The Research Behind Inositol for PCOS

Today I want to examine the research behind inositol for PCOS. If you are looking into natural remedies to manage your PCOS symptoms there is a lot of supporting evidence that inositol offers many benefits. Below I will break down all of the studies and research supporting the use of inositol for PCOS.

What is Inositol?

Inositol is a vitamin-like substance found in beans and fruit. It can also be made in a laboratory.

Inositol is similar to sorbitol and mannitol.

It is estimated that Americans get 800 -1,000 mg daily of inositol from their diet.

There are nine different types of inositol but the most common two are Myo and D-chiro inositol.

The reason that we focus on Myo-inositol (MYO) and D-chiro-inositol (DCI) for PCOS is because they serve as secondary messengers for insulin receptors.

The 2 Types of Inositol

Myo-inositol is the most common form and when looking at the type found in human tissues, 99% of the inositol is Myo-inositol.

Myo-inositol promotes insulin and FSH (follicle-stimulating hormone- a reproductive hormone) signaling in the ovary.

Myo-inositol for PCOS is shown to improve insulin resistance, egg quality, and reduces the risk of gestational diabetes in women with PCOS.

D-chiro-inositol is only 1% of the inositol found in human tissues.

When the body needs D-chiro-inositol, it produces it by converting Myo-inositol.

D-chiro-inositol plays an important role in insulin’s action in the peripheral tissues (muscle, fat).

D-chiro-inositol for PCOS is shown to improve insulin and androgens.

Why Inositol is Important for PCOS?

Most women with PCOS have some degree of insulin resistance.

When you have excess insulin in the blood also known as hyperinsulinemia caused by insulin resistance, this can lead to negative effects in the ovary.

For example, when the ovary produces too much testosterone this can cause hair and skin issues. Also, ovulation is impaired.

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Women with PCOS who are insulin resistant are also found to have an abnormal ratio of Myo-inositol to D-chiro-inositol. 

It is found that low levels of Myo-inositol can adversely impact ovarian function and egg quality. In turn, elevated levels of D-chiro-inositol in the ovary can cause increased androgen production.

Restoring a normal balance between Myo-inositol and D-chiro-inositol will reduce insulin resistance in PCOS patients.

And when you address insulin resistance in PCOS a lot of your symptoms will improve such as menstruation, weight loss, acne, and issues with hair loss and excess hair growth.

RELATED: Ovasitol FAQS

Inositol Studies and PCOS

There have been a number of studies looking at inositols and its metabolic benefits and its ability to restore ovulation.

More recent trials have studied the role of inositols in improving reproductive outcomes. 

All of these studies have been conducted in Europe so the United States has been slower to adopt this information.

However, there are currently two university-based trials now underway in the U.S,  including one that is funded by the National Institute of Health.

Two US trials are underway:

1. “Inositol Supplementation to Treat Polycystic Ovary Syndrome: A Double-Blind Dose Ranging RCT”

·        Underway at Penn State Hershey Medical School led by Dr. Legro

·        Being funded by NIH

·        Study will be done with Ovasitol

·        Looking to assess metabolic endpoints to confirm best daily dosage for multi-center fertility-focused study

o   Serum T, free T, SHBG

o   Fasting insulin, AUC of 2 hr OGTT

2. Myo-Inositol as an Adjuvant to Letrozole for fertility in Polycystic Ovary Syndrome (MALI-PCOS): a Randomized Pilot Trial”

·        University of Oklahoma Health Sciences Center led by Dr. Heather Burks

·        168 women with PCOS randomized to either letrozole alone OR letrozole plus 4 grams Ovasitol daily

·        The main outcome measure of MALI-PCOS will be clinical pregnancy rate

Inositol and Fertility

PCOS is the leading cause of female infertility.

So doctors have been looking at ways to help women with PCOS conceive.

Let’s look at some of these studies that are evaluating inositol for fertility.

This is the first study I want to discuss:

Raffone, Emanuela et al. “Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women.” Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology vol. 26,4 (2010): 275-80. 

This study looked at 120 women with PCOS and chronic anovulation.

These women were randomized to either 1500 mg metformin or 4 grams of Myo-inositol daily for 6 months.

Researchers looked at the ovulation rate and live birth rate between the two groups.

It was found that the women who took the Myo-inositol had a higher ovulation rate (69.6%) and live birth rate (25.7%) compared to those women who were taking metformin.

The next study examined the use of inositols during IVF for PCOS.

Zheng, Xiangqin et al. “Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET.” Medicine vol. 96,49 (2017): e8842

Researchers did a meta-analysis and systematic review of seven randomized controlled trials (RCTs) with 935 PCOS subjects. 

The study found that women who took inositols needed 14% less medication, saw an 8% improvement in better quality embryos, 66% reduction in miscarriage rate, and 21% improvement in clinical pregnancy rate.

Using inositols during IVF can improve the outcome of IVF for PCOS women.

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This next study looked at inositols plus melatonin for PCOS.

Pacchiarotti, Alessandro et al. “Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome.” Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology vol. 32,1 (2016): 69-73. 

The study consisted of 526 PCOS patients undergoing IVF. They were randomized into 3 groups:  Placebo, 4000 mg of Myo-inositol, and 4000mg Myo-inositol + 3 mg of melatonin.

Participants were treated from the first day of their menstrual cycle until 14 days after embryo transfer.

The addition of melatonin produced statistically significant improvement in egg and embryo quality, and reduced the required dosage of fertility drugs needed.  The clinical pregnancy rate was 65% in Myo-inositol + melatonin vs. 58% in Myo-inositol group.

Melatonin has been shown to improve egg quality in both PCOS and non-PCOS patients.

