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Preventive and Therapeutic Role of Dietary Inositol Supplementation in Periconceptional Period and During Pregnancy: A Summary of Evidences and Future Applications

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Abstract

Although inositol dietary deficiency in the general population has not been demonstrated at the serum level, several findings are emerging regarding the impact of inositol supplementation in periconceptional period and in early phases of pregnancy. We are aimed to summarize all experimental (murine in vivo and in vitro murine embryo studies) and clinical (human) evidences regarding the role of inositol in the prevention and treatment of folate-resistant embryo neural tube defects (FR-NTDs) and gestational diabetes mellitus (GDM). We also collected all information regarding the effect that inositol supplementation may have in the metabolic reassessment of early and late pregnancy in order to draw evidence-based conclusions and suggest further studies defining the potential therapeutic role of this molecule in human reproduction. The systematic review of literature clearly showed that inositol supplementation in preconceptional period and in early phase of pregnancy reduces the risk of developing GDM in patients at increased risk. Furthermore, continued intake during pregnancy improves the metabolic status of affected patients, but further studies are needed to confirm this end point. All women at risk of FR-NTDs assuming inositol from the periconceptional period until late pregnancy are reported to have healthy newborns without any significant complications linked to inositol supplementation.

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References

  1. Cetin I, Berti C, Calabrese S. Role of micronutrients in the peri-conceptional period. Hum Reprod Update. 2010;16(1):80–95.

    CAS  PubMed  Google Scholar 

  2. Sinclair KD, Allegrucci C, Singh R, et al. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci USA. 2007;104(49):19351–19356.

    CAS  PubMed  Google Scholar 

  3. Junien C. Impact of diets and nutrients/drugs on early epigenetic programming. J Inherit Metab Dis. 2006;29(2–3):359–365.

    CAS  PubMed  Google Scholar 

  4. Gizzo S, Patrelli TS, Rossanese M, et al. An update on diabetic women obstetrical outcomes linked to preconception and pregnancy glycemic profile: a systematic literature review. Scientific-WorldJournal. 2013;2013:254901.

    Google Scholar 

  5. Smith BJ, Cinnadaio N, Cheung NW, Bauman A, Tapsell LC, van der Ploeg HP. Investigation of a lifestyle change strategy for highrisk women with a history of gestational diabetes. Diabetes Res Clin Pract. 2014;106(3):e60–e63.

    PubMed  Google Scholar 

  6. Hui AL, Back L, Ludwig S, et al. Effects of lifestyle intervention on dietary intake, physical activity level, and gestational weight gain in pregnant women with different pre-pregnancy Body Mass Index in a randomized control trial. BMC Pregnancy Childbirth. 2014;14:331.

    PubMed  PubMed Central  Google Scholar 

  7. Facchinetti F, Dante G, Petrella E, Neri I. Dietary interventions, lifestyle changes, and dietary supplements in preventing gestational diabetes mellitus: a literature review. Obstet Gynecol Surv. 2014;69(11):669–680.

    PubMed  Google Scholar 

  8. Vitagliano A, Noventa M, Gizzo S. Is it time to consider patients suffering from endometriosis-related infertility as ‘‘novel candidates’’ for targeted peri-conceptional D-chiro inositol supplementation? Hypothesis, rationale and some considerations. J Assist Reprod Genet. 2015;32(3):407–408.

    PubMed  Google Scholar 

  9. Colazingari S, Treglia M, Najjar R, Bevilacqua A. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiroinositol, is able to improve IVF outcomes: results from a randomized controlled trial. Arch Gynecol Obstet. 2013;288(6): 1405–1411.

    CAS  PubMed  Google Scholar 

  10. Lisi F, Carfagna P, Oliva MM, et al. Pretreatment with myoinositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study. Reprod Biol Endocrinol. 2012;10:52.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Bizzarri M, Carlomagno G. Inositol: history of an effective therapy for polycystic ovary syndrome. Eur Rev Med Pharmacol Sci. 2014;18(13):1896–1903.

