Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Vitamin D3-fortified milk did not affect glycemic control, lipid profile, and anthropometric measures in patients with type 2 diabetes, a triple-blind randomized clinical trial

Abstract

Background/objectives

The effect of vitamin D on glycemic status of diabetes patients is controversial. The objective was to assess the effect of vitamin D3-fortified milk on cardiometabolic markers of patients with type 2 diabetes.

Subjects/methods

In this randomized triple-blind, placebo-controlled trial, 102 patients (34 males and 68 females) aged 31–74 years with type 2 diabetes were randomized to receive either 250 ml unfortified or 250 ml 1000 IU vitamin D3-fortified milk daily for 9 weeks. Anthropometric characteristics, blood pressure, and serum levels of glucose, insulin, and lipids were determined at baseline and after 9 weeks.

Results

Serum 25-hydroxy vitamin D concentrations improved in the fortified milk group compared to the control group (+14 ± 20 vs. +4 ± 17 ng/ml; P = 0.001). Both groups showed significant increases in serum calcium (P < 0.01) and decreases in total cholesterol, waist and hip circumference, and systolic and diastolic blood pressure (P < 0.001). Also, there was a significant reduction in body mass index of fortified milk group (P < 0.001). None of these changes were statistically significant between the two groups. Glycosylated hemoglobin (HbA1c) significantly decreased in both groups with a more remarkable reduction in the plain milk consumers, making a significant between-group difference (7.5% compared to 3.1%; P = 0.01).

Conclusions

Overall, daily consumption of one cup of milk containing 1000 IU vitamin D3 for 9 weeks substantially improved vitamin D deficiency in patients with type 2 diabetes but it did not affect cardiometabolic parameters over that of plain milk.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144:138–45.

    Article  CAS  Google Scholar 

  2. Engelsen O, Brustad M, Aksnes L, Lund E. Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness. Photochem Photobiol. 2005;81:1287–90.

    Article  CAS  Google Scholar 

  3. Allen RE, Dangour AD, Tedstone AE, Chalabi Z. Does fortification of staple foods improve vitamin D intakes and status of groups at risk of deficiency? A United Kingdom modeling study. Am J Clin Nutr. 2015;102:338–44.

    Article  CAS  Google Scholar 

  4. Carmeliet G, Dermauw V, Bouillon R. Vitamin D signaling in calcium and bone homeostasis: a delicate balance. Best Pract Res Clin Endocrinol Metab. 2015;29:621–31.

    Article  CAS  Google Scholar 

  5. Wimalawansa SJ, Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome. J Steroid Biochem Mol Biol. 2016;175:177–89. https://doi.org/10.1016/j.jsbmb.2016.09.017.

    Article  CAS  PubMed  Google Scholar 

  6. Krishnan AV, Feldman D. Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol Toxicol. 2011;51:311–36.

    Article  CAS  Google Scholar 

  7. Vangoitsenhoven R, Wolden-Kirk H, Lemaire K, Verstuyf A, Verlinden L, Yamamoto Y, et al. Effect of a transcriptional inactive or absent vitamin D receptor on beta-cell function and glucose homeostasis in mice. J Steroid Biochem Mol Biol. 2016;164:309–17. https://doi.org/10.1016/j.jsbmb.2016.02.011.

    Article  CAS  PubMed  Google Scholar 

  8. Wolden-Kirk H, Rondas D, Bugliani M, Korf H, Van Lommel L, Brusgaard K, et al. Discovery of molecular pathways mediating 1,25-dihydroxyvitamin D3 protection against cytokine-induced inflammation and damage of human and male mouse islets of Langerhans. Endocrinology. 2014;155:736–47.

    Article  CAS  Google Scholar 

  9. Takiishi T, Gysemans C, Bouillon R, Mathieu C. Vitamin D and diabetes. Endocrinol Metab Clin N Am. 2010;39:419–46.

    Article  CAS  Google Scholar 

  10. Illario M, Monaco S, Cavallo AL, Esposito I, Formisano P, D’Andrea L, et al. Calcium-calmodulin-dependent kinase II (CaMKII) mediates insulin-stimulated proliferation and glucose uptake. Cell Signal. 2009;21:786–92.

