DESPITE GREAT RESEARCH EFFORTS, there is no consensus on whether vitamin D has an anti-cancer effect. That is the conclusion of a 2018 review.

Today we explore the clinical literature showing some studies reporting an association between low vitamin D levels and an increased risk of colorectal cancer, but others finding no such link.

Vitamin D and cancer — A randomized study

A 2018 clinical trial randomized participants to a control (marine omega-3 fatty acids, one gram daily) or vitamin D (cholecalciferol, 2000 IU daily).

The VITamin D and OmegA-3 TriaL (VITAL) clinical trial enrolled nearly 26,000 American men (50 and older) and women (55 and older) to examine the impact of vitamin D3 on several outcomes:

• Cancer prevention
• Cardiovascular disease risk (heart attack, stroke, and cardiovascular mortality).
• Secondary endpoints included site-specific cancers, cancer mortality, and additional cardiovascular events.

The results? With a median 5.3-year intervention, vitamin D supplementation did not reduce cancer or cardiovascular risk, the study’s two primary endpoints.

There appeared to be no significant differences in the secondary endpoints, either. The vitamin D3 intervention did not reduce the incidence of total cancer mortality or breast, prostate, or colorectal cancer. Finally, treatment effects did not differ by baseline vitamin D blood levels.

The researchers reported no excess risks of high calcium levels (hypercalcemia) or other side effects associated with vitamin D supplementation.

But are we sure that vitamin D3 supplementation does not reduce cancer risk? A 2019 meta-analysis analysis of the scientific literature concluded that:

Vitamin D3 did not reduce cancer incidence but did drop cancer mortality.

In addition, a secondary analysis of the VITAL clinical trial published in 2019 showed that while vitamin D supplementation did not lower cancer incidence, it appeared to be associated with a reduced incidence of advanced cancer.

My take

The VITAL clinical trial has tremendous strengths, including a large population with racial and geographic diversity. The daily vitamin D dosing seems reasonable, with follow-up blood collection in many participants showing blood levels in the target range.

The study has some significant limitations, however. For example, the researchers examined only a single dose of vitamin D3. Hopefully, future studies will look at another dose. Finally, the follow-up is not nearly long enough. For example, cancer can take decades from its birth before it is clinically observable.

We may also need to consider cancer risk by genotypes of vitamin D-associated genes.

Here are the US Preventative Services Task Force recommendations:

• Premenopausal women. The USPSTF recommends against daily supplementation with 400 IU or less of vitamin D and 1000 mg or less of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women. Current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with doses greater than 400 IU of vitamin D and greater than 1000 mg of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women.
• Men and premenopausal women. The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of vitamin D and calcium supplementation, alone or combined, for the primary prevention of fractures in men and premenopausal women.

Note this USPSTF observation: “These recommendations do not apply to persons with a history of osteoporotic fractures, increased risk for falls, or a diagnosis of osteoporosis or vitamin D deficiency.” Given we don’t routinely test for deficiency, how would I know if I am deficient?

Daily vitamin D3 supplementation for five years among initially healthy adults does not appear to lower cancer or major cardiovascular event risk. The evidence is insufficient to make supplement recommendations for community-dwelling individuals.

Thank you for joining me in this look at vitamin D and cancer risk. Today, I will not examine the impact of vitamin D (and vitamin K) on bone fracture risk.