Absorption and chemopreventive targets of sulforaphane in humans following consumption of broccoli sprouts or a myrosinase-treated broccoli sprout extract

Abstract

Scope Sulforaphane (SFN), an isothiocyanate derived from crucifers, has numerous health benefits. SFN bioavailability from dietary sources is a critical determinant of its efficacy in humans. A key factor in SFN absorption is the release of SFN from its glucosinolate precursor, glucoraphanin, by myrosinase. Dietary supplements are used in clinical trials to deliver consistent SFN doses, but myrosinase is often inactivated in available supplements. We evaluated SFN absorption from a myrosinase-treated broccoli sprout extract (BSE) and are the first to report effects of twice daily, oral dosing on SFN exposure in healthy adults. Methods and results Subjects consumed fresh broccoli sprouts or the BSE, each providing 200 μmol SFN daily, as a single dose and as two 100-μmol doses taken 12 h apart. Using HPLC-MS/MS, we detected ~3 x higher SFN metabolite levels in plasma and urine of sprout consumers, indicating enhanced SFN absorption from sprouts. Twelve-hour dosing retained higher plasma SFN metabolite levels at later time points than 24-hour dosing. No dose responses were observed for molecular targets of SFN (i.e. heme oxygenase-1, histone deacetylase activity, p21). Conclusion We conclude that the dietary form and dosing schedule of SFN may impact SFN absorption and efficacy in human trials.

A Randomized Controlled Trial of the Effect of Broccoli Sprouts on Antioxidant Gene Expression and Airway Inflammation in Asthmatics

“…However, there were marked increases in serum SFN levels following ingestion of whole BS, although it is possible that the concentrations of SFN were not sufficiently high to have biologic activity. The total SFN conjugate levels detected in our study were similar to some of the published studies, although a lot of variability exists in the SFN conjugate/metabolite measured as well as timing and methods of detection, making it difficult to compare systemic SFN levels among studies 10, 11, 27 . Second, our study was conducted in adults with atopic asthma and the other studies were all conducted in healthy subjects, so it is possible that the dose and/or duration of treatment needed among a population of asthmatics, who may have impaired activation of Nrf2 and induction of the antioxidant pathway, may be greater than that needed for healthy adults.…”

“…Two doses, 12h apart compared to consuming a single dose, resulted in higher plasma concentrations of SFN metabolites 24 h post-consumption. However, neither 200 μmol once daily or 100 μmol twice daily induced significant antioxidant gene expression in blood 27 , suggesting that more frequent dosing of whole BS would not result in biologic activity. This study, like ours, suggests that whole BS, despite resulting in marked increases in serum SFN, has little biologic activity in doses that could reasonably be consumed by an adult.…”

“…In that study, subjects consumed whole BS each providing 200 μmol of SFN (which is approximately equivalent to 127gm of BS) daily as a single dose or as two 100 μmol doses taken 12h apart 27 . Two doses, 12h apart compared to consuming a single dose, resulted in higher plasma concentrations of SFN metabolites 24 h post-consumption.…”

Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy

“…Additional studies are needed to evaluate dose-responses and responses of other relevant molecular targets to consuming foods and supplements that provide SFN. While the supplements used in this study were well-tolerated, recent work indicated that other broccoli extract preparations may be more bioavailable and should be considered for use in future studies to enhance SFN absorption from these forms (33). Overall, this work provides important information for future larger population-based clinical trials investigating the impacts of consuming dietary sources of SFN.…”

“…Creatinine concentrations were determined using the Jaffe reaction method as previous described (33). SFN and SFN metabolite concentrations in urine were normalized using creatinine concentrations to control for differences in urine volume.…”