    CAS  PubMed  Google Scholar 

  12. Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013;95(10): 1811–1827.

    CAS  PubMed  Google Scholar 

  13. Laganà AS, Barbaro L, Pizzo A. Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-Chiro-Inositol. Arch Gynecol Obstet. 2015;291(5):1181–1186.

    PubMed  Google Scholar 

  14. Malvasi A, Casciaro F, Minervini MM, et al. Myo-inositol, D-chiro-inositol, folic acid and manganese in second trimester of pregnancy: a preliminary investigation. Eur Rev Med Pharmacol Sci. 2014;18(2):270–274.

    CAS  PubMed  Google Scholar 

  15. Larner J, Brautigan DL, Thorner MO. D-chiro-inositol glycans in insulin signaling and insulin resistance. Mol Med. 2010; 16(11–12):543–552.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Unfer V, Porcaro G. Updates on the myo-inositol plus D-chiroinositol combined therapy in polycystic ovary syndrome. Expert Rev Clin Pharmacol. 2014;7(5):623–631.

    CAS  PubMed  Google Scholar 

  17. Larner J. D-chiro-inositol–its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1): 47–60.

    PubMed  PubMed Central  Google Scholar 

  18. Wilson MP, Hugge C, Bielinska M, Nicholas P, Majerus PW, Wilson DB. Neural tube defects in mice with reduced levels of inositol 1,3,4-trisphosphate 5/6-kinase. Proc Natl Acad Sci USA. 2009;106(24):9831–9835.

    CAS  PubMed  Google Scholar 

  19. Khandelwal M, Reece EA, Wu YK, Borenstein M. Dietary myoinositol therapy in hyperglycemia-induced embryopathy. Teratology. 1998;57(2):79–84.

    CAS  PubMed  Google Scholar 

  20. Scioscia M, Gumaa K, Selvaggi LE, Rodeck CH, Rademacher TW. Increased inositol phosphoglycan P-type in the second trimester in pregnant women with type 2 and gestational diabetes mellitus. J Perinat Med. 2009;37(5):469–471.

    CAS  PubMed  Google Scholar 

  21. Baker L, Piddington R, Goldman A, Egler J, Moehring J. Myo-inositol and prostaglandins reverse the glucose inhibition of neural tube fusion in cultured mouse embryos. Diabetologia. 1990;33(10):593–596.

    CAS  PubMed  Google Scholar 

  22. Hashimoto M, Akazawa S, Akazawa M, et al. Effects of hyperglycaemia on sorbitol and myo-inositol contents of cultured embryos: treatment with aldose reductase inhibitor and myoinositol supplementation. Diabetologia. 1990;33(10):597–602.

    CAS  PubMed  Google Scholar 

  23. Akashi M, Akazawa S, Akazawa M, et al. Effects of insulin and myo-inositol on embryo growth and development during early organogenesis in streptozocin-induced diabetic rats. Diabetes. 1991;40(12):1574–1579.

    CAS  PubMed  Google Scholar 

  24. Greene ND, Copp AJ. Inositol prevents folate-resistant neural tube defects in the mouse. Nat Med. 1997;3(1):60–66.

    CAS  PubMed  Google Scholar 

  25. Reece EA, Khandelwal M, Wu YK, Borenstein M. Dietary intake of myo-inositol and neural tube defects in offspring of diabetic rats. Am J Obstet Gynecol. 1997;176(3):536–539.

    CAS  PubMed  Google Scholar 

  26. Cogram P, Tesh S, Tesh J, et al. D-chiro-inositol is more effective than myo-inositol in preventing folate-resistant mouse neural tube defects. Hum Reprod. 2002;17(9):2451–2458.

    CAS  PubMed  Google Scholar 

  27. Cavalli P, Copp AJ. Inositol and folate resistant neural tube defects. J Med Genet. 2002;39(2):E5.02 Sep;17(9):2451–2458.

