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:

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

European Journal of Clinical Nutrition volume 72, pages 526–533 (2018)Cite this article

Subjects

Abstract

Background/objectives

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.

Subjects/methods

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.

Results

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.

Conclusions

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.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

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

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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

Authors and Affiliations

  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

Authors
  1. Rolf Jorde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guri Grimnes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rolf Jorde.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jorde, R., Grimnes, G. Exploring the association between serum 25-hydroxyvitamin D and serum lipids—more than confounding?. Eur J Clin Nutr 72, 526–533 (2018). https://doi.org/10.1038/s41430-018-0088-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-018-0088-z

This article is cited by

Search

Advanced search

Quick links