Horm Metab Res 2017; 49(08): 612-617
DOI: 10.1055/s-0043-112346
Endocrine Care

Effect of Two Different Doses of Vitamin D Supplementation on Metabolic Profiles of Insulin-Resistant Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Fatemeh Foroozanfard
1   Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, I. R. Iran
,
Maesoomeh Talebi
1   Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, I. R. Iran
,
Mansooreh Samimi
1   Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, I. R. Iran
,
Sahar Mehrabi
2   Endocrinology and Metabolism Research Center, Arak University of Medical Sciences, Arak, I. R. Iran
,
Bita Badehnoosh
3   Department of Gynecology and Obstetrics, School of Medicine, Alborz University of Medical Sciences, Karaj, I. R. Iran
,
Mehri Jamilian
2   Endocrinology and Metabolism Research Center, Arak University of Medical Sciences, Arak, I. R. Iran
,
Maryam Maktabi
2   Endocrinology and Metabolism Research Center, Arak University of Medical Sciences, Arak, I. R. Iran
,
Zatollah Asemi
4   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I. R. Iran
› Author Affiliations

Abstract

The current study was conducted to evaluate the effects of 2 different doses of vitamin D supplementation on metabolic profiles of insulin-resistant patients with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was performed on 90 insulin-resistant patients with PCOS according to the Rotterdam criteria aged 18–40 years old. Participants were randomly allocated into 3 groups to receive either 4 000 IU of vitamin D (n=30) or 1 000 IU of vitamin D (n=30) or placebo (n=30) per day for 12 weeks. Vitamin D supplementation (4 000 IU), compared with vitamin D (1 000 IU) and placebo, led to reduced fasting plasma glucose (−4.3±8.6 vs. −4.7±7.1 and +0.1±6.7 mg/dl, respectively, p=0.02), serum insulin concentrations (−2.7±2.7 vs. −1.4±4.2 and −0.1±4.1 μIU/ml, respectively, p=0.02), and HOMA-IR (−0.6±0.6 vs. −0.4±1.0 and −0.1±0.9, respectively, p=0.02). In addition, we found significant decreases in mean change of serum triglycerides (−10.3±7.3 vs. −3.6±14.5 and +6.9±23.8 mg/dl, respectively, p=0.001), VLDL- (−2.0±1.5 vs. −0.7±2.9 and +1.4±4.8 mg/dl, respectively, p=0.001), total- (−14.0±9.5 vs. −6.2±24.0 and +7.1±29.7 mg/dl, respectively, p=0.002), LDL- (−10.8±8.3 vs. −5.7±21.9 and +6.8±28.2 mg/dl, respectively, p=0.005), and total-/HDL-cholesterol ratio (−0.2±0.3 vs. −0.1±0.6 and +0.2±0.7 mg/dl, respectively, p=0.003) in the high-dose vitamin D group compared with low-dose vitamin D and placebo groups. Overall, vitamin D supplementation at a dosage of 4 000 IU/day for 12 weeks in insulin-resistant patients with PCOS had beneficial effects of glucose metabolism and lipid profiles compared with 1 000 IU/day of vitamin D and placebo groups.

