Germany, the Netherlands, Norway, New Zealand, Sweden, United Kingdom, United States, Japan, Scotland, Taiwan. One cohort study included participants from 40 countries	All‐cause mortality; cardiovascular disease; stroke; coronary heart disease	5508 participants	Decreased sodium intake	Sodium intake was estimated to equal 24‐h urinary sodium excretion	Sodium intake was associated with an increased risk of stroke, stroke mortality, and coronary heart disease mortality (risk ratio: 1.24, 1.63, and 1.32, respectively)