Probiotics for Polycystic Ovary Syndrome (PCOS)

Probiotics have become all the rage recently, and as we learn more about the effects of the gut microbiome on the rest of the body, it is becoming increasingly clear that gut health plays a bigger role than most of us imagined.

Due to the potential widespread impact of the gut microbiome and gut health, the microbiome might play a role in polycystic ovary syndrome. This article explores what recent studies have found about the use of probiotic supplements for PCOS symptoms and various markers of health.

There are some promising results, so read on!

The Effects of Probiotics on Weight Loss, Metabolic Health, and Cardiovascular Health for women with pcos

Women with PCOS tend to struggle with weight gain and insulin resistance, and we are at higher risk for things like high blood pressure, high cholesterol, and heart disease. Ahmadi et al. (2017) used a randomized controlled trial to explore the potential effects of probiotics on these risk factors for women with PCOS. Sixty women of reproductive age with PCOS were recruited from the Taleghani and Emam Reza Clinic in Arak, Iran. The study excluded anyone with type 2 diabetes, active liver disease, or histories of heart or liver failure, and anyone taking any hormonal medications, anti-obesity medications, or antidepressants.

Half of the participants were assigned to the treatment group. This group consumed:

• Probiotic capsules containing:

  1. Lactobacillus acidophilus (2x 10^9 CFU/g)

  2. Lactobacillus casei (2 x 10^9 CFU/g)

  3. Bifidobacterium bifidum (2x 10^9 CFU/g)                                    

The other half of the participants were assigned to the control group. This group consumed placebo capsules that looked identical to the probiotic capsules. 

Both groups took their respective capsules for 12 weeks.

The table below shows the percent change in measures of metabolic health and cardiovascular health for the placebo and treatment groups after 12 weeks of taking their respective capsules.

The effects of 12 weeks of supplementation with probiotics or a placebo on metabolic and cardiovascular health for women with polycystic ovary syndrome (PCOS). Results compiled from Ahmadi et al. (2017). “-” means there was no statistically significant difference between the changes observed across groups.

In terms of metabolic syndrome indicators, the probiotic group experienced improvements in 4 of the 5 metrics. They experienced about a 3% decrease in fasting blood sugar, a 14% decrease in fasting insulin, almost a 16% decrease in HOMA-IR (a measure of insulin resistance), and a small increase in QUICKI, a measure of insulin sensitivity. The only measure that experienced a decline was HOMA-B, a measure of the function of beta cells, which are the pancreatic cells that produce insulin. The overall improvement in insulin resistance likely also led to improvements in PCOS symptoms and potentially improved the regularity of their menstrual cycles. Unfortunately, this study did not measure these metrics.

Regarding cardiovascular health, the probiotic group experienced an 11% decrease in triglyceride and VLDL cholesterol levels. As we learn more about cholesterol and its links to heart disease, there is increasing evidence that VLDL cholesterol has a stronger link to plaque build-up in arteries than other forms of cholesterol. Similarly, blood triglyceride levels are associated with an increased risk of heart attacks, strokes, and heart disease. The probiotic group also experienced small increases in total cholesterol, HDL cholesterol (generally considered a good form of cholesterol), and LDL cholesterol (typically considered a higher-risk form of cholesterol). However, there were no statistically significant differences between the placebo and probiotic groups for these latter three metrics.

The Effects of Probiotic and Prebiotic Supplementation Body Composition, Metabolic Health, and Reproductive Health for women with pcos

While the study above considered supplementation with just probiotics, three studies experiment with synbiotic supplements - supplements that contain both probiotics as well as prebiotics, which are food sources for probiotics, and measure similar metrics as the study above. The combination of pre- and probiotics may be better than supplementing with probiotics alone because the prebiotics support the supplemented probiotics as well as other probiotics already present in the gut.

Chudzicka-Strugala et al. (2021) recruited 65 overweight or obese women (BMI > 25) with PCOS from patients receiving medical care at the Reproductive Endocrinology & Infertility Clinical Services Department at the Poznan University of Medical Sciences Hospital in Poland.

This study used a randomized controlled trial design, and randomly assigned half of the participants to the placebo group who:

• Consumed 4 capsules of placebo daily.

And half of the participants to the treatment group who:

• Consumed 4 synbiotic supplement capsules daily. These capsules contained:

  • Bifidobacterium lactis (W51 and W52)

  • Lactobacillus acidophilus (W22)

  • Lactobacillus paracasei (W20)

  • Lactobacillus plantarum (W21)

  • Lactobacillus salivarius (W24)

  • Lactobacillus lactis (W19)                        

Both groups were counseled on lifestyle changes that included:

• Consuming 1400 - 1800 kcal per day based on their individual body compositions

• Individualized advice about foods to include or exclude

• Encouragement to refrain from consuming alcohol

• Encouragement to walk 30 - 40 minutes per day

For all participants, baseline measurements were taken either during the follicular phase of their naturally occurring cycle or after medroxyprogesterone-induced menstruation (for more information on menstrual cycle phases, check out this post).

Participants followed their respective plans for 3 months, and then measurements were retaken. The table below contains the percent change in each metric measured for the placebo group and the probiotic + prebiotic group.

The effects of three months of diet and lifestyle changes and supplementation with either a synbiotic (probiotics + prebiotics) or a placebo on body weight, body composition, reproductive hormones, metabolic health, and cardiovascular health. Results compiled from Chudzicka-Strugala et al. (2021). “-” means there was no statistically significant difference between the changes observed across groups.

Given that both groups followed a calorie-restricted diet and added in physical activity, it is not surprising that both groups experienced reductions in body weight, BMI, body fat percentage, and various body measurements like waist and hip circumference.

Interestingly, the group consuming probiotics and prebiotics experienced bigger decreases in weight, BMI, and waist circumference than the placebo group. Improvements in gut health led to bigger effects of diet and exercise! 

While the placebo group did not experience any reductions in total testosterone or the Ferriman-Gallway score (a measure of excessive facial and/or body hair growth), the supplement group experienced reductions in both of these measures. Excessive body hair is one of the most frustrating symptoms of PCOS, so it is pretty exciting to see that synbiotic supplementation could play an important role in reducing this symptom. 

The placebo group experienced reductions in luteinizing hormone (LH), which is often high in women with PCOS. However, this group also experienced a reduction in follicle-stimulating hormone, which can be low relative to LH in women with PCOS. Thus, it is not clear that these changes, in combination, are necessarily helpful, and indeed, the LH to FSH ratio remained unchanged for the placebo group. 

Unfortunately, neither group experienced improvements in measures of metabolic health like fasting blood glucose or fasting insulin, and neither group experienced improvements in cholesterol levels. Both groups did experience a decrease in triglycerides, suggesting some improved cardiovascular health from the lifestyle modifications.

Hariri et al. (2023) followed a similar protocol with lifestyle modifications and a synbiotic supplement. Like the previous study, they found no effects of supplementation on cholesterol levels, nor did they find any effects of supplementation on triglycerides or c-reactive protein, a measure of inflammation.

Darvishi et al. (2021) also studied the effects of synbiotic supplementation on women with PCOS. This study recruited 68 overweight or obese women with PCOS from the General Gynaecology Clinic Department at the Alzahra Hospital in Iran. Like the previous study, this study also used a randomized controlled trial, and randomly assigned participants to either:

The control group who:

• Consumed one placebo capsule containing starch each day after lunch

Or the treatment group who:

• Consumed one synbiotic capsule that contained:

  • Lactobacillus casei

  • Lactobacillus rhamnosus

  • Lactobacillus bulgaris

  • Lactobacillus acidohilus

  • Bifidobacterium longum

  • Streptococcus thermophilus

  • fructooligosaccarides (an inulin-type prebiotic).

