A controlled feeding study demonstrated that 85% of premenopausal women following a ketogenic diet reported menstrual changes, including restoration of menses in women with prior amenorrhea. The changes occurred despite similar weight loss in women following a low-fat diet, who reported no menstrual changes.
In the 6-week randomized trial, published in PLOS ONE, researchers at The Ohio State University enrolled 19 premenopausal women (mean age = 34 ± 10 years, mean body mass index [BMI] = 32.3 ± 2.7 kg/m²). Thirteen participants were assigned to follow either a ketogenic diet (KD) with ketone salt supplements (KD + KS, n = 6) or KD with placebo (KD + PL, n = 7), while six age- and BMI-matched participants followed an isocaloric low-fat diet (LFD).
Both diets produced significant metabolic changes:
- Weight loss: –7.0 ± 0.5 kg (P < .001)
- Fat mass reduction: –4.6 ± 0.3 kg (P < .001)
- Fat-free mass loss: –1.7 ± 1.7 kg (P = .002)
- Body fat percentage decrease: –3.6 ± 4.9% (P = .033).
The KD groups maintained nutritional ketosis throughout the study, with mean β-hydroxybutyrate levels increasing by 1.2 ± 0.3 mM (P < .001), regardless of ketone salt supplementation.
The feeding protocol provided participants with preweighed meals:
- KD: 40 g/day carbohydrates
- LFD: 25% energy from lipids, < 10% saturated fat, < 30 g added oils
- Both diets: hypocaloric (75% of maintenance energy needs).
Blood chemistry showed improvements in both groups:
- Fasting insulin: –4.2 ± 3.6 μU/mL (P < .001)
- HOMA-IR: –0.9 ± 0.9 (P < .001)
- Total cholesterol: –28.3 ± 32.9 mg/dL (P = .01)
- HDL-C: –10.4 ± 13.9 mg/dL (P = .03).
The study protocol included:
- Bi-weekly in-person visits
- Fasting blood draws
- DXA body composition analysis
- Self-reported menstrual change surveys
- Daily blood ketone monitoring.
Two KD participants using oral contraceptives reported no menstrual changes. All menstrual effects occurred in non–birth control users.
The study documented menstrual changes specifically associated with the ketogenic diet separate from weight loss effects. Future research with larger sample sizes will investigate the relationship between ketosis and female reproductive health, including ovulation and hormonal parameters.
A statement of competing interests can be found in the study.