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Wednesday, March 1, 2017

PCOS and Inositol

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women. This disease is characterized by infertility, menstrual dysfunction, and hyperandrogenism. Also, PCOS is often associated with hyperlipidemia and impaired glucose tolerance, conditions that are associated with cardiovascular disorder, type 2 diabetes, cancer and hypertension. Evidence supports that some nutrients may affect the hormonal and metabolic disturbances of PCOS. Here in this study, we aimed to review the available literature that assessed the nutrients such as inostol, isoflavonids, resveratrol, vitamin D, and PUFA (polyunsaturated fatty acids), known to influence the hormonal and metabolic disturbances of PCOS, along with the strategies and future directions of nutrient supplementations in such patients.


Two isomers of inositol (myo-inositol and D-chiro-inositol) are mediators of insulin action (Bizzarri and Carlomagno, 2014[7]). Myo-inositol is a nutrient belonging to vitamin B complex (Papaleo et al., 2009[58]). Myo-inositol is found in various types of foods (e.g. whole grains, seeds, and fruits) and also can be produced from glucose in the human body (Carlomagno and Unfer, 2011[10]). Evidence have shown that this nutrient could have a helpful role in decreasing the hormonal profile, oxidative abnormalities, and as well as the metabolic factors in patients with PCOS, probably due to the amelioration of insulin resistance in these patients (Costantino et al., 2009[13]; Donà et al., 2012[16]). In a placebo-controlled trial, women with PCOS were randomized to receive either oral myo-inositol (4 g/d) plus folic acid (400 mcg/d) or folic acid alone for 12-16 weeks (Costantino et al., 2009[13]). Results showed that myo-inositol administration diminished the serum androgen levels. Moreover, this treatment improved the glucose tolerance and other metabolic profiles of these women (Costantino et al., 2009[13]). Similar results were reported when the effects of myo-inositol (3 g/d) on hormonal profiles and insulin response during an oral glucose tolerance test (OGTT) in normal weight PCOS patients were analyzed (Genazzani et al., 2014[27]). Genazzani et al. (2008[25]) reported that myo-inositol supplementation (2 g/d) plus folic acid (200 µg/ d) was effective in the amelioration of plasma luteinizing hormone (LH), Prolactin (PRL), and testosterone levels in overweight PCOS patient after 12 weeks consumption, probably through the reduction in plasma insulin concentration (Genazzani et al., 2008[25]). The mechanism by which the myo-inositol induces its effect is probably through the induction of inositolphosphoglycans (IPG) release (Genazzani et al., 2008[25]). In fact, an IPG molecule containing D-chiro-inositol plays a key role in activating enzymes that control glucose uptake and usage. IPG performs as a putative post-receptor mediator of insulin signaling pathway or as a second-messenger (Baillargeon et al., 2010[4]; Papaleo et al., 2009[58]). Consequently, authors suggested that the insulin resistance observed in PCOS women is related, at least partially, to the defect in one of the mediators of insulin containing D-chiro-inositol (Bromberg and Edlich, 1994[8]). Metformin ameliorates insulin action in PCOS patients through releasing D-chiro-inositol-IPG mediator (Galazis et al., 2011[24]). Myo-inositol is the most common form of inositol, which is converted to D-chiro-inositol by an epimerase (Larner, 2002[40]). For the first time Bizzarri and Carlomagno (2014[7]) showed that D-chiro-inositol is reduced in the urine and tissues of non-insulin-dependent diabetic patients. A review examined the status of D-chiro-inositol in animals and suggested that the oral supplementation of D-chiro-inositol may perform to bypass an absence in conversion of myo-inoistol to d- chiro inositol. D-chiro-inositol administration may be effective in improving insulin resistance (Larner, 2002[40]). In the study of Nestler et al. (1999[48]), D-chiro-inositol taken orally (1200 mg/d) for 6-8 weeks, reduced the serum androgen levels and improved the insulin resistance associated with metabolic imbalances in obese women with the PCOS. Similar effects were observed with the consumption of small amounts of D-chiro-inositol (500 mg/d) for 12 weeks in obese hyperinsulinemia PCOS women (Genazzani et al., 2014[26]). Furthermore, in agreement with these findings, a very recent data by Laganà et al. (2015[39]) showed improved results in hormonal, metabolic, endocrine and the indices of ovarian function in PCOS women, following the oral ingestion of 1 gr of D-chiro-inositol plus 400 mcg of folic acid for 6 months. Surprisingly, a study performed in 50 overweight women with PCOS reported that 550 mg of myo-inositol plus 13.8 mg D-chiro-inositol in soft gel capsule consumed twice a day could better restore the metabolic parameters compared to the consumption of 2 g of myo-inositol in powder format. This observation indicates that the combination of such compound in physiological blood ratio (40:1) could be a useful tool for nutrition therapy of PCOS overweight patients, due to the beneficial effects of these agents on alleviation of metabolic syndrome risk (Nordio and Proietti, 2012[49]). Furthermore, the available data support the idea that both the inositol isoforms are effective in the treatment of patients with PCOS. Nevertheless, myo-inositol potentially improves the metabolic profile, whereas D-chiro-inositol exerts positive effects on hyperandrogenism (Pizzo et al., 2014[60]). Yet, a systematic review assessing the effects of D-chiro-inositol on ovulation and/or metabolic markers in PCOS failed to find consistent conclusion, mostly because of heterogeneity in the method of each study and also lack of relevant trials and small sample sizes (Galazis et al., 2011[24]). Finally, Unfer et al. (2012[76]) performed a meta-analysis of 6 randomized placebo-controlled trials which used a range of 0.2-4 g/day myo-inositol in PCOS patients and concluded that myo-inositol supplementation can decrease the levels of various hormones such as LH, LH/follicle stimulating hormone (FSH), PRL, and testosterone and improve the dyslipidemia by reducing insulin concentrations. Furthermore, authors suggested that 4 g/day myo-inositol treatment is more effective in the treatment of entire symptom spectrum. Interestingly, no side effects have been reported by doses used in all these studies (Carlomagno and Unfer, 2011[10]).


Since oxidative stress, metabolic, hormonal and endocrine imbalance has been implicated in the development of PCOS, antioxidant agents and nutrients that improve such abnormality have the potential to reduce the risk of this syndrome. Findings of different several studies suggest that the nutrients are not equally effective in improving hormonal and metabolic disturbances of PCOS. As an example, among the nutrient studies in PCOS, inositol has shown the most promise. Yet, PUFA administration had been less effective to improve hormonal imbalances in such patients. The combined effects of specific nutrients in PCOS women need to be investigated in future studies. Finally, additional researches using antioxidants interventions such as vitamin E, vitamin C, and lycopene are warranted in PCOS patients.


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