Both groups took their respective capsules for 8 weeks. 

Unlike Chudzicka-Strugala et al., neither group made adjustments to their diets or their activity levels.

The table below shows the percent changes in various metrics across the 8 weeks of the intervention.

The effects of 8 weeks of supplementation with a synbiotic (probiotics + prebiotics) on body weight, body composition, metabolic health, and cardiovascular health for women with polycystic ovary syndrome (PCOS). Results compiled from Darvishi et al. (2021). “-” means there was no statistically significant difference between the changes observed across groups.

Interestingly, the placebo group experienced increases in body weight and BMI and increases in fasting glucose, fasting insulin, and HOMA-IR (a measure of insulin resistance), indicating worsened metabolic health. They also experienced increases in total cholesterol and LDL cholesterol alongside decreases in HDL cholesterol, all indicating worsened cardiovascular health.

These trends of the placebo group have been seen in other studies because women with PCOS often experience worsened body composition, metabolic health, and cardiovascular health over time in the absence of any intervention. For this study, however, I question whether the starch used in the placebo capsule contributed to these results. I would be curious to see how their metrics would have changed if provided with a non-starchy placebo, given the tendency of women with PCOS to exhibit insulin resistance and reduced carbohydrate tolerance.

While the placebo group experienced worsened health, the group consuming the probiotic + prebiotic supplement experienced decreases in body weight, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, fasting insulin, and HOMA-IR (a measure of insulin resistance). All of these trends indicate improved body composition and improved metabolic health. While the body composition changes were small, they were still the opposite trend experienced by the control group, and they were simply the result of taking a supplement, in the absence of any diet or exercise intervention. 

The supplement did not have any significant effect on any measure of cardiovascular health.

The results of this study call into question the "calories in, calories out" model of weight loss. Caloric consumption did not change, but the treatment group still saw modest decreases in body composition, suggesting that eliminating gut dysbiosis and improving gut health can potentially lead to weight loss.

The Effects of Probiotics on Reproductive Hormone Levels and Symptoms of PCOS

While many studies of PCOS patients do not directly measure symptoms of PCOS like acne and hirsutism (excessive growth of hair on the face and body), a study by Arab et al. (2020) does measure these things. This study recruited 99 women with PCOS from the Arash Women's Hospital in Tehran, Iran. Participants were aged 19 to 37 years old, with body mass indexes of 25 or higher (associated with being overweight or obese). As usual, this study excluded participants with other health challenges including diabetes, lung, pancreatic, kidney, liver, or cardiovascular disease, or any autoimmune diseases. 

50 of the participants were randomly assigned to the probiotic group. This group consumed: 

• 2 capsules per day, which contained 7 strains of beneficial bacteria, including 

  • Lactobacillus acidophilus (ATCC: 4357) 3 × 10^10 colony-forming units (CFU)

  • Lacticaseibacillus casei (ATCC: 393) 3 × 10^9 CFU

  • Lactobacillus bulgaricus (ATCC: 11842) 5 × 10^8 CFU

  • Lacticaseibacillus rhamnosus (ATCC: 7469) 7 × 10^9 CFU

  • Bifidobacterium longum (ATCC: 15697) 1 ×10^9 CFU

  • Bifidobacterium breve (ATCC: 15700) 2 × 10^10 CFU

  • Streptococcus thermophilus (ATCC: 19258) 3 × 10^8 CFU) 

  • 21 mg inulin, a prebiotic that can support beneficial gut bacteria                  

The control group took two placebo capsules each day which contained 250 mg starch and 250 mg maltodextrin.

Each group took their respective capsules for 12 weeks.

The table below shows the percent change in reproductive hormones for the probiotic and placebo groups.

The effects of 12 weeks of synbiotic (probiotics + prebiotics) supplementation on women with polycystic ovary syndrome (PCOS). Results compiled from Arab et al. (2020). “-” means there was no statistically significant difference between the changes observed across groups or for that group alone.

Women with PCOS tend to have elevated luteinizing hormone (LH) and in particular, LH is high relative to follicle-stimulating hormone (FSH). Thus, we want interventions that lower the ratio of LH to FSH. In this study, neither group experienced statistically significant changes in FSH, and both groups experienced increases in LH, which is the opposite of what we want to see. The increase in LH to FSH ratio was statistically significant for the probiotic group, but not the placebo group. 

The probiotic group did not experience any changes in total testosterone levels, sex hormone-binding globulin, or free androgen index. The placebo group experienced an increase in their levels of total testosterone and free androgen index and decreases in sex hormone binding globulin. In this sense, if the probiotic helped the probiotic group prevent worsening hormonal imbalances, then we could consider this a benefit of probiotic supplementation, even though they did not experience changes themselves. Both groups experienced an increase in DHEAS, which is another androgen hormone. 

In terms of symptoms of PCOS, the probiotic group experienced statistically significant changes in the percentage of participants experiencing different categories of acne, while the placebo group did not. In particular, the probiotic group saw an increase in the percent who had no acne and a decrease in the percent who had severe acne. 

Pre- and post-intervention acne severity for women with polycystic ovary syndrome (PCOS) taking either a probiotic supplement or a placebo for 12 weeks. Results compiled from Arab et al. (2020).

The placebo group also experienced small changes in the percentage experiencing different levels of hirsutism, while the placebo group did not. After the intervention, the probiotic group had a larger percent with no hirsutism and smaller percentages with mild or moderate hirsutism. The percentage with severe hirsutism did not change. 

Pre- and post-intervention hirsutism (excessive facial and/or body hair growth) severity for women with polycystic ovary syndrome (PCOS) taking either a probiotic supplement or a placebo for 12 weeks. Results compiled from Arab et al. (2020).

It is quite interesting that this study did not find beneficial effects of probiotics on lab-measured hormone levels, but did observe positive effects of probiotic supplementation in terms of the symptoms of PCOS. This suggests that a healthy gut may play a role in symptoms, regardless of hormone levels. It also suggests that more studies of women with PCOS should measure symptoms, and not just lab values.

Probiotic Supplements and Menstrual cycle Regularity

Menstrual cycle regularity is often considered to be a woman's 6th vital sign. And for women with PCOS, our cycles are usually especially sensitive to changes in our mental and physical health. It is surprising to me that so few studies exploring the effects of probiotics on women with PCOS track menstrual cycle regularity. Fortunately, Kaur et al. (2022) did track menstrual cycle regularity and found positive effects of supplementation for some participants.

This study recruited 104 participants from the Gynaecology Out-Patient Department (OPD) at the Postgraduate Institute of Medical Education and Research in India.

Participants were split into:

• A treatment group, who consumed capsuled containing 10 billion colony forming units (CFU) consisting of the following probiotic strains and prebiotics:

  • Lactobacillus acidophilus

  • Lactobacillus rhamnosis, UBLR-58

  • Lactobacillus reuteri, UBLR-87

  • Lactobacillus plantarum, UBLP-40

  • Lactobacillus casei, UBLC-42

  • Lactobacillus fermentum, UBLF-31

  • Bifidobacterium bifidum, UBBB-55

  • Fructo-oligosaccharide (100 mg)

And a control group who consumed similar capsules containing maltodextrin.

For the first two months, all participants took 1 of their respective capsules per day. For the next four months, all participants took two capsules per day.

The table below reports the changes, if any, experienced by participants in each group.

The effects of 6 months of supplementation with either a probiotic or placebo on menstrual cycle regularity, metabolic health, and body composition for women with polycystic ovary syndrome (PCOS). Results compiled from Kaur et al. (2022). “-” means there was no statistically significant difference between the changes observed across groups.

