Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli

• Published in: The American journal of clinical nutrition Vol. 82; no. 6; pp. 1283 - 1291
• Main Authors: Gasper, Amy V, Al-janobi, Ahmed, Smith, Julie A, Bacon, James R, Fortun, Paul, Atherton, Clare, Taylor, Moira A, Hawkey, Christopher J, Barrett, David A, Mithen, Richard F
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.12.2005; American Society for Clinical Nutrition, Inc
• Subjects: Adolescent; Adult; Alleles; anticarcinogenic activity; antinutritional factors; Area Under Curve; biochemical pathways; Biological and medical sciences; Brassica - chemistry; Brassica oleracea var. italica; broccoli; chemical composition; chemoprevention; Comparative analysis; Cross-Over Studies; Double-Blind Method; Female; Food industries; Fruit and vegetable industries; Fundamental and applied biological sciences. Psychology; Genetics; Genotype & phenotype; glucobrassicin; Glucosinolates - administration & dosage; Glucosinolates - metabolism; glutathione transferase; Glutathione Transferase - deficiency; Glutathione Transferase - genetics; Humans; Isothiocyanates; Male; metabolic detoxification; Metabolism; Middle Aged; Neoplasms - prevention & control; nutrition-genotype interaction; Polymorphism; Polymorphism, Genetic; randomized clinical trials; Risk Factors; structure-activity relationships; Sulfoxides; Thiocyanates - blood; Thiocyanates - pharmacokinetics; Thiocyanates - urine; Vegetables; Human; Glucosinolate; Vegetables; GSTM1; Enzyme; Transferases; Metabolism; Feeding; super broccoli; Broccoli; Food intake; Glutathione transferase; Sulforaphane; glucosinolates; Isothiocyanates; chemoprotection; Polymorphism
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/82.6.1283

Broccoli consumption is associated with a reduction in the risk of cancer, particularly in persons with a functional glutathione S-transferase M1 allele, as opposed rotrose whose GSTM1 gene has been deleted. Sulforaphane, the major isothiocyanate derived from 4-methylsulfinylbutyl glucosinolate, is thought to be the main agent conferring protection. We compared sulforaphane metabolism in GSTM1-null and GSTM1-positive subjects after they consumed standard broccoli and high-glucosinolate broccoli (super broccoli). Sixteen subjects were recruited into a randomized, 3-phase crossover dietary trial of standard broccoli, super broccoli, and water. Liquid chromatography linked to tandem mass spectrometry was used to quantify sulforaphane and its thiol conjugates in plasma and urine. GSTM1-null subjects had slightly higher, but statistically significant, areas under the curve for sulforaphane metabolite concentrations in plasma, a greater rate of urinary excretion of sulforaphane metabolites during the first 6 h after broccoli consumption, and a higher percentage of sulforaphane excretion 24 h after ingestion than did GSTM1-positive subjects. Consumption of high-glucosinolate broccoli led to a 3-fold greater increase in the areas under the curve and maximum concentrations of sulforaphane metabolites in plasma, a greater rate of urinary excretion of sulforaphane metabolites during the first 6 h after consumption, and a lower percentage of sulforaphane excretion after its ingestion than did the consumption of standard broccoli. GSTM1 genotypes have a significant effect on the metabolism of sulforaphane derived from standard or high-glucosinolate broccoli. It is possible that the difference in metabolism may explain the greater protection that GSTM1-positive persons gain from consuming broccoli. The potential consequences of consuming glucosinolate-enriched broccoli for GSTM1-null and -positive persons are discussed.