Vitamin D does not improve gastrointestinal cancer outcomes, clinical trial finds


Possible roles for the vitamin in cancer treatments have been debated for more than a decade, and results are mixed. Natalie Parletta reports.


High doses of Vitamin D have been suggested as a useful treatment adjunct for gastrointestinal cancer, but findings are mixed.

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High doses of vitamin D do not improve survival rates for patients with gastrointestinal cancer, according to a new clinical trial. The finding follows a body of studies suggesting the vitamin is associated with reduced risk of several cancers.

During an eight-year Japanese study, published in the journal JAMA, 417 patients aged 30 to 90 with cancers throughout the digestive tract received 2000 international units (IU) of oral vitamin D or placebo daily, from two to four weeks after surgical treatment until the study’s end.

Patient diagnoses included oesophageal, stomach, small bowel and colorectal cancer in early to late stages. Overall results showed vitamin D supplementation did not reduce risk of relapse or death compared with placebo.

Specifically, 15% of patients in each group died during follow up, while 16% in the vitamin D group and 22% in the placebo group had a relapse. Five-year relapse-free survival was 77% in the vitamin D group and 69% in the placebo group.

Secondary analyses suggest the findings are not clear cut. Delving further, the researchers investigated blood serum markers for the major from of vitamin D, called 25-hydroxycholecalciferol, or 25(OH)D, and separated patients with low versus high levels.

Those with levels below 25 nanograms per millilitre at the study’s inception showed an increase in median level from 16 to 36 ng/mL over one year. Those with higher levels saw their median increase from 26.5 to 45 ng/mL.

In the latter group, the number experiencing five-year relapse-free survival hit 85% following vitamin D supplementation, compared to 71% for the placebo cohort. There was no difference between the groups with lower 25(OH)D levels.

Mitsuyoshi Urashima, from the Jikei University School of Medicine in Japan, and co-authors, caution that “this finding must be considered exploratory and interpreted with caution in the context of the null findings for the primary outcome measures”.

But they add that the supplement dose “may have been insufficient to increase vitamin D levels sufficiently in the subgroup with low 25(OH)D levels”.

Further inspection also revealed the vitamin D group had older patients than the placebo group. Adjusting for this difference showed that cumulative risk of death or relapse, but not death alone, was lower in the vitamin D group than the placebo group.

The study follows more than a decade of curiosity about possible links between vitamin D deficiency and cancer.

This interest stems from the discovery that cells throughout the body have receptors for calcitriol, the biologically active form of vitamin D. Intriguingly, the receptors also appear on malignant cells.

Several mechanisms for calcitriol’s possible anti-cancer effects have been suggested. These include inhibiting growth and inducing apoptosis – cell death – of malignant cells, blocking cell invasion and metastasis, and reducing inflammation.

Most of the research testing links between vitamin D and cancer has been observational, which does not establish causation.

A meta-analysis of 64 such studies found that higher 25(OH)D levels were associated with better outcomes and survival. Another analysis of eight cohort studies found that people with low 25(OH)D levels had higher cancer mortality.

But clinical trial results have been mixed. One large study found that vitamin D supplementation did not reduce risk of cancer mortality in people with no previous history of cancer.

Another meta-analysis of three smaller clinical trials found that while vitamin D supplementation did not prevent cancer incidence, it did reduce mortality from cancer.

Urashima and co-authors suggest discrepancies between studies may be attributed to different lifestyle habits.

In one large study, for instance, patients who maintained a healthy body weight, physical activity and a diet high in vegetables, fruits and whole grains after an advanced colon cancer diagnosis had higher survival rates.

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  1. https://doi.org/10.1001/jama.2019.2210
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788175/
  3. https://www.ncbi.nlm.nih.gov/pubmed/28301870
  4. https://www.ncbi.nlm.nih.gov/pubmed/24938302
  5. https://www.nejm.org/doi/full/10.1056/NEJMoa1809944
  6. https://www.ncbi.nlm.nih.gov/pubmed/24918818
  7. https://www.ncbi.nlm.nih.gov/pubmed/29710284
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