There was a significant reduction in participants with irregular menstrual cycles and polycystic ovaries among the probiotic group, and the number of participants with regular menstrual cycles more than doubled among probiotic users. It should be noted, however, that 37 out of the 52 participants in the probiotic group still experienced irregular periods at the end of the study period, as shown in the graphs below. While the use of probiotics did help some women achieve menstrual cycle regularity, probiotics should not be seen as a cure-all for menstrual and fertility challenges for women with PCOS.

The effects of 6 months of probiotic supplementation (or placebo) on menstrual cycle regularity for women with polycystic ovary syndrome (PCOS). Irregular periods are a hallmark of PCOS and contribute to infertility struggles.

When considering the effects of probiotics on androgen hormones, we see that those taking the probiotic dietary supplements experienced reductions in total testosterone, which tends to be elevated in women with PCOS. Neither group, however, experienced a change in DHEAS, another important androgen hormone. 

In terms of metabolic effects, the placebo group actually experienced an increase in fasting blood sugar (a negative change), while the probiotic group experienced no change in fasting blood sugar. Both groups experienced decreases in fasting insulin levels, but only the probiotic group experienced a decrease in HOMA-IR, a measure of insulin resistance. Women with PCOS almost always have some degree of insulin resistance driving their symptoms, so any intervention that reduces insulin resistance can help reduce PCOS symptoms and improve overall health.

Lastly, in terms of weight management, the probiotic group experienced decreases in weight, waist circumference, hip circumference, waist-to-hip ratio, and body mass index. While the placebo group also experienced reductions in some of these measures, the probiotic group experienced larger reductions for all measures.

Probiotic and Prebiotic Supplements and Mental Health

While most studies stick to measuring objective things like fasting glucose and body weight, Jamilian et al. (2018) chose to focus on subjective measures of well-being in addition to several objective health measures. Mental health challenges are common among women with PCOS, so assessing the effects of supplements on indicators of mental health is important. This study recruited 60 females with PCOS aged 18 - 40 years old.

Participants were divided into a treatment group who took capsules containing:

• Lactobacillus acidophilus

• Lactobacillus reuteri

• Lactobacillus fermentum

• Bifidobacterium bifidum

• 200 micrograms of Selenium

And a control group who took placebo capsules that were a similar shape and size to the probiotic capsules.

Both groups took their respective capsules for 12 weeks. 

The effects of 12 weeks of supplementation with a probiotic + selenium or a placebo on measures of mental health, reproductive hormones, hirsutism (excessive facial and/or body hair), and measures of inflammation. Results compiled from Jamilian et al. (2018). “-” means there was no statistically significant difference between the changes observed across groups.

Neither group of participants experienced significant reductions in body weight or BMI.

However, the probiotic + selenium supplement was associated with both physical and mental health benefits. The study used three measures of mental health: The Beck Depression Inventory, the General Health Questionnaire, and the Depression, Anxiety, and Stress Scale. For all three measures, lower scores indicate better mental health. While the control group's scores decreased by about 1.4% to 1.9%, the treatment group experienced reductions ranging from 3.1% to 7.1%.

In terms of sex hormones, the treatment group experienced a 21.4% reduction in testosterone and a 5.1% increase in sex hormone-binding globulin (SHBG). SHBG binds free testosterone, reducing the effects of this androgen hormone. Both of these changes likely contributed to the reduction in the modified Ferriman-Gallway score experienced by the treatment group. This is a measure of hirsutism, or excess hair growth on the face and body, resulting from high male hormones. 

Lastly, the study considered several measures of cardiovascular health and overall antioxidant capacity. For all measures, the treatment group experienced improvements, while the placebo group experienced some changes that were actually in the wrong direction.

This study shows the positive effects of probiotic supplementation across several different categories of health, suggesting that probiotics are helpful for overall health, as well as for PCOS, specifically.

Take Home Points

For women with PCOS, probiotic supplementation may:

• Improve mental health

• Improve menstrual cycle regularity

• Reduce symptoms of PCOS like acne and hirsutism

• Increase weight loss when reducing calories

• Contribute to weight loss without reducing calories

• Improve metabolic health by reducing insulin resistance

The effects of probiotic supplementation on cardiovascular health appear to be limited.

The effects of probiotic supplementation on reproductive hormone levels were inconsistent across studies.

While probiotics are helpful for some women with PCOS, not all women experience substantial benefits from supplementation.

While these studies focused on probiotic supplementation, fermented foods are also a great source of probiotics! Check out this stew and this breakfast bowl that contain fermented foods.

Always talk to your healthcare provider before starting any supplementation program!

About the author

Kelly Grogan, Ph.D., NTM, is a holistic nutrition therapist who is passionate about helping females with PCOS. She currently manages her own PCOS with nutrition and lifestyle tools that she developed through extensive review of the scientific literature on PCOS interventions.

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 healthcare regimen.

References

Ahmadi S, Jamilian M, Karamali M, Tajabadi-Ebrahimi M, Jafari P, Taghizadeh M, Memarzadeh MR and Asemi Z. 2017. Probiotic supplementation and the effects on weight loss, glycaemia and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Human Fertility, 20(4):254-261, DOI: 10.1080/14647273.2017.1283446

Arab A, Hossein-Boroujerdi M, Moini A, Sepidarkish M, Shirzad N, and Karimi E. 2022. Effects of probiotic supplementation on hormonal and clinical outcomes of women diagnosed with polycystic ovary syndrome: A double-blind, randomized, placebo-controlled clinical trial. Journal of Functional Foods, 96:105203, https://doi.org/10.1016/j.jff.2022.105203

Chudzicka-Strugała I, Kubiak A, Banaszewska B, Zwozdziak B, Siakowska M, Pawelczyk L, Duleba AJ. 2021. Effects of Synbiotic Supplementation and Lifestyle Modifications on Women With Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism, 106(9):2566–2573, https://doi.org/10.1210/clinem/dgab369

Darvishi S, Rafraf M, Asghari-Jafarabadi M, and Farzadi L. 2021. Synbiotic Supplementation Improves Metabolic Factors and Obesity Values in Women with Polycystic Ovary Syndrome Independent of Affecting Apelin Levels: A Randomized Double-Blind Placebo-Controlled Clinical Trial. International Journal of Fertility and Sterility, 15(1):51-59. doi: 10.22074/ijfs.2021.6186.

Hariri Z, Yari Z, Hoseini S, Mehrnami A, Abhari K, and Sohrab G. 2023. Effects of Synbiotic-Containing Bacillus coagulans (GBI-30) on the Cardiovascular Status of Patients With Polycystic Ovary Syndrome: A Triple-blinded, Randomized, Placebo-controlled Study. Clinical Therapeutics, 45(10):e193-e199. doi: 10.1016/j.clinthera.2023.07.024.

Hariri Z, Yari Z, Hoseini S, Abhari K, Sohrab G. 2024. Synbiotics as an ameliorating factor in the health-related quality of life in women with polycystic ovary syndrome. A randomized, triple-blind, placebo-controlled trial. BMC Women's Health, 24(1):19. doi: 10.1186/s12905-023-02868-1. 

Jamilian M, Mansury S, Bahmani F, Heidar Z, Amirani E, Asemi Z. 2108. The effects of probiotic and selenium co-supplementation on parameters of mental health, hormonal profiles, and biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome. Journal of Ovarian Research, 11(1):80. doi: 10.1186/s13048-018-0457-1. 