    Article  CAS  Google Scholar 

  11. Gauthier BR, Wollheim CB. Synaptotagmins bind calcium to release insulin. Am J Physiol Endocrinol Metab. 2008;295:E1279–1286.

    Article  CAS  Google Scholar 

  12. Sadiya A, Ahmed SM, Carlsson M, Tesfa Y, George M, Ali SH, et al. Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial. Eur J Clin Nutr. 2015;69:707–11.

    Article  CAS  Google Scholar 

  13. Kampmann U, Mosekilde L, Juhl C, Moller N, Christensen B, Rejnmark L, et al. Effects of 12 weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function, and metabolic markers in patients with type 2 diabetes and vitamin D insufficiency—a double-blind, randomized, placebo-controlled trial. Metabolism. 2014;63:1115–24.

    Article  CAS  Google Scholar 

  14. Ryu OH, Lee S, Yu J, Choi MG, Yoo HJ, Mantero F. A prospective randomized controlled trial of the effects of vitamin D supplementation on long-term glycemic control in type 2 diabetes mellitus of Korea. Endocr J. 2014;61:167–76.

    Article  CAS  Google Scholar 

  15. Elkassaby S, Harrison LC, Mazzitelli N, Wentworth JM, Colman PG, Spelman T, et al. A randomised controlled trial of high dose vitamin D in recent-onset type 2 diabetes. Diabetes Res Clin Pract. 2014;106:576–82.

    Article  CAS  Google Scholar 

  16. Nikooyeh B, Neyestani TR, Farvid M, Alavi-Majd H, Houshiarrad A, Kalayi A, et al. Daily consumption of vitamin D− or vitamin D+ calcium-fortified yogurt drink improved glycemic control in patients with type 2 diabetes: a randomized clinical trial. Am J Clin Nutr. 2011;93:764–71.

    Article  CAS  Google Scholar 

  17. Shab-Bidar S, Neyestani TR, Djazayery A, Eshraghian MR, Houshiarrad A, Gharavi A, et al. Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial. BMC Med. 2011;9:125.

    Article  CAS  Google Scholar 

  18. Akhlaghi M, Kamali M, Dastsouz F, Sadeghi F, Amanat S. Increased waist-to-height ratio may contribute to age-related increase in cardiovascular risk factors. Int J Prev Med. 2016;7:68.

    Article  Google Scholar 

  19. Lee PH, Macfarlane DJ, Lam TH, Stewart SM. Validity of the International Physical Activity Questionnaire Short Form (IPAQ-SF): a systematic review. Int J Behav Nutr Phys Act. 2011;8:115.

    Article  Google Scholar 

  20. Hanwell HE, Vieth R, Cole DE, Scillitani A, Modoni S, Frusciante V, Ritrovato G, Chiodini I, Minisola S, Carnevale V. Sun exposure questionnaire predicts circulating 25-hydroxyvitamin D concentrations in Caucasian hospital workers in southern Italy. J Steroid Biochem Mol Biol. 2010;121:334–7.

    Article  CAS  Google Scholar 

  21. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.

    Article  CAS  Google Scholar 

  22. McAuley KA, Williams SM, Mann JI, Walker RJ, Lewis-Barned NJ, Temple LA, Duncan AW. Diagnosing insulin resistance in the general population. Diabetes Care. 2001;24:460–4.

    Article  CAS  Google Scholar 

  23. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  Google Scholar 

  24. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85:2402–10.

    Article  CAS  Google Scholar 

  25. Badenhoop K, Kahles H, Penna-Martinez M. Vitamin D, immune tolerance, and prevention of type 1 diabetes. Curr Diabetes Rep. 2012;12:635–42.

    Article  CAS  Google Scholar 

  26. Pilz S, Kienreich K, Rutters F, de Jongh R, van Ballegooijen AJ, Grübler M, et al. Role of vitamin D in the development of insulin resistance and type 2 diabetes. Curr Diabetes Rep. 2013;13: 261–70.

    Article  CAS  Google Scholar 

  27. Krul-Poel YH, Westra S, ten Boekel E, ter Wee MM, van Schoor NM, van Wijland H, et al. Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes (sunny trial): a randomized placebo-controlled trial. Diabetes Care. 2015;38: 1420–6.

