What Determines Human Sodium Intake: Policy or Physiology?^,,,,

Abstract

Past and current U.S. sodium and health policy focused on population-wide reductions in sodium intake. Underlying that policy are a number of assumptions that recent scientific publications challenged. The assumptions include the following: 1) that current intakes are excessive; 2) that the “healthy range” must be below current intakes; 3) that sodium intake can be substantially reduced by public policy; 4) that human intake is dictated by the sodium content of the food supply; and 5) that, unlike all other essential nutrients in which a healthy range is defined by a Gaussian distribution, lower sodium intake is always better. Drawing on the most current published evidence, this review addresses each of these long-standing assumptions. Based on worldwide surveys that assessed sodium intake by 24-h urinary sodium measurements, it is now evident that, across 45 societies and 5 decades, humans consume a reproducible, narrow range of sodium: ∼2600–4800 mg/d. This range is independent of the food supply, verifiable in randomized controlled trials, consistent with the physiologic regulators of sodium intake and is not modifiable by public policy interventions. These findings indicate that human sodium intake is controlled by physiology and cannot be modified by public health policies.

Background

No nutrition recommendation of the past 100 y is more deeply ingrained in society than “eat less salt.” It is beyond the scope of this review to trace the precise origins of this notion. However, it is clear that, in the past 50 y, it was driven by government policies that progressed from simply advising caution in one’s salt consumption to the dictates of today that all healthy individuals should substantially reduce their salt intake by at least one-third of what is typically consumed (1). For those aged >50 y and/or at risk of cardiovascular disease (CVD)6, intake should be <40% of current intakes (2). Government agencies and advocacy groups, such as the AHA and the Center for Science in the Public Interest (CSPI), became increasingly aggressive in calling for dramatic alterations in the food supply, likely due in part to frustration with the failure of this policy to modify the population’s sodium intake (3).

The “scientific roots” of this policy rest on several experimental studies and a limited number of human experiments. In the late 1930s, Goldblatt (4) created salt-induced hypertension in rats whose kidney mass had been reduced by five-sixths and then fed excessive sodium. In the mid-1940s, Kempner’s (5) use of extreme sodium restriction in a small cohort of patients with renal failure and malignant hypertension created the early clinical justification that high salt could induce hypertension and low salt could lower blood pressure (BP) led to several decades of research focusing on the notion that sodium restriction could be used to manage hypertension. This hypothesis was based primarily on an array of scientific models in which extreme amounts of salt intake (8–12 times human intake) induced elevated BP (6).

Several decades later, the first randomized clinical trials of sodium restriction in humans with hypertension were reported. However, these trials were initiated before the question of whether the BP of a population or prevalence of hypertension tracked with salt intake. When completed, the INTERSALT (International Study of Salt) study failed to document any association of salt intake with either the actual BP of a population or the prevalence of hypertension (7). Nevertheless, 167 sodium-restriction randomized clinical trials were subsequently reported (8). Of these, only a few involved individuals with normal BPs, and virtually all the interventions required moving the participants through a range of sodium intake that was never documented to be achievable in free-living individuals and produced minimal reductions in BP.

Implementation of a Low-Sodium Health Policy

Despite the lack of supporting evidence, early advocates of salt restriction began the call for a public health policy of population-wide salt reduction. One of their most compelling pleas came in 1982 in the cover story of Time magazine (9). The decision that year by the FDA to pursue such a policy launched the sequence of events that has the agency now proposing voluntary or possibly mandatory limits of the sodium content of specific foods items for the purpose of reducing CVD (10). That goal was solely predicated on the notion that even modest reductions in BP would substantially reduce CVD morbidity and mortality (11). Relying on an array of computer models that extrapolated small BP reductions to major CVD event reductions, advocates postulated that thousands of lives would be saved and health care costs dramatically reduced (12, 13). These computer models were based on wide-ranging assumptions that hid or ignored data regarding potentially serious feasibility and health consequences. These computer models failed consistently to incorporate the published data that documents the adverse health outcomes associated with reduced sodium intake. In addition, they routinely ignored the published data on normal sodium intake and the neuroscience data that provided the biologic mechanisms supporting that intake was a physiologically set variable (14).

The Assumptions

The development and expansion of the low-sodium health policy by the FDA and vigorously propagated by entities such as the AHA and CSPI is based on a number of unsupported assumptions that this review addresses: 1) that current intakes are excessive; 2) that “healthy ranges” must be below current intakes; 3) that sodium intake can be substantially reduced by public policy; 4) that human intake is dictated by the sodium content of the food supply; and 5) that, unlike all other essential nutrients in which a healthy range is defined by a Gaussian distribution, lower sodium intake is always better.