Kaur I, Suri V, Sachdeva N, Rana SV, Medhi B, Sahni N, Ahire J, Singh A. 2022. Efficacy of multi-strain probiotic along with dietary and lifestyle modifications on polycystic ovary syndrome: a randomized, double-blind placebo-controlled study. European Journal of Nutrition, 61(8):4145-4154. doi: 10.1007/s00394-022-02959-z.

The Benefits of Omega-3 Fatty Acid Supplements for Polycystic Ovary Syndrome (PCOS)

Omega-3 fatty acid supplements have been recommended for a wide variety of health reasons, including to support females with polycystic ovary syndrome (PCOS). This post will describe exactly what omega-3 fatty acids are, and of course, tell you what the research says about their use for PCOS. And I’ll give you a little sneak peek… studies find beneficial effects!

what are omega-3 fatty acids?

Let’s start with the basics. What are omega-3’s and why might we think they’d help for PCOS?

To really understand omega-3 fatty acids, we need to talk about fatty acids more broadly.

If you don’t care about the science side of things, just skip down to the research results! But if you want a better understanding of what omega-3’s actually are… read on!

In general, we can think of fatty acids as long chains of carbon atoms. For simplicity, we’re going to ignore the carbons on either end of the chain and just think about those in the middle of the chain. Each carbon atom has four possible bonds. We can think of these as arms and hands it's using to hold onto its neighbors. Its options include:

1. Using 2 of its arms for its two carbon atom neighbors + using 2 of its arms for 2 hydrogen atoms

2. Using 1 of its arms for 1 carbon atom neighbor + using 1 of its arms for 1 hydrogen atom + using 2 of its arms to hold 2 arms of its other carbon atom neighbor. We call this use of 2 arms a “double bond”

When all the carbons are following the first option, the chain has as many hydrogens as possible, and we call this kind of fatty acid a “saturated” fat because it’s saturated with hydrogen atoms.

An example of a saturated fatty acid, where each inner carbon is bonded to its neighboring carbon atoms and two hydrogen atoms.

An unsaturated fat is not saturated with hydrogens. At least one pair of neighboring carbon atoms is using 2 of their respective arms to hold on extra tight to each other, reducing the number of hydrogens attached to the chain.

An example of a monounsaturated fatty acid, where one carbon pair is double-bonded, resulting in fewer hydrogen atoms in the molecule.

Monounsaturated fats have just one carbon pair that has a double bond and the rest of the carbons are packed with hydrogen atoms. Polyunsaturated fats have multiple carbon pairs with double bonds and even fewer hydrogen atoms.

Omega-3 fatty acids are polyunsaturated fatty acids that have their first double-bonded carbon 3 carbons from the methyl end (the methyl end is not critical to understand here, so let’s skip it!). Omega-6 fatty acids have their first double bond 6 carbons from the end. Omega-9, 9 carbons from the end… and you get the picture!

An example of a polyunsaturated fatty acid with its first double-bonded carbon pair 3 carbons from the methyl end.

The location of the double bond(s) determines the shape of the fatty acid. Each double-bonded carbon pair puts a bend in the fatty acid. Saturated fats have no bends, so the molecules pack together well. That’s why these fats are solid at room temperature (think butter, coconut oil, palm oil). 

Unsaturated fatty acids remain liquid at room temperature (olive oil, vegetable oil, sesame oil, etc.) because of the bends that keep them from packing tightly together.

While all foods have a variety of fatty acids making up their fat molecules, most foods have a dominant kind of fatty acid that gives it its characteristic solid/liquid form and determines how we generally categorize the kind of fat. So foods high in omega-3 fatty acids also have other kinds of fatty acids in them. Dietary supplements, however, can isolate specific fatty acids. 

Essential fatty acids are fatty acids that our bodies need and that we must consume from food, either directly or indirectly, because our bodies cannot make them ourselves. These include:

• Arachidonic acid (AA), an omega-6 fatty acid

• Dihomo-gamma-linoleic acid (DGLA), an omega-6 fatty acid

• Eicosapentaenoic acid (EPA), omega-3 fatty acid

• Docosahexaenoic acid (DHA), omega-3 fatty acid

EPA and DHA are needed to make “eicosanoids” that are responsible for regulating inflammation, reducing oxidative stress, vasodilation (widening of blood vessels, arteries, and veins), aggregation of platelets (necessary for things like clotting after an injury), and signaling in the cardiovascular (heart, arteries, veins), immune, pulmonary (lungs), and endocrine (hormones) systems. DHA and EPA are important building blocks of neurons and the retina, making them important for brain and eye health.

Given these roles, we can see how supplementing with these essential fatty acids might help with disorders driven by chronic inflammation (which can be an underlying factor for PCOS), endocrine disorders like PCOS, and things like high blood pressure, where more vasodilation is needed.

In contrast, the omega-6 fatty acids tend to increase inflammation. Inflammation is a first line of defense for our immune systems, so we want our bodies to have the ability to create inflammation. However, excessive consumption of omega-6 fatty acids, especially relative to omega-3 fatty acids, can increase inflammation beyond what is necessary or healthy. 

While we can eat the essential fatty acids directly, our bodies can also make AA and DGLA from linoleic acid and EPA and DHA from alpha-linolenic acid (ALA). However, diabetes and insulin resistance inhibit the conversion of linoleic acid and alpha-linolenic acid to essential fatty acids. The process also requires vitamin B6 and magnesium, so if you are deficient in either of these nutrients, conversion will also be inhibited.

food sources of Omega-3

I am always a fan of getting nutrients from food sources first, and EPA and DHA can be found in high amounts in a variety of fatty fish and seafood.

The best food sources of EPA are listed below with the amount of EPA per serving listed. All data come from the USDA’s exhaustive list of EPA sources:

• Pacific herring, cooked, (1 fillet), 1.79 g

• Atlantic herring, cooked, (1 fillet), 1.30 g

• Salted mackerel, (1 piece), 1.30 g

• Raw Atlantic mackerel, (1 fillet), 1.01 g

• Sockeye salmon, smoked with skin, (1 fillet), 0.98 g

• Chinook salmon, cooked, (3 oz.), 0.86 g

• Sablefish, cooked, (3 oz.), 0.74 g

• Atlantic farmed salmon, raw, (3 oz.), 0.73 g

• Atlantic canned sardines, (1 cup, drained), 0.71 g

• Wild rainbow trout, cooked, (1 fillet), 0.67 g

• Atlantic farmed salmon, cooked, (3 oz.), 0.59 g

• Fresh halibut, cooked, (3 oz.), 0.57 g

• Atlantic wolffish, cooked (0.5 fillet), 0.47 g

• Alaskan king crab, (1 leg), 0.40 g

• Bluefish, cooked, (1 fillet), 0.38 g

The best food sources of DHA are listed below with the amount of DHA per serving listed. All data come from the USDA’s exhaustive list of DHA sources:

• Salted mackerel (1 piece), 2.48 g

• Sockeye salmon, smoked with skin, (1 fillet), 1.64 g

• Atlantic herring, cooked, (1 fillet), 1.58 g

• Spanish mackerel, cooked, (1 fillet), 1.39 g

• Pacific herring, cooked (1 fillet), 1.27 g

• Farmed Atlantic salmon, cooked, (3 oz.), 1.24 g

• Wild Atlantic salmon, cooked, (3 oz.), 1.22 g

• Tilefish, cooked, (0.5 fillet), 1.10 g

• Bluefin tuna, cooked, (3 oz.), 0.97 g

• Striped bass, cooked, (1 fillet), 0.93 g

• Sablefish, cooked, (3 oz.), 0.78 g

• Atlantic sardine, canned, (1 cup), 0.76 g

• Wild rainbow trout, cooked, (1 fillet), 0.74 g

• Cooked swordfish, (3 oz.), 0.66 g

• Sea bass, cooked (1 fillet), 0.56 g

• White tuna, canned, (3 oz), 0.54 g

Fish like mackerel are amazing sources of omega-3 fatty acids for females with polycystic ovary syndrome (PCOS).

