Reduced risk of cancer in vitamin D and calcium supplementation
Those involved in setting health policy for oral vitamin D intake (IOM) have been saying that until there are more randomized controlled trials (RCTs) reporting beneficial effects, they are unwilling to accept other evidence showing beneficial effects of vitamin D for non-skeletal health conditions [Ross, 2011]. To date, we have three RCTs on whether vitamin D plays a role in preventing cancer.
One RCT on the matter showed a beneficial effect in vitamin D reducing the risk of cancer, reporting a 77% reduced risk of all-cancer incidence between the ends of the first and fourth years of 1100 IU/day vitamin D3 and 1450 mg/day calcium supplementation [Lappe, 2007]. The IOM chose not to accept this study as basis for new recommendations.
However, the IOM accepted an RCT from the Tufts Evidence-based Practice Center [Chung, 2009], based on a full four year study. The IOM report stated:
“One RCT showed no effect of combined vitamin D3 (1000 IU/day) and calcium (~1500 mg/day) supplementation versus calcium supplementation (~1500 mg/day) alone on the risk of total cancer in healthy postmenopausal women (>55 years old) living in Nebraska (latitude 41°N).”
The largest RCT to date using vitamin D and calcium was the Women’s Health Initiative (WHI). It gave women 400 IU/day vitamin D3 and/or 1500 mg/day calcium or a placebo. Initially, researchers concluded that no beneficial effects were found for the entire set of participants for colorectal cancer [Wactawski-Wende, 2006], breast cancer [Chlebowski, 2008], any other cancers or all cancers combined [Brunner, 2011].
However, a group of researchers led by Mark J Bolland recently reexamined the data set from the WHI study and found promising data. They found that a subset of the participants, those who had not taken vitamin D or calcium supplements prior to enrollment in the study, showed a -18% (95% confidence interval, -30%, -3%) reduced risk in breast cancer, -17% (-40%, +15%) in colorectal cancer, and -14% (-22%, -4%) in total cancer incidence [Bolland, 2011]. The results for breast and total cancer are considered significant, while that for colorectal cancer is not.
Thus, there are now two RCTs supporting the role of vitamin D and calcium in reducing the risk of cancer [Bolland, 2011; Lappe, 2007]. While neither RCT clearly separated the effects of vitamin D and calcium, the two RCTs can be considered as experimental support for the UVB-vitamin D-cancer hypothesis [Grant, 2009].
The relationship between vitamin D blood levels and incidence of cancer shows that cancer risk drops rapidly in individuals who increase their low vitamin D levels. Even in individuals with relatively high vitamin D levels, the cancer risk drops with further increased blood levels, albeit at a slower rate [Abbas, 2009; Grant, 2010]. Based on the serum blood level-cancer incidence rate relationship for breast and colorectal cancer [Grant, 2010], blood levels above 40 ng/ml (100 nmol/L) may reduce the risk of total cancer by about 25% [Giovannucci, 2006; Grant, 2010; Grant and Garland, 2006].
Note that between the two beneficial RCTs, the benefit of 1100 IU/day vitamin D3 was much higher than for 400 IU/day, even though those in the Lappe  study started near 30 ng/ml and increased to near 40 ng/ml.
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