Supplementary Material



Publication History

Received: 09 April 2017

Accepted: 08 May 2017

Article published online:
05 July 2017

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Baskind NE, Balen AH. Hypothalamic-pituitary, ovarian and adrenal contributions to polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2016; 37: 80-97
  • 2 Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, Lizneva D, Natterson-Horowtiz B, Teede HJ, Yildiz BO. Polycystic ovary syndrome. Nat Rev Dis Primers 2016; 2: 16057
  • 3 Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 2013; 6: 1-13
  • 4 Wild RA, Rizzo M, Clifton S, Carmina E. Lipid levels in polycystic ovary syndrome: systematic review and meta-analysis. Fertil Steril 2011; 95: 1073-0179 e1–11
  • 5 Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 2004; 27: 2813-2818
  • 6 Mattila C, Knekt P, Mannisto S, Rissanen H, Laaksonen MA, Montonen J, Reunanen A. Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care 2007; 30: 2569-2570
  • 7 Kotsa K, Yavropoulou MP, Anastasiou O, Yovos JG. Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome. Fertil Steril 2009; 92: 1053-1058
  • 8 Yildizhan R, Kurdoglu M, Adali E, Kolusari A, Yildizhan B, Sahin HG, Kamaci M. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch Gynecol Obstet 2009; 280: 559-563
  • 9 Wehr E, Pieber TR, Obermayer-Pietsch B. Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: A pilot study. J Endocrinol Invest 2011; 34: 757-763
  • 10 Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 2007; 92: 2017-2029
  • 11 Reid IR. Effects of calcium supplementation on circulating lipids: potential pharmacoeconomic implications. Drugs Aging 2004; 21: 7-17
  • 12 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81: 19-25
  • 13 Asemi Z, Foroozanfard F, Hashemi T, Bahmani F, Jamilian M, Esmaillzadeh A. Calcium plus vitamin D supplementation affects glucose metabolism and lipid concentrations in overweight and obese vitamin D deficient women with polycystic ovary syndrome. Clin Nutr 2015; 34: 586-592
  • 14 Fulghesu AM, Romualdi D, Di Florio C, Sanna S, Tagliaferri V, Gambineri A, Tomassoni F, Minerba L, Pasquali R, Lanzone A. Is there a dose-response relationship of metformin treatment in patients with polycystic ovary syndrome? Results from a multicentric study. Hum Reprod 2012; 27: 3057-3066
  • 15 Pisprasert V, Ingram KH, Lopez-Davila MF, Munoz AJ, Garvey WT. Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: Impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans. Diabetes Care 2013; 36: 845-853
  • 16 Asemi Z, Hashemi T, Karamali M, Samimi M, Esmaillzadeh A. Effects of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation, and oxidative stress in gestational diabetes: A double-blind randomized controlled clinical trial. Am J Clin Nutr 2013; 98: 1425-1432
  • 17 Asemi Z, Esmaillzadeh A. DASH diet, insulin resistance, and serum hs-CRP in polycystic ovary syndrome: A randomized controlled clinical trial. Horm Metab Res. 2015; 47: 232-238
  • 18 Jamilian M, Razavi M, Fakhrie Kashan Z, Ghandi Y, Bagherian T, Asemi Z. Metabolic response to selenium supplementation in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf) 2015; 82: 885-891
  • 19 Azadi-Yazdi M, Nadjarzadeh A, Khosravi-Boroujeni H, Salehi-Abargouei A. The effect of vitamin D supplementation on the androgenic profile in patients with polycystic ovary syndrome: A systematic review and meta-analysis of clinical trials. Horm Metab Res 2017; 49: 174-179
  • 20 Razavi M, Jamilian M, Karamali M, Bahmani F, Aghadavod E, Asemi Z. The effects of vitamin D-K-Calcium co-supplementation on endocrine, inflammation, and oxidative stress biomarkers in vitamin d-deficient women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Horm Metab Res 2016; 48: 446-451
  • 21 Sinha-Hikim I, Duran P, Shen R, Lee M, Friedman TC, Davidson MB. Effect of long term vitamin D supplementation on biomarkers of inflammation in Latino and African-American subjects with pre-diabetes and hypovitaminosis D. Horm Metab Res 2015; 47: 280-283
  • 22 Strobel F, Reusch J, Penna-Martinez M, Ramos-Lopez E, Klahold E, Klepzig C, Wehrle J, Kahles H, Badenhoop K. Effect of a randomised controlled vitamin D trial on insulin resistance and glucose metabolism in patients with type 2 diabetes mellitus. Horm Metab Res 2014; 46: 54-58
