Abstract LB-30: Metabolomic profile of response to β-carotene supplementation reveals potential for pharmacologic interactions with β-carotene in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.
Authors: Mondul Alison M. , Moore Steven C. , Sampson Joshua N. , Weinstein Stephanie J. , Karoly Edward D. , Virtamo Jarmo , Albanes Demetrius 
Published: August 2014

Background: Two chemoprevention trials, the ATBC Study and the Beta-Carotene and Retinol Efficacy Trial (CARET) observed that β-carotene supplementation increased lung cancer incidence and total mortality rates, and the ATBC Study found other cancers adversely impacted as well. The biologic basis of these findings is not known. We compared the on-study change in metabolomic profiles of men randomized to the trial β-carotene supplements with those who did not receive β-carotene in the ATBC Study.

Methods: A randomized, double-blind, placebo-controlled, primary cancer prevention trial with participants assigned to one of four supplementation groups: 1) α-tocopherol, 2) β-carotene, 3) both vitamins, or 4) placebo. Fifty participants were randomly selected from each of these groups, and LC/GC-MS metabolomic profiling of baseline and follow-up fasting serum samples was conducted. The association between change in each metabolite over time by intervention assignment (β-carotene vs. no β-carotene) was estimated by linear regression.

Results: We identified 516 metabolites; 17 metabolites changed with β-carotene supplementation at p&lt;0.05 (Table). More of these 17 metabolites were xenobiotics (n=10) than would be expected by chance (p=0.001), and all were increased in those supplemented with β-carotene. We also found a suggestive inverse association with 1,5-anhydroglucitol, a marker of glycemic control (β=-0.148, p=0.007, Table).

Conclusions: Male smokers supplemented with β-carotene developed metabolomic profiles suggesting induction of cytochrome P450 enzymes and possibly poorer glycemic control. These findings may shed light on the cancer and mortality outcomes associated with β-carotene supplementation in the ATBC Study and CARET, and highlight the need to understand the potential drug interactions resulting from use of nutritional supplements.

Metabolites that changed significantly (p&lt;0.05) in response to beta-carotene supplementation Metabolite Chemical class Effect size p-value threonine amino acid −0.071 0.0067 1,5-anhydroglucitol carbohydrate −0.148 0.0071 hippurate xenobiotics 0.387 0.0084 3-(3-hydroxyphenyl) propionate non-standard amino acid 0.665 0.0111 3-hydroxyhippurate xenobiotics 0.545 0.0126 dihydroferulic acid xenobiotics 0.408 0.0131 2-hydroxyaceaminophen sulfate xenobiotics 0.398 0.0179 3,7-dimethylurate xenobiotics 0.271 0.0240 5-acetylamino-6-amino-3-methyluracil xenobiotics 0.295 0.0241 beta-sitosterol lipid −0.235 0.0262 xylose carbohydrate −0.213 0.0358 1-methylurate xenobiotics 0.026 0.0372 2-hydroxyisobutyrate xenobiotics 0.099 0.0378 10-nonadecenoate (19:1n9) lipid 0.169 0.0434 catechol sulfate xenobiotics 0.138 0.0451 cinnamoylglycine xenobiotics 0.341 0.0475 7-ketodeoxycholate lipid 0.283 0.0498

Citation Format: Alison M. Mondul, Steven C. Moore, Joshua N. Sampson, Stephanie J. Weinstein, Edward D. Karoly, Jarmo Virtamo, Demetrius Albanes. Metabolomic profile of response to β-carotene supplementation reveals potential for pharmacologic interactions with β-carotene in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-30. doi:10.1158/1538-7445.AM2013-LB-30