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What is it?

Description

Inositol is a constituent of phospholipids in cellular membranes, a precursor of secondary messengers in metabolic pathways, a component of reproductive fluids, and essential for tissue growth. (32)(39) Previously considered an essential B vitamin (vitamin B8), it is now known that the human body can synthesize four grams of inositol per day, whereas approximately one gram per day can be obtained from the diet. (14) For this reason, inositol is now mainly referred to as an essential pseudovitamin. (24)

Not be confused with: D-pinitol (structurally related)

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Main uses

Endocrine disorders
Hormonal and reproductive disorders
Metabolic disorders
Neurological disorders

Formulations

Form
Comparison
Myo-inositol
Hormonal and reproductive:
↑ mature oocytes, embryo quality, & sex hormone-binding globulin (SHGB);
Hormonal and reproductive: ↓ LH/FSH ratio, total testosterone, HOMA index, and immature oocytes by MI compared with D-chiro-inositol supplements in polycystic ovarian syndrome patients (34)(40)
Endocrine:
More involved in regulating intestinal glucose absorption in rats (9)
More involved in glucose uptake from plasma via glucose receptor activation (16)
More involved in glucose utilization via its synthesis from glucose-6-phosphate, producing up to 4-5g of myoinositol per day (14)(16)
D-chiro-inositol
Endocrine:
More involved in glycogenesis than myoinositol with up to 50-100x more activity in rats (16)(23)
Can be synthesized from myoinositol via an epimerase enzyme, but in the presence of insulin resistance less can be synthesized due to impaired epimerase activity (4)(27)

Dosing & administration

Adverse effects

At doses greater than 12 g per day, gastrointestinal effects, such as nausea, flatulence, and diarrhea, may occur. However, the incidence of these events is considered mild and does not increase in severity as the dose increases. (8) Increasing doses (300 to 2400mg) of DCI has been shown to negatively impact oocyte quality in patients with PCOS. (25)

Pharmacokinetics

Absorption

  • Intestinal transportation of MI across the apical membrane is accomplished by the sodium/inositol symporter 2 (SMIT2) in rats. (1)
  • Softgel capsules with lower doses (0.6 g) provide equal bioavailability to higher doses of powder (2 g). (7)

Distribution

  • SMIT1/SMIT2 and the H+ myo-inositol transporter are responsible for inositol uptake throughout the body and brain. (14) 
  • Myoinositol can pass the blood-brain barrier for distribution to the brain and cerebrospinal fluid in rats. (36)(37)
  • Myoinositol is also distributed to seminal fluids, prostate, epididymis, and seminal vesicles, and is high in follicular fluid of healthy Px, but low in PCOS Px. (4)
  • D-chiro-inositol is highly distributed to fat, muscle, and the liver, but is low in the brain and heart in humans. (31)
  • D-chiro-inositol is high in follicular fluid of PCOS Px, but low in healthy Px. (4)

Metabolism

  • Myo-inositol is metabolized to D-glucuronic acid in the renal cortical tubules by myoinositol oxygenase. (14)
  • D-glucuronic acid is then converted by aldehyde reductase to L-gluconate. The metabolism of L-gluconate results in xylulose and ribulose, which can both be degraded through glycolysis. (14)