Inositol and Pregnancy

There are a lot of questions about whether inositol is safe to use during pregnancy.

Studies have shown that it is not only safe but it significantly reduces the risk of gestational diabetes.

Women with PCOS have 3 times the risk of developing gestational diabetes. 

This study examined inositol use during pregnancy to determine if it helps prevent gestational diabetes.

Vitagliano, Amerigo et al. “Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials.” Archives of gynecology and obstetrics vol. 299,1 (2019): 55-68. doi:10.1007/s00404-018-5005-0

The study looked at 5 random controlled trials which consisted of 965 subjects.

Researchers found a 51% reduction in gestational diabetes with inositol supplementation and 65% reduction in preterm delivery.

There were no adverse effects reported by subjects who used inositol during the duration of their pregnancy.

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Inositol Benefits for PCOS

Women with PCOS struggle to maintain normal insulin and glucose levels and have varying degrees of insulin resistance.

Several studies have looked at the use of inositol and its effect on metabolic health.

The first study I want to talk about is by

Costantino, D et al. “Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial.” European review for medical and pharmacological sciences vol. 13,2 (2009): 105-10.

They looked at 42 women with PCOS and randomized them to a group that either took 4 grams of Myo-inositol (MI) or a placebo.

And the results showed the women who took  Myo-inositol had a 65% reduction in serum testosterone, a 51% reduction in serum triglycerides, a 35% reduction in plasma insulin (24 hour) , and 80% increase in insulin sensitivity.

The next study examines inositols vs metformin to see which one produced better results in women with PCOS.

Facchinetti, Fabio et al. “Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials.” Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology vol. 35,3 (2019): 198-206. doi:10.1080/09513590.2018.1540578

This study was a systematic review and meta-analysis of 6 randomized controlled trials between 2013 and 2017.

There were a total of 355 patients. The study found that Myo-inositol was as effective or more effective than metformin in normalizing fasting insulin, insulin resistance, serum testosterone, SHBG, and BMI.

The only difference that was found was that metformin subjects were 5 times more likely to experience significant side effects.

This study looked at women with PCOS and compared fasting insulin, 24 hour insulin production, and fasting glucose in the group that took Myo-inositol or the combined ratio of Myo-inositol to D-chiro-inositol (40:1).

Nordio, M, and E Proietti. “The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone.” European review for medical and pharmacological sciences vol. 16,5 (2012): 575-81. 

In PCOS, the peripheral tissues also known as muscle and fat are deficient in D-chiro-inositol, while the ovary is deficient in Myo-inositol. In the plasma of your blood the ratio of Myo-inositol to D-chiro-inositol is 40:1.

In this study, 50 patients with PCOS with high BMI were randomized to either Myo-inositol or Myo-inositol + D-chiro-inositol (40:1) for 12 weeks.

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The results showed that when PCOS women took the 40:1 ratio of Myo-inositol to D-chiro-inositol they had better rates than just taking Myo-inositol alone.

In another study by the same researcher several years later, looked at different ratios of Myo-inositol to D-chiro-inositol to see what ratio worked best for women with PCOS.

 Nordio, M et al. “The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios.” European review for medical and pharmacological sciences vol. 23,12 (2019): 5512-5521. doi:10.26355/eurrev_201906_18223

This study consisted of 56 women with PCOS. The participants were randomized into 7 groups with different ratios of Myo-inositol to D-chiro-inositol. 

All subjects took 4 grams of inositols daily (2 grams in AM and 2 grams in PM) for 3 months. The study was evaluating the return of ovulation, free testosterone level, estrogen level and insulin resistance.

The 40:1 group had the best results in all endpoints.

Evaluating Inositol Supplements

Stick to a 40:1 ratio because that is the physiologic ratio in both the peripheral tissues and ovary.

Most studies focus on a dose of 4 grams per day.

Avoid products with fillers such as maltodextrin, inulin, magnesium stearate, silicon dioxide, microcrystalline cellulose, rice flour.

Look for products that are independently certified by either NSF or USP.

Avoid products that have additional nutrients mixed into the supplement (Absorbing inositols is not easy so want to take just inositols to maximize absorption.).

Best Inositol for PCOS

It is evident that inositol is very effective for women with PCOS. Myo-inositol and D-chiro-inositol given in combination will improve metabolic and reproductive endpoints in most PCOS patients. 

A 40:1 inositol supplementation restores ovulation in most PCOS patients and can improve fertility outcomes in both PCOS and non-PCOS patients.

Also, a 40:1 Myo-inositol: D-chiro-inositol supplementation is as effective as metformin in reducing insulin resistance and excess testosterone production and will improve metabolic issues in most PCOS patients.

Ovasitol by Theralogix is the first and only inositol supplement that is in the 40:1 ratio and is independently tested and verified by the NSF (a not-for-profit certification program) for content purity and accuracy.

Want to know more about Ovasitol? I have a detailed review of my experience with Ovasitol for PCOS.

Inositol Side Effects

Inositol supplementation is safe and well-tolerated. Most women do not report any side effects while taking inositol.

How Long Does it Take for Inositol to Work?

Restoring ovulation usually takes at least 3 months of inositol supplementation. To see an improvement in testosterone/metabolic issues may take up to 6 months of inositol supplementation.

Summing Up Inositol Benefits for PCOS

Myo-inositol and D-chiro-inositol play a key role in insulin receptor signaling.

Women with PCOS have an abnormal ratio of Myo-inositol to D-chiro-inositol ratio in the body.

It is found that the best ratio that has shown proven results for women with PCOS is 40:1.

It can improve fertility as well as metabolic health in women with PCOS.

Inositol supplementation is considered safe and well-tolerated.

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