The ketogenic diet (KD), characterized by its very-low-carbohydrate and high-fat composition, has garnered attention for its potential impact on various aspects of health, including women's menstrual cycles. Recent research suggests that increasing ketones in the blood through a keto diet or supplements may help regulate irregular menstrual cycles or even restart periods that have ceased. This article delves into the emerging evidence surrounding the keto diet and its effects on menstruation, exploring the underlying mechanisms and potential implications for women's health.
Ketogenic Diet and Ketone Bodies
The keto diet converts fat into ketones used by cells in the body and brain as an alternative to glucose. The goal of a KD is to put the body in nutritional ketosis, which refers to a state in which the body has greater access to ketones for fuel and as a signaling molecule. Supplements also elevate blood ketones without a change in eating habits. All are designed to put the body in nutritional ketosis - the human body’s state when it has greater access to ketones as both fuel and a signaling molecule. Ketone bodies (KBs) levels are recognized as helpful to check compliance to the KDT and to attempt titration of the diet according to the individualized needs. KBs might undergo inter-individual and intra-individual variability and can be affected by several factors.
Emerging Research on Keto and Menstruation
In a study comparing weight loss results on low-fat and ketogenic diets with and without the addition of ketone supplements, 11 of 13 pre-menopausal participants who achieved nutritional ketosis reported at least one change in menstrual frequency, intensity - or both - during the intervention. Women on low-fat diets did not report any change to their periods. All women had lost the same relative percentage of weight. Their average age was 34, and all were healthy but overweight.
Madison Kackley, lead author of the study and a research scientist and lecturer in human sciences at The Ohio State University, noted that "There were six women who hadn’t had a period in over a year - who felt like their typical cycles were over. And their periods actually restarted on the diet." The study was published recently in PLOS ONE.
The researchers hypothesize that the presence of ketones may help regulate women’s health in regard to endocrine, cognitive and metabolic influences.
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Study Design and Findings
Nineteen women participated in the weight-loss diet trial - seven on a ketogenic diet alone, six on a keto diet combined with ketone salt supplements, and six on a low-fat diet. Researchers provided all of the food for the six-week study.
Both interventions resulted in clinically significant weight loss, less body fat, healthier cholesterol levels and better insulin sensitivity. The women who were randomized to the KD+PL diet attained clinically meaningful weight-loss (weight loss of ≥ 5% from baseline) at day 14, and by day 28 on the KD+KS and the LFD achieved clinically meaningful weight loss. Weight loss primarily originated from fat mass losses (Δ: -4.6 ± 1.3 kg; p < 0.001), with a minor but significant portion from fat-free mass (Δ: -1.7 ± 1.7 kg; p = 0.002). Overall body composition improved as reflected by total body fat percentage (Δ: -3.6 ± 4.9%; p = 0.033).
Menstrual history was one of dozens of lifestyle questions researchers asked about in biweekly assessments. Participants’ self-reports about their cycles took Kackley and colleagues by surprise.
Kackley stated, “It’s not a validated survey, but when we were reviewing responses, we realized we were changing the majority of these women’s cycles. Even for women who had normal menstrual cycles, their frequency changed,” Kackley said. “One of our participants was 33 years old and had never had a period in her life. She had her period for the first time after being in nutritional ketosis for five days.”
The two women who reported no change to their cycles were taking oral contraceptives. Women who reported menstrual changes were not using birth control.
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Role of Ketone Supplementation
Digging deeper into findings related to ketone supplementation is one goal of Kackley’s research program going forward. While the addition of keto salts to the diet did not contribute to improved weight or health markers, ketone levels were high in all of the women on the keto diet - including the two whose menstruation didn’t change. The finding hints at an individualized effect of added ketones in the blood.
“It was just the presence of ketones that essentially changed the menstrual cycle,” she said. “So if we’re looking for that signaling effect as opposed to a weight loss effect, then I think ketone supplementation could actually play a role in the grand scheme of hormonal regulation.”
