Higher vitamin D levels linked to lower cancer risk, but subject to 'ceiling effect': Japan cohort study

By Cheryl Tay

- Last updated on GMT

Vitamin D concentration was found to be inversely associated with the risk of total cancer. ©Getty Images
Vitamin D concentration was found to be inversely associated with the risk of total cancer. ©Getty Images
Higher vitamin D concentration may be linked to lower total cancer risk, according to a cohort study in Japan.

While vitamin D's bone health benefits have been well-researched, more recent studies have suggested it also protects against chronic diseases, including cancer.

In vitro ​studies have found that vitamin D has a pro-differentiating and an anti-proliferative impact on malignant cells due to its regulation of multiple signalling pathways involved in apoptosis, angiogenesis and inflammation.

In experimental animal models, the activation of the vitamin D endocrine axis by vitamin D itself or its analogues has been shown to restrict tumour development and progression on the breast, colon, prostate, and other tissues, implying that vitamin D has a chemo-preventive role in carcinogenesis.

Specific and overall focus

Researchers at Japan's National Cancer Center and Shiga University of Medical Science therefore sought to determine the relationship between pre-diagnostic circulating vitamin D concentration and the risk of overall and site-specific cancer.

They conducted a nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort, which involved nine public health centre areas across the country.

A total of 3,301 cancer patients and 4,044 randomly selected sub-cohort participants were recruited for the study. Their plasma concentration of 25-hydroxyvitamin D was measured, and they were divided into quarters based on sex- and season-specific distribution of vitamin D among the sub-cohorts.

The researchers subsequently observed that vitamin D concentration was inversely associated with the risk of total cancer, while the results for site-specific cancers showed an inverse association between vitamin D levels and liver cancer risk.

Furthermore, a sensitivity analysis found that alternately removing cases of cancer at specific sites from the total number of cancer cases "did not substantially change the overall hazard ratios"​.

They added that this showed that higher levels of vitamin D were linked to a lower risk of total cancer, and that their findings supported the hypothesis that vitamin D is able to protect against cancers at numerous sites.

A ceiling effect

Despite their observation that a higher circulating concentration of vitamin D was linked to a lower risk of subsequent cancer, the researchers concluded: "Nevertheless, the lower risk associated with higher circulating vitamin D concentration seemed to show a ceiling effect, which may suggest that although maintaining an optimal 25-hydroxyvitamin D concentration is important for (the) prevention of cancer, having a concentration beyond this optimal level may provide no further benefit.

"Future studies are needed to clarify the dose-response pattern and the optimal concentrations for cancer prevention."


Source: The British Medical Journal


"Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort"

Authors: Sanjeev Budhathoki, et al.

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