Sulforaphane

Clinical Summary

Sulforaphane is an isothiocyanate produced when the enzyme myrosinase hydrolyzes glucoraphanin in cruciferous vegetables (broccoli sprouts = highest concentration, ~10-100x mature broccoli weight-for-weight). It is the most-studied Nrf2 activator on the planet — and it is also the most Rhonda-Patrick-branded compound, which dominates lay discourse to a degree unmatched by any other supplement/influencer pair.

The underlying mechanism (covalent modification of Keap1 cysteines → Nrf2 nuclear translocation → upregulation of >200 cytoprotective genes) is robust. Human clinical translation is uneven. Best human evidence: HbA1c reduction in dysregulated obese T2DM (Axelsson 2017, PMID 28615356; 2025 prediabetes replication missed primary endpoint — PMID 39929977); autism behavioral improvement in small-to-mid trials with substantial heterogeneity (2025 MAs positive but small effect sizes); schizophrenia negative symptoms as antipsychotic adjunct (Huang 2025, PMID 39832347); post-MI depression (single RCT); liver ALT reduction in high-normal subjects (Kagome Japan); H. pylori colonization attenuation (not eradication); narrow airborne pollutant detoxification in high-exposure populations (Qidong PMID 24913818).

Who benefits most: adults with documented metabolic dysregulation (HbA1c >7.5%, elevated ALT in NAFLD range), parents of children with ASD willing to try a low-risk 12-18 week adjunct, people living in high-air-pollution environments, and anyone eating a cruciferous-poor diet who wants a low-cost lever. Who doesn't benefit: people with well-controlled metabolic markers chasing longevity abstractions (animal-only data), people expecting BP drops (null in Christiansen 2010, PMID 20805984), and anyone expecting cancer prevention with clinical endpoints (human trials show biomarker changes only — classic surrogate endpoint trap).

Food-first is the rational default. Three days of home-grown broccoli sprouts (75 g) deliver 200-400 μmol glucoraphanin at ~$0.10/day versus $30-50/mo for Avmacol. The clinical trial literature uses Avmacol, BroccoMax, or Prostaphane — whether that brand specificity generalizes to generic broccoli sprout extract is not well-studied.

Indications & Evidence

Reading this table: Stars = evidence volume. Type = evidence kind (legend below). BH = Bradford Hill causal strength (/9). Safety = FAERS/trial signals. One row = one decision. Star rating cannot exceed causal taxonomy ceiling.

Type codes: DC=Direct causation | PC=Probable causation | UCC=Unreplicated causal | BC=Biomarker correlation | SE=Surrogate endpoint | ME=Mechanistic extrapolation | AHE=Animal→human | OA=Observational | RC=Reverse causation | CF=Confounded | FA=Folk/anecdotal | NE=No evidence BH: 7-9 strong causal | 5-6 moderate | 3-4 weak | 1-2 speculative | 0 none Safety flags: -- no FAERS signals | MON monitor known AEs | WARN FAERS/trial safety signal | AVOID contraindicated

Star legend: 5/5 multiple large RCTs + MAs | 4/5 several human RCTs | 3/5 some human pilot/mixed | 2/5 animal/very limited human | 1/5 none or debunked

Why cancer prevention is 2/5 not 5/5: Every human oncology trial completed to date (lung, prostate, breast, bladder, melanoma, panc) used biomarker endpoints — Ki-67, c-Myc, FASN, PSA velocity, histone acetylation, GST activity. Zero trials have reported survival, incidence, or recurrence endpoints with SFN monotherapy. Epidemiology on cruciferous intake (OR 0.64 case-control) is population-level dietary data that does not transfer directly to concentrated supplements. Per surrogate endpoint rule: biomarker improvement ≠ clinical benefit; cap claims at 3/5 for surrogate-only trials.

Prescribing

Dosing Table

Formulation Table

Bioavailability rule: Adding exogenous myrosinase (mustard seed powder, daikon radish) doubles SFN recovery from glucoraphanin — Mastaloudis/Fahey 2026 (PMID 41692762): 39.8% vs 18.6%. GR-only products without myrosinase waste ~50% of the glucoraphanin dose in people without the right gut bacteria.

Condition-Specific Protocols

T2DM (HbA1c >7.5%) Adjunct Protocol

Evidence: 3/5 (single large RCT positive in dysregulated subgroup; 2025 prediabetes replication missed primary — PMID 28615356, 39929977)

Phase 1 — Initiation (Weeks 1-2): 100 μmol GR/day (1 cap Avmacol or equivalent) AM with breakfast. Monitor: fasting glucose daily if on insulin/sulfonylurea; GI tolerance. Phase 2 — Therapeutic (Weeks 3-12): 225 μmol GR/day (Axelsson dose) split AM + PM with meals. Continue standard T2DM regimen (metformin not replaced). Recheck HbA1c at 12 wk. Phase 3 — Maintenance (Week 12+): If HbA1c improved ≥0.3%, continue at 200-225 μmol/day indefinitely with 6-monthly HbA1c. If no response, discontinue (cost-ineffective). Drug Interaction Timing: No interaction with metformin (synergistic AMPK); no interaction with GLP-1 agonists, SGLT2i, insulin. Expected Outcomes: HbA1c −0.3 to −0.4% at 12 wk in obese HbA1c>7.5% subgroup. No effect in HbA1c<7%. Stop/Reassess: No HbA1c improvement at 12 wk → discontinue.

