Influence of inositol on the metabolic profile in women with diabetes and other insulin-resistant conditions

Literature review

Authors

DOI:

https://doi.org/10.18370/2309-4117.2025.80.48-60

Keywords:

inositol, myo-inositol, D-chiro-inositol, diabetes mellitus, gestational diabetes, insulin resistance, fetal development

Abstract

The literature review summarizes the current data on the biological properties of inositols - a natural group of polyols (sugars) classified as cyclohexanols. These compounds are widely represented in food products (cereals, legumes, nuts, seeds, melons, vegetables and fruits).
In the human body, inositol is an integral component of phospholipids of cell membranes, nuclear phosphates and blood plasma lipoproteins. As a result, inositol participates in numerous cellular functions: osmoregulation, regulation of ion channels and signaling of hormones such as insulin, follicle-stimulating hormone and others. Inositol is a metabolic regulator with a pronounced multisystem effect.
Isomers myo-inositol (MI) and D-chiro-inositol (DCI) increase insulin sensitivity, reducing the need for it and, as a result, reducing hyperinsulinemia. For this reason, inositols are recognized as secondary insulin mediators. They modulate intracellular signaling pathways: translocation of glucose transporters, glycogen synthesis, activity of phosphatidylinositol-3-kinase and protein kinase B. DCI also stimulates pyruvate dehydrogenase and energy metabolism in mitochondria. The tissue-specific ratio of MI: DCI regulates the physiological response of target tissues to insulin. Disruption of this balance correlates with the development of insulin resistance, hyperglycemia, and compensatory hyperinsulinemia.
Meta-analyses have demonstrated the efficacy and safety of MI for the prevention of gestational diabetes and intrauterine fetal development. In particular, in women at high risk of gestational diabetes, MI at a dose of 4 g/day significantly reduces its risk by 47–66%, as well as the risk of preterm birth and macrosomia. MI may also help prevent neural tube defects in conditions of folic acid deficiency or hyperglycemia.
Preclinical and clinical data indicate the benefits of MI and DXI isomers in the treatment of metabolic-associated steatosis of the liver. In addition, MI has a positive effect on glycemia and the HOMA index, atherogenic indices, regulation of SIRT1 genes, antioxidant status and hematological parameters. Osteogenic and anti-osteoclastogenic properties of inositols open new prospects for their use in the therapy of osteoporosis.

Author Biographies

L.K. Sokolova, SI «V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine», Kyiv

MD, endocrinologist, senior researcher, head of the Department of Diabetology

Y.B. Belchina, SI «V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine», Kyiv

