Indirect antioxidant activity of sulforaphane lasts significantly longer than direct antioxidants


Cellular protection against oxidative and electrophile toxicities is provided by two types of small-molecule antioxidants: [1]

Direct antioxidants

Direct antioxidants are redox active, short-lived, are sacrificed in the process of their antioxidant actions and need to be replenished or regenerated, and may evoke pro-oxidant effects.

Examples of direct antioxidants are:

  • Glutathione
  • Vitamin C
  • Vitamin E
  • Carotenoids

Indirect antioxidants

Indirect antioxidants may or may not be redox active. Indirect antioxidants activate the Keap1/Nrf2/ARE pathway resulting in transcriptional induction of a battery of cytoprotective proteins (also known as phase 2 enzymes) that act catalytically, are not consumed, have long half-lives, and are unlikely to evoke pro-oxidant effects. [2]

Examples of indirect antioxidants are:

  • Isothiocyanates (sulforaphane)
  • Curcuminoids
  • Resveratrol
  • Ecklonia cava
  • Milk thistle
  • Ashwaganda

Sulforaphane works as a potent catalyst to boost Phase II enzymes in the body. These detoxification enzymes trigger ongoing antioxidant action for at least 72 hours. As a result, the indirect antioxidant activity of sulforaphane lasts significantly longer than that of direct antioxidants due to the fact that the half-life of the Phase II enzymes it activates is measured in days. The half-life of direct antioxidants is usually measure in hours depending on the antioxidant in question. [3]

Indirect antioxidants, such as sulforaphane can induce the body to produce its own store of antioxidants, providing powerful defenses against oxidative stress for days after they are consumed.


[1] Direct and indirect antioxidant properties of inducers of cytoprotective proteins

[2] Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders.

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Sulforophane glucosinolate. Monograph. Altern Med Rev. 2010 Dec;15(4):352-60. Review. [PMID: 21194251]

Boddupalli S, Mein JR, Lakkanna S, et al. Induction of phase 2 antioxidant enzymes by broccoli sulforaphane: perspectives in maintaining the antioxidant activity of vitamins a, C, and e. Front Genet. 2012;3:7. Epub 2012 Jan 24. [PMID: 22303412]

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 USA. 1997 Sep 16;94(19):10367-72. [PMID: 9294217]

West LG, Meyer KA, Balch BA, et al. 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 Feb 25;52(4):916-26. [PMID: 14969551]

Riedl MA, Saxon A, Diaz-Sanchez D. Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clin Immunol. 2009 Mar;130(3):244-51. [PMID: 19028145]

Shapiro TA, Fahey JW, Wade KL, et al. Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. Cancer Epidemiol Biomarkers Prev. 2001 May;10(5):501-8. [PMID: 11352861]

Nestle M. Broccoli sprouts as inducers of carcinogen-detoxifying enzyme systems: clinical, dietary, and policy implications. Proc Natl Acad Sci USA. 1997 Oct 14;94(21):11149-51. [PMID: 9326574]

Wagner AE, Ernst I, Iori R, et al. Sulforaphane but not ascorbigen, indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture. Exp Dermatol. 2010 Feb;19(2):137-44. [PMID: 19558496]

Holst B, Williamson G. Nutrients and phytochemicals: from bioavailability to bioefficacy beyond antioxidants. Curr Opin Biotechnol. 2008 Apr;19(2):73-82. [PMID: 18406129]

Informational Reference:

Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxification enzymes (PDF)

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