Experts’ opinion on inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: a further help for human reproduction and beyond

ABSTRACT

Introduction: This Experts’ opinion provides an updated scientific support to gynecologists, obstetricians, endocrinologists, nutritionists, neurologists and general practitioners on the use of Inositols in the therapy of Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM).

Areas covered: This paper summarizes the physiology of Myo-Inositol (MI) and D-Chiro-Inositol (DCI), two important molecules present in human organisms, and their therapeutic role, also for treating infertility. Some deep differences between the physiological functions of MI and DCI, as well as their safety and intestinal absorption are discussed. Updates include new evidence on the efficacy exerted in PCOS by the 40:1 MI/DCI ratio, and the innovative approach based on alpha-lactalbumin to overcome the decreased therapeutic efficacy of Inositols in some patients.

Expert opinion: The evidence suggests that MI, alone or with DCI in the 40:1 ratio, offers a promising treatment for PCOS and NIDDM. However, additional studies need to evaluate some still unresolved issues, such as the best MI/DCI ratio for treating NIDDM, the potential cost-effectiveness of reduced gonadotropins administration in IVF due to MI treatment, or the benefit of MI supplementation in ovulation induction with clomiphene citrate in PCOS patients.

KEYWORDS:

• Myo-inositol (MI)
• D-chiro-inositol (DCI)
• alpha-lactalbumin (alpha-LA)
• insulin resistance
• polycystic ovary syndrome (PCOS)
• non-insulin dependent (type 2) diabetes mellitus (NIDDM)
• absorption
• inositol-resistance

Article Highlights

• Myo-inositol (MI) and D-chiro-inositol (DCI) are the most important stereoisomers of inositol: MI can be transformed into DCI by a specific epimerase under insulin control and their respective concentrations (ratio) depends on the specific tissue needs.

• The MI/DCI physiological ratio is 40:1 in plasma and 100:1 in the ovary.

• MI and DCI play several different roles, in some cases also exerting opposite effects (high concentrations of DCI in the follicular fluid are detrimental for blastocyst quality, whereas the MI role is beneficial).

• MI and DCI are insulin sensitizers although using distinct pathways. MI is involved in the cellular uptake of glucose, whereas DCI in glycogen synthesis; furthermore, DCI affects steroidogenesis. DCI reduces in dose–response manner the expression of aromatase gene (CYP19A1) and consequently the conversion of testosterone to estrogen. In addition, MI in the ovary (as InsP3) is one of the second messengers of FSH.

• MI alone or with DCI, in the 40:1 physiological ratio proven to be effective in the treatment of Polycystic Ovary Syndrome and Type 2 diabetes.

• The combination of MI and alpha-lactalbumin (alpha-LA) was found to increase the intestinal absorption and the therapeutic effects of MI.

• Several studies demonstrated that MI and alpha-LA are safe at therapeutic doses. The U.S. Food and Drug Administration included them in the list of generally recognized as safe (GRAS) compounds.

This box summarizes the key points contained in the article.

Acknowledgments

The authors would like to thank Dr. Simone Garzon (Department of Obstetrics and Gynecology, University of Insubria, Varese, Italy) for providing Figure 1. Vittorio Unfer and Fabio Facchinetti thank Dr. Giovanni Monastra for his collaboration in all phases of realization of this Experts’ opinion.

Declaration of interest

Vittorio Unfer is an employee at Lo.Li. Pharma s.r.l., Rome, Italy. Fabio Facchinetti has been a consultant of the same company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Obituary

The authors express their most heartfelt condolences for the premature departure of Prof. Francesco Orio, a high skilled researcher and loyal friend, who spent his life with a deep dedication to the patients.

Additional information

Funding

This work was not funded.