Sulforaphane is subjectively quiet — most users feel nothing acute. This is mechanistically expected: NRF2 activation is a transcriptional event, peaks 12-24 hours after dose, and produces a defensive state rather than a stimulating one. Compare to caffeine (acute), creatine (subtle endurance), or modafinil (loud) — sulforaphane sits at the far quiet end of the subjective spectrum.

Subtle effects sometimes reported in chronic use (≥4 weeks):

• Slight reduction in seasonal allergic symptoms (NRF2-mediated airway inflammation modulation).
• Easier recovery from heavy training sessions — less soreness on day 2 (Malaguti-style endogenous antioxidant story, plus small reduction in baseline inflammatory tone).
• Reduced "stuffy room" reactivity (subjective tolerance of poor indoor air, smoky environments).
• Modestly clearer skin in some users (likely NRF2 induction in keratinocytes + hepatic detox capacity).
• No mood elevation, no cognitive sharpening, no energy effect. Anyone claiming acute nootropic benefit from sulforaphane is reading placebo or attribute-confusing it with the rest of their stack.

Possible aversive signal — the "sulforaphane belly": ~10-15% of users get bloating, gas, or loose stools from broccoli sprouts (FODMAP raffinose family + isothiocyanate GI irritation). Avmacol/Prostaphane capsule forms cause less GI complaint than fresh sprouts. Some users report mild nausea on empty stomach at first dose — solved by taking with food.

Subjective placebo problem. Because the effect is transcriptional and slow-onset, sulforaphane sits in the category where "feel-based" titration doesn't work. You take it because the mechanism is well-characterized and the biomarker shifts are documented (urinary metabolites, GSH:GSSG ratio, NQO1 enzyme activity in lymphocytes) — not because Tuesday felt better than Monday.

• Pharmacodynamic tolerance: minimal-to-none in human data. Egner 2014 Qidong trial showed sustained urinary metabolite excretion across 12 weeks with no signal of waning effect. NRF2 doesn't down-regulate to chronic stimulation the way classical receptor systems do — instead the system maintains a higher transcriptional set-point.
• Theoretical over-induction concern. Sustained NRF2 activation in cancer cells confers chemo-resistance; in normal cells, no analogous problem documented. NRF2-addicted tumors (KEAP1 loss-of-function mutants) constitute a different scenario — chronically high NRF2 from genetic deficiency, not from periodic dietary stimulation.
• Cycling: not required. A pragmatic 5 days on / 2 days off pattern mirrors weekly biorhythms and saves on supplement cost without compromising benefit.
• Reset protocol: not needed. Discontinuation returns NRF2 baseline within a week; no rebound oxidative stress.

Synergistic with

• NAC (N-acetylcysteine): Complementary — NAC provides cysteine substrate for the glutathione synthesis NRF2 is upregulating. Stack works upstream (sulforaphane increases GCLC/GCLM enzyme machinery) and substrate-wise (NAC supplies precursor). Dylan: NAC already in V4 — natural pairing.
• Curcumin: Independent NRF2 activator + NF-κB suppressor. Different cysteine pattern on Keap1 (Cys151 and Cys288); plausibly additive transcriptional output.
• Resveratrol / pterostilbene: Sirtuin/AMPK and NRF2 modulators; modest additive antioxidant defense.
• Selenium (Se-methionine 100-200 µg/day): Selenium is required cofactor for selenoproteins including thioredoxin reductase and glutathione peroxidases — the enzymes NRF2 upregulates. Without adequate selenium, the NRF2 response is functionally incomplete.
• Glycine + cysteine (or whey protein): Substrate support for glutathione synthesis.
• Vitamin C / E (modest doses, e.g., food and standard multi): Compatible. Avoid megadoses (≥1 g vit C, ≥400 IU vit E) chronically around training — they blunt training-induced redox signaling (Paulsen 2014, Ristow 2009) without obvious upside.
• Quercetin / EGCG: Mild NRF2 activators; non-redundant addition for users targeting broad phase II support.

Avoid stacking with

• High-dose synthetic antioxidants chronically around training adaptations (1+ g vit C, 400+ IU vit E) — see above.
• Chemotherapy regimens (without oncologist sign-off): Sulforaphane's NRF2 induction may protect tumor cells from chemotherapy-induced oxidative stress; conversely, in some preclinical models it sensitizes. The interaction is context-dependent — discuss with oncology, do not self-stack during active cancer treatment.

Neutral / safe co-administration

• All of Dylan's V4 stack (Mg, NAC, citicoline, PS, DHA, curcumin, rhodiola, L-theanine, glycine, D3/K2, beta-alanine, vitamin C at moderate dose, ashwagandha) — neutral-to-positive.
• Modafinil — neutral. No mechanistic interaction.
• Peptides (BPC-157, TB-500, Semax, Selank) — neutral.
• SSRIs / SNRIs / common antidepressants — neutral.

Sulforaphane is mostly a transcriptional inducer, not a CYP substrate, so direct pharmacokinetic interactions are limited but real where they exist.

