Sulforaphane: Translational research from laboratory bench to clinic

Nutrition Reviews

Volumn 71, Issue 11, 2013, Pages 709-726

  Houghton, Christine A ^a   Fassett, Robert G ^a,b   Coombes, Jeff S ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b ROYAL BRISBANE AND WOMEN'S HOSPITAL   (Australia)

Author keywords

Bioactivity; Bioavailability; Broccoli seed extract; Broccoli sprout; Glucoraphanin; Myrosinase active; Sulforaphane

Indexed keywords

ANTIOXIDANT; ASCORBIC ACID; CYTOCHROME P450 3A4; ERUCIC ACID; GLUCOSINOLATE; GLUTATHIONE TRANSFERASE; HISTONE DEACETYLASE; LIOTHYRONINE; LIPID; PHYTOMENADIONE; RETINOL; SULFORAPHANE; THIOGLUCOSIDASE; THYROXINE; TRANSCRIPTION FACTOR NRF2; WARFARIN;

AMBIGUITY; ARTICLE; BRASSICA OLERACEA; BROCCOLI; CANCER CELL; CARCINOGENESIS; CELL CYCLE ARREST; CELL STRAIN LNCAP; CHEMOPROPHYLAXIS; CLINICAL TRIAL (TOPIC); DETOXIFICATION; ENZYME ACTIVITY; HUMAN; IN VITRO STUDY; NUTRIGENOMICS; PLANT SEED; PROSTATE CANCER; RAPESEED; SINGLE NUCLEOTIDE POLYMORPHISM; SPROUT; THYROID DISEASE; TRANSLATIONAL RESEARCH; VEGETABLE; VITAMIN SUPPLEMENTATION;

BRASSICA OLERACEA VAR. ITALICA;

BIOACTIVITY; BIOAVAILABILITY; BROCCOLI SEED EXTRACT; BROCCOLI SPROUT; GLUCORAPHANIN; MYROSINASE-ACTIVE; SULFORAPHANE;

ANTICARCINOGENIC AGENTS; BRASSICA; DIETARY SUPPLEMENTS; HUMANS; ISOTHIOCYANATES; NEOPLASMS; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84887612717     PISSN: 00296643     EISSN: 17534887     Source Type: Journal    
DOI: 10.1111/nure.12060     Document Type: Article

References (149)

