Salt: How much less should we eat for health? Understanding the recent IOM report

Transcription

1 Salt: How much less should we eat for health? Understanding the recent IOM report We should all eat less salt but how much less? 1500 milligrams a day has been recommended as a target but the US Institute of Medicine caused a media storm this spring with a report that did not support this. Nancy R. Cook, a co-author of the report, explains the evidence, and the reasoning. Measuring salt intake is difficult. So is measuring the effects on health. The evidence is complex, contradictory, and unclear, but sensible recommendations can still be made The Institute of Medicine (IOM) released a report in May that reviewed the evidence on the effects of low sodium intake on health 1. It supported a population-wide lowering of sodium from the current average of about 3400 mg/day; but it did not lend support to current dietary guidelines, which have been in place since These recommend lowering of sodium intake to less than 2300 overall but to 1500 mg/day among certain subgroups, including all those over 50 years of age, African Americans, and those with hypertension, diabetes, or chronic kidney disease 2. Not surprisingly, the IOM report has caused much consternation in the press. It has also brought rather heated reactions from scientists and organisations, including the American Heart Association, which recommends a lowering of sodium to 1500 mg/day not just for subgroups but for everyone. As a member of the IOM committee, I would like to provide some background and some perspective on the report s conclusions. Please note that this article reflects the views of the author and does not represent the IOM or the committee. Blood pressure versus health outcomes The task of the committee was to review the effects of low sodium intake on health outcomes, which were defined as hard clinical endpoints. The previous guidelines were based primarily on studies of sodium and blood pressure. The evidence for the effect of sodium on blood pressure is strong, and is supported by numerous randomised trials, with a greater blood pressure reduction among those with current hypertension. An overview of trials of sodium reduction found an average decrease in systolic/diastolic pressures of 4.8/2.5 mmhg among hypertensive subjects and 1.9/1.1 mmhg in trials of normotensive subjects 3. While many trials of sodium included a lifestyle intervention in which participants were taught to consume foods with lower sodium, a lack of compliance is a problem in these trials it is difficult for participants to maintain low sodium intake on their own. The strongest evidence of a direct sodium effect comes from feeding studies. Participants in the DASH- trial of 2001 were given food that differed only in sodium level for thirty days each in a cross-over design 4. There was a consistent effect of lower sodium on lowering blood pressure overall and across groups defined by race, gender, and hypertension. These data on blood pressure, particularly from the DASH- trial, were used as evidence in developing the previous guidelines. The lowest sodium diet in DASH- had a target of 1150 mg/day, but the average level achieved was 1500 mg/day. Largely based on this result, Dietary Guidelines for Americans, 2005 (and 2010) recommended that everyone reduce sodium 6 october The Royal Statistical Society

2 to less than 2300 mg/day, and to 1500 mg/day among the susceptible subgroups noted above; these groups comprised roughly one-half of the US population. The American Heart Association (AHA) and the World Health Organization (WHO) went even further, recommending that everyone reduce their sodium consumption to 1500 mg/day or 2000 mg/ day, respectively. These blood pressure studies were reviewed by the IOM committee, but they were not considered in the conclusions regarding sodium s effects on cardiovascular disease () or other outcomes. The rationale was that while blood pressure is a strong intermediate variable, it is a surrogate, and beneficial effects on surrogates do not always translate into positive effects on clinical outcomes. Some examples are the effects of hormone therapy on low-density cholesterol, which didn t translate into a benefit on outcomes (although this has been attributed to differences in timing), and effects of various nutritional supplements. In the language of causal inference, while there may be an indirect effect of sodium through blood pressure (Figure 1a), the task was to evaluate evidence regarding the total effect on health outcomes, especially on. Evidence relating sodium and blood pressure alone was not considered strong enough. Reducing the nation s blood pressure might not of itself reduce the nation s heart disease. A question of quality In observational studies, as