Need for Randomized Controlled Sodium Reduction Trial

To the Editor:—We disagree with He and MacGregor1 who contend that blood pressure (BP) effect, despite small BP change, wide intra-individual variation, and attenuation of effect over time,2 is by itself an adequate surrogate for health outcomes of population-wide sodium reduction. Reduced sodium intake can stimulate the renin-angiotensin and sympathetic nervous systems, increase insulin resistance, and lead to diet changes that impact other nutritional factors, so that the overall morbidity and mortality consequences, if any, cannot be assumed. To date, at least 11 observational studies of lower sodium with clinical outcomes have shown mixed results-some positive, some negative and some null-and even when benefits of lower sodium were observed they occurred in population subsets that cannot be generalized to all.3 Among other misrepresentations, He and MacGregor inaccurately claim that “the top quartile in [our] study had a salt intake ≈15–16 g/day…exactly the amount of salt consumed in Finland.”1 In fact, the upper quartile for NHANES lll reported ≥4048 mg sodium. Correcting for discretionary salt as estimated by the USDA and HHS, yields 4453 mg sodium, or 194 mmol of sodium (11.3 g salt)-equal to the upper quartile of Finnish study women - in whom no significant sodium to mortality association was identified. In fact, only over weight Finnish men had a significant direct association. Upper quartile consumption of men was ≥262 mmol sodium (15.3 g salt).4 He and MacGregor cite an important observational follow-up study of TOHP5 but mischaracterize it as a “randomized trial.” TOHP participants had baseline characteristics similar to about 4% of the U.S. population. Those in the TOHP II sodium reduction group had no significant BP decline at 36 months despite a 33 mmol/24 h sodium decline. A significant association of sodium reduction with all CVD was found among those who responded, a subgroup of 77% no longer protected by randomization. For mortality outcomes, where follow-up data were available for almost all, there were no significant associations of outcome with the sodium intervention group. TOHP does show, however, that a randomized controlled trial of sodium reduction with clinical outcome measures is feasible and we think such a trial is needed. Without clinical outcome trial evidence, He and MacGregor nonetheless have faith that it is “extremely likely” that universal salt reduction will convey “large benefits.”1 Perhaps. But the experience of low fat diets and hormone replacement therapy suggest that policy and practice interventions not supported by trial data can be problematic. Thus, we urge science as superior to faith as a guide to safe and beneficial health practice.