Nutraceutical prospective: The synergetic mechanism of action of inositols and resveratrol on metabolic syndrome

Open access


It has been known that inositols function as insulin second messengers and mediate different insulin-dependent processes and are a valid natural, non-pharmaceutical alternative to contrast insulin-resistance as well as associated metabolic syndrome in women with Polycystic ovarian disease (PCOS). Several studies also have shown positive effects of resveratrol in reducing glucose and lipid concentrations in patients. Recently, clinical evidence has proven that an D-chiro-inositol/resveratrol combination has a potential role to play in maintaining metabolic and endocrine health, however no large clinical trials have demonstrated the medical effectiveness of the combination, and the combined mode of action remains poorly discussed. Herein, we address the hypothesis of a synergistic mechanism adopted by D-chiro-inositol and resveratrol in reducing insulin resistance and hyperlipidemia and thus showing a greater therapeutic potential compared to treatment with inositol’s alone.

1. Iqbal J, Al Qarni A. Metabolic syndrome, dyslipidemia and regulation of lipoprotein metabolism. Curr Diabetes Rev. 2017 Jul 5.

2. Chen C, Jing G. Insulin resistance and polycystic ovary syndrome in a chinese population. Endocr Pract. 2017 Jul 6.

3. Leite PB, Dâmaso AR. Long-term interdisciplinary therapy decreases symptoms of binge eating disorder and prevalence of metabolic syndrome in adults with obesity. Nutr Res. 2017 Apr;40:57-64.

4. Al-Dughaishi T, Nikolic D. Nutraceuticals as Lipid-Lowering Treatment in Pregnancy and Their Effects on the Metabolic Syndrome. Curr Pharm Biotechnol. 2016;17(7):614-23.

5. Dong D, Reece EA. New development of the yolk sac theory in diabetic embryopathy: molecular mechanism and link to structural birth defects. Am J Obstet Gynecol. 2016 Feb;214(2):192-202.

6. Greene ND, Leung KY, Copp AJ. Inositol, neural tube closure and the prevention of neural tube defects. Birth Defects Res. 2017 Jan 30;109(2):68-80.

7. Farren M, Daly N. The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial. Diabetes Care. 2017 Jun;40(6):759-763.

8. Brown J, Crawford TJ. Dietary supplementation with myo-inositol in women during pregnancy for treating gestational diabetes. Cochrane Database Syst Rev. 2016 Sep 7;9:CD012048.

9. Malvasi A, Casciaro F. 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):270-4

10. Singh CK, Kumar A. Diabetic complications in pregnancy: is resveratrol a solution? Exp Biol Med (Maywood). 2013 May;238(5):482-90.

11. Malvasi A, Kosmas I. 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.

12. Timmers S, Konings E. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011 Nov 2;14(5):612-22.

13. Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Carmina E, Chang J, Yildiz BO, Laven JS, Boivin J, Petraglia F, Wijeyeratne CN, Norman RJ, Dunaif A, Franks S, Wild RA, Dumesic D, Barnhart K. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop GroupFertil Steril. 2012 Jan;97(1):28-38.e25.

14. Baillargeon JP, Iuorno MJ, Nestler JE. Insulin sensitizers for polycystic ovary syndrome. Clin Obstet Gynecol. 2003 Jun;46(2):325-40. Review.

15. Højlund K. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance. Dan Med J. 2014 Jul;61(7):B4890. Review.

16. De Leo V, Musacchio MC, Cappelli V, Massaro MG, Morgante G, Petraglia F. Genetic, hormonal and metabolic aspects of PCOS: an update.. Reprod Biol Endocrinol. 2016 Jul 16;14(1):38

17. 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;17:17-33.

18. Toprak S, Yönem A, Cakir B, Güler S, Azal O, Ozata M, Corakçi A. Insulin resistance in nonobese patients with polycystic ovary syndrome. Horm Res. 2001;55(2):65-70.

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

20. Nestler J, Unfer V. Reflections on inositol(s) for PCOS therapy: steps toward success. Gynecol Endocrinol 2015; 31: 501-505.

21. Larner J, Huang LC, Tang G, Suzuki S, Sch wartz CF, Romero G, Roulidis Z, Zeller K, Shen TY , Oswald AS. Insulin mediators: structure and formation. Cold Spring Harb Symp Quant Biol 1988; 53: 965-97.

22. Dresner A., Laurent D., Marcucci M., et al. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. Journal of Clinical Investigation. 1999;103(2):253-259.

23. Laganà AS, Rossetti P, Buscema M, La Vignera S, Condorelli RA, Gullo G, Granese R, Triolo O.Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols. Int J Endocrinol. 2016;2016:6306410.

24. Pizzo A, Lagan`a AS, and Barbaro A, Comparison betweeneffects ofmyo-inositol and d-chiro-inositol on ovarian function and metabolic factors in women with PCOS, Gynecological Endocrinology 2014; 30 (3), 205-208.

25. Nonomura S, Kanagawa H, Makimoto A. Chemical constituents of polygonaceous plants. I. Studies on the components of Ko-J O-Kon. Polygonum cuspidatum Sieb Et Zucc Yakugaku Zasshi 1963; 83 988-990.

26. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW,. Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan, Nature 2003; 425 191-196.

27. Um JH, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, Kim MK, Viollet B, Chung JH. AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes. 2010 Mar;59(3):554-63.

28. Hardie DG. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 13, 251-262.

29. Chung JH, Manganiello V, Dyck JR. Resveratrol as a calorie restriction mimetic: therapeutic implications. Trends Cell Biol. 2012; 22(10):546-54.

30. Zang M. Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 55, 2180-2191.

31. Chan V, Fenning A, Iyer A, Hoey A, Brown L. Resveratrol improves cardiovascular function in DOCA-salt hypertensive rats. Current Pharmaceutical Biotechnology. 2011;12(3):429-436.

32. Joshi MS, Williams D, Horlock D, Samarasinghe T, Andrews KL, Jefferis AM, Berger PJ, Chin-Dusting JP, Kaye DM. Role of mitochondrial dysfunction in hyperglycaemia-induced coronary microvascular dysfunction: Protective role of resveratrol. Diab Vasc Dis Res. 2015 May;12(3):208-16.

33. Zhu KN, Jiang CH. Two triterpeniods from Cyclocarya paliurus (Batal) Iljinsk (Juglandaceae) promote glucose uptake in 3T3-L1 adipocytes: The relationship to AMPK activation. Phytomedicine. 2015 Aug 15;22(9):837-46.

34. Wang S, Song P, Zou MH. AMP-activated protein kinase, stress responses and cardiovascular diseases. Clin Sci (Lond). 2012 Jun;122(12):555-73.

Journal Information


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 236 236 38
PDF Downloads 112 112 17