Detoxification enzymes play an important role in the metabolism and detoxification of xenobiotics, toxins, carcinogens, medicine, and endogenous substances to support healthy functions of many systems in the body. The cytochrome P450 enzyme family acts as the starting point for the metabolism of many xenobiotics and endogenous metabolites during phase 1 detoxification. Enzymes such as sulfotransferases, glutathione S-transferases, uridine 5'-diphospho-glucuronosyltransferase, and quinone reductases, such as NQO1, catalyze the conjugation of compounds for phase 2 detoxification. Certain dietary compounds, such as isothiocyanates, may support detoxification through their effect on these enzymes.
Isothiocyanates and their Action on Detox Enzymes
Dietary isothiocyanates (compounds created when the enzyme myrosinase acts upon the phytochemical glucosinolates found in cruciferous vegetables) have the potential to modify the expression of many detoxification enzymes. In one animal study, there was a correlation between plasma concentrations of sulforaphane after consuming unblanched brussels sprouts (active myrosinase) and the expression of several phase 1 and 2 enzymes, including CYP1A1, CYP1A2, CYP1B1, uridine 5'-diphospho-glucuronosyltransferase, and quinone reductases (QR) in liver and lung tissue.
The effect may be both isothiocyanate and organ-specific. One in vitro study compared the ability of six different isothiocyanates (allyl-isothiocyanate, iberverin, erucin, sulforaphane, iberin, and cheirolin) on inducing phase 2 detoxification enzymes; all of these, except cheirolin increased QR and glutathione S-transferases (GST), even at a low dose. The upregulation of the detoxification enzymes differed in the tissues tested (with the duodenum, forestomach, and/or urinary bladder undergoing changes) and with many of the other tissues experiencing no effect, including the liver, spleen, lungs, and kidneys.
There may also be a dose-dependent response. One in vitro study found four different isothiocyanates (allyl-isothiocyanate, benzyl-isothiocyanate, phenethyl-isothiocyanate, and sulforaphane) led to increased GST and QR activity in the range of 1.8-fold to 5.4-fold. Higher doses caused an even greater effect for most of the isothiocyanates, except sulforaphane, which experienced very high increases at low doses. The researchers postulated that most of the isothiocyanates, except sulforaphane, may have already reached maximal induction at these lower doses.
Supporting the Elimination of Toxins
Some clinical studies demonstrate this potential for upregulation of detox enzymes may correlate with practical effects. In one randomized phase 2 clinical trial, cigarette smokers took a supplement with 30 mg/day of 2-phenethyl isothiocyanate (PEITC) in divided doses for 5 days, which led to a 24.6% increase in urinary benzene metabolites and 15.1% increase in urinary acrolein metabolites. Those with the null genotype of both GSTM1 and GSTT1 experienced an even greater increase, with an increase in benzene metabolites excretion by 95.4%, acrolein metabolites by 15.1%, and crotonaldehyde metabolites by 29.8%. However, PEITC exhibited no effect on smokers with both genes. Another study on smokers found that consuming watercress led to an increase in urinary metabolites of PEITC, which correlated with an increase in urinary metabolites of nicotine-derived nitrosamine ketone, a tobacco-specific lung carcinogen.
These studies demonstrate the potential for isothiocyanates to upregulate key detoxification enzymes, although more studies are necessary to fully elucidate their abilities. Consuming broccoli, other cruciferous vegetables, or additional sources of isothiocyanates as part of a healthy diet may support healthy detoxification.
By Kendra Whitmore, MS, CNS