The Use of the Ketogenic Diet for Polycystic Ovary Syndrome (PCOS)
This post one of a series of posts discuss the peer-reviewed research on the potential of popular diets to address PCOS symptoms. You can also learn about the use of fasting or time restricted eating, the Mediterranean Diet, low glycemic index or load diets, the bean diet, and plant-based diets for PCOS.
Due to the prevalence of insulin resistance among women with PCOS, the ketogenic diet is often suggested for women with polycystic ovary syndrome (PCOS). Insulin resistance impairs the body’s ability to regulate blood sugar levels, and this is particularly problematic when large amounts of carbohydrates are consumed. The body has to pump out large amounts of insulin, and these high insulin levels cause increased production of testosterone in women with PCOS and hormonal imbalances. High levels of free testosterone contribute many of the symptoms of PCOS, including excessive hair growth on the face and body, acne, and male pattern baldness.
The ketogenic diet is a low-carb diet that restricts carbohydrate intake to less than 50 grams per day and emphasizes consuming the majority of your calories from fat, in order for the body to move into ketosis. In ketosis, the body is primarily fueled by ketones instead of glucose.
Keeping carbohydrates minimal is one (but not the only!) way to keep blood glucose levels stable without the need for a large release of insulin, and this can lead to significant reductions in PCOS symptoms.
Like other topics I’ve discussed, I’m a little disappointed with the existing literature on the use of the ketogenic diet for managing PCOS. I’d love to see a large, randomized controlled trial of the use of the diet across females with PCOS who span the range of possible BMIs and who also have co-morbidities.
I’d also love to see longer-term studies where participants are followed for several years. Following a ketogenic diet requires eliminating things like sugar, refined carbohydrates, whole grains, legumes, most fruits, and starchy vegetables. While eliminating sugar and refined carbohydrates may be beneficial, other carbohydrate sources contain important micronutrients and fiber. There is evidence that following a ketogenic diet reduces populations of Bifidobacterium and Firmicutes species, microorganisms found in the GI tract that have strong associations with gut and colon health (Rew et al. 2022). All of the studies discussed below only follow participants for 12 weeks, so long-term gut health and its implications for PCOS and the participants’ health more broadly cannot be determined.
While we wait for better studies, in the meantime, I’ve summarized the existing studies for you below, and then provided some take-home points at the end.
The ketogenic diet and its effects on liver function, menstrual cycle regularity, and metabolic health
There is one, lone randomized controlled trial (Li et al. 2021) examining the use of the ketogenic diet among women with PCOS, but this one restricts its sample to women who also have liver dysfunction, as measured by elevated levels of the liver enzymes alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST).
This study recruited females with PCOS between the ages of 18 and 50 with a body mass index (BMI) between 28 and 32 (in the upper range of overweight and lower range of obese).
Ketogenic diet participants consumed:
1300 - 1500 calories per day (chosen to maintain current body weight)
<50g of carbohydrates per day (5 - 10% of caloric intake)
18 - 27% of their calories from protein
70 - 75% of their calories from fat
There were no restrictions on the kinds of fats or animal products that the participants consumed.
The control diet participants:
Ate as they previously had
Took a polyene phosphatidylcholine capsule daily, a medication commonly used to treat liver damage
Took oral contraceptives once liver enzymes returned to lower levels
This study also included lifestyle changes. All participants were asked to undertake resistance training three times per week and were told that heavy aerobic exercise was not recommended.
The table below shows the results of the 12-week intervention for the control group and the ketogenic diet group.
Over the course of the 12-week intervention, keto diet participants experienced improvements in body composition which included about a 16% decrease in body fat percentage and a 14% decrease in total body weight, on average. The control group experienced no statistically significant changes in any measure of body weight or body fat. It is not clear if the weight loss came from the diet alone or if their caloric intake during the 12 weeks was lower than what they had been eating prior to the intervention, so these results may not occur on a higher-calorie ketogenic diet.
On average, neither group experienced significant changes in any of the measured hormone levels, which included follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen, progesterone, total testosterone, prolactin, and the LH to FSH ratio. However, there is a lot of variation in these measures, and that noise may be masking potential improvements that occurred for some of the women.
Even though there were no statistically significant changes in hormone levels, among keto diet participants, the average menstrual cycle length went from 72.5 days to 32.5 days, without the use of oral contraceptives. Irregular periods are generally defined as menstrual cycles longer than 35 days, so following this low-carbohydrate diet eliminated this symptom of PCOS.
The control group’s cycle “regulated” as well, but this group relied on an oral contraceptive for this regulation.
