A recent study from The University of Texas Health Science at San Antonio (UT Health San Antonio) suggests that a ketogenic diet might influence males and females differently. The research, published in the journal Cell Reports, indicates that estrogen could provide distinct protective effects against negative consequences of the diet, such as cellular senescence.
The study discovered that while male mice on a ketogenic diet exhibited an accumulation of cells expressing markers of senescence, female mice did not. A keto diet is a popular low-carb, high-fat regimen that helps manage blood sugar in type 2 diabetes and controls seizures in epilepsy. Cells displaying senescence markers can contribute to age-related declines in bodily function.
"These findings suggest sex-specific responses to a ketogenic diet with significant clinical implications," said David Gius, MD, Ph.D., Assistant Dean of Research and Professor at UT Health San Antonio's Department of Radiation Oncology, Associate Cancer Director for Translational Research at the Mays Cancer Center and investigator at its Barshop Institute for Longevity and Aging Studies. He is the lead author of the study titled "Divergent sex-specific effects on a ketogenic diet: Male mice, but not female mice, exhibit oxidative stress and cellular senescence."
Ketogenic diets promote ketogenesis, generating ketone bodies from fat as fuel instead of glucose. These diets benefit conditions like refractory epilepsy and are explored for other health issues.
Over the past decades, keto diets have gained popularity in North America and Europe for weight loss.
While keto diets can improve certain health parameters, evidence suggests that effects may depend on factors like adherence, metabolism, and sex. Gius notes that gender's role in response to keto diets has been underexplored due to historical biases in using male mice in research, though recent studies challenge this bias.
Gius’s team observed increased cellular senescence only in males on a keto diet unless supplemented with estrogen. Male mice also showed higher oxidative stress markers, contributing to cellular senescence. Notably, estrogen or estradiol treatment prevented these increases in male mice on the diet, as did antioxidants.
When females were administered tamoxifen (a selective estrogen receptor inhibitor), they exhibited increased oxidative stress and senescence markers similar to males. Gius concluded, "Estrogen is a critical factor in response to ketogenic diets."
The researchers also found that high-fat diets induced cellular senescence in male but not female mice.
Other authors of the study are associated with the Mays Cancer Center, Barshop Institute, Long School at UT Health San Antonio, Houston Methodist Cancer Center, Houston Methodist Research Institute, and Galera Therapeutics Inc.