ASD Adjunct Protocol (Parent-Supervised, 12-18 Week Trial)

Evidence: 3/5 (mixed MAs; Singh 2014 pilot positive, Zimmerman 2021 primary missed, Ou 2024 multicenter primary NS, 2025 Wang MA shows small-moderate effects on hyperactivity/social interaction — PMID 25313065, 34034808, 36427174, 40458076)

Phase 1 — Titration (Weeks 1-2): Start 50 μmol SFN/day AM. Avmacol pediatric 1 tab/day typical. Monitor: GI (expect transient gas), sleep, irritability. Phase 2 — Therapeutic (Weeks 3-18): 2.5 μmol/kg/day; typical 100-150 μmol split AM + PM with meals. Document behavior weekly (standardized: ABC-irritability subscale or parent-report scale). Phase 3 — Assessment (Week 18): Objective response = ≥25% improvement on baseline scale; continue. Non-responder = discontinue (cost/compliance burden). Expected Outcomes: Responder rate in RCTs ~30-50%; typical effect moderate hyperactivity and social interaction; irritability and repetitive behavior less consistent. Stop/Reassess: No improvement at 18 wk → discontinue. Discontinuation may cause reversion (Singh 2014 observed loss of improvement within 4 wk post-stop).

NAFLD / Elevated ALT Protocol

Evidence: 3/5 (Kikuchi 2015 Japan + Satomi/Kagome 2022 — PMID 26604653, 36618707)

Phase 1-3: 200-300 μmol GR/day (or 30 mg BSE) AM with breakfast, continuous. Recheck ALT/AST/GGT at 12 and 24 wk. Expected Outcomes: ALT reduction ~5-10 U/L at 24 wk in high-normal baseline; no effect if ALT already normal. Stop/Reassess: No ALT improvement at 24 wk → discontinue.

Safety

Interactions Table

Contraindications

• Known cruciferous allergy (rare IgE-mediated reactions to broccoli/cabbage)
• SOD1 familial ALS — avoid (hypothetical concern with antioxidant pathway activation in proteinopathy; no direct data)
• Active chemotherapy/radiation — discuss with oncologist; Nrf2 activation context-dependent
• Pregnancy (high-dose supplementation) — avoid >200 μmol/day supplemental; dietary cruciferous is fine
• Severe GI disease with extreme sulfur sensitivity — start low

Adverse Effects (ranked by frequency)

• Flatulence / sulfur breath ("broccoli burps"): 15-25% — mostly with fresh sprouts; gut bacterial metabolism to H₂S
• GI cramping, bloating, loose stools: 10-20% (dose-dependent) — reduce dose, take with meals, titrate
• Mild nausea: 5-10% — resolves with food
• Headache: <5% — transient
• Altered taste/urine odor (isothiocyanate metabolites): common, benign
• Skin rash (rare): <0.1%, discontinue if occurs
• Thyroid changes at supplement doses: not observed in 2024 SR with adequate iodine

SFX-01 (synthetic d,l-SFN) Phase I: 94% TEAE rate but all mild GI (Clack 2025, PMID 39520658) — typical cruciferous profile, not toxicity.

FAERS Signal Table (from BioMCP/OpenFDA)

No FAERS signal attributable to sulforaphane. Consistent with the general pattern that supplement FAERS data is primarily pharma-report noise where SFN is concomitant, not causative.

Monitoring Table

Special Populations

Renal Impairment

Hepatic Impairment

Synergies & Stacking

Antagonisms

• PPIs / antacids: reduce gastric-acid-dependent myrosinase activity — use pre-formed SFN
• Broad-spectrum antibiotics: deplete GR-converting gut bacteria — use pre-formed SFN during and 2-4 wk after
• Cooking at >60°C without added mustard: destroys native myrosinase; bioavailability drops to 3-12%

Individual Response Modifiers

Sex-Specific Considerations

No sulforaphane sex-dimorphism pharmacokinetic studies identified in 2024-2026.

Genetic Modifiers

Pragmatic rule: If uncertain about genotype or microbiome, use broccoli sprouts chewed thoroughly + mustard seed powder or Avmacol/BroccoMax with added myrosinase — both bypass the GSTM1/Bacteroides uncertainty.