    Article  CAS  Google Scholar 

  28. Lips P, Eekhoff M, van Schoor N, Oosterwerff M, de Jongh R, Krul-Poel Y, et al. Vitamin D and type 2 diabetes. J Steroid Biochem Mol Biol.2017;173:280–285.

    Article  CAS  Google Scholar 

  29. Soheilykhah S, Mojibian M, Moghadam MJ, Shojaoddiny-Ardekani A. The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy. Gynecol Endocrinol. 2013;29:396–9.

    Article  CAS  Google Scholar 

  30. Soric MM, Renner ET, Smith SR. Effect of daily vitamin D supplementation on HbA1c in patients with uncontrolled type 2 diabetes mellitus: a pilot study. J Diabetes. 2012;4:104–5.

    Article  CAS  Google Scholar 

  31. Dutta D, Mondal SA, Choudhuri S, Maisnam I, Hasanoor Reza AH, Bhattacharya B, et al. Vitamin-D supplementation in prediabetes reduced progression to type 2 diabetes and was associated with decreased insulin resistance and systemic inflammation: an open label randomized prospective study from Eastern India. Diabetes Res Clin Pract. 2014;103:e18–23.

    Article  CAS  Google Scholar 

  32. Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in non-diabetic adults. Diabetes Care. 2007;30:980–6.

    Article  CAS  Google Scholar 

  33. Jafari T, Faghihimani E, Feizi A, Iraj B, Javanmard SH, Esmaillzadeh A, et al. Effects of vitamin D-fortified low fat yogurt on glycemic status, anthropometric indexes, inflammation, and bone turnover in diabetic postmenopausal women: a randomised controlled clinical trial. Clin Nutr. 2016;35:67–76.

    Article  CAS  Google Scholar 

  34. Ostman EM, Liljeberg Elmståhl HG, Björck IM. Inconsistency between glycemic and insulinemic responses to regular and fermented milk products. Am J Clin Nutr. 2001;74:96–100.

    Article  CAS  Google Scholar 

  35. Yamaguchi T, Kanazawa I, Takaoka S, Sugimoto T. Serum calcium is positively correlated with fasting plasma glucose and insulin resistance, independent of parathyroid hormone, in male patients with type 2 diabetes mellitus. Metabolism. 2011;60:1334–9.

    Article  CAS  Google Scholar 

  36. Sun G, Vasdev S, Martin GR, Gadag V, Zhang H. Altered calcium homeostasis is correlated with abnormalities of fasting serum glucose, insulin resistance, and beta-cell function in the Newfoundland population. Diabetes. 2005;54:3336–9.

    Article  CAS  Google Scholar 

  37. Satin LS. Localized calcium influx in pancreatic beta-cells: its significance for Ca2+-dependent insulin secretion from the islets of Langerhans. Endocrine. 2000;13:251–62.

    Article  CAS  Google Scholar 

  38. Tai K, Need AG, Horowitz M, Chapman IM. Vitamin D, glucose, insulin, and insulin sensitivity. Nutrition. 2008;24:279–85.

    Article  CAS  Google Scholar 

  39. von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient—a randomised, placebo-controlled trial. Br J Nutr. 2010;103:549–55.

    Article  Google Scholar 

  40. Sepehrmanesh Z, Kolahdooz F, Abedi F, Mazroii N, Assarian A, Asemi Z, et al. Vitamin D supplementation affects the beck depression inventory, insulin resistance, and biomarkers of oxidative stress in patients with major depressive disorder: a randomized, controlled clinical trial. J Nutr. 2016;146:243–8.

    Article  CAS  Google Scholar 

  41. Yeow TP, Lim SL, Hor CP, Khir AS, Wan Mohamud WN, Pacini G. Impact of vitamin D replacement on markers of glucose metabolism and cardio-metabolic risk in women with former gestational diabetes—a double-blind, randomized controlled trial. PLoS One. 2015;10:e0129017.

    Article  Google Scholar 

  42. Barchetta I, Del Ben M, Angelico F, Di Martino M, Fraioli A, La Torre G, et al. No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. BMC Med. 2016;14:92.

    Article  Google Scholar 

  43. Breslavsky A, Frand J, Matas Z, Boaz M, Barnea Z, Shargorodsky M. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin Nutr. 2013;32:970–5.

