Making Sense of the Science of Sodium

Abstract

Despite the Institute of Medicine’s commitment to base its nutrient intake recommendations in evidence, the 2004/2005 Dietary Reference Intakes for sodium were not supported by evidence, as the subsequent 2013 Institute of Medicine review admitted. In this review, I suggest an approach to setting nutrient intake requirements based in physiology. Briefly, the requirement of a given nutrient can best be said to be the intake that calls for the least adaptation or compensation by the intact organism. For sodium, evidence indicates that such an intake is typically between 3000 and 5000 mg/d.

DIETARY REFERENCE INTAKES: THE BACKGROUND

In the early 1990s, a decision was made by the Food and Nutrition Board of the Institute of Medicine (IOM) to the effect that, in the future, nutrient intake recommendations (ie, Dietary Reference Intakes [DRIs]), would be “evidence based.” Any implication that previous editions of the intake recommendations had not been based in evidence would certainly not be correct. What was to be different, going forward, was how the evidence was gathered and evaluated.1,2 The expectation was that this process would be explicitly set forth so that the basis for the recommendations would be transparent, and subsequent revisions would be built upon what the previously available evidence had supported. Although the objectives of this process seemed sensible, and even ideal, its implementation over the past 20-plus years has often been inconsistent and even internally contradictory. And, rather than eliminating controversy, both the process and the outcomes have, in many cases, been hotly contested. The casualties of the several controversies have been the American public, patients with chronic disease whose diets were altered to accord with the DRIs, and, for some nutrients (such as sodium), the food industry.

SALT CONCERNS

As has been exhaustively reviewed previously,3 the general populations of the United States and United Kingdom have been subjected to a steady program aimed at decreasing sodium intake, dating back to at least the early 1980s, and probably a decade or 2 earlier. The justification for this policy effort was the fact that blood pressure is, to some extent, dependent upon sodium intake, particularly in individuals deemed “salt sensitive.”4 It had long been recognized that high blood pressure is a risk factor for cardiovascular disease (CVD) and cardiovascular mortality and that reducing elevated blood pressure lowers that risk. These general relationships are widely accepted and are not in question. However, these findings derived from patients with hypertension were extrapolated to conclude that lowering sodium intake in nonhypertensive individuals would lower blood pressure in them as well and would thereby reduce risk of heart disease. There are 2 components to this presumption: (1) that lowering salt intake in normotensive individuals will, in fact, lower blood pressure meaningfully and (2) that lowering salt intake in normotensive individuals will reduce adverse health outcomes. Both are false. It is important to recall that in a recent Cochrane analysis of nearly 170 randomized controlled trials, Graudal et al5 found not a single example of a study with a blood pressure effect from sodium intake reduction in normotensive individuals. There were no studies of health benefits accruing to the reduction of salt intakes of healthy adults to levels below those prevailing in Europe and North America (~3450 mg/d; 150 mmol/d).4,6 Thus, the presumptions expressed in the 2004/2005 DRIs have never been supported by evidence. Nevertheless, a presumption of benefit continues to be expressed in the sodium intake recommendations of numerous otherwise authoritative bodies.7 Reflecting this lacuna, Drummond Rennie, editor of JAMA, was quoted in an interview in Science as saying that the “…authorities pushing the ‘eat-less-salt’ message had made a commitment to salt education that goes way beyond the scientific facts.”3

The problem with drawing any conclusion from the limited evidence available—and this cannot be stressed too strongly—was that the studies concerned had been done in individuals who already had a metabolic abnormality (ie, hypertension) and who often, as well, had above average sodium intakes.

In its review and evaluation of the more recent evidence (up to 2012), the IOM published a revised analysis in 2013,8 stating belatedly that there was no evidence of benefit for reduction of sodium intake below 2300 mg/d (100 mmol/d). Nevertheless, the 2004/2005 DRIs from the IOM have been allowed to stand and remain the basis for federal salt policy today.

In brief, blood pressure reduction is a reasonable proxy for health outcomes in hypertensive individuals on high sodium intakes, but it simply does not track health outcomes in normotensive individuals at average or below average sodium intakes. Finally, it is important to note that the 2004/2005 IOM task force did not evaluate the risk of adverse health outcomes, if any, produced as a consequence of lowering salt intake in nonhypertensive individuals,9 and it was in part to rectify this omission that the 2012/2013 IOM panel was convened.

