<sc>d</sc>-Chiro-Inositol in Clinical Practice: A Perspective from the Experts Group on Inositol in Basic and Clinical Research (EGOI)

doi:10.1159/000536081

Review

. 2024;89(4):284-294.

doi: 10.1159/000536081. Epub 2024 Feb 19.

<sc>d</sc>-Chiro-Inositol in Clinical Practice: A Perspective from the Experts Group on Inositol in Basic and Clinical Research (EGOI)

Simona Dinicola^{1

2}, Vittorio Unfer^{1

3}, Christophe O Soulage^{1

4}, Maria Isidora Margarita Yap-Garcia^{1

5}, Arturo Bevilacqua^{1

6}, Salvatore Benvenga^{1

7}, Daniele Barbaro^{1

8}, Artur Wdowiak^{1

9}, Maurizio Nordio^{1

10}, Didier Dewailly^{1

11}, Marialuisa Appetecchia^{1

12}, Cesare Aragona^{1

2}, Maria Salomè Bezerra Espinola^{1

2}, Mariano Bizzarri^{1

2

13}, Pietro Cavalli^{1

14}, Annamaria Colao^{1

15}, Rosario D'Anna^{1

16}, Mónica Hebe Vazquez-Levin^{1

17}, Imelda Hernàndez Marin^{1

18}, Zdravko Kamenov^{1

19}, Antonio Simone Laganà^{1

20}, Giovanni Monastra¹, Mario Montanino Oliva^{1

21}, Ali Cenk Özay^{1

22}, Basilio Pintaudi^{1

23}, Giuseppina Porcaro^{1

24}, Olga Pustotina^{1

25}, Lali Pkhaladze^{1

26}, Nikos Prapas^{1

27}, Scott Roseff^{1

28}, Saghar Salehpour^{1

29}, Annarita Stringaro^{1

30}, Marat Tugushev^{1

31}, Virginia Unfer^{1

32}, Ivana Vucenik^{1

33}, Fabio Facchinetti^{1

34

35}

Affiliations

¹ The Experts Group on Inositol in Basic and Clinical Research (EGOI), Rome, Italy.
² Systems Biology Group Lab, Rome, Italy.
³ UniCamillus - Saint Camillus International University of Health Sciences, Rome, Italy.
⁴ INSERM U1060, INSA de Lyon, University of Lyon, Université Claude Bernard Lyon 1, Villeurbanne, France.
⁵ St. Luke's Medical Center College of Medicine, William H. Quasha Memorial, Quezon, Philippines.
⁶ Department of Dynamic, Clinical Psychology and Health, Sapienza University of Rome, Rome, Italy.
⁷ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
⁸ Director of U.O. Endocrinology in Livorno Hospital, Livorno, Italy.
⁹ Faculty of Medicine and Dentistry, Medical University of Lublin, Lublin, Poland.
¹⁰ A.S.L. RMF, Civitavecchia, Italy.
¹¹ Faculty of Medicine Henri Warembourg, University of Lille, Lille Cedex, France.
¹² Oncological Endocrinology Unit, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
¹³ Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
¹⁴ Humanitas Research Hospital, Rozzano, Milan, Italy.
¹⁵ Department of Clinical Medicine and Surgery, Endocrinology, Diabetology and Andrology Unit, Italian Society of Endocrinology, Federico II University of Naples, Naples, Italy.
¹⁶ Department of Human Pathology, University of Messina, Messina, Italy.
¹⁷ National Council of Scientific and Technical Research, Instituto de Biología y Medicina Experimental (IBYME), Buenos Aires, Argentina.
¹⁸ Human Reproduction Department, Hospital Juárez de México, and Universidad Nacional Autónoma de México (UNAM), México, Mexico.
¹⁹ Department of Internal Medicine, University Hospital "Alexandrovska", Clinic of Endocrinology and Metabolism, Medical University, Sofia, Bulgaria.
²⁰ Unit of Obstetrics and Gynecology, "Paolo Giaccone" Hospital, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.
²¹ Department of Obstetrics and Gynecology, Santo Spirito Hospital, Rome, Italy.
²² Department of Obstetrics and Gynecology, Faculty of Medicine, Cyprus International University, Nicosia, Cyprus.
²³ ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
²⁴ Women's Health Centre, USL UMBRIA 2, Terni, Italy.
²⁵ Department of Obstetrics and Gynecology with Reproductive Medicine, F.I. Inozemtsev Academy of Medical Education, Saint Petersburg, Russian Federation.
²⁶ Zhordania and Khomasuridze Institute of Reproductology, Tbilisi, Georgia.
²⁷ Third Department of OB-GYNAE, Aristotle University of Thessaloniki, and IVF Laboratory, IAKENTRO Fertility Centre, Thessaloniki, Greece.
²⁸ Reproductive Endocrinology and Infertility, South Florida Institute for Reproductive Medicine (IVFMD), Jupiter, Florida, USA.
²⁹ Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³⁰ National Center for Drug Research and Evaluation, Italian National Institute of Health, Rome, Italy.
³¹ Department of Reproductive Medicine, Clinical Embryology and Genetics of Samara State Medical University, Samara, Russian Federation.
³² A.G.Un.Co. Obstetrics and Gynecology Center, Rome, Italy.
³³ Department of Medical and Research Technology and Pathology, University of Maryland School of Medicine in Baltimore, Baltimore, Maryland, USA.
³⁴ University of Modena and Reggio Emilia, Modena, Italy.
³⁵ President Italian Society of Perinatal Medicine (SIMP), Modena, Italy.

