The Effects of Calcium, Vitamins D and K co-Supplementation on Markers of Insulin Metabolism and Lipid Profiles in Vitamin D-Deficient Women with Polycystic Ovary Syndrome

Abstract

Background

Data on the effects of calcium, vitamins D and K co-supplementation on markers of insulin metabolism and lipid profiles among vitamin D-deficient women with polycystic ovary syndrome (PCOS) are scarce.

Objective

This study was done to determine the effects of calcium, vitamins D and K co-supplementation on markers of insulin metabolism and lipid profiles in vitamin D-deficient women with PCOS.

Methods

This randomized double-blind, placebo-controlled trial was conducted among 55 vitamin D-deficient women diagnosed with PCOS aged 18–40 years old. Subjects were randomly assigned into 2 groups to intake either 500 mg calcium, 200 IU vitamin D and 90 µg vitamin K supplements (n=28) or placebo (n=27) twice a day for 8 weeks.

Results

After the 8-week intervention, compared with the placebo, joint calcium, vitamins D and K supplementation resulted in significant decreases in serum insulin concentrations (−1.9±3.5 vs. +1.8±6.6 µIU/mL, P=0.01), homeostasis model of assessment-estimated insulin resistance (−0.4±0.7 vs. +0.4±1.4, P=0.01), homeostasis model of assessment-estimated b cell function (−7.9±14.7 vs. +7.0±30.3, P=0.02) and a significant increase in quantitative insulin sensitivity check index (+0.01±0.01 vs. −0.008±0.03, P=0.01). In addition, significant decreases in serum triglycerides (−23.4±71.3 vs. +9.9±39.5 mg/dL, P=0.03) and VLDL-cholesterol levels (−4.7±14.3 vs. +2.0±7.9 mg/dL, P=0.03) was observed following supplementation with combined calcium, vitamins D and K compared with the placebo.

Conclusion

Overall, calcium, vitamins D and K co-supplementation for 8 weeks among vitamin D-deficient women with PCOS had beneficial effects on markers of insulin metabolism, serum triglycerides and VLDL-cholesterol levels.

Key words

supplementation - polycystic ovary syndrome - insulin metabolism - lipid profiles

