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Myo-Inositol & PCOS
Polycystic ovary syndrome is the most common endocrine disorder and the cause of up to 30% of infertility in couples seeking treatment. It is commonly underdiagnosed and may affect up to as many as 15% of females during reproductive years. Research carried out at South Australia’s University of Adelaide and published in The Lancet has predicted that the global scale of this disorder is set to worsen.1

In this research review article, we take a closer look at a lesser known compound called myo-inositol. This intelligent compound features on our list of the best supplements for PCOS and has been found to have significant potential to improve many of the prevalent features of this disorder. Read on to find out more.

What is PCOS?
The term ‘polycystic ovary syndrome’ (PCOS) describes a complex disorder with a range of symptoms. There is no single known cause and it is likely to be caused by a combination of genetic and environmental factors. It is characterised by chronic anovulation and excess ovarian activity, with the main feature being the presence of multiple underdeveloped tiny sacs (follicles) on the ovaries - often these underdeveloped follicles are unable to release an egg which means ovulation doesn’t take place.

In addition, a large proportion of women also have excessive androgen secretion or activity (hyperandrogenism) and abnormal insulin activity.2 Many body systems are affected in polycystic ovary syndrome resulting in several health complications which may include menstrual dysfunction, infertility, miscarriage, acne, oily skin, depression, obesity, hirsutism, hair loss, insulin resistance and increased risk of metabolic syndrome, cardiovascular disease, non-alcoholic fatty liver disease and chronic low grade inflammation.2,3

In 2003, The Rotterdam consensus defined the diagnostic criteria of PCOS as the presence of any two of the following three features: hyperandrogenism (clinical or biochemical), ovulatory dysfunction (often manifested by menstrual irregularities), and polycystic ovarian morphology (PCOM) by ultrasound. The Rotterdam criteria remains the most used diagnostic criteria for both individual diagnosis and research and yet is still generally accepted to have limitations.

Needless to say, polycystic ovary syndrome is complex, commonly difficult to diagnose and is often missed completely.4,5

Nutrition & PCOS
The good news is that targeted dietary and lifestyle changes can be of significant help to women affected by this debilitating disorder. Whilst every case is unique, and requires an individualised and multi-faceted approach, effective treatment protocols commonly centre around the nutritional support of these four key areas:

1. Weight management
2. Blood sugar balance and insulin function normalisation
3. Hormone balance
4. Ovarian health support

Patients often experience significant improvement in symptoms when these areas are addressed with targeted dietary and lifestyle strategies, and supplementation with specific nutrients and botanicals.

Myo-inositol is one supplement in particular which has received widespread attention for the potential role it has to play in supporting women with PCOS. And much research to date indicates that this novel supplement has the potential to provide support for many of these key areas.

What is Myo-inositol?
Myo-inositol is one of nine different types of inositol. It is a naturally occurring substance produced in the human body from glucose, although it is not a sugar. Better described as a ‘vitamin-like’ substance, myo-inositol is often considered to be a member of the B complex group of vitamins. However, because it is produced by the body in amounts considered sufficient to support health, it is not officially termed an essential nutrient. In addition to the body’s own production from glucose, myo-inositol is also found naturally in many foods such as organ meats, fruit, grains, nuts and beans.

Myo-inositol - Key role in insulin signalling
Myo-inositol is involved in the metabolism, transport and breakdown of glucose and its conversion to glycogen. It is a key factor involved in insulin signalling, and is an immediate precursor to another type of inositol, D-chiro-inositol, which interacts with select sugars in the body to form inositol phosphoglycans – these play an important role in mediating the actions of insulin.6-12 Low levels of myo-inositol, D-chiro-inositol and inositol phosphoglycans have been observed in individuals with impaired insulin sensitivity and PCOS.6-12

Myo-inositol & PCOS
A number of recent studies have found myo-inositol to be an effective support in PCOS, in part due to its ability to improve insulin sensitivity, restore hormonal balance, improve menstrual regularity, reduce hyperandrogenism and influence ovarian function. Research has also demonstrated fertility-improving effects of myo-inositol among women with PCOS; and since the syndrome is the leading cause of female infertility, these results are particularly encouraging.13-22

So, what’s the evidence?