The best food sources of alpha-linolenic acid (ALA) are listed below with the amount of ALA per serving listed. All data come from the USDA’s exhaustive list of ALA sources:

• Cold pressed flaxseed oil, (1 tbsp), 7.26 g

• Chia seeds, dried, (1 oz.) 5.06 g

• Black walnuts, dried, (1 cup, chopped), 3.35 g

• Mixed nuts, dry roasted, (1 cup), 2.66 g

• Hemp seeds, hulled, (3 tbsp), 2.61 g

• Refried beans, canned, (1 serving), 0.99 g

• Edamame, frozen, prepared, (1 cup), 0.56 g

• Peanut butter with added omega-3, creamy (1 tbsp), 0.47 g

Omega-3 fatty acid supplementation and polycystic Ovary Syndrome: What does the literature say?

I’m going to cover three major studies, two of which use randomized control trials and one of which uses a randomized crossover design (I’ll explain this soon!), to determine the potential effects of omega-3 supplementation for PCOS.

In the first of these studies, Cusson et al. (2009), recruited 25 women of reproductive age with PCOS. Given the smaller sample size, this study uses a “randomized crossover design,” which essentially means that each participant serves as their own control group.

Half of the respondents were assigned to the initial treatment group, and they consumed:

• 4 g of omega-3 fatty acids, which were composed of 56% DHA and 27% EPA, and was split into four 1,000 mg capsules daily.

The other half were assigned to the initial control group, and they consumed:

• 4 g of olive oil, which was composed of 67% oleic acid, and was split into four 1,000 mg capsules daily.

Each group followed their treatment protocol for 8 weeks.

Then both groups spent 8 weeks without taking either supplement.

After this “washout” period, those who started in the control group became the treatment group and vice versa. In this way, every participant had an 8-week period supplementing with omega-3 and an 8-week period “supplementing” with olive oil. 

The table below shows a comparison of the effects of the supplementation regimens when all participants are grouped together. Omega-3 supplements did not outperform the olive oil capsules in terms of body mass index (BMI), waist-to-hip ratio, ALT (a measure of liver health), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, fasting insulin levels, fasting blood sugar levels, testosterone levels or any other reproductive hormone levels.

When taking the omega-3 supplements, participants had a 17.6% lower liver fat percentage than when they took the olive oil supplement. High amounts of fat stored in the liver can damage the liver and cause liver cirrhosis.

 They also had 1.5% lower systolic blood pressure (top number in the reading), 4.8% lower diastolic blood pressure (lower number in the reading), and 14.3% lower triglycerides. These latter three measures indicate improved cardiovascular health and decreased risk of heart disease and heart attacks.

A comparison of the effects of supplementing with 4 g of omega-3 fatty acids or 4 g of olive oil over 8 weeks among females with polycystic ovary syndrome (PCOS). Source: Cusson et al. (2009).

The team also split their sample up based on starting liver fat percentage. As we might expect, those starting with low liver fat did not experience any benefits of omega-3 fatty acids in terms of liver fat, while those starting with a high liver fat percentage did.

Interestingly, the group with low starting liver fat percentage experienced improvements in their blood pressure while supplementing with omega-3 fatty acids while those with high liver fat did not experience reductions in blood pressure. 

Conversely, those with high liver fat experienced reductions in triglyceride levels while those with low liver fat did not.

Lastly, those with high liver fat experienced significant improvement in metabolic health, as demonstrated by a 13.8% reduction in fasting insulin and a 13.4% reduction in HOMA-IR, a measure of insulin resistance. While insulin resistance can lead to non-alcoholic fatty liver disease, high liver fat can also contribute to insulin resistance (Liu et al, 2020). This study’s results suggest that supplementation with omega-3 fatty acids appears to improve insulin resistance via improvements in liver fat and reduces indicators of metabolic syndrome.

A comparison of the effects of supplementing with 4 g of omega-3 fatty acids or 4 g of olive oil over 8 weeks among females with polycystic ovary syndrome (PCOS), with participants separated by starting liver fat percentage. Source: Cusson et al. (2009).

The next study (Mohammadi et al. 2012) recruited 64 PCOS patients from the department of obstetrics at the Alzahra Hospital in Iran. 

Half of the participants were randomly assigned to the treatment group, and they consumed:

• 4 g of omega-3 fatty acids, composed of 720 mg of EPA and 480 mg of DHA, split across four 1,000 mg capsules daily.

The other half of the participants were randomly assigned to the control group, and they consumed:

• 4 placebo capsules that each contained 500 mg of liquid paraffin daily.

Each group took their respective capsules for 8 weeks. The table below shows the health benefits of 8 weeks of supplementation.

As we might expect, consuming the capsules with paraffin oil did not result in any changes.

The group supplementing with omega-3 fatty acids experienced a 14.4% increase in adiponectin, which is a substance associated with improved insulin sensitivity and reduced inflammation. This increase is thus a positive effect.

The omega-3 group also experienced improvements in metabolic health, including a 10.3% decrease in fasting glucose, an 8.5% decrease in fasting insulin, and an 18.2% decrease in HOMA-IR, a measure of insulin resistance.

The omega-3 group also experienced improvements in cardiovascular health, including a 9.1% decrease in total cholesterol, a 13.6% decrease in LDL cholesterol (the “bad” kind), a 9.3% increase in HDL cholesterol (the “good” kind), and a 6.3% decrease in triglycerides. 

The only metric that did not change for the omega-3 group was hs-CRP, a broad measure of inflammation.

A comparison of the effects of supplementing with 4 g of omega-3 fatty acids vs. placebo over 8 weeks among females with polycystic ovary syndrome (PCOS). “No significant change” means that any changes found were not statistically significantly different than zero. “No significant difference” means that any differences between groups was not statistically significantly different than zero. Source: Mohammadi et al. (2012).

Ebrahimi et al. (2017) recruited 68 females with PCOS. In contrast with the previous studies, this study used flaxseed oil, which is predominantly alpha-linolenic acid (ALA) instead of primarily DHA/EPA as used in the previous studies. This study also combined the omega-3 fatty acids with vitamin E. Vitamin E is commonly added to omega-3 supplements to prevent oxidation of the fatty acids (all polyunsaturated fats are prone to oxidation).

Half of the participants were randomly assigned to the treatment group, and they consumed:

• 1 g of omega-3 fatty acids from flaxseeds, containing 400 mg of alpha-linolenic acid, and 400 IU of vitamin E daily.

The other half of the participants were randomly assigned to the control group. The paper does not state what was used as the placebo, but this group also took capsules of similar size and shape as the treatment group.

Both groups took their respective capsules for 12 weeks.

The table below shows the results of this intervention. Unlike previous studies, this study’s placebo group experienced several statistically significant changes, although most were not positive changes. The group experienced increases in fasting glucose, fasting insulin, HOMA-IR, and HOMA-B, and a decrease in QUICKI. These changes suggest that their metabolic health worsened throughout the study. Given the prevalence of insulin resistance among females with PCOS, it is not hard to imagine that we would see declines over time. However, these declines are relatively large. More information on what constituted the placebo would help determine what is going on here.

