Experts’ opinion on inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: a further help for human reproduction and beyond

References

• Facchinetti F, Bizzarri M, Benvenga S, et al. Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS. Eur J Obstet Gynecol Reprod Biol. 2015 Dec;195:72–76. PubMed PMID: 26479434
   Google Scholar
• Bevilacqua A, Carlomagno G, Gerli S, et al. Results from the international consensus conference on myo-inositol and d-chiro-inositol in obstetrics and gynecology–assisted reproduction technology. Gynecol Endocrinol. 2015 Jun;31(6):441–446. PubMed PMID: 26036719
   Google Scholar
• Condorelli RA, Calogero AE, Di Mauro M, et al. PCOS and diabetes mellitus: from insulin resistance to altered beta pancreatic function, a link in evolution. Gynecol Endocrinol. 2017 Sep;33(9):665–667. PubMed PMID: 28644709
   Google Scholar
• Agranoff BW. Turtles all the way: reflections on myo-inositol. J Biol Chem. 2009 Aug 7;284(32):21121–21126. PubMed PMID: 19447884; PubMed Central PMCID: PMCPMC2755834
   Google Scholar
• Parthasarathy R, Eisenberg F Jr. The inositol phospholipids: a stereochemical view of biological activity. Biochem J. 1986 Apr 15;235(2):313–322. . PubMed PMID: 3017301; PubMed Central PMCID: PMCPMC1146689
   Google Scholar
• Michell RH. Inositol and its derivatives: their evolution and functions. Adv Enzyme Regul. 2011;51(1):84–90. . PubMed PMID: 21070803
   Google Scholar
• Michell RH. Do inositol supplements enhance phosphatidylinositol supply and thus support endoplasmic reticulum function?. Br J Nutr. 2018 Jun;3:1–16. PubMed PMID: 29859544
   Google Scholar
• Beemster P, Groenen P, Steegers-Theunissen R. Involvement of inositol in reproduction. Nutr Rev. 2002 Mar;60(3):80–87. . PubMed PMID: 11908744
   Google Scholar
• Clements RS Jr., Diethelm AG. The metabolism of myo-inositol by the human kidney. J Lab Clin Med Eng. 1979 Feb;93(2):210–219. PubMed PMID: 372466
   Google Scholar
• Wong YH, Kalmbach SJ, Hartman BK, et al. Immunohistochemical staining and enzyme activity measurements show myo-inositol-1-phosphate synthase to be localized in the vasculature of brain. J Neurochem. 1987 May;48(5):1434–1442. PubMed PMID: 2435847
   Google Scholar
• Loewus MW, Loewus FA, Brillinger GU, et al. Stereochemistry of the myo-inositol-1-phosphate synthase reaction. J Biol Chem. 1980 Dec 25;255(24):11710–11712. PubMed PMID: 7002927.
   Google Scholar
• Sun TH, Heimark DB, Nguygen T, et al. Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. Biochem Biophys Res Commun. 2002 May 10;293(3):1092–1098. PubMed PMID: 12051772
   Google Scholar
• Heimark D, McAllister J, Larner J. Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls. Endocr J. 2014;61(2):111–117. PubMed PMID: 24189751.
   Google Scholar
• Monastra G, Unfer V, Harrath AH, et al. Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients. Gynecol Endocrinol. 2017 Jan;33(1):1–9. PubMed PMID: 27898267
   Google Scholar
• Facchinetti F, Dante G, Neri I. The ratio of MI to DCI and its impact in the treatment of polycystic ovary syndrome: experimental and literature evidences. Front Gynecol Endocrinol. 2016;3:103–109.
   Google Scholar
• Unfer V, Carlomagno G, Papaleo E, et al. Hyperinsulinemia alters myoinositol to d-chiroinositol ratio in the follicular fluid of patients with PCOS. Reprod Sci. 2014 Jul;21(7):854–858. . PubMed PMID: 24501149.
   Google Scholar
• Yancey PH. Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. J Exp Biol. 2005 Aug;208(15):2819–2830. . PubMed PMID: 16043587
   Google Scholar
• 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):1181–1196. . PubMed PMID: 27351907.
   Google Scholar
• Lagana AS, Garzon S, Casarin J, et al. Inositol in polycystic ovary syndrome: restoring fertility through a pathophysiology-based approach. Trends Endocrinol Metab. 2018 Nov;29(11):768–780. . PubMed PMID: 30270194.
   Google Scholar
• Nestler JE, Unfer V. Reflections on inositol(s) for PCOS therapy: steps toward success. Gynecol Endocrinol. 2015 Jul;31(7):501–505. . PubMed PMID: 26177098.