    Article  CAS  Google Scholar 

  44. Strobel F, Reusch J, Penna-Martinez M, Ramos-Lopez E, Klahold E, Klepzig C, et al. 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.

    CAS  PubMed  Google Scholar 

  45. Ryu OH, Chung W, Lee S, Hong KS, Choi MG, Yoo HJ. The effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with type 2 diabetes. Korean J Intern Med. 2014;29:620–9.

    Article  CAS  Google Scholar 

  46. Patel P, Poretsky L, Liao E. Lack of effect of subtherapeutic vitamin D treatment on glycemic and lipid parameters in Type 2 diabetes: a pilot prospective randomized trial. J Diabetes. 2010;2:36–40.

    Article  Google Scholar 

  47. 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;50:303–12.

    Article  CAS  Google Scholar 

  48. Aslam M, Aggarwal S, Sharma KK, Galav V, Madhu SV. Postprandial hypertriglyceridemia predicts development of insulin resistance glucose intolerance and type 2 diabetes. PLoS One. 2016;11:e0145730.

    Article  Google Scholar 

  49. Muñoz-Aguirre P, Flores M, Macias N, Quezada AD, Denova-Gutiérrez E, Salmerón J. The effect of vitamin D supplementation on serum lipids in postmenopausal women with diabetes: a randomized controlled trial. Clin Nutr. 2015;34:799–804.

    Article  Google Scholar 

  50. Pilz S, Gaksch M, Kienreich K, Grübler M, Verheyen N, Fahrleitner-Pammer A, et al. Effects of vitamin D on blood pressure and cardiovascular risk factors: a randomized controlled trial. Hypertension. 2015;65:1195–201.

    Article  CAS  Google Scholar 

  51. Boon N, Hul GB, Stegen JH, Sluijsmans WE, Valle C, Langin D, et al. An intervention study of the effects of calcium intake on faecal fat excretion, energy metabolism and adipose tissue mRNA expression of lipid-metabolism related proteins. Int J Obes. 2007;31:1704–12.

    Article  CAS  Google Scholar 

  52. Bozic M, Guzmán C, Benet M, Sánchez-Campos S, García-Monzón C, Gari E, et al. Hepatocyte vitamin D receptor regulates lipid metabolism and mediates experimental diet-induced steatosis. J Hepatol. 2016;65:748–57.

    Article  CAS  Google Scholar 

  53. Soares MJ, Murhadi LL, Kurpad AV, Chan She Ping-Delfos WL, Piers LS. Mechanistic roles for calcium and vitamin D in the regulation of body weight. Obes Rev. 2012;13:592–605.

    Article  CAS  Google Scholar 

  54. Pathak K, Soares MJ, Calton EK, Zhao Y, Hallett J. Vitamin D supplementation and body weight status: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2014;15:528–37.

    Article  CAS  Google Scholar 

  55. Cicero AF, Aubin F, Azais-Braesco V, Borghi C. Do the lactotripeptides isoleucine-proline-proline and valine-proline-proline reduce systolic blood pressure in European subjects? A meta-analysis of randomized controlled trials. Am J Hypertens. 2013;26: 442–9.

    Article  CAS  Google Scholar 

  56. Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, et al. Effect of vitamin D supplementation on blood pressure: a systematic review and meta-analysis incorporating individual patient data. JAMA Intern Med. 2015;175: 745–54.

    Article  Google Scholar 

Download references

Acknowledgements

The results presented herein were extracted from the thesis written by Ms. Saedeh Salehi. The project was financially supported by Shiraz University of Medical Sciences, Grant No. 93-7350.

Author information

Authors and Affiliations

Authors

Contributions

Author contributions

S.S. and M.A. designed the study. S.S., F.S., M.A.H., and M.R. conducted the research. S.S. and M.A. analyzed the data and drafted the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Masoumeh Akhlaghi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salehi, S., Sadeghi, F., Akhlaghi, M. et al. Vitamin D3-fortified milk did not affect glycemic control, lipid profile, and anthropometric measures in patients with type 2 diabetes, a triple-blind randomized clinical trial. Eur J Clin Nutr 72, 1083–1092 (2018). https://doi.org/10.1038/s41430-017-0062-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-017-0062-1

Search

Quick links