Sodium and Mortality – An Inverse Relationship

Also see:
Aldosterone, Sodium Deficiency, and Insulin Resistance
The Randle Cycle
Free Fatty Acids Suppress Cellular Respiration
Aldosterone as an endogenous cardiovascular toxin
Aldosterone and Thrombosis
Sodium Deficiency and Stress
Low Sodium Diet: High FFA, Insulin Resistance, Atherosclerosis

“One way of looking at those facts is to see that a lack of sodium slows metabolism, lowers carbon dioxide production, and creates inflammation, stress and degeneration. Rephrasing it, sodium stimulates energy metabolism, increases carbon dioxide production, and protects against inflammation and other maladaptive stress reactions.”
-Ray Peat, PhD

“Dietary salt restriction has become a cultural cliché, largely as a consequence of the belief that sodium causes edema and hypertension.” -Ray Peat, PhD

Lancet. 1998 Mar 14;351(9105):781-5.
Dietary sodium intake and mortality: the National Health and Nutrition Examination Survey (NHANES I).
Alderman MH, Cohen H, Madhavan S.
Population-wide restriction of dietary sodium has been recommended. However, little evidence directly links sodium intake to morbidity and mortality. The aim of this study was to assess the relation of sodium intake to subsequent all-cause and cardiovascular-disease (CVD) mortality in a general population.
The first National Health and Nutrition Examination Survey established baseline information during 1971-75 in a representative sample of 20729 US adults (aged 25-75). 11348 underwent medical examination and nutritional examination based on 24 h recall. Two had no data on sodium intake available. Vital status at June 30, 1992, was obtained for the 11346 participants through interview, tracing, and searches of the national death index. Mortality was examined in sex-specific quartiles of sodium intake, calorie intake, and sodium/calorie ratio. Multiple regression analyses were done to assess the relations with mortality.
There were 3923 deaths, of which 1970 were due to CVD. All-cause mortality (per 1000 person-years; adjusted for age and sex) was inversely associated with sex-specific quartiles of sodium intake (lowest to highest quartile 23.18 to 19.01, p<0.0001) and total calorie intake (25.03 to 18.40, p<0.0001) and showed a weak positive association with quartiles of sodium/calorie ratio (20.27 to 21.71, p=0.14). The pattern for CVD mortality was similar (sodium 11.80 to 9.60, p<0.0019; calories 12.80 to 8.94, p<0.0002; sodium/calorie ratio 9.73 to 11.35, p=0.017). In Cox multiple regression analysis, sodium intake was inversely associated with all-cause (p=0.0069) and CVD mortality (p=0.086) and sodium/calorie ratio was directly associated with all-cause (p=0.0004) and CVD mortality (p=0.0056). By contrast, calorie intake in the presence of the two measures of sodium intake was not independently associated with mortality (all-cause p=0.86; CVD p=0.74). Analysis restricted to participants with no history of CVD at baseline gave similar results.
This observational study does not justify any particular dietary recommendation. Specifically, these results do not support current recommendations for routine reduction of sodium consumption, nor do they justify advice to increase salt intake or to decrease its concentration in the diet.

Am J Med. 2006 Mar;119(3):275.e7-14.
Sodium intake and mortality in the NHANES II follow-up study.
Cohen HW, Hailpern SM, Fang J, Alderman MH.
US Dietary Guidelines recommend a daily sodium intake <2300 mg, but evidence linking sodium intake to mortality outcomes is scant and inconsistent. To assess the association of sodium intake with cardiovascular disease (CVD) and all-cause mortality and the potential impact of dietary sodium intake <2300 mg, we examined data from the Second National Health and Nutrition Examination Survey (NHANES II). METHODS: Observational cohort study linking sodium, estimated by single 24-hour dietary recall and adjusted for calorie intake, in a community sample (n = 7154) representing 78.9 million non-institutionalized US adults (ages 30-74). Hazard ratios (HR) for CVD and all-cause mortality were calculated from multivariable adjusted Cox models accounting for the sampling design. RESULTS: Over mean 13.7 (range: 0.5-16.8) years follow-up, there were 1343 deaths (541 CVD). Sodium (adjusted for calories) and sodium/calorie ratio as continuous variables had independent inverse associations with CVD mortality (P = .03 and P = .008, respectively). Adjusted HR of CVD mortality for sodium <2300 mg was 1.37 (95% confidence interval [CI]: 1.03-1.81, P = .033), and 1.28 (95% CI: 1.10-1.50, P = .003) for all-cause mortality. Alternate sodium thresholds from 1900-2700 mg gave similar results. Results were consistent in the majority of subgroups examined, but no such associations were observed for those <55 years old, non-whites, or the obese. CONCLUSION: The inverse association of sodium to CVD mortality seen here raises questions regarding the likelihood of a survival advantage accompanying a lower sodium diet. These findings highlight the need for further study of the relation of dietary sodium to mortality outcomes.