   Google Scholar
• Larner J, Huang LC, Tang G, et al. Insulin mediators: structure and formation. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 2):965–971. . PubMed PMID: 3076102
   Google Scholar
• Huang LC, Fonteles MC, Houston DB, et al. 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. 1993 Feb;132(2):652–657. PubMed PMID: 8425485
   Google Scholar
• Bevilacqua A, Bizzarri M. Inositols in insulin signaling and glucose metabolism. Int J Endocrinol. 2018;2018:1968450. . PubMed PMID: 30595691; PubMed Central PMCID: PMCPMC6286734
   Google Scholar
• Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013 Oct;95(10):1811–1827. PubMed PMID: 23764390
   Google Scholar
• Holm C, Langin D, Manganiello V, et al. Regulation of hormone-sensitive lipase activity in adipose tissue. Methods Enzymol. 1997;286:45–67. . PubMed PMID: 9309644
   Google Scholar
• Londos C, Honnor RC, Dhillon GS. cAMP-dependent protein kinase and lipolysis in rat adipocytes. III. Multiple modes of insulin regulation of lipolysis and regulation of insulin responses by adenylate cyclase regulators. J Biol Chem. 1985 Dec 5;260(28):15139–15145. PubMed PMID: 3905791
   Google Scholar
• Honnor RC, Dhillon GS, Londos C. cAMP-dependent protein kinase and lipolysis in rat adipocytes. II. Definition of steady-state relationship with lipolytic and antilipolytic modulators. J Biol Chem. 1985 Dec 5;260(28):15130–15138. PubMed PMID: 3877723
   Google Scholar
• Degerman E, Belfrage P, Manganiello VC. Structure, localization, and regulation of cGMP-inhibited phosphodiesterase (PDE3). J Biol Chem. 1997 Mar 14;272(11):6823–6826. . PubMed PMID: 9102399
   Google Scholar
• Machicao F, Mushack J, Seffer E, et al. Mannose, glucosamine and inositol monophosphate inhibit the effects of insulin on lipogenesis. Further evidence for a role for inositol phosphate-oligosaccharides in insulin action. Biochem J. 1990 Mar 15;266(3):909–916. PubMed PMID: 2158304; PubMed Central PMCID: PMCPMC1131225
   Google Scholar
• Ghoshal S, Tyagi R, Zhu Q, et al. Inositol hexakisphosphate kinase-1 interacts with perilipin1 to modulate lipolysis. Int J Biochem Cell Biol. 2016 Sep;78:149–155. PubMed PMID: 27373682; PubMed Central PMCID: PMCPMC5003629
   Google Scholar
• Toth JT, Gulyas G, Toth DJ, et al. BRET-monitoring of the dynamic changes of inositol lipid pools in living cells reveals a PKC-dependent PtdIns4P increase upon EGF and M3 receptor activation. Biochim Biophys Acta. 2016 Mar;1861(3):177–187. PubMed PMID: 26692031; PubMed Central PMCID: PMCPMC4733596
   Google Scholar
• Pak Y, Huang LC, Lilley KJ, et al. In vivo conversion of [3H]myoinositol to [3H]chiroinositol in rat tissues. J Biol Chem. 1992 Aug 25;267(24):16904–16910. PubMed PMID: 1387397.
   Google Scholar
• Gaspers LD, Pierobon N, Thomas AP. Intercellular calcium waves integrate hormonal control of glucose output in the intact liver. J Physiol. 2019 Jun;597(11):2867–2885. . PubMed PMID: 30968953; PubMed Central PMCID: PMCPMC6647271
   Google Scholar
• Gassaway BM, Petersen MC, Surovtseva YV, et al. PKCε contributes to lipid-induced insulin resistance through cross talk with p70S6K and through previously unknown regulators of insulin signaling. Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):E8996–E9005. PubMed PMID: 30181290; PubMed Central PMCID: PMCPMC6156646
   Google Scholar
• Cheng F, Han L, Xiao Y, et al. d- chiro-inositol ameliorates high fat diet-induced hepatic steatosis and insulin resistance via PKCepsilon-PI3K/AKT pathway. J Agric Food Chem. 2019 May 29;67(21):5957–5967. PubMed PMID: 31066268
   Google Scholar
• Chukwuma CI, Ibrahim MA, Islam MS. Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study. J Physiol Biochem. 2016 Dec;72(4):791–801. PubMed PMID: 27601253
   Google Scholar
• Kim JN, Han SN, Kim HK. Phytic acid and myo-inositol support adipocyte differentiation and improve insulin sensitivity in 3T3-L1 cells. Nutr Res. 2014 Aug;34(8):723–731. PubMed PMID: 25174657
   Google Scholar
• Lazar MA. PPARγ, 10 years later. Biochimie. 2005 Jan;87(1):9–13. . PubMed PMID: 15733730
   Google Scholar
• Lagana AS, Vitale SG, Nigro A, et al. Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors (PPARs) in dysregulated metabolic homeostasis, inflammation and cancer: current evidence and future perspectives. Int J Mol Sci. 2016 Jun 24;17(7). PubMed PMID: 27347932; PubMed Central PMCID: PMCPMC4964375. DOI:10.3390/ijms17070999.
   Google Scholar
• Lehrke M, Lazar MA. The many faces of PPARgamma. Cell. 2005 Dec 16;123(6):993–999. PubMed PMID: 16360030
   Google Scholar
• Vitale SG, Lagana AS, Nigro A, et al. Peroxisome proliferator-activated receptor modulation during metabolic diseases and cancers: master and minions. PPAR Res. 2016;2016:6517313. . PubMed PMID: 28115924; PubMed Central PMCID: PMCPMC5225385 publication of this paper
   Google Scholar
• Gavrilova O, Haluzik M, Matsusue K, et al. Liver peroxisome proliferator-activated receptor γ contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J Biol Chem. 2003 Sep 5;278(36):34268–34276. PubMed PMID: 12805374
   Google Scholar
• Ricote M, Li AC, Willson TM, et al. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature. 1998 Jan 1;391(6662):79–82. PubMed PMID: 9422508
   Google Scholar
• Milewska EM, Czyzyk A, Meczekalski B, et al. Inositol and human reproduction. From cellular metabolism to clinical use. Gynecol Endocrinol. 2016 Sep;32(9):690–695. PubMed PMID: 27595157
   Google Scholar
• Lewin LM, Yannai Y, Melmed S, et al. myo-inositol in the reproductive tract of the female rat. Int J Biochem. 1982;14(2):147–150. PubMed PMID: 7200041
   Google Scholar
• Stocco C,Tissue physiology and pathology of aromatase. Steroids. 2012 Jan 77;1–2 . 27-35. DOI10.1016/j.steroids.2011.10.013. PubMed PMID: 22108547; PubMed Central PMCID: PMCPMC3286233
   Google Scholar
• 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. PubMed PMID: 27582109; PubMed Central PMCID: PMCPMC5006365.
