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

Abstract

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 (<600 kcal or >4200 kcal per day for men and <500 kcal or >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 (<40%) and high 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.

Figure 1:. U-shaped association between percentage of energy from carbohydrate and all-cause mortality in the ARIC cohort

The reference level is 50% energy from carbohydrate. Results are adjusted for age, sex, race, ARIC test centre, total energy consumption, diabetes, cigarette smoking, physical activity, income level, and education. ARIC=Atherosclerosis Risk in Communities.

Figure 2:. Carbohydrate intake and mortality risk across multiple cohort studies

Mean values of percentage of energy from carbohydrate (% carbohydrate) reported in previously studied cohorts from lowest to highest quantiles. Adjusted HRs are from analyses of low carbohydrate scores versus high carbohydrate scores (n=432179, all-cause deaths=40 181). Dotted lines indicate cutoffs for low carbohydrate (<40%) and high carbohydrate (>70%). (A) Low carbohydrate versus moderate carbohydrate (40–70%) reference group. (B) High carbohydrate versus moderate carbohydrate reference group. HR=hazard ratio. ARIC=Atherosclerosis Risk in Communities. NHS=Nurses Health Study. HPFS=Health Professionals Follow-up Study.

Figure 3:. U-shaped association between percentage of energy from carbohydrate and all-cause mortality in the ARIC and PURE cohort studies

The reference level is 46·4% energy from carbohydrate. ARIC results are adjusted for age, sex, education, waist-to-hip ratio, smoking, physical activity, diabetes, ARIC test centre, and energy intake. PURE results are are adjusted for age, sex, education, waist-to-hip ratio, smoking, physical activity, diabetes, urban or rural location, centre, geographical regions, and energy intake. The mean percentage of energy from carbohydrate in ARIC is 49%, and from PURE it is 61%. ARIC=Atherosclerosis Risk in Communities. PURE=Prospective Urban Rural Epidemiology.