Publication History

Received: 14 October 2016
Received: 20 January 2017

Accepted: 22 February 2017

Article published online:
13 April 2017

• References

• 1 Pasquali R, Gambineri A. A comprehensive approach in diagnosing the polycystic ovary syndrome. Womens Health (Lond) 2015; 11: 501-512
• 2 Vagi SJ, Azziz-Baumgartner E, Sjodin A. et al. Exploring the potential association between brominated diphenyl ethers, polychlorinated biphenyls, organochlorine pesticides, perfluorinated compounds, phthalates, and bisphenol A in polycystic ovary syndrome: a case-control study. BMC Endocr Disord 2014; 14: 86 DOI: 10.1186/1472-6823-14-86.
• 3 Dhesi AS, Murtough KL, Lim JK. et al. Metabolic screening in patients with polycystic ovary syndrome is largely underutilized among obstetrician-gynecologists. am j obstet gynecol 2016; 215: 579.e1-579.e5 DOI: 10.1016/j.ajog.2016.07.
• 4 DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril 2005; 83: 1454-1460
• 5 Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 2001; 111: 607-613
• 6 Tomlinson J, Millward A, Stenhouse E. et al. Type 2 diabetes and cardiovascular disease in polycystic ovary syndrome: what are the risks and can they be reduced?. Diabet Med 2010; 27: 498-515
• 7 Chakraborty P, Ghosh S, Goswami SK. et al. Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome. Biol Trace Elem Res 2013; 152: 9-15
• 8 Kim JJ, Choi YM, Chae SJ. et al. Vitamin D deficiency in women with polycystic ovary syndrome. Clin Exp Reprod Med 2014; 41: 80-85
• 9 Asemi Z, Foroozanfard F, Hashemi T. et al. 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
• 10 Asemi Z, Raygan F, Bahmani F. et al. The effects of vitamin D, K and calcium co-supplementation on carotid intima-media thickness and metabolic status in overweight type 2 diabetic patients with CHD. Br J Nutr 2016; 116: 286-293
• 11 Gagnon C, Daly RM, Carpentier A. et al. Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and beta-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: A pilot randomized, placebo-controlled trial. PLoS One 2014; 9: e109607 DOI: 10.1371/journal.pone.0109607. eCollection 2014
• 12 Yoshida M, Jacques PF, Meigs JB. et al. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care 2008; 31: 2092-2096
• 13 Maestro B, Molero S, Bajo S. et al. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3). Cell Biochem Funct 2002; 20: 227-232
• 14 Sergeev IN, Rhoten WB. 1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. Endocrinology 1995; 136: 2852-2861
• 15 Lee NK, Sowa H, Hinoi E. et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456-469
• 16 Tabesh M, Azadbakht L, Faghihimani E. et al. Effects of calcium-vitamin D co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: A randomised controlled clinical trial. Diabetologia 2014; 57: 2038-2047
• 17 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
• 18 Jamilian M, Foroozanfard F, Bahmani F. et al. Effects of zinc supplementation on endocrine outcomes in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Biol Trace Elem Res 2016; 170: 271-278
• 19 Pisprasert V, Ingram KH, Lopez-Davila MF. et al. 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
• 20 Kayaniyil S, Vieth R, Retnakaran R. et al. Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes. Diabetes Care 2010; 33: 1379-1381
• 21 Dalgard C, Petersen MS, Weihe P. et al. Vitamin D status in relation to glucose metabolism and type 2 diabetes in septuagenarians. Diabetes Care 2011; 34: 1284-1288
• 22 Guducu N, Gormus U, Kutay SS. et al. 25-Hydroxyvitamin D levels are related to hyperinsulinemia in polycystic ovary syndrome. Gynecol Endocrinol 2014; 30: 557-560
• 23 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
• 24 Tehrani HG, Mostajeran F, Shahsavari S. The effect of calcium and vitamin D supplementation on menstrual cycle, body mass index and hyperandrogenism state of women with poly cystic ovarian syndrome. J Res Med Sci 2014; 19: 875-880
• 25 Pittas AG, Harris SS, Stark PC. et al. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care 2007; 30: 980-986
• 26 Pal L, Berry A, Coraluzzi L. et al. Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome. Gynecol Endocrinol 2012; 28: 965-968
• 27 Legro RS. Polycystic ovary syndrome and cardiovascular disease: A premature association?. Endocr Rev 2003; 24: 302-312
• 28 Cassar S, Teede HJ, Harrison CL. et al. Biomarkers and insulin sensitivity in women with PCOS: Characteristics and predictive capacity. Clin Endocrinol (Oxf) 2015; 83: 50-58
• 29 Unfer V, Porcaro G. Updates on the myo-inositol plus D-chiro-inositol combined therapy in polycystic ovary syndrome. Expert Rev Clin Pharmacol 2014; 7: 623-631
• 30 Reddi K, Henderson B, Meghji S. et al. Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by naphthoquinone (vitamin K) compounds. Cytokine 1995; 7: 287-290
• 31 Jorde R, Grimnes G. Vitamin D and metabolic health with special reference to the effect of vitamin D on serum lipids. Prog Lipid Res 2011; 50: 303-312
• 32 Ditscheid B, Keller S, Jahreis G. Cholesterol metabolism is affected by calcium phosphate supplementation in humans. J Nutr 2005; 135: 1678-1682
• 33 Major GC, Alarie F, Dore J. et al. Supplementation with calcium+vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations. Am J Clin Nutr 2007; 85: 54-59
• 34 Rajpathak SN, Xue X, Wassertheil-Smoller S. et al. 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
• 35 Hsia J, Heiss G, Ren H. et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007; 115: 846-854
• 36 Macut D, Bjekic-Macut J, Savic-Radojevic A. Dyslipidemia and oxidative stress in PCOS. Front Horm Res 2013; 40: 51-63
• 37 Ozler S, Oztas E, Tokmak A. et al. The association of thiol/disulphide homeostasis and lipid accumulation index with cardiovascular risk factors in overweight adolescents with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2016; 84: 516-523
• 38 Reid IR. Effects of calcium supplementation on circulating lipids: potential pharmacoeconomic implications. Drugs Aging 2004; 21: 7-17
• 39 Cho HJ, Kang HC, Choi SA. et al. The possible role of Ca2+ on the activation of microsomal triglyceride transfer protein in rat hepatocytes. Biol Pharm Bull 2005; 28: 1418-1423
• 40 Wehmeier K, Beers A, Haas MJ. et al. Inhibition of apolipoprotein AI gene expression by 1, 25-dihydroxyvitamin D3. Biochim Biophys Acta 2005; 1737: 16-26
• 41 Irani M, Seifer DB, Grazi RV. et al. Vitamin D supplementation decreases TGF-beta1 bioavailability in PCOS: A randomized placebo-controlled Trial. J Clin Endocrinol Metab 2015; 100: 4307-4314
• 42 Garg G, Kachhawa G, Ramot R. et al. 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