PMID: 38373412
PMCID: PMC11309080
DOI: 10.1159/000536081

Review

<sc>d</sc>-Chiro-Inositol in Clinical Practice: A Perspective from the Experts Group on Inositol in Basic and Clinical Research (EGOI)

Simona Dinicola et al. Gynecol Obstet Invest. 2024.

. 2024;89(4):284-294.

doi: 10.1159/000536081. Epub 2024 Feb 19.

Authors

Affiliations

¹ The Experts Group on Inositol in Basic and Clinical Research (EGOI), Rome, Italy.
² Systems Biology Group Lab, Rome, Italy.
³ UniCamillus - Saint Camillus International University of Health Sciences, Rome, Italy.
⁴ INSERM U1060, INSA de Lyon, University of Lyon, Université Claude Bernard Lyon 1, Villeurbanne, France.
⁵ St. Luke's Medical Center College of Medicine, William H. Quasha Memorial, Quezon, Philippines.
⁶ Department of Dynamic, Clinical Psychology and Health, Sapienza University of Rome, Rome, Italy.
⁷ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
⁸ Director of U.O. Endocrinology in Livorno Hospital, Livorno, Italy.
⁹ Faculty of Medicine and Dentistry, Medical University of Lublin, Lublin, Poland.
¹⁰ A.S.L. RMF, Civitavecchia, Italy.
¹¹ Faculty of Medicine Henri Warembourg, University of Lille, Lille Cedex, France.
¹² Oncological Endocrinology Unit, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
¹³ Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
¹⁴ Humanitas Research Hospital, Rozzano, Milan, Italy.
¹⁵ Department of Clinical Medicine and Surgery, Endocrinology, Diabetology and Andrology Unit, Italian Society of Endocrinology, Federico II University of Naples, Naples, Italy.
¹⁶ Department of Human Pathology, University of Messina, Messina, Italy.
¹⁷ National Council of Scientific and Technical Research, Instituto de Biología y Medicina Experimental (IBYME), Buenos Aires, Argentina.
¹⁸ Human Reproduction Department, Hospital Juárez de México, and Universidad Nacional Autónoma de México (UNAM), México, Mexico.
¹⁹ Department of Internal Medicine, University Hospital "Alexandrovska", Clinic of Endocrinology and Metabolism, Medical University, Sofia, Bulgaria.
²⁰ Unit of Obstetrics and Gynecology, "Paolo Giaccone" Hospital, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.
²¹ Department of Obstetrics and Gynecology, Santo Spirito Hospital, Rome, Italy.
²² Department of Obstetrics and Gynecology, Faculty of Medicine, Cyprus International University, Nicosia, Cyprus.
²³ ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
²⁴ Women's Health Centre, USL UMBRIA 2, Terni, Italy.
²⁵ Department of Obstetrics and Gynecology with Reproductive Medicine, F.I. Inozemtsev Academy of Medical Education, Saint Petersburg, Russian Federation.
²⁶ Zhordania and Khomasuridze Institute of Reproductology, Tbilisi, Georgia.
²⁷ Third Department of OB-GYNAE, Aristotle University of Thessaloniki, and IVF Laboratory, IAKENTRO Fertility Centre, Thessaloniki, Greece.
²⁸ Reproductive Endocrinology and Infertility, South Florida Institute for Reproductive Medicine (IVFMD), Jupiter, Florida, USA.
²⁹ Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³⁰ National Center for Drug Research and Evaluation, Italian National Institute of Health, Rome, Italy.
³¹ Department of Reproductive Medicine, Clinical Embryology and Genetics of Samara State Medical University, Samara, Russian Federation.
³² A.G.Un.Co. Obstetrics and Gynecology Center, Rome, Italy.
³³ Department of Medical and Research Technology and Pathology, University of Maryland School of Medicine in Baltimore, Baltimore, Maryland, USA.
³⁴ University of Modena and Reggio Emilia, Modena, Italy.
³⁵ President Italian Society of Perinatal Medicine (SIMP), Modena, Italy.