  • 23 Karamali M, Beihaghi E, Mohammadi AA, Asemi Z. Effects of high-dose vitamin D supplementation on metabolic status and pregnancy outcomes in pregnant women at risk for pre-eclampsia. Horm Metab Res 2015; 47: 867-872
  • 24 Sollid ST, Hutchinson MY, Fuskevag OM, Joakimsen RM, Jorde R. Large individual differences in serum 25-hydroxyvitamin D response to vitamin d supplementation: effects of genetic factors, body mass index, and baseline concentration. Results from a randomized controlled trial. Horm Metab Res 2016; 48: 27-34
  • 25 Selimoglu H, Duran C, Kiyici S, Ersoy C, Guclu M, Ozkaya G, Tuncel E, Erturk E, Imamoglu S. The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome. J Endocrinol Invest 2010; 33: 234-238
  • 26 Raja-Khan N, Shah J, Stetter CM, Lott ME, Kunselman AR, Dodson WC, Legro RS. High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: A randomized, controlled pilot trial. Fertil Steril 2014; 101: 1740-1746
  • 27 Xue Y, Xu P, Xue K, Duan X, Cao J, Luan T, Li Q, Gu L. Effect of vitamin D on biochemical parameters in polycystic ovary syndrome women: A meta-analysis. Arch Gynecol Obstet 2017; 295: 487-496
  • 28 Garg G, Kachhawa G, Ramot R, Khadgawat R, Tandon N, Sreenivas V, Kriplani A, Gupta N. Effect of vitamin D supplementation on insulin kinetics and cardiovascular risk factors in polycystic ovarian syndrome: a pilot study. Endocr Connect 2015; 4: 108-116
  • 29 Teede H, Deeks A, Moran L. Polycystic ovary syndrome: A complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 2010; 8: 41
  • 30 Yang R, Yang S, Li R, Liu P, Qiao J, Zhang Y. Effects of hyperandrogenism on metabolic abnormalities in patients with polycystic ovary syndrome: a meta-analysis. Reprod Biol Endocrinol 2016; 14: 67
  • 31 Ali AT. Polycystic ovary syndrome and metabolic syndrome. Ceska Gynekol 2015; 80: 279-289
  • 32 Maestro B, Molero S, Bajo S, Davila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3). Cell Biochem Funct 2002; 20: 227-232
  • 33 Sergeev IN, Rhoten WB. 1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. Endocrinology 1995; 136: 2852-2861
  • 34 Mohamad MI, El-Sherbeny EE, Bekhet MM. The Effect of Vitamin D Supplementation on Glycemic Control and Lipid Profile in Patients with Type 2 Diabetes Mellitus. J Am Coll Nutr 2016; 35: 399-404
  • 35 Longenecker CT, Hileman CO, Carman TL, Ross AC, Seydafkan S, Brown TT, Labbato DE, Storer N, Tangpricha V, McComsey GA. Vitamin D supplementation and endothelial function in vitamin D deficient HIV-infected patients: a randomized placebo-controlled trial. Antivir Ther 2012; 17: 613-621
  • 36 Salekzamani S, Mehralizadeh H, Ghezel A, Salekzamani Y, Jafarabadi MA, Bavil AS, Gargari BP. Effect of high-dose vitamin D supplementation on cardiometabolic risk factors in subjects with metabolic syndrome: A randomized controlled double-blind clinical trial. J Endocrinol Invest 2016; 39: 1303-1313
  • 37 Razzaghi R, Pourbagheri H, Momen-Heravi M, Bahmani F, Shadi J, Soleimani Z, Asemi Z. The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. J Diabetes Complicat 2017; 31: 766-772
  • 38 Al-Daghri NM, Alkharfy KM, Al-Othman A, El-Kholie E, Moharram O, Alokail MS, Al-Saleh Y, Sabico S, Kumar S, Chrousos GP. Vitamin D supplementation as an adjuvant therapy for patients with T2DM: An 18-month prospective interventional study. Cardiovasc Diabetol 2012; 11: 85
  • 39 Wang H, Xia N, Yang Y, Peng DQ. Influence of vitamin D supplementation on plasma lipid profiles: A meta-analysis of randomized controlled trials. Lipids Health Dis 2012; 11: 42
  • 40 Jorde R, Sneve M, Torjesen P, Figenschau Y. No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin D3 for 1 year. J Intern Med 2010; 267: 462-472
  • 41 Alexander CJ, Tangchitnob EP, Lepor NE. Polycystic ovary syndrome: A major unrecognized cardiovascular risk factor in women. Rev Obstet Gynecol 2009; 2: 232-239
  • 42 Rajpathak SN, Xue X, Wassertheil-Smoller S, Van Horn L, Robinson JG, Liu S, Allison M, Martin LW, Ho GY, Rohan TE. Effect of 5 y of calcium plus vitamin D supplementation on change in circulating lipids: Results from the Women’s Health Initiative. Am J Clin Nutr 2010; 91: 894-899