Supplements for PCOS: Insoitol, omega 3s, & probiotics

This article reviews the best evidence for dietary supplements for PCOS. Inositol supplements are the star supplements for POCS, improving ovulation, egg quality and reducing insulin sensitivity. Other supplements for PCOS with good data includes omega 3 fish oils and probiotics. Read on to find out how inositol and other dietary supplements can help with PCOS.

Contents

What Is PCOS?

Polycystic ovary syndrome (PCOS) is a common metabolic hormonal disorder among women of reproductive age. It can cause infertility, obesity, and a variety of other health problems. In 2018 it was declared a major public health issue for women as women with PCOS not only have classic coronary heart disease risks such as hypertension, increased weight, diabetes mellitus and dyslipidemia, but also non-classic cardiovascular risks factors like mood disorder, depression and anxiety.

It affects approximately 1 in 10 women. Although PCOS can affect the ovaries and therefore fertility it is a condition that stems from the endocrine system. The condition occurs when there is an imbalance of male hormones (androgens) in women and usually some degree of insulin resistance.

Women with PCOS can present with symptoms affecting various body systems including reproductive, hair and skin, endocrine and psychological. PCOS is typically treated with medications to manage each symptoms. However some women prefer to either manage their symptoms or treat the insulin resistance at the root cause with lifestyle changes such as a healthy diet, exercise and supplements rather than medications.

What are the symptoms of PCOS?

Irregular periods (cycles > 35 days) or no periods
High testosterone signs such as acne or excess facial/body hair growth or thinning of hair on the head
Elevated testosterone levels in the blood
Multiple cysts on the ovaries on pelvic ultrasound
Elevated insulin (i.e. evidence of insulin resistance)
Weight gain, or difficulty losing weight
Difficulty getting pregnant.

What Causes PCOS?

The cause of PCOS is multifactorial, but the combination of genetic predisposition and environmental factors which switch on or off genes, make a woman with PCOS more prone to insulin resistance and chronic inflammation. Insulin resistance plays a key role in irregular periods, anovulation, ovarian testosterone production. PCOS is related to metabolic syndrome. Some contributors to PCOS include:

A diet high in sugars and refined carbohydrates
Chronic, low-grade inflammation
Gut dysbiosis (imbalance in gut bacteria)
Hormonal imbalances caused by excess male hormones

Treatment Options for PCOS

While there is no one “standard” medical advice for PCOS, many treatments focus on a healthful diet, sleep, and stress levels in order to manage the condition.

Prescription drugs are often used to treat PCOS, but they often come with side effects. Additionally, these medications do not address the lifestyle issues that contribute to the development of PCOS.

There are growing trend towards lifestyle and natural approaches to treating PCOS. These treatments involve improving diet, getting enough sleep, and managing stress levels. Many women use at least one dietary supplement to enhance their treatment alongside lifestyle changes.

Top Supplements for PCOS

There are many dietary supplements that have beneficial effects for women with PCOS.

The best supplements for PCOS are those that improve insulin sensitivity and should be used in conjunction with diet and exercise to be as optimally effective as possible.

Improving insulin sensitivity has direct positive impacts on improving weight, fertility, reducing androgens – so improved acne and reduced facial hair.

The supplements with the most beneficial effects got women with PCOS according to systematic review and meta analysis data includes:

Inositol
Fish oil
Probiotic supplements

Do Inositol supplements helps improve metabolic dysfunction in PCOS?

Inositol is a carbohydrate molecule that is produced in the body and also found in many food sources. It is found in the phospholipid cell membrane of cells, in lipoprotein in the blood and in phosphate form in the cell nucleus. It’s chemical structure is similar to glucose and it is used in cell signaling. Of importance in PCOS it is it’s ability to act as a chemical mediator of insulin and influence blood sugar levels.

There are 2 main isoforms of inositol; myo-inositol and di-chiro inositol. They are 2 of 9 inositol stereoisomers (i.e. they have the same molecular structure but are arranged differently in 3D space).

Myo-inositol is the most common form and is found in a variety of food sources. In plant foodstuffs such as fruits, vegetables, seeds and nuts a considerable portion is present as phytic acid. In animal products such as meat, fish and dairy inositol is present in free form and as a phospholipid phosphatidylinositol. Di-chiro inositol is scarce in diet and is mostly derived from conversion from myo-inositol. The average diet contains just over 1000mg of myo-inositol.

