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Exploring the association between serum 25-hydroxyvitamin D and serum lipids—more than confounding?

European Journal of Clinical Nutritionvolume 72pages526533 (2018) | Download Citation



In observational, but not interventional, studies there are strong associations between serum 25-hydroxyvitamin D (25(OH)D) and serum lipids. The purpose of the present study was to examine potential causes of this association.


A total of 17,411 subjects participating in the seventh survey of the Tromsø Study were included in the cross-sectional study; 5384 subjects who participated in both the sixth and seventh survey were included in the longitudinal study; 2365 subjects who participated in both the fourth and seventh survey were included in the genetic study; and 479 subjects with impaired glucose tolerance were included in the vitamin D binding protein (DBP) analyses.


For serum 25(OH)D, there were strong and positive associations with LDL-, HDL-, and total-cholesterol, and a negative association with triglycerides that remained after adjustment for gender, age, BMI, diet, supplements, and lifestyle factors. These associations were seen in winter as well as summer. Except for serum cholesterol, change of season for blood sampling did not affect lipid levels. However, when analyzing separately, subjects with low or no intake of vitamin D supplements, fish oil and fat fish, only the association between 25(OH)D and HDL-cholesterol remained significant. Serum DBP or single-nucleotide polymorphisms related to 25(OH)D had no relation to lipid levels.


The associations between 25(OH)D and lipids (except for HDL-cholesterol) can be explained by known confounding factors. However, for HDL-cholesterol, the cause of the association with 25(OH)D still remains unknown.

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  1. 1.

    DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004;80(6 Suppl):1689S–96S.

  2. 2.

    Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168:1174–80.

  3. 3.

    Melamed ML, Muntner P, Michos ED, Uribarri J, Weber C, Sharma J, et al. Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to 2004. Arterioscler Thromb Vasc Biol. 2008;28:1179–85.

  4. 4.

    Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, et al. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008;168:1340–9.

  5. 5.

    Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168:1629–37.

  6. 6.

    Gaksch M, Jorde R, Grimnes G, Joakimsen R, Schirmer H, Wilsgaard T. et al. Vitamin D and mortality: individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium. PLoS ONE. 2017;12:e0170791

  7. 7.

    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.

  8. 8.

    Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326:469.

  9. 9.

    Scragg R, Stewart AW, Waayer D, Lawes CMM, Toop L, Sluyter J, et al. Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the vitamin D assessment study: a randomized clinical trial. JAMA Cardiol. 2017;2:608–16.

  10. 10.

    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;267:462–72.

  11. 11.

    Liu D, Fernandez BO, Hamilton A, Lang NN, Gallagher JM, Newby DE, et al. UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase. J Invest. 2014;134:1839–46.

  12. 12.

    Fleury N, Geldenhuys S, Gorman S. Sun exposure and its effects on human health: mechanisms through which sun exposure could reduce the risk of developing obesity and cardiometabolic dysfunction. Int J Environ Res Public Health. 2016;13:E999.

  13. 13.

    Minihane AM. Fish oil omega-3 fatty acids and cardio-metabolic health, alone or with statins. Eur J Clin Nutr. 2013;67:536–40.

  14. 14.

    Jacobsen BK, Eggen AE, Mathiesen EB, Wilsgaard T, Njølstad I. Cohort profile: the Tromso Study. Int J Epidemiol. 2012;41:961–7.

  15. 15.

    Sollid ST, Hutchinson MY, Berg V, Fuskevåg OM, Figenschau Y, Thorsby PM, et al. Effects of vitamin D binding protein phenotypes and vitamin D supplementation on serum total 25(OH)D and directly measured free 25(OH)D. Eur J Endocrinol. 2016;174:445–52.

  16. 16.

    Jorde R, Schirmer H, Wilsgaard T, Joakimsen RM, Mathiesen EB, Njølstad I, et al. Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromsø Study. PLoS ONE. 2012;7:e37295.

  17. 17.

    Grimnes G, Almaas B, Eggen AE, Emaus N, Figenschau Y, Hopstock LA, et al. Effect of smoking on the serum levels of 25-hydroxyvitamin D depends on the assay employed. Eur J Endocrinol. 2010;163:339–48.