   Google Scholar
• Nestler JE, Jakubowicz DJ, de Vargas AF, et al. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab. 1998 Jun;83(6):2001–2005. PubMed PMID: 9626131
   Google Scholar
• Chiu TT, Rogers MS, Briton-Jones C, et al. Effects of myo-inositol on the in-vitro maturation and subsequent development of mouse oocytes. Hum Reprod. 2003 Feb;18(2):408–416. PubMed PMID: 12571181
   Google Scholar
• Breen SM, Andric N, Ping T, et al. Ovulation involves the luteinizing hormone-dependent activation of G(q/11) in granulosa cells. Mol Endocrinol. 2013 Sep;27(9):1483–1491. PubMed PMID: 23836924; PubMed Central PMCID: PMCPMC3753423
   Google Scholar
• Orihuela PA, Parada-Bustamante A, Zuñiga LM, et al. Inositol triphosphate participates in an oestradiol nongenomic signalling pathway involved in accelerated oviductal transport in cycling rats. J Endocrinol. 2006 Mar;188(3):579–588. PubMed PMID: 16522737
   Google Scholar
• G Rs C, Harter S, Murphy Cohen S, et al., editor. A novel approach for treating infertile patients with diminished ovarian reserve (DOR). Paris, France: Monduzzi Eds; 2011.
   Google Scholar
• Ravanos K, Monastra G, Pavlidou T, et al. Can high levels of D-chiro-inositol in follicular fluid exert detrimental effects on blastocyst quality? Eur Rev Med Pharmacol Sci. 2017 Dec;21(23):5491–5498. PubMed PMID: 29243796.
   Google Scholar
• Lagana AS, Unfer V. D-chiro-inositol’s action as aromatase inhibitor: rationale and potential clinical targets. Eur Rev Med Pharmacol Sci. 2019 Dec;23(24):10575–10576. PubMed PMID: 31858524
   Google Scholar
• FDA. Opinion: Inositol 2017. Available from: http://wayback.archive-it.org/7993/20171031060738/https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/SCOGS/ucm260436.htm
   Google Scholar
• Carlomagno G, Unfer V. Inositol safety: clinical evidences. Eur Rev Med Pharmacol Sci. 2011 Aug;15(8):931–936. PubMed PMID: 21845803.
   Google Scholar
• 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. PubMed PMID: 30564926
   Google Scholar
• Crawford TJ, Crowther CA, Alsweiler J, et al. Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes. Cochrane Database Syst Rev. 2015 Dec;17(12):CD011507. PubMed PMID: 26678256; PubMed Central PMCID: PMCPMC6599829
   Google Scholar
• 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). PubMed PMID: 29053604; PubMed Central PMCID: PMCPMC5666868. DOI:10.3390/ijms18102187.
   Google Scholar
• Iuorno MJ, Jakubowicz DJ, Baillargeon JP, et al. Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract. 2002 Nov-Dec;8(6):417–423. PubMed PMID: 15251831
   Google Scholar
• Nestler JE, Jakubowicz DJ, Reamer P, et al. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999 Apr 29;340(17):1314–1320. PubMed PMID: 10219066
   Google Scholar
• Muscogiuri G, Palomba S, Lagana AS, et al. Inositols in the treatment of insulin-mediated diseases. Int J Endocrinol. 2016;2016:3058393. PubMed PMID: 27688754; PubMed Central PMCID: PMCPMC5027050
   Google Scholar
• McCormack CE. Acute effects of altered photoperiods on the onset of ovulation in gonadotropin-treated immature rats. Endocrinology. 1973 Aug;93(2):403–410. PubMed PMID: 4352442
   Google Scholar
• Zurvarra FM, Salvetti NR, Mason JI, et al. Disruption in the expression and immunolocalisation of steroid receptors and steroidogenic enzymes in letrozole-induced polycystic ovaries in rat. Reprod Fertil Dev. 2009;21(7):827–839. PubMed PMID: 19698287
   Google Scholar
• Lambert HH. Intensity of continuous light: threshold lower for persistent estrus than for retinal degeneration. Biol Reprod. 1975 Dec;13(5):576–580. PubMed PMID: 1239315
   Google Scholar
• Bevilacqua A, Dragotto J, Giuliani A, et al. Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model. J Cell Physiol. 2019 Jun;234(6):9387–9398. PubMed PMID: 30317628
   Google Scholar
• Gilling-Smith C, Willis DS, Beard RW, et al. Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J Clin Endocrinol Metab. 1994 Oct;79(4):1158–1165. PubMed PMID: 7962289
   Google Scholar
• Carlomagno G, Unfer V, Roseff S. The D-chiro-inositol paradox in the ovary. Fertil Steril. 2011 Jun 30;95(8):2515–2516. PubMed PMID: 21641593.