Community & Anecdotal Evidence

Disclaimer: Real-world reports from online communities. None constitutes clinical evidence. N-sizes approximate. Selection bias, placebo, recall bias inherent. Presented for completeness, not medical guidance.

Dominant Sentiment

Mixed-positive across ~several hundred substantive threads (Reddit + Longecity + YouTube). Enthusiasm runs moderately ahead of the RCT signal. Community discourse is overwhelmingly shaped by Rhonda Patrick/FoundMyFitness content (90%+ of English-language lay material).

What Users Report

Community Dosing vs Clinical

Under-dosing likely explains a portion of "nothing happened" community reports.

Popular Stacks (Community)

Red Flags & Skepticism Notes

• MLM involvement: None specifically built on SFN. Truehope EMPowerplus (Canadian MLM) operates in adjacent autism/psychiatric supplement space — worth monitoring for future SFN product launches. No Black-Oxygen-Organics-scale MLM concentration.
• Influencer concentration — MAJOR: Rhonda Patrick / FoundMyFitness dominates >90% of English SFN discourse. FMF's premium membership business model (Supercast: $15-250/mo tiers, 4x MRR growth) depends on audience trust in her signature compounds. She states no affiliation with Avmacol/Thorne/BROQ, but functional promotional effect is massive; she is the single biggest discourse-shaping variable in this entire space.
• Academic-industry ties: Jed Fahey co-founded Brassica Protection Products LLC (1997) with Paul Talalay; patents on broccoli sprout cultivation invalidated by federal court 2001. Fahey advises Kuli Kuli (moringa). Most-quoted SFN scientist in popular media; podcast disclosure inconsistent across outlets. Mastaloudis (2026 bioavailability paper) = Dynamis Nutrition Science industry affiliation.
• Academic review concentration: Johns Hopkins Sawa/Fahey/Kensler lineage dominates positive reviews (PMID 40988712 favorable framing). ~50% of completed ClinicalTrials.gov SFN trials are unpublished (Saito 2025 — publication bias flag).
• Brand concentration: Avmacol (Nutramax, Maryland) is the supplement used in most Hopkins ASD + Smith schizophrenia RCTs — a near-monopoly on clinical evidence that may not generalize to generic products. Independent third-party assays (referenced on BROQ comparison page) show BrocElite delivers ~1.9 mg SFN/serving vs marketing-implied higher values — industry label variance is real.
• Astroturfing: Not a coordinated campaign comparable to spermidine (Oxford Healthspan/Leslie Kenny) or urolithin A (Timeline/Amazentis). The Patrick-Fahey-Avmacol triangle is concentration risk, not astroturfing per se.
• Pharma pipeline failure: SFX-01 (TheraCryf plc, formerly Evgen Pharma) Phase 2 NULL for SAH and TERMINATED for futility in CAP/COVID. Western pharma narrative effectively dead; supplement/food-based evidence stands or falls on its own.
• Dave Asprey's Mara Labs placement: Podcast episode #1175 is essentially product placement for BrocElite — the same product shown via independent assay to under-deliver SFN.
• Counter-narrative wing: Paul Saladino carnivore sphere attacks cruciferous goitrogens; 2024 SR (PMID 38612798) shows with adequate iodine this concern is overblown — folk anxiety runs ahead of evidence.

Folk vs Clinical Reality Check

Folk aligns with RCT data: H. pylori colonization attenuation, exercise/DOMS (older pilots only — most recent RCT null), benzene/acrolein excretion in polluted environments, liver ALT reductions in high-normal subjects.

Folk overstates evidence: BP drops (null Christiansen 2010), autism broad behavioral improvement (Zimmerman 2021 missed primary; Bent 2018 null), prediabetes glucose control (2025 Nat Microbiol missed primary — effect only in Bacteroides-operon+ subgroup), cancer prevention clinical endpoints (no completed trial), hair regrowth (no human RCT), general "detoxification" beyond narrow airborne pollutants.

Folk is more cautious than data warrants: Thyroid risk (2024 SR reassuring with adequate iodine).

Notable under-appreciated counter-signal: Peter Attia, one of the more skeptical longevity voices, treats SFN as "probably not harmful, possibly beneficial, not a priority" and rarely features it — in contrast to his enthusiastic treatment of rapamycin, creatine, vitamin D. The absence of Attia enthusiasm is informative.

Deep Dive: Mechanisms & Research

Nrf2-Keap1 Pathway (Primary Mechanism)

SFN covalently modifies cysteines on Keap1 → Nrf2 accumulates → nuclear translocation → binds Antioxidant Response Elements (ARE) → upregulates Phase II detox enzymes (GST, NQO1, UGT), glutathione synthesis (γ-GCS), antioxidant enzymes (SOD, catalase, GPx), heme oxygenase-1. Onset 24-72 h for gene expression changes; effect 4-8 h per dose.