  18. 18.

    Jorde R, Sollid ST, Svartberg J, Schirmer H, Joakimsen RM, Njølstad I, et al. Vitamin D 20,000 IU per week for five years does not prevent progression from prediabetes to diabetes. J Clin Endocrinol Metab. 2016;101:1647–55.

  19. 19.

    Johnsen MS, Grimnes G, Figenschau Y, Torjesen PA, Almås B, Jorde R. Serum free and bio-available 25-hydroxyvitamin D correlate better with bone density than serum total 25-hydroxyvitamin D. Scand J Clin Lab Invest. 2014;74:177–83.

  20. 20.

    Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocriol Metab. 1999;84:3666–72.

  21. 21.

    Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, et al. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res. 2011;26:1609–16.

  22. 22.

    Qin Y, Zhou Y, Chen SH, Zhao XL, Ran L, Zeng XL, et al. Fish oil supplements lower serum lipids and glucose in correlation with a reduction in plasma fibroblast growth factor 21 and prostaglandin E2 in nonalcoholic fatty liver disease associated with hyperlipidemia: a randomized clinical trial. PLoS ONE. 2015;10:e0133496.

  23. 23.

    Ockene IS, Chiriboga DE, Stanek EJ 3rd, Harmatz MG, Nicolosi R, Saperia G, et al. Seasonal variation in serum cholesterol levels: treatment implications and possible mechanisms. Arch Intern Med. 2004;164:863–70.

  24. 24.

    Ponda MP, Liang Y, Kim J, Hutt R, Dowd K, Gilleaudeau P, et al. A randomized clinical trial in vitamin D-deficient adults comparing replenishment with oral vitamin D3 with narrow-band UV type B light: effects on cholesterol and the transcriptional profiles of skin and blood. Am J Clin Nutr. 2017;105:1230–8.

  25. 25.

    Mazidi M, Rezaie P, Vatanparast H, Kengne AP. Effect of statins on serum vitamin D concentrations: a systematic review and meta-analysis. Eur J Clin Invest. 2017;47:93–101.

  26. 26.

    Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, Cooper JD, et al. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013;10:e1001383.

  27. 27.

    Ooi EM, Afzal S, Nordestgaard BG. Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: Mendelian randomization study. Circ Cardiovasc Genet. 2014;7:650–8.

  28. 28.

    Holick MF, MacLaughlin JA, Clark MB, Holick SA, Potts JT Jr, Anderson RR, et al. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science. 1980;210:203–5.

  29. 29.

    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.

  30. 30.

    Cho HJ, Kang HC, Choi SA, Ju YC, Lee HS, Park HJ. The possible role of Ca2+ on the activation of microsomal triglyceride transfer protein in rat hepatocytes. Biol Pharm Bull. 2005;28:1418–23.

  31. 31.

    Zemel MB, Shi H, Greer B, Dirienzo D, Zemel PC. Regulation of adiposity by dietary calcium. ASEB J. 2000;14:1132–8.

  32. 32.

    Kamycheva E, Jorde R, Figenschau Y, Haug E. Insulin sensitivity in subjects with secondary hyperparathyroidism and the effect of a low serum 25-hydroxyvitamin D level on insulin sensitivity. J Endocrinol Invest. 2007;30:126–32.

  33. 33.

    Howard BV. Insulin resistance and lipid metabolism. Am J Cardiol. 1999;84:28J–32J.

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The superb assistance from the staff at the Clinical Research Unit at the University Hospital of North Norway is gratefully acknowledged. The study was supported by grants from the Novo Nordisk foundation (grant number R195-A16126), the North Norway Regional Health Authorities (grant number 6856/SFP1029-12), UiT The Arctic University of Norway, the Norwegian Diabetes Association, and the Research Council of Norway (grant number 184766).

Author information


  1. Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway

    • Rolf Jorde
    •  & Guri Grimnes
  2. Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway

    • Rolf Jorde
    •  & Guri Grimnes


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The authors declare that they have no conflict of interest.

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Correspondence to Rolf Jorde.

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