Broccoli or Sulforaphane: Is It the Source or Dose That Matters?

Yoko Yagishita (Lead / Corresponding author), Jed W. Fahey, Albena T. Dinkova-Kostova, Thomas W. Kensler

Research output: Contribution to journalReview article

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Abstract

There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. We pay special attention to the challenges for better integration of animal model and clinical studies, particularly with regard to selection of dose and route of administration. More effort is required to elucidate underlying mechanisms of action and to develop and validate biomarkers of pharmacodynamic action in humans. A sobering lesson is that changes in approach will be required to implement a public health paradigm for dispensing benefit across all spectrums of the global population.

Original languageEnglish
Article number3593
Pages (from-to)1-38
Number of pages38
JournalMolecules and Cells
Volume24
Issue number19
DOIs
Publication statusPublished - 6 Oct 2019

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Keywords

  • broccoli
  • sulforaphane
  • glucoraphanin
  • myrosinase
  • chemoprotection
  • allometric scaling
  • clinical trials
  • Nrf2
  • toxicity

Cite this

Yagishita, Yoko ; Fahey, Jed W. ; Dinkova-Kostova, Albena T. ; Kensler, Thomas W. / Broccoli or Sulforaphane : Is It the Source or Dose That Matters?. In: Molecules and Cells. 2019 ; Vol. 24, No. 19. pp. 1-38.
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title = "Broccoli or Sulforaphane: Is It the Source or Dose That Matters?",
abstract = "There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. We pay special attention to the challenges for better integration of animal model and clinical studies, particularly with regard to selection of dose and route of administration. More effort is required to elucidate underlying mechanisms of action and to develop and validate biomarkers of pharmacodynamic action in humans. A sobering lesson is that changes in approach will be required to implement a public health paradigm for dispensing benefit across all spectrums of the global population.",
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author = "Yoko Yagishita and Fahey, {Jed W.} and Dinkova-Kostova, {Albena T.} and Kensler, {Thomas W.}",
note = "This work was supported by the Japan Society for the Promotion of Science [OT 290125], the National Institutes of Health [R35 CA197222], Washington State Andy Hill CARE Fund, The Lewis B. and Dorothy Cullman Foundation, Cancer Research UK [C20953/A18644], and BBSRC [BB/L01923X/1].",
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Broccoli or Sulforaphane : Is It the Source or Dose That Matters? / Yagishita, Yoko (Lead / Corresponding author); Fahey, Jed W.; Dinkova-Kostova, Albena T.; Kensler, Thomas W.

In: Molecules and Cells, Vol. 24, No. 19, 3593, 06.10.2019, p. 1-38.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Broccoli or Sulforaphane

T2 - Is It the Source or Dose That Matters?

AU - Yagishita, Yoko

AU - Fahey, Jed W.

AU - Dinkova-Kostova, Albena T.

AU - Kensler, Thomas W.

N1 - This work was supported by the Japan Society for the Promotion of Science [OT 290125], the National Institutes of Health [R35 CA197222], Washington State Andy Hill CARE Fund, The Lewis B. and Dorothy Cullman Foundation, Cancer Research UK [C20953/A18644], and BBSRC [BB/L01923X/1].

PY - 2019/10/6

Y1 - 2019/10/6

N2 - There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. We pay special attention to the challenges for better integration of animal model and clinical studies, particularly with regard to selection of dose and route of administration. More effort is required to elucidate underlying mechanisms of action and to develop and validate biomarkers of pharmacodynamic action in humans. A sobering lesson is that changes in approach will be required to implement a public health paradigm for dispensing benefit across all spectrums of the global population.

AB - There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. We pay special attention to the challenges for better integration of animal model and clinical studies, particularly with regard to selection of dose and route of administration. More effort is required to elucidate underlying mechanisms of action and to develop and validate biomarkers of pharmacodynamic action in humans. A sobering lesson is that changes in approach will be required to implement a public health paradigm for dispensing benefit across all spectrums of the global population.

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KW - sulforaphane

KW - glucoraphanin

KW - myrosinase

KW - chemoprotection

KW - allometric scaling

KW - clinical trials

KW - Nrf2

KW - toxicity

U2 - 10.3390/molecules24193593

DO - 10.3390/molecules24193593

M3 - Review article

C2 - 31590459

VL - 24

SP - 1

EP - 38

JO - Molecules and Cells

JF - Molecules and Cells

SN - 1016-8478

IS - 19

M1 - 3593

ER -