Secondary Mechanisms with Clinical Translation

• NF-κB inhibition: Reduced TNF-α, IL-1β, IL-6, IL-8; COX-2, iNOS suppression. Relevant to IBD, RA, post-cardiac depression, schizophrenia negative symptoms.
• HDAC inhibition (particularly HDAC3): Epigenetic reactivation of tumor suppressors; informs cancer chemoprevention mechanism. Clinical translation: unclear — no trials with epigenetic endpoints.
• Mitochondrial biogenesis via PGC-1α: Hippocampal mitochondrial gene expression in mouse (PMID 35955572 Kagome/Hirosaki). May underpin the 42-mo MCI cognitive signal (PMID 41669080).
• Fatty acid synthesis inhibition (FASN, ACC1): Demonstrated in prostate cancer trial tumor tissue (PMID 41738426 Pitt 2026). Surrogate biomarker only.
• Anti-AGE axis: Endothelial protection in diabetic rats (PMID 29085055). Limited human translation.

Refuted Mechanisms

• Circulating extracellular-vesicle Nrf2 gene transfer: 2026 pilot (PMID 41603376) detected urinary SFN but NO change in Nrf2-regulated genes in sEVs.
• SFX-01 systemic pharma applications for SAH and CAP: Phase 2 NULL / TERMINATED.

Pharmacokinetics

• Tmax 1-3 h | Cmax 0.5-7 μmol/L dose-dependent | T½ 1.77-2.23 h plasma SFN; metabolites 24-48 h
• Volume of distribution: high (lipophilic); crosses BBB, placenta, prostate, bladder, breast tissue (Atwell 2015)
• Metabolism: mercapturic acid pathway (GST → cysteinyl-glycine → cysteine → N-acetylcysteine conjugate = major urinary metabolite)
• Excretion: renal (>90% within 24 h)
• Inter-individual variability: 2-40 fold, driven by GSTM1/GSTT1 + Bacteroides operon + myrosinase activity

Clinical Trials (Selected — from BioMCP)

Scope: ~91 registered sulforaphane trials + 33 broccoli-sprout-extract trials; ~60 completed; ~50% of completed trials remain unpublished (Saito/Sawa 2025 review, PMID 40988712) — major publication bias flag.

Regulatory Status

• FDA: Not approved as drug. Marketed as dietary supplement (DSHEA). No FDA warning letters for SFN or BSE products identified (Jan 2025 Walmart Marketside broccoli recall was fresh florets, Listeria — unrelated).
• EMA: No EMA authorization.
• EU Novel Food: No dedicated SFN/BSE novel food authorization; broccoli sprout products marketed under national food-supplement pathways. Prostaphane (Nutrinov/Sulfodyne) sold in French pharmacies since 2012 as complément alimentaire.
• Japan: FOSHU / Food with Function Claims. Kagome Co. runs commercial broccoli sprout extract market with UMIN-CTR-registered clinical support.
• Medical guidelines: NOT mentioned in ADA 2024-2026 diabetes standards, AASLD MASLD/MASH guidance, Toronto Consensus or Maastricht VI H. pylori, NCCN oncology (bladder, prostate, H&N, melanoma), AAP/NICE autism, APA/Maudsley schizophrenia. Siafis 2022 NMA rates SFN evidence in autism as "very low / low confidence."
• Cochrane: No dedicated sulforaphane Cochrane review.

Ataraxia Verdict (as of 2026-04-17)

Evidence Classification (Mode 5: Evidence Classifier)

Hype Check (Mode 1: Fallacy Radar)

• Appeal to authority: "Rhonda Patrick takes it" / "Jed Fahey at Johns Hopkins says..." — dominant in lay discourse. Fahey has undisclosed/variably-disclosed Brassica Protection Products LLC and Kuli Kuli commercial ties.
• Hasty generalization: Singh 2014 N=44 male-only pilot → "SFN treats autism"; Axelsson 2017 N=97 dysregulated T2DM → "SFN improves diabetes" — both overgeneralized.
• Surrogate endpoint trap: Cancer chemoprevention trials show Ki-67 or c-Myc or PSA-velocity changes — not cancer incidence or survival. This is the classic vitamin-E precedent (biomarker improvement, clinical endpoint failure). Cap cancer claims at 2/5 until a trial with clinical endpoints completes.
• Cherry-picking: Saito 2025 (PMID 40988712) flags ~50% of completed ClinicalTrials.gov SFN trials as unpublished. Published corpus is likely biased toward positive results.
• Appeal to nature: "It's from broccoli, so it's safe/natural/therapeutic" — ignores that concentrated extracts at 225+ μmol/day are not a natural dietary pattern.
• Argument from popularity: "Millions use Avmacol" — Avmacol's near-monopoly on clinical evidence doesn't validate generic BSE products.

