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Information on the latest vitamin D news and research.

Find out more information on deficiency, supplementation, sun exposure, and how vitamin D relates to your health.

Vitamin D and lipids: More research required?

An editorial published in this month’s issue of Circulation examined the evidence for the role of vitamin D in lipid profiles.

Jorde R, Grimnes G. Vitamin d and lipids: do we really need more studies? Circulation. 2012;126(3):252-4.

Numerous epidemiological studies correlate higher 25(OH)D levels with a decreased risk of cardiovascular disease. For example:

  • The Norwegian Tromsø study followed 4,751 participants for 11 years and found that those in the lowest serum 25(OH)D quartile had a 32% greater risk of mortality from cardiovascular disease than those in the  highest serum 25(OH)D quartile.
  • The Framingham Offspring Study also found a significant inverse association between vitamin D levels and heart disease. Among its 1,739 participants, those with serum 25(OH)D levels <10 ng/mL had a hazard ratio of 1.80 for a cardiovascular event as compared to participants with serum 25(OH)D levels >15 ng/mL.

One possible mechanism proposed for these observations is that vitamin D has a lipid-lowering effect. In general, the observational data show that higher serum 25(OH)D levels are associated with more favorable lipid profiles. However, randomized controlled trials (RCT) are necessary to establish a causal role for vitamin D in heart disease prevention. These trials are costly, time-consuming, and require thousands of subjects to achieve statistically significant results.

The authors of this editorial therefore promote the cost-effective alternative performed by Ponda et al. From a pool of > 4 million laboratory tests, 108,711 individuals were selected who had undergone repeated serum 25(OH)D and lipid testing 4 to 26 weeks apart. In men and women, they found that those with higher serum 25(OH)D levels had lower total cholesterol, LDL cholesterol, and triglycerides and higher levels of HDL cholesterol.

Of these 108, 711 participants, 6,260 had 25(OH)D serum levels <20 ng/mL that had increased to between 30 and 100 ng/mL after the second blood measurement. 81% of the increase in this group was from vitamin D2 supplementation, and no statistically significant improvement in lipid profiles was observed. A group of 2,332 individuals who had blood levels <20 ng/mL at their initial serum 25(OH)D test as well as following the second test served as a control group.

The authors compare these results with the conclusions of the only published meta-analysis involving vitamin D supplementation and lipid profiles, which involved 12 clinical trials and 1,346 participants. The only statistically significant effect reported was a small increase in LDL cholesterol of 3.23 mg/mL. Limitations of the trials included small sample sizes, variations in vitamin D forms and doses, study duration from 8 weeks to 3 years, at baseline the majority of the subjects were not vitamin D deficient, and no studies specified high lipid levels as inclusion criteria.

The authors then attempt to explain the inconsistent results of the meta-analysis with those of the Ponda et al. data. Because the patients who received treatment for vitamin D deficiency were more likely to have a diagnosis of a lipid disorder than the subset of patients that remained vitamin D deficient, they speculate that the physicians of these patients would also have advised some form of treatment for their hyperlipidemia along with their vitamin D deficiency, and that it was therefore reasonable to expect a positive change in the lipid profile.

Because no such change was observed and the results of the meta-analysis revealed a statistically significant rise in LDL cholesterol with vitamin D supplementation, the authors go so far as to suggest that the study design of Ponda et al. potentially masked an effect of vitamin D on lipid profiles. This concern, coupled with the data from observational studies showing the greatest benefit of vitamin D on cardiovascular health occurs with 25(OH)D serum levels above 15 ng/mL, led the authors to conclude that further RCT’s examining the effect of vitamin D supplementation on lipid levels should be restricted to individuals that are both vitamin D deficient and hyperlipidemic.

At present, supplementation with vitamin D does not appear to improve serum lipid profiles. However, the Ponda et al. data cited by the authors utilized D2 supplementation, as did roughly a third of the trials included in the meta-analysis. It is possible that D3 supplements or UV radiation could yield different results, or that improvement in the lipid profile is not the mechanism by which vitamin D and UV exposure have been shown to reduce the risk of cardiovascular disease.

  About: Rebecca Oshiro

Rebecca has a master of science degree in nutrition from Bastyr University where she conducted a university-funded study on vitamin D and athletic performance. She has a certificate in applied behavior analysis from the Florida Institute of Technology, and her passion is using behavioral technologies to assist others in making meaningful changes in their lives.

7 Responses to Vitamin D and lipids: More research required?

  1. Umileritac@aol.com says:

    Very interesting!
    Rita Umile

  2. Ian says:

    Is anyone still using D2 in experimentation?
    D2 is an example of where pharmaceutical dominance/manipulation has caused a lot of confusion and possibly negative results

  3. Rebecca Oshiro says:

    Ian, I looked into the meta-analysis cited here and found that it analyzed the results of 12 RCT’s. Of these 12, 7 used D3 and the remaining used either D2, alpha-calcidol, or calcitriol. Studies administering a daily dose of vitamin D dosed anywhere from 300 to 3332 IU/day. Two of the studies administered a single, large dose and one administered vitamin D to participants every two weeks. Duration ranged anywhere from 42 days to 3 years.

  4. Only 6% of the people has an increase in vitamin D levels.
    Here are some of the reasons for increased vitamin D levels
    Have recovered from surgery
    Have recovered from trauma
    Have recovered from a burn
    Have recovered from Cancer
    Have recovered from pregnancy
    Have recovered from Earthquake trauma
    Had more sunshine (vacation, season, etc.)
    Lost weight
    Stopped medications which had reduced vitamin D levels
    Gut absorption no longer a problem
    Kidney operating again perhaps transplant
    Supplementation (D2, D3, etc)
    – – – Details at http://www.vitamindwiki.com/tiki-index.php?page_id=3010

  5. Margaret says:

    Why is supplementation with D2 even permissable, at all, in these scientific studies? What type of studies support D2 as helpful, in any capacity, as compared to D3?

    • Brant Cebulla says:

      Good question Margaret. I would say that D2 supplementation in RCTs is becoming rarer and rarer (though you’ll still see them from time to time), but in meta-analysis, D2 trials will always pop up as we look at past trials.

      I have spoken to one researcher who could only use D2 in his trial; something about needing to get the product from a pharmacy for IRB approval(?), and as you know, pharmacies usually only stock D2. Perhaps a researcher here cares to offer some insight on why using D2 in trials would be more convenient for their protocol?

  6. Rebecca Oshiro says:

    “Supplemental vitamin D is available in 2 distinct forms: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Pharmacopoeias have officially regarded these 2 forms as equivalent and interchangeable, yet this presumption of equivalence is based on studies of rickets prevention in infants conducted 70 y ago. The emergence of 25-hydroxyvitamin D as a measure of vitamin D status provides an objective, quantitative measure of the biological response to vitamin D administration. As a result, vitamin D3 has proven to be the more potent form of vitamin D in all primate species, including humans. Despite an emerging body of evidence suggesting several plausible explanations for the greater bioefficacy of vitamin D3, the form of vitamin D used in major preparations of prescriptions in North America is vitamin D2. The case that vitamin D2 should no longer be considered equivalent to vitamin D3 is based on differences in their efficacy at raising serum 25-hydroxyvitamin D, diminished binding of vitamin D2 metabolites to vitamin D binding protein in plasma, and a nonphysiologic metabolism and shorter shelf life of vitamin D2. Vitamin D2, or ergocalciferol, should not be regarded as a nutrient suitable for supplementation or fortification. ”