PhD, endocrinologist

References

  1. Romeo P, D’Anna R, Corrado F. Myoinositol and Metformin in the Prevention of Gestational Diabetes in High-Risk Patients: A Narrative Review. J Clin Med. 2024 Sep 12;13(18):5387. DOI: 10.3390/jcm13185387.
  2. Dinicola S, Minini M, Unfer V, et al. Nutritional and Acquired Deficiencies in Inositol Bioavailability. Correlations with Metabolic Disorders. Int J Mol Sci. 2017 Oct 20;18(10):2187. DOI: 10.3390/ijms18102187.
  3. Dinicola S, Unfer V, Facchinetti F, et al. Inositols: From Established Knowledge to Novel Approaches. Int J Mol Sci. 2021 Sep 30;22(19):10575. DOI: 10.3390/ijms221910575.
  4. Chatree S, Thongmaen N, Tantivejkul K, et al. Role of Inositols and Inositol Phosphates in Energy Metabolism. Molecules. 2020 Nov 1;25(21):5079. DOI: 10.3390/molecules25215079.
  5. DiNicolantonio JJ, O’Keefe JH. Myo-inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes. Open Heart. 2022 Mar;9(1):e001989. DOI: 10.1136/openhrt-2022-001989.
  6. Wojciechowska A, Osowski A, Jźwik M, et al. Inositols’ Importance in the Improvement of the Endocrine-Metabolic Profile in PCOS. Int J Mol Sci. 2019 Nov 18;20(22):5787. DOI: 10.3390/ijms20225787
  7. World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Part 1: Diagnosis and Classification of Diabetes Mellitus. WHO/NCD/NCS/99.2 ed. [Internet]. Geneva: World Health Organization; 1999. Available from: https://www. paho.org/en/documents/who-definition-diagnosis-and-classification-diabetes-mellitus-and-its-complications-1999
  8. IDF Global Clinical Practice Recommendations for Managing Type 2 Diabetes 2025. Diabetes Res Clin Pract. 2025 Jun;224:112238. DOI: 10.1016/j.diabres.2025.112238.
  9. Choudhury AA, Devi Rajeswari V. Gestational diabetes mellitus - A metabolic and reproductive disorder. Biomed Pharmacother. 2021 Nov;143:112183. DOI: 10.1016/j.biopha.2021.112183
  10. Pintaudi B, Di Vieste G, Bonomo M. The Effectiveness of Myo-Inositol and D-Chiro Inositol Treatment in Type 2 Diabetes. Int J Endocrinol. 2016;2016:9132052. DOI: 10.1155/2016/9132052.
  11. Sanchis P, Calvo P, Pujol A, et al. Daily phytate intake increases adiponectin levels among patients with diabetes type 2: a randomized crossover trial. Nutr Diabetes. 2023 Feb 28;13(1):2. DOI: 10.1038/s41387-023-00231-9.
  12. Laganà AS, Myers SH, Forte G, et al. Inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: now and the future. Expert Opin Drug Metab Toxicol. 2024 Jan-Feb;20(1-2):61-72. DOI: 10.1080/17425255.2024.2306851
  13. Sharma I, Deng F, Liao Y, Kanwar YS. Myo-inositol Oxygenase (MIOX) Overexpression Drives the Progression of Renal Tubulointerstitial Injury in Diabetes. Diabetes. 2020 Jun;69(6):1248-63. DOI: 10.2337/db19-0935.
  14. Qi H, Deng F, Wang Y, et al. Myo-Inositol Supplementation Alleviates Cisplatin-Induced Acute Kidney Injury via Inhibition of Ferroptosis. Cells. 2022 Dec 21;12(1):16. DOI: 10.3390/cells12010016.
  15. Pani A, Giossi R, Menichelli D, et al. Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation. Nutrients. 2020 Nov 3;12(11):3379. DOI: 10.3390/nu12113379.
  16. Arefhosseini S, Roshanravan N, Tutunchi H, et al. Myo-inositol supplementation improves cardiometabolic factors, anthropometric measures, and liver function in obese patients with non-alcoholic fatty liver disease. Front Nutr. 2023 Feb 7;10:1092544. DOI: 10.3389/fnut.2023.1092544.
  17. Arefhosseini S, Ebrahimi-Mameghani M, Asghari S, et al. Myo-inositol supplementation in obese patients with non-alcoholic fatty liver disease: Assessment of sirtuin-1 pathway, atherogenic and hematological parameters. J Funct Foods. 2024;116:106197. DOI: 10.1016/j.jff.2024.106197.
  18. Krishnan A, Muthusami S. Hormonal alterations in PCOS and its influence on bone metabolism. J Endocrinol. 2017 Feb;232(2):R99–R113. DOI: 10.1530/JOE-16-0405.
  19. Pouresmaeili F, Kamalidehghan B, Kamarehei M, Goh YM. A comprehensive overview on osteoporosis and its risk factors. Ther Clin Risk Manag. 2018 Nov 6;14:2029–49. DOI: 10.2147/TCRM.S138000.