   Google Scholar
• Arya BK, Haq AU, Chaudhury K. Oocyte quality reflected by follicular fluid analysis in poly cystic ovary syndrome (PCOS): a hypothesis based on intermediates of energy metabolism. Med Hypotheses. 2012 Apr;78(4):475–478. PubMed PMID: 22336088
   Google Scholar
• Hipps PP, Sehgal RK, Holland WH, et al. Identification and partial characterization of inositol: NAD+ epimerase and inosose: NAD(P)H reductase from the fat body of the American cockroach, Periplaneta americana L. Biochemistry. 1973 Nov 6;12(23):4507–4512. PubMed PMID: 4149348
   Google Scholar
• Suzuki S, Kawasaki H, Satoh Y, et al. Urinary chiro-inositol excretion is an index marker of insulin sensitivity in Japanese type II diabetes. Diabetes Care. 1994 Dec;17(12):1465–1468. PubMed PMID: 7882818
   Google Scholar
• Chang HH, Chao HN, Walker CS, et al. Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease. Am J Physiol Renal Physiol. 2015 Nov 1;309(9):F755–63. PubMed PMID: 26311112
   Google Scholar
• Kawa JM, Przybylski R, Taylor CG. Urinary chiro-inositol and myo-inositol excretion is elevated in the diabetic db/db mouse and streptozotocin diabetic rat. Exp Biol Med (Maywood). 2003 Sep;228(8):907–914. PubMed PMID: 12968062
   Google Scholar
• 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):5924–5928. PubMed PMID: 8392181; PubMed Central PMCID: PMCPMC46839. eng.
   Google Scholar
• Kunjara S, Wang DY, Greenbaum AL, et al. Inositol phosphoglycans in diabetes and obesity: urinary levels of IPG A-type and IPG P-type, and relationship to pathophysiological changes. Mol Genet Metab. 1999 Dec;68(4):488–502. PubMed PMID: 10607479
   Google Scholar
• Ostlund RE Jr., McGill JB, Herskowitz I, et al. D-chiro-inositol metabolism in diabetes mellitus. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9988–9992. PubMed PMID: 8234346; PubMed Central PMCID: PMCPMC47698
   Google Scholar
• Unfer V, Facchinetti F, Orru B, et al. Myo-inositol effects in women with PCOS:a meta-analysis of randomized controlled trials. Endocr Connect. 2017 Nov;6(8):647–658. PubMed PMID: 29042448; PubMed Central PMCID: PMCPMC5655679
   Google Scholar
• Artini PG, Di Berardino OM, Papini F, et al. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol. 2013 Apr;29(4):375–379. PubMed PMID: 23336594
   Google Scholar
• Costantino D, Minozzi G, Minozzi E, et al. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci. 2009 Mar-Apr;13(2):105–110. PubMed PMID: 19499845.
   Google Scholar
• Genazzani AD, Lanzoni C, Ricchieri F, et al. Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol. 2008 Mar;24(3):139–144. PubMed PMID: 18335328
   Google Scholar
• Gerli S, Papaleo E, Ferrari A, et al. Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci. 2007 Sep-Oct;11(5):347–354. PubMed PMID: 18074942.
   Google Scholar
• Pizzo A, Lagana 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 Mar;30(3):205–208. PubMed PMID: 24351072
   Google Scholar
• 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):575–581. PubMed PMID: 22774396.
   Google Scholar
• Benelli E, Del Ghianda S, Di Cosmo C, et al. A combined therapy with myo-inositol and D-chiro-inositol improves endocrine parameters and insulin resistance in PCOS young overweight women. Int J Endocrinol. 2016;2016:3204083. PubMed PMID: 27493664; PubMed Central PMCID: PMCPMC4963579
   Google Scholar
• Pkhaladze L, Barbakadze L, Kvashilava N. Myo-inositol in the treatment of teenagers affected by PCOS. Int J Endocrinol. 2016;2016:1473612. PubMed PMID: 27635134; PubMed Central PMCID: PMCPMC5007307
   Google Scholar
• Emekci Ozay Ö, Ozay AC, Cagliyan E, et al. Myo-inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: a prospective, controlled, randomized trial. Gynecol Endocrinol. 2017 Jul;33(7):524–528. PubMed PMID: 28277112
   Google Scholar
• Zeng L, Yang K. Effectiveness of myoinositol for polycystic ovary syndrome: a systematic review and meta-analysis. Endocrine. 2018 Jan;59(1):30–38. PubMed PMID: 29052180
   Google Scholar
• Dona G, Sabbadin C, Fiore C, et al. Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome. Eur J Endocrinol. 2012 Apr;166(4):703–710. PubMed PMID: 22223702
   Google Scholar
• Nehra J, Kaushal J, Singhal SR, et al. A comparative study of myo inositol versus metformin on biochemical profile in polycystic ovarian syndrome in women. Int J Pharm Sci Res. 2017;8:1664–1670.
   Google Scholar
• Fruzzetti F, Perini D, Russo M, et al. Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2017 Jan;33(1):39–42. PubMed PMID: 27808588
   Google Scholar
• Gerli S, Mignosa M, Di Renzo GC. Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci. 2003 Nov-Dec;7(6):151–159. PubMed PMID: 15206484.
