Unexpected effects of treating insulin-resistant obese women with high-dose D-chiro-inositol: opening Pandora’s box

PurposeThe combination of lifestyle changes and nutraceuticals, such as inositols, can reduce excess weight, leading to a reduction in insulin resistance and a normalization of the metabolic profile. As such, this study investigated the metabolic and hormonal changes observed in women who were overw...

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Main Authors: Sabrina Basciani, Maurizio Nordio, Maria Letizia Spizzichini, Lucio Gnessi
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1399308/full
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author Sabrina Basciani
Maurizio Nordio
Maurizio Nordio
Maria Letizia Spizzichini
Lucio Gnessi
author_facet Sabrina Basciani
Maurizio Nordio
Maurizio Nordio
Maria Letizia Spizzichini
Lucio Gnessi
author_sort Sabrina Basciani
collection DOAJ
description PurposeThe combination of lifestyle changes and nutraceuticals, such as inositols, can reduce excess weight, leading to a reduction in insulin resistance and a normalization of the metabolic profile. As such, this study investigated the metabolic and hormonal changes observed in women who were overweight/obese with insulin resistance undergoing a hypocaloric Mediterranean diet combined with high-dose D-chiro-inositol (DCI) treatment.MethodsIn total, 48 insulin-resistant women between 25 and 40 years old, with a body mass index (BMI) between 26 and 32 were divided into two groups: both groups followed a hypocaloric Mediterranean diet for 4 months, and patients in the treated group also underwent treatment with 2400 mg/day of DCI for the same period. We evaluated the homeostasis model assessment (HOMA) index, body weight, BMI, blood glucose, fasting insulin, lipid profile [cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides] and hormonal profile [total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and menstrual length] at baseline and at the end of treatment.ResultsAfter 4 months, both groups displayed a significant improvement in insulin sensitivity, as reflected by a reduction in the HOMA index, blood glucose level, fasting insulin level, and lipid profile. Furthermore, we observed a significant decrease in body weight and BMI in both groups. However, the evaluation of the hormonal profiles revealed unexpected findings, with the DCI-supplemented group exhibiting hyperandrogenism and menstrual irregularity, as demonstrated by the significant increase of total testosterone, androstenedione, LH, and menstrual length.ConclusionThe study strengthens the evidence regarding the metabolic benefits of the hypocaloric Mediterranean diet, independent from the association with DCI, on women with insulin resistance and excess weight, while also acknowledging the complex hormonal impact of high-dose DCI supplementation for medium-to-long periods.
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spelling doaj-art-50afd1fcba304d1ab460e53568cc55f12025-08-20T01:50:31ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-04-011610.3389/fendo.2025.13993081399308Unexpected effects of treating insulin-resistant obese women with high-dose D-chiro-inositol: opening Pandora’s boxSabrina Basciani0Maurizio Nordio1Maurizio Nordio2Maria Letizia Spizzichini3Lucio Gnessi4Section of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalyThe Experts Group on Inositol in Basic and Clinical Research, and on PCOS (EGOI-PCOS), Rome, ItalySection of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome, Rome, ItalySection of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome, Rome, ItalyPurposeThe combination of lifestyle changes and nutraceuticals, such as inositols, can reduce excess weight, leading to a reduction in insulin resistance and a normalization of the metabolic profile. As such, this study investigated the metabolic and hormonal changes observed in women who were overweight/obese with insulin resistance undergoing a hypocaloric Mediterranean diet combined with high-dose D-chiro-inositol (DCI) treatment.MethodsIn total, 48 insulin-resistant women between 25 and 40 years old, with a body mass index (BMI) between 26 and 32 were divided into two groups: both groups followed a hypocaloric Mediterranean diet for 4 months, and patients in the treated group also underwent treatment with 2400 mg/day of DCI for the same period. We evaluated the homeostasis model assessment (HOMA) index, body weight, BMI, blood glucose, fasting insulin, lipid profile [cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides] and hormonal profile [total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and menstrual length] at baseline and at the end of treatment.ResultsAfter 4 months, both groups displayed a significant improvement in insulin sensitivity, as reflected by a reduction in the HOMA index, blood glucose level, fasting insulin level, and lipid profile. Furthermore, we observed a significant decrease in body weight and BMI in both groups. However, the evaluation of the hormonal profiles revealed unexpected findings, with the DCI-supplemented group exhibiting hyperandrogenism and menstrual irregularity, as demonstrated by the significant increase of total testosterone, androstenedione, LH, and menstrual length.ConclusionThe study strengthens the evidence regarding the metabolic benefits of the hypocaloric Mediterranean diet, independent from the association with DCI, on women with insulin resistance and excess weight, while also acknowledging the complex hormonal impact of high-dose DCI supplementation for medium-to-long periods.https://www.frontiersin.org/articles/10.3389/fendo.2025.1399308/fullD-chiro-inositolinsulin resistancehyperandrogenismlifestylemenstrual regularityobesity
spellingShingle Sabrina Basciani
Maurizio Nordio
Maurizio Nordio
Maria Letizia Spizzichini
Lucio Gnessi
Unexpected effects of treating insulin-resistant obese women with high-dose D-chiro-inositol: opening Pandora’s box
Frontiers in Endocrinology
D-chiro-inositol
insulin resistance
hyperandrogenism
lifestyle
menstrual regularity
obesity
title Unexpected effects of treating insulin-resistant obese women with high-dose D-chiro-inositol: opening Pandora’s box
title_full Unexpected effects of treating insulin-resistant obese women with high-dose D-chiro-inositol: opening Pandora’s box
title_fullStr Unexpected effects of treating insulin-resistant obese women with high-dose D-chiro-inositol: opening Pandora’s box
title_full_unstemmed Unexpected effects of treating insulin-resistant obese women with high-dose D-chiro-inositol: opening Pandora’s box
title_short Unexpected effects of treating insulin-resistant obese women with high-dose D-chiro-inositol: opening Pandora’s box
title_sort unexpected effects of treating insulin resistant obese women with high dose d chiro inositol opening pandora s box
topic D-chiro-inositol
insulin resistance
hyperandrogenism
lifestyle
menstrual regularity
obesity
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1399308/full
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