• In a 2009 double blind clinical trial, 42 women with PCOS received myo-inositol (4 grams daily plus 400mcg folic acid) or placebo (folic acid alone). Results showed that myo-inositol increased insulin sensitivity, improved glucose tolerance and decreased glucose-stimulated insulin release. In addition, the researchers noted a positive effect on ovulation - 16 out of 23 women in the myo-inositol group ovulated, compared to 4 out of 19 women in the placebo group. In these women, there was also a 66% reduction of serum total testosterone and a 73% reduction of serum free testosterone concentrations. Cardiovascular markers, systolic and diastolic blood pressures, plasma triglycerides and total cholesterol concentrations also decreased in the myo-inositol group.13

• Another study in 20 overweight women with PCOS found that 12 weeks of supplementation with myo-inositol improved insulin sensitivity and reproductive hormone balance and completely restored the menstrual cycle in all amenorrheic and oligomenorrheic subjects.14

• Research carried out in 2011 showed a combination of the contraceptive pill and myo-inositol (4 grams daily for 12 months) to be more effective in controlling the endocrine, metabolic and clinical profile in patients with PCOS than the contraceptive pill alone; the same study also found myo-inositol reduced insulin levels and insulin resistance.15

• In a prospective clinical study carried out in Rome in 2008, researchers investigated the effects of myo-inositol on two of the most common features of PCOS, hirsutism and hyperandrogenism. In the study, 46 women were evaluated at baseline and then again, following treatment with myo-inositol for 6 months. Results showed that treatment with myo-inositol significantly reduced hirsutism, hyperandrogenism and insulin resistance.16

Learn More
• SUPPLEMENTS: Inositol & Myo-Inositol Range 
• SUPPLEMENTS: Women's Health Supplements
• FERTILITY: How Myo-Inositol Supports Fertility
• MAGNESIUM FOCUS: Magnesium, PMS & Menopause

• In a double blind trial published in 2011 in the European Review for Medical and Pharmacological Sciences, researchers compared the effects of supplementation with 2g myo-inositol and 200 mcg folic acid compared to 200 mcg folic acid taken twice daily for 3 months in women with PCOS undergoing IVF and ovulation induction. At the end of the treatment, in the group taking myo-inositol, both the number and quality of oocytes (immature egg cells) was greatly improved. The authors concluded, “these data suggest that myo-inositol may be useful in the treatment of PCOS patients undergoing ovulation induction, both for its insulin sensitizing activity, and its role in oocyte maturation.”17 Additional research has found myo-inositol to be useful for improving oocyte quality, ovulation and pregnancy outcomes.18-22

• In a 2018 randomised controlled trial published in the Journal of Psychosomatic Obstetrics and Gynaecology researchers compared the effects of 12 weeks of intervention with either myo-inositol or metformin on mental health parameters and biomarkers of oxidative stress in 60 subjects with PCOS. Results showed that after the 12-week intervention, changes in general health, depression, anxiety & stress, and plasma total antioxidant capacity (TAC) concentrations in the myo-inositol group were significantly different from the changes in these indicators in the metformin group. The researchers concluded that their data supported that myo-inositol supplementation for 12 weeks among patients with PCOS has favourable effects on parameters of mental health and plasma TAC levels.23

• In a 2017 randomised controlled trial published in Gynecological Endocrinology, researchers compared the effects of metformin and myo-inositol on the clinical and metabolic features in PCOS. Fifty women with PCOS and either insulin resistance or hyperinsulinaemia were randomised to receive treatment with either metformin (1500 mg/day) or myo-inositol (4g / day). Results in both groups were similar: insulin sensitivity and BMI significantly improved in both groups, and the menstrual cycle was normalised in about 50% of the women. The researchers concluded that both metformin and myo-inositol have been demonstrated to be useful in women with PCOS for lowering BMI, improving insulin sensitivity, and improving menstrual cycle, without significant differences between the two treatments.24

• In a 2017 review on using inositols in PCOS, and published in Gynecological Endocrinology, the authors found combined treatment with myo-inositol and d-chiro inositol to be effective in restoring ovary function and metabolic balance in PCOS.25

• A 2017 randomised controlled trial was carried out to compare the effects of metformin and myo-inositol on clinical, metabolic and genetic parameters in women with PCOS. The researchers concluded that, “overall, taking myo-inositol, compared with metformin, for 12 weeks in patients with PCOS with hyperinsulinism and normoinsulinism had beneficial effects on total testosterone, mFG scores, serum hs-CRP levels and gene expression of IL-1, but did not affect other hormonal profiles, NO levels or gene expression of IL-8 and TNF-α.”26

• A 2017 randomised controlled crossover study was carried out to investigate which is more effective between metformin and myo inositol on hormonal, clinical and metabolic parameters in obese patients with PCOS. In the study, 34 PCOS obese women were randomised to receive metformin (850mg twice daily) or myo-inositol (1000mg twice daily) for 6 months. After a 3-month washout period, the same subjects received the other compound for the following 6 months. Results showed that both treatments improved the glyco-insulinaemic features of obese PCOS patients, but only metformin seems to exert a beneficial effect on the endocrine and clinical features of the syndrome.27

