Sodium and Health: Another Challenge to the Current Dogma

Andrew Mente; Martin O'Donnell; Salim Yusuf

Disclosures

Eur Heart J. 2021;42(21):2116-2118. 

Graphical Abstract A schematic diagram summarizing the lack of clear evidence for sodiumrestriction.

A very low sodium intake (<2.3 g/day, 100 mmol, 5.8 g/day of salt) has been recommended for the entire population by some guidelines.[1,2] But how robust is this recommendation? This advice is based on the premise that reductions in sodium intake, irrespective of the current levels, will lower blood pressure. Further, it assumes that extreme lowering of sodium will be beneficial and have no harmful effects. Reducing blood pressure, in turn, should reduce cardiovascular disease and deaths. Unfortunately, definitive evidence including that from randomized controlled trials achieving sustained low sodium intake in free-living individuals is not available, nor has any study shown a clear reduction in clinical outcomes from reducing sodium intake. Meanwhile, more than a dozen recent epidemiological studies done by many separate investigators, using different methods to measure sodium, and in different populations have shown that low sodium intake (in the range currently recommended) compared with moderate (average) intake is not associated with lower risk of cardiovascular events and mortality, and may even be associated with an increased risk.[3] Of these studies, the largest and the most diverse was the PURE study, which spanned five continents and 70 centres from 21 countries and involved 102 000 individuals followed for a mean of 9 years. This study showed that a moderate intake (3–5 g/day) of sodium was optimal,[4–7] with lower and higher intakes being associated with higher mortality and cardiovascular disease. The PURE study provided a unique opportunity to employ two approaches to analyses—first the conventional one where sodium intake in individuals was correlated with blood pressure (which they did) and also with events during follow-up. The second approach was to determine the association of community-level mean sodium intake with mean rates of mortality and cardiovascular disease in 667 communities, given that the study enrolled individuals from the general population from a large sample of communities in different countries, and recorded standardized and detailed data on exposure, confounders, and outcomes, permitting both individual- and group-level analyses.[4–7] This second approach overcomes the concerns about lack of precision of sodium measurements in individuals, as the mean value of sodium intake or risk of events in a community is more stable than the value in an individual. Both approaches reached similar conclusions, thereby excluding the possibility that measurement errors in sodium intake or biases may have led to incorrect conclusions.

In this issue of the European Heart Journal, Messerli et al.[8] examine the relationship between sodium intake and life expectancy using a third approach—an ecological study of mean sodium intake across 181 countries vs. their life expectancy. The authors correlated age-standardized estimates of country-specific average sodium consumption with healthy life expectancy at birth and at age 60 years, and with all-cause mortality in 2010, after adjusting for potential confounders such as GDP per capita and body mass index. The authors found a positive correlation between sodium intake and life expectancy at birth (i.e. 2.6 years higher life expectancy per 1 g increment of daily sodium intake; P < 0.001), and, more modestly, with life expectancy at age 60 (0.3 years per 1 g of sodium; P = 0.048). In parallel, countries with higher sodium intake had lower all-cause mortality (β = –131 events/g of daily sodium intake, P < 0.001). A sensitivity analysis restricted to 46 high-income countries showed similar results.

The message from this study is straightforward—there is a lower mortality in countries with a higher sodium consumption. This goes against conventional thinking and the contention that high sodium intake is an important determinant of premature death globally. However, the finding is supported by independent studies with different designs. Observational studies of individual participants have found U-shaped or inverse associations between sodium and mortality, with consistency of results observed in those with and without vascular disease, those with and without diabetes, those with and without hypertension, and in studies using different methods of sodium estimation (i.e. repeated 24-h urine, single 24-h urine, an overnight urine, and dietary assessment). A meta-analysis of prospective cohort studies reported that the range of sodium consumption associated with the lowest cardiovascular event rates is between 3 and 5 g/day.[9] While ecological studies have inherent limitations, if they provide results that are consistent with those obtained using other epidemiological methods (e.g. the methods used in PURE), the general conclusions are likely to be real.