Myo-inositol mediates glucose uptake and FSH (follicle stimulating hormone). Myo-inositol is the form in which inositol exists in the cell membrane and it is the pre-cursor of inositol triphosphate which acts as a second messenger, regulating the activities of hormones including FSH, TSH and insulin.

Di-chiro inositol is involved in insulin-dependent synthesis of androgens and glycogen synthesis to store glucose.

In women with PCOS women, reduced tissue availability or altered metabolism of inositol and/or inositol-derived mediators contributes to elevated insulin resistance. This causes an impairment in FSH signaling and increased production of androgens. This results in stimulation of multiple follicles that are poorly developed with poor ovulation and egg quality.

Inositol supplementation was the only non-pharmaceutical to be assessed in the PCOS international guidelines, 2018. Their recommendation was that inositol supplements should currently be considered an experimental therapy in PCOS, with emerging evidence on efficacy. They look forward to more research in this space.

A meta-analysis of 10 studies, using myoinositol or di-chiro-inositotol in 2017 reported many positive benefits for women with PCOS.

8 clinical trials used myo-inositol and doses ranged from 1.2 to 4g daily
2 clinical trials used di-chiro-inositol and doses ranged from 600mg to 1.2g

How can inositol help PCOS?

Beneficial Effects of inositol on Ovulation (5 trials)

increased ovulation rate 2-fold and was as effective as metformin
increased frequency of menstrual cycle 6-fold (no difference between use of myo or di-chiro inositol)
improved egg quality

Beneficial Effects of inositol on Pregnancy (2 trials)

only 1 study looked at pregnancy outcomes with inositol compared with placebo with only 92 women so the study was not powered to examine this outcome and did not show a significant improvement in pregnancy rates.
1 study of 120 women compared inositol with metformin and found both it to be as effective as metformin in pregnancy outcomes.
This is an area of research currently unexplored and urgently needed.

Beneficial Effects on hormonal balance (6 trials)

decrease in total androgen
decrease in total testosterone, free testosterone and dehydroepiandrosterone
increase in sex-hormone binding globulin (SHBG)

additionally myo-inositol

corrects FSH/LH ratio and
induces ovulation by adequately luteal phase progesterone production.

Beneficial Effects on markers of insulin resistance (6 trials)

reduced fasting insulin levels
reduced fasting glucose
reduced HOMA-IR (a measure of insulin resistance)
increased glucose to insulin ratio (lower than 4.5 is sensitive and specific for insulin resistance)

As inositol supplementation improves insulin resistance, it is likely to improve cardiovascular risk. One study of post-menopausal women with PCOS using 4g/day of myo-inositol also found a reduction in fasting glucose, fasting insulin and HOMA-IR.

Inositol also reduce diabetes health risks including a decreased risk of gestational diabetes in pregnancy by 80%.

As inositol regulates menstrual cycles it also has the potential to reduce the burden of endometrial hyperplasia and endometrial cancer in women with PCOS.

A further metanalysis in 2019 found myo-inositol as effective at metformin for improving insulin resistance and reducing androgens. The main benefit was the absence of side effects in those using myo-inositol.

How many mg of inositol should I take for PCOS?

Clinical consensus suggests that 2g twice daily of myo-inositol should be used to treat PCOS – for metabolic, hormonal and ovulation benefits and to prevent gestational diabetes.

Is Inositol Safe in Pregnancy

Myoinositol is found in food. It is important in the first 12 weeks of pregnancy. If the levels of myoinositol are too low, miscarriage of pregnancy will occur. In mouse models inositol is used in those folate resistant for preventing neural tube defects. In trials of pregnant women in Italy and UK among women with previous neural tube defects (high risk) using folate with inositol in subsequent pregnancy, no neural tube defects occurred.

How long does it take for inositol to work for PCOS?

Most clinical trials have used inositol for 12 weeks, so these amazing benefits are able to be felt at only 3 months of treatment.

Does the type of inositol matter?

Yes.

In the ovaries of healthy women most (99%) of inositol is myo-inositol. This is a ratio of myoinositol: di-chiro-inositol of 100:1, compared with 0.2:1 in women with PCOS. It is thought that in PCOS, there is upregulation of epimerase the enzyme that converts myo-inositol to di-chiro-inositol.

Most studies have used supplements that are either all myoinositol or predominantly myoinositol. As the body can convert myoinositol to di-chiro-inositol and should have more myoinositol than di-chiro-inositol the current research suggests the use of myoinositol supplementation is best in PCOS.

