TitleBenzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts.
Publication TypeJournal Article
Year of Publication2023
AuthorsMonica L Vermillion Maier, Siddens, LK, Pennington, JM, Uesugi, SL, Tilton, SC, Vertel, EA, Anderson, KA, Tidwell, LG, Ognibene, TJ, Turteltaub, KW, Smith, JN, Williams, DE
JournalToxicol Appl Pharmacol
Date Published2023 Feb 01
KeywordsBenzo(a)pyrene, Carcinogens, Dietary Supplements, Humans, Toxicokinetics

Utilizing the atto-zeptomole sensitivity of UPLC-accelerator mass spectrometry (UPLC-AMS), we previously demonstrated significant first-pass metabolism following escalating (25-250 ng) oral micro-dosing in humans of [C]-benzo[a]pyrene ([C]-BaP). The present study examines the potential for supplementation with Brussels sprouts (BS) or 3,3'-diindolylmethane (DIM) to alter plasma levels of [C]-BaP and metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [C]-BaP. Volunteers were dosed with [C]-BaP following fourteen days on a cruciferous vegetable restricted diet, or the same diet supplemented for seven days with 50 g of BS or 300 mg of BR-DIM® prior to dosing. BS or DIM reduced total [C] recovered from plasma by 56-67% relative to non-intervention. Dietary supplementation with DIM markedly increased T and reduced C for [C]-BaP indicative of slower absorption. Both dietary treatments significantly reduced C values of four downstream BaP metabolites, consistent with delaying BaP absorption. Dietary treatments also appeared to reduce the T and the plasma AUC() for Unknown Metabolite C, indicating some effect in accelerating clearance of this metabolite. Toxicokinetic constants for other metabolites followed the pattern for [C]-BaP (metabolite profiles remained relatively consistent) and non-compartmental analysis did not indicate other significant alterations. Significant amounts of metabolites in plasma were at the bay region of [C]-BaP irrespective of treatment. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen.

Alternate JournalToxicol Appl Pharmacol
PubMed ID36642108
PubMed Central IDPMC9946811
Grant ListR01 ES028600 / ES / NIEHS NIH HHS / United States
P30 ES030287 / ES / NIEHS NIH HHS / United States
R24 GM137748 / GM / NIGMS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
T32 ES007060 / ES / NIEHS NIH HHS / United States