SHIFTING SALT POLICY

To review, the 2004/2005 sodium intake recommendation, termed “AI” (for adequate intake), was set at 1500 mg/d (65 mmol/d) for adults up to age 50 years, 1300 mg/d (57 mmol/d) for adults between 50 and 70 years, and 1200 mg/d (52 mmol/d) for adults older than 70 years.5 As has been pointed out previously,10 an AI is specifically defined as the intake found in a healthy population.1,2 However, no first-world population has a sodium intake anywhere near the 2004/2005 IOM targets. Surprisingly, in his letter transmitting the 2013 report of the special panel of the IOM to the secretary of the Department of Health and Human Services,11 Harvey Fineberg, president of IOM, stated “…the evidence linking sodium intake to health outcomes supports current efforts by the Centers for Disease Control and Prevention (CDC) and other authoritative bodies to reduce sodium intake in the U.S. population below the current average adult intake of 3400 mg/d.” There is essentially nothing in the actual report to back that statement. Certainly, as already noted, there were no randomized controlled trials showing improved health outcomes as a result of reducing sodium intake from the current average (3450 mg/d) to 2300 mg/d, let alone 1500 mg/d.6

Here is where the evidence-based medicine (EBM) approach should have come to the rescue. In the absence of reliable evidence for benefit accruing to the intended reductions, the use of EBM would logically have led to the conclusion that no such reduction was justified. Despite Fineberg’s assurances, the evidence summarized in the IOM’s 2013 report does not support current efforts to reduce sodium intake in the US population below the average adult intake. However, it may be argued that absence of evidence supporting reduction does not, in itself, mean that doing so would not produce benefit. Thus, lacking hard evidence, one must then ask whether evidence of countervailing harm is associated with reduction in sodium intake below current population average values.

As it turns out, several recent population-based studies have shown persuasively that risk of both CVD and mortality follow U-shaped (or J-shaped) curves relative to sodium intake, with risk of mortality and CVD rising both as intakes drop below 3000 mg/d and as they rise above 7000 mg/d.12–15 In this behavior, sodium acts exactly like most nutrients.2,10 The reports concerned have dealt with patients with diabetes and CVD, as well as the general population. In all these studies, risk was lowest at a sodium intake in the range between 2800 and 6000 mg/d. Concordant with these findings is a report by Stolarz-Skrzypek et al,16 who pooled 2 large prospective European studies, with up to 15 years’ follow-up. They found a nearly 4-fold increase in cardiovascular mortality as sodium intake decreased from the highest tertile to the lowest and an approximate doubling of CVD events across the same decrease in intake. The long duration of observation in these studies virtually excludes reverse causality (ie, the possibility that the low-sodium-intake groups were such because of preexisting CVD). Finally, even in a large cohort of hypertensive patients (N = 398 419), lowering of blood pressure below “normal” values (130–139 mm Hg) prospectively resulted in increased risk of both mortality and end-stage renal disease.17

Although these papers11–16 are relatively recent and would not have been accessible to the panel formulating the 2004/2005 guidelines, their findings were not actually without precedent. For example, Alderman et al,18 in their 1995 publication of the Work-Site Hypertension Study, reported an approximate doubling of both CVD events and myocardial infarctions as sodium intake fell from the highest quartile to the lowest. In this study and in the pooled European16 studies, the highest sodium intake was actually not particularly high. In the Work-Site Hypertension Study, the boundary of the fourth quartile began at about 4000 mg/d, and in the European studies, the third tertile began at about 4600 mg/d, well within the range of lowest risk in the population-based studies.13–16

Based on the criterion of the intake that requires least adaptation or compensation by the intact organism, intakes of 3000 to 5000 mg/d seem to be optimal.

These studies focused mainly on the rise in risk of adverse outcomes at sodium intakes lower than prevailing intakes in the general population. Risk associated with substantially higher intakes, of course, is not to be discounted or dismissed. Nevertheless, in the current context, the emphasis is on intakes lower than current population averages. Here, the evidence from all the studies cited indicates that there is probable increased risk of harm at intakes below 2800 mg/d in normal-weight adults. In addition, it is now becoming clear also that sodium restriction in patients with congestive heart failure can actually worsen outcomes.19 As an aside, one must ask, if it is not good for sick people, why would one think it good for the well? Thus, considering this diverse body of evidence, and as the most recent IOM report indicated, lowering population-level intake recommendations below current intakes, and certainly below 2300 mg/d, cannot be defended by available evidence.

