Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis

BACKGROUND: Low carbohydrate diets, which restrict carbohydrate in favour of increased protein or fat intake, or both, are a popular weight-loss strategy. However, the long-term effect of carbohydrate restriction on mortality is controversial and could depend on whether dietary carbohydrate is replaced by plant-based or animal-based fat and protein. We aimed to investigate the association between carbohydrate intake and mortality. METHODS: We studied 15 428 adults aged 45-64 years, in four US communities, who completed a dietary questionnaire at enrolment in the Atherosclerosis Risk in Communities (ARIC) study (between 1987 and 1989), and who did not report extreme caloric intake (4200 kcal per day for men and 3600 kcal per day for women). The primary outcome was all-cause mortality. We investigated the association between the percentage of energy from carbohydrate intake and all-cause mortality, accounting for possible non-linear relationships in this cohort. We further examined this association, combining ARIC data with data for carbohydrate intake reported from seven multinational prospective studies in a meta-analysis. Finally, we assessed whether the substitution of animal or plant sources of fat and protein for carbohydrate affected mortality. FINDINGS: During a median follow-up of 25 years there were 6283 deaths in the ARIC cohort, and there were 40 181 deaths across all cohort studies. In the ARIC cohort, after multivariable adjustment, there was a U-shaped association between the percentage of energy consumed from carbohydrate (mean 48·9%, SD 9·4) and mortality: a percentage of 50-55% energy from carbohydrate was associated with the lowest risk of mortality. In the meta-analysis of all cohorts (432 179 participants), both low carbohydrate consumption (70%) conferred greater mortality risk than did moderate intake, which was consistent with a U-shaped association (pooled hazard ratio 1·20, 95% CI 1·09-1·32 for low carbohydrate consumption; 1·23, 1·11-1·36 for high carbohydrate consumption). However, results varied by the source of macronutrients: mortality increased when carbohydrates were exchanged for animal-derived fat or protein (1·18, 1·08-1·29) and mortality decreased when the substitutions were plant-based (0·82, 0·78-0·87). INTERPRETATION: Both high and low percentages of carbohydrate diets were associated with increased mortality, with minimal risk observed at 50-55% carbohydrate intake. Low carbohydrate dietary patterns favouring animal-derived protein and fat sources, from sources such as lamb, beef, pork, and chicken, were associated with higher mortality, whereas those that favoured plant-derived protein and fat intake, from sources such as vegetables, nuts, peanut butter, and whole-grain breads, were associated with lower mortality, suggesting that the source of food notably modifies the association between carbohydrate intake and mortality. FUNDING: National Institutes of Health.