    Google Scholar 

  28. Cavalli P, Tedoldi S, Riboli B. Inositol supplementation in pregnancies at risk of apparently folate-resistant NTDs. Birth Defects Res A Clin Mol Teratol. 2008;82(7):540–542.

    CAS  PubMed  Google Scholar 

  29. Cavalli P, Tonni G, Grosso E, Poggiani C. Effects of inositol supplementation in a cohort of mothers at risk of producing an NTD pregnancy. Birth Defects Res A Clin Mol Teratol. 2011;91(11): 962–965.

    CAS  PubMed  Google Scholar 

  30. 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;28(8):972–975.

    CAS  PubMed  Google Scholar 

  31. D’Anna R, Di Benedetto V, Rizzo P, et al. Myo-inositol may prevent gestational diabetes in PCOS women. Gynecol Endocrinol. 2012;28(6):440–442.

    PubMed  Google Scholar 

  32. 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; 36(4):854–857.

    PubMed  PubMed Central  Google Scholar 

  33. Matarrelli B, Vitacolonna E, D’Angelo M, et al. Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: a randomized controlled trial. J Matern Fetal Neonatal Med. 2013; 26(10):967–972.

    CAS  PubMed  Google Scholar 

  34. Gizzo S, Andrisani A, Esposito F, Oliva A, Zicchina C, Capuzzo D, Gangemi M, Nardelli GB. Ovarian reserve test: an impartial means to resolve the mismatch between chronological and biological age in the assessment of female reproductive chances. Reprod Sci. 2014 May;21(5):632–9.

    PubMed  Google Scholar 

  35. Steegers-Theunissen RP, Twigt J, Pestinger V, Sinclair KD. The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Hum Reprod Update. 2013;19(6):640–655.

    CAS  PubMed  Google Scholar 

  36. Leary C, Leese HJ, Sturmey RG. Human embryos from overweight and obese women display phenotypic and metabolic abnormalities. Hum Reprod. 2015;30(1):122–132.

    PubMed  Google Scholar 

  37. Schulte MM, Tsai JH, Moley KH. Obesity and PCOS: the effect of metabolic derangements on endometrial receptivity at the time of implantation. Reprod Sci. 2015;22(1):6–14.

    PubMed  PubMed Central  Google Scholar 

  38. Rondanelli M, Perna S, Faliva M, Monteferrario F, Repaci E, Allieri F. Focus on metabolic and nutritional correlates of polycystic ovary syndrome and update on nutritional management of these critical phenomena. Arch Gynecol Obstet. 2014 Dec; 290(6):1079–92;.

    CAS  PubMed  Google Scholar 

  39. Qiao J, Feng HL. Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum Reprod Update. 2011;17(1):17–33.

    PubMed  Google Scholar 

  40. Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999;340(17):1314–20.

    CAS  PubMed  Google Scholar 

  41. Pizzo A, Laganà AS, Barbaro L. Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecol Endocrinol. 2014; 30(3):205–208.

    CAS  PubMed  Google Scholar 

  42. Copp AJ, Greene ND. Genetics and development of neural tube defects. J Pathol. 2010;220(2):217–230.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Groenen PM, Wevers RA, Janssen FS, Tuerlings JH, Merkus JM, Steegers-Theunissen RP. Are myo-inositol, glucose and zinc concentrations in amniotic fluid of fetuses with spina bifida different from controls? Early Hum Dev. 2003;71(1):1–8.

    CAS  PubMed  Google Scholar 

  44. Dawson EB, Evans DR, Van Hook JW. Amniotic fluid B12 and folate levels associated with neural tube defects. Am J Perinatol. 1998;15(9):511–514.

    CAS  PubMed  Google Scholar 

  45. Scioscia M, Vimercati A, Selvaggi LE, Rodeck CH, Rademacher TW. Inositol phosphoglycan putative insulin mediator in human amniotic fluid. J Matern Fetal Neonatal Med. 2006; 19(1):9–12.