Phase II enzyme induction is the dominant interaction theme. NRF2 upregulates GSTs, UGTs, NQO1, and the MRP family of efflux transporters. This can theoretically reduce exposure to drugs cleared by these pathways:

• Acetaminophen / paracetamol: Sulforaphane is protective in acetaminophen-induced hepatotoxicity models (more GSH available to conjugate NAPQI). Counterintuitively makes acetaminophen overdose less dangerous, not more. Not clinically relevant at therapeutic acetaminophen doses.
• Chemotherapy agents (cisplatin, doxorubicin, paclitaxel, etc.): Mixed signals — protective for normal tissues in some models; can increase tumor MRP-mediated efflux and chemoresistance in NRF2-active tumors. Do not stack during active chemotherapy without oncologist sign-off.
• Warfarin: Theoretical mild reduction in INR via phase II induction; routinely monitored INR in real warfarin users would catch any meaningful effect. Vitamin K content of broccoli sprouts is a bigger concern than sulforaphane itself.
• Immunosuppressants (cyclosporine, tacrolimus): Theoretical reduction via MRP induction; not clinically documented but worth monitoring drug levels.
• Statins: No documented clinically relevant interaction.

Sulforaphane does NOT meaningfully affect CYP450 enzymes at dietary or supplemental doses (modest in vitro effects on CYP3A4 not replicated in human PK studies).

Hormonal contraceptives: No documented interaction. Sulforaphane does not induce CYP3A4 in vivo.

Alcohol: Hepatoprotective in animal models (NRF2 induction protects against alcohol-induced oxidative liver injury). For Dylan: zero alcohol baseline, moot.

Caffeine: No interaction.

Sulforaphane has the richest gene-diet interaction literature of any compound in this wiki — driven by the GST and NRF2 axis.

GSTM1 null (deletion of GSTM1 gene, ~50% of Caucasians, ~50% of Asians):

• GSTM1 conjugates sulforaphane to glutathione, the first step of mercapturate elimination.
• Null carriers clear sulforaphane more slowly → higher and more prolonged plasma SFN exposure (Steck 2007, Gasper 2005, PMC2441942).
• Counterintuitive consequence: GSTM1-null users may benefit more from sulforaphane because the active compound persists longer at target. Epidemiology confirms: in the Singapore Chinese Health Study, GSTM1/T1 double-null carriers showed 57% colon cancer risk reduction at high ITC intake vs minimal benefit in wild-type.
• Dylan's 23andMe data (June 2026) will report GSTM1 and GSTT1 deletion status. If null, prioritize sulforaphane more aggressively; if intact, dose-response may be milder.

GSTT1 null (~20% Caucasians, ~50% Asians):

• Similar logic; null carriers benefit more from dietary ITC exposure.
• Combined GSTM1/T1 double-null is most strongly associated with cancer chemoprevention benefit.

GSTP1 Ile105Val (rs1695):

• The Val/Val variant has reduced enzymatic activity toward sulforaphane → again, slower clearance, longer exposure.
• Less robust signal than GSTM1/T1 null but worth flagging.

*NQO1 2 (Pro187Ser, rs1800566):

• 187Ser allele has near-zero enzyme activity. ~4% of Caucasians homozygous.
• These individuals may need sulforaphane more (deficient phase II baseline) and respond more dramatically to NRF2 induction of compensatory enzymes.

NFE2L2 promoter polymorphisms (NRF2 gene):

• rs6721961 (-617 C>A) — A allele associated with reduced NRF2 expression; carriers may benefit from supplemental NRF2 induction.

Practical takeaway. No genotype contraindicates sulforaphane. Several genotypes (GSTM1-null, GSTT1-null, GSTP1 Val/Val, NQO1*2, NFE2L2 -617A) amplify expected benefit. Dylan should re-read this section after his 23andMe upload (target: June 2026 results).

This is the section that matters most for sulforaphane, because the gap between "active product" and "inert product" is wider than any other compound in the wiki. The #1 user error is buying broccoli seed extract without active myrosinase and getting essentially no sulforaphane.

Tier 1: Most reliable

Tier 2: Inferior but acceptable

• Stabilized free sulforaphane capsules (e.g., MaxN-Fuze, Pure Encapsulations Sulforaphane Glucosinolate): Capsules of preformed SFN are unstable on shelf — degradation 20-50% within 6-12 months even refrigerated. Some products use cyclodextrin or other stabilizers. Verify recent third-party assay before buying.
• Sulforaphane in functional beverages, candies, etc.: Marketing claims dramatically exceed actual SFN delivery. Skip.

Tier 3: Mostly inert — AVOID

• "Broccoli seed extract" or "glucoraphanin"-only products without myrosinase — what almost every Amazon seller sells. Conversion in gut depends on β-glucosidase activity of resident microbiota, which varies 10-100× between individuals. Some users get ~10% conversion; many get effectively zero. You can spend $30/month on inert powder and get nothing. Read the supplement facts panel — if "myrosinase" or "active enzyme" isn't listed, skip.
• "Broccoli supplement" / "broccoli concentrate" without specified glucoraphanin content — meaningless.
• Cooked broccoli, frozen broccoli, broccoli powder: Myrosinase is destroyed by heat >70°C. The pre-formed glucoraphanin is still present, but with no plant enzyme. Rescue trick: sprinkle freshly ground mustard seed powder (raw — never cooked) over cooked broccoli. Mustard contains thermