The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Safety, Tolerance, and Metabolism of Broccoli Sprout Glucosinolates and Isothiocyanates: A Clinical Phase I Study
Abstract
Broccoli sprouts are widely consumed in many parts of the world. There have been no reported concerns with respect to their tolerance and safety in humans. A formal phase I study of safety, tolerance, and pharmacokinetics appeared justified because these sprouts are being used as vehicles for the delivery of the glucosinolate glucoraphanin and its cognate isothiocyanate sulforaphane [1-isothiocyanato-(4R)-(methylsulfinyl)butane] in clinical trials. Such trials have been designed to evaluate protective efficacy against development of neoplastic and other diseases. A placebo-controlled, double-blind, randomized clinical study of sprout extracts containing either glucosinolates (principally glucoraphanin, the precursor of sulforaphane) or isothiocyanates (principally sulforaphane) was conducted on healthy volunteers who were in-patients on our clinical research unit. The subjects were studied in three cohorts, each comprising three treated individuals and one placebo recipient. Following a 5-day acclimatization period on a crucifer-free diet, the broccoli sprout extracts were administered orally at 8-h intervals for 7 days (21 doses), and the subjects were monitored during this period and for 3 days after the last treatment. Doses were 25 micromol of glucosinolate (cohort A), 100 micromol of glucosinolate (cohort B), or 25 micromol of isothiocyanate (cohort C). The mean cumulative excretion of dithiocarbamates as a fraction of dose was very similar in cohorts A and B (17.8 +/- 8.6% and 19.6 +/- 11.7% of dose, respectively) and very much higher and more consistent in cohort C (70.6 +/- 2.0% of dose). Thirty-two types of hematology or chemistry tests were done before, during, and after the treatment period. Indicators of liver (transaminases) and thyroid [thyroid-stimulating hormone, total triiodothyronine (T3), and free thyroxine (T4)] function were examined in detail. No significant or consistent subjective or objective abnormal events (toxicities) associated with any of the sprout extract ingestions were observed.
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Citations
Cites
The chemical diversity and distribution of glucosinolates and isothiocyanates among plants
Fahey, J. W., Zalcmann, A. T., & Talalay, P. (2001) · Phytochemistry · doi:10.1016/s0031-9422(00)00316-2 · Cited by 2,964
Self-citationDinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947
Self-citationNrf2–Keap1 defines a physiologically important stress response mechanism
Motohashi, H., & Yamamoto, M. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.09.003 · Cited by 1,725 · cited 2×
“hydrolytic conversion of glucosinolates to isothiocyanates is important because the isothiocyanates and not their glucosinolate precursors are the active moieties that react with Keap1, the sensor for inducers that signals transcription of phase 2 genes (9,11,12).”
BackgroundZhang, Y., Talalay, P., Cho, C. G., & Posner, G. H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.6.2399 · Cited by 1,682
Self-citationFahey, J. W., Zhang, Y., & Talalay, P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.19.10367 · Cited by 1,376
Self-citationZhang, Y., Kensler, T. W., Cho, C. G., Posner, G. H., & Talalay, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.3147 · Cited by 745
Self-citationPhytochemicals from Cruciferous Plants Protect against Cancer by Modulating Carcinogen Metabolism
Talalay, P., & Fahey, J. W. (2001) · The Journal of Nutrition · doi:10.1093/jn/131.11.3027s · Cited by 609
Self-citationProchaska, H. J., & Santamaria, A. B. (1988) · Analytical Biochemistry · doi:10.1016/0003-2697(88)90292-8 · Cited by 495
Shapiro, T. A., Fahey, J. W., Wade, K. L., Stephenson, K. K., & Talalay, P. (2001) · PubMed · Cited by 476
Self-citationShapiro, T. A., Fahey, J. W., Wade, K. L., Stephenson, K. K., & Talalay, P. (1998) · PubMed · Cited by 424
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Cited by
Small Molecule Modulators of Keap1‐ Nrf2‐ ARE Pathway as Potential Preventive and Therapeutic Agents
Magesh, S., Chen, Y., & Hu, L. (2012) · Medicinal Research Reviews · doi:10.1002/med.21257 · Cited by 760
“200, 201 In presence of oxygen and transition metals, tBHQ (42) was oxidized to tBQ (43) and rapidly underwent Michael addition with Keap1 protein and activated ARE-dependent transcription.”
MethodSulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells
Li, Y., Zhang, T., Korkaya, H., Liu, S., Lee, H.-F., Newman, B., Yu, Y., Clouthier, S. G., Schwartz, S. J., Wicha, M. S., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2937 · Cited by 559
Nrf2: friend or foe for chemoprevention?
Kensler, T. W., & Wakabayashi, N. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp231 · Cited by 484
Axelsson, A. S., Tubbs, E., Mecham, B., Chacko, S., Nenonen, H. A., Tang, Y., Fahey, J. W., Derry, J. M. J., Wollheim, C. B., Wierup, N., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah4477 · Cited by 323
Self-citationPreclinical and clinical evaluation of sulforaphane for chemoprevention in the breast
Cornblatt, B. S., Ye, L., Dinkova-Kostova, A. T., Erb, M., Fahey, J. W., Singh, N. K., Chen, M.-S. A., Stierer, T., Garrett-Mayer, E., Argani, P., et al. (2007) · Carcinogenesis · doi:10.1093/carcin/bgm049 · Cited by 320
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Metadata
- Authors
- Shapiro, T. A., Fahey, J. W., Dinkova-Kostova, A. T., Holtzclaw, W. D., Stephenson, K. K., Wade, K. L., Ye, L., & Talalay, P.
- Venue
- Nutrition and Cancer
- Publisher
- Informa UK Limited
- Published
- 2006-07
- Volume
- 55
- Issue
- 1
- Pages
- 53-62
- ISSN
- 0163-5581 (ISSN-L)
- 1532-7914
- OpenAlex
- W1976406882
- Cited by
- 330
- References
- 22
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- closed
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