The keto diet group also saw a 17% reduction in LDL cholesterol levels (the kind associated with cardiovascular disease) and a 14% reduction in fasting blood glucose. The control group saw no improvements in any of the metabolic markers tested.
Lastly, in terms of liver function, using the standard medical approach to liver function among PCOS patients (medication + birth control pills), ALT and AST decreased by 47% and 41%, respectively.
This might seem great, but… using just the keto diet, ALT and AST decreased by 69% and 59% respectively.
Nutrition had a bigger impact on liver function than the standard medication used! And nutrition had the added benefit of regulating menstrual cycles, decreasing body fat, and improving cardiovascular health.
I’d say that’s a win!
The Ketogenic diet, In Vitro Fertilization (IVF), & PCOS
While this next study (Palafox-Gomez et al. 2023) does not use a control group, I think the magnitude of its results is compelling.
This recent study makes use of data from the Ingenes Institute, a fertility clinic in Mexico City. At this clinic, when an overweight or obese patient experiences a failed first in vitro fertilization (IVF) cycle, they are advised to try one of several nutritional interventions before trying a second IVF cycle.
Between 2020 and 2022, 32 patients with PCOS were referred for nutritional counseling. Of those 32, 12 chose to follow a ketogenic diet before starting their next IVF cycle. These patients were advised to:
Consume 1800 - 2000 calories/day (adjusted based on individual needs)
Consume ≤ 50 g of carbohydrates per day
Consume 1.5 g of protein per kilogram of body weight (or about 0.7 g per lb of body weight)
Consume the remainder of calories from fat (≥60% of calories)
The duration of the intervention depended on the patient's needs.
The table below shows the effects of the ketogenic diet on body composition indicators and metabolic health.
On average, patients lost about 11% of their body weight, which is pretty significant weight loss. Their triglycerides (correlated with risk for cardiovascular disease) fell by 25%. All markers of insulin resistance showed significant improvements, including a 12% decrease in fasting glucose, a 53% decrease in fasting insulin, and a 59% decrease in HOMA-IR (a measure of insulin resistance using both fasting glucose levels and fasting insulin levels).
Of the 12 patients, 7 successfully gave birth from their next round of IVF and 1 was pregnant at the time of publication. Two patients experienced miscarriages and two did not get pregnant during their next IVF cycle.
This group of patients had a 58% success rate (or 67% if the pregnancy at the time of publication resulted in a live birth). Leijdekkers et al. (2018) report success rates for two cohorts with a total of 115,384 women of reproductive age and find only a 24% success rate for those undertaking a second cycle of IVF after a failed first cycle.
The ketogenic diet resulted in an IVF success rate of more than double the reported rate for a second cycle of IVF.
The table below summarizes these results.
The ketogenic diet study uses a much smaller sample size, so it is possible that the group was just an exceptionally lucky group. Further research would help to determine if this is the case.
It should also be noted that patients self-selected to use the ketogenic diet instead of alternative options. It is possible that their inclination towards a low carbohydrate diet was due to biological factors that made the diet more effective for them. A randomized control trial would be helpful to know if the results are generalizable to all women with PCOS.
In the meantime, the ketogenic diet might still be something for women with PCOS to try before a cycle of IVF.
A Ketogenic Mediterranean Diet & PCOS
The next study (Paoli et al. 2020) considers a ketogenic version of the Mediterranean diet with added phytoextracts (compounds extracted from plants) obtained through supplements. It should be noted that the Mediterranean diet places a large emphasis on whole grains, so I personally don’t love their claim that this is a version of the Mediterranean diet. But that said, their version of the diet did improve the health of participants.
This study recruited 14 overweight women with PCOS in the Padova and Vincenza territories in Italy. Women ranged in age from 18 to 45 years old. Women were excluded from the study for any disorders involving the liver, kidneys, heart, or thyroid, and women were excluded if they were using any pharmacological treatments for PCOS.
For 12 weeks, participants consumed:
1600 - 1700 calories per day
Unlimited green leafy vegetables, cruciferous vegetables (broccoli, kale, cauliflower, etc.), zucchini, cucumbers, and eggplants
120 g of meat or 20 g of fish or 2 eggs per day
Four food supplements daily that contained 19 g of protein per portion and only 3.5 g of carbohydrates with added dry phytoextracts
Four liquid herbal extracts daily containing a variety of herbs intended to decrease common side effects of ketogenic diets including headaches, constipation, and bad breath
The remainder of their calories from fats (71% of total calories)
While I would much prefer that people consume real, whole food instead of supplements, this protocol allowed the researchers to standardize consumption across participants. Presumably, meals that mimic these (high protein, high vegetables, low carb, high fat) would produce similar results.
