Combination of inositol and alpha lipoic acid in metabolic syndrome-affected women: a randomized placebo-controlled trial

Trials

Gennaro Ciliberto²  Giuseppe D’Aiuto²  Giuseppe Brillante²  Alfredo Fucito²  Giuseppe Esposito⁵  Ernesta Cavalcanti¹  Maria Grimaldi⁴  Gerardo Botti⁶  Giuseppe Frasci²  Massimiliano D’Aiuto²  Michelino De Laurentiis²  Anna Crispo⁴  Maurizio Montella⁴  Nicola Maurea³  Emanuela Esposito²  Immacolata Capasso² 

[1] Division of Medicine Laboratory and Clinical Pathology, National Cancer Institute of Naples - Fondazione G. Pascale, Via Mariano Semmola, Naples, 80131, Italy;Department of Senology, National Cancer Institute of Naples - Fondazione G. Pascale, Via Mariano Semmola, Naples, 80131, Italy;Department of Division of Cardiology, National Cancer Institute of Naples - Fondazione G. Pascale, Via Mariano Semmola, Naples, 80131, Italy;Division of Epidemiology, National Cancer Institute of Naples - Fondazione G. Pascale, Via Mariano Semmola, Naples, 80131, Italy;Division of Immunohematology, National Cancer Institute of Naples - Fondazione G. Pascale, Via Mariano Semmola, Naples, 80131, Italy;Division of Pathology, National Cancer Institute of Naples - Fondazione G. Pascale, Via Mariano Semmola, Naples, 80131, Italy

关键词: Breast cancer;    Alpha lipoic acid;    Inositol;    HDL cholesterol;    Insulin resistance;    Metabolic syndrome;   

Others  :  1093159
DOI  :  10.1186/1745-6215-14-273

 received in 2013-01-10, accepted in 2013-08-05,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Capasso et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]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.
• [2]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. [Epub ahead of print] BioMed Central Full Text
• [3]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. Epub 2009 Apr 10
• [4]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.
• [5]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. Epub 2009 Jun 30
• [6]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.
• [7]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. Epub 2011 Aug
• [8]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. Epub 2010 Oct 26
• [9]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.
• [10]Saltiel AR: Second messengers of insulin action. Diabetes Care 1990, 13:244-256.
• [11]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.
• [12]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.
• [13]Sample Size Calculator http://www.surveysystem.com/sscalc.htm webcite
• [14]American Diabetes Association: Standards of medical care in diabetes-2012. Diabetes Care 2012, Suppl 1:S11-S63.
• [15]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. Epub 2009 Jun 13