Protection of Humans by Plant Glucosinolates: Efficiency of Conversion of Glucosinolates to Isothiocyanates by the Gastrointestinal Microflora

Abstract

Plant-based diets rich in crucifers are effective in preventing cancer and other chronic diseases. Crucifers contain very high concentrations of glucosinolates (GS; β-thioglucoside-N- hydroxysulfates). Although not themselves protective, GS are converted by coexisting myrosinases to bitter isothiocyanates (ITC) which defend plants against predators. Coincidentally, ITC also induce mammalian genes that regulate defenses against oxidative stress, inflammation, and DNA-damaging electrophiles. Consequently, the efficiency of conversion of GS to ITC may be critical in controlling the health-promoting benefits of crucifers. If myrosinase is heat-inactivated by cooking, the gastrointestinal microflora converts GS to ITC, a process abolished by enteric antibiotics and bowel cleansing. When single oral doses of GS were administered as broccoli sprout extracts (BSE) to two dissimilar populations (rural Han Chinese and racially mixed Baltimoreans) patterns of excretions of urinary dithiocarbamates (DTC) were very similar. Individual conversions in both populations varied enormously, from about 1% to more than 40% of dose. In contrast, administration of ITC (largely sulforaphane)-containing BSE, resulted in uniformly high (70-90%) conversions to urinary DTC. Despite the remarkably large range of conversion efficiencies between individuals, repeated determinations within individuals were much more consistent. The rates of urinary excretion (slow or fast) were unrelated to the ultimate magnitudes (low or high) of these conversions. Although no demographic factors affecting conversion efficiency have been identified, there are clearly diurnal variations: conversion of GS to DTC was greater during the day, but conversion of ITC to DTC was more efficient at night.

Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition

“…Although promising, results displayed significant variability in the bioavailability of the active compound. Consistent with this finding, Fahey et al found that administration of a sulforaphane-rich broccoli sprout extract to two distinct populations (Chinese and Baltimoreans) resulted in varied bioavailability between individuals in both populations, ranging from 1% to 40% (72). In a recent intervention study, the total sulforaphane metabolite concentration in plasma was the highest ( > 2 lM) at 3 h in human subjects who consumed fresh broccoli sprouts (40g) in the first phase of study, compared with that measured after administration of a commercially available broccoli supplementation in the second phase (42).…”

Glucosinolate hydrolysis and bioavailability of resulting isothiocyanates: Focus on glucoraphanin

“…This idea is supported by the work of Llanos et al, who grew Lactobacillus agilis by feeding sinigrin, Table 1 (Llanos et al, 1995). One might also suggest that this could be the cause for variation in the fractional SF production in a group of individuals given a GSL source with no myrosinase present (Egner et al, 2011;Fahey et al, 2012). Here, individuals from Baltimore were found to vary in the fraction of GSL appearing as urinary ITC, from approximately 1-40% of the dose (median was 10%).…”

“…It is possible that free SF detected in plasma or urine was generated from its metabolites during sample preparation, since these metabolites are known to be unstable and to allow SF dissociation (Conaway, Krzeminski, Amin, & Chung, 2001). However, in a study of almost 100 subjects given broccoli sprout extract daily for 14 days, urinary SF was relatively consistent at 6% of the metabolites, suggesting that free SF may be naturally present in the urine (Fahey et al, 2012). One study found that, although urinary SF-NAC was preponderant throughout the full 24 h, during the first 4 h other metabolites, i.e.…”

Insights into the Mode of Action of Benzyl Isothiocyanate on Campylobacter jejuni

“…ITCs are products of the degradation of plant glucosinolates by the enzyme myrosinase, found in plants and in microbes of the gut microbiota (17). Plants of the Brassicaceae family produce glucosinolates; these plants include mustard, wasabi, horseradish, and broccoli.…”