One-dose-might-not-fit-all with vitamin D (December 2023)

—Carrie Dennett, MPH, RDN

About a decade ago, there was a flurry of vitamin D research underway to test the theory that low blood levels of vitamin D contributed to just about every chronic disease under the sun. But over the years, potential links between vitamin D and one health condition after another broke, although the link between vitamin D and bone health still seemed certain. Last year, data from the Vitamin D and Omega-3 Trial (VITAL) appeared to knock down even that last bit of nutritional “certainty”—participants randomly assigned to take 2,000 IU (international units) of vitamin D3 per day were no less likely to suffer a bone fracture than those taking a placebo pill.

Researchers followed the 25,871 VITAL participants—half were women and 20% were Black—for an average of 5.3 years. That was long enough to observe 769 new fractures in the vitamin D group, and 782 fractures in the placebo group. Yes, more fractures happened in the placebo group, but the difference was not statistically significant—in other words, the difference was small enough that it could simply be due to chance.

An accompanying editorial—written by high-caliber vitamin D researchers—recommended that providers stop testing vitamin D levels or recommending taking vitamin D supplements in the general population, and that “people should stop taking vitamin D supplements to prevent major diseases or extend life.”

VITAL researchers previously found that vitamin D did not reduce the risk of developing cancer, having a heart attack or stroke, dying from cardiovascular disease, suffering a fall, or experiencing depression. It also did not affect body fat. The Vitamin D and Type 2 Diabetes (D2d) randomized controlled trial found that after 2.5 years, taking 4,000 IU of vitamin D3 daily was no better than a placebo at preventing diabetes in high-risk adults.

As it turns out, that wasn’t the end of the story. A new analysis of data from 16,515 VITAL participants, published in January in the JAMA Network Open, found that vitamin D supplementation was associated with a number of positive health effects, but only in people with a BMI less than 25. Along those lines, the study results showed that while vitamin D supplementation increased most of the biomarkers associated with the body’s metabolism of the vitamin, biomarker levels were lower in people with higher BMIs. The authors said it appears that people at higher body weights may be metabolizing vitamin D differently, which would explain why they don’t see the same health benefits. They also said this suggests that vitamin D doses need to be personalized, and that future studies on vitamin D should take BMI into account when evaluating results.

Current vitamin D recommendations are 15 mcg (600 IU) for ages 1 through 70, and 20 mcg (800 IU) for adults age 71 and older, with the caveat that some people, including people in larger bodies, may have trouble getting enough vitamin D, which already points to the need for some personalization of dosing.

Also interesting are the results of a systematic review and meta-analysis of 20 observational studies and 18 randomized controlled clinical trials. The review, published in July in Nature Scientific Reports, looked at the association between vitamin D (looking at levels in the blood and intake of supplements) and insulin resistance among people with type 2 diabetes. The results showed that people with higher blood levels of vitamin D tended to have less severe insulin resistance.

If it feels like watching results of vitamin D research is like watching a tennis match, you’re not alone. If you have concerns about whether you should be taking vitamin D, or how much you should take, a first step may be to have your blood levels tested. Levels below 30 nmol/L (12 ng/mL) are too low, which may have negative effects on your bones and other aspects of health. Levels of 50 nmol/L (20 ng/mL) or slightly above are considered adequate for bones and health. Note that vitamin D testing is not always covered by insurance.

Links:

LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. N Engl J Med. 2022 Jul 28;387(4):299-309. https://www.nejm.org/doi/full/10.1056/NEJMoa2202106

Cummings SR, Rosen C. VITAL Findings – A Decisive Verdict on Vitamin D Supplementation. N Engl J Med. 2022 Jul 28;387(4):368-370. https://www.nejm.org/doi/10.1056/NEJMe2205993

VITAL researchers announce landmark trial findings. https://www.vitalstudy.org/findings.html

LeBoff MS, Murata EM, Cook NR, et al. VITamin D and OmegA-3 TriaL (VITAL): Effects of Vitamin D Supplements on Risk of Falls in the US Population. J Clin Endocrinol Metab. 2020 Sep 1;105(9):2929–38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365686/

Okereke OI, Reynolds CF 3rd, Mischoulon D, et al. Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2020 Aug 4;324(5):471-480. https://pubmed.ncbi.nlm.nih.gov/32749491/

Chou SH, Murata EM, Yu C, et al. Effects of Vitamin D3 Supplementation on Body Composition in the VITamin D and OmegA-3 TriaL (VITAL). J Clin Endocrinol Metab. 2021 Apr 23;106(5):1377-1388. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063236/

NIH-funded trial finds vitamin D does not prevent type 2 diabetes in people at high risk. https://www.nih.gov/news-events/news-releases/nih-funded-trial-finds-vitamin-d-does-not-prevent-type-2-diabetes-people-high-risk

Tobias DK, Luttmann-Gibson H, Mora S, et al. Association of Body Weight With Response to Vitamin D Supplementation and Metabolism. JAMA Netw Open. 2023 Jan 3;6(1):e2250681. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800490?

National Institutes of Health: Vitamin D Fact Sheet for Consumers. https://ods.od.nih.gov/factsheets/VitaminD-Consumer/

Lei X, Zhou Q, Wang Y, Fu S, Li Z, Chen Q. Serum and supplemental vitamin D levels and insulin resistance in T2DM populations: a meta-analysis and systematic review. Sci Rep. 2023 Jul 31;13(1):12343. https://www.nature.com/articles/s41598-023-39469-9