Targeting Metabolic Consequences of Insulin Resistance in Polycystic Ovary Syndrome by D-chiro-inositol and Emerging Nutraceuticals: A Focused Review

Abstract

Polycystic ovary syndrome (PCOS) is a complex disorder associated with ovarian dysfunction, infertility, menstrual irregularity, and hormonal impairments. Over the last decade, several studies have shown that some PCOS women have insulin resistance (InsR) and hyperinsulinemia, apart from being overweight or obese. Therefore, a crucial clinical aspect is that PCOS patients might develop glucose intolerance and type 2 diabetes. Insulin-sensitizing drugs have been used as first-line treatment to improve hyperinsulinemia in women with PCOS. Although reducing PCOS symptoms and signs, several used insulin-sensitizer drugs may induce side effects, which reduces compliance. D-chiro-inositol (DCI), which is a naturally occurring stereoisomer of inositol, has been classified as an insulin-sensitizer and seems to mitigate multiple InsR-related metabolic alterations in PCOS with a safe profile. However, according to a multi-targeted design, the supplementation with DCI can be synergistically integrated by combining other potential insulin-sensitizing drugs and/or nutraceuticals. The literature provides the initial support for using several unexplored nutraceutical interventions that may target relevant metabolic abnormalities associated with InsR in PCOS. With a need to promote interest in clinical research, this review aims to discuss the efficacy of DCI and the role of emerging nutraceuticals for managing InsR in PCOS.

Direct Effects of D-Chiro-Inositol on Insulin Signaling and Glucagon Secretion of Pancreatic Alpha Cells

“…Certainly, another limit of our work is that these data require more preclinical and clinical validation. Although DCI is normally used in the clinical treatment of women with PCOS and to treat insulin resistance during pregnancy [ 17 , 66 ], the use of DCI to treat insulin resistance of α-cells in diabetic patients needs appropriate clinical trials.…”

“…It is widely reported in the literature that several drugs, compounds, molecules, and plant extracts are able to improve the insulin resistance state in humans [ 15 , 16 ]. Among them, D-chiro-inositol (DCI) is commonly used in clinical practice for polycystic ovary syndrome (PCOS), a specific clinical condition in which a profound insulin resistance state underlies the physiopathological mechanisms of the syndrome [ 17 ].…”

D-Chiro-Inositol Treatment Affects Oocyte and Embryo Quality and Improves Glucose Intolerance in Both Aged Mice and Mouse Models of Polycystic Ovarian Syndrome

“…When there is insulin resistance, it seems that the conversion rate of MI into DCI is compromised, reducing cellular levels of DCI [ 47 ]. Accordingly, the exogenous administration of DCI may enhance the activity of the insulin-receptor, reducing glucose levels [ 47 ]. DCI has been shown to have insulin-like bioactivity and to reduce meal-induced hyperglycemia [ 48 ].…”

Nutraceuticals and diet in human health and disease. The special issue at a glance

“…Accordingly, supplementation with the isoform D-chiro-inositol helps to manage the metabolic alterations associated with PCOS. 44 …”