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Journal Articles International Journal of Molecular Sciences Year : 2021

Inositols: From Established Knowledge to Novel Approaches

1 SBGL - Systems Biology Group Lab [Rome, Italy]
2 Azienda Ospedaleria Universitaria di Modena = University Hospital of Modena
3 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
4 UCL - University College of London [London]
5 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
6 Uninsubria - Universitá degli Studi dell’Insubria = University of Insubria [Varese]
7 NUS - National University of Singapore
8 ZKIR - Zhordania and Khomasuridze Institute of Reproductology [Tbilisi, Georgia]
9 University of Messina
10 National Center for Drug Research and Evaluation [Rome, Italy]
11 AUTNO - Azienda Usl Toscana nord ovest [Livorno, Italy]
12 Regina Elena National Cancer Institute [Rome]
13 2ICT - Institute for Interpersonal Cognitive Therapy [Rome, Italy]
14 IRCCS Milan - Istituto Clinico Humanitas [Milan]
15 CUHK - The Chinese University of Hong Kong [Hong Kong]
16 Université de Lille
17 Hygeia Hospital
18 UNAM - Universidad Nacional Autónoma de México = National Autonomous University of Mexico
19 TAU - Tel Aviv University
20 Medical University of Sofia [Bulgarie]
21 2SH - Santo Spirito Hospital [Athens, Greece]
22 VCU - Virginia Commonwealth University
23 ASL - Azienda Sanitaria Locale [ROMA]
24 Near East University
25 USLU - USL UMBRIA [Terni, Italy]
26 IAKENTRO [Thessaloniki, Greece]
27 IVFMD - South Florida Institute for Reproductive Medicine [Boca Raton, FL, USA]
28 IBYME - Instituto de Biología y Medicina Experimental [Buenos Aires]
29 University of Maryland [Baltimore]
30 Medical University of Lublin
R. d'Anna
  • Function : Author
D. Dewailly
  • Function : Author
M. Hod
  • Function : Author
E. Kandaraki
  • Function : Author
A. C. Ozay
  • Function : Author
O. Papalou
  • Function : Author


Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.
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Dates and versions

inserm-03834381 , version 1 (29-10-2022)



S. Dinicola, V. Unfer, F. Facchinetti, C. O. Soulage, N. D. Greene, et al.. Inositols: From Established Knowledge to Novel Approaches. International Journal of Molecular Sciences, 2021, 22 (19), pp.10575. ⟨10.3390/ijms221910575⟩. ⟨inserm-03834381⟩
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