Lower carbohydrate diets and all-cause and cause-specific mortality: a population-based cohort study and pooling of prospective studies

Abstract Aims Little is known about the long-term association between low-carbohydrate diets (LCDs) and mortality. We evaluated the link between LCD and overall or cause-specific mortality using both individual data and pooled prospective studies. Methods and results Data on diets from the National Health and Nutrition Examination Survey (NHANES; 1999–2010) were analysed. Multivariable Cox proportional hazards were applied to determine the hazard ratios and 95% confidence intervals (CIs) for mortality for each quartile of the LCD score, with the lowest quartile (Q1—with the highest carbohydrates intake) used as reference. We used adjusted Cox regression to determine the risk ratio (RR) and 95% CI, as well as random effects models and generic inverse variance methods to synthesize quantitative and pooled data, followed by a leave-one-out method for sensitivity analysis. Overall, 24 825 participants from NHANES study were included (mean follow-up 6.4 years). After adjustment, participants with the lowest carbohydrates intake (quartile 4 of LCD) had the highest risk of overall (32%), cardiovascular disease (CVD) (50%), cerebrovascular (51%), and cancer (36%) mortality. In the same model, the association between LCD and overall mortality was stronger in the non-obese (48%) than in the obese (19%) participants. Findings on pooled data of nine prospective cohort studies with 462 934 participants (mean follow-up 16.1 years) indicated a positive association between LCD and overall (RR 1.22, 95% CI 1.06–1.39, P < 0.001, I2 = 8.6), CVD (RR 1.13, 95% CI 1.02–1.24, P < 0.001, I2 = 11.2), and cancer mortality (RR 1.08, 95% CI 1.01–1.14, P = 0.02, I2 = 10.3). These findings were robust in sensitivity analyses. Conclusion Our study suggests a potentially unfavourable association of LCD with overall and cause-specific mortality, based on both new analyses of an established cohort and by pooling previous cohort studies. Given the nature of the study, causality cannot be proven; we cannot rule out residual bias. Nevertheless, further studies are needed to extend these important findings, which if confirmed, may suggest a need to rethink recommendations for LCD in clinical practice.