Vitamin D supplementation decreases serum 27-hydroxycholesterol in a pilot breast cancer trial
27-hydroxycholesterol (27HC), an endogenous selective estrogen receptor modulator (SERM), drives the growth of estrogen receptor-positive (ER+) breast cancer. 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D, is known to inhibit expression of CYP27B1, which is very similar in structure and function to CYP27A1, the synthesizing enzyme of 27HC. Therefore, we hypothesized that 1,25(OH)2D may also inhibit expression of CYP27A1, thereby reducing 27HC concentrations in the blood and tissues that express CYP27A1, including breast cancer tissue.
27HC, 25-hydroxyvitamin D (25OHD), and 1,25(OH)2D were measured in sera from 29 breast cancer patients before and after supplementation with low-dose (400 IU/day) or high-dose (10,000 IU/day) vitamin D in the interval between biopsy and surgery.
A significant increase (p = 4.3E−5) in 25OHD and a decrease (p = 1.7E−1) in 27HC was observed in high-dose versus low-dose vitamin D subjects. Excluding two statistical outliers, 25OHD and 27HC levels were inversely correlated (p = 7.0E−3).
Vitamin D supplementation can decrease circulating 27HC of breast cancer patients, likely by CYP27A1 inhibition. This suggests a new and additional modality by which vitamin D can inhibit ER+ breast cancer growth, though a larger study is needed for verification.
KeywordsVitamin D Calcitriol 27-hydroxycholesterol ER+ breast cancer CYP27A1
Liquid chromatography tandem mass spectrometry
Selective estrogen receptor modulator
Selected reaction monitoring
The authors would like to acknowledge funding for this project from the Vincent Coates Foundation Mass Spectrometry Laboratory in the form of a SUMS Seed Grant. We are grateful to Dr. Melinda Telli, Dr. Kristin Jensen, and members of the Feldman Lab that carried out this trial for their generous access to serum specimens of many of the subjects.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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