In small doses1 October 2020
An extensive body of evidence has shown that an increased level of dietary sodium intake is associated with higher blood pressure. A new study from researchers at the University of Sydney and the George Institute for Global Health explores recommended salt intake and the benefits of potassium chloride as a sodium reduction solution. Ingredients Insight presents an edited version of ‘Effect of dose and duration of reduction in dietary sodium on blood pressure levels: systematic review and meta-analysis of randomised trials’, originally published in the British Medical Journal.
High blood pressure is a leading modifiable risk factor for cardiovascular disease, which causes at least 17.9 million deaths each year worldwide. A higher intake of dietary sodium is associated with a higher level of blood pressure in animals and humans. The physiological requirement for sodium in humans is less than 1g/ day; however, most populations consume a much higher level. The maximum daily intake of dietary sodium recommended by WHO is 2g (5g salt) for adults – though most countries recommend reducing intake to less than 2.4g/day, as part of a dietary approach to prevent high blood pressure and cardiovascular disease.
The effect of sodium reduction on blood pressure and the risk of cardiovascular disease has been examined in numerous studies. Although there is a consensus among health and scientific organisations to reduce the intake of dietary sodium in the general population, a few scientists have claimed that the benefit of sodium restriction for populations with normal blood pressure is small, and could increase blood lipid levels and the risk of mortality. Others suggest that a higher risk of mortality at low-sodium intake levels is an artefact attributable to factors such as r everse causation and biased estimation of sodium intake.
The nature of the association between change in sodium intake and blood pressure is key to understanding the potential for health interventions based on sodium reduction. Previous overviews of the data were limited because a definitive doseresponse relation could not be determined, especially for participants with normal blood pressure. A specific issue in previous meta-analyses was the inclusion of studies with sodium intake, estimated from fractional urine samples. Fractional urine samples can produce overestimates of sodium intake when true intake is low, but can underestimate when true intake is high. Studies of short duration might also confound estimates of the average effect of change in sodium intake on blood pressure because large, short-term reductions in sodium could elicit a different type of blood pressure response. A previous analysis, which included studies with measurements made at multiple time-points, was unable to determine whether the effects of sodium reduction on blood pressure were sustained, declined or increased with greater duration of intervention.
The objective of this systematic review and metaanalysis was to examine the dose-response relation between dietary sodium reduction and blood pressure change, and explore the impact of intervention duration by applying more restricted inclusion criteria compared with previous reviews. In order to examine this relationship and the impact of restricted criteria, a group of academics carried out a search following this strategy developed for a previous meta-analysis that used keyword searches based on: ‘sodium chloride, dietary’, ‘sodium, dietary’ or ‘diet, sodium-restricted’; and ‘randomised controlled trial’, ‘controlled clinical trial,’ or ‘randomised’. Additionally, they reviewed the references of pertinent original studies and reviewed articles to identify additional studies.
The meta-analysis showed that sodium reduction leads to a significant reduction in systolic blood pressure in adults – both female and male – including all ethnic groups, and in both hypertensive and normotensive populations. Diastolic blood pressure also decreased significantly in most participants. There was a doseresponse relation with a greater reduction in sodium intake, producing a greater fall in blood pressure. Older populations with higher baseline blood pressure achieved greater blood pressure lowering from the same amount of sodium reduction and so did other ethnicities, compared with white populations.
Overall, the duration of the sodium reduction intervention was not associated with the amount of change in blood pressure, although short-term studies of less than 15 days’ duration appear to underestimate the effect of sodium reduction on blood pressure. With few long-term studies available, additional research is required to draw a definitive conclusion about whether prolonged sodium reduction influences the magnitude of the blood pressure lowering.
Comparison with other studies
The overall effect of sodium reduction on blood pressure was observed in several previous metaanalyses, despite different trial selection criteria. The academics also observed strong associations of the magnitude of sodium reduction with the lowering of systolic blood pressure, and interactions of age, race and baseline blood pressure with the size of the systolic blood pressure fall, as shown in previous reviews.
Previous overviews have generated uncertainty regarding the effects of sodium reduction among individuals with different levels of starting blood pressure. Some reports have suggested much larger effects in hypertensive individuals compared with non-hypertensive individuals, while others suggested that sodium reduction is of value only in those with hypertension. The conclusion that there is no value in non-hypertensive individuals is dependent on the results from short-term studies in which sodium reduction had a limited effect on blood pressure and there were adverse effects on other markers of cardiovascular risk.