Evidence Gaps

• No completed cancer prevention trial with clinical endpoints (incidence, survival, recurrence)
• No head-to-head trial vs metformin (T2DM) or vs PPI-triple (H. pylori)
• No adequately-powered hypertension trial with modern methodology
• No multi-year safety data (>2 years continuous)
• No completed Phase 3 trial of any kind in any indication (NCT03932136 CHR-P is still recruiting)
• Sex-dimorphism pharmacokinetics not characterized
• Pediatric (<6 yr) safety absent
• Pregnancy/lactation safety absent
• Responder phenotyping beyond Bacteroides operon / GSTM1 incomplete
• Autism subgroup analysis suggests responder phenotypes exist but no biomarker is clinically actionable

Bias Flags (Mode 4: First Principles)

• Publication bias: ~50% of completed trials unpublished (Saito 2025) — published literature likely skewed positive.
• Academic concentration: Johns Hopkins Sawa/Fahey/Kensler/Talalay lineage authors ~30% of top-cited positive SFN papers; reviews tend favorable.
• Industry concentration: Avmacol/Nutramax provides study product for most Hopkins/Smith Avmacol RCTs; BroccoMax/Jarrow for Pitt prostate Phase 2; SFX-01 for TheraCryf's failed Phase 2 pipeline; Kagome for most Japanese RCTs.
• Evidence transportability: Avmacol-specific trial data may not generalize to generic BSE products with different glucoraphanin content, myrosinase activity, or stabilization.
• Population narrowness: Trial positives concentrate in narrow phenotypes — dysregulated obese T2DM, male ASD children, Chinese high-pollution exposure, post-MI depression, Japanese high-normal ALT. Generalization to "longevity/healthspan for healthy adults" is not evidence-based.
• Surrogate endpoint dominance: Every positive cancer signal is biomarker-based; no clinical-endpoint trial has completed positive.

Manipulation Flags (Mode 2: Manipulation Shield)

• Industry marketing: Avmacol/BroccoMax/Prostaphane/BROQ/BrocElite compete on near-identical claims with opaque label-to-content variance (independent assays show BrocElite under-delivers).
• Influencer economics: Rhonda Patrick's FoundMyFitness premium membership ($15-250/mo) depends on audience trust in signature compounds; SFN is her #1 branded compound. No disclosed affiliation with specific brands, but functional promotional effect is enormous. Dave Asprey hosts BrocElite founders (Mara Labs) in product-placement podcast episode. Ben Greenfield generic enthusiasm.
• Academic-industry pipeline: Jed Fahey — Brassica Protection Products LLC co-founder (patents invalidated 2001), Kuli Kuli SAB; disclosure inconsistent across media appearances. Mastaloudis/Fahey 2026 bioavailability paper = Dynamis Nutrition Science industry affiliation. Kagome employs Shimizu (first-author on 42-mo cognition pilot).
• Counter-narrative manipulation: Paul Saladino carnivore sphere attacks cruciferous goitrogens; 2024 SR (PMID 38612798) refutes with adequate iodine. Counter-narrative serves carnivore-product sales.
• Pharma FUD absent: No pharma fearmongering campaign — SFN doesn't displace a specific drug profitably (metformin is generic, PPIs are OTC), so no competitor has incentive to attack it.
• Cui bono summary:
  • If you take it: Avmacol/Nutramax, Jarrow, Thorne, TheraCryf investors, FoundMyFitness membership, Fahey's advisory roles, Kagome, broccoli seed sellers win.
  • If you don't: carnivore-product sellers (Saladino ecosystem), competing longevity supplement makers (NAD+, senolytics) win.
  • Most honest framing: dietary broccoli sprouts at $3-15/mo captures most of the benefit at the lowest manipulation surface.
• Red team highlight (single most concerning angle): The publication-bias + narrow-Avmacol-product combination means published trial data is likely simultaneously (a) selected for positive outcomes and (b) tied to a specific commercial formulation that may not generalize. Even if Avmacol works, the generic SFN supplement market may be substantially less effective than the published corpus suggests.

Decision Support (Mode 3: Clarity Compass)

• Health utility score: 5/10 — Real but modest effects in specific conditions with specific baselines. Useful as a narrow adjunct; not a longevity panacea. The mechanism (Nrf2) is real; the clinical translation is uneven; the hype outruns the data.
• Opportunity cost: Low financial ($3-50/mo depending on form), low complexity, minor GI nuisance. Food-first option (home-grown sprouts + mustard) has near-zero opportunity cost.
• Verdict: CONDITIONAL. Reasonable choice IF one or more of:
  • Dysregulated obese T2DM (HbA1c >7.5%) on metformin, as 12-wk adjunct with HbA1c endpoint
  • ASD parent-supervised 12-18 wk trial with documented baseline behavior scale
  • Chronic schizophrenia with residual negative symptoms on stable antipsychotics, under psychiatrist supervision, as 24-wk adjunct
  • Post-MI/ACS depression, as adjunct
  • High-normal ALT (NAFLD range) for 24-wk ALT trial
  • High air-pollution exposure environment
  • Cruciferous-poor diet seeking a cheap, low-risk Nrf2 lever
• SKIP if:
  • Expecting BP reduction, weight loss, hair growth, or cancer prevention with clinical endpoints
  • Well-controlled metabolic markers, chasing longevity abstractions
  • Pregnancy (use dietary cruciferous instead)
  • Hemodialysis (null Nrf2/NF-κB response in crossover)
• Preferred form: Home-grown or purchased fresh broccoli sprouts chewed thoroughly or blended with mustard seed powder (>2x bioavailability boost vs capsules without myrosinase). Capsule fallback: Avmacol or BroccoMax with confirmed myrosinase content.

