Demetrius Albanes

M.D.

National Cancer Institute, NIH

Senior Investigator

PLCO (Learn more about this study)

PLCO-849

Nov 3, 2021

Serum / plasma metabolomic profiling of vitamin supplement use

Vitamin biochemical status and supplement use have been associated with risk of cancer and other outcomes. For example, low-dose vitamin E supplementation prevented prostate cancer in the ATBC trial, while it was causal in SELECT, and higher vitamin D status is associated with increased prostate cancer risk but supplementation did not impact incidence in the VITAL trial. Most of the associations to date have not had biological mechanisms established for them. At the same time, metabolomic profiling of vitamin status and supplement use has revealed a large number of associated circulating metabolites: xenobiotics with beta-carotene supplementation, carboxy-methyl-propyl-furanpropanoic acid (CMPF) and DHA/EPA with vitamin D biochemical status, and most recently, a novel C22 lactone compound with high-dose vitamin E supplementation that was not observed for low dose vitamin E. Such discoveries offer mechanistic insights into both the metabolism of the vitamins as well as their potential impact on health outcomes including cancer.

This study will examine serum metabolomic profiles of self-reported vitamin supplement use (from the DHQ) in PLCO women and men who have had metabolite assays in prior nested case-control sets. Profiles of users (i.e., current use at baseline), along with more detailed history of use including vitamin dosages, will be compared to those of non-users of the specific supplements. Vitamins D, E, A, and C, beta-carotene, folic acid and calcium will be the primary initial focus, along with multiple-vitamin/complex use. Conditional logistic regression models will provide beta-estimates of vitamin supplement associations with specific metabolites. Women and men will be analyzed together and separately to allow for biological interactions with sex-specific factors, along with race-specific and ethnicity-specific analysis.

1. Examine the serum/plasma metabolomic profile of vitamin supplement users as compared with non-users of specific vitamins, including vitamins D, E, A, and C, beta-carotene, folic acid and calcium.

2. Evaluate sex-specific, race-specific and ethnicity-specific differences in vitamin supplement metabolomic profiles.

3. Examine differences in metabolomic profiles of vitamin supplement use across range daily dosages.