Can I take inositol if I don’t have PCOS?

Yes.

It is a dietary supplement, it is found in many plant foods. It helps with insulin sensitivity and ovarian function. Besides PCOS, it is a safe supplement to use for;

reducing insulin resistance in type II diabetes.
reducing gonadotropin use for follicle stimulation in non-PCOS women undergoing IVF treatment.

Given the excellent evidence for whole-food diets, exercise in PCOS and metformin, combining these with inositol is an attractive option.

Are Omega-3 fish oil supplements good for PCOS?

Omega-3 fatty acids are found in the diet. The main animal sources is from fatty fish like salmon, herring, and anchovies. This provides two omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) both of which have anti-inflammatory properties.

The type of omega-3 found in a plant sources is alpha-linolenic acid (ALA). This is found in walnuts & almonds and seeds like hemp, chia, flax & oils (like olive oil). ALA needs to be converted to EPA and DHA in the body by enzymes, with only an estimated 10-15% of dietary ALA being converted to EPA and DHA.

Nutrition guidelines recommend consumption of cold water fish two times per week to reap the health benefits of omega-3 fatty acids.

For vegans and those following a plant-based diet an adequate intake alpha-linolenic acid requires a tablespoon of chia seed or ground linseed, 2 tablespoons of hemp seed or 6 walnut halves daily.

Omega-3 fatty acid supplementation has become popular in recent years because of its many health benefits. Omega-3 supplements are beneficial for people with PCOS because they have anti-inflammatory properties. Additionally, omega 3 supplements can help improve insulin resistance and lower cholesterol and blood pressure levels.

Do omega-3 fatty acids regulate hormones?

A recent clinical trial in 2018 examined the effects of omega-3 fish oil supplements on mental health and metabolic profiles in women with PCOS.

reduced insulin levels
reduced HOMA-IR
reduced total testosterones
reduced facial and body hair

a meta-analysis also found that omega-3 supplements:

reduced cholesterol
reduced triglycerides

The 2018 clinical trial also showed the following benefits of omega 3 fish oil supplements for PCOS:

Anti-inflammatory benefits of omega-3 fatty acids

reduced CRP (a marker of inflammation)
reduced malondialdehyde (a marker of lipid peroxidation)
elevated glutathione (a cellular antioxidant)

Do omega-3 fish oil supplements improve mental health in women with PCOS?

In peer reviewed studies, omega-3 fish oil supplements in women with PCOS was associated with;

improved mood scores (Beck depression inventory)
improved general health questionnaire
improved depression anxiety and stress scale.

Does omega-3 fish oil supplements change PCOS gene expression?

A randomized controlled trial in 2018 showed that omega-3 supplementation altered gene expression of the following genes;

Increases gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) a receptor that improves insulin sensitivity
reduces gene expression of IL-1 and IL-8 – markers of inflammation

What dose of omega 3 fatty acids should be used for PCOS

Studies looking at women with PCOS use a dose of 3500-4000mg of fish oil. This equates to approximately:

EPA (eicosapentaenoic acid): 675-2450 mg
DHA (docosahexaenoic acid): 480-1400 mg

Probiotic Supplements for PCOS

The gut microbiome performs key role in human health and disease. The gut microbiome plays important roles in regulating human metabolism, and gut microbiome phenotypes have been identified as being associated with chronic disease.

Gut microbes and their metabolites influences a number of processes connected to PCOS including energy homeostasis, glucose metabolism, and systemic inflammation.

The ‘Dysbiosis of gut microbiota theory of PCOS’ published in 2012 suggests in women with PCOS, a dysbiotic gut microbiome triggers the host’s immune system to produce a chronic inflammatory response resulting in;

impaired insulin receptor function that results in a hyper-insulin state and insulin resistance.
The higher insulin interferes with follicle development and
drives excess androgen production by ovarian thecal cells.

Probiotics supplements contain live microorganisms that are administered with the goal of improving gut health, reducing inflammation, and correcting hormonal imbalances in PCOS patients.

A meta-analysis in 2020 of 587 women in 9 studies examined the use of probiotics or synbiotics (a combined supplement of prebiotics and probiotics) in women with PCOS. It demonstrates that administering probiotics confer metabolic, anti-inflammatory and hormonal balancing effects.