   Google Scholar
• Le Donne M, Metro D, Alibrandi A, et al. Effects of three treatment modalities (diet, myoinositol or myoinositol associated with D-chiro-inositol) on clinical and body composition outcomes in women with polycystic ovary syndrome. Eur Rev Med Pharmacol Sci. 2019 Mar;23(5):2293–2301. PubMed PMID: 30915778
   Google Scholar
• Nordio M, Basciani S, Camajani E. The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios. Eur Rev Med Pharmacol Sci. 2019 Jun;23(12):5512–5521. . PubMed PMID: 31298405.
   Google Scholar
• Minozzi M, D’Andrea G, Unfer V. Treatment of hirsutism with myo-inositol: a prospective clinical study. Reprod Biomed Online. 2008 Oct;17(4):579–582. . PubMed PMID: 18854115
   Google Scholar
• Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961 Nov;21:1440–1447. PubMed PMID: 13892577
   Google Scholar
• Diamanti-Kandarakis E, Baillargeon JP, Iuorno MJ, et al. A modern medical quandary: polycystic ovary syndrome, insulin resistance, and oral contraceptive pills. J Clin Endocrinol Metab. 2003 May;88(5):1927–1932. PubMed PMID: 12727935
   Google Scholar
• Giordano N, Nardi P, Santacroce C, et al. Acute hepatitis induced by cyproterone acetate. Ann Pharmacother. 2001 Sep;35(9):1053–1055. PubMed PMID: 11573856
   Google Scholar
• Abenavoli L, Milic N, Beaugrand M. Severe hepatitis induced by cyproterone acetate: role of corticosteroids. A case report. Ann Hepatol. 2013 Jan-Feb;12(1):152–155. PubMed PMID: 23293208
   Google Scholar
• Minozzi M, Costantino D, Guaraldi C, et al. The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome. Gynecol Endocrinol. 2011 Nov;27(11):920–924. PubMed PMID: 21417594
   Google Scholar
• Ozay AC, Emekci Ozay O, Okyay RE, et al. Different effects of myoinositol plus folic acid versus combined oral treatment on androgen levels in PCOS women. Int J Endocrinol. 2016;2016:3206872. . PubMed PMID: 27882049; PubMed Central PMCID: PMCPMC5110892 impartiality of the research reported
   Google Scholar
• Dumesic DA, Lobo RA. Cancer risk and PCOS. Steroids. 2013 Aug;78(8):782–785. PubMed PMID: 23624028
   Google Scholar
• Li W, Saud SM, Young MR, et al. Targeting AMPK for cancer prevention and treatment. Oncotarget. 2015 Apr 10;6(10):7365–7378. PubMed PMID: 25812084; PubMed Central PMCID: PMCPMC4480686
   Google Scholar
• Showkat M, Beigh MA, Andrabi KI. mTOR signaling in protein translation regulation: implications in cancer genesis and therapeutic interventions. Mol Biol Int. 2014;2014:686984. . PubMed PMID: 25505994; PubMed Central PMCID: PMCPMC4258317
   Google Scholar
• Eskander RN, Tewari KS. Exploiting the therapeutic potential of the PI3K-AKT-mTOR pathway in enriched populations of gynecologic malignancies. Expert Rev Clin Pharmacol. 2014 Nov;7(6):847–858. . PubMed PMID: 25301678
   Google Scholar
• Algire C, Moiseeva O, Deschenes-Simard X, et al. Metformin reduces endogenous reactive oxygen species and associated DNA damage. Cancer Prev Res (Phila). 2012 Apr;5(4):536–543. PubMed PMID: 22262811
   Google Scholar
• Lauretta R, Lanzolla G, Vici P, et al. Insulin-sensitizers, polycystic ovary syndrome and gynaecological cancer risk. Int J Endocrinol. 2016;2016:8671762. . PubMed PMID: 27725832; PubMed Central PMCID: PMCPMC5048026 publication of this paper
   Google Scholar
• Ferrannini E. The target of metformin in type 2 diabetes. N Engl J Med. 2014 Oct 16;371(16):1547–1548. PubMed PMID: 25317875
   Google Scholar
• Madiraju AK, Erion DM, Rahimi Y, et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014 Jun 26;510(7506):542–546. PubMed PMID: 24847880; PubMed Central PMCID: PMCPMC4074244
   Google Scholar
• Diamanti-Kandarakis E, Kouli CR, Bergiele AT, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999 Nov;84(11):4006–4011. PubMed PMID: 10566641
   Google Scholar
• Clement NS, Oliver TR, Shiwani H, et al. Metformin for endometrial hyperplasia. Cochrane Database Syst Rev. 2017 Oct;27(10):CD012214. PubMed PMID: 29077194; PubMed Central PMCID: PMCPMC6485333
   Google Scholar
• Moghetti P, Castello R, Negri C, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab. 2000 Jan;85(1):139–146. PubMed PMID: 10634377
   Google Scholar
• Unluhizarci K, Kelestimur F, Bayram F, et al. The effects of metformin on insulin resistance and ovarian steroidogenesis in women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 1999 Aug;51(2):231–236. PubMed PMID: 10468995
   Google Scholar
• Yang PK, Hsu CY, Chen MJ, et al. The efficacy of 24-month metformin for improving menses, hormones, and metabolic profiles in polycystic ovary syndrome. J Clin Endocrinol Metab. 2018 Mar 1;103(3):890–899. PubMed PMID: 29325133
   Google Scholar