The responses of the renin-angiotensin system and sympathetic nervous system, as well as adverse metabolic effects associated with acute large falls in dietary sodium, do not, however, appear to be present in long-term interventions and it is unlikely that shortterm unfavourable metabolic effects would override the long-term benefits anticipated from sustained blood pressure lowering of moderate magnitude. Their review identifies an approximate doubling of the effect of sodium reduction on blood pressure in studies of longer than two weeks’ duration versus shorter studies, indicating that the full effects of dietary sodium reduction requires weeks to become apparent. Short-term studies of sodium reduction are not a sound basis for drawing conclusions about the effects of sodium reduction on blood pressure and are not helpful in formulating policy recommendations for public health.
Analyses that simply separate studies based on those that included hypertensive, non-hypertensive, or mixed populations are weak because the definition of hypertension is arbitrary, and there is a rationale for expecting a graded interaction between sodium reduction, blood pressure reduction and starting blood pressure. In this analysis, meta-regressions – based on the mean starting blood pressure levels of participants in each study – provided a more nuanced evaluation of the effects of starting blood pressure on the size of the blood pressure fall achieved with sodium reduction. These analyses showed that sodium reduction produced a progressively greater reduction in blood pressure among those with higher starting blood pressure levels, but also that sodium reduction substantially lowered blood pressure, even among those with starting systolic blood pressure levels as low as 120mm/Hg. These findings indicate potentially important health benefits from sodium reduction among normotensive as well as hypertensive individuals. More importantly, sodium reduction among normotensive individuals could potentially avert or delay the development of hypertension with ageing, as the association between sodium intake and blood pressure is greater at an older age.
The differential blood pressure-lowering effect of sodium reduction across different ethnic groups has been observed in various studies and meta-analyses; specifically, there was a greater blood pressure reduction in non-white populations compared with white populations for the same amount of sodium reduction. Some authors explained that this phenomenon is caused by differential ‘salt sensitivity’. Others have shown that the difference in the responsiveness of the renin-angiotensin system to sodium reduction among various ethnic groups is, at least partially, responsible. Nonetheless, while population-wide sodium reduction is recommended, the cost-effectiveness for some particular populations is potentially greater. This has important public health implications, especially in regions where resources are constrained.
The findings from their overview of randomised trials conflicts directly with findings from the Prospective Urban Rural Epidemiology (PURE) study, which reported that associations between sodium intake and systolic blood pressure are only observed among communities with very high sodium intake (>5.08g or 221mmol sodium/day, equivalent to 13g/day salt). They observed very clear effects of sodium reduction on both systolic and diastolic blood pressure, at levels of sodium intake far below this. Measurement errors and uncontrolled confounding in the PURE study have likely biased conclusions about the association of sodium intake and blood pressure.
Impact of intervention duration of sodium reduction
Sodium reduction resulted in lower blood pressure among a very broad group of populations, with a strong dose-response relation between the magnitude of the sodium reduction achieved and the magnitude of the fall in blood pressure. The effects of sodium reduction were more evident at higher starting blood pressure levels, older ages and among non-white populations, but almost every population group examined achieved a reduction in blood pressure. In trials of more than two weeks’ duration, the doseresponse relation between sodium reduction and blood pressure fall was greater than that in trials of shorter duration, but there was limited evidence that interventions of longer duration further increased the effects of sodium reduction on blood pressure. Longterm trials that achieve sustained sodium reduction and make multiple assessments of blood pressure are required to properly assess this issue.
The full paper with references is available from www.bmj.com.
What is already known on this topic
An extensive body of evidence has shown that a higher level of dietary sodium intake is associated with higher blood pressure.
There are clear effects of sodium reduction on blood pressure in those with hypertension, but uncertainty persists about the comparability of effects in different population subsets. In addition, the impact of intervention duration is not yet fully understood.
What this study adds
Evidence shows that sodium reduction lowers blood pressure in both hypertensive and non-hypertensive individuals, with greater effects in high-risk subsets.
The magnitude of blood pressure lowering achieved with sodium reduction showed a dose-response relation.
Very short-term trials could substantially underestimate the effect of sodium reduction on blood pressure.
The maximum daily recommended intake of dietary sodium (5g of salt) for adults.