The table below summarizes the results of the 12-week intervention.
Like previous studies, participants in this study experienced a 12% reduction in body weight and a similar reduction in BMI. Insulin resistance improved with a 9% decrease in fasting blood glucose, a 10% decrease in fasting insulin, and a 19% decrease in HOMA-IR.
This study also found improvements in both triglycerides (19% reduction) and LDL cholesterol (25% reduction).
Lastly, this study finds significant differences in hormone levels, including a reduction in LH/FSH ratio (generally elevated in women with PCOS), a 14% reduction in total testosterone, and a 42% reduction in free testosterone (this latter measure is what drives acne, excess body hair growth, and male pattern baldness), and increases in progesterone, estradiol (a form of estrogen), and sex hormone binding globulin.
It should be noted that some of the herbs included in the herbal extracts are recommended for women with PCOS to lower testosterone levels, so it is unclear what portion of the impact on testosterone (and potentially the other sex hormones) is a result of the ketogenic nature of the diet or a result of consuming these herbs. Given that other studies did not observe changes in testosterone under the ketogenic diet, further research is warranted to explore further.
Very Low Calorie Ketogenic Diet vs. the Mediterranean Diet & PCOS
For completeness, I will briefly discuss Cincionne et al. (2023), which explores the effects of a very low-calorie ketogenic diet vs. the Mediterranean diet on PCOS symptoms. I strongly disagree with the use of very low-calorie diets in most (and possibly all!) cases. It is not a sustainable form of weight loss and may result in later weight gain, nor does it teach healthy habits. However, in the short term, it may reduce PCOS symptoms.
In this study, the very low-calorie ketogenic diet group participants consumed:
1.1 - 1.2 g of protein per kg of ideal body weight per day coming from a whey protein beverage and animal products
less than 30 g of carbohydrates per day
30 g of fat per day, mainly in the form of olive oil
about 600 calories of food per day
The Mediterranean diet group participants consumed:
About 500 calories less than their individual maintenance calorie amount
55% of their calories from whole grains (primarily whole wheat)
25% of their calories from fat (primarily polyunsaturated fatty acids like olive oil, pistachios, and almonds)
20% of their calories from protein (primarily meat and legumes)
Both groups followed their respective diets for 45 days.
The table below summarizes the results for both groups.
Given the larger caloric deficit among the keto diet group, it is unsurprising that this group lost more weight and experienced larger improvements in insulin sensitivity. They also experienced larger positive changes in reproductive hormone levels in the short term. Out of the 73 keto diet participants, 25 experienced a menstrual cycle in the 45-day intervention period despite previously experiencing amenorrhea (the absence of a menstrual cycle).
While these results are great, we have no data on what happened to these participants once they returned to their previous ways of eating. It is very likely that results were reversed.
It is possible to get the same results more sustainably, so unless there is some need for rapid weight loss, I would strongly urge more sustainable eating habits.
Limitations in the existing literature
While the studies above provide some evidence that a ketogenic diet could be beneficial for women with PCOS who are trying to lose weight, trying to improve liver health, and/or trying to become pregnant through the use of IVF, they have several limitations.
The first and perhaps most important limitation is the exclusion of women with hypothyroidism from these studies. While the link is not fully understood, women with PCOS are more likely to have auto-immune hypothyroidism than the general population (Zecker-Lubecka and Hennig 2021). There have also been studies that demonstrate a decline in thyroid hormone production, in particular Triiodothyronine (T3), with low carbohydrate diets (Bisschop et al. 2001, Volek et al. 2002). If you choose to follow a ketogenic diet, you might consider periodic thyroid hormone testing to make sure that T3 levels are not declining.
Second, all of these studies focused on women with BMIs consistent with being overweight or obese and all induce weight loss as part of the intervention. Weight loss by itself can improve insulin sensitivity and hormone levels, so it is unclear if the use of the ketogenic diet would help improve PCOS symptoms in the absence of weight loss.
Third, as mentioned above, the ketogenic diet can adversely affect gut health, so I am concerned about someone following this diet for the long term.
Lastly, like most studies of women with PCOS, this set of studies does not consider the interplay between the diet intervention and physical activity. In a previous post, I summarized the literature on exercise and PCOS. High-intensity interval training turns out to be great for improving insulin sensitivity and hormone levels (Patten et al. 2022). To truly exercise at high intensity, your muscles need stores of glycogen (glucose-based fuel), which do not get restored under a ketogenic diet. This will make high-intensity interval training workouts feel pretty awful (I know this from experience!), and studies have shown that it decreases your maximum workload (Zajac et al. 2014). Thus, the use of a ketogenic diet may not pair well with those who perform high-intensity exercise.