opposed to randomised trials, it is more difficult to define the sodium exposure. intake is notoriously difficult to measure. This has major implications for evaluating the strength of the evidence for or against sodium. One typical means of estimating intake of dietary nutrients in epidemiologic studies is through a food frequency questionnaire, which asks, for example, how often you consumed particular types of foods over the past month or year. While this does not necessarily reflect what the person ate on any given day, it is meant to reflect the long-term average intake for nutrients such as total and saturated fat, protein, and carbohydrates as well as micronutrients such as calcium and potassium. There may be systematic bias if a person under-reports all foods consumed. Adjusting for total reported calories, however, should provide reasonable estimates of relative rankings of consumption. Blood pressure an indicator for cardiovascular disease, but reducing blood pressure may not alone reduce the disease. istockphoto/webphotographeer It is difficult to measure sodium with the typical food questionnaire, though. It is far from being simply the amount of salt that we add to our plates at the table. Most of the sodium we consume comes from processed foods, and the sodium in these varies from brand to brand and even by item within brand. For example, sodium in microwave popcorn can vary from 160 to 620 mg. Soups are usually high in sodium, but may be low-sodium, reduced-sodium or low salt, and the labelling for these can be unclear. The salt added at the table or in cooking is of course another source, but even this is difficult to quantify with a food frequency questionnaire. In fact it contributes less than processed foods to overall sodium consumption. A more commonly used measure of assessing sodium intake in large populations is the 24-hour recall. This simply asks what you ate within the last 24 hours. This measure provides a generally inaccurate measure of average sodium consumption because it obviously changes from day to day. But such a measure is used in all the reports using data from the National Health and Nutrition Examination Surveys (NHANES). While one day s recall may be adequate for estimates of population averages, more than one non-consecutive day of diet recalls are needed to accurately capture individual intake. Besides the inherent day-today variability, the recall can be subject to systematic bias and should be corrected for total calories to allow for over- or under-reporting of all foods. The most accurate measure of sodium intake comes from sodium excretion. A 24- hour urine specimen provides an objective estimate unaffected by recall bias. This is the best measure so far available and is used in trials or observational studies as the current gold standard. But this too can suffer from bias, due to day-to-day variation or due to undercollection. An even better estimate would average sodium over several measures of excretion to reduce within-person variability. Overnight or 8-hour excretions or spot urines are sometimes used, but these are subject to diurnal variation and need to be calibrated to 24-hour levels. Evidence for cardiovascular disease and mortality We have discussed above the evidence linking sodium with blood pressure. What we really need, however, is evidence linking sodium with and this has been curiously conflicting. In fact, even reports using the same data have found opposite effects. The NHANES surveys mentioned above have been used to support a) an inverse effect less sodium linking to more, b) a positive effect less sodium linking to less, and c) a positive effect but only in those who are overweight. As described above, NHANES collected a single 24-hour recall of sodium intake, which is generally unreliable. Studies using food frequency questionnaires have generally found an increased risk october2013 7

3 of stroke with increased sodium. Many of these were conducted in Japan, however, where sodium consumption is much higher than in the US. There is a large amount of sodium contained in popular foods such as soy sauce, pickled vegetables, miso soup, and salted fish. Few studies have been conducted in major cohorts in the US using food frequency questionnaires. This is likely due to the difficulties in estimating portion size, in estimating the sodium consumed in the abundance of processed foods available here, and due to generally limited information on salt added at the table or in cooking. Varied effects have also been found in studies using the gold standard 24-hour urine excretion. Some found an inverse association with myocardial infarction or for all-cause mortality, or no effect, while others found a positive direct effect. Most of these used a single excretion measure, which remains