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 (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.
Generated Summary
This research presents a prospective cohort study and meta-analysis investigating the association between dietary carbohydrate intake and mortality. The study utilized data from the Atherosclerosis Risk in Communities (ARIC) study, a cohort of 15,428 adults aged 45-64 years from four US communities, who were enrolled between 1987 and 1989. The primary outcome was all-cause mortality, and the researchers examined the association between the percentage of energy from carbohydrate intake and mortality, considering potential non-linear relationships. In addition to the ARIC data, the study incorporated data from seven multinational prospective studies in a meta-analysis to further explore these associations. Furthermore, the study assessed whether the substitution of animal or plant sources of fat and protein for carbohydrate affected mortality. The methodology involved dietary questionnaires, followed by a median follow-up of 25 years, with statistical analyses including Cox proportional hazards regression models and restricted cubic splines. The aim was to determine how different levels of carbohydrate intake, as well as the source of macronutrients replacing carbohydrates, related to mortality rates. The study explores a U-shaped association between carbohydrate intake and mortality, with the lowest risk observed at an intake of 50-55% energy from carbohydrates. Furthermore, the study distinguishes the impact of replacing carbohydrates with animal-derived versus plant-based sources of fat and protein, finding differential effects on mortality.
Key Findings & Statistics
- The ARIC cohort, with a median follow-up of 25 years, recorded 6,283 deaths.
- Across all cohort studies in the meta-analysis, there were 40,181 deaths.
- In the ARIC cohort, a U-shaped association was found between energy from carbohydrate and mortality, with the lowest risk at 50-55% carbohydrate intake.
- Meta-analysis of all cohorts (432,179 participants) showed that both low (70%) carbohydrate consumption were associated with greater mortality risk than moderate intake.
- Pooled hazard ratio for low carbohydrate consumption: 1.20 (95% CI 1.09–1.32).
- Pooled hazard ratio for high carbohydrate consumption: 1.23 (1.11–1.36).
- Mortality increased when carbohydrates were exchanged for animal-derived fat or protein: 1.18 (1.08–1.29).
- Mortality decreased when the substitutions were plant-based: 0.82 (0.78-0.87).
- Mean carbohydrate intake in ARIC cohort: 48.9% (SD 9.4).
- 50-year-old participant with intake of less than 30% carbohydrate: projected life expectancy of 29.1 years.
- 50-year-old participant with intake of 50-55% carbohydrate: projected life expectancy of 33.1 years.
- 50-year-old participant with high carbohydrate intake (>65%): projected life expectancy of 32.0 years.
- In the ARIC cohort, the animal-based low carbohydrate dietary score associated with an increased all-cause mortality (p<0.0001; table 3).
- Plant-based low carbohydrate diet scores were associated with a significant decrease in all-cause mortality (p<0.0001; table 3).
Other Important Findings
- Both high and low percentages of carbohydrate diets were associated with increased mortality.
- Low carbohydrate dietary patterns favoring animal-derived protein and fat sources were associated with higher mortality.
- Diets favoring plant-derived protein and fat intake were associated with lower mortality.
- The study found a non-linear (U-shaped) association between carbohydrate intake and mortality.
- The association between carbohydrate consumption and mortality was dependent on the range of carbohydrate intake.
- Low carbohydrate diets, particularly those with animal-based protein and fat, were associated with increased mortality risk.
Limitations Noted in the Document
- The study is observational and not a clinical trial.
- Diet was assessed at two time intervals over a 6-year period, and dietary patterns could have changed over the 25 years.
- Dietary assessment methods have inherent measurement error.
- The study focused on general carbohydrate intake, which represents a heterogeneous group of dietary components.
- The international data about very high carbohydrate intakes may be less reliable due to the inclusion of data from countries such as China.
- The study did not definitively examine the relative benefits of diets with mainly plant-based protein and fat sources due to the small number of individuals on such diets.
Conclusion
In conclusion, the study’s findings emphasize a U-shaped relationship between carbohydrate intake and mortality, with moderate carbohydrate consumption (50-55% of energy) associated with the lowest risk of mortality. The results, which were corroborated by a meta-analysis of multiple studies, suggest that both very low and very high carbohydrate intakes are associated with increased mortality risk. However, the study’s key insight lies in the source of macronutrients replacing carbohydrates. When carbohydrates were replaced with animal-derived fats and proteins, mortality risk increased. Conversely, when carbohydrates were replaced with plant-based fats and proteins, mortality risk decreased. This suggests that the source of the replaced macronutrients is a crucial factor in determining the long-term health effects of carbohydrate restriction. The study’s findings also underscore the importance of considering the broader context of dietary patterns. The differing impacts of animal-based versus plant-based diets highlight the need for nuanced dietary recommendations. The authors advocate for discouraging animal-based low carbohydrate diets, which are prevalent in some populations, while supporting the use of plant-based fats and proteins to replace carbohydrates as a potentially healthier long-term strategy. In essence, the study indicates that while the total carbohydrate intake matters, the composition of the diet and the food sources chosen play a critical role in influencing health outcomes. The study suggests that previous analyses of carbohydrate intake that focused on quantiles of consumption, and then searched for a trend across those quantiles, may have overlooked valuable information. This continuous data, the authors suggest, highlights the importance of food source and the potentially adverse effects of high consumption of animal derived sources.
IFFS Team Summary
- See full study in Low Carbohydrate High Protein section