Take-home points
A ketogenic diet has been shown to reduce body weight, improve liver function, and improve menstrual regularity among overweight or obese women with PCOS.
The diet may also improve IVF outcomes, although additional research is needed to confirm current findings.
A ketogenic diet generally consists of consuming less than 50 g of carbohydrates a day, consuming about 70% to 75% of calories from fat, and consuming the remainder of calories from protein.
More research is needed to determine the impact of using the ketogenic diet when weight loss is not a goal.
More research on the long-term impacts of the ketogenic diet on thyroid function and thyroid hormones is needed.
References
Bisschop PH, Sauerwein HP, Endert E. and Romijn JA. 2001. Isocaloric carbohydrate deprivation induces proteincatabolism despite a low T3-syndrome in healthy men. Clinical Endocrinology, 54:75-80 https://doi.org/10.1046/j.1365-2265.2001.01158.x
Cincione IR, Graziadio C, Marino F, Vetrani C, Losavio F, Savastano S, Colao A, and Laudisio D. 2023. Short‐time effects of ketogenic diet or modestly hypocaloric Mediterranean diet on overweight and obese women with polycystic ovary syndrome. Journal of Endocrinological Investigation 46:769–777 https://doi.org/10.1007/s40618-022-01943-y
Leijdekkers JA, Eijkemans MJC, van Tilborg TC, Oudshoorn SC, McLernon DJ, Bhattacharya S, Mol BWJ, Broekmans FJM, and Torrance HL. 2018. Predicting the cumulative chance of live birth over multiple complete cycles of in vitro fertilization: an external validation study. Human Reproduction, 33(9):1684–1695 https://doi.org/10.1093/humrep/dey263
Li J, Bai W, Jiang B, Bai L, Gu B, Yan S, Li F, and Huang B. 2021. Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open- label, parallel-group, controlled pilot trial. J. Obstet. Gynaecol. Res. 47(3):1145–1152 https://doi.org/10.1111/jog.14650
Palafox-Gómez C, Ortiz G, Madrazo I, and López-Bayghen E. 2023. Adding a ketogenic dietary intervention to IVF treatment in patients with polycystic ovary syndrome improves implantation and pregnancy. Reproductive Toxicology 119:108420 https://doi.org/10.1016/j.reprotox.2023.108420
Patten RK, McIlvenna LC, Levinger I, Garnham AP, Shorakae S, Parker AG, McAinch AJ, Rodgers RJ, Hiam D, Moreno-Asso A, and Stepto NK. 2022. High-intensity training elicits greater improvements in cardio-metabolic and reproductive outcomes than moderate-intensity training in women with polycystic ovary syndrome: A randomized clinical trial. Human Reproduction 37(5):1018–1029, https://doi.org/10.1093/humrep/deac047
Paoli A, Mancin L, Giacona MC, Bianco A, and Caprio M. 2020. Effects of a ketogenic diet in overweight women with polycystic ovary syndrome. Journal of Translational Medicine 18:104 https://doi.org/10.1186/s12967-020-02277-0
Rew L, Harris MD, and Goldie J. 2022. The ketogenic diet: its impact on human gut microbiota and potential consequent health outcomes: a systematic literature review. Gastroenterology and Hepatology From Bed to Bench 15(4):326-342. https://doi.org/10.22037/ghfbb.v15i4.2600
Volek JS, Sharman MJ, Love DM, Avery NG, Gómez AL, Scheett TP, and Kraemer WJ. 2002. Body Composition and Hormonal Responses to a Carbohydrate-Restricted DietMetabolism, 51(7):864-870 https://doi.org/10.1053/meta.2002.32037
Zajac A, Poprzecki S, Maszczyk A, Czuba M, Michalczyk M,and Zydek G. 2014. The Effects of a Ketogenic Diet on Exercise Metabolism and Physical Performance in Off-Road Cyclists. Nutrients, 6(7):2493–2508 https://doi.org/10.3390/nu6072493
Zecker-Lubecka N and Hennig EE. 2021. Genetic Susceptibility to Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto’s Thyroiditis: How Far Is Our Understanding? Frontiers in Immunology, 12 https://doi.org/10.3389/fimmu.2021.606620
Disclaimer: This post is not intended to diagnose or treat any medical issues. It is intended for informational purposes only. I am not a medical practitioner. Always consult a trusted healthcare provider with any questions you may have about a medical condition or treatment and before starting any new health care regimen.