Bottom Line

Sulforaphane is the most-studied Nrf2 activator with the most-hyped lay discourse and the most-consistent gap between hype and data. It is not a longevity miracle. It has real, modest, indication-specific value: dysregulated obese T2DM adjunct, ASD 12-18 wk trial, SCZ negative symptoms adjunct, NAFLD ALT, H. pylori colonization attenuation, airborne pollutant detox. Food-first (fresh sprouts + mustard) is the rational default at ~$3-15/mo. Capsule products carry brand-specific risk; Avmacol has the most trial evidence but a near-monopoly on it. ~50% of completed trials are unpublished — the real evidence base is smaller than the published corpus. Cancer chemoprevention claims ride almost entirely on surrogate biomarkers; the classic vitamin-E precedent is a live risk. Bradford Hill ceiling for most claims is 3-5 / 9.

Practical Notes

Brands & Product Selection

• Avmacol / Avmacol Extra Strength (Nutramax, Maryland) — used in Singh 2014 ASD pilot, Huang 2025 SCZ trial. Glucoraphanin + active myrosinase. NSF-certified. Most-trial-validated. $30-50/mo.
• BroccoMax (Jarrow) — used in Pitt Phase 2 prostate trial. Glucoraphanin + myrosinase. Third-party tested. $20-35/mo.
• Prostaphane (Nutrinov France) — glucoraphanin-only, no added myrosinase; relies on gut Bacteroides operon. Pharmacy-distributed in EU since 2012. €30-40/mo.
• SFX-01 / Sulforadex (TheraCryf) — synthetic d,l-SFN in α-cyclodextrin; pharma-grade; primarily research; Phase 2 failures in SAH and CAP limit consumer availability.
• BROQ — stabilized SFN; emerging premium market; $50-80/mo.
• Thorne Crucera-SGS — glucoraphanin-only, medical channel; $20-30/mo.
• BrocElite / Mara Labs — independent third-party assay showed delivery of ~1.9 mg SFN/serving vs marketing-implied higher values (BROQ comparison page). Caution warranted; industry label variance is real.
• Home-grown sprouting seeds — Mumm's (organic, high germination), Handy Pantry (non-GMO, tested for pathogens). $10-20 starter kit; pennies per dose.

Red flags: "proprietary blend" without glucoraphanin μmol disclosed, no myrosinase listed on GR products, no CoA available, MLM-only distribution, "cures cancer/reverses autism" claims.

Storage & Handling

• Fresh sprouts: refrigerate 35-40°F, 3-7 d shelf life. Rinse twice daily during sprouting; sanitize seeds with 3% H₂O₂ pre-soak to reduce Listeria/Salmonella risk (2011 German E. coli O104:H4 outbreak on sprouts remains the cautionary precedent).
• Capsules: room temp if shelf-stable; refrigerate after opening for enzyme-containing products (check label).
• Powders: mix into COLD or room-temperature liquids only — hot beverages destroy myrosinase.
• Freeze sprouts before blending (Rhonda Patrick method): Freezing then thawing preserves myrosinase activity while reducing pungency — now citation-verified via Okunade 2018.

Palatability & Compliance

• Fresh sprouts: pungent, radish-like bitter. Blend with banana/mango/pineapple + yogurt + honey; layer into sandwiches with hummus/avocado/cheese to buffer.
• Chew thoroughly (myrosinase release requires plant-cell rupture); swallowing whole wastes dose.
• Capsules: tasteless. Split AM + PM dose improves both PK and GI tolerability.
• Compliance tip: pair with an existing AM routine (coffee, breakfast, metformin); the #1 determinant of supplement efficacy is whether you actually take it consistently.

Exercise & Circadian Timing

• AM preferred — Nrf2 activation transient (4-8 h per dose); daily AM dosing aligns with waking hours when oxidative stress is rising.
• Split AM + PM for therapeutic doses (>300 μmol/day).
• Pre-workout caution: high-dose antioxidants immediately pre-exercise may blunt hormetic ROS-signaling and training adaptations. Take >2 h before OR immediately post-workout, not within 30 min pre.

Reference Ranges (Expected Biomarker Changes)

Cost

Best value: home-grown sprouts + mustard powder (~$3/mo for therapeutic dose). Best convenience/evidence balance: Avmacol or BroccoMax.