subject to within-person variation or to collection error. The studies also adjusted for different potential confounding variables. Many of them adjusted for blood pressure or for the presence of hypertension. This, though, is in the causal pathway: so such adjustment can nullify any effect, particularly on the indirect pathway through blood pressure, which is presumably the main mechanism for any sodium effect on (Figure 1a). In addition, because of the known effects of sodium on blood pressure, particularly among those with hypertension, many patients with high blood pressure are advised by their physicians to reduce their sodium intake (Figure 1b). This can lead to confounding, and to the appearance of reverse causation in which those with higher blood pressure, including for reasons other than sodium, actually have lower sodium intake. These patients are also often started on anti-hypertensive medications, which further distorts the observed blood pressure level. This will effectively eliminate the ability to estimate the indirect effect of sodium through blood pressure, and biases the overall effect of sodium on cardiovascular disease. In addition, some studies included those with prior. This leads to still more complexity and still greater distortion (Figure 1c). Even adjusting for this will lead to similar problems. The Trials of Hypertension Prevention (TOHP) Follow-up Study was an observational follow-up of trials of lifestyle and supplement interventions to reduce blood (a) (b) Prior sodium (c) Prior Prior Advice Prior Advice meds meds Prior sodium Figure 1. Causal directed acyclic graphs for the mediation of the sodium effect on cardiovascular disease () through blood pressure (): (a) simple direct and indirect effects; (b) additionally including anti0hypertensive medications; (c) additionally including prior. The green lines indicate paths that can be estimated, and red lines indicate paths that are biased. From DAGitty 5 pressure; one was a reduction in sodium intake. Participants were healthy and had high normal blood pressure, now known as pre-hypertension. They did not have prior cardiovascular disease, and were not on anti-hypertensive medications, so they did not suffer from the reverse causation noted above. The trials lasted for 1½ or 3 years, with urine collected several times throughout that period. Among those who were not on the reduced-sodium regime the average of 3 6 sodium excretions was used as a measure of usual sodium intake. This is the only study to date to include multiple measures of 24-hour sodium excretion, which greatly reduced measurement error. Follow-up for was conducted for years after the trials ended. There was an approximately linear direct effect of sodium on incidence, with a 42% increase in risk per 2300 mg/day increase in average sodium intake 6. Evidence from trials While the above was an observational analysis of the effect of average sodium on cardiovascular disease in those not trying to limit their sodium, TOHP also provided the opportunity to examine the long-term effects of the randomised sodium intervention on later 7. While there was a small 1 2 mmhg reduction in blood pressure during the trial periods, those in the active sodium reduction interventions experienced a significant 25% lower risk of years afterwards. There were no measurements of blood pressure or of sodium following the initial trial, but participants did report on preferences for salty and for unsalted foods. Those who had been put on the low-sodium regime were more likely to use low-sodium products and to prefer less salty foods, suggesting that the lessons of the lifestyle intervention may still be altering behaviour many years later. Another randomised trial, of elderly men in veteran s homes, took place in Taiwan. It used potassium-enriched salt as a substitute for the usual sodium chloride 8. It found a 41% reduction in mortality in the group on potassium; it also found that this group had significantly lower medical expenditures for inpatient care of. This was a trial designed to examine health outcomes; nevertheless, the IOM committee did not consider it in their deliberations, since the effects of sodium vs. potassium could not be sorted out. While increased sodium may lead to increased risk, potassium has the opposite effect and leads to decreased risk. Indeed, the effects of sodium and potassium seem to be synergistic, with associations for both electrolytes becoming stronger when the other is considered. The sodium-potassium ratio has been found to be a particularly strong risk factor for incidence and mortality in several studies. Also factoring into the committee conclusions were several reports of randomised 8 october2013