• In a 2020 study published in the American Journal of Physiology - Endocrinology and Metabolism, researchers evaluated the insulin-sensitising mechanisms of myo-inositol in human endometrial cells exposed to a PCOS environment. The researchers concluded that “myo-inositol is a potential insulin-sensitising agent that could be used as an effective treatment option in women with PCOS by improving their metabolic parameters as well as their reproductive status.”37

Myo-Inositol – From Research to Clinical Application
As you will no doubt be gathering by now, there is significant potential for the use of myo-inositol. For women suffering with the many debilitating faces of PCOS; from insulin resistance to excess androgens, anovulation and more, myo-inositol has the potential to offer significant and wide-ranging benefits. And whilst myo-inositol has demonstrated significant benefits in women with PCOS, its use is not limited here.

Myo-inositol may be of benefit for a range of applications related to female health, and additional research in the area has found this to be the case. Clinical studies have shown benefits of using myo-inositol in patients with premenstrual dysphoric disorder (a severe form of PMS) and in postmenopausal women with metabolic syndrome.28-30 Research shows that myo-inositol also has an integral role in the activation of serotonin receptors (the ‘feel-good’ neurotransmitter), thus supporting its use for mood balance in the premenstrual phase of the menstrual cycle and also potential uses in depression and panic disorder.31

The clinical applications of myo-inositol are already wide ranging and it’s likely, as research in the area gathers momentum, more may be added. For women with PCOS though, research shows that myo-inositol is a useful consideration as part of their treatment protocol.

Myo-Inositol – How much to take?
Current research suggests that for women with PCOS, 2000mg myo-inositol taken 1-2 times daily for 3 months is an effective protocol to begin with before reviewing the programme.13-22,32 32 Clinical doses of myo-inositol may be best achieved in supplemental powdered form. Myo-inositol may also be taken along with folic acid. The benefits demonstrated by research so far have involved myo-inositol in supplemental form rather than from food sources; it is also unlikely that food sources can supply high enough levels to achieve a therapeutic effect.

Myo-Inositol – Is it safe?
Myo-inositol appears to be safe and well tolerated by most. There have been some mild reported side effects in the scientific literature, which include mild gastrointestinal side effects such as nausea, flatulence and diarrhoea, and dizziness, tiredness and headache32-35 but these appear to occur at doses higher than are generally recommended. Patients with bi-polar disorder are also advised to avoid supplementation with myo-inositol before further research can determine its safety.32-35 As with all supplementation, patients with existing medical conditions or taking prescribed medication should always consult a healthcare practitioner before starting to take myo-inositol.

Myo-inositol – A promising emerging support for PCOS…
Currently, the evidence to support using myo-inositol in PCOS is rapidly emerging and promising particularly with regard to hormonal, ovulatory and metabolic benefits. As with many aspects of nutrition-based interventions however, the research is still considered to be limited by small study group sizes. According to the International PCOS Network, inositol (in any form) should be considered an experimental therapy in PCOS, “as this agent is freely available as a nutritional supplement, at low to moderate cost and appears to have a limited side effect profile, it may warrant consideration for use despite limited and low quality evidence. As with other supplements or complementary therapies, women taking this agent are encouraged to advise their health care team.”36

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15. Minozzi M, Costantino D et al. The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome. Gynecol Endocrinol. 2011 Nov;27(11):920-4.
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17. Ciotta L, Stracquadanio M, et al. Effects of myo-inositol supplementation on oocyte's quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci. 2011 May; 15(5): 509-14.
18. Rizzo P, Raffone E, Benedetto V. Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial. Eur Rev Med Pharmacol Sci. 2010 Jun;14(6):555-61.

19. Papaleo E, Unfer V, et al. Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril. 2009 May;91(5):1750-4.
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21. Gerli S, Mignosa M, et al. Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci. 2003 Nov-Dec; 7(6):151-9.
22. Papaleo E, Unfer V et al. Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol. 2007 Dec; 23(12):700-3.
23. Jamilian H, Jamilian M et al. Comparison of myo-inositol and metformin on mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomised, double-blind, placebo-controlled trial. J Psychosom Obstet Gynaecol. 2018 Dec; 39(4): 307-314
24. Fruzzetti F, Perini D, et al. Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2017 Jan; 33 (1): 39-42
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