June 15, 2018
Higher circulating levels of 25 hydroxyvitamin D (25[OH]D) up to 100 nmol/L are associated with a significantly lower risk for colorectal cancer (CRC) in women and a nonsignificantly lower risk in men compared with concentrations that are considered deficient for bone health, an international collaborative meta-analysis suggests.
"Previous studies have suggested that there might be a lower CRC risk with higher vitamin D levels in the blood, but studies have been inconsistent and generally smaller," lead author Marjorie McCullough, ScD, RD, a nutritional epidemiologist with the American Cancer Society in Atlanta, Georgia, told Medscape Medical News.
The authors used original data from 17 studies, allowing the team to control for different risk factors for CRC as well as analyze subgroups in the population, which is not possible in typical meta-analyses.
The team found that circulating 25(OH)D levels of less than 30 nmol/L, which are considered deficient for bone health by the Institute of Medicine (IOM), were associated with a 31% greater risk for CRC compared with levels of 50 to <62.5 nmol/L, the lower range of 25[OH]D considered sufficient for bone health.
The study was published online June 14 in the Journal of the National Cancer Institute.
The researchers pooled participant-level data from 17 cohorts involving 5706 patients with CRC and 7107 control persons.
"Importantly, in eight of the studies, we newly measured vitamin D in the blood, and for the other studies that had previously measured vitamin D, we got samples across the range [of 25[OH]D] concentrations] within those studies and reassessed them in the same laboratory we used for the new studies so that we could calibrate previously measured values and use the same cut points when we looked at the relationship of CRC across a range of vitamin D seen internationally," McCullough explained.
In the past, substantial differences between assays made it challenging for researchers to integrate vitamin D data from different studies, the authors explain.
After an average follow-up of 5.5 years, participants in the lowest quintile of 25(OH)D concentrations had a 23% higher relative risk for CRC, while those in the highest quintile had a 21% lower risk for CRC in an unadjusted model.
Adjustment for body mass index and physical activity minimally affected these risk estimates, the authors note.
The researchers also assessed the association of 25(OH)D levels between 75 and <87.5 nmol/L.
At these levels, they observed a significant 19% lower relative risk for CRC. For participants with circulating 25(OH)D levels between 75 and <100 nmol/L, the relative risk of CRC was 22% lower compared to participants with the lowest levels of circulating 25(OH)D considered inadequate for bone health.
Participants with 25(OH)D levels of 100 nmol/L or more were not further protected against CRC risk, the authors note.
"In continuous models, each 25 nmol/L increase in circulating 25(OH)D was associated with a statistically significantly lower risk of colorectal cancer in women and men combined," the researchers observe. The relative risk reduction was 13%.
In women, this risk reduction was slightly greater than 19%. However, among men, it was no longer significant, at a relative risk reduction of only 7%, they add.
Protective associations with higher circulating 25(OH)D levels were observed in all subgroups.
"In summary, by demonstrating a strong, statistically significant, and robust inverse association between prediagnostic circulating vitamin D and colorectal cancer risk, we substantially strengthen the evidence, previously considered inconclusive, for a causal relationship [of circulating 25(OH)D levels and CRC]," the investigators state.
"Our study suggests that optimal circulating 25(OH)D concentrations for colorectal cancer risk reduction are 75-100 nmol/L, higher than current IOM recommendations for bone health," the investigators conclude.
Supplementation Not Recommended
Asked if everyone should use vitamin D supplements to ensure that 25(OH)D levels are in the optimal range to protect against CRC, McCullough said they do not recommend vitamin D supplements for most people because most people already have sufficient circulating levels of vitamin D.
"In our population, only about 8% of participants were deficient in vitamin D, and in the US, that number is only about 7%, so fortunately, not a lot of people are deficient, and it doesn't take a lot to get out of the deficient range," she explained.
Vitamin D can be found naturally in foods such as salmon and tuna and especially milk, including soy milk and almond milk, as well as in some yogurts that are fortified with vitamin D.
"People who live in sunny climates or even those living during warm summer months naturally have higher levels of vitamin D in their blood because the skin is very efficient at stimulating the formation of vitamin D," McCullough added.
The risk for vitamin D deficiency is higher for those with very dark skin; for older adults, whose skin may not be as efficient at synthesizing vitamin D; and for those who do not go outside at all.
These individuals may be the exception and may require supplementation, especially if they are not eating fortified foods, McCullough suggested.
"It's really going to be up to future committees who will have to review all the evidence for the RDAs [recommended daily allowances] to determine whether some people will need more vitamin D or not to reach sufficient levels," McCullough said.
"However, there is an upper tolerable intake level of vitamin D at 4000 IU, and it is not recommended people go beyond this level, because really high levels of vitamin D can be toxic," she cautioned.
The study was funded by the National Heart, Blood, and Lung Institute and the National Cancer Institute Intramural Research Program. Dr McCullough has disclosed no relevant financial relationships.