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 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.

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!

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

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.

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.

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.

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.

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.

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.