Sulforaphane — The Nrf2 Activator
Sulforaphane is an isothiocyanate derived from glucoraphanin (found in cruciferous vegetables, especially broccoli sprouts) via the enzyme myrosinase. It is the most potent known natural activator of Nrf2 — the master transcription factor for the cellular antioxidant and detoxification response. Broccoli sprouts contain 20–100× more glucoraphanin than mature broccoli.
Mechanism of Action
Sulforaphane reacts with Keap1 (the Nrf2 inhibitor), releasing Nrf2 to translocate to the nucleus and activate the antioxidant response element (ARE). This upregulates >200 cytoprotective genes including glutathione synthesis enzymes, NQO1, HO-1, and thioredoxin reductase. Sulforaphane also inhibits NF-κB, activates AMPK, and has direct anti-cancer effects via histone deacetylase (HDAC) inhibition.
Human Trial Evidence
A 2014 Cancer Prevention Research RCT showed sulforaphane-rich broccoli sprout extract significantly reduced urinary aflatoxin-DNA adducts in a high-risk population. A 2017 Science Translational Medicine study showed sulforaphane improved social behaviour in autism spectrum disorder. Multiple RCTs confirm reductions in inflammatory markers and improved detoxification capacity.
Dosing Protocol
10–100 μmol/day of sulforaphane (equivalent to 30–300g broccoli sprouts). Supplements: 100–400 mg/day of broccoli sprout extract standardised to sulforaphane or glucoraphanin. Best taken with myrosinase-containing foods (mustard powder, daikon radish) if using glucoraphanin supplements. Avoid cooking broccoli above 70°C (destroys myrosinase).
Safety & Contraindications
Well-tolerated. GI discomfort at high doses. May cause hypothyroidism with very high intake (goitrogenic effect of cruciferous vegetables) — not a concern at typical supplement doses. Inhibits CYP3A4 — potential drug interactions. Avoid in pregnancy at high doses.
Key Papers
Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors
PNAS · 2002
Pharmacokinetics and pharmacodynamics of broccoli sprouts on the suppression of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice
Cancer Prevention Research · 2009