Is There a Normal or Healthy Range?

Although it is important to understand the validity of each of these assumptions, at the core is the simple issues of whether there is a normal or healthy range of sodium intake, and, if so, what are its limits and how is it determined. If the answers to these questions are not consistent with our current policy, then the policy of population-wide sodium restriction is unattainable and potentially harmful. As remarkable as it seems, this constellation of issues, until recently, was only assumed but was never adequately addressed. There have long been clues and data indicating that human sodium intake is a physiologic variable that, when disrupted, can produce unintended consequences (15).

In 2009, we reported a range of sodium intake in humans that was based on a large number (33) of government-sponsored surveys of 24-h urinary sodium excretion values (24-h UNaVs) from around the world from 1982 to 2008 (16). The 24-h UNaVs were collected in 19,151 presumably healthy, free-living individuals. The data were reported from these individual studies or surveys but until 2009 never collated into a single database. The range we reported had a mean value of 162.4 ± 22.4 mmol/d (3700 mg/d) and 95% CI: 115, 210 mmol/d (2650–4830 mg/d) (Fig. 1). What was most remarkable was that the data represented collections from multiple diverse cultures over a 3-decade period and their unique culinary habits. That fact spoke powerfully to the notion that the food supply did not dictate human intake.

FIGURE 1.

24-h urinary sodium excretion worldwide. Data from 62 survey sites in 33 countries; n = 19,151 individuals. The mean ± SD 24-h urinary sodium excretion value (UNaV) is 162.4 ± 22.4 mmol/d per person. IJE, International Journal of Epidemiology; IS, Intersalt Data from BMJ 1988; UNaV, urinary sodium excretion value. Reproduced from reference 16 with permission.

One year later, Bernstein and Willett (17) reported a summary analysis of 38 published studies from 1957 to 2003 that collected 24-h UNaVs from 26,271 individuals in the United States. They reported a mean sodium intake of 3526 ± 75 mg/d or 154 mmol/d, statistically within the range that we reported. They noted that the mean value was consistent across study year, age, gender, and race. These findings too were consistent with biologic or physiologic control and argued against the assumption that the sodium content of the American diet determines the intake of the society.

In 2013, we expanded our analysis of worldwide surveys or studies that collected 24-h UNaV (18). Those data, originally developed at the request of the 2013 Institute of Medicine Committee on Sodium Intakes in Populations, replicated our previous observation of the mean and range of human sodium intake. The new data represented 129 surveys involving 50,060 individuals. The mean and range of each of these datasets were within 1 SD of our previous estimate, and their combined mean and range was 158.3 ± 22.5 mmol/d, statistically identical to our previous estimate. The combined 2009 and 2013 datasets yielded a mean of 159.4 ± 22.3 mmol/d (3666 mg/d; range of 2622–4830 mg/d), with n = 69,011. When we divided the range of sodium intake by quintiles in this expanded cohort, the distribution depicted a classic bell-shaped curve consistent with the parabolic nature of the normal range of virtually all essential nutrients (Fig. 2). Based on the 95% CIs of this normal range, the lower limit of a healthy intake would be 2600–2700 mg/d (114–117 mmol/d), and the upper limit would be 4800–4900 mg/d (209–213 mmol/d).

FIGURE 2.

The normal distribution of sodium intake of the population by quintiles of the 24-h UNaV. Q, quintile; UNaV, urinary sodium excretion value. Reproduced from reference 18 with permission.

Is Current U.S. Sodium Intake “Excessive”?

The means and ranges of sodium intake described above are consistent with past estimates of sodium intake in the United States (17). A recent analysis by the CDC of estimated 24-h UNaV data from NHANES samples from 1988 to 2010 defined a comparable mean value for U.S. intake (∼3200 mg/d; 140 mmol/d) (19). The often-stated opinion that mean sodium intake in the United States is “excessive” is not consistent with the data. Sodium intake in the United States, as defined by the Bernstein and Willett publication (17) and the recent CDC data (19), has not changed over decades and readily matches the mean and range of intake from >45 other societies worldwide. Given the changes in the U.S. food supply and the dramatic variation in societal cuisine worldwide, it is difficult to envision how the sodium content of the food supply of a country could dictate such a reproducible range and mean sodium intake.

That conclusion does not rule out the likelihood that a small percentage of adults consume excessive sodium or salt, but that would be defined as intakes above the upper limit of the normal range that the 24-h UNaV data established: ∼4900 mg/d (215 mmol/d). There is a note of caution in this definition of excessive as discussed below. What was defined in the past as excessive in selected disease states, such as heart failure and renal disease, may reflect an appropriate physiologic adjustment to suppress the renin–angiotensin system and the adverse vascular actions of that hormone system (14).

