Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design

Abstract

Broccoli consumption may reduce the risk of various cancers and many broccoli supplements are now available. The bioavailability and excretion of the mercapturic acid pathway metabolites isothiocyanates after human consumption of broccoli supplements has not been tested. Two important isothiocyanates from broccoli are sulforaphane and erucin. We employed a cross-over study design in which 12 subjects consumed 40 grams of fresh broccoli sprouts followed by a 1 month washout period and then the same 12 subjects consumed 6 pills of a broccoli supplement. As negative controls for isothiocyanate consumption four additional subjects consumed alfalfa sprouts during the first phase and placebo pills during the second. Blood and urine samples were collected for 48 hours during each phase and analyzed for sulforaphane and erucin metabolites using LC-MS/MS. The bioavailability of sulforaphane and erucin is dramatically lower when subjects consume broccoli supplements compared to fresh broccoli sprouts. The peaks in plasma concentrations and urinary excretion were also delayed when subjects consumed the broccoli supplement. GSTP1 polymorphisms did not affect the metabolism or excretion of sulforaphane or erucin. Sulforaphane and erucin are able to interconvert in vivo and this interconversion is consistent within each subject but variable between subjects. This study confirms that consumption of broccoli supplements devoid of myrosinase activity does not produce equivalent plasma concentrations of the bioactive isothiocyanate metabolites compared to broccoli sprouts. This has implications for people who consume the recommended serving size (1 pill) of a broccoli supplement and believe they are getting equivalent doses of isothiocyanates.

Cruciferous Vegetables: Dietary Phytochemicals for Cancer Prevention

“…It is relevant to point out that erucin is extensively metabolised to form sulforaphane as a result of the oxidation of its sulphide group and, furthermore, sulforaphane is reduced to form erucin in vivo. Such an inter-conversion of sulforaphane and erucin may occur in vitro during tissue incubation, and in humans consuming broccoli sprouts or broccoli supplements (Kassahun et al, 1997;Clarke et al, 2011). There have been a few studies concerned with the concentrations of isothiocyanates in plasma and/ or their pharmacokinetic behaviour so as to allow the in vitro effects of these compounds to be extrapolated in in vivo situation.…”

“…In a human study (Cramer et al, 2012), participants consumed meals supplemented with broccoli sprouts equivalent to 70 µmol sulforaphane or glucoraphanin powder equivalent to 120 µmol sulforaphane, achieved plasma levels of about 0.22 µM and 0.25 µM, respectively 3 hours after consumption. In another study, subjects consumed 40 g of broccoli sprouts (150 and 71 µmol glucoraphanin and glucoerucin, respectively) or 6 supplement pills (121 and 40 µmol glucoraphanin and glucoerucin, respectively) achieved maximum plasma concentrations of sulforaphane and erucin metabolites at 3 h post consumption (Clarke et al, 2011). Nevertheless, intracellular concentrations of isothiocyanates may be higher than those in the plasma; it has already been demonstrated that intracellular concentration may reach 200-fold higher than extracellular concentration within a 3 h of exposure (Ye and Zhang, 2001;Zhang and Callaway, 2002).…”

The role of phytochemicals in modulating intrinsic human cellular defence processes

“…397,398 A close investigation of many of the phytochemical-derived supplements popular with consumers reveals that many of these exhibit poor bioavailability, in contrast to that of SFN. 399,400,41 As a result, it is doubtful that some of the bioactive compounds which demonstrate impressive effects in highlypublicised in vitro studies exist in sufficient systemic concentration to exhibit a clinical effect.…”

“…A number of MYR-inactive broccoli seed extracts are commercially-available; these products are a source of glucoraphanin but are devoid of the MYR necessary to convert it to SFN on ingestion. 397 …”

“…37,38,41,197,245,318,[383][384][385][397][398][399]412,[424][425][426][427][428][429][430][431][432] These materials include mature broccoli vegetable (raw and cooked), fresh broccoli sprouts, MYR-inactive broccoli extract beverage, MYR-inactive powdered broccoli sprout extract (BSE), MYR-active broccoli sprout powder and capsules made from MYRinactive broccoli extract. Several of the studies 38,397,398,430 confirm the necessity for MYR in optimising SFN Yield, citing cooking and extraction as being the primary processes leading to loss of activity. confirm the necessity for MYR in optimising SFN Yield, citing cooking and extraction as being the primary processes leading to loss of activity.…”