  20. Dai Z, Chung SK, Miao D, et al. Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation. J Bone Miner Res. 2011 Mar;26(3):582–90. DOI: 10.1002/jbmr.240.
  21. Zulfarina MS, Syarifah-Noratiqah SB, Nazrun SA, et al. Pharmacological Therapy in Panic Disorder: Current Guidelines and Novel Drugs Discovery for Treatment-resistant Patient. Clin Psychopharmacol Neurosci. 2019 May 31;17(2):145–54. DOI: 10.9758/cpn.2019.17.2.145.
  22. Kim H, McGrath BM, Silverstone PH. A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI-cycle) to psychiatric disorders--focus on magnetic resonance spectroscopy (MRS) studies. Hum Psychopharmacol. 2005 Jul;20(5):309–26. DOI: 10.1002/hup.693.
  23. Bizzarri M, Fuso A, Dinicola S, et al. Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease. Expert Opin Drug Metab Toxicol. 2016 Oct;12(10):1181–96. DOI: 10.1080/17425255.2016.1206887.
  24. Owczarczyk-Saczonek A, Lahuta LB, Ligor M, et al. The Healing-Promoting Properties of Selected Cyclitols-A Review. Nutrients. 2018 Dec 3;10(12):1891. DOI: 10.3390/nu10121891
  25. Ishikawa H, Reierstad S, Demura M, et al. High aromatase expression in uterine leiomyoma tissues of African-American women. J Clin Endocrinol Metab. 2009 May;94(5):1752–6. DOI: 10.1210/jc.2008-2327.
  26. Roshdy E, Rajaratnam V, Maitra S, et al. Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study. Int J Womens Health. 2013 Aug 7;5:477–86. DOI: 10.2147/IJWH.S41021.
  27. Ciavattini A, Delli Carpini G, Serri M, et al. Hypovitaminosis D and “small burden” uterine fibroids: Opportunity for a vitamin D supplementation. Medicine (Baltimore). 2016 Dec;95(52):e5698. DOI: 10.1097/MD.0000000000005698.
  28. Miriello D, Galanti F, Cignini P, et al. Uterine fibroids treatment: do we have new valid alternative? Experiencing the combination of vitamin D plus epigallocatechin gallate in childbearing age affected women. Eur Rev Med Pharmacol Sci. 2021 Apr;25(7):2843–51. DOI: 10.26355/eurrev_202104_25537.
  29. Graf E, Eaton JW. Dietary suppression of colonic cancer. Fiber or phytate? Cancer. 1985 Aug 15;56(4):717–8. DOI: 10.1002/1097-0142(19850815)56:4<717::aid-cncr2820560402>3.0.co;2-4.
  30. Afrin S, AlAshqar A, El Sabeh M, et al. Diet and Nutrition in Gynecological Disorders: A Focus on Clinical Studies. Nutrients. 2021 May 21;13(6):1747. DOI: 10.3390/nu13061747
  31. Pillai RA, Islam MO, Selvam P, et al. Placental Inositol Reduced in Gestational Diabetes as Glucose Alters Inositol Transporters and IMPA1 Enzyme Expression. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e875–e890. DOI: 10.1210/clinem/dgaa814.
  32. D’Anna R, Di Benedetto V, Rizzo P, et al. Myo-inositol may prevent gestational diabetes in PCOS women. Gynecol Endocrinol. 2012 Jun; 28(6):440–2. DOI: 10.3109/09513590.2011.633665.
  33. D’Anna R, Scilipoti A, Giordano D, et al. myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study. Diabetes Care. 2013 Apr;36(4):854–7. DOI: 10.2337/dc12-1371.
  34. D’Anna R, Di Benedetto A, Scilipoti A, et al. Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese Pregnant Women: A Randomized Controlled Trial. Obstet Gynecol. 2015 Aug;126(2):310–5. DOI: 10.1097/AOG.0000000000000958.
  35. Santamaria A, Di Benedetto A, Petrella E, et al. Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial. J Matern Fetal Neonatal Med. 2016 Oct;29(19):3234–7. DOI: 10.3109/14767058.2015.1121478.
  36. Santamaria A, Alibrandi A, Di Benedetto A, et al. Clinical and metabolic outcomes in pregnant women at risk for gestational diabetes mellitus supplemented with myo-inositol: a secondary analysis from 3 RCTs. Am J Obstet Gynecol. 2018 Sep;219(3):300.e1–300.e6. DOI: 10.1016/j.ajog.2018.05.018.
  37. Zheng X, Liu Z, Zhang Y, et al. Relationship Between Myo-Inositol Supplementary and Gestational Diabetes Mellitus: A Meta-Analysis. Medicine (Baltimore). 2015 Oct;94(42):e1604. DOI: 10.1097/MD.0000000000001604.
  38. Farren M, Daly N, McKeating A, et al. The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial. Diabetes Care. 2017 Jun;40(6):759–63. DOI: 10.2337/dc16-2449.
