The Study
Sex Differences in Ketogenic Diet Response Reveal Gonadal Hormone Interaction With FGF21 in Mice
This study looked at how male and female mice react to a special high-fat diet. It found that the diet made male mice lose weight but made female mice gain weight—but this doesn't mean the same thing will happen to people. It's like noticing that your dog gets excited when you shake a treat bag, but that doesn't mean all dogs or humans will react the same way.
Analysis score
Maximum 72 for a cohort study.
Where the score came from
Scientists fed male and female mice a super fatty, low-sugar diet to see how their bodies reacted. Boys lost weight and burned more energy; girls got fatter and had trouble controlling blood sugar.
Where does this study sit?
Reviews of RCTs (Meta-analyses)
Max 100Randomized Trials
Max 90Reviews of Cohort Studies
Max 85Cohort Studies
Max 72Reviews of Case-Control Studies
Max 63Case-Control Studies
Max 58Cross-Sectional & Case Series
Max 50Expert Opinion
Max 518 / 100
Quality score
Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.
Key takeaways
Summary
Based on the study abstract and findings.
- 1This suggests keto diets might help men lose weight but could make women gain weight — and that hormones like estrogen and testosterone play a big role.
- 2Male mice lost weight and fat; female mice gained weight and fat.
- 3Removing ovaries made females lose weight on keto, but still had high blood sugar.
- 4Removing testes made males gain weight like females.
Score breakdown, methodology, conflicts of interest, evidence analysis & raw study data
Publication
Journal
Journal of the Endocrine Society
Year
2025
Authors
Yuan Zhang, J. Cochran, Rhonda A Souvenir, Warren Tai, Rui Xia, Brendan S Gladwin, Natalie B Barton, Renata Oliveira Pereira, E. Dale, MD E. Dale Abel
Related Content
Claims (5)
Dietary fat is required to produce steroid hormones and is the main source of energy when carbohydrate intake is low.
In male C57BL/6J mice, a ketogenic diet reduces body weight and fat mass, while in female C57BL/6J mice, the same diet increases body weight and fat mass, even though both sexes produce the same levels of ketones.
In female mice, removing the ovaries reduces weight and fat gained from a ketogenic diet but does not improve blood sugar control, showing that estrogen influences fat storage but is not the only factor affecting insulin resistance during ketosis.
In male mice, a ketogenic diet raises levels of the protein FGF21 in the blood, and this increase is linked to higher FGF21 activity in brown fat tissue. In female mice, the same diet does not raise FGF21 levels.
In male mice, removing the testes prevents the weight loss and causes glucose intolerance that normally occur on a ketogenic diet, making their metabolism resemble that of female mice. This shows that hormones from the testes are required for the metabolic changes caused by ketosis in males.
Not medical advice. For informational purposes only. Always consult a qualified healthcare professional before making health decisions.