4 trials among heart failure patients, who are advised to lower their sodium. Three trials were conducted by a group in Italy 1. All three showed better results for hospitalisation and mortality among those on a higher (2760 mg/ day) than a lower (1840 mg/day) sodium diet. All patients, however, were on strict fluid restriction and also on diuretics. This aggressive therapeutic regimen may lead to harm with low sodium, and differs from the US standard of care. These results thus may not be generaliseable to other settings or patients. New contradictory reports The data on blood pressure from DASH and on from TOHP are compelling and contributed to previous dietary recommendations. Two more recent studies with contradictory findings generated interest that may have led to the commissioning of the IOM report. Both suggested a U-shaped or J-shaped curve, with increased risk at both higher and lower levels of sodium intake. First, data from two cohorts constituted to study genetic effects on health collected a single 24-hour urine collection. Their data suggested an increase in mortality but not incidence among those in the lowest tertile of sodium intake 9. In contrast, in the more expected direction, sodium was directly related to systolic blood pressure. Concerns have been raised about possible incomplete sodium collections in these studies. There is also possible confounding by indication, as described above, since many participants had hypertension, were on blood pressure medication, and may have been advised to lower sodium (Figure 1b). More recently, data from two trials of anti-hypertensive agents among patients with or diabetes suggested a J-shaped curve, with an increase in risk of and of mortality at both the upper and the lower levels of sodium intake 10. The Kawasaki formula was used to convert a fasting morning excretion to an estimated 24-hour excretion. This formula was based on Asian populations, who generally have higher sodium consumption; this may have led to an overestimate of intake in these data. Since all participants either had prior or were at high risk of, there is also a possibility of reverse causation among these patients, who would generally be treated and advised to lower their sodium intake (Figure 1c). A little of what you fancy but only a very little. istockphoto/chrisgramly How low to go Most of the data supports the idea that there is an increase in risk among those consuming high levels of sodium, and the IOM committee agreed with this. There remains, though, the question of how low sodium levels need to go. Based on NHANES data the current mean sodium level in US adults is 3400 mg/day 11. That corresponds to about 8½ grams of salt, which is equivalent to 1½ teaspoons. Current guidelines recommend reducing sodium by about one-third, down to 2300 mg/day, with a further reduction to 1500 mg/day among high risk groups. The latter corresponds to only 3.8 g of salt, or 0.65 teaspoons. Fewer than 10% of US adults currently consume less than 2300 mg/day. Further, fewer than 1% consume less than 1500 mg/day, a figure that is even lower in men. These low levels are extreme, at least for a US population. They would be difficult to implement, particularly with the ubiquity october2013 9

5 of high-sodium processed foods in the current US diet. It is also possible that not everyone is affected by high sodium levels. Some individuals are more salt-sensitive than others, an effect that may be partially genetic. Effects on blood pressure are strongest among those who already have hypertension. These may indeed be people who are most sensitive to salt, and who have elevated blood pressure because of it. Among those with pre-hypertension, the effects of sodium on blood pressure are present, but not as strong. Little is known about the effects of lowering sodium among those who do not have high blood pressure. It is possible, however, that the latter group would also benefit from sodium reduction. The TOHP trials showed only small effects on blood pressure but did show quite a strong effect on ; this suggests that there may be other mechanisms through which sodium is working. Alternatively, it is possible that the sodium reduction led to a damped increase in blood pressure with aging. At this time the mechanisms as well as the totality of effects of sodium are unclear. What does the public need to know? The conclusion of the committee was that the data supported a population-wide lowering of sodium from the current average levels of 3400 mg/day. Where it questioned current recommendations was as to how low the goal needs to be. The TOHP data suggests that risk continues to fall as sodium intake gets ever-lower; but the data are not all consistent. Newer studies may well suffer from methodological flaws, but their publication in prominent journals raises questions among scientists and in the public eye. Note that the IOM