1. Verhoeven DT, Goldbohm RA, van Poppel G, etal. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers Prev. 1996;5:733-748.
2. Traka MH, Mithen RF. Plant science and human nutrition: challenges in assessing health-promoting properties of phytochemicals. Plant Cell. 2011;23:2483-2497.
3. 105Val genetic polymorphism, and breast cancer risk. Am J Clin Nutr. 2008;87:753-760.
4. Bao YP. Bioactivities of dietary isothiocyanates. Agro Food Ind Hi-Tech. 2005;16:24-26.
5. Nestle M. Broccoli sprouts in cancer prevention. Nutr Rev. 1998;56:127-130.
6. Vasanthi HR, Mukherjee S, Das DK. Potential health benefits of broccoli - a chemico-biological overview. Mini Rev Med Chem. 2009;9:749-759.
7. Jin Y, Wang M, Rosen RT, etal. Thermal degradation of sulforaphane in aqueous solution. J Agric Food Chem. 1999;47:3121-3123.
8. Wu H, Liang H, Yuan Q, etal. Preparation and stability investigation of the inclusion complex of sulforaphane with hydroxypropyl-cyclodextrin. Carbohydr Polym. 2010;82:613-617.
9. Kaput J, Rodriguez RL. Nutritional genomics: the next frontier in the postgenomic era. Physiol Genomics. 2004;16:166-177.
10. Fenech M, El-Sohemy A, Cahill L, etal. Nutrigenetics and nutrigenomics: viewpoints on the current status and applications in nutrition research and practice. J Nutrigenet Nutrigenomics. 2011;4:69-89.
11. Joost HG, Gibney MJ, Cashman KD, etal. Personalised nutrition: status and perspectives. Br J Nutr. 2007;98:26-31.
12. Mancinelli L, Cronin M, Sadée W. Pharmacogenomics: the promise of personalized medicine. AAPS PharmSci. 2000;2:E4.
13. Costa V, Casamassimi A, Ciccodicola A. Nutritional genomics era: opportunities toward a genome-tailored nutritional regimen. J Nutr Biochem. 2010;21:457-467.
14. Surh Y-J, Dong Z, Cadenas E, Packer L (eds). Dietary Modulation of Cell Signaling Pathways. Boca Raton, FL: Taylor & Francis; 2008.
15. Klaassen CD, Reisman SA. Nrf2 to the rescue: effects of the antioxidative/electrophilic response on the liver. Toxicol Appl Pharmacol. 2010;244:57-65.
16. Hu R, Xu C, Shen G, etal. Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice. Cancer Lett. 2006;243:170-192.
17. Zhu H, Jia Z, Strobl JS, etal. Potent induction of total cellular and mitochondrial antioxidants and phase 2 enzymes by cruciferous sulforaphane in rat aortic smooth muscle cells: cytoprotection against oxidative and electrophilic stress. Cardiovasc Toxicol. 2008;8:115-125.
18. Hayes JD, McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci. 2009;34:176-188.
19. Niture SK, Kaspar JW, Shen J, etal. Nrf2 signaling and cell survival. Toxicol Appl Pharmacol. 2010;244:37-42.
20. Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med. 2008;74:1526-1539.
21. Lee JM, Johnson JA. An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol. 2004;37:139-143.
22. Lewis KN, Mele J, Hayes JD, etal. Nrf2, a guardian of healthspan and gatekeeper of species longevity. Integr Comp Biol. 2010;50:829-843.
23. Hart C, Cohen R, Norwood M, etal. The emerging harm of antioxidants in carcinogenesis. Future Oncol. 2012;8:535-548.
24. Zhang Q, Pi J, Woods CG, etal. A systems biology perspective on Nrf2-mediated antioxidant response. Toxicol Appl Pharmacol. 2010;244:84-97.
25. Mutch DM, Wahli W, Williamson G. Nutrigenomics and nutrigenetics: the emerging faces of nutrition. FASEB J. 2005;19:1602-1616.
26. Ambrosone CB, Tang L. Cruciferous vegetable intake and cancer prevention: role of nutrigenetics. Cancer Prev Res (Phila). 2009;2:298-300.
27. Kim MK, Park JH. Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence. Proc Nutr Soc. 2009;68:103-110.
28. Joseph MA, Moysich KB, Freudenheim JL, etal. Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk. Nutr Cancer. 2004;50:206-213.
29. Obeidat M, Wain LV, Shrine L, etal. A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample. PLoS ONE. 2011;6:e19382.