Metabolic

lower blood sugar levels
reduced HOMA-IR (insulin resistance) was reduced
reduced weight
reduced fasting insulin
reduced triglycerides

Inflammation

reduced markers of inflammation including hs-CRP and nitric oxide
improved glutathione (a powerful anti-oxidant)
reduced malondialdehyde (a marker of lipid peroxidation)

Hormones

reduced facial/body hair
reduced testosterone levels

It is impressive that these studies were able to show such improvements given that they used such different probiotic preparations. They had different strengths and strains of probiotics. The diverse products included combinations of species, the most frequently used including

Lactobacillus acidophilus (8 studies)
Lactobacillus casei (6 studies)
Bifidobacterium bifidum (5 studies)

Some of these probiotics were used in combined with prebiotics.

Other evidence for supplements for PCOS

Vitamin D supplements for PCOS

Vitamin D is a nutrient that is critically important for many bodily functions. Adequate levels of vitamin D helps to boost the immune system, keep bones healthy and strong, improve cognition, and more. Randomized controlled trials have found many connections with vitamin D deficiency and poorer outcomes with PCOS. Vitamin D deficiency is associated with low mood and depression and increased inflammation in people who have PCOS.

Vitamin D deficiency is also associated with poor ovarian stimulation in women with PCOS, Vitamin D supplements increase uterine lining in women needing fertility support. It also improves

weight loss,
follicle maturation,
menstrual regularity, and
reduces excess facial and body hair.

Vitamin D deficiency levels are associated with a 44% reduction in live birth rate compared to women with sufficient vitamin D levels with PCOS.

If you are trying to get pregnant and have PCOS, it is essential to ensure you are getting enough sun exposure, especially during late autumn and winter and if you live at latitudes above 37 degrees north or below 37 degrees south of the equator.

If you have limited sun exposure, many health professionals recommend vitamin D supplements: a dose of 400 – 1,000 iu of vitamin D each day is ideal.

N-Acetylcysteine (NAC) supplements for PCOS

N-acetylcysteine (NAC) is a supplement that has been found to be beneficial for women with polycystic ovary syndrome (PCOS). NAC is an antioxidant and amino acid, which helps protect against free radical damage and oxidative stress. It also supports the immune system when taken as a supplement.

When compared to metformin, NAC and metformin both result in significant and equal decreases in BMI, hirsutism, fasting insulin, free testosterone, and menstrual irregularity. However, NAC was more effective than Clomid when evaluated by three randomized studies that compared it to Clomid in women with PCOS. In two of these studies, Clomid plus NAC led to a better ovulation and pregnancy rate than either drug alone. This suggests that NAC supplementation can be beneficial when used in combination with clomid to improve pregnancy rates.

Berberine for PCOS

Berberine is a herb used in traditional Chinese medicine for centuries. It is comparable to the popular diabetes medication, metformin, in its effect on metabolic parameters. Berberine works as an insulin-sensitizer and can reverse many of the symptoms of diabetes.

Because of its potential benefits, berberine is sometimes used as a treatment for PCOS in women who have insulin resistance, particularly those wanting to use herbal support. However, it’s important to note that not all women will experience the same results from taking this supplement.

The dose of berberine commonly used in randomized controlled trials is 300-500mg 3x per day.

Melatonin supplements for PCOS

Melatonin is a hormone that is produced by the body and helps to regulate sleep and wake cycles. Women with PCOS have been found to have abnormally low levels of melatonin in their follicular fluid, which may be linked to infertility.

A controlled clinical trial using 10mg per night of melatonin resulted in improved metabolic profile and mental health wellbeing in women with PCOS.

A randomized clinical trial in 2019 also showed increase in pregnancy rates in women with PCOS undergoing artificial insemination who took 3mg melatonin per night from the 3rd day of menstruation to the day of gonadotropin injections started.

Supplements for PCOS to avoid: Selenium

A meta analysis found a clinical trial in 2016 using 200 μg selenium. In this study selenium increased insulin resistance so at this stage selenium supplementation is NOT recommended in women with PCOS.

Comprehensive PCOS Care

If you’re looking for comprehensive PCOS care seek professional medical advice from a health professional who specializes in lifestyle and integrative medicine. They can take an integrative approach to medicine, targeting lifestyle interventions to reverse insulin resistance that can help overcome the symptoms of PCOS. Supplements for PCOS can support and augment these lifestyle interventions.

Dr Brunt is experienced in working in integrative women’s health, with a particular focus on helping women with PCOS. In her clinical practice, she takes an individualized approach to using lifestyle intervention and evidence-based approaches to hormonal imbalances in her patients.

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