report did not say that there was no benefit to lowering sodium to 1500 mg/day; it said that there were insufficient data on outcomes to support lowering sodium all the way down to this level. Since those with hypertension are known generally to have a strong blood pressure response to sodium, there is likely a cardiovascular benefit to lowering sodium in that group. The TOHP trial was conducted among those with pre-hypertension, and found a benefit there. Whether those with lower blood pressure would also benefit is unknown, but that group represents less than half of the US adult population. A population-wide lowering would thus benefit at least half the population and prevent many cardiovascular events. Even if there is a clinical benefit to lowering sodium to 1500 mg/day, however, questions may reasonably be raised about the practicality of getting to such a low level, as well as the inconvenience and the willingness of the public to give up salt. Some studies show that individuals acclimate to lower levels of sodium, and foods start tasting too salty. Regardless of whether a more appropriate goal is 1500 or 2300 mg/day, though, Americans have a long way to go in lowering sodium consumption. Rational judgements are in the best interest of the public. We should not lose sight of the fact that our sodium levels are currently too high Since most sodium in our current diet comes from processed foods, the cooperation of the food industry is essential in lowering overall sodium levels. Recently food manufacturers have introduced a host of low-sodium or reduced sodium products, including soups, snacks, and canned vegetables. They are to be congratulated for their efforts. While this may initially be met with some resistance from consumers, research has shown that individuals eventually become accustomed to the taste of low sodium products. A gradual reduction in sodium is less likely to even be noticeable. The food manufacturers have the ability to influence sodium intake in ways that are hardly apparent to consumers. Such efforts need to be encouraged and maintained. Progress is already being made. In the public debate surrounding the role of sodium, all of the evidence must be considered, including the strengths and limitations of each study. Flawed studies lead to erroneous conclusions and misleading information. While emotions may be high on both sides of the debate, only rational judgments are in the best interest of the public. There was a great deal of media reaction to the recent IOM report, and the report was often misinterpreted. The New York Times claimed that it undercut years of public warnings 12. This was not so. Getting down even as low as 2300 mg/day in the population is a challenge, never mind down to 1500 mg/day. We should not lose sight of the fact that our sodium levels are currently excessive. Any lowering, whether down to 2300 or 1500 mg/day, would be beneficial. References 1. IOM (Institute of Medicine) (2013) intake in populations: Assessment of evidence. Washington, DC: The National Academies Press. 2. US Department of Agriculture and US Department of Health and Human Services (2010) Dietary Guidelines for Americans, Washington, DC: US Government Printing Office, December. 3. Cutler J.A., Follman D. and Allender P.S. (1997) Randomized trials of sodium reduction: an overview. Am J Clin Nutr., 65 (suppl), 643S 652S. 4. Sacks F.M., Svetkey L.P., Vollmer W.M., et al (2001) Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med., 344, Textor J., Hardt J. and Knüppel S. (2011) DAGitty: A graphical tool for analyzing causal diagrams. Epidemiol, 5, Cook N.R., Obarzanek E., Cutler J.A., et al. (2009) Joint effects of sodium and potassium intake on subsequent cardiovascular disease: The Trials of Hypertension Prevention (TOHP) Follow-up Study. Arch Intern Med., 169, Cook N.R., Cutler J.A., Obarzanek E., et al. (2007) The long-term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the Trials of Hypertension Prevention. BMJ., 334, Chang H-Y., Hu Y-W., Yue C-S.J., et al. (2006) Effect of potassium-enriched salt on cardiovascular mortality and medical expenses of elderly men. Am J Clin Nutr., 83, Stolarz-Skrzypek K., Kuznetsova T., Thijs L., et al. (2011) Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA, 305, O Donnell M.J., Yusuf S., Mente A., et al. (2011) Urinary sodium and potassium excretion and risk of cardiovascular events. JAMA, 306, Cogswell M.E., Zhang Z., Carriquiry A.L., et al. (2012) and potassium intakes among US adults: NHANES Am J Clin Nutr, 96, Kolata G. (2013) No benefit seen in sharp limits on salt in diet. New York Times, May 14. Nancy R. Cook is Professor of Medicine at Harvard Medical School, and a member of the Institute of Medicine Committee on the Consequences of Reduction in Populations. 10 october2013