Does Inositol Have Proven Benefits? 22 Studies Reviewed

Some of the claimed health benefits of Inositol, that are quickly stumbled upon online, include that it fights depressive symptoms, improves fertility, assists with weight loss, lowers cholesterol, promotes sleep, eases constipation and promotes strong, healthy hair. Hey, how come I’ve never heard of this treatment?

I noticed that none of these benefits, at least the ones that I found, were scientifically referenced on these websites. This doesn’t give me a great deal of confidence in their validity.

Time to put on my investigators cap and find out for myself.

How long has it been around for?

There is quite a history to the use of Inositol compounds, especially in clinical gynaecology where their use is now widespread.

It was 1850 when Inositol was first extracted from the muscle, by scientist Johanes Joseph Scherer (1814-1869) (1). After which time, many researchers began to study its role in different tissues and organs. Several preliminary findings related Inositol-based compounds to germ-cell (e. sperm and egg related) physiology. (1)

In 1988, during research in to diabetes, Inositol compounds were found to be chemical mediators of insulin. (6) At around this time, the gynaecological disorder Polycystic Ovarian Syndrome (PCOS) was, for the first time, linked to insulin-resistance. (1) The link between PCOS and Inositol was made.

What Is It?

Inositol is an organic compound, important for several important biological roles and processes in the body. (2) Inositol and its derivatives (salts, phosphates and associated lipids) are found abundantly in nature, present in many plant foods, especially fruits, seeds, wholegrains and beans. (513) It is also present in animals and can be artificially-made in the laboratory.

It is often incorrectly classified as a B-vitamin. Belonging formally to the sugar family (3), its structure allows the formation of nine different forms of Inositol. (1) The two forms most present in the human body, and that you will most commonly hear of, are: myo-inositol (MI) and D-chiro-inositol (DCI). (1, 2)  The physiological ratio of these two forms in the human body is 40:1 (MI/DCI).(1)

Clearly, MI is, by far, the most abundant, biologically, and it is the most “interesting” form, physiologically. (1) It is currently even thought of as a prebiotic molecule. (4) Apart from dietary intake, MI can also be made, from glucose, by the human body. (1, 13)

How Much Research Is There?

The amount, and quality, of research on the health benefits of Inositol largely depends on the area that is being studied. Overall, there is not a large amount of high-quality research available, though there are a number of systematic reviews (S/R), and a few meta-analysis (M/A) papers, emerging in the fields of gynaecology and mental health, with relation to Inositol. Especially in the fields of gynaecology and reproduction, Inositol has quite a long research history. In the area of mental health, the studies have generally been scarce and under-powered.

Does Inositol Help With Getting Pregnant?

MI, in particular, is understood to be important in several areas of human reproduction and has long been studied. (9) It is found in high levels in women’s follicular fluid, where elevated amounts appear to play a positive function in follicular maturity and provide a marker of good-quality egg cells. (2, 9) MI is also found in high levels in men’s semen. (2)

All-cause subfertility

I was unable to find M/A papers analysing Inositol and its role in fertility, conception and reproduction. A 2013 S/R, assessing a range of antioxidants for female sub-fertility and where MI was included as an oral antioxidant, concluded that “antioxidants were not associated with an increased live birth rate or clinical pregnancy rate”. The quality of evidence in this review was assessed to be ‘very low’ and they were unable to assess whether one antioxidant was, overall, better than another. (12) Other clinical trials have explored this area with mixed results.

PCOS and Insulin-resistance

There is a fair bit of research available on Inositol and the roles it plays in PCOS, which is the most common cause of infertility in women. (1, 2, 8) PCOS is associated with ovarian dysfunction, metabolic and hormonal impairments, and menstrual irregularity, and affects up to 10% of reproductive-age women. (1,8) It is associated with, and possible caused by, insulin-resistance (1). Inositol deficiency, and the impairment of the inositol-dependent pathways, are thought to play an important role in the development of insulin-resistance (2, 6).

A critical review of 12 randomised-controlled-trials, included in a 2016 S/R, highlighted that oral intake of MI, alone or in combination with DCI, is capable of restoring spontaneous ovulation and improving fertility in women with PCOS. (16)

However, the optimal infertility treatment for PCOS women is not yet clear. (9, 10, 11) In those who desire an immediate pregnancy (eg. older women), MI supplementation does not appear to be the most appropriate choice. (9) For those with more time up their sleeve for achieving a pregnancy (eg. younger women), MI may be the treatment of choice to re-establish ovulatory menses and fertility. It provides a gradual onset of action minus the potential risk of a multiple-birth pregnancy. (9)

There are websites advocating Inositol supplementation for older women desiring a healthy pregnancy. However, the evidence isn’t there to support this, at this time.