    CAS  PubMed  Google Scholar 

  46. Groenen PM, Peer PG, Wevers RA, et al. Maternal myoinositol, glucose, and zinc status is associated with the risk of offspring with spina bifida. Am J Obstet Gynecol. 2003; 189(6):1713–1719.

    CAS  PubMed  Google Scholar 

  47. Scalera V, Natuzzi D, Prezioso G. myo-inositol transport in rat intestinal brush border membrane vesicles, and its inhibition by D-glucose. Biochim Biophys Acta. 1991;1062(2):187–192.

    CAS  PubMed  Google Scholar 

  48. Genazzani AD, Prati A, Santagni S, et al. Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients. Gynecol Endocrinol. 2012;28(12):969–973.

    CAS  PubMed  Google Scholar 

  49. Baptiste CG, Battista MC, Trottier A, Baillargeon JP. Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid BiochemMolBiol. 2010 Oct;122(1–3):42–52.

    CAS  Google Scholar 

  50. Wilmot EG, Mansell P. Diabetes and pregnancy. Clin Med. 2014; 14(6):677–680.

    Google Scholar 

  51. Kaul P, Savu A, Nerenberg KA, et al. Impact of gestational diabetes mellitus and high maternal weight on the development of diabetes, hypertension and cardiovascular disease: a populationlevel analysis. Diabet Med. 2015;32(2):164–173.

    CAS  PubMed  Google Scholar 

  52. International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010; 33(3):676–682.

    PubMed Central  Google Scholar 

  53. D’Anna R Sr, Santamaria A, Corrado F, Benedetto AD, Petrella E, Facchinetti F. [11-OR]: Myo-inositol in the prevention of gestational diabetes and its complications. Pregnancy Hypertens. 2015;5(1):6.

    Google Scholar 

  54. Patrelli TS, Dall’asta A, Gizzo S, et al. Calcium supplementation and prevention of preeclampsia: a meta-analysis. J Matern Fetal Neonatal Med. 2012;25(12):2570–2574.

    CAS  PubMed  Google Scholar 

  55. Gizzo S, Noventa M, Di Gangi S, et al. Could molecular assessment of calcium metabolism be a useful tool to early screen patients at risk for pre-eclampsia complicated pregnancy? Proposal and rationale. Clin Chem Lab Med. 2015;53(7):975–979.

    CAS  PubMed  Google Scholar 

  56. Vitagliano A, Quaranta M, Noventa M, Gizzo S. ‘‘Empiric’’ inositol supplementation in normal-weight non insulin resistant women with polycystic ovarian disease: from the absence of benefit to the potential adverse effects. Arch Gynecol Obstet. 2015; 291(5):955–957.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Woman and Child Health, University of Padua, Padua, Italy

    Marco Noventa MD, Amerigo Vitagliano MD, Shara Borgato MD & Salvatore Gizzo MD

  2. Department of Obstetrics and Gynaecology, University of Verona, Verona, Italy

    Michela Quaranta MD

  3. Department of Obstetrics and Gynecology, NHS Trust, Northampton General Hospital, Northampton, United Kingdom

    Baydaa Abdulrahim MD & Salvatore Gizzo MD

  4. Dipartimento di Salute della Donna e del Bambino, U.O.C. di Ginecologia e Ostetricia, Via Giustiniani 3, Padova, 35128, Italy

    Salvatore Gizzo MD

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  1. Marco Noventa MD
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  2. Amerigo Vitagliano MD
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  4. Shara Borgato MD
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  6. Salvatore Gizzo MD
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Correspondence to Salvatore Gizzo MD.

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Noventa, M., Vitagliano, A., Quaranta, M. et al. Preventive and Therapeutic Role of Dietary Inositol Supplementation in Periconceptional Period and During Pregnancy: A Summary of Evidences and Future Applications. Reprod. Sci. 23, 278–288 (2016). https://doi.org/10.1177/1933719115594018

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  • DOI: https://doi.org/10.1177/1933719115594018

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