MECHANISMS OF RISK

The reason for the observed increase in cardiovascular risk at low sodium intakes is not hard to discern. In fact, consideration of the underlying physiology shifts the focus constructively from the phenomena concerned to the relevant body control systems. It also directs attention to the criteria used for the establishment of a “normal” or “ideal” intake. As I have pointed out elsewhere,20 and as others have suggested also,21 perhaps the best criterion for the determination of “normal” (at least where it can be applied) is the intake that requires the least day-to-day compensation or adaptation by the intact organism—adaptation needed precisely for homeostasis at prevailing intakes. It is important to keep in mind that the ultimate physiological purpose of sodium intake is precisely the maintenance of blood pressure. Demonizing sodium is not only unsupported by evidence but is counterphysiological as well, as it ignores sodium’s most basic function in mammalian bodies.

Adequate total body sodium content (and extracellular fluid sodium concentration) is necessary for maintenance of central blood volume and renal perfusion. For this reason, these variables are strongly defended by the body’s homeostatic apparatus. On the low intake side, these defense mechanisms include salt hunger and reduction of urine and sweat sodium losses.22,23 Together, these effects function to increase sodium intake and reduce losses and are mediated by the renin-angiotensin-aldosterone system (RAAS), which begins to be engaged as sodium intakes drop below 3000 mg/d in an average-weight adult.24,25 And on the high intake side, the salt receptors on the tongue “flip” from positive to negative; that is, they produce an aversive sensation that is quite unlike the response of the other 4 basic taste sensors and that thereby tends to decrease intake of salty foods.22

There is no disagreement about the importance or necessity of homeostatic compensation, as intakes and losses from the body fluctuate widely and adjustments must be made to offset these perturbations. However, the RAAS, in defending central blood volume, exacts a toll on several body systems when it is continuously deployed. This toll has been shown to include increased risk of myocardial infarction and cardiac death.26,27 The RAAS is, in effect, a “rescue” mechanism,22 invoked in response to serious threat and hence necessary for survival. One might reasonably argue that an intake that did not constantly evoke such compensation would be not only more salubrious for the organism but, in fact, the one that is to be recommended. The recently published U-shaped risk curves12–15 would place that intake in the range between roughly 3000 and 6000 mg sodium/d (Figure). Such a U-shaped curve is, in fact, the standard model used by the IOM for all nutrients.2 It is, in a sense, reassuring to note that sodium is thus like most other nutrients in that there is potential harm at both extremes of intake.

Figure.

Observed risk of cardiovascular events plotted as a function of sodium intake, redrawn from the data of O’Donnell et al.13 Note that risk rises both as sodium intake falls below 3 to 4 g/d and rises above intakes of 6 to 7 g/d and also that, in this dataset, the risk is numerically higher at lower rather than at higher intakes. Copyright 2014, Robert P. Heaney, MD. Used with permission.

As an illustration of the role of compensatory responses to reduced sodium intake, one may recall the observation of McCarron et al,28 more than 30 years ago, showing that sodium intake in National Health & Nutrition Examination Survey (NHANES) was inversely correlated with blood pressure, not directly as conventional wisdom asserts. This finding has been widely ignored or criticized29 as it simply could not be “correct.” But, in fact, such a relationship is precisely what one would expect as an expression of extracellular fluid homeostasis. The sodium requirement, as with essentially all nutrients, varies considerably from individual to individual. Those with a higher sodium requirement unconsciously choose higher sodium intakes, not for taste, but for maintenance of central volume.22 And those with lower requirements choose diets lower in sodium, again not for taste but as expression of the body’s wisdom. The finding of high salt intake in NHANES in individuals with lower blood pressure is thus not so much paradoxical, as an expression of homeostasis at work.

In conclusion, it is worth noting that the approach to “normal” nutrition based upon minimizing the need for compensation, which I have articulated here, constitutes, in effect, an aesthetic criterion, one testable through the methods of physiology, but not easily susceptible of testing by the methods of EBM. But then, as noted above, EBM had not actually been used in setting recent sodium intake recommendations in the first place.