Table 2.

Foods and nutrients that modulate the activity of Phase I/Phase II enzymes and their interaction with genotype.

Food/Nutrient	Gene	Effects on Enzymatic Function
Caffeine	CYP1A2	Caffeine is an inducer and substrate of CYP1A2. rs762551-C allele carriers are “slow” caffeine metabolizers, and they should limit coffee consumption to <1 cup/day or caffeine from other drinks to <100 mg/day to avoid being at higher risks of hypertension and myocardial infarction. In contrast, those with the AA genotype are “rapid” caffeine metabolizers and may benefit from consuming 1–4 cups of coffee/day due to increased consumption of phytonutrients presumed to be protective against heart disease.
Cruciferous vegetables (broccoli, Brussels sprouts, cauliflower, watercress, and cabbage)	CYP1A2	May increase CYP1A2 activity, but it is unclear whether the magnitude of this effect may depend on CYP1A genotype.
	GSTM1, GSTT1	Individuals carrying gene deletions in GSTM1 or GSTT1, especially those carrying deletions in both genes, may have a more rapid excretion of bioactive nutrients found in cruciferous vegetables such as isothiocyanates and sulforaphane. Consequently, they may need to consume greater amounts of cruciferous vegetables than those who carry at least one copy of either GSTM1 or GSTT1. On the other side, double-deletion carriers tend to experience a greater increase in GST activity and GST-mediated detoxification upon consumption of cruciferous vegetables or cruciferous-based supplements such as 2-phenethyl isothiocyanate (PEITC). The GST-inducing effects of cruciferous vegetables are more pronounced in females than in males.
	UGT1A1	May decrease serum bilirubin levels in rs3064744-TA allele carriers with greater effects observed for TA/TA homozygous.
Apiaceous vegetables (carrots, celery, dill, parsley, parsnips, etc.)	CYP1A2	May decrease CYP1A2 activity, but it is unclear whether the magnitude of this effect may depend on CYP1A genotype. May exert inhibitory effects on GSTM-1 in men, not women, who carry at least one copy of the GSTM1 gene.
	GSTM1, GSTT1	May exert inhibitory effects on GSTM1 in men, not women, who carry at least one copy of the GSTM1 gene.
	UGTA1	May decrease serum bilirubin levels in rs3064744-TA allele carriers with greater effects observed for TA/TA homozygous.
Quercetin and antioxidant rich foods (citrus fruits, apples, onions, red wine, olive oil, dark berries, etc.)	CYP1B1	Quercetin may reduce oxidative stress to a greater extent in rs1056836-G allele carriers than in those with the CC genotype. These findings were made with quercetin from fruit juices at doses significantly lower (~100 mg) than those typically used for supplementation (500–1000 mg).
	GSTM1, GSTT1	Quercetin and other antioxidants from blueberry, apples, and purple grapes may reduce oxidative stress to a greater extent in GST double deletion carriers than GST-positive individuals. Smokers who carry GST deletions may especially benefit from supplementation with antioxidants because carcinogens in cigarette smoke can overload their detox capacity and induce a higher production of ROS byproducts. However, quercetin and other antioxidants seem to improve certain oxidative stress markers such as glutathione levels and vitamin C to a greater extent in those with at least one copy of GSTM-1 or GSTT-1.
Tea catechins	COMT	Individuals with the rs4680 AA genotype, who have slow COMT activity, may be slow catechin metabolizers and retain more catechins in the blood than those with the GG genotype. As a result, they may benefit from a lower intake of tea catechins. In contrast, those with the GG genotype, who have higher COMT activity, may be more sensitive to the short-term effects of tea catechins, such as an increase in insulin secretion and blood pressure (BP).
Olive oil, red wine	COMT	Individuals with the rs4680 GG genotype, who have higher COMT activity, may experience the health benefits of olive oil and red wine at lower intakes than those with the AA genotype. This is due to a greater ability to convert hydroxytyrosol, a phenolic compound in virgin olive oil and red wine, into its cardioprotective metabolite homovanillyl alcohol (HVAL).
Citrus fruit	UGT1A1	May help lower serum bilirubin in women with the rs3064744 TA/TA genotype. These effects may be noticeable in all TA allele carriers.

Abbreviations: SNP identification numbers (noted as “rs...”) are the unique SNP identifiers from the NCBI dbSNP database. CYP1A2: Cytochrome P-450 1A2; CYP1B1: Cytochrome P-450 1B1; GST: Glutathione S-transferase; GSTM1: Glutathione S-transferase mu 1; GSTT1: Glutathione S-transferase theta 1; COMT: Catechol-O-methyltransferase; UGT1A1: UDP-glucuronosyltransferase A-1; ROS: Radical Oxygen Species.