Abstract
Objective: Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence. Data sources: MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles published as of September 2012. Cohort studies of at least one year’s follow-up period were included. Review methods: Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting. Results: We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07-1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98-1.24) and 0.98 (0.78–1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results. Conclusion: Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.
Generated Summary
This meta-analysis of observational studies investigated the long-term effects of low-carbohydrate diets on all-cause mortality, cardiovascular disease (CVD) mortality, and CVD incidence. The study reviewed and synthesized data from multiple cohort studies, aiming to elucidate the relationship between low-carbohydrate diets and these health outcomes. The methodology involved a systematic review of articles published up to September 2012, followed by a meta-analysis of studies that provided relevant data. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model with inverse-variance weighting to assess the impact of low-carbohydrate diets. The study included cohort studies with a follow-up period of at least one year. The primary objective was to determine the impact of low-carbohydrate diets on mortality and CVD incidence. The studies analyzed data from various sources, including MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov. The study specifically examined whether low-carbohydrate diets were associated with increased or decreased risks of mortality and cardiovascular-related events, a topic of growing interest due to the diets’ increasing popularity. The analysis also considered the potential benefits of shifting diets toward more plant-based options.
Key Findings & Statistics
- The risk of all-cause mortality among those with a high low-carbohydrate score was significantly elevated, with a pooled RR (95% CI) of 1.31 (1.07-1.59).
- A total of 15,981 (5.9%) cases of death from all causes were reported among 272,216 people in 4 cohort studies using the low-carbohydrate score.
- The risks of CVD mortality and incidence were not statistically increased.
- The pooled RRs (95% CIs) for CVD mortality were 1.10 (0.98-1.24) and for CVD incidence, 0.98 (0.78-1.24).
- The analysis using the low-carbohydrate/high-protein (LC/HP) score yielded similar results.
- A total of 3,214 (1.3%) cases of CVD death were reported among 249,272 subjects in 3 cohort studies.
- A total of 5,081 (2.3%) incident CVD cases were reported among 220,691 people in 4 cohort studies.
- In the meta-analysis, each adjusted relative risk with low-carbohydrate intake was combined, and the pooled RR with a 95% CI was calculated using the random-effects model with inverse-variance weighting.
- In 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported among 272,216 people.
- The pooled RRs of the studies conducted in Europe and the United States (RR 1.42 [1.18-1.72] vs 1.12 [1.01-1.24]) were both significantly elevated.
- The pooled RR for men was statistically elevated while that for women was not (RR 1.19 [1.08–1.31] vs 1.34 [0.96–1.87]).
- The analysis of low-carbohydrate score demonstrated that the pooled RR (95% CI) 1.31 (1.07-1.59); p = 0.007; I2 = 53% (p = 0.09).
- Analysis using the LC/HP score yielded a similar significant increase in the risk of all-cause mortality: RR 1.30 (1.01-1.68); p=0.04; I² = 65% (p=0.04).
Other Important Findings
- Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality.
- Low-carbohydrate diets were not significantly associated with a risk of CVD mortality and incidence.
- Analyses using low-carbohydrate/high-protein score yielded similar results.
- The study found a significantly increased risk associated with low-carbohydrate diets (relative risk range 1.12-25.0).
- One diet quality study suggested 0.27 shorter years of life in 10 years.
- Only two out of five studies demonstrated a significantly elevated risk of CVD mortality (relative risk range 2.17-3.52) evaluated by the LC-HP score.
- One article showed a significantly elevated risk of CVD incidence estimated by the low-carbohydrate score and the LC-HP score (relative risk range 1.42-1.55).
- Three diet quality researches suggested a significantly increased risk of incident CVD (relative risk range 1.30-1.56).
- The estimates in all the other analyses using either score were non-significant, and none of these studies revealed that low-carbohydrate diets were associated with a significantly decreased risk of these outcomes.
- The risk of mortality and CVD in animal-based dietary patterns whereas they might decrease the risk in plant-based diets.
Limitations Noted in the Document
- The observational studies were scarce and moderately heterogeneous, and thus a publication bias and a residual confounding bias may have existed.
- In the analysis of CVD mortality risk, there may not have been enough statistical power.
- The representativeness of the cohort may be poor since the data of healthcare professionals dominated.
- The relation may not necessarily be causal, particularly in the observational studies.
- The results may not be generalizable to all populations, as the studies were conducted mainly in Western countries with a predominance of healthcare professionals.
- Dietary patterns may vary over time, and updating dietary information was not consistently done across all studies.
- It is difficult to distinguish the effects of individual nutritional components.
Conclusion
The meta-analysis concluded that low-carbohydrate diets were associated with a higher risk of all-cause mortality, while they did not significantly impact CVD mortality and incidence. This study supports the hypothesis that the short-term benefits of low-carbohydrate diets for weight loss are potentially irrelevant. The findings highlight the need for further investigation into the long-term health effects of low-carbohydrate diets and other nutritional factors. The strength of the study lies in its use of long-term, population-based data from multiple nations, along with its high level of precision. The increased risks for CVD mortality and morbidity, even if not statistically significant, are concerning, and emphasize the need for caution. The study suggests that there is no cardiovascular benefit and supports the potential long-term health harm when nutritional quality is not considered. The study implies the need for large-scale trials to investigate the complex interactions between low-carbohydrate diets and long-term health outcomes. In light of the fact that the number of people with obesity is exponentially increasing worldwide, this study’s findings have substantial clinical and public implications on a global scale. The study underscores the importance of considering the nature of carbohydrates and the source of protein when evaluating dietary interventions. Given the facts that low-carbohydrate diets are likely unsafe and that calorie restriction has been demonstrated to be effective in weight loss regardless of nutritional composition, it would be prudent not to recommend low-carbohydrate diets for the time being.
IFFS Team Summary
- meta-analysis of 17 different studies including 272 000 subjects
- Those with a high low-carbohydrate score had ~31% increased all cause mortality
- Cardiovascular mortality was equivocal between groups
- could this be due to deaths that were undifferentiated, i.e. sudden death, that were likely cardiovascular but not diagnosed clinically
- could this be due to deaths that were undifferentiated, i.e. sudden death, that were likely cardiovascular but not diagnosed clinically
- Involved percentile type studies, dividing people by low carb and low carb/high protein scores