Study under review: Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials
Recent epidemiologic evidence has suggested that vitamin D may influence the risk of some cancers, particularly colon and breast cancer. 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. Furthermore, review articles of preclinical and epidemiological studies 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, there is an equal and opposite clinical trial demonstrating no benefit. 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 (discussed in greater detail in Study Deep Dives #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 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 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.
Other Articles in Issue #54 (April 2019)
Mini: What’s magnesium good for?
In this Mini, we give a quick summary of a recent umbrella review's findings concerning which of magnesium's many purported effects are most well supported by the evidence.
Investigating arginine for erectile dysfunction
The amino acid L-arginine is used to make nitric oxide, a potent vasodilator which could possibly help mitigate erectile dysfunction. But does it?
Does physical activity prevent depression or does depression prevent physical activity?
The evidence is pretty clear that depression and low physical activity are correlated. This Mendelian randomization study explored whether this link is causal, and in which direction the causal arrow points.
Does cinnamon spice up weight loss?
There are some mechanistic reasons to think that cinnamon may help shed some pounds. This recent meta-analysis found an effect, but the significance of its impact is open to question.
Mini: Folic acid intake and neural tube defects
Neural tube defects are potentially serious problems for developing embryos. Its risk is lowered, but not eliminated, by mothers-to-be getting enough folic acid. This Mini explores a recent meta-analysis examining how folate levels are impacted by folic acid intake.
The (mild) health risks of energy drinks
Energy drinks can make a small, potentially negative impact in certain metabolic measures in young, relatively healthy people. But do these changes really matter?
Peppermint oil soothes symptoms of irritable bowel syndrome
Enteric coated peppermint oil may help relieve some of the symptoms of IBS according to this recent meta-analysis, at least in the short term.