Policy Cannot Change Sodium Intake

The simplest answer as to whether public policy can change sodium intake is the American experience. Since the mid-1980s, the U.S. sodium-and-health policy focused on reducing salt intake, particularly in individuals at risk of CVD. In the past decade, the effort was much broader, i.e., the entire population (20). However, sodium intake has not changed, despite the extensive public messaging effort, food labeling, and reformulation or introduction of hundreds of lower-sodium food products (19). Advocates of sodium restriction routinely and aggressively argued that the failure of the policy is the fault of the food industry (21). The more likely explanation is simply that public policy cannot change sodium intake because intake is set by human physiology (14).

Several lines of evidence support this explanation. The longest and largest NIH trial intended to test the BP benefits of a lower-sodium diet, the TOHP II (Trials of Hypertension Prevention II), used commonly available reduced-sodium foods, donated by industry, to construct low-sodium diets coupled with intense dietary counseling (22). The protocol called for a target intake of 85 mmol/d (∼2000 mg/d). In the first 6 mo, the lowest achievable sodium intake was 110–115 mmol/d, identical to the lower limit that the United States and worldwide 24-h UNaV data defined. Despite the remarkable structure of this experimental intervention, low-sodium foods, constructed diets, and intense counseling, sodium intake of the participants over the next 30 mo of the trial regressed to the mean intake defined by the population surveys: 138–145 mmol/d. Thus, even in this rigorously controlled intervention in several thousand motivated participants, a reduction in sodium intake could not be achieved or maintained outside the normal range.

The second line of evidence comes from the recent experience in the United Kingdom (23). In 2006, an aggressive campaign to lower the sodium intake of the UK population was initiated. The campaign included a large-scale, nationwide social marketing effort, a commitment from food manufacturers to dramatically lower the sodium content of many common foods, and for retailers to promote them within stores. In 2009, campaign supporters claimed that sodium intake was lowered by 12% based on 24-h UNaV surveys of the general population (24). However, as we and Bernstein and Willett reported, the claim by the UK government that the campaign was successful is not supported by their own data (16, 17). Using the 24-h UNaV surveys performed by UK agencies over the previous 2 decades, it is evident that the 12% decrease simply represented variation around a mean intake of ∼3700 mg/d.

In a recent update of the UK approach, advocates reported that the sodium content of the food supply decreased 20–55% depending on the food category, with a mean reduction of ∼35% (25). In the face of that substantial change in the food supply, 24-h UNaV declined by only 10%, from 155 to 140 mmol/d. Although this appears successful, 140 mmol/d remains well within 1 SD of the mean intake of the normal distribution of worldwide sodium or salt intake (18). Equally important is the discordance between the 35% reduction in the sodium content of the food supply and only a 10% change in intake (25). In the United Kingdom, the population adjusted its intake pattern by 1 of 2 strategies: 1) more food (calories); or 2) consumption of higher-sodium food items. Both explanations are consistent with physiologic mechanisms controlling intake when exposure to dietary sodium is reduced.

Physiology Maintains a Minimal and Optimal Intake

A multicenter, university-based study assessed the BP and sodium intake relation in 99 individuals with mild hypertension (26). Using an established, validated CRC protocol to achieve short-term, substantial reductions in sodium intake, individuals were stabilized at an intake of 76 mmol/d for 4 wk. They were then randomly assigned to receive either 100 mmol/d as slow sodium in a tablet form or a placebo. After 4 wk, the treatment was crossed over to the alternative sodium intake. As is shown in Table 1, with the administration of 100 mmol/d slow sodium, 24-h UNaV increased to 176 mmol/d, i.e., there was no change in food sodium intake. However, individuals randomly assigned to placebo increased their sodium intake from food by 45 mmol/d, resulting in an intake of 121 mmol/d. The placebo-phase amounts of sodium intake, 120 mmol/d, and slow-sodium phase intakes, 176 mmol/d, achieved in this double-blind, randomized trial, are consistent with the human organism maintaining a minimal sodium intake nearly identical to the lower limit of the normal range and approaching the upper limit defined by the worldwide surveys of 24-h UNaV.

TABLE 1.