While metabolic health worsened for the placebo group, they experienced improvements in two reproductive hormones. First, they experienced a 14.8% increase in sex hormone binding globulin (SHBG), a hormone that tends to be low in females with PCOS. SHBG binds to androgens, reducing their effects on the body. Second, they experienced a decrease in DHEAS, an androgen hormone. Testosterone is generally the androgen that is elevated with PCOS, but DHEAS can be elevated as well.

Interestingly, the treatment group experienced a small reduction in fasting glucose, but no changes in any other measure of metabolic health. However, given that they didn’t experience a decline in metabolic health, statistically speaking, this group is the “winner,” if we assume their metabolic health would have declined, like the placebo group, in the absence of treatment. This is a prime example of why it is so important to have a perfect placebo and control group. Ideally, we can use them as the counterfactual for what we don’t observe with the treatment group.

Unlike the placebo group, the treatment group experienced reductions in all measured androgen levels, including a 41.7% decrease in total testosterone and a 26.7% decrease in free testosterone. However, these decreases only led to a small reduction in Ferriman-Galway score, a measure of the effects of free testosterone on excessive hair growth on the face and body, common symptoms of PCOS.

A comparison of the effects of supplementing with 1 g of omega-3 fatty acids vs. placebo over 12 weeks among females with polycystic ovary syndrome (PCOS). “No significant change” means that any changes found were not statistically significantly different than zero. “No significant difference” means that any differences between groups was not statistically significantly different than zero. Source: Ebrahimi et al. (2017)

take home points on the benefits of OMEGA-3 supplementation for PCOS

All studies find some benefits of omega-3 fatty acid supplementation, but the benefits vary by study.

In some individuals, omega-3 fatty acid supplementation may improve metabolic health by decreasing insulin resistance or by preventing the worsening of insulin resistance. This benefit may be more likely for individuals with higher percentages of fat in their livers.

Omega-3 fatty acid supplementation appears to consistently lower triglyceride levels among females with PCOS, which should correspond to a lower risk of cardiovascular disease and heart attacks.

There is conflicting evidence on the effectiveness of omega-3 supplementation in correcting hormonal imbalances and reducing the excess androgen hormones common with PCOS.

These studies either do not measure or do not find effects of supplementation on things like preventing weight gain or aiding in weight loss.

Common dosing among studies ranges from 1 to 4 grams of omega-3 fatty acids (or 1,000 to 4,000 mg of omega-3). Most supplements include EPA and DHA because they can be directly converted to eicosanoids. In contrast, ALA must be converted to EPA or DHA first, and only about 10% gets converted. Conversion will be even lower for those with insulin resistance or diabetes.

It is quite possible to get the dosing used in these studies from food sources! If you need help incorporating this foods into your diet, consider checking out my meal plan membership.

About the author

Kelly Grogan, Ph.D., NTM, is a holistic nutrition therapist who is passionate about helping females with PCOS. She currently manages her own PCOS with nutrition and lifestyle tools that she developed through extensive review of the scientific literature on PCOS interventions.

references

Cussons AJ, Watts GF, Mori TA, and Stuckey BGA. 2009. Omega-3 Fatty Acid Supplementation Decreases Liver Fat Content in Polycystic Ovary Syndrome: A Randomized Controlled Trial Employing Proton Magnetic Resonance Spectroscopy. Journal of Clinical Endocrinology and Metabolism 94(10):3842–3848.

Ebrahimi FA, Samimi M, Foroozanfard F, Jamilian M, Akbari H, Rahmani E, Ahmadi S, Taghizadeh M, Memarzadeh MR, and Asemi Z. 2017. The Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Indices of Insulin Resistance and Hormonal Parameters in Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Experimental and Clinical Endocrinology & Diabetes, 125:353–359. http://dx.doi.org/10.1055/s-0042-117773

Liu Z, Zhang Y, Graham S, Wang X, Cai D, Huang M, Pique-Regi R, Dong XC, Chen YE, Willer C, and Liu W. 2020. Causal relationships between NAFLD, T2D and obesity have implications for disease subphenotyping. Journal of Hepatology, 73(2):263-276. https://doi.org/10.1016/j.jhep.2020.03.006.

Mohammadi E, Rafraf M, Farzadi L, Asghari-Jafarabadi M, and Sabour S. 2012. Effects of omega−3 fatty acids supplementation on serum adiponectin levels and some metabolic risk factors in women with polycystic ovary syndrome. Asia Pacific Journal of Clinical Nutrition, 21(4):511-518.

Nadjarzadeh A, Dehghani-Firouzabadi R, Daneshbodi H, Lotfi MH, Vaziri N, and Mozaffari-Khosravi H. 2015. Effect of Omega-3 Supplementation on Visfatin, Adiponectin, and Anthropometric Indices in Women with Polycystic Ovarian Syndrome. Journal of Reproductive Infertility, 16(4):212-220.

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.

Is Vitamin D Supplementation Helpful for PCOS?

Vitamin D supplementation has recently become all the rage. Many popular podcasts advertise a promo for Athletic Greens that provides a free year’s supply of Vitamin D. Their supplement contains 1000 IU of Vitamin D, while the recommended daily allowance for Vitamin D is 600 IU for adults aged 19 - 70.

Do you actually need a year’s supply of 1000 IU of Vitamin D? Let’s see what the literature says!

what is vitamin D?

Vitamin D is a rare vitamin that our bodies can actually make! When our skin is exposed to UVB radiation from the sun, a form of cholesterol in the skin gets converted to previtamin D3, which eventually gets converted into the active form of vitamin D3 that our bodies use through processes in the kidney and liver (NIH 2023).

However, there is substantial variation in just how much vitamin D gets produced from any given bout of sun exposure. Time of day, season, cloud cover, smog, skin color, and sunscreen use all affect the amount of UVB radiation that actually hits and penetrates the skin. And then on top of that, humans vary tremendously in their abilities to produce vitamin D. People who are older tend to produce less vitamin D, and studies show that even among non-elderly adults, there is substantial variation in the blood levels of vitamin D resulting from the same level of sun exposure (Giustina et al. 2020). It is unclear why this variation occurs, but there is some evidence that it is the result of genetic variation.

Vitamin D is perhaps most commonly associated with bone health. It plays a major role in increasing the levels of calcium in the blood to be used in bone and teeth. People taking calcium supplements are often encouraged to supplement with vitamin D as well because vitamin D increases the absorption of calcium from the intestines.

Vitamin D also rose in popularity during the COVID-19 pandemic when some studies showed that vitamin D supplementation could reduce the severity of COVID infections (Shah et al. 2022). And indeed, vitamin D plays a role in stimulating immune system responses, and frequent colds can be a sign of vitamin D deficiency.

Other studies have linked increased levels of vitamin D with improved metabolic, cardiovascular, and reproductive health, which is how the supplement became a popular one for polycystic ovary syndrome (PCOS).

sunshine and vitamin d

In the right conditions, about 10 to 15 minutes of sunshine on your arms and legs a few times a week could generate enough vitamin D to meet your needs. However, if you live at even moderately high latitudes (north of 37 degrees N or south of 37 degrees S), only summer time will provide rays strong enough to stimulate much production of vitamin D. Not to mention that in these regions, people often don’t walk around with their arms and legs exposed all year long!

Food sources of vitamin D

While we often associate vitamin D with sunshine, some foods also provide vitamin D, and these foods may be especially important for people living farther from the equator.

The list below contains the best food sources, with vitamin D content listed in IU (international units). As a reminder, the RDA is 600 IU per day for adults. All data from USDA (2019).

