Metabolomic change due to combined treatment with myo-inositol, D-chiro-inositol and glucomannan in polycystic ovarian syndrome patients: a pilot study

Jacopo Troisi, Claudia Cinque, Luigi Giugliano, Steven Symes, Sean Richards, David Adair, Pierpaolo Cavallo, Laura Sarno, Giovanni Scala, Maria Caiazza, Maurizio Guida, Jacopo Troisi, Claudia Cinque, Luigi Giugliano, Steven Symes, Sean Richards, David Adair, Pierpaolo Cavallo, Laura Sarno, Giovanni Scala, Maria Caiazza, Maurizio Guida

Abstract

Background: Polycystic ovarian syndrome (PCOS) is a highly variable syndrome and one of the most common female endocrine disorders. Although the association inositols-glucomannan may represent a good therapeutic strategy in the treatment of PCOS women with insulin resistance, the effect of inositols on the metabolomic profile of these women has not been described yet.

Results: Fifteen PCOS-patients and 15 controls were enrolled. Patients were treated with myo-inositol (1.75 g/day), D-chiro-inositol (0.25 g/day) and glucomannan (4 g/day) for 3 months. Blood concentrations of glucose, insulin, triglycerides and cholesterol, and ovary volumes and antral follicles count, as well as metabolomic profiles, were evaluated for control subjects and for cases before and after treatment. PCOS-patients had higher BMI compared with Controls, BMI decreased significantly after 3 months of treatment although it remained significantly higher compared to controls. 3-methyl-1-hydroxybutyl-thiamine-diphosphate, valine, phenylalanine, ketoisocapric, linoleic, lactic, glyceric, citric and palmitic acid, glucose, glutamine, creatinine, arginine, choline and tocopherol emerged as the most relevant metabolites for distinguishing cases from controls.

Conclusion: Our pilot study has identified a complex network of serum molecules that appear to be correlated with PCOS, and with a combined treatment with inositols and glucomannan.

Trial registration: ClinicalTial.gov, NCT03608813 . Registered 1st August 2018 - Retrospectively registered, .

Keywords: Inositols-glucomannan association; Metabolomics; Polycystic ovary syndrome.

Conflict of interest statement

Ethics approval and consent to participate

The study was carried out in accordance with the ethical principles of the declaration of Helsinki and approved by the ethics committee CEI “Comitato etico Campania Sud” (IRB N. 78/2016).

Consent for publication

The manuscript describes anonymized data.

Competing interests

JT and GS work for companies (Theoreo srl and Hosmotic srl, respectively) dealing with the development and marketing of diagnostic tests based on metabolomics. All other authors declare no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
a Partial least square discriminant analysis (PLS-DA) models to discriminate Controls (CTRL, yellow circles), PCOS patients at enrolment (PCOS-T0, green circles) and PCOS patients after 3-months treatment (PCOS-T1, purple circles). The explained variance of each component is shown in parentheses on the corresponding axis. b The 15 top-scoring VIP metabolites (VIP-score ≥ 1.5) are shown. The colored boxes on the right indicate the relative amount of the corresponding metabolite in each group under study
Fig. 2
Fig. 2
Box and Whisker plot of the VIP metabolites in the cohort of patients and controls. Boxes represent controls (CTRL) n = 15; PCOS patients at the basal enrolment time (PCOS-T0), n = 15; and PCOS patients after 3-months treatment (PCOS-T1), n = 15). The vertical axis reports the log of the GC-MS value of the normalized area of each metabolite. Abbreviations: Gas Chromatography-Mass Spectrometry (GC-MS), Polycystic Ovary Syndrome (PCOS), Thiamine Phosphate (ThPP)
Fig. 3
Fig. 3
Metabolic systems map summarizing the shortest route that may explain the interactions among the 15 selected metabolites. There is a clear interplay of several pathways involving: Biopterin metabolism; De novo fatty acid biosynthesis; Di-unsaturated fatty acid beta-oxidation; Glycerophospholipid metabolism; Glycine, serine, alanine and threonine metabolism; Linoleate metabolism; Saturated fatty acids beta-oxidation; TCA cycle; Tyrosine metabolism; Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine; Valine, leucine and isoleucine degradation; Vitamin B3 (nicotinate and nicotinamide) metabolism; Vitamin E metabolism

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