Ongoing Research and Future Directions
Kackley is now working to pin down the mechanisms that explain this association. She has established a new lab at Ohio State dedicated to studying links between nutrition, exercise and women’s health.
As part of evaluating and selecting a tool to standardize tracking of research participants’ menstrual cycles in future studies, her team is currently monitoring a pilot group of women for the range of changes that occur between and during periods: muscle strength, fat composition, water retention, energy expenditure, hormone levels, body temperature and more. As far as Kackley is aware, this comprehensive data has never been collected before for the purposes of addressing cyclical changes with nutrition and/or exercise.
She envisions identifying interventions that not only help resolve women’s health concerns - such as polycystic ovary syndrome, perimenopause and postpartum depression, which her lab is currently studying - but also take some of the mystery out of menstruation, especially when it’s irregular or stops. An estimated 5 to 7% of women of reproductive age in the United States experience three months without a period each year.
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Kackley stated that this research is incredibly important because there are so many unanswered questions for women and that they are trying to change things for women and give them some control - something we historically haven’t had over our reproductive status.
Ketogenic Diet and Polycystic Ovary Syndrome (PCOS)
Another study aimed to investigate the use of a KD to help women with PCOS restore regular menstruation and achieve pregnancies. The ketogenic diet involved limiting carbohydrate intake to 20 grams daily, with specific protein and fat guidelines. The study excluded those who did not adhere to the diet for at least three months, those who used contraception, or postmenopausal women. Participants had monthly check-ups to monitor their weight, overall health, and menstrual cycles. The study's main focus was on the return of regularity to menstrual cycles and pregnancy rates, with additional attention on the time taken to conceive and any weight changes.
The average age of participants was 31 years, and their average body mass index (BMI) was 43.4. After six months, 92% of the women regained regular menstrual cycles; by 15 months, all had regular cycles. Of the 18 women who wanted to conceive, 55.6% became pregnant, with 63% achieving pregnancy within 12 months. Interestingly, all women who did not take metformin achieved pregnancy, compared to 38.5% in the metformin group. For women with available anti-mullerian hormone (AMH) data, those with lower AMH levels struggled to conceive, even with fertility treatments. This study highlights that a KD may improve menstruation regularity and increase pregnancy rates in women who have PCOS.
Ketogenic Diet Therapies (KDT) and Menstruation
Ketogenic dietary therapies (KDT) are well-established, safe, non-pharmacologic treatments used for children and adults with drug-resistant epilepsy and other neurological disorders. We report the preliminary results on six female patients affected by GLUT1DS or drug resistant epilepsy, undergoing a stable classic ketogenic diet.
There are currently four major KDTs: the classic ketogenic diet (CKD), the modified Atkins diet (MAD), the medium chain triglyceride diet (MCT), and the low glycemic index treatment (LGIT).
Monitoring Ketone and Glucose Levels During Menstruation
There are currently no data on possible variations in glucose blood levels and ketone bodies blood levels according to different phases of the menstrual cycle in patients undergoing CKD. And, conversely, there is no data in literature about possible variations of the menstrual cycle induced by CKD. Whether a variability could actually occur should be worthy of investigation since reduced KBs levels could lead to increased seizure presentation in patients with drug resistant epilepsy and even movement disorder manifestation or increased fatigue and reduced attention in patients with GLUT1-DS.
A longitudinal multicenter study aimed at investigating the ketone bodies and glucose blood levels during menstrual cycle in female patients with a diagnosis of GLUT1-DS or drug resistant epilepsy undergoing CKD.
During the study, patients or caregivers were asked to compile a diary made up of 2 distinct sections: the clinical diary and the nutritional diary. The first one included information about the menstrual cycle (date of the menstrual period and its duration, possible symptoms, i.e., headache or stomach ache), ketone bodies and glucose blood levels, neurological symptoms (seizures, movement disorders, fatigue and/or a worsening of concentration skills) and physical activity (at rest/normal daily activities/physical activity). Ketone bodies and glucose blood levels were measured in fasting conditions (i.e., before meals) twice a day, both in the morning and in the evening, through a reflectometer, for 3 months. The nutritional diary serves to verify whether the patient is correctly following the dietary prescription and to rule out any possible bias influencing glucose and ketone bodies blood levels.