In the PURE study, in community-level analyses of 102 000 adults from 21 countries in multiple world regions followed-up for a decade[6] and using individual-level data to adjust for known confounders, a positive association between sodium and stroke was found, but only among communities in the upper third of sodium intake (i.e. >5 g/day), which were largely confined to China where mean sodium intake was 5.6 g/day. In contrast, an inverse association with myocardial infarction and mortality was found, despite a strong positive association with systolic blood pressure across communities (+2.5 mmHg per 1 g of sodium). The PURE study complements the current study, which showed lower mortality with higher sodium intake at the country level. Taken together, the findings indicate that a strategy that targets communities and countries with high mean sodium intake (e.g. >5 g/day such as China) and lowers sodium to a moderate level (3–5 g/day) might be preferable to a global strategy of extreme sodium reduction in all communities.

The current study has some important strengths. Sodium intake was estimated from a 24-h urine collection, the reference method for estimating sodium intake. With the use of an ecological design, the study is less subject to random measurement error in the assessment of sodium intake that is likely to occur at the individual level.

However, the study by Messerli et al. is ecological, with inherent limitations, including uncontrolled confounding and the potential for ecological fallacy. For example, some of the 'low sodium countries' are also identified as 'low life expectancy' countries (i.e. in sub-Saharan Africa), where there are other potential causes of low life expectancy (i.e. undernutrition). Further, the estimation of sodium intake is less reliable for countries without primary data (i.e. some low- and middle-income countries). However, restriction of the analyses to the 46 high-income countries produced similar results. Dietary sodium intake was estimated at a single time point, but sodium intake is known to be remarkably consistent in groups of people (as opposed to individuals) over time, and so changes in sodium consumption are unlikely to materially distort the findings.

Despite these potential limitations, this analysis provides a new perspective on the association of sodium intake and health, and adds to the mounting evidence challenging current public health advice for low sodium intake in the entire population.

Sodium is an essential nutrient as it is integrally involved in homeostasis and numerous physiological pathways. Therefore, it is not at all surprising that very low intake of sodium is associated with increased risk of death. Excessively high intakes are also likely to be harmful, as shown in PURE which included 89 communities in China where high sodium is related to stroke. Thus, there may be an optimal range or 'sweet spot' for sodium intake, which is observed with most physiological variables and essential nutrients such as vitamin or iron intakes.

The authors rightly emphasize that this is not an interventional study and so the inferences from this study need to be treated with caution. Taken together with the totality of evidence from all cohort studies, the collective information questions whether the current recommendations on sodium intake are valid. Indeed the evidence to support the current recommendations to reduce sodium to very low levels has never been strong (Graphical abstract). Therefore, these data, as well as those from several other studies which are cited by the authors, should challenge the conventional recommendations and lead to silence on the part of guidelines writers. By acknowledging that the available data are not sufficient to support extreme sodium reductions by individuals, we can encourage and enable researchers to conduct studies that can clarify the optimal levels of sodium intake.

In the absence of such data, it is premature to recommend reducing sodium to low levels if we are to avoid a large waste of resources or potentially risk the lives of millions of people worldwide. This has been echoed in two recent reviews by a group of experts (with a range of views and backgrounds).[3,10] It is worth noting that in 2021, the results of a few randomized trials of sodium restriction are expected. These trials will hopefully clarify whether or not sodium reduction should be recommended and, if so, the optimal range of sodium intake compatible with human health.

Diet is complex, and trying to isolate the effects of a particular nutrient is very difficult (e.g. the effects of sodium may be modulated by potassium intake). We suggest avoiding recommending a specific g/day sodium target, but instead focusing on an overall healthy dietary pattern which includes reducing ultraprocessed foods. This advice should be embedded within recommendations to improve all-round dietary quality by emphasizing consumption of plenty of fruits and vegetables, moderate quantities of nuts, dairy, unprocessed meats, and fish, and minimizing the intake of refined grains and ultraprocessed foods.[13]

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