What We Don't Know

• Whether Avmacol-specific trial data generalizes to other BSE products at equivalent glucoraphanin dosing
• Whether >2 yr continuous high-dose supplementation is safe (clinical literature caps at ~24 wk)
• Whether GSTT1-null carriers need lower doses or benefit differently
• Whether the Bacteroides GR-converting operon is modifiable (probiotic augmentation unproven)
• Whether any cancer chemoprevention trial with clinical endpoints will be completed (all current human data is surrogate)
• What the 50% unpublished trials show — publication bias is likely material
• Whether the Kagome 42-mo MCI cognitive signal replicates in larger trials
• Whether the ADHD effect size from Iranian trial (d=0.97-1.45) replicates in non-Iranian populations
• Pediatric safety <6 yr
• Pregnancy/lactation safety at supplement doses
• Long-term thyroid safety in iodine-insufficient diets
• Whether NCT03932136 DROPS (Phase 3 CHR-P psychosis prevention, Shanghai, 300 N) replicates the negative-symptoms signal at psychosis conversion endpoint

References

Systematic Reviews & Meta-Analyses

• PMID 40988712 — Saito/Sawa/Ishizuka 2025, J Nutr Sci — Comprehensive review of 84 ClinicalTrials.gov trials, 39 published. ~50% unpublished — publication bias flag.
• PMID 41184790 — Kassar 2025, BMC Psychiatry — First SR/MA of SFN in schizophrenia (4 RCTs, N=369). Modest negative-symptoms improvement at 12 wk (MD −1.06), not sustained. LDL/TG reduced.
• PMID 40458076 — Wang 2025, EXCLI J — Autism SR/MA (6 RCTs). ABC SMD −0.43 hyperactivity, −0.43 social; irritability NS.
• PMID 41275316 — Long/Zhang 2025, BMC Pharmacol Toxicol — Autism integrated SR + network pharmacology (N=333).
• PMID 41071465 — Ramírez-Guerrero 2025, J Autism Dev Disord — Antioxidant therapies SR.
• PMID 38892516 — Baladia 2024, Nutrients — Broccoli consumption & cancer SR/MA. Cohort RR 0.89; case-control OR 0.64.
• PMID 38074675 — ElKhalifa 2023 — SFN in cancer SR (RCTs). 8 RCTs; heterogeneity precluded MA; no safety signal; 75% high RoB.
• PMID 38612798 — 2024 SR — Brassica & thyroid with adequate iodine. Reassures goitrogen concern.
• PMID 39741515 — 2024 SR — Brassicaceae for H. pylori. Reduces colonization, does NOT eradicate.
• PMID 38824824 — 2024 SR — SFN protection vs toxicants.
• PMID 31784171 — Uddin 2020 — Neuroprotection review (Nrf2 cascade in AD, PD, HD, stroke, TBI).
• PMID 33805772 — Kim 2021 — Preclinical AD review.
• PMID 33207780 — Schepici 2020 — Neurodegenerative disease review.
• PMID 37703962 — Mthembu 2023 — Diabetes complications review.
• PMID 36442719 — Holman 2023 — IBD + microbiota review.

Landmark Human RCTs

• PMID 25313065 — Singh 2014, PNAS — Original ASD pilot (N=44 males, 18 wk, 50-150 μmol/day). ABC-irritability −34% vs placebo; reversed upon stop.
• PMID 28615356 — Axelsson 2017, Sci Transl Med — T2DM RCT (N=97, obese, 225 μmol GR/day x 12 wk). HbA1c −0.41% in dysregulated HbA1c>7.5% subgroup.
• PMID 39929977 — Dwibedi/Fahey/Rosengren 2025, Nat Microbiol — Prediabetes RCT (N=74, 12 wk BSE). Missed primary endpoint. Responders = mild obesity + Bacteroides GR-converting operon+. −0.4 mmol/L FBG subgroup.
• PMID 39832347 — Huang/Smith 2025, J Clin Psychiatry — SCZ negative symptoms RCT (N=77, 24 wk, 1,700 mg Avmacol ES). PANSS-neg d≈0.8.
• PMID 40133020 — Chen/Huang 2025, J Psychiatr Res — Same NCT04521868 subset (N=42). Negative symptoms p=0.007; MATRICS cognitive NS.
• PMID 34033171 — Ghazizadeh-Hashemi 2021, Phytother Res — Post-MI depression RCT (N=60, 30 mg SFN x 8 wk). Positive.
• PMID 34034808 — Zimmerman 2021, Mol Autism — ASD RCT (N=57, 15 wk). Primary endpoints missed; metabolomic changes.
• PMID 36427174 — Ou 2024, J Autism Dev Disord (China multicenter, N=108). Primary outcomes NS; subgroup signals.
• PMID 24913818 — Egner 2014, Cancer Prev Res — Qidong China airborne pollutant RCT (N=291, 600 μmol GR/day). +40% benzene-GSH excretion.
• PMID 40041932 — Yuan/Kensler 2025, Cancer Prev Res — Phase II former smokers lung (N=43, 95 μmol x 12 mo). Ki-67 −20% vs +65% placebo (surrogate).
• PMID 41738426 — Hahm/Singh 2026, Cancer Prev Res — BroccoMax prostate Phase I/II (N=41, 4 wk). Tumor c-Myc, ACC1, FASN, Ki-67 reduced (surrogate).
• PMID 26604653 — Kikuchi 2015, World J Gastroenterol — NAFLD RCT (N=52, Kagome Japan).
• PMID 36618707 — Satomi/Kagome 2022, Front Nutr — Middle-aged high-normal ALT (N=70, 24 wk). ALT improved.
• PMID 41669080 — Shimizu/Itoh 2026, Front Nutr — Kagome/Hirosaki 42-mo MCI RCT (N=26, 30 mg GR/day). MPI p=0.012.
• PMID 41604557 — Ghannadi/Akhondzadeh 2025, Clin Neuropharmacol — Pediatric ADHD adjunct to MPH (N=70, 8 wk). Cohen's d 0.97-1.45.
• PMID 19349290 — Yanaka 2009 — H. pylori colonization (Qidong/JHU).
• PMID 25287166 — Chang 2015 — H. pylori Korean adjunct.