• Fleming R, Hopkinson ZE, Wallace AM, et al. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab. 2002 Feb;87(2):569–574. PubMed PMID: 11836287
   Google Scholar
• Velazquez E, Acosta A, Mendoza SG. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol. 1997 Sep;90(3):392–395. PubMed PMID: 9277650
   Google Scholar
• Genazzani AD, Battaglia C, Malavasi B, et al. Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):114–119. PubMed PMID: 14711553
   Google Scholar
• Eisenhardt S, Schwarzmann N, Henschel V, et al. Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2006 Mar;91(3):946–952. PubMed PMID: 16352680
   Google Scholar
• Essah PA, Apridonidze T, Iuorno MJ, et al. Effects of short-term and long-term metformin treatment on menstrual cyclicity in women with polycystic ovary syndrome. Fertil Steril. 2006 Jul;86(1):230–232. PubMed PMID: 16716324
   Google Scholar
• Ibáñez L, Valls C, Ferrer A, et al. Sensitization to insulin induces ovulation in nonobese adolescents with anovulatory hyperandrogenism. J Clin Endocrinol Metab. 2001 Aug;86(8):3595–3598. PubMed PMID: 11502783
   Google Scholar
• Carmina E, Lobo RA. Does metformin induce ovulation in normoandrogenic anovulatory women? Am J Obstet Gynecol. 2004 Nov;191(5):1580–1584. PubMed PMID: 15547527
   Google Scholar
• Tso LO, Costello MF, Albuquerque LE, et al. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2014 Nov;18(11):CD006105. PubMed PMID: 25406011
   Google Scholar
• Palomba S, Falbo A, La Sala GB. Effects of metformin in women with polycystic ovary syndrome treated with gonadotrophins for in vitro fertilisation and intracytoplasmic sperm injection cycles: a systematic review and meta-analysis of randomised controlled trials. BJOG. 2013 Feb;120(3):267–276. PubMed PMID: 23194199
   Google Scholar
• Abdalmageed OS, Farghaly TA, Abdelaleem AA, et al. Impact of metformin on IVF outcomes in overweight and obese women with polycystic ovary syndrome: a randomized double-blind controlled trial. Reprod Sci. 2018 Jan;1:1933719118765985. PubMed PMID: 29576001
   Google Scholar
• Palomba S, Falbo A, Carrillo L, et al. Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Fertil Steril. 2011 Dec;96(6):1384–1390 e4. PubMed PMID: 21982727
   Google Scholar
• Niafar M, Hai F, Porhomayon J, et al. The role of metformin on vitamin B12 deficiency: a meta-analysis review. Intern Emerg Med. 2015 Feb;10(1):93–102. PubMed PMID: 25502588
   Google Scholar
• Hanem LGE, Stridsklev S, Juliusson PB, et al. Metformin use in PCOS pregnancies increases the risk of offspring overweight at 4 years of age: follow-up of two RCTs. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1612–1621. PubMed PMID: 29490031
   Google Scholar
• Morin-Papunen LC, Vauhkonen I, Koivunen RM, et al. Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab. 2000 Sep;85(9):3161–3168. PubMed PMID: 10999803
   Google Scholar
• Martin KA, Anderson RR, Chang RJ, et al. Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1233–1257. PubMed PMID: 29522147
   Google Scholar
• Siebert TI, Viola MI, Steyn DW, et al. Is metformin indicated as primary ovulation induction agent in women with PCOS? A systematic review and meta-analysis. Gynecol Obstet Invest. 2012;73(4):304–313. . PubMed PMID: 22516925
   Google Scholar
• Misso ML, Costello MF, Garrubba M, et al. Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2013 Jan-Feb;19(1):2–11. PubMed PMID: 22956412
   Google Scholar
• Facchinetti F, Orru B, Grandi G, et al. Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials. Gynecol Endocrinol. 2019 Mar;35(3):198–206. PubMed PMID: 30614282
   Google Scholar
• R Ss A, Jajoo C, Chimote A. A comparative study of metabolic and hormonal effects of myoinositol vs. metformin in women with polycystic ovary syndrome: a randomised controlled trial. Int J Reprod Contracept Obstet Gynecol. 2015;4:189–194.
   Google Scholar
• Jamilian M, Farhat P, Foroozanfard F, et al. Comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in polycystic ovary syndrome: A randomized controlled clinical trial. Clin Endocrinol (Oxf). 2017 Aug;87(2):194–200. PubMed PMID: 28485095
   Google Scholar
• De Leo V, Musacchio MCCV. A combined treatment with myo-inositol and monacolin k improve the androgen and lipid profiles of insulin-resistant PCOS patients. J Metabolic Synd. 2013;2.DOI: 10.4172/2167-0943.1000127
   Google Scholar
• Tagliaferri V, Romualdi D, Immediata V, et al. Metformin vs myoinositol: which is better in obese polycystic ovary syndrome patients? A randomized controlled crossover study. Clin Endocrinol (Oxf). 2017 May;86(5):725–730. PubMed PMID: 28092404
   Google Scholar
• Hudecova M, Jan H, Christian B, et al. Long-term reproductive and metabolic consequences of PCOS. Curr Diabetes Rev. 2012 Nov;8(6):444–451. PubMed PMID: 22934549.