1. Cod liver oil, 1 tbsp, 1360 IU

2. Rainbow trout, 1 oz., 215 IU

3. Salmon, 1 oz., 128 - 190 IU

4. Canned light tuna, 1 oz., 77 IU

5. Herring, 1 oz., 61 IU

6. Milk, 1/2 cup, 59 IU

7. Yogurt, 4 oz., 58 IU

8. Mushrooms, 1/2 cup, 57 - 555 (mushrooms exposed to sunlight synthesize vitamin D!)

9. Canned sardines, 1 oz., 55 IU

10. Eggs, 1 egg, 50 IU

11. Fortified orange juice, 1/2 cup, 50 IU

12. Tilapia, 1 oz., 42 IU

13. Flounder, 1 oz., 39

Salmon is a great food source of vitamin D! This ginger miso salmon with Napa cabbage salad is featured in an upcoming Women’s Health Meal Plan.

To help my members get adequate vitamin D, I include salmon and eggs regularly in my meal plans and often include canned tuna. If you struggle to incorporate these foods in your diet, consider signing up for my meal plans. Your first month is free!

Vitamin D and polycystic ovary syndrome: Is there a relationship between Vitamin D levels and PCOS?

Early research on the subject of vitamin D and PCOS looked for correlations between blood levels of vitamin D and the likelihood that someone had PCOS. The literature finds that, on average, females with PCOS tend to have lower levels of serum vitamin D, although not every study finds this difference to be statistically significant, likely due to substantial variation across individuals (Davis et al. 2019, Krul-Poel et al. 2018, Li et al. 2011).

One study splits its sample into lean vs. overweight females. Among lean females, there is no difference in average vitamin D levels in females with or without PCOS, while among overweight women, those with PCOS had vitamin D levels that were about 33% lower than those without PCOS (Joham et al. 2016). This difference may explain some of the variation in findings that do not separate participants by body weight category.

While correlations suggest that there may be a relationship between vitamin D levels and PCOS, they cannot tell us conclusively if low vitamin D levels contribute to PCOS or if PCOS leads to low vitamin D levels. Nor does it tell us conclusively that vitamin D supplementation is necessarily helpful for PCOS.

So let’s discuss that literature next!

does supplementation with vitamin D help with pcos?

There are a lot of studies that have used randomized control trials (our gold standard for researching interventions) to determine whether vitamin D supplementation improves various markers of health for females with PCOS.

I have chosen to highlight four studies below based on the following criteria: 1) the study was published in a reputable journal (there are a lot of open access journals out there where you basically pay to get it published without it going through a legitimate peer-review process), 2) the paper was accessible to me without a paywall (most were, thankfully!), 3) the study considers markers prominent markers of health (a few studied fairly obscure markers that don’t tell us much about the key concerns for females with PCOS).

Vitamin D and Menstrual Cycle Regularity

I am going to start with two studies that included menstrual cycle length in addition to other markers because I think this is an especially important marker of health for females with PCOS. It’s our 6th vital sign!

The first of these studies (Irani et al. 2015) recruited 68 females with PCOS who were also deficient in vitamin D.

Of these participants, 45 were randomly assigned to supplement with vitamin D and consumed:

• One capsule of 50,000 IU of vitamin D each week.

23 were randomly assigned to the control group, and they consumed:

• One capsule filled with lactose monohydrate powder, which looked similar to the vitamin D capsule.

Both groups consumed their respective capsules weekly for 8 weeks.

The table below summarizes the results after 8 weeks of supplementation. As expected, the group consuming the placebo experienced no changes in any marker of health.

The group supplementing with vitamin D experienced an almost 34% reduction in menstrual cycle length, which is pretty significant. However, it should be noted that the average cycle length after treatment was 60 days, which is still considered to be longer than “normal” (23 - 35 days).

They also experienced a 21% decrease in Ferriman-Gallway score, which is a marker of hirsutism (masculine patterns of facial and/or body hair). Interestingly, despite these changes in cycle length and overt symptoms of excess androgen hormones, no changes in any reproductive hormones occurred.

While most markers of cardiovascular health remained unchanged with supplementation, the treatment group did experience an 18% decrease in triglyceride levels, which indicates a lower risk for cardiovascular disease.

Percent change in various markers of health after 8 weeks of supplementation with vitamin D among females with polycystic ovary syndrome (PCOS). “No significant change” means that any changes found were not statistically significantly different than zero. Source: Irani et al. (2015).

While the intervention in the paper above only included vitamin D supplementation, Jafari-Sfidvajani et al. (2018), considered vitamin D supplementation among females with PCOS who were also following a calorie-restricted diet.

This study recruited 60 females with PCOS who had BMIs of 25 or higher (overweight or obese) and who had deficient serum vitamin D levels.

Thirty of the participants were randomly assigned to the treatment group, and they consumed:

• One capsule of 50,000 IU of vitamin D each week.

Thirty of the participants were randomly assigned to the control group, and they consumed:

• One capsule filled with paraffin oil, which looked similar to the vitamin D capsule.

Both groups followed a diet consisting of:

• 500 calorie deficit relative to their estimated caloric needs

• 55% of their calories from carbohydrates

• 15% of calories from protein

• 30% of calories from fat

The intervention lasted for 12 weeks. The table below contains the percent change for various markers of health after the 12-week intervention.

Both groups experienced similar decreases in body weight, BMI, waist circumference, waist-to-hip ratio, and fat mass. Neither group experienced any improvements in reproductive hormone levels, and the control group even experienced an increase in DHEA, an androgen hormone which can be elevated in females with PCOS.

As expected, the group supplementing with vitamin D saw an increase in their serum vitamin D levels, while those taking the placebo did not.

Like the previous study, this one recorded effects on menstrual cycle regularity. It is unclear exactly how they defined “regularity.” Menstrual cycles between 23 and 35 days are generally considered “regular” or “normal” and I am assuming that was their definition. Similarly, their definition of oligomenorrhea is unclear. It usually means fewer than 6 to 8 cycles per year. Given that their intervention lasted only 12 weeks, they must have used a different metric, but they do not state what. Amenorrhea is the absence of any period, which is fairly straightforward.

Given the lack of clarity on regularity, I think these results should be interpreted with caution.

While both groups experienced increases in likelihood of having a regular period and decreases in likelihood of having either oligomenorrhea or amenorrhea, a larger portion of participants in the group supplementing with vitamin D experienced improvements in cycle regularity.

Percent change in various markers of health after 12 weeks of supplementation with vitamin D among females with polycystic ovary syndrome (PCOS). “No significant change” means that any changes found were not statistically significantly different than zero, and “No statistically significant difference” indicates that the difference between groups was not statistically significant. Source: Jafari-Sfidvajani et al. (2018).

Vitamin D & Cardiovascular and Metabolic Health

The next two studies ignored menstrual cycle regularity and instead chose to focus on only metabolic and cardiovascular health.

The earlier of these studies was done by Ardabili et al. (2012 and 2013). This study recruited 60 females with PCOS who were deficient in vitamin D.

Half of the participants were randomly assigned to the treatment group, and consumed:

• One capsule containing 50,000 IU of vitamin D every 20 days.

The other half was assigned to the control group, and consumed:

• One capsule containing paraffin oil every 20 days.

The study lasted for two months. The table below shows the changes in various health markers after the two-month intervention. As expected, the placebo group experienced no changes during the intervention period.

Similarly, as we’d expect, the treatment group experienced an increase in serum vitamin D levels. They also experienced a decrease in parathyroid hormone, a hormone that gets released when your body detects low calcium levels. Increasing vitamin D increases absorption and retention of calcium, so less parathyroid hormone gets released. This is a positive shift because elevated parathyroid hormone means your body is pulling calcium from your bones to keep blood calcium levels in the optimal range.

