People with low vitamin D levels are at increased risk of dying from cancer ― but only if they have already had cancer, report the authors of a meta-analysis.
All-cause mortality was 1.57 times higher among older adults in the lowest quintile of 25-hydroxyvitamin D [25(OH)D] level, but cancer-related deaths were significantly higher only among persons in that grouping with a history of cancer.
The study also showed, however, that levels of 25(OH)D are all over the map, varying considerably by country, sex, and time of year, note Ben Schöttker, PhD, from the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center in Heidelberg, and colleagues.
"Results from a long term randomized controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels," they write in a BMJ open-access study published online.
In an interview with Medscape Medical News, coauthor Paolo Boffetta, MD, MPH, director of the Institute for Translational Epidemiology and professor of hematology and medical oncology at Mount Sinai Hospital in New York City, said that the investigators are not sure why they saw an effect of vitamin D only in patients with a history of cancer.
"One specific aspect of our study was that it was conducted in the elderly population, so we had a large proportion of people with a previous cancer," which could have skewed results, Dr. Boffetta said.
"Whether vitamin D may be particularly related to risk of multiple cancers or some general susceptibility to cancer which may be related to reaction to inflammatory conditions, this is the sort of thing we speculated about. But this is the first time that this has been reported, and clearly it needs to be confirmed in other investigations, particularly in elderly cohorts," he said.
The BMJ editors note that the study hints at a role of vitamin D in cancer prognosis and suggests that for clinical purposes, cutoff values for determining vitamin D deficiency many need to be customized by geography, age, sex, and season.
However, a cancer specialist is not so sure about the prognostic value of vitamin D.
"I agree that the study might be interpreted 'from either side' as supporting a role for vitamin D deficiency in cancer risk — though only in prior cancer patients — or it can be viewed as demonstrating lack of correlation or weakness of correlation overall," commented David E. Fisher, MD, PhD, Edward Wigglesworth Professor and chairman of the Department of Dermatology, Harvard Medical School, and director of the Melanoma Program at Massachusetts General Hospital Cancer Center in Boston.
He was not involved in the study and was asked for comment.
"As pointed out by the authors, a 'reverse' correlation cannot be ruled out (ie, multicancer patients may be more prone to become vitamin D deficient). I believe the studies, while somewhat provocative, do not support an obvious role for vitamin D in cancer prevention," Dr. Fisher said.
D and Death: A Mixed Picture
As reported by Medscape Medical News, another recent meta-analysis of 17,000 cancer patients in China found better overall survival for patients with lymphoma, colorectal cancer, or breast cancer who were in the highest quartile of circulating 25(OH)D levels compared with lowest quartile.
Higher circulating levels of vitamin D were also significantly associated with lower cancer-specific mortality rates among patients with both colorectal cancer and lymphoma, and disease-free survival rates were also significantly improved for patients with breast cancer and those with lymphoma.
A different meta-analysis, also recently reported, found that women with high levels of vitamin in their blood when they were diagnosed with breast cancer were almost twice as likely to survive as those with low levels of vitamin D.
But vitamin D skeptics can point to yet another meta-analysis looking at vitamin D supplements for the prevention of myocardial infarction, stroke, cancer, or hip fracture in seniors, which found that, in general, taking vitamin D does not lower the incidence of these outcomes.
In the current study, the investigators consolidated data on 26,018 participants from the age of 50 to 79 years in 7 European cohorts and one US study (the National Health and Nutrition Examination Survey III).
Mean follow-up times in the studies ranged from 4.2 to 15.9 years. During follow-up, 6695 participants died ― 2227 from cancer, 2624 from cardiovascular diseases, and the remainder from other causes.
To account for variations in vitamin D levels across the regions and cohorts in the study, the investigators defined 25(OH)D quintiles with cohort- and subgroup-specific cutoff values.
They found that all-cause mortality in the lowest vs highest quintiles was 1.5 times higher (pooled risk ratio, 1.57; 95% confidence interval [CI], 1.36 - 1.81).
But when they looked at cancer-specific mortality, they found a significant association only for those with a history of cancer (risk ratio, 1.70; 95% CI, 1.00 - 2.88).
There was a consistent inverse dose-response trend seen across the studies for all-cause and cardiovascular mortality and for cancer mortality in patients with a history of cancer.
D Still Gets Good Grade
Although the relationship between vitamin D and mortality may be fuzzy, the benefits for D in overall health are clear, Dr. Fisher emphasized.
"From a dermatology perspective, I would add that vitamin D is solidly established to be important for other medical/health reasons, especially pertaining to calcium and bone metabolism. Therefore, establishing and maintaining a healthy vitamin D level is part of good health maintenance," he told Medscape Medical News.
"I would add that this should be done by measuring blood levels of vitamin D and if necessary using oral supplements to achieve the necessary levels. Sun exposure as a means of establishing a healthy vitamin D level is both dangerous (carcinogenic) and unreliable (due to variations in sun intensity, skin pigmentation, geographical location, time of day, etc)," he wrote.
The meta-analysis was part of the CHANCES project, funded by a grant from the European Commission. The authors and Dr. Fisher reported no relevant financial relationships.
BMJ. 2014;348:g3656. Full article
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Cite this: 'D' Levels Linked to Cancer Death Risk Only in Survivors - Medscape - Jun 20, 2014.
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