   Google Scholar
• Palomba S, Santagni S, Falbo A, et al. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health. 2015;7:745–763. PubMed PMID: 26261426; PubMed Central PMCID: PMCPMC4527566
   Google Scholar
• Shokrpour M, Foroozanfard F, Afshar Ebrahimi F, et al. Comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome: a randomized controlled clinical trial. Gynecol Endocrinol. 2019 May;35(5):406–411. PubMed PMID: 30608001
   Google Scholar
• Wang YX, Zhu WJ, Xie BG. Expression of PPAR-γ in adipose tissue of rats with polycystic ovary syndrome induced by DHEA. Mol Med Rep. 2014 Mar;9(3):889–893. PubMed PMID: 24425206
   Google Scholar
• Jamilian H, Jamilian M, Foroozanfard F, et al. Comparison of myo-inositol and metformin on mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. J Psychosom Obstet Gynaecol. 2018 Dec;39(4):307–314. PubMed PMID: 28980870
   Google Scholar
• 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):511–514. PubMed PMID: 30614289
   Google Scholar
• 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. . PubMed PMID: 27807448; PubMed Central PMCID: PMCPMC5078644
   Google Scholar
• Agostini R, Rossi F, Pajalich R. Myoinositol/folic acid combination for the treatment of erectile dysfunction in type 2 diabetes men: a double-blind, randomized, placebo-controlled study. Eur Rev Med Pharmacol Sci. 2006 Sep-Oct;10(5):247–250. PubMed PMID: 17121317.
   Google Scholar
• Reece EA, Khandelwal M, Wu YK, et al. Dietary intake of myo-inositol and neural tube defects in offspring of diabetic rats. Am J Obstet Gynecol. 1997 Mar;176(3):536–539. PubMed PMID: 9077602
   Google Scholar
• Gateva A, Unfer V, Kamenov Z. The use of inositol(s) isomers in the management of polycystic ovary syndrome: a comprehensive review. Gynecol Endocrinol. 2018 Jul;34(7):545–550. . PubMed PMID: 29309199
   Google Scholar
• Dinicola S, Chiu TT, Unfer V, et al. The rationale of the myo-inositol and D-chiro-inositol combined treatment for polycystic ovary syndrome. J Clin Pharmacol. 2014 Oct;54(10):1079–1092. PubMed PMID: 25042908
   Google Scholar
• Lagana AS, Vitagliano A, Noventa M, et al. Myo-inositol supplementation reduces the amount of gonadotropins and length of ovarian stimulation in women undergoing IVF: a systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet. 2018 Oct;298(4):675–684. PubMed PMID: 30078122
   Google Scholar
• Papaleo E, Unfer V, Baillargeon JP, et al. Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril. 2009 May;91(5):1750–1754. PubMed PMID: 18462730
   Google Scholar
• Imani B, Eijkemans MJ, Te Velde ER, et al. Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab. 1998 Jul;83(7):2361–2365. PubMed PMID: 9661609
   Google Scholar
• Morley LC, Tang T, Yasmin E, et al. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2017 Nov;29(11):CD003053. PubMed PMID: 29183107; PubMed Central PMCID: PMCPMC6486196
   Google Scholar
• Mohsen IA. A randomized controlled trial of the effect of rosiglitazone and clomiphene citrate versus clomiphene citrate alone in overweight/obese women with polycystic ovary syndrome. Gynecol Endocrinol. 2012 Apr;28(4):269–272. PubMed PMID: 21970545
   Google Scholar
• Ghazeeri G, Kutteh WH, Bryer-Ash M, et al. Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome. Fertil Steril. 2003 Mar;79(3):562–566. PubMed PMID: 12620440
   Google Scholar
• Rouzi AA, Ardawi MS. A randomized controlled trial of the efficacy of rosiglitazone and clomiphene citrate versus metformin and clomiphene citrate in women with clomiphene citrate-resistant polycystic ovary syndrome. Fertil Steril. 2006 Feb;85(2):428–435. PubMed PMID: 16595222
   Google Scholar
• Kamenov Z, Kolarov G, Gateva A, et al. Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance. Gynecol Endocrinol. 2015 Feb;31(2):131–135. PubMed PMID: 25259724
   Google Scholar
• Rolland AL, Peigne M, Plouvier P, et al. Could myo-inositol soft gel capsules outperform clomiphene in inducing ovulation? Results of a pilot study. Eur Rev Med Pharmacol Sci. 2017 Jun;21(2 Suppl):10–14. PubMed PMID: 28724178.
   Google Scholar
• Pundir J, Psaroudakis D, Savnur P, et al. Inositol treatment of anovulation in women with polycystic ovary syndrome: a meta-analysis of randomised trials. BJOG. 2018 Feb;125(3):299–308. PubMed PMID: 28544572
   Google Scholar
• Showell MG, Mackenzie-Proctor R, Jordan V, et al. Inositol for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2018 Dec;20(12):CD012378. PubMed PMID: 30570133; PubMed Central PMCID: PMCPMC6516980
   Google Scholar
• Omu AE. Sperm parameters: paradigmatic index of good health and longevity. Med Princ Pract. 2013;22(Suppl 1):30–42. PubMed PMID: 24051979; PubMed Central PMCID: PMCPMC5586815
   Google Scholar
• Condorelli RA, La Vignera S, Mongioi LM, et al. Myo-inositol as a male fertility molecule: speed them up! Eur Rev Med Pharmacol Sci. 2017 Jun;21(2 Suppl):30–35. PubMed PMID: 28724176
   Google Scholar
• Cryns K, Shamir A, Van Acker N, et al. IMPA1 is essential for embryonic development and lithium-like pilocarpine sensitivity. Neuropsychopharmacology. 2008 Feb;33(3):674–684. PubMed PMID: 17460611
   Google Scholar
• Colone M, Marelli G, Unfer V, et al. Inositol activity in oligoasthenoteratospermia–an in vitro study. Eur Rev Med Pharmacol Sci. 2010 Oct;14(10):891–896. PubMed PMID: 21222378.