30. Reszka E, Wasowicz W. Significance of genetic polymorphisms in glutathione S-transferase multigene family and lung cancer risk. Int J Occup Med Environ Health. 2001;14:99-113.
31. Clarke JD, Dashwood RH, Ho E. Multi-targeted prevention of cancer by sulforaphane. Cancer Lett. 2008;269:291-304.
32. Gasper AV, Al-Janobi A, Smith JA, etal. Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr. 2005;82:1283-1291.
33. Gasper AV, Traka M, Bacon JR, etal. Consuming broccoli does not induce genes associated with xenobiotic metabolism and cell cycle control in human gastric mucosa. J Nutr. 2007;137:1718-1724.
34. Hanlon N, Coldham N, Gielbert A, etal. Repeated intake of broccoli does not lead to higher plasma levels of sulforaphane in human volunteers. Cancer Lett. 2009;284:15-20.
35. Saha S, Hollands W, Teucher B, etal. Isothiocyanate concentrations and interconversion of sulforaphane to erucin in human subjects after consumption of commercial frozen broccoli compared to fresh broccoli. Mol Nutr Food Res. 2012;56:1906-1916.
36. West LG, Meyer KA, Balch BA, etal. Glucoraphanin and 4-hydroxyglucobrassicin contents in seeds of 59 cultivars of broccoli, raab, kohlrabi, radish, cauliflower, brussels sprouts, kale, and cabbage. J Agric Food Chem. 2004;52:916-926.
37. Kushad MM, Brown AF, Kurilich AC, etal. Variation of glucosinolates in vegetable crops of Brassica oleracea. J Agric Food Chem. 1999;47:1541-1548.
38. Ketterer B. Dietary isothiocyanates as confounding factors in the molecular epidemiology of colon cancer. Cancer Epidemiol Biomarkers Prev. 1998;7:645-646.
39. Seow A, Vainio H, Yu MC. Effect of glutathione-S-transferase polymorphisms on the cancer preventive potential of isothiocyanates: an epidemiological perspective. Mutat Res. 2005;592:58-67.
40. Lin HJ, Probst-Hensch NM, Louie AD, etal. Glutathione transferase null genotype, broccoli, and lower prevalence of colorectal adenomas. Cancer Epidemiol Biomarkers Prev. 1998;7:647-652.
41. Lampe JW, Peterson S. Brassica, biotransformation and cancer risk: genetic polymorphisms alter the preventive effects of cruciferous vegetables. J Nutr. 2002;132:2991-2994.
42. Juge N, Mithen RF, Traka M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci. 2007;64:1105-1127.
43. Fruth K, Best N, Amro M, etal. No evidence for a correlation of glutathione S-tranferase polymorphisms and chronic rhinosinusitis. Rhinology. 2011;49:180-184.
44. Gross-Steinmeyer K, Stapleton PL, Tracy JH, etal. Sulforaphane- and phenethyl isothiocyanate-induced inhibition of aflatoxin B-mediated genotoxicity in human hepatocytes: role of GSTM1 genotype and CYP3A4 gene expression. Toxicol Sci. 2010;116:422-432.
45. Reinhardt HC, Schumacher B. The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends Genet. 2012;28:128-136.
46. Bourdon JC. p53 family isoforms. Curr Pharm Biotechnol. 2007;8:332-336.
47. Brooks JD, Paton VG, Vidanes G. Potent induction of phase 2 enzymes in human prostate cells by sulforaphane. Cancer Epidemiol Biomarkers Prev. 2001;10:949-954.
48. Fimognari C, Sangiorgi L, Capponcelli S, etal. A mutated p53 status did not prevent the induction of apoptosis by sulforaphane, a promising anti-cancer drug. Invest New Drugs. 2005;23:195-203.
49. Clarke JD, Hsu A, Riedl K, etal. Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design. Pharmacol Res. 2011;64:456-463.
50. Cramer JM, Jeffery EH. Sulforaphane absorption and excretion following ingestion of a semi-purified broccoli powder rich in glucoraphanin and broccoli sprouts in healthy men. Nutr Cancer. 2011;63:196-201.
51. Vermeulen M, Klopping-Ketelaars IW, van den Berg R, etal. Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli. J Agric Food Chem. 2008;56:10505-10509.
52. Anand P, Kunnumakkara AB, Newman RA, etal. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4:807-818.
53. Riedl MA, Saxon A, Diaz-Sanchez D. Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clin Immunol. 2009;130:244-251.
