A D-fence against cancer?

Recent epidemiologic evidence^[1] has suggested that vitamin D may influence the risk of some cancers, particularly colon and breast cancer^[2]. This idea is also supported in rodent and cellular studies. For instance, the activation of vitamin D receptors can reduce liver inflammation and fibrosis in mice and in human tissue samples^[3]. Furthermore, review articles^[4] of preclinical and epidemiological studies^[5] indicate that vitamin D plays a role in anticancer signaling by reducing cell proliferation, reducing inflammation, and increasing apoptosis. However, the results of human trials have been inconsistent. It seems that for every observational study suggesting a cancer-protective effect^[6], there is an equal and opposite clinical trial demonstrating no benefit^[7]. Call it Newton’s Third Law of Nutrition Science. This discrepancy comes from the fact that in observational studies, the exposures to a supplement and risk factors are not randomly distributed, which can lead to overinterpretation and generally more positive results. This concept is illustrated in Figure 1.

Emblematic of this incongruity is perhaps the VITAL trial^[8] (discussed in greater detail in NERD #51, Volume 1). In that large study with a median follow-up duration of 5.3 years, there was virtually no difference in the development of cancer between participants taking vitamin D supplements and those taking a placebo. On the other hand, the group taking the vitamin D supplements did have significantly less death from cancer than the placebo group.

The question of how vitamin D affects cancer incidence versus cancer mortality is an interesting and confusing one. A 2014 Cochrane Review^[9] indicates that vitamin D does not offer a reduced risk of cancer development, but does decrease both cancer mortality and death from any cause, while a meta-analysis including trials up to the year 2016^[10] indicated there was no evidence to suggest that vitamin D supplementation reduces either cancer incidence or mortality. Since the publication of that meta-analysis, there have been other trials published on the subject, including the VITAL trial. The newer trials that have been published since have typically used higher doses with higher quality supplements than are available over-the-counter, which would increase the chances of finding a benefit of supplementation if there truly is one.

The study under review is an attempt to review and update the evidence on vitamin D and cancer from randomized controlled trials (RCTs).

Although epidemiological and animal data suggests vitamin D may be protective of cancer, evidence from randomized controlled trials is inconsistent. The meta-analysis under review analyzes data from the latest human trials to determine if vitamin D supplementation has any effect on cancer incidence or mortality.