Reply to SN Thornton.

Dear Editor:The comments and concerns expressed by Thornton (1) relate to our recent reviews from the ASN Scientific Sessions at Experimental Biology 2014 symposium regarding sodium intake and health outcomes. His comments appropriately expand the discussion of whether to reduce sodium intakes to low amounts. Our intent with the cited papers was never to exclude critical cofactors such as water. The neural regulation of water and sodium are physiologically interrelated (2), because optimizing both volume and osmolality are essential elements of cardiovascular health. As noted by Thornton, the hormonal response to decreased perfusion invokes angiotensin II, aldosterone, and vasopressin release, all of which have potent vascular actions that potentially increase cardiovascular disease (CVD) risk.Thornton’s argument that overlooking the role of water intake in understanding the association of sodium with health outcomes raises another question as to the safety of a health policy directed at lowering sodium intake across the entire population. Hyponatremia at hospital admission and in free-living populations has been associated with both increased morbidity and mortality (3–6). Those findings are consistent with the proposition that sodium and water intake must be considered in tandem when assessing health outcomes. As opposed to previous hypotheses that comorbidities accounted for an increased risk of death, recent data indicate that the greatest risk appears in those with few comorbid conditions (5, 6).Hyponatremia is the most common electrolyte disturbance in the general population (6). Reduced sodium intake in and of itself can impair the healthy kidney’s ability to excrete excess free water (7). Therefore, a lower sodium diet would promote the development of a reduced serum sodium concentration, or hyponatremia. Although it is typically assumed that with normal kidney function there is a large excess renal capacity to excrete water, what is not generally appreciated is that reduced solute intake impairs the healthy kidney’s capacity to excrete excess water (7). Sodium intake is one of the principle contributors to the renal solute load. Thus, lower sodium intake potentially sets in motion a normal physiologic response that would contribute to the development of hyponatremia in a segment of the general population. If healthy persons lower their sodium intake as recommended by current guidelines, but maintain water consumption that exceeds requirements (as is widely promoted to the general population, especially physically active people), those guidelines may well set the stage for the emergence of hyponatremia even in otherwise healthy people. The hyponatremia-related mortality and morbidity data published to date and the physiology of sodium and water handling by the kidney provide a plausible explanation to account for the increased risk of death from lower sodium intake in healthy, low-risk individuals (8). Furthermore, such a risk would not solely rest on activation of the renin-angiotensin system and aldosterone invoked for those already at risk of CVD.Perhaps the simplest and most important aspect of the issue raised by Thornton is his reminder that water metabolism is linked to sodium. That obvious and accepted physiologic link should serve as a note of caution that there are many “moving parts” associated with reducing sodium intake in the general population. The longstanding assumption that sodium restriction to amounts below that normally consumed in modern societies is safe and effective fails to consider that complex physiology. The old adage that “it is too good to be true” may well apply to the simplistic policy view that sodium restriction lowers blood pressure and therefore reduces CVD risk.