In PCOS overweight patients, combined therapy of MI and DCI, compared to MI therapy alone, has been suggested as the first-line approach treatment. (8) In order to establish the proper therapeutic dose to ensure effectiveness, without comprimising ovarian function, an Inositol product was specifically designed according to the bodies own physiological plasma ration of MI/DCI which is 40:1. (7) This combined therapy had a two-fold effect: (a) an action on the liver, mainly through DCI, aimed at reducing insulin levels; and (b) a selective effect on the ovary, where MI acts to re-establish follicle-stimulating hormone sensitivity. (7, 8)

Reproductive technologies

There is potential benefit to Inositol supplementation in the context of assisted reproductive technologies (ART) and in-vitro fertilisation (IVF), with relation to the role of MI on egg and sperm cell quality. (14) It is an area that is only recently being explored with a growing number of papers and definitive results pending. (2, 14)

Bottom Line:

For women considered sub-fertile, there is currently no credible research suggesting oral Inositol supplementation assists with achieving a successful pregnancy. (12)

For younger PCOS patients undergoing fertility treatment (ICSI cycles), long-term co-treatment with MI does appear to significantly improve egg cell quality and reduces the risk of Ovarian Hyper-stimulation Syndrome. It does not improve the response to stimulation. For older PCOS, or other, patients desiring an immediate pregnancy, MI therapy is not considered the best choice. (9)

The potential benefit of Inositol in the field of reproductive technologies is currently being explored. (14)

Does Inositol Help Sleep?

There were virtually no papers directly exploring Inositol with relation to insomnia and other sleep disorders.

A 2010 review of complementary and alternative medicines (CAMs) did not find evidence for Inositol in the treatment of sleep disorders. It did find preliminary supportive evidence for Inositol treatment of anxiety, but not depression (15), which may indirectly improve sleep quality.

To put this in context, how about if we consider a more commonly used and better researched sleep-aid? The same review found that, “melatonin is likely to be useful in treating delayed sleep phase, jet lag, or shift work”. (15) A PubMed search of melatonin combined with insomnia yielded about fifty meta-analysis and systematic review papers.

Bottom Line:

There is no evidence that Inositol benefits sleep. There is some evidence that it  improves certain mood disorders, such as anxiety, and thereby may alleviate insomnia indirectly.

Does Inositol Reduce Testosterone?

There is currently very limited research on this topic. Counter-intuitively, the information that is available relates to women and not to men.

One of the known indicators of PCOS is hyper-androgenism, a medical condition where excessive levels of the “male” sex hormones (a.k.a. androgens), such as testosterone, are present in the female body. (13,16) Various studies have shown that DCI, at low-dose, lowers levels of serum androgen in PCOS patients. (13,16) MI has also been shown to lower serum androgen levels, in separate studies. (13, 16) This is thought to be due to the improvement in insulin-resistance in PCOS patients following Inositol therapy. (13)

Bottom Line:

Inositol therapy is an effective treatment for PCOS, and there is some evidence available that it lowers the level of androgens, such as testosterone, in these women as part of the treatment. There is currently no research demonstrating a role for Inositol in reducing testosterone levels in men, or in women without PCOS.

Does Inositol Reduce Cholesterol and Blood Pressure?

Once again, to date, this has been demonstrated in PCOS patients only, following on from Inositol therapy.

PCOS is associated with insulin-resistance, which has among its many symptoms, high cholesterol levels and elevated blood pressure. (13) A 2016 review found several studies that have reported on the positive effects of MI and DCI on clinical, metabolic, endocrine, hormonal, and oxidative abnormalities in women with PCOS. (13) As one example, MI supplementation was found to be effective in improving abnormal cholesterol levels in one clinical trial of 42 PCOS women. (13)

Other than that, all I came across was a 1999 study that examined the role of Inositol hexaphosphate (IP6), a major dietary source of Inositol phosphates, and high cholesterol levels in a rat model. It found “a role for IP6 as a potential therapeutic agent in the treatment of high lipid levels”. (17)

Bottom Line:

Through its treatment of PCOS, Inositol can also improve the associated symptoms, such as high cholesterol and, likely, high-blood pressure. There is very little to no research suggesting Inositol to be beneficial as a cholesterol-lowering agent and/or anti-hypertensive in the general public.

Does Inositol Help Treat Depression?

This has been explored quite a bit and there are a number of M/A and S/R emerging on the topic.

A 2016 M/A and S/R found “non-significant results” for Inositol as a treatment for depression. (18) A further 2010 review had the same conclusion. (15) A 2014 M/A on the same topic suggests that “inositol may be beneficial for depressed patients, especially those with premenstrual dysphoric disorder”, despite finding “no statistically significant effects of inositol on depressive symptoms”. They did acknowledge, however, a main limitation of their M/A being that a small number of studies were included (that being, 7 studies). (19)

Specifically with regards to bipolar depression, there was, similarly, little to no evidence of Inositol’s effectiveness. However, again, there were only a few small studies and further research was requested in this area. (2021)

Bottom Line:

Weak evidence, if any, exists for Inositol as an effective treatment for depression. More research is required in this area.

Is It Safe?

According to a 2011 review of the safety of Inositol therapy, there is scarce information on the safety/ side-effects of MI, despite its wide clinical use. What they did find was that, “only the highest dose of MI (12 g/day) induced mild gastrointestinal side effects such as nausea, flatus and diarrhoea”. (22) The severity of side-effects did not increase with the dosage.