  39. Vitagliano A, Saccone G, Cosmi E, et al. Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet. 2019 Jan;299(1):55–68. DOI: 10.1007/s00404-018-5005-0.
  40. Mashayekh-Amiri S, Mohammad-Alizadeh-Charandabi S, Abdolalipour S, Mirghafourvand M. Myo-inositol supplementation for prevention of gestational diabetes mellitus in overweight and obese pregnant women: a systematic review and meta-analysis. Diabetol Metab Syndr. 2022 Jul 6;14(1):93. DOI: 10.1186/s13098-022-00862-5.
  41. Wei J, Yan J, Yang H. Inositol Nutritional Supplementation for the Prevention of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022 Jul 9;14(14):2831. DOI: 10.3390/nu14142831
  42. Motuhifonua SK, Lin L, Alsweiler J, et al. Antenatal dietary supplementation with myo-inositol for preventing gestational diabetes. Cochrane Database Syst Rev. 2023 Feb 15;2(2):CD011507. DOI: 10.1002/14651858.CD011507.pub3.
  43. Lubin V, Shojai R, Darmon P, Cosson E. A pilot study of gestational diabetes mellitus not controlled by diet alone: First-line medical treatment with myoinositol may limit the need for insulin. Diabetes Metab. 2016 Jun;42(3):192–5. DOI: 10.1016/j.diabet.2016.01.005.
  44. Guarnotta V, Cuva G, Imbergamo MP, Giordano C. Myoinositol supplementation in the treatment of gestational diabetes mellitus: effects on glycaemic control and maternal-foetal outcomes. BMC Pregnancy Childbirth. 2022 Jun 26;22(1):516. DOI: 10.1186/s12884-022-04852-3
  45. Kulshrestha V, Balani S, Kachhawa G, et al. Efficacy of myoinositol in treatment of gestational diabetes mellitus in Asian Indian women: A pilot randomized clinical trial. Eur J Obstet Gynecol Reprod Biol. 2021 May;260:42-7. DOI: 10.1016/j.ejogrb.2021.02.017.
  46. Corrado F, D’Anna R, Di Vieste G, et al. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med. 2011 Aug;28(8):972-5. DOI: 10.1111/j.1464-5491.2011.03284.x.
  47. Malvasi A, Kosmas I, Mynbaev OA, et al. Can trans resveratrol plus d-chiro-inositol and myo-inositol improve maternal metabolic profile in overweight pregnant patients? Clin Ter. 2017 Jul-Aug;168(4):e240-e247. DOI: 10.7417/T.2017.2013.
  48. D’Anna R, Corrado F, Loddo S, et al. Myoinositol plus α-lactalbumin supplementation, insulin resistance and birth outcomes in women with gestational diabetes mellitus: a randomized, controlled study. Sci Rep. 2021 Apr 23;11(1):8866. DOI: 10.1038/s41598-021-88329-x.
  49. Fraticelli F, Celentano C, Zecca IA, et al. Effect of inositol stereoisomers at different dosages in gestational diabetes: an open-label, parallel, randomized controlled trial. Acta Diabetol. 2018 Aug;55(8):805–12. DOI: 10.1007/s00592-018-1157-4.
  50. Goedegebure EAR, Koning SH, Hoogenberg K, et al. Pregnancy outcomes in women with gestational diabetes mellitus diagnosed according to the WHO-2013 and WHO-1999 diagnostic criteria: a multicentre retrospective cohort study. BMC Pregnancy Childbirth. 2018 May 10;18(1):152. DOI: 10.1186/s12884-018-1810-5.
  51. Kramer CK, Campbell S, Retnakaran R. Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis. Diabetologia. 2019 Jun;62(6):905–14. DOI: 10.1007/s00125-019-4840-2.
  52. Chen A, Tan B, Du R, et al. Gestational diabetes mellitus and development of intergenerational overall and subtypes of cardiovascular diseases: a systematic review and meta-analysis. Cardiovasc Diabetol. 2024 Aug 28;23(1):320. DOI: 10.1186/s12933-024-02416-7.
  53. Nakshine VS, Jogdand SD. A Comprehensive Review of Gestational Diabetes Mellitus: Impacts on Maternal Health, Fetal Development, Childhood Outcomes, and Long-Term Treatment Strategies. Cureus. 2023 Oct 23;15(10):e47500. DOI: 10.7759/cureus.47500.
  54. Raffone E, Rizzo P, Benedetto V. Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol. 2010 Apr;26(4):275–80. DOI: 10.3109/09513590903366996.
  55. Agrawal A, Mahey R, Kachhawa G, et al. Comparison of metformin plus myoinositol vs metformin alone in PCOS women undergoing ovulation induction cycles: randomized controlled trial. Gynecol Endocrinol. 2019 Jun;35(6):511–4. DOI: 10.1080/09513590.2018.1549656.