The treatment group also experienced reductions in total cholesterol and triglycerides. This study is one of the few studies that not only tests for HDL and LDL cholesterol (commonly thought of as good and bad cholesterol, respectively), but also VLDL cholesterol. VLDL cholesterol is a subset of LDL cholesterol, and there is increasing evidence that we actually care about VLDL levels in terms of artery health and heart attack risk. Importantly, this study found a 20% reduction in VLDL levels among those who supplemented with vitamin D.

While they tested for a variety of measures of metabolic health, the treatment group only experienced a significant improvement in one of those measures, suggesting a weak effect on metabolic health. Had the study continued for longer, perhaps we would see changes in other measures of metabolic health, but we can’t say for sure.

Percent change in various markers of health after 2 months of supplementation with vitamin D among females with polycystic ovary syndrome (PCOS). “No significant change” means that any changes found were not statistically significantly different than zero, and “No statistically significant difference” indicates that the difference between groups was not statistically significant. Sources: Ardabili et al. (2012 and 2013).

The last study I will discuss here was conducted by Trummer et al. (2019). They recruited 180 females with PCOS who were also deficient in vitamin D.

Two-thirds of their participants were randomly assigned to the treatment group, and they consumed:

• 50 oily drops that contained a total of 20,000 IU weekly

One-third of their participants were assigned to the control group, and they consumed:

• 50 oily drops of placebo weekly

Both groups consumed their respective drops for 24 weeks. The table below shows the effects of the 24-week intervention. As we saw with previous studies, no changes were observed for the group taking the placebo.

The group supplementing with vitamin D saw increases in two forms of serum vitamin D levels. The first is the form of vitamin D tests usually capture. This form is one step away from the active form that our bodies actually use. This form tends to persist in the body for a longer period of time and tells us more about long term vitamin D status. The active form does not persist very long and can be influenced by recent consumption of vitamin D or sun exposure.

As expected, parathyroid hormone also decreased among the vitamin D group. As discussed above, parathyroid hormone is released when blood calcium levels get too low, and it stimulates the release of calcium from bones.

This study used 7 measures of insulin resistance, and only one indicated an improvement in insulin resistance. This test, a 60-minute oral glucose tolerance test, measures blood sugar levels 60-minutes after consumption of 75 g of glucose. A lower score indicates better insulin sensitivity and better blood sugar management. However, the fact that none of the other metrics improved suggests that affects on insulin resistance are marginal at best.

Lastly, it’s important to note that this study did not find any effects on measures of cardiovascular health, unlike previous studies. This could be a result of the lower dose used in this study, but without further investigation, we cannot know for sure.

Percent change in various markers of health after 24 weeks of supplementation with vitamin D among females with polycystic ovary syndrome (PCOS). “No significant change” means that any changes found were not statistically significantly different than zero, and “No statistically significant difference” indicates that the difference between groups was not statistically significant. Sources: Trummer et al. (2019).

take home points

• Vitamin D supplementation improved menstrual cycle regularity. However, in one study, these effects were not large enough to result in normal-length cycles, and in the other study, in is unclear how cycle regularity categories were defined. This intervention alone likely does not solve all menstrual cycle problems associated with PCOS.

• There is some evidence that supplementation leads to small improvements in insulin resistance and metabolic health.

• Some, but not all, studies find positive effects of supplementation on triglyceride and cholesterol levels.

• All studies excluded participants with adequate levels of vitamin D. Given the relatively small and inconsistent effects found for those who were deficient, I suspect those who are not deficient will not experience benefits.

• Studies all used supplementation that was at most once a week, unlike most supplements that encourage daily consumption.

• You can consume too much vitamin D! Blood testing is recommended prior to supplementation and should ideally be repeated to ensure your vitamin D levels do not get too high.

References

Ardabilia HR, Gargarib BP, and Farzadic L. 2012b. Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency. Nutrition Research, 32:195–201. doi:10.1016/j.nutres.2012.02.001

Ardabili HR, Pourghassem Gargari B, and Farzadi L. 2013. Effects of vitamin D on cardiovascular disease risk factors in polycystic ovary syndrome women with vitamin D deficiency. Journal of Endocrinological Investigation, 36(1):28-32. doi: 10.3275/8303.

Davis EM, Peck JD, Hansen KR, Neas BR, and Craig LB. 2019. Associations between vitamin D levels and polycystic ovary syndrome (PCOS) phenotypes. Minerva Endocrinology, 44(2): 176–184. doi:10.23736/S0391-1977.18.02824-9.

Giustina A, Bouillon R, Binkley N, Sempos C, Adler RA, Bollerslev J, Dawson-Hughes B, Ebeling PR, Feldman D, Heijboer A, Jones G, Kovacs CS, Lazaretti-Castro M, Lips P, Marcocci C, Minisola S, Napoli N, Rizzoli R, Scragg R, White JH, Formenti AM, Bilezikian JP. 2020. Controversies in Vitamin D: A Statement From the Third International Conference. JBMR Plus. 4(12):e10417. doi: 10.1002/jbm4.10417.

Irani M, Seifer DB, Grazi RV, Julka N, Bhatt D, Kalgi B, Irani S, Tal O, Lambert-Messerlian G, and Tal R. 2015. Vitamin D Supplementation Decreases TGF-􏰆1 Bioavailability in PCOS: A Randomized Placebo- Controlled Trial. The Journal of Clinical Endocrinology & Metabolism, 100(11):4307– 4314. doi: 10.1210/jc.2015-2580.

Jafari‐Sfidvajani S, Ahangari R, Hozoori M, Mozaffari‐Khosravi H, Fallahzadeh H, and Nadjarzadeh A. The effect of vitamin D supplementation in combination with low‐calorie diet on anthropometric indices and androgen hormones in women with polycystic ovary syndrome: A double‐blind, randomized, placebo‐controlled trial. Journal of Endocrinological Investigation, 41:597–607 https://doi.org/10.1007/s40618-017-0785-9

Joham AE, Teede HJ, Cassar S, Stepto NK, Strauss BJ, Harrison CL, Boyle J and de Courten B. 2019. Vitamin D in polycystic ovary syndrome: Relationship to obesity and insulin resistance. Molecular Nutrition & Food Research. 60:110–118. https://doi.org/10.1002/mnfr.201500259

Krul-Poel YHM, Koenders PP, Steegers-Theunissen RP, ten Boekel E, ter Wee MM, Louwers Y, Lips P, Laven JSE, Simsek S. 2018. Vitamin D and metabolic disturbances in polycystic ovary syndrome (PCOS): A cross- sectional study. PLoS ONE, 12:e0204748. https://doi.org/10.1371/journal. pone.0204748

Li HWR, Breretona RE, Anderson RA, Wallace A, and Ho CKM. 2011. Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metabolism Clinical and Experimental 60:1475-1481.

National Institutes of Health. 2023. Vitamin D: Fact Sheet for Health Professionals. Available: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed January 9, 2023.

Shah K, Varna VP, Sharma U, Mavalankar D. 2022. Does vitamin D supplementation reduce COVID-19 severity? A systematic review. QJM. 115(10):665-672. doi: 10.1093/qjmed/hcac040.

Trummer C, Schwetz V, Kollmann M, Wölfler M, Münzker J, Pieber TR, Pilz S, Heijboer AC, Obermayer‐Pietsch B, and Lerchbaum E. 2019. Effects of vitamin D supplementation on metabolic and endocrine parameters in PCOS: a randomized-controlled trial. European Journal of Nutrition 58:2019–2028. https://doi.org/10.1007/s00394-018-1760-8.

U.S. Department of Agriculture, Agricultural Research Service. FoodData Central, 2019. fdc.nal.usda.gov.

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.