Salt and Cardiovascular Disease: Insufficient Evidence to Recommend Low Sodium intake

Martin O'Donnell; Andrew Mente; Michael H. Alderman; Adrian J.B. Brady; Rafael Diaz; Rajeev Gupta; Patricio López-Jaramillo; Friedrich C. Luft; Thomas F. Lüscher; Giuseppe Mancia; Johannes F.E. Mann; David McCarron; Martin McKee; Franz H. Messerli; Lynn L. Moore; Jagat Narula; Suzanne Oparil; Milton Packer; Dorairaj Prabhakaran; Alta Schutte; Karen Sliwa; Jan A. Staessen; Clyde Yancy; Salim Yusuf

Disclosures

Eur Heart J. 2020;41(35):3363-3373. 

In This Article

Abstract and Introduction

Abstract

Several blood pressure guidelines recommend low sodium intake (<2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. <2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world's population consume a moderate range of dietary sodium (2.3–4.6g/day; 1–2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of <5 g/day in populations with mean sodium intake of >5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.

Introduction

Several blood pressure guidelines recommend low sodium intake (<2.3 g/day, 100 mmol sodium, ~1 teaspoon of salt, Table 1) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence.[1–5] Some advocates of low sodium intake contend that it is unnecessary to set a lower limit of unsafe sodium intake, and that the current range of average sodium intake is harmful to all (majority of most populations have intake between 2.3 and 4.6 g/day (100–200 mmol/day), ~1–2 teaspoons of salt).[5–7] However, sodium is an essential nutrient, required for normal cardiovascular physiology and health, and therefore expected to have a physiologic 'healthy' range of intake, as is the case for other essential electrolytes[8,9] (Figure 1). Sodium is most often (>90%) consumed in the form of sodium chloride (salt), and sodium homeostasis is tightly governed by numerous neurohormonal and central neurophysiologic mechanisms.[8,9] One role of sodium, among many, is to maintain intravascular volume, as the main extracellular cation in the body. Infusion, or ingestion, of sodium chloride has a pressor effect in most people, which is the rationale for using sodium chloride infusions in acute shock and increasing daily sodium intake among those with symptomatic orthostatic hypotension.[10] Sodium is also the main cation governing osmolality and a positive sodium balance shifts dose-response curves of angiotensin or noradrenalin to the left.[9] Sodium also appears to have a role in immune modulation.[11]

Figure 1.

Relationship of essential electrolyte with health.

Consistent with its physiologic role, increased sodium intake is associated with increases in blood pressure in most, but not all, individuals.[12] Extreme reductions in sodium intake, as part of a multi-component dietary therapy, were first reported for heart failure in 1866[13] (constituent of a milk diet), and as part of a rice diet in managing malignant hypertension in 1949.[14,15] Subsequent clinical trials, conducted mainly in the 1980s and 90 s, reported modest group-level reductions in mean blood pressure when lowering sodium intake in those with hypertension or pre-hypertension. The largest of these trials, Trial of Nonpharmacological Intervention in the Elderly (TONE)[16] and Trial of Hypertension Prevention (TOHP-II),[17] targeted sodium intakes of <1.8 g/day, and achieved modest reductions in sodium intake (~1 g/day) to mean levels of 2.3–3.2 g/day through intensive individual dietary counselling, and resulted in modest reductions in mean blood pressure, over ~2 years of follow-up. The Dietary Approaches to Stop Hypertension-Sodium (DASH-Sodium) trial,[18] a 30-day cross-over trial (n = 412), had the greatest influence on the specific target in current sodium intake guidelines; it reported reductions in blood pressure with sodium intake reduced to <1.5 g/day when food intake was entirely controlled by the investigators. At the time this trial was published, it was generally assumed that any reductions in blood pressure, regardless of intervention or mechanism, would result in reductions in cardiovascular events at the population level and in a reduction in individual risk.[19,20] Subsequent guidelines placed greater emphasis on a specific sodium intake target of <1.5 g/day for those with hypertension, directly implementing findings from the DASH-Sodium trial.[18] Today, most dietary guidelines recommend low sodium intake (<2.3 g/day), albeit with slightly different targets (e.g. WHO recommend <2.0 g/day, American Heart Association recommends a target of <2.3 and <1.5 g/day in high-risk individuals).[1–4] Mean sodium intake globally is estimated at 3.95 g/day;[21] therefore, achieving currently recommended low sodium intake levels will require a dramatic alteration in dietary patterns, something that would be difficult to achieve in free-living individuals, especially in regions where most sodium intake is derived from non-discretionary sources (e.g. processed foods), necessitating major changes to intake, and/or sodium content of manufactured foods.[22,23]

These guidelines were originally developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). To date, these critical deficits remain.

With few exceptions,[24,25] the recommendation for low sodium intake has been remarkably resistant to change or challenge, even with evolution in our understanding of physiology of sodium[26] and increasingly strong evidence that the relation of sodium intake with cardiovascular events is J-shaped.[27–31] These prospective cohort studies reporting a J-shaped association of sodium intake and cardiovascular events provide contradictory evidence for the fundamental assumption upon which all guidelines are based, that all reductions in sodium intake will translate directly into less cardiovascular disease. From a health policy perspective, the current message from prospective cohort studies is mostly consistent, that high sodium intake (>4.6 g/day) is associated with higher mortality and cardiovascular risk, compared with average sodium intakes of 2.3–4.6 g/day. However, no convincing evidence exists (including from randomized controlled trials) of a significantly lower cardiovascular risk with low sodium intake (<2.3 g/day) compared with moderate (average) intake.[24] Guideline recommendations for low sodium intake were first introduced at a time when there was limited evidence on the association of sodium intake and cardiovascular events. As evidence has evolved, most guideline panels have been reluctant to incorporate the findings from these large, more recent, epidemiologic studies into evolving thinking and recommendations. Most guideline panels have not seriously considered the substantial body of work that contradicts a 'low sodium' recommendation.

In 2013, an independent review of the evidence by the National Academy of Medicine (NAM) concluded there to be insufficient evidence to support a recommendation of low sodium intake for cardiovascular prevention.[25] However, in 2019, a re-constituted panel[5] provided a strong recommendation for low sodium intake, despite the absence of any new evidence to support low sodium intake for cardiovascular prevention, and substantially more data, e.g. on 100 000 people from Prospective Urban Rural Epidemiology (PURE) study[29] and 300 000 people from the UK-Biobank study,[32] suggesting that the range of sodium intake between 2.3 and 4.6 g/day is more likely to be optimal. Observational studies have inherent limitations (e.g. potential for reverse causation or confounding despite extensive adjustments for covariates and inability to evaluate the effects of interventional reductions in sodium intake). However, in the absence of large randomized controlled trial data demonstrating the efficacy and safety of reducing sodium intake to low levels (<2.3 g/day), observational studies provide the 'best available evidence' of the association of exposures like sodium intake and long-term cardiovascular risk in populations.

In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake. We suggest that a specific low sodium intake target (e.g. <2.3 g/day) for individuals may be unfeasible, have uncertain consequences for other dietary factors, and have unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world's population consume a moderate range of dietary sodium (1–2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day.

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