Ketogenic diet lowers mortality by 24% while maintaining heart health

New research highlights the ketogenic diet’s ability to lower overall mortality by 25% while posing no added risk to heart health—ushering in new perspectives on its long-term safety and efficacy.

Study: The ketogenic diet has the potential to decrease all-cause mortality without a concomitant increase in cardiovascular-related mortality. Image Credit: Yulia Furman / Shutterstock

In a recent study published in the journal Scientific Reports, researchers used a long-term large United States (US)-based cohort (NHANES study) comprising more than 43,775 adults from 2001 to 2018 to evaluate the associations between the ketogenic diet (KD) and all-cause or cardiovascular disease (CVD) risk. Multivariable Cox proportional hazards regression models revealed that while adherence to KD can significantly reduce the risk of all-cause mortality (HR = 0.76, 95% CI: 0.63–0.9), no significant association was found between KD and increased CVD mortality risk (HR = 1.13, P = 0.504).

Together, these findings highlight KD’s benefits beyond just its use as an intervention against childhood epilepsy, underscoring the need for further research leveraging KD and similar beneficial diets in the quest for overall human health and longevity.

Background

The ketogenic (‘keto’) diet (KD) is a dietary intervention that prioritizes low carbohydrate consumption in favor of high fat intake, forcing the human body to switch from carbs to fats as a primary fuel source. This state, called ketosis, was initially developed to treat childhood epilepsy but has since been revealed to present profound health benefits in weight loss and metabolic disease management.

Unfortunately, the widespread promotion and adoption of KD are hampered by ongoing scientific debates on its safety and the potential for high ketone levels (e.g., acetoacetate, β-hydroxybuty-rate) to increase the risk of cardiovascular diseases (CVDs). Although KD is associated with high fat intake, no consistent evidence has confirmed its detrimental effects on cardiovascular health. Surprisingly, despite years of debate, hypotheses about KD’s potentially negative health effects have never been scientifically verified.

“CVD risk is a significant contributor to global morbidity and mortality, with dietary factors playing a pivotal role in its pathogenesis. Recent research has elucidated the intricate and nuanced relationship between the KD and CVD risk. On one hand, reducing carbohydrate intake and enhancing insulin sensitivity may confer beneficial effects on CVD risk factors such as blood pressure regulation, lipid levels, and inflammation. Conversely, the high-fat content of the KD, particularly saturated fat, may exert detrimental effects on lipid metabolism, trigger inflammatory responses, and augment CVD risk.”

Objectively elucidating KD’s long-term effects on human health, specifically all-cause mortality and CVD mortality, would allow for the development of scientifically accurate dietary guidelines, thereby mitigating the steady rise of chronic disease in today’s globally aging population.

About the study

The present study evaluates the long-term associations between KD and mortality (all-cause) and CVD mortality. Data for the study were obtained from the United States (US) National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. This cohort study is nationally representative and includes follow-up data on over 91,351 participants. The study is a nationally representative cross-sectional survey of adult US civilians conducted by the National Center for Health Statistics (NCHS).

It includes follow-up data on anthropometric measurements, dietary intake, clinical laboratory testing, and participant outcomes. After excluding participants under 20 years of age and those with missing data, 43,776 participants were ultimately included in the analysis. Dietary intake data were measured through two 24-hour dietary recall interviews, and nutrient intake was calculated using the Food and Nutrition database.

Nutrient data were then used to calculate a Dietary Ketogenic Ratio (DKR), thereby establishing patterns capable of achieving nutritional ketosis (higher DKR = higher likelihood of ketosis). The DKR calculation involved the ratio of macronutrients with ketogenic versus anti-ketogenic properties, following established formulas. Sociodemographic and lifestyle data (obtained from NHANES) were used to establish and characterize covariates. Participants were classified into categories: age, race/ethnicity, education, marital status, BMI, and smoking status.

Finally, all-cause mortality was the study’s primary outcome, while CVD risk was the secondary outcome. CVD mortality was defined based on clinically confirmed diagnoses, including heart failure, coronary heart disease, and myocardial infarction. Additionally, hypertension and diabetes were included due to their strong association with CVD.

Multivariate-adjusted Cox proportional hazard models were used to compute hazard ratios (HRs), thereby estimating the associations between KD and outcomes. Restricted cubic spline (RCS) analysis was conducted to explore potential non-linear associations between KD and mortality risk.

Study findings

Of the 91,351 participants enrolled in the NHANES cohort, 43,776 met the inclusion criteria and were evaluated in the present work. The participants were predominantly male (51.7%) and presented a mean age of 49.4 years. After a median of 9.1 years of follow-up, 6,508 (13.8%) of participants lost their lives to all-cause mortality, while 1,533 (3.5%) lost it to CVD-related causes. Significant risk factors included sex, age, marital status, smoking status, and BMI.

Cox proportional hazard models (adjusted) revealed a dose-dependent correlation between KD and decreased risk of all-cause mortality. In contrast, models exploring the association between KD and CVD mortality found no significant relationship. Both results were supported and validated by RCS analyses. Further stratified sensitivity analyses across subgroups confirmed these findings, showing a clear reduction in all-cause mortality without a significant increase in CVD mortality risk.

“Notably, in adjusted models, each standard deviation increase in DKR resulted in a noteworthy 24% reduction in the risk of death. Furthermore, when comparing patients in different quartiles of DKR, those in the higher quartiles exhibited a stronger protective effect compared to those in lower quartiles.”

Conclusions

The present study establishes the health benefits of KDs by verifying that the dietary pattern reduces all-cause mortality risk without a corresponding increase in the risk of CVD or similar chronic cardiovascular conditions. The data from more than 43,776 US adults over a 9.1-year follow-up period highlight that KD adherence can reduce all-cause mortality risk by up to 24%, underscoring the need for additional research to further optimize the KD for public health recommendations.