   Google Scholar
• Condorelli RA, La Vignera S, Bellanca S, et al. Myoinositol: does it improve sperm mitochondrial function and sperm motility? Urology. 2012 Jun;79(6):1290–1295. PubMed PMID: 22656408
   Google Scholar
• Montanino Oliva M, Minutolo E, Lippa A, et al. Effect of myoinositol and antioxidants on sperm quality in men with metabolic syndrome. Int J Endocrinol. 2016;2016:1674950. . PubMed PMID: 27752262; PubMed Central PMCID: PMCPMC5056296
   Google Scholar
• Lotti F, Corona G, Degli Innocenti S, et al. Seminal, ultrasound and psychobiological parameters correlate with metabolic syndrome in male members of infertile couples. Andrology. 2013 Mar;1(2):229–239. PubMed PMID: 23315971
   Google Scholar
• Calogero AE, Gullo G, La Vignera S, et al. Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study. Andrology. 2015 May;3(3):491–495. PubMed PMID: 25854593
   Google Scholar
• Dinkova A, Martinov D, Konova E. Efficacy of myo-inositol in the clinical management of patients with asthenozoospermia. Eur Rev Med Pharmacol Sci. 2017 Jun;21(2 Suppl):62–65. PubMed PMID: 28724182.
   Google Scholar
• Schneider S. Inositol transport proteins. FEBS Lett. 2015 Apr 28;589(10):1049–1058. PubMed PMID: 25819438
   Google Scholar
• Garzon S, Lagana AS, Monastra G. Risk of reduced intestinal absorption of myo-inositol caused by D-chiro-inositol or by glucose transporter inhibitors. Expert Opin Drug Metab Toxicol. 2019 Aug;8:1–7. PubMed PMID: 31382802
   Google Scholar
• Lin X, Ma L, Fitzgerald RL, et al. Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. Arch Biochem Biophys. 2009 Jan 15;481(2):197–201. PubMed PMID: 19032932; PubMed Central PMCID: PMCPMC3732106
   Google Scholar
• Aouameur R, Da Cal S, Bissonnette P, et al. SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine. Am J Physiol Gastrointest Liver Physiol. 2007 Dec;293(6):G1300–7. PubMed PMID: 17932225
   Google Scholar
• 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):275–280. . PubMed PMID: 20222840
   Google Scholar
• Permyakov EA, Berliner LJ. α-Lactalbumin: structure and function. FEBS Lett. 2000 May 19;473(3):269–274. PubMed PMID: 10818224
   Google Scholar
• Kamau SM, Cheison SC, Chen W, et al. Alpha-Lactalbumin: its production technologies and bioactive peptides. Compr Rev Food Sci Food Saf. 2010;9:197–212.
   Google Scholar
• Wang X, Ai T, Meng XL, et al. In vitro iron absorption of α-lactalbumin hydrolysate-iron and β-lactoglobulin hydrolysate-iron complexes. J Dairy Sci. 2014 May;97(5):2559–2566. PubMed PMID: 24612808
   Google Scholar
• Delavari B, Saboury AA, Atri MS, et al. Alpha-lactalbumin: A new carrier for vitamin D3 food enrichment. Food Hydrocolloids. 2015;45(Supplement C):124–131.
   Google Scholar
• Available from: https://www.ams.usda.gov/sites/default/files/media/Whey%20Protein%20Concentrate%20TR.pdf.
   Google Scholar
• Monastra G, Sambuy Y, Ferruzza S, et al. Alpha-lactalbumin effect on myo-inositol intestinal absorption: in vivo and in vitro. Curr Drug Deliv. 2018;15(9):1305–1311. PubMed PMID: 29745333.
   Google Scholar
• Sambuy Y, De Angelis I, Ranaldi G, et al. The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol Toxicol. 2005 Jan;21(1):1–26. PubMed PMID: 15868485
   Google Scholar
• Lemmer HJ, Hamman JH. Paracellular drug absorption enhancement through tight junction modulation. Expert Opin Drug Deliv. 2013 Jan;10(1):103–114. PubMed PMID: 23163247
   Google Scholar
• Montanino Oliva M, Buonomo G, Calcagno M, et al. Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women. J Ovarian Res. 2018 May 10;11(1):38. PubMed PMID: 29747700; PubMed Central PMCID: PMCPMC5944130.
   Google Scholar
• Yamaguchi M, Yoshida K, Uchida M. Novel functions of bovine milk-derived α-lactalbumin: anti-nociceptive and anti-inflammatory activity caused by inhibiting cyclooxygenase-2 and phospholipase A2. Biol Pharm Bull. 2009 Mar;32(3):366–371. PubMed PMID: 19252279; eng.
   Google Scholar
• Yamaguchi M, Takai S. Chronic administration of bovine milk-derived α-lactalbumin improves glucose tolerance via enhancement of adiponectin in Goto-Kakizaki rats with type 2 diabetes. Biol Pharm Bull. 2014;37(3):404–408. . PubMed PMID: 24583859; eng.
   Google Scholar