  56. Rajasekaran K, Malhotra N, Mahey R, et al. Myoinositol versus metformin pretreatment in GnRH-antagonist cycle for women with PCOS undergoing IVF: a double-blinded randomized controlled study. Gynecol Endocrinol. 2022 Feb;38(2):140-7. DOI: 10.1080/09513590.2021.1981282.
  57. Esser N, Utzschneider KM, Kahn SE. On the causal relationships between hyperinsulinaemia, insulin resistance, obesity and dysglycaemia in type 2 diabetes: Reply to Johnson JD [letter]. Diabetologia. 2021 Oct;64(10):2345–7. DOI: 10.1007/s00125-021-05511-6.
  58. Zhao X, An X, Yang C, et al. The crucial role and mechanism of insulin resistance in metabolic disease. Front Endocrinol (Lausanne). 2023 Mar 28;14:1149239. DOI: 10.3389/fendo.2023.1149239.
  59. Li M, Chi X, Wang Y, et al. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther. 2022 Jul 6;7(1):216. DOI: 10.1038/s41392-022-01073-0.
  60. Armandi A, Rosso C, Caviglia GP, et al. The Impact of Dysmetabolic Sarcopenia Among Insulin Sensitive Tissues: A Narrative Review. Front Endocrinol (Lausanne). 2021 Nov 10;12:716533. DOI: 10.3389/fendo.2021.716533.
  61. Martiniakova M, Biro R, Penzes N, et al. Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target. Int J Mol Sci. 2024 Apr 28;25(9):4827. DOI: 10.3390/ijms25094827.
  62. Kennington AS, Hill CR, Craig J, et al. Low urinary chiro-inositol excretion in non-insulin-dependent diabetes mellitus. N Engl J Med. 1990 Aug 9;323(6):373–8. DOI: 10.1056/NEJM199008093230603
  63. Haneda M, Kikkawa R, Arimura T, et al. Glucose inhibits myo-inositol uptake and reduces myo-inositol content in cultured rat glomerular mesangial cells. Metabolism. 1990 Jan;39(1):40–5. DOI: 10.1016/0026-0495(90)90145-3.
  64. Asplin I, Galasko G, Larner J. Chiro-inositol deficiency and insulin resistance: a comparison of the chiro-inositol- and the myo-inositol-containing insulin mediators isolated from urine, hemodialysate, and muscle of control and type II diabetic subjects. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5924-8. DOI: 10.1073/pnas.90.13.5924.
  65. Nordio M, Proietti E. The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci. 2012 May;16(5):575-81
  66. Galazis N, Galazi M, Atiomo W. D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol Endocrinol. 2011 Apr;27(4):256-62. DOI: 10.3109/09513590.2010.538099.
  67. Minozzi M, Nordio M, Pajalich R. The Combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients. Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):537–40.
  68. Roseff S, Montenegro M. Inositol Treatment for PCOS Should Be Science-Based and Not Arbitrary. Int J Endocrinol. 2020 Mar 27;2020:6461254. DOI: 10.1155/2020/6461254.
  69. Elnashar AM. Update on obesity and assisted reproductive technology. Middle East Fertil Soc J. 2023; 28 (1). DOI: 10.1186/s43043-022-00126-2
  70. Basciani S, Nordio M, Spizzichini ML, Gnessi L. Unexpected effects of treating insulin-resistant obese women with high-dose D-chiro-inositol: opening Pandora’s box. Front Endocrinol (Lausanne). 2025 Apr 1;16:1399308. DOI: 10.3389/fendo.2025.1399308.
  71. Sacchi S, Marinaro F, Tondelli D, et al. Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol. Reprod Biol Endocrinol. 2016 Aug 31;14(1):52. DOI: 10.1186/s12958-016-0189-2.
  72. Bevilacqua A, Dragotto J, Lucarelli M, et al. High Doses of D-Chiro-Inositol Alone Induce a PCO-Like Syndrome and Other Alterations in Mouse Ovaries. Int J Mol Sci. 2021 May 26;22(11):5691. DOI: 10.3390/ijms22115691

Downloads

Published

2025-11-28

How to Cite

Sokolova, L., & Belchina, Y. (2025). Influence of inositol on the metabolic profile in women with diabetes and other insulin-resistant conditions: Literature review. REPRODUCTIVE ENDOCRINOLOGY, (80), 48–60. https://doi.org/10.18370/2309-4117.2025.80.48-60

Issue

No. 80 (2025)

Section

Endocrinology

License

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

    1. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.