Combination of inositol and alpha lipoic acid in metabolic syndrome-affected women: a randomized placebo-controlled trial
Immacolata Capasso, Emanuela Esposito, Nicola Maurea, Maurizio Montella, Anna Crispo, Michelino De Laurentiis, Massimiliano D'Aiuto, Giuseppe Frasci, Gerardo Botti, Maria Grimaldi, Ernesta Cavalcanti, Giuseppe Esposito, Alfredo Fucito, Giuseppe Brillante, Giuseppe D'Aiuto, Gennaro Ciliberto, Immacolata Capasso, Emanuela Esposito, Nicola Maurea, Maurizio Montella, Anna Crispo, Michelino De Laurentiis, Massimiliano D'Aiuto, Giuseppe Frasci, Gerardo Botti, Maria Grimaldi, Ernesta Cavalcanti, Giuseppe Esposito, Alfredo Fucito, Giuseppe Brillante, Giuseppe D'Aiuto, Gennaro Ciliberto
Abstract
Background: Inositol has been reported to improve insulin sensitivity since it works as a second messenger achieving insulin-like effects on metabolic enzymes. The aim of this study was to evaluate the inositol and alpha lipoic acid combination effectiveness on metabolic syndrome features in postmenopausal women at risk of breast cancer.
Methods: A six-month prospective, randomized placebo-controlled trial was carried out on a total of 155 postmenopausal women affected by metabolic syndrome at risk of breast cancer, the INOSIDEX trial. All women were asked to follow a low-calorie diet and were assigned randomly to daily consumption of a combination of inositol and alpha lipoic acid (77 pts) or placebo (78 pts) for six months. Primary outcomes we wanted to achieve were both reduction of more than 20% of the HOMA-IR index and of triglycerides serum levels. Secondary outcomes expected were both the improvement of high-density lipoprotein cholesterol levels and the reduction of anthropometric features such as body mass index and waist-hip ratio.
Results: A significant HOMA-IR reduction of more than 20% was evidenced in 66.7% (P <0.0001) of patients, associated with a serum insulin level decrease in 89.3% (P <0.0000). A decrease in triglycerides was evidenced in 43.2% of patients consuming the supplement (P <0.0001). An increase in HDL cholesterol (48.6%) was found in the group consuming inositol with respect to the placebo group. A reduction in waist circumference and waist-hip ratio was found in the treated group with respect to the placebo group.
Conclusions: Inositol combined with alpha lipoic acid can be used as a dietary supplement in insulin-resistant patients in order to increase their insulin sensitiveness. Daily consumption of inositol combined with alpha lipoic acid has a significant bearing on metabolic syndrome. As metabolic syndrome is considered a modifiable risk factor of breast tumorigenesis, further studies are required to assess whether inositol combined with alpha lipoic acid can be administered as a dietary supplement in breast cancer primary prevention.
Trial registration: Current Controlled Trial ISRCTN74096908.
References
- Capasso I, Esposito E, Pentimalli F, Crispo A, Montella M, Grimaldi M, De Marco M, Cavalcanti E, D’Aiuto M, Fucito A, Frasci G, Maurea N, Esposito G, Pedicini T, Vecchione A, D’Aiuto G, Giordano A. Metabolic syndrome affects breast cancer risk in postmenopausal women National Cancer Institute of Naples experience. Cancer Biol Ther. 2010;10:1240–1243. doi: 10.4161/cbt.10.12.13473.
- Capasso I, Esposito E, Pentimalli F, Montella M, Crispo A, Maurea N, D Aiuto M, Fucito A, Grimaldi M, Cavalcanti E, Esposito G, Brillante G, Lodato S, Pedicini T, D Aiuto G, Ciliberto G, Giordano A. Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experience. J Exp Clin Cancer Res. 2013;32:14. doi: 10.1186/1756-9966-32-14. [Epub ahead of print]
- Agnoli C, Berrino F, Abagnato CA, Muti P, Panico S, Crosignani P, Krogh V. Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort: a nested case–control study. Nutr Metab Cardiovasc Dis. 2010;20:41–48. doi: 10.1016/j.numecd.2009.02.006. Epub 2009 Apr 10.
- Carr DB, Utzschneider KM, Hull RL, Kodama K, Retzlaff BM, Brunzell JD, Shofer JB, Fish BE, Knopp RH, Kahn SE. Intra-abdominal fat is a major determinant of the national cholesterol education program adult treatment panel III criteria for the metabolic syndrome. Diabetes. 2004;53:2087–2094. doi: 10.2337/diabetes.53.8.2087.
- Kabat GC, Kim M, Chlebowski RT, Khandekar J, Ko MG, McTiernan A, Neuhouser ML, Parker DR, Shikany JM, Stefanick ML, Thomson CA, Rohan TE. A longitudinal study of the metabolic syndrome and risk of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:2046–2053. doi: 10.1158/1055-9965.EPI-09-0235. Epub 2009 Jun 30.
- Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) JAMA. 2001;285:2486–2497. doi: 10.1001/jama.285.19.2486.
- Stebbing J, Sharma A, North B, Athersuch TJ, Zebrowski A, Pchejetski D, Coombes RC, Nicholson JK, Keun HC. A metabolic phenotyping approach to understanding relationships between metabolic syndrome and breast tumour responses to chemotherapy. Ann Oncol. 2012;23:860–866. doi: 10.1093/annonc/mdr347. Epub 2011 Aug.
- Goodwin PJ, Stambolic V, Lemieux J, Chen BE, Parulekar WR, Gelmon KA, Hershman DL, Hobday TJ, Ligibel JA, Mayer IA, Pritchard KI, Whelan TJ, Rastogi P, Shepherd LE. Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agents. Breast Cancer Res Treat. 2011;126:215–220. doi: 10.1007/s10549-010-1224-1. Epub 2010 Oct 26.
- Castaneda CA, Cortes-Funes H, Gomez HL, Ciruelos EM. The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer. Cancer Metastasis Rev. 2010;29:751–759. doi: 10.1007/s10555-010-9261-0.
- Saltiel AR. Second messengers of insulin action. Diabetes Care. 1990;13:244–256. doi: 10.2337/diacare.13.3.244.
- Giordano D, Corrado F, Santamaria A, Quattrone S, Pintaudi B, Di Benedetto A, D'Anna R. Effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome: a perspective, randomized, placebo-controlled study. Menopause. 2011;18:102–104. doi: 10.1097/gme.0b013e3181e8e1b1.
- Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM. Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol. 2008;24:139–144. doi: 10.1080/09513590801893232.
- Sample Size Calculator. .
- American Diabetes Association. Standards of medical care in diabetes-2012. Diabetes Care. 2012;Suppl 1:S11–S63.
- Pfeiler G, Treeck O, Wenzel G, Goerse R, Hartmann A, Schmitz G, Ortmann O. Influence of insulin resistance on adiponectin receptor expression in breast cancer. Maturitas. 2009;63:253–256. doi: 10.1016/j.maturitas.2009.04.006. Epub 2009 Jun 13.
Source: PubMed