54. Johanningsmeier SD, Harris GK. Pomegranate as a functional food and nutraceutical source. Annu Rev Food Sci Technol. 2011;2:181-201.
55. Fahey JW, Kensler TW. Role of dietary supplements/nutraceuticals in chemoprevention through induction of cytoprotective enzymes. Chem Res Toxicol. 2007;20:572-576.
56. D'Archivio M, Filesi C, Vari R, etal. Bioavailability of the polyphenols: status and controversies. Int J Mol Sci. 2010;11:1321-1342.
57. Jeffery EH, Keck AS. Translating knowledge generated by epidemiological and in vitro studies into dietary cancer prevention. Mol Nutr Food Res. 2008;52(Suppl 1):S7-S17.
58. Cornblatt BS, Ye L, Dinkova-Kostova AT, etal. Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis. 2007;28:1485-1490.
59. Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci U S A. 1997;94:10367-10372.
60. Gorrisen A, Kraut NU, de Visser R, etal. No de novo sulforaphane biosynthesis in broccoli seedlings. Food Chem. 2011;127:192-196.
61. Bekaert M, Edger PP, Hudson CM, etal. Metabolic and evolutionary costs of herbivory defense: systems biology of glucosinolate synthesis. New Phytol. 2012;196:596-605.
62. Zhang Y, Talalay P, Cho CG, etal. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A. 1992;89:2399-2403.
63. Basten GP, Bao Y, Williamson G. Sulforaphane and its glutathione conjugate but not sulforaphane nitrile induce UDP-glucuronosyl transferase (UGT1A1) and glutathione transferase (GSTA1) in cultured cells. Carcinogenesis. 2002;23:1399-1404.
64. Jeffery EH, Stewart KE. Upregulation of quinone reductase by glucosinolate hydrolysis products from dietary broccoli. Methods Enzymol. 2004;382:457-469.
65. Matusheski NV, Swarup R, Juvik JA, etal. Epithiospecifier protein from broccoli (Brassica oleracea L. ssp. italica) inhibits formation of the anticancer agent sulforaphane. J Agric Food Chem. 2006;54:2069-2076.
66. Matusheski NV, Juvik JA, Jeffery EH. Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli. Phytochemistry. 2004;65:1273-1281.
67. West L, Tsui I, Balch B, etal. Determination and health implication of the erucic acid content of broccoli florets, sprouts, and seeds. J Food Sci. 2002;67:2641-2643.
68. US Food and Drug Administration. Code of Federal Regulations Title 21. Subchapter B. Food for Human Consumption. Part 184 - Direct Food Substances Affirmed as Generally Recognized as Safe (GRAS). Published 2012; http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=184.1555. Accessed October 5, 2013.
69. Kwak MK, Itoh K, Yamamoto M, etal. Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: role of antioxidant response element-like sequences in the nrf2 promoter. Mol Cell Biol. 2002;22:2883-2892.
70. Prawan A, Kundu JK, Surh YJ. Molecular basis of heme oxygenase-1 induction: implications for chemoprevention and chemoprotection. Antioxid Redox Signal. 2005;7:1688-1703.
71. Ye L, Dinkova-Kostova AT, Wade KL, etal. Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans. Clin Chim Acta. 2002;316:43-53.
72. Ritz SA, Wan J, Diaz-Sanchez D. Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract. Am J Physiol Lung Cell Mol Physiol. 2007;292:L33-L39.
73. Juge N, Mithen RF, Traka M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci. 2007;64:1105-1127.
74. Myzak MC, Tong P, Dashwood W-M, etal. Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol Med (Maywood) 2007;232:227-234.
75. Dashwood RH, Myzak MC, Ho E. Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention? Carcinogenesis. 2006;27:344-349.
76. Bertl E, Bartsch H, Gerhauser C. Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention. Mol Cancer Ther. 2006;5:575-585.
77. Chu WF, Wu DM, Liu W, etal. Sulforaphane induces G2-M arrest and apoptosis in high metastasis cell line of salivary gland adenoid cystic carcinoma. Oral Oncol. 2009;45:998-1004.
78. Keck AS, Qiao Q, Jeffery EH. Food matrix effects on bioactivity of broccoli-derived sulforaphane in liver and colon of F344 rats. J Agric Food Chem. 2003;51:3320-3327.