PMID: 38373412
PMCID: PMC11309080
DOI: 10.1159/000536081

Abstract

Background: <sc>d</sc>-Chiro-inositol is a natural molecule that, in association with its well-studied isomer myo-inositol, may play a role in treating various metabolic and gynecological disorders.

Objectives: This perspective seeks to explore the mechanisms and functions of <sc>d</sc>-chiro-inositol, laying the foundations to discuss its use in clinical practice, across dysmetabolism, obesity, and hormonal dysregulation.

Methods: A narrative review of all the relevant papers known to the authors was conducted.

Outcome: <sc>d</sc>-Chiro-inositol acts through a variety of mechanisms, acting as an insulin sensitizer, inhibiting the transcription of aromatase, in addition to modulating white adipose tissue/brown adipose tissue transdifferentiation. These different modes of action have potential applications in a variety of therapeutic fields, including PCOS, dysmetabolism, obesity, hypoestrogenic/hyperandrogenic disorders, and bone health.

Conclusions: <sc>d</sc>-Chiro-inositol mode of action has been studied in detail in recent years, resulting in a clear differentiation between <sc>d</sc>-chiro-inositol and its isomer myo-inositol. The insulin-sensitizing activities of <sc>d</sc>-chiro-inositol are well understood; however, its potential applications in other fields, in particular obesity and hyperestrogenic/hypoandrogenic disorders in men and women, represent promising avenues of research that require further clinical study.

Keywords: d-Chiro-inositol; Androgens; Aromatase; Estrogens; Insulin resistance.

PubMed Disclaimer

Conflict of interest statement

S.D. and V.U. are employees of Lo.Li Pharma s.r.l. All other authors have no conflicts of interest to declare.

Figures

**Fig. 1.**
A Venn diagram comparing the known mechanisms of D-chiro-inositol and the pathologies discussed within the review. The placement of each pathology represents to which mechanism a potential treatment with D-chiro-inositol could take effect.

See this image and copyright information in PMC

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References

1. Irvine RF. A short history of inositol lipids. J Lipid Res. 2016;57(11):1987–94. - PMC - PubMed
1. Croze M, Soulage C. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013;95(10):1811–27. - PubMed
1. Greene ND, Leung KY, Copp AJ. Inositol, neural tube closure and the prevention of neural tube defects. Birth Defects Res. 2017;109(2):68–80. - PMC - PubMed
1. Tahir F, Majid Z. Inositol supplementation in the prevention of gestational diabetes mellitus. Cureus. 2019;11(9):e5671. - PMC - PubMed
1. Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, et al. . Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10. - PMC - PubMed

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[1] Irvine RF. A short history of inositol lipids. J Lipid Res. 2016;57(11):1987–94. - PMC - PubMed

[2] Irvine RF. A short history of inositol lipids. J Lipid Res. 2016;57(11):1987–94. - PMC - PubMed

[3] Croze M, Soulage C. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013;95(10):1811–27. - PubMed

[4] Croze M, Soulage C. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013;95(10):1811–27. - PubMed

[5] Greene ND, Leung KY, Copp AJ. Inositol, neural tube closure and the prevention of neural tube defects. Birth Defects Res. 2017;109(2):68–80. - PMC - PubMed

[6] Greene ND, Leung KY, Copp AJ. Inositol, neural tube closure and the prevention of neural tube defects. Birth Defects Res. 2017;109(2):68–80. - PMC - PubMed

[7] Tahir F, Majid Z. Inositol supplementation in the prevention of gestational diabetes mellitus. Cureus. 2019;11(9):e5671. - PMC - PubMed

[8] Tahir F, Majid Z. Inositol supplementation in the prevention of gestational diabetes mellitus. Cureus. 2019;11(9):e5671. - PMC - PubMed

[9] Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, et al. . Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10. - PMC - PubMed

[10] Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, et al. . Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10. - PMC - PubMed

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<sc>d</sc>-Chiro-Inositol in Clinical Practice: A Perspective from the Experts Group on Inositol in Basic and Clinical Research (EGOI)

Affiliations

<sc>d</sc>-Chiro-Inositol in Clinical Practice: A Perspective from the Experts Group on Inositol in Basic and Clinical Research (EGOI)

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