Excretion

  • If not reabsorbed by the SMT2 transporters on the apical membrane of the proximal convoluted tubules, MI and DCI inositol are both excreted in the urine. (14)(28)
References
  1. Aouameur, R., Cal, S. D., Bissonnette, P., Coady, M. J., & Lapointe, J. (2007). SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine. American Journal of Physiology-Gastrointestinal and Liver Physiology, 293(6). ()
  2. Benelli, E., Ghianda, S. D., Cosmo, C. D., & Tonacchera, M. (2016). A combined therapy with myo-inositol and d-chiro-inositol improves endocrine parameters and insulin resistance in PCOS young overweight women. International Journal of Endocrinology, 2016, 1-5. ()
  3. Benjamin, J., Levine, J., Fux, M., Aviv, A., Levy, D., & Belmaker, R. H. (1995). Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. The American Journal of Psychiatry, 152(7), 1084-1086. ()
  4. Bizzarri, M., & Carlomagno, G. (2014). Inositol: History of an effective therapy for polycystic ovary syndrome. European Review for Medical and Pharmacological Sciences, 18(13), 1896-1903. ()
  5. Calogero, A. E., Gullo, G., Vignera, S. L., Condorelli, R. A., & Vaiarelli, A. (2015). Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: A prospective double-blind randomized placebo-controlled study. Andrology, 3(3), 491-495. ()
  6. Caprio, F., D’Eufemia, M. D., Trotta, C., Campitiello, M. R., Ianniello, R., Mele, D., & Colacurci, N. (2015). Myo-inositol therapy for poor-responders during IVF: A prospective controlled observational trial. Journal of Ovarian Research, 8(1), 37. ()
  7. Carlomagno, G., Grazia, S. D., Unfer, V., & Manna, F. (2012). Myo-inositol in a new pharmaceutical form: A step forward to a broader clinical use. Expert Opinion on Drug Delivery, 9(3), 267-271. ()
  8. Carlomagno, G., & Unfer, V. (2011). Inositol safety: Clinical evidences. European Journal of Medical and Pharmacological Science, 15(8), 931-936. ()
  9. Chukwuma, C. I., Ibrahim, M. A., & Islam, M. S. (2016). Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: A dual approach study. Journal of Physiology and Biochemistry, 72(4), 791-801. ()
  10. Ciotta, L., Stracquadanio, M., Pagano, I., Carbonaro, A., Palumbo, M., & Gulino, F. (2011). Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: A double blind trial. European Review for Medical and Pharmacological Sciences, 15, 509-514. ()
  11. Corrado, F., D’Anna, R., Vieste, G. D., Giordano, D., Pintaudi, B., Santamaria, A., & Benedetto, A. D. (2011). The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabetic Medicine, 28(8), 972-975. ()
  12. Costantino, D., Minozzi, G., Minozzi, F., & Guaraldi, C. (2009). Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: A double-blind trial. European Review for Medical and Pharmacological Sciences, 13, 105-110. ()
  13. D'Anna, R., Di Benedetto, A., Scilipoti, A., Santamaria, A., Interdonato, M. L., Petrella, E., & Facchinetti, F. (2015). Myo-inositol supplementation for prevention of gestational diabetes in obese pregnant women: A randomized controlled trial. Obstetrics and Gynecology, 126(2), 310-315. ()
  14. Dinicola, S., Minini, M., Unfer, V., Verna, R., Cucina, A., & Bizzarri, M. (2017). Nutritional and acquired deficiencies in inositol bioavailability: Correlations with metabolic disorders. International Journal of Molecular Sciences, 18(10), 2187. ()
  15. Donà, G., Sabbadin, C., Fiore, C., Bragadin, M., Giorgino, F. L., Ragazzi, E., . . . Armanini, D. (2012). Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome. European Journal of Endocrinology, 166(4), 703-710. ()
  16. Facchinetti, F., Dante, G., & Neri, I. (2015). The ratio of MI to DCI and its impact in the treatment of polycystic ovary syndrome: Experimental and literature evidences. ISGE Series Frontiers in Gynecological Endocrinology, 103-109. ()
  17. Genazzani, A. D., Lanzoni, C., Ricchieri, F., & Jasonni, V. M. (2008). Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecological Endocrinology, 24(3), 139-144. ()
  18. Gerli, S., Mignosa, M., & Di Renzo, G. C. (2003). Effects of inositol on ovarian function and metabolic factors in women with PCOS: A randomized double blind placebo-controlled trial. European Review for Medical and Pharmacological Sciences, 7, 151-159. ()
  19. Gerli, S., Papaleo, E., Ferrari, A., & Di Renzo, G. C. (2007). Randomized, double blind placebo-controlled trial: Effects of Myo-inositol on ovarian function and metabolic factors in women with PCOS. European Review for Medical and Pharmacological Sciences, 11, 347-354. ()
  20. Giordano, D., Corrado, F., Santamaria, A., Quattrone, S., Pintaudi, B., Benedetto, A. D., & Danna, R. (2011). Effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome. Menopause, 18(1), 102-104. ()