79. Veeranki OL, Bhattacharya A, Marshall JR, etal. Organ-specific exposure and response to sulforaphane, a key chemopreventive ingredient in broccoli: implications for cancer prevention. Br J Nutr. 2013;109:25-32.
80. Ye L, Zhang Y. Total intracellular accumulation levels of dietary isothiocyanates determine their activity in elevation of cellular glutathione and induction of Phase 2 detoxification enzymes. Carcinogenesis. 2001;22:1987-1992.
81. Munday R, Mhawech-Fauceglia P, Munday CM, etal. Inhibition of urinary bladder carcinogenesis by broccoli sprouts. Cancer Res. 2008;68:1593-1600.
82. Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 2000;92:61-68.
83. Gao X, Talalay P. Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage. Proc Natl Acad Sci U S A. 2004;101:10446-10451.
84. 2/M arrest and caspase-mediated apoptosis induced by sulforaphane in DU145 prostate cancer cells. Nutr Cancer. 2005;52:213-224.
85. Angeloni C, Leoncini E, Malaguti M, etal. Modulation of phase II enzymes by sulforaphane: implications for its cardioprotective potential. J Agric Food Chem. 2009;57:5615-5622.
86. Song M-Y, Kim E-K, Moon W-S, etal. Sulforaphane protects against cytokine- and streptozotocin-induced beta-cell damage by suppressing the NF-κB pathway. Toxicol Appl Pharmacol. 2009;235:57-67.
87. Kivelä AM, Mäkinen PI, Jyrkkänen HK, etal. Sulforaphane inhibits endothelial lipase expression through NF-κB in endothelial cells. Atherosclerosis. 2010;213:122-128.
88. Mas S, Gassó P, Trias G, etal. Sulforaphane protects SK-N-SH cells against antipsychotic-induced oxidative stress. Fundam Clin Pharmacol. 2012;26:712-721.
89. Tan XL, Shi M, Tang H, etal. Candidate dietary phytochemicals modulate expression of phase II enzymes GSTP1 and NQO1 in human lung cells. J Nutr. 2010;140:1404-1410.
90. Vauzour D, Buonfiglio M, Corona G, etal. Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes. Mol Nutr Food Res. 2010;54:532-542.
91. Shan Y, Wu K, Wang W, etal. Sulforaphane down-regulates COX-2 expression by activating p38 and inhibiting NF-κB-DNA-binding activity in human bladder T24 cells. Int J Oncol. 2009;34:1129-1134.
92. Myzak MC, Hardin K, Wang R, etal. Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells. Carcinogenesis. 2006;27:811-819.
93. Conaway CC, Getahun SM, Liebes LL, etal. Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli. Nutr Cancer. 2000;38:168-178.
94. Galan MV, Kishan AA, Silverman AL. Oral broccoli sprouts for the treatment of Helicobacter pylori infection: a preliminary report. Dig Dis Sci. 2004;49:1088-1090.
95. Murashima M, Watanabe S, Zhuo XG, etal. Phase 1 study of multiple biomarkers for metabolism and oxidative stress after one-week intake of broccoli sprouts. Biofactors. 2004;22:271-275.
96. Kensler TW, Chen JG, Egner PA, etal. Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China. Cancer Epidemiol Biomarkers Prev. 2005;14:2605-2613.
97. Shapiro TA, Fahey JW, Dinkova-Kostova AT, etal. Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study. Nutr Cancer. 2006;55:53-62.
98. Rungapamestry V, Duncan AJ, Fuller Z, etal. Effect of meal composition and cooking duration on the fate of sulforaphane following consumption of broccoli by healthy human subjects. Br J Nutr. 2007;97:644-652.
99. Traka M, Gasper AV, Melchini A, etal. Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate. PLoS ONE. 2008;3:e2568.
100. Yanaka A, Fahey JW, Fukomota A, etal. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Cancer Prev Res (Phila). 2009;2:353-360.
101. Kumar A, Vineis P, Sacerdote C, etal. Determination of new biomarkers to monitor the dietary consumption of isothiocyanates. Biomarkers. 2010;15:739-745.
102. Egner PA, Chen JG, Wang JB, etal. Bioavailability of sulforaphane from two broccoli sprout beverages: results of a short-term, cross-over clinical trial in Qidong, China. Cancer Prev Res (Phila). 2011;4:384-395.
