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Sulforaphane
The most potent dietary NRF2 activator ever characterized — an isothiocyanate generated in vivo from broccoli-family glucoraphanin by the enzyme myrosinase.
Aliases (1)
Overview
What is Sulforaphane?
The most potent dietary NRF2 activator ever characterized — an isothiocyanate generated in vivo from broccoli-family glucoraphanin by the enzyme myrosinase. Mechanism is unusually clean: covalent modification of Keap1's Cys151 frees the NRF2 transcription factor to induce ~200 cytoprotective genes (glutathione synthesis, NQO1, HO-1, GSTs, thioredoxin reductase). For Dylan — MMA training load + indoor air quality concerns + cancer family history risk-class — this is a MODERATE fit at 20-40 mg sulforaphane equivalent/day from 30-60 g broccoli sprouts or Avmacol Extra Strength 2 caps. The #1 user error is buying broccoli seed extract without myrosinase (mostly inactive in supplement form because cooking destroys the plant enzyme and gut β-glucosidase conversion is highly variable). Sourcing matters more than dose.
Pharmacokinetics
Research Indications
Glutathione synthesis
GCLC (glutamate-cysteine ligase catalytic), GCLM (modifier subunit) — the rate-limiting enzymes for GSH biosynthesis. Sulforaphane reliab…
Phase II conjugation enzymes
NQO1 (NAD(P)H quinone oxidoreductase 1), HMOX1 (heme oxygenase-1), GSTs (M1, T1, P1, A1) for xenobiotic conjugation.
Thioredoxin system
TXN, TXNRD1 (thioredoxin reductase 1).
Multidrug resistance proteins
MRP1, MRP2, MRP3 — efflux of conjugated toxins.
Aldehyde dehydrogenases
detoxify lipid peroxidation products.
Peptide Interactions
Complementary — NAC provides cysteine substrate for the glutathione synthesis NRF2 is upregulating. Stack works upstream (sulforaphane increases GCLC/GCLM en…
Independent NRF2 activator + NF-κB suppressor. Different cysteine pattern on Keap1 (Cys151 and Cys288); plausibly additive transcriptional output.
Sirtuin/AMPK and NRF2 modulators; modest additive antioxidant defense.
Selenium is required cofactor for selenoproteins including thioredoxin reductase and glutathione peroxidases — the enzymes NRF2 upregulates. Without adequate…
Substrate support for glutathione synthesis.
Compatible. Avoid megadoses (≥1 g vit C, ≥400 IU vit E) chronically around training — they blunt training-induced redox signaling (Paulsen 2014, Ristow 2009)…
Mild NRF2 activators; non-redundant addition for users targeting broad phase II support.
(1+ g vit C, 400+ IU vit E) — see above.
Sulforaphane's NRF2 induction may protect tumor cells from chemotherapy-induced oxidative stress; conversely, in some preclinical models it sensitizes. The i…
What to Expect
- Week 1Tolerability and dose-response.
- Week 2-4Early effect window.
- Week 4-8Peak benefit assessment.
- Week 8+Cycle decision point.
Side Effects & Safety 5
Side Effects
- 1GI upset — gas, bloating, loose stool, mild nausea — especially from fresh sprouts (raffinose + isothiocyanate GI signaling). Avmacol caps are gentler. Mitigation: take with food; start at half-dose; reduce sprout volume; consider dried-sprout extract if fresh causes issues.
- 2Sulfur burp / cruciferous breath — cosmetic only.
- 3Headache (rare, usually first 1-2 days)
- 4Heartburn from raw sprout fiber
- 5Subjective sense of "detox" symptoms — likely the mild Herxheimer-style induction of phase II enzymes mobilizing stored xenobiotics. Resolves within days.
When to Stop
- Thyroid concern (overstated in most contexts): Glucosinolate-derived thiocyanates compete with iodine at the sodium-iodide symporter. In iodine-deficient populations with very heavy cruciferous intake, clinical hypothyroidism has been documented (e.g., the famous "10 lb of bok choy/day case"). In iodine-replete populations (US adults consuming iodized salt, sea-vegetable, or eggs), the 2024 systematic review (PMC11012840) and the broccoli-sprout-beverage RCT both show no clinically meaningful effect on TSH, free T4, thyroglobulin, or autoimmune thyroid markers. Dylan eats normal iodized table salt + occasional fish — not a relevant risk.
- Pregnancy: Dietary cruciferous fine and widely consumed. High-dose supplemental sulforaphane has insufficient human data — avoid concentrated supplements during pregnancy out of precaution, not because of any specific signal.
- Bleeding risk: Theoretical from in vitro platelet aggregation suppression; no clinical reports of clinically meaningful bleeding.
- Drug-detox interactions: NRF2 induces phase II enzymes and MRP efflux — could theoretically reduce drug exposure for medications cleared by these pathways. See Drug Interactions.
- Week 1-2: GI adjustment to fresh sprouts. If persistent bloating, switch to Avmacol caps.