This finding was supported in a 2014 M/A where Inositol slightly caused gastrointestinal upset compared with placebo. (19) However, more research is needed in this area considering the widespread use of Inositol in certain fields of medicine.

Summary

There are a lot of health claims being attributed to Inositol, on the web, without the research to back it up. Yet, the strength of Inositol, at least according to my research in to certain health areas, lies in its promise as a treatment for PCOS, and the flow-on effects it has for women with this condition. They include, potentially improving fertility in a sub-set of PCOS patients, and reducing the indicators/ side-effects associated with PCOS, such as high-testosterone levels, high cholesterol and high blood pressure.

With that understanding, I’m once again happy to take off my investigators cap.

References

  1. Bizzarri M1, Carlomagno G. Inositol: history of an effective therapy for Polycystic Ovary Syndrome. Eur Rev Med Pharmacol Sci. 2014 Jul;18(13):1896-903.
  2. Milewska EM, Czyzyk A, Meczekalski B, Genazzani AD. Inositol and human reproduction. From cellular metabolism to clinical use. Gynecol Endocrinol. 2016 Sep;32(9):690-695.
  3. The cell biology of inositol lipids and phosphates. Proceedings of the 2006 Biochemical Society Annual Symposium. Birmingham, United Kingdom. March 29-30, 2006. Biochemical Society symposium. 2007(74): pp. 1-271.
  4. AGRANOFF BW. Turtles All the Way: Reflections on myo-Inositol. J Biol Chem 2009; 284: 21121- 21126.
  5. CLEMENTS RS, JR., DARNELL B. Myo-inositol content of common foods: development of a high-myoinositol diet. Am J Clin Nutr 1980; 33: 1954-1967.
  6. LARNER J, HUANG LC, TANG G, SUZUKI S, SCHWARTZ CF, ROMERO G, ROULIDIS Z, ZELLER K, SHEN TY, OSWALD AS, et al. Insulin mediators: structure and formation. Cold Spring Harb Symp Quant Biol 1988; 53 Pt 2: 965-971.
  7. CARLOMAGNO G, DE GRAZIA S, UNFER V, MANNA F. Myo-inositol in a new pharmaceutical form: a step forward to a broader clinical use. Expert Opin Drug Deliv 2012; 9: 267-271.
  8. NORDIO M, PROIETTI E. 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. Eur Rev Med Pharmacol Sci 2012; 16: 575-581.
  9. Papaleo E, Unfer V, Baillargeon JP, Chiu TT. Contribution of myo-inositol to reproduction. Eur J Obstet Gynecol Reprod Biol. 2009 Dec;147(2):120-3.
  10. Consensus on infertility treatment related to polycystic ovary syndrome. The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group* March 2–3, 2007, Thessaloniki, Greece. Hum Reprod 2007;23: 462–477.
  11. Palomba S, Orio F, Zullo F. Ovulation induction in women with polycystic ovary syndrome. Fertil Steril 2008;86(Suppl 1):s26–7.
  12. Showell MG, Brown J, Clarke J, Hart RJ. Antioxidants for female subfertility. Cochrane Database Syst Rev. 2013 Aug 5;(8):CD007807.
  13. Mansour A, Hosseini S, Larijani B. Nutrients as novel therapeutic approaches for metabolic disturbances in polycystic ovary syndrome. EXCLI J. 2016 Sep 5;15:551-564.
  14. Bevilacqua A, Carlomagno G, Gerli S, et al. Results from the International Consensus Conference on myo-inositol and D-chiro-inositol in Obstetrics and Gynecology–assisted reproduction technology. Gynecol Endocrinol. 2015 Jun;31(6):441-6.
  15. Larzelere MM1, Campbell JS, Robertson M. Complementary and alternative medicine usage for behavioral health indications. Prim Care. 2010 Jun;37(2):213-36.
  16. Unfer V, Nestler JE, Kamenov ZA. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. Int J Endocrinol. 2016;2016:1849162.
  17. Jariwalla RJ. Inositol hexaphosphate (IP6) as an anti-neoplastic and lipid-lowering agent. Anticancer Res. 1999 Sep-Oct;19(5A):3699-702.
  18. Sarris J, Murphy J, Mischoulon D. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. Am J Psychiatry. 2016 Jun 1;173(6):575-87.
  19. Mukai T, Kishi T, Matsuda Y. A meta-analysis of inositol for depression and anxiety disorders. Hum Psychopharmacol. 2014 Jan;29(1):55-63.
  20. Rakofsky JJ, Dunlop BW. Review of nutritional supplements for the treatment of bipolar depression. Depress Anxiety. 2014 May;31(5):379-90.
  21. Sienaert P, Lambrichts L, Dols A, Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review. Bipolar Disord. 2013 Feb;15(1):61-9.
  22. Carlomagno G, Unfer V. Inositol safety: clinical evidences. Eur Rev Med Pharmacol Sci. 2011 Aug;15(8):931-6.
Summary
Does Inositol Have Proven Benefits? 22 Studies Reviewed
Article Name
Does Inositol Have Proven Benefits? 22 Studies Reviewed
Author
Healthy But Smart

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