103. Bahadoran Z, Mirmirian P, Hosseinpanah F, etal. Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind clinical trial. Eur J Clin Nutr. 2011;65:972-977.
104. Clarke JD, Riedl K, Bella D, etal. Comparison of isothiocyanate metabolite levels and histone deacetylase activity in human subjects consuming broccoli sprouts or broccoli supplement. J Agric Food Chem. 2011;59:10955-10963.
105. Bahadoran Z, Mirmirian P, Hosseinpanah F, etal. Broccoli sprouts powder could improve serum triglyceride and oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Diabetes Res Clin Pract. 2012;96:348-354.
106. Yanaka A. Sulforaphane enhances protection and repair of gastric mucosa against oxidative stress in vitro, and demonstrates anti-inflammatory effects on Helicobacter pylori-infected gastric mucosae in mice and human subjects. Curr Pharm Des. 2011;17:1532-1540.
107. Yanaka A, Tauchi M, Yamamoto M. Effects of sulforaphane-rich broccoli sprouts on H. pylori-infected gastric mucosa [in Japanese]. Nihon Rinsho. 2005;63(Suppl 11):582-586.
108. Clarke JD, Hsu A, Yu Z, etal. Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol Nutr Food Res. 2011;55:999-1009.
109. Munday R, Munday CM. Induction of phase II detoxification enzymes in rats by plant-derived isothiocyanates: comparison of allyl isothiocyanate with sulforaphane and related compounds. J Agric Food Chem. 2004;52:1867-1871.
110. Robbins RJ, Keck AS, Banuelos G, etal. Cultivation conditions and selenium fertilization alter the phenolic profile, glucosinolate, and sulforaphane content of broccoli. J Med Food. 2005;8:204-214.
111. Zhang Y, Callaway EC. High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem J. 2002;364:301-307.
112. Newton JM, Bader F. The prediction of the bulk densities of powder mixtures, and its relationship to the filling of hard gelatin capsules. J Pharm Pharmacol. 1981;33:621-626.
113. Xue M, Qian Q, Adaikalakoteswari A, etal. Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes. 2008;57:2809-2817.
114. Ioannides C, Hanlon N, Konsue N. Isothiocyanates: a chemical class of potential nutraceuticals. Open Nutraceuticals J. 2010;3:55-62.
115. Ioannides C. Drug-phytochemical interactions. Inflammopharmacology. 2003;11:7-42.
116. Ioannides C. Pharmacokinetic interactions between herbal remedies and medicinal drugs. Xenobiotica. 2002;32:451-478.
117. Williams JA, Ring BJ, Cantrell VE, etal. Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002;30:883-891.
118. Hanley MJ, Cancalon P, Widmer WW, etal. The effect of grapefruit juice on drug disposition. Expert Opin Drug Metab Toxicol. 2011;7:267-286.
119. Imboden M, Downs SH, Senn O, etal. Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study. Respir Res. 2007;8:2.
120. Engdal S, Nilsen OG. In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients. Phytother Res. 2009;23:906-912.
121. Rodríguez-Antona C, Leskelä S, Zajac M, etal. Expression of CYP3A4 as a predictor of response to chemotherapy in peripheral T-cell lymphomas. Blood. 2007;110:3345-3351.
122. Mahéo K, Morel F, Langouët S, etal. Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphane in primary human and rat hepatocytes. Cancer Res. 1997;57:3649-3652.
123. Lubelska K, Milczarek M, Modzelewska K, etal. Interactions between drugs and sulforaphane modulate the drug metabolism enzymatic system. Pharmacol Rep. 2012;64:1243-1252.
124. Booth SL, Centurelli MA. Vitamin K: a practical guide to the dietary management of patients on warfarin. Nutr Rev. 1999;57:288-296.
125. Bolton-Smith C, Price RJ, Fenton ST, Harrington DJ, Shearer MJ. Compilation of a provisional UK database for the phylloquinone (vitamin K1) content of foods. Br J Nutr 2000;83:389-399.
126. Brassica Protection Products LLC. Brassica.com FAQs. 2010; Available at: http://www.sgs-broccoli.com/emerging-science/faqs. Accessed October 5, 2012.
127. Schurgers LJ, Shearer MJ, Hamulyak K, etal. Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects. Blood. 2004;104:2682-2689.