Negative / Null / Terminated Trials

• PMID 20805984 — Christiansen 2010, J Hum Hypertens — Null endothelial function in hypertensives.
• PMID 39028412 — Zolnourian/Bulters 2025 — SFX-01 SAS Study SAH Phase 2 (N=105). All primary endpoints NULL. GSTT1-null pharmacogenomic signal.
• PMID 38469377 — Long/Chalmers 2024 — SFX-01 CAP/COVID Phase 2 (N=133) TERMINATED for futility.
• PMID 41754227 — Cesanelli 2026, Nutrients — Eccentric exercise recovery crossover NULL.
• PMID 41603376 — Mitra 2026, Mol Nutr Food Res — NULL sEV Nrf2 gene modulation pilot.
• PMID 37619675 — Ribeiro 2024, J Ren Nutr — Hemodialysis crossover NULL (Nrf2/NF-κB/IL-6/TNF).

Pharmacogenomics, PK, Bioavailability

• PMID 41692762 — Mastaloudis/Fahey 2026, Sci Rep — Mustard myrosinase DOUBLES SFN bioavailability (39.8% vs 18.6%). Bacteroides GR-converting genes identified.
• PMID 16332662 — Gasper 2005, AJCN — GSTM1-null and SFN metabolism.
• PMID 21294053 — Cramer/Jeffery 2011, Nutr Cancer — PK (Tmax ~2h, T½ 1.77-2.23h).
• PMID 16848517 — Vermeulen 2006, J Agric Food Chem — Urinary ITC metabolites as biomarker.
• PMID 31590262 — Yagishita/Fahey/Dinkova-Kostova 2019, Molecules — Source vs dose review.
• PMID 39670818 — Zhu/Cremonini/Mastaloudis 2025, Food Funct — Bioavailability optimization model.
• PMID 39520658 — Clack 2025, Adv Ther — SFX-01 Phase I healthy males.

Mechanistic / Preclinical

• PMID 18504070 — Clarke 2008 — Multi-targeted cancer prevention seminal.
• PMID 38902597 — Liu 2024, Cancers — SFN cancer prevention mechanisms comprehensive review.
• PMID 35955572 — Shimizu/Kagome 2022, IJMS — Hippocampal mitochondrial biogenesis, mouse cognitive decline.
• PMID 33160067 — Calabrese 2020, Mol Aspects Med — Hormesis / vitagenes.
• PMID 33471780 — Qi 2021, Sci Rep — HCC anti-angiogenesis + C. elegans lifespan.
• PMID 34935814 — Wei 2022 — Intestinal inflammation review.
• PMID 28274798 — Deng 2017, Mol Ther — Broccoli nanoparticles colitis.
• PMID 29085055 — Pereira 2017 — Diabetic endothelial.
• PMID 26583056 — Bai 2015 — Diabetic cardiomyopathy.
• PMID 32471217 — Kuran 2020 — Breast cancer review.
• PMID 24117885 — Houghton 2013, Nutr Rev — Translational safety review (up to 800 μmol/day well tolerated).

Prostate Cancer (Phase II)

• PMID 25431127 — Alumkal 2015, Invest New Drugs — OHSU recurrent prostate (N=20, 200 μmol x 20 wk). Mild GI only.
• PMID 25968598 — Cipolla 2015 — Prostaphane biochemical recurrence.

Celiac / Gluten

• PMID 39203879 — Sonzogni 2024 — Celiac organoid in vitro.