  21. Hallman, M., Bry, K., Hoppu, K., Lappi, M., & Pohjavuori, M. (1992). Inositol supplementation in premature infants with respiratory distress syndrome. The New England Journal of Medicine, 326, 1233-1239. ()
  22. Hallman, M., Jarvenpaa, A. L., & Pohjavuori, M. (1986). Respiratory distress syndrome and inositol supplementation in preterm infants. Archives of Disease in Childhood, 61(11), 1076-1083. ()
  23. Huang, L. C., Fonteles, M. C., Houston, D. B., Zhang, C., & Larner, J. (1993). Chiroinositol deficiency and insulin resistance. III. Acute glycogenic and hypoglycemic effects of two inositol phosphoglycan insulin mediators in normal and streptozotocin-diabetic rats in vivo. Endocrinology, 132(2), 652-657. ()
  24. Indyk, H., & Committee on Food Nutrition. (2006). Nonvitamin micronutrients. Journal of AOAC International, 89(1), 288-289. ()
  25. Isabella, R., & Raffone, E. (2012). Concern: Does ovary need d-chiro-inositol? Journal of Ovarian Research, 5(1), 14. ()
  26. Iuorno, M. J., Jakubowicz, D. J., Baillargeon, J., Dillon, P., Gunn, R. D., Allan, G., & Nestler, J. E. (2002). Effects Of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocrine Practice, 8(6), 417-423. ()
  27. Kennington, A.S., Hill, C.R., Craig, J., Bogardus, C., Raz, I. Ortmeyer, H., … Larner, J. (1990). Low urinary chiro-inositol excretion in non-insulin-dependent diabetes mellitus. New England Journal of Medicine, 323(6), 373-378. ()
  28. Lahjouji, K., Aouameur, R., Bissonnette, P., Coady, M.J., Bichet, D.G., & Lapointe, J.Y. (2007). Expression and functionality of the Na+/myo-inositol cotransporter SMIT2 in rabbit kidney. Biochimica et Biophysica Acta, 1768(5), 1154-1159. ()
  29. Lisi, F., Carfagna, P., Oliva, M., Rago, R., Lisi, R., Poverini, R., . . . Moscarini, M. (2012). Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: A pilot study. Reproductive Biology and Endocrinology, 10(1), 52. ()
  30. Matarrelli, B., Vitacolonna, E., D’Angelo, M., Pavone, G., Mattei, P. A., Liberati, M., & Celentano, C. (2013). Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: A randomized controlled trial. The Journal of Maternal-Fetal & Neonatal Medicine, 26(10), 967-972. ()
  31. Mancini, M. Andreassi, A., Salvioni, M, Pelliccione, F., Mantellassi, G., & Banderali, G. (2016). Myoinositol and D-chiro inositol in improving insulin resistance in obese male children: Preliminary data. International Journal of Endocrinology, 2016, 8720342. ()
  32. Milewska, E. M., Czyzyk, A., Meczekalski, B., & Genazzani, A. D. (2016). Inositol and human reproduction. From cellular metabolism to clinical use. Gynecological Endocrinology, 32(9), 690-695. ()
  33. Nestler, J. E., Jakubowicz, D. J., Reamer, P., Gunn, R. D., & Allan, G. (1999). Ovulatory and metabolic effects of d-chiro-inositol in the polycystic ovary syndrome. The New England Journal of Medicine, 340(17), 1314-1320. ()
  34. Pizzo, A., Laganà, A. S., & Barbaro, L. (2013). Comparison between effects of myo-inositol and d-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecological Endocrinology, 30(3), 205-208. ()
  35. Santamaria, A., Giordano, D., Corrado, F., Pintaudi, B., Interdonato, M. L., Vieste, G. D., . . . Danna, R. (2011). One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome. Climacteric, 15(5), 490-495. ()
  36. Spector, R. (1988). Myo-inositol transport through the blood-brain barrier. Neurochemical Research, 13(8), 785-7. ()
  37. Spector, R., & Lorenzo, A.V. (1975). Myo-inositol transport in the central nervous system. American Journal of Physiology, 228(5), 1510-18. ()
  38. Tabrizi, R., Ostadmohammadi, V., Lankarani, K. B., Peymani, P., Akbari, M., Kolahdooz, F., & Asemi, Z. (2018). The effects of inositol supplementation on lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Lipids in Health and Disease, 17(1), 123. ()
  39. Thomas, M. P., Mills, S. J., & Potter, B. V. (2016). The “other” inositols and their phosphates: Synthesis, biology, and medicine (with recent advances in myo-Inositol chemistry). Angew Chem Int Ed England, 55(5), 1614-1650. ()
  40. Unfer, V., Carlomagno, G., Rizzo, P., Raffone, E., & Roseff, S. (2011). Myo-inositol rather than D-chiro-inositol is able to improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. European Review for Medical and Pharmacological Sciences, 15(4), 452-457. ()
  41. Unfer, V., Facchinetti, F., Orrù, B., Giordani, B., & Nestler, J. (2017). Myo-inositol effects in women with PCOS: A meta-analysis of randomized controlled trials. Endocrine Connections, 6(8), 647-658. ()
  42. Vitagliano, A., Saccone, G., Cosmi, E., Visentin, S., Dessole, F., Ambrosini, G., & Berghella, V. (2018). Inositol for the prevention of gestational diabetes: A systematic review and meta-analysis of randomized controlled trials. Archives of Gynecology and Obstetrics, 299(1), 55-68. ()

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