Opposing effects of sodium intake on uric acid and blood pressure and their causal implication

Abstract

Reducing uric acid is hypothesized to lower blood pressure, although evidence is inconsistent. In this ancillary of the DASH-Sodium trial, we examined whether sodium-induced changes in serum uric acid (SUA) were associated with changes in blood pressure. One hundred and three adults with pre- or stage 1 hypertension, were randomly assigned to receive either the DASH diet or a control diet (typical of the average American diet) and were fed each of 3 sodium levels (low, medium, and high) for 30 days in random order. Body weight was kept constant. SUA was measured at baseline and following each feeding period. Participants were 55% women and 75% black. Mean age was 52 (SD, 10) years, and mean SUA at baseline was 5.0 (SD, 1.3) mg/dL. Increasing sodium intake from low to high reduced SUA (−0.4 mg/dL; P < 0.001), but increased systolic (4.3 mm Hg; P < 0.001) and diastolic blood pressure (2.3 mm Hg; P < 0.001). Furthermore, changes in SUA were independent of changes in systolic (P = 0.15) and diastolic (P = 0.63) blood pressure, regardless of baseline blood pressure, baseline SUA, and randomized diet, as well as sodium sensitivity. While both SUA and blood pressure were influenced by sodium, a common environmental factor, their effects were in opposite directions and were unrelated to each other. These findings do not support a consistent causal relationship between SUA and BP.

High sodium intake increases blood pressure and risk of kidney disease. From the Science of Salt: A regularly updated systematic review of salt and health outcomes (August 2016 to March 2017)

“…A total of 47 dietary salt studies met the inclusion criteria: Six meta‐analyses, six RCTs, 11 prospective cohort studies, two retrospective cohort studies, 20 cross‐sectional studies and two case‐control studies, two post hoc analyses of RCTs. The outcomes examined were diverse: Six studies assessed mortality outcomes, four studies assessed morbidity outcomes, three studies assessed outcomes related to symptoms/quality of life/functional status, studies assessed BP outcomes; eight studies assessed other clinically relevant surrogate outcomes; and nine studies assessed physiologic outcomes (Table ) . A range of outcomes were captured by the studies considered lower quality, including all‐cause mortality, gastric cancer, end‐stage renal disease requiring dialysis or transplant, cardiovascular events, hypertension prevalence, headaches/migraines, quality of life, multiple sclerosis, BP, cognitive function, osteoporosis risk and prevalence, nonalcoholic fatty liver disease, type 2 diabetes, carotid atherosclerosis, bone mineral density, changes in left ventricular mass, inflammatory markers, albuminuria, and other urinary markers .…”

“…Of 47 identified studies, eight met the inclusion criteria for outcomes examined and methodological quality and thus were included in the detailed risk of bias assessments and critical appraisals: Two meta‐analyses, one RCT, four prospective cohort studies, and one post hoc analysis of two RCTs . The studies found that: Dietary modifications, including low sodium diets, are associated with a variable reduction in BP; dietary sodium modification did not affect BP in normotensive individuals; medium‐high sodium intake in combination with the DASH diet lowered BP and uric acid levels in pre‐stage or stage 1 hypertensive individuals compared to a control diet; sodium excretion is not associated with risk of CKD; healthy dietary patterns reduce risk of major renal outcomes (composite of death due to renal causes and dialysis, with death due to a nonrenal cause); higher sodium excretion was associated with an increased risk of CVD in individuals with CKD; higher sodium excretion was associated with increased risk of mortality in pre‐hypertensive adults; a low sodium diet is associated with improved markers of kidney function in individuals with autosomal dominant polycystic kidney disease (ADPKD) . Therefore, most of these high‐quality studies (n = 5) found adverse effects of excess sodium on health outcomes; one study reported the benefits of sodium restriction on BP and two studies reported neutral results.…”

Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults

“…Another trial performed in 27 men showed that increasing sodium intake from 20 mEq/day to 200 mEq/day decreased UA levels by 1 mg/dL 33 . In addition, a randomized crossover trial of 103 adults with prehypertension or stage I hypertension showed that 30 days of low versus high sodium intake (60 versus 180 mmol/day) significantly decreased serum UA 18 , 19 . In this study, we showed that the serum UA levels were similar between each quartile of estimated sodium excretion in prehypertensive subjects.…”

“… 16 , 17 found that serum UA could predict not only short-term but also long-term incidence of cardiovascular events as well as cardiovascular death and all-cause mortality. Recent studies have shown that increased sodium intake significantly lowers serum UA 18 , 19 . However, no research has focused on the relationship between dietary salt intake and UA levels, especially urinary UA excretion, in prehypertensive participants.…”

Identification of 22 novel loci associated with urinary biomarkers of albumin, sodium, and potassium excretion

“…37 Regarding the association with BP, another study reported that sodium intake was significantly associated with uric acid and BP in opposite directions. 40 The increase in sodium intake was associated with lower uric acid and higher BP. These findings suggest that uric acid is unlikely to mediate changes in BP in the context of dietary sodium intake.…”