- Month 1-3: Monitor any rare detox-symptom complaints (skin breakouts, headache, fatigue) — usually resolves; persistent issues warrant dose reduction.
- Long-term: No documented chronic toxicity. Routine bloodwork yearly is sufficient surveillance for any user.
References
Egner et al. 2014 — Detoxication of airborne pollutants by broccoli sprout beverage in Qidong, China
PMID 24913818. The landmark human pollutant-detox RCT; 291 adults × 12 weeks, benzene conjugate +61%, acrolein +23%.
View StudyEgner et al. 2011 — Bioavailability of sulforaphane from two broccoli sprout beverages, Qidong crossover
PMID 21372038. Establishes the SFN vs glucoraphanin bioavailability ratio and myrosinase requirement.
View StudySingh et al. 2014 PNAS — Sulforaphane treatment of autism spectrum disorder
PMID 25313065. 40 young men, ASD, 50-150 µmol/day × 18 wks, ABC and SRS improvement in 46%.
View StudyAxelsson et al. 2017 Sci Transl Med — Sulforaphane reduces hepatic glucose production in obese T2D
PMID 28615356. 97 T2D patients, 150 µmol/day × 12 wks, fasting glucose + HbA1c reduction.
View StudyFahey, Zhang & Talalay 1997 PNAS — Broccoli sprouts as exceptionally rich source of phase II inducers
PMID 9294217. The foundational paper — 3-day sprouts contain 10-100× more glucoraphanin than mature broccoli.
View StudyMalaguti et al. 2009 J Appl Physiol — Sulforaphane protects skeletal muscle from exhaustive exercise damage
PMID 19713431. Rat exhaustion-exercise model, 25 mg/kg × 3 days, reduced CK + LDH.
View StudyCipolla et al. 2015 — Sulforaphane in men with biochemical recurrence after radical prostatectomy
PMID 25968598. 78 men, 60 mg stabilized free SFN × 6 mo, PSA doubling time +86%.
View StudyChristiansen et al. 2010 PLoS One — Broccoli sprouts and endothelial function in hypertension
PMID 20805984. Negative trial — no BP or FMD change at 4 weeks.
View StudyKomine et al. 2021 — Sulforaphane on muscle soreness post eccentric exercise
Human pilot, modest reduction in soreness and inflammatory markers.
View StudySaito et al. 2024 — KEAP1 sensor systems for electrophilic and oxidative stress (Cys151 / Cys273 / Cys288)
Mechanism paper resolving the Cys151 controversy; classifies SFN as Class I Cys151-dependent.
View StudyModification of Keap1 cysteine residues by sulforaphane (2011)
PMID 21391649. Mass-spec characterization of Keap1 cysteine modification by SFN.
View StudySteck et al. 2007 GSTM1 polymorphism and ITC metabolism
GSTM1 null carriers excrete ITC metabolites differently, supporting the slow-clearance / longer-exposure model.
View StudyOkunade et al. 2018 — Exogenous myrosinase from mustard seed increases SFN bioavailability
PMID 29806738. The mustard-seed-rescues-cooked-broccoli paper.
View StudyHoughton 2019 review — Sulforaphane "coming of age" as clinical nutraceutical
PMID 31737162. Synthesis of 20+ human trials.
View StudySulforaphane as a potential therapeutic agent — 2025 comprehensive review (84 clinical trials)
Most current systematic review; J Nutr Sci 2025.
View StudyBroccoli for the brain — 2025 review of neuroprotective mechanisms
Frontiers Cell Neurosci 2025; NRF2/BDNF/MeCP2 axis.
View StudyDo Brassica vegetables affect thyroid function? — 2024 systematic review
Resolves the goitrogen concern for iodine-replete adults.
View StudyBioavailability of sulforaphane from glucoraphanin-rich broccoli — control by active endogenous myrosinase
PMID 26524341. Quantifies the myrosinase-conversion bioavailability advantage.
View StudyKEAP1 and done? Targeting the NRF2 pathway with sulforaphane (Houghton 2017)
Mechanism review focused on the NRF2 pathway target.
View StudyAvmacol product information / Nutramax clinical-trial-grade formulation
Manufacturer reference for the best-validated supplement form.
View StudyLatest research
- reviewSulforaphane as a potential therapeutic agent — comprehensive analysis of 84 clinical trials84 registered trials, 39 published; effective doses 100-150 µmol/day; strongest evidence in healthy detoxification, early prostate/breast cancer (GSTM1-positive), T2D glycemic control; weakest in hypertension and respiratory disease.
- reviewBroccoli for the brain — review of neuroprotective mechanisms of sulforaphaneNeuroprotective efficacy demonstrated at 0.01-0.1 µM in cell culture; NRF2/BDNF/MeCP2 axis central to behavioral effects in autism and schizophrenia trials.
- mechanismSensor systems of KEAP1 — Cys151 vs Cys273/Cys288 electrophile classificationConfirmed sulforaphane is a Class I (Cys151-dependent) NRF2 inducer alongside dimethyl-fumarate and CDDO-Im; mass-spec resolved the 2010s Cys151 controversy.
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