TY - JOUR
T1 - Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates
T2 - A clinical phase I study
AU - Shapiro, Theresa A.
AU - Fahey, Jed W.
AU - Dinkova-Kostova, Albena T.
AU - Holtzclaw, W. David
AU - Stephenson, Katherine K.
AU - Wade, Kristina L.
AU - Ye, Lingxiang
AU - Talalay, Paul
N1 - Funding Information:
their equity interest in BPP is managed according to university policies. P. Talalay’s son is the CEO of BPP. A portion of the proceeds of BPP is used to support cancer research, but no funds were provided to support this study. We thank Elizabeth Martinez (Coordinator) and Jared Christopher (Study Nurse) of the Drug Development Unit, Division of Clinical Pharmacology, Johns Hopkins School of Medicine, for help in carrying out these studies. These studies were supported by NIH Grant (RO1 CA093780), by the Johns Hopkins General Clinical Research Center (NIH Grant MO1-RR-00052), by the Lewis B. and Dorothy Cullman Foundation, by the McMullan Family Fund, and by the Monsanto Company. Address correspondence to Paul Talalay, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205. Phone: 410–955–3499. FAX: 410–502–6818. E-mail: ptalalay@jhmi.edu.
PY - 2006
Y1 - 2006
N2 - 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 μmol of glucosinolate (cohort A), 100 μmol of glucosinolate (cohort B), or 25 μmol 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.
AB - 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 μmol of glucosinolate (cohort A), 100 μmol of glucosinolate (cohort B), or 25 μmol 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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U2 - 10.1207/s15327914nc5501_7
DO - 10.1207/s15327914nc5501_7
M3 - Article
C2 - 16965241
AN - SCOPUS:33749165612
SN - 0163-5581
VL - 55
SP - 53
EP - 62
JO - Nutrition and Cancer
JF - Nutrition and Cancer
IS - 1
ER -