Plain language summary
Approximately 40% of adult women in the U.S. have diabetes or pre-diabetes which can lead to hormone-related disorders. The aim of this study was to evaluate the effects of a ketogenic diet (KD) with or without ketone supplementation on anthropometric and biochemical parameters and menstrual regularity. 13 pre-menopausal women with overweight or obesity were randomly assigned to a calorie-reduced KD with ketones or with placebo, with all meals provided for 6 weeks. A matched cohort of 6 women was given a low-fat diet (LFD) with the same calorie and nitrogen (protein) content plus placebo. Women in both KD groups maintained nutritional ketosis for the duration of the intervention. Women in all 3 groups lost weight, mostly in the form of fat loss, and improved insulin sensitivity and blood lipids, with no significant differences between groups. Significant changes in menstruation were reported by women in both KD groups, but not in the LCD control group, with 6 of the 13 women reporting that they regained menstruation after more than 1 year within 28 days on the KD. 3 of these were on the ketone supplement and 3 on the placebo. The authors state that the mechanisms by which the KD may influence menstrual physiology is not known.
Abstract
Weight loss can positively alter female physiology; however, whether dietary carbohydrate- or fat- restriction confer unique effects is less studied. Precisely designed, hypocaloric well-formulated ketogenic diets (KD; ~75% energy for weight maintenance) were compared to isocaloric/isonitrogenous low-fat diet (LFD) on self-reported menses in pre-menopausal overweight and obese women (mean ± SD: 34 ± 10 years, BMI: 32.3 ± 2.7 kg/m2). Women received a precisely-weighed and formulated KD with either twice-daily with ketone salts (KS; n = 6) or a flavor-matched placebo (PL; n = 7) daily for six-weeks. An age and BMI-matched cohort (n = 6) was later assigned to the LFD and underwent the same testing procedures as the KD. Self-reported menses fluctuations were assessed bi-weekly along with measures of body weight, body composition, and fasting serum clinical chemistries using repeated measures ANOVA with Bonferroni post-hoc corrections. Both diets elicited clinically-significant weight-loss (Δ: -7.0 ± 0.5 kg; p < 0.001), primarily from fat-mass (Δ: -4.6 ± 0.3 kg; p < 0.001), and improved insulin-sensitivity and serum lipids (all p < 0.05). Fasting plasma glucose and inflammatory markers were not different between diets. Fasting capillary beta-hydroxybutyrate (R-βHB) increased significantly during the KD, independent of supplementation (Δ: 1.2 ± 0.3 mM R-βHB; p < 0.001). Women randomized to the KD+KS (30%) and KD+PL (43%) reported subjective increases in menses frequency and intensity after 14 days, whereas another third reported a regain of menses (>1 year since the last period) after 28 days. No LFD participants reported menses changes. Nutrient-dense, whole-food KDs and LFD improved weight, BMI, body composition, and blood parameters in pre-menopausal women after six-weeks. Changes in self-reported menses were described by most of the KD participants, but none of the LFD women suggesting there may be unique effects of nutritional ketosis, independent of weight loss.
Methodological quality
Jadad score
:
2
Allocation concealment
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Not applicable