Means ± SDs values for blood pressure, UNaV, and body weight in participants administered a placebo or sodium supplement.¹

	Sodium Chloride Intake
	Open-Label (Weeks 1–8)			Double-Blind (Weeks 9–16)
	Week 4 Ad Libitum	Week 8 Baseline*	P	Restricted	Supplemented	P
Blood pressure, mm Hg
Systolic	134.1 ± 11.1	132.1 ± 12.2	NS	133.6 ± 12.6	138.5 ± 12.8	<0.01
Diastolic	85.9 ± 6.3	84.7 ± 5.9	NS	84.8 ± 8.3	87.7 ± 8.1	0.01
24-h UNaV, mmol	140.6 ± 61.9	76.9 ± 32.4	≤0.0001	120.5 ± 68.9	175.9 ± 68.7	≤0.0001
Body weight, kg	89.1 ± 18.4	88.1 ± 17.9	NS	88.6 ± 18.1	88.4 ± 18.0	NS

¹Reproduced from reference 26 with permission. 24-h UNaV, 24-h urinary sodium excretion value.

*After 4 wk of open-label NaCl restriction (60 ± 80 mmol/24 h).

Sodium Appetite Is Centrally Regulated

Decades of neuroscience research defined neural circuits that are interfaced with peripheral hormonal signals to maintain sodium intake within an optimal range (14). Basic research identified the physiologic mechanisms underlying the maintenance of an appropriate sodium intake in vertebrates. Fundamental to that peripheral input to the brain are circulating amounts of angiotensin II and aldosterone, which are the principal stimuli to the neural circuits that activate sodium appetite (Fig. 3).

FIGURE 3.

 Various stimulatory and inhibitory signals act on the brain to regulate sodium appetite. CNS, central nervous system; Osm, osmolality. Reproduced from reference 14 with permission.

As sodium intake is reduced and delivery to renal tubules declines, plasma renin secretion (PRA) by the kidney increases. Angiotensin II production rises, and aldosterone secretion increases in parallel. The angiotensin II and aldosterone increases are reflected in the neural circulation and prompt an activation of sodium appetite. Data in humans published in 1972 defined the parabolic relation of 24-h UNaV to PRA (Fig. 4) (15). Recently reanalyzed, those data predicted the optimal intake of sodium in humans (Fig. 5) (18). The point on the PRA/24-h UNaV curve where the asymptote of the relation intersects the lower 95% CI should be the amount of sodium intake (24-h UNaV) associated with the population mean intake. This reanalysis generated an approximate mean sodium intake of 156 mmol/d (3550 mg/d), a value quite consistent with the mean intake that the 24-h UNaV surveys of populations worldwide identified.

FIGURE 4.

 Relation of noon plasma renin activity and the corresponding daily aldosterone excretion to the concurrent daily rate of sodium excretion in 52 normal individuals. Reproduced from reference 18 with permission.

FIGURE 5.

 Physiologic relation of the 24-h UNaV to PRA predicts mean sodium intake. PRA, plasma renin activity; UNaV, urinary sodium excretion value. Reproduced from reference 18 with permission.

Clinical Implications of Maintaining an Optimal Intake

Clinical evidence raises a potentially critical issue for patients whose renal perfusion is compromised, such as in congestive heart failure and renal disease, including diabetes. The elevated PRA/angiotensin II typically encountered in these disease states might dictate a neural-driven increase in sodium intake in an attempt to increase renal perfusion and suppress PRA, and the subsequent generation of angiotensin II and its pathologic impact on the heart and vasculature. This sequence of events would explain the observation that sodium intake is often increased in these disease states. Rather than these amounts of sodium intakes being causative, as often assumed, they are more likely a secondary, compensatory response mechanism. That interpretation is consistent with several recent studies in patients with congestive heart failure and renal disease (27–30). It would be predicted that abrogating that compensatory response by restricting salt intake actually enhances progression of the underlying disease. The adverse health outcomes data related to lower sodium intake supports that possibility: lower sodium intake is associated with increased all-cause and CVD mortality (27, 31–34).

Summary

As described here, many of the assumptions underlying the genesis of the U.S. sodium reduction health policy are not supported by data from basic science, clinical interventions, 24-h UNaV surveys, and, of greatest importance, measures of health outcomes. Setting aside the vehement objections to this synthesis of the scientific data by government agencies, such as the CDC (35) and FDA (36), as well as major advocacy groups, such as the AHA (37) and CSPI (38), the sodium and health policy of our nation should no longer be based on decades-old assumptions and computer models based upon them (39) but rather on proven, up-to-date science as articulated in the 2013 IOM Report on Sodium Intake in Populations (40) and recently validated in numerous publications (18,19,30,31,32,41,42,43). As stated in the editorial accompanying the most recent publications, “…the results argue against reduction of dietary sodium as an isolated public health recommendation.” (43).