J Gen Intern Med. 2008 Sep;23(9):1297-302. Epub 2008 May 9.
Sodium intake and mortality follow-up in the Third National Health and Nutrition Examination Survey (NHANES III).
Cohen HW, Hailpern SM, Alderman MH.
Sodium restriction is commonly recommended as a measure to lower blood pressure and thus reduce cardiovascular disease (CVD) and all-cause mortality. However, some studies have observed higher mortality associated with lower sodium intake.
To test the hypothesis that lower sodium is associated with subsequent higher cardiovascular disease (CVD) and all cause mortality in the Third National Health and Nutrition Examination Survey (NHANES III).
Observational cohort study of mortality subsequent to a baseline survey.
Representative sample (n = 8,699) of non-institutionalized US adults age > or = 30, without history of CVD events, recruited between 1988-1994.
Dietary sodium and calorie intakes estimated from a single baseline 24-h dietary recall. Vital status and cause of death were obtained from the National Death Index through the year 2000. Hazard ratio (HR) for CVD mortality of lowest to highest quartile of sodium, adjusted for calories and other CVD risk factors, in a Cox model, was 1.80 (95% CI 1.05, 3.08, p = 0.03). Non-significant trends of an inverse association of continuous sodium (per 1,000 mg) intake with CVD and all-cause mortality were observed with a 99% CI of 0.73, 1.06 (p = 0.07) and 0.86, 1.04 (p = 0.11), respectively, while trends for a direct association were not observed.
Observed associations of lower sodium with higher mortality were modest and mostly not statistically significant. However, these findings also suggest that for the general US adult population, higher sodium is unlikely to be independently associated with higher CVD or all-cause mortality.

Nutr Rev. 1998 Oct;56(10):311-3.
Dietary sodium intake and mortality.
Esslinger KA, Jones PJ.
Results of a recent study of data from the National Health and Nutrition Examination Survey (NHANES I) on sodium intake and all-cause and cardiovascular mortality may call into question current recommendations to limit salt intake. Further research is needed to explore the relationship between sodium, cardiovascular disease, and mortality.

Heart. 2012 Aug 21. [Epub ahead of print]
Low sodium versus normal sodium diets in systolic heart failure: systematic review and meta-analysis.
Dinicolantonio JJ, Pasquale PD, Taylor RS, Hackam DG.
A low sodium diet has been proposed to reduce the risk of heart failure (HF) hospitalisations and is currently advocated in consensus guidelines, yet some evidence suggests adverse neurohumoral activation for sodium restriction in the HF setting.
To evaluate the effects of a restricted sodium diet in patients with systolic HF.
A systematic review and meta-analysis of randomised trials OVID MEDLINE, PubMed, Excerpta Medica (Embase), the Cochrane Controlled Trials Register, Scopus, Web of Science and Google Scholar were searched up to April 2012.
Two independent reviewers selected studies for inclusion on the basis of a randomised controlled trial design that included adults with systolic HF receiving a restricted salt diet or control diet and reporting mortality (all-cause, sudden death or HF-related) and HF-related hospitalisations.
Descriptive and quantitative information was extracted from included studies. A random-effects model was used to compute pooled risk ratios (RR) for mortality and morbidity outcomes.
Six randomised trials comparing low sodium diets (1.8 g/day) with normal sodium diets (2.8 g/d) in 2747 patients with systolic HF were identified. Compared with a normal sodium diet, a low sodium diet significantly increased all cause mortality (RR 1.95, 95% CI 1.66 to 2.29), sudden death (RR 1.72, 95% CI 1.21 to 2.44), death due to HF (RR 2.23, 95% CI 1.77 to 2.81) and HF readmissions (RR 2.10, 95% CI 1.67 to 2.64).
Compared with a normal sodium diet, a low sodium diet significantly increases morbidity and mortality in systolic HF.

Am J Med. 2013 Nov;126(11):951-5. doi: 10.1016/j.amjmed.2013.05.020. Epub 2013 Sep 18.
Dietary sodium restriction: take it with a grain of salt.
DiNicolantonio JJ, Niazi AK, Sadaf R, O’ Keefe JH, Lucan SC, Lavie CJ.
The American Heart Association recently strongly recommended a dietary sodium intake of <1500 mg/d for all Americans to achieve "Ideal Cardiovascular Health" by 2020. However, low sodium diets have not been shown to reduce cardiovascular events in normotensive individuals or in individuals with pre-hypertension or hypertension. Moreover, there is evidence that a low sodium diet may lead to a worse cardiovascular prognosis in patients with cardiometabolic risk and established cardiovascular disease. Low sodium diets may adversely affect insulin resistance, serum lipids, and neurohormonal pathways, leading to increases in the incidence of new cardiometabolic disease, the severity of existing cardiometabolic disease, and greater cardiovascular and all-cause mortality. Although a high sodium intake also may be deleterious, there is good reason to believe that sodium intake is regulated within such a tight physiologic range that there is little risk to leaving sodium intake to inherent biology as opposed to likely futile attempts at conscious control.

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