128. Cheung KL, Kong AN. Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS J. 2010;12:87-97.
129. Mithen RF, Dekker M, Verkerk R, etal. The nutritional significance, biosynthesis and bioavailability of glucosinolates in human foods. J Sci Food Agric. 2000;80:967-984.
130. Verkerk R, Schreiner M, Krumbein A, etal. Glucosinolates in Brassica vegetables: the influence of the food supply chain on intake, bioavailability and human health. Mol Nutr Food Res. 2009;53(Suppl 2):S219.
131. McMillan M, Spinks EA, Fenwick GR. Preliminary observations on the effect of dietary brussels sprouts on thyroid function. Hum Toxicol. 1986;5:15-19.
132. Truong T, Baron-Dubourdieu D, Rougier Y, etal. Role of dietary iodine and cruciferous vegetables in thyroid cancer: a countrywide case-control study in New Caledonia. Cancer Causes Control. 2010;21:1183-1192.
133. Assayed ME, Abd El-Aty AM. Cruciferous plants: phytochemical toxicity versus cancer chemoprotection. Mini Rev Med Chem. 2009;9:1470-1478.
134. Romanque P, Cornejo P, Valdes S, etal. Thyroid hormone administration induces rat liver Nrf2 activation: suppression by N-acetylcysteine pretreatment. Thyroid. 2011;21:655-662.
135. Wagner AE, Boesch-Saadatmandi C, Breckwoldt D, etal. Ascorbic acid partly antagonizes resveratrol mediated heme oxygenase-1 but not paraoxonase-1 induction in cultured hepatocytes - role of the redox-regulated transcription factor Nrf2. BMC Complement Altern Med. 2011;11:1.
136. Halliwell B. Vitamin C: antioxidant or pro-oxidant in vivo? Free Radic Res. 1996;25:439-454.
137. Peternelj TT, Coombes JS. Antioxidant supplementation during exercise training: beneficial or detrimental? Sports Med. 2011;41:1043-1069.
138. Bjelakovic G, Gluud C. Vitamin and mineral supplement use in relation to all-cause mortality in the Iowa Women's Health Study. Arch Intern Med. 2011;171:1633-1634.
139. Pashkow FJ. Oxidative stress and inflammation in heart disease: do antioxidants have a role in treatment and/or prevention? Int J Inflamm. 2011;2011:514623.
140. Pustateri DJ, Chiang WC, Letiz REA, Sperrazzo PM, inventors. Amway Corporation, assignee. Brassica vegetable supplement and process for manufacture. US patent 5, 882, 646. March 16, 1999.
141. [No authors listed]. Sulforaphane glucosinolate. Monograph. Altern Med Rev. 2010;15:352-360.
142. Rungapamestry V, Rabot S, Fuller Z, etal. Influence of cooking duration of cabbage and presence of colonic microbiota on the excretion of N-acetylcysteine conjugates of allyl isothiocyanate and bioactivity of phase 2 enzymes in F344 rats. Br J Nutr. 2008;99:773-781.
143. Wang W, Wang S, Howie AF, etal. Sulforaphane, erucin, and iberin up-regulate thioredoxin reductase 1 expression in human MCF-7 cells. J Agric Food Chem. 2005;53:1417-1421.
144. Zhang Y, Talalay P. Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic phase 2 enzymes. Cancer Res. 1998;58:4632-4639.
145. US Food and Drug Administration. Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related Issues. Published July 2011; Available at: http://www.fda.gov/food/guidanceregulation/guidancedocumentsregulatoryinformation/dietarysupplements/ucm257563.htm. Accessed October 7, 2013.
146. Egan B, Hodgkins C, Shepherd R, etal. An overview of consumer attitudes and beliefs about plant food supplements. Food Funct. 2011;2:747-752.
147. US Food and Drug Adminstration. Dietary Supplement and Health Education Act. http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/ucm148003.htm. Published 1994; Accessed January 18, 2012.
148. Bailey RL, Gahche JJ, Lentino CV, etal. Dietary supplement use in the United States, 2003-2006. J Nutr. 2011;141:261-266.
149. Umhau JC, Garg K, Woodward AM. Dietary supplements and their future in health care: commentary on draft guidelines proposed by the Food and Drug Administration. Antioxid Redox Signal. 2012;16:461-462.