Six patients were recruited among the three participating Centers. Three patients were affected by GLUT1-DS and the others had drug-resistant epilepsy. Age range was 13-18 years. All were in the normal weight range and maintained it for the duration of the study. All of them were following a stable CKD for a long time interval (time range 1-8 years) when included in the study. The compliance to the ketogenic dietary therapy was high in the entire cohort according to the food diaries provided. Two out of six patients (33,3%), both with a diagnosis of GLUT1-DS, were found to have an increased fatigue during days of menstruation. No changes in seizures or movement disorder manifestations, when present, were found in patients with GLUT1-DS according to menstrual period.
In the overall cohort, glycemia levels were found to be significantly higher (value of p 0.003) during menstruations compared to the remaining days. Ketone bodies blood levels were found to be lower during menstruations in 4/6 patients, even if not statistically significant.
To the best of our knowledge, the present study is the first one aimed at observing the course of KBs blood levels during the menstrual cycle in patients with GLUT1-DS and drug-resistant epilepsy undergoing KDT. Longitudinal studies serve in identifying changes in one or more variables between different periods, describing participants’ intra-individual and inter-individual changes over time and monitoring the degree and pattern of those changes (18). This is relevant for the proposed research since whether considered a reliable biomarker of KDT intervention, detecting whether KBs blood level changes are likely to occur in specific conditions, might lead to consideration of the suitability of transient preventive diet adjustments. Monitoring of urine and blood ketosis is recognized as helpful to check compliance to the KDT and to attempt titration of the diet according to the individualized needs.
Preliminary results showed a significant increase in glycemia levels during menstruation in the entire cohort and an inversely proportional trend of KB levels compared to glycemia.
Potential Risks and Considerations
Any diet that severely restricts calories, including some low carb diets, may disrupt certain hormones in some women.
If your diet is very restrictive, you may experience irregular menstrual cycles or amenorrhea. Amenorrhea is defined as the absence of a menstrual cycle for 3 months or more. Restricting carbs could contribute to some of these causes.
Amenorrhea occurs as a result of the drop in levels of many hormones, such as gonadotropin-releasing hormone, which starts the menstrual cycle. This results in a domino effect, causing a drop in the levels of other hormones such as luteinizing hormone, follicle-stimulating hormone, estrogen, progesterone, and testosterone.
If your carb or calorie consumption is too low, it may suppress your leptin levels and interfere with leptin’s ability to regulate your reproductive hormones. This is particularly true for underweight or lean women on a low carb diet.
Following a very low carb (ketogenic) diet over a long period of time may cause irregular menstrual cycles or amenorrhea.
Very low carb diets may cause a drop in thyroid function in some people. This may result in fatigue, weight gain, and low mood.
Optimal Carb Intake
The optimal amount of dietary carbs varies for each individual. However, the Dietary Guidelines for Americans recommend that carbs make up 45-65% of your daily calorie intake. Furthermore, the Food and Drug Administration states that for a 2,000-calorie diet, the Daily Value for carbs is 275 grams per day.
Given the potential side effects of restictive diets, certain women may do better consuming a moderate amount of carbs. This may include women who:
- are very active and struggle to recover after training
- have an underactive thyroid, despite taking medication
- struggle to lose weight or start gaining weight, even on a low carb diet
- have stopped menstruating or are having an irregular cycle
- have been on a very low carb diet for an extended period of time
- are pregnant or breastfeeding
For these women, benefits of a moderate-carb diet may include weight loss, improved mood and energy levels, normal menstrual function, and better sleep. Other women, such as athletes or those trying to gain weight, may find a higher daily carb intake appropriate.
A lower carb intake may benefit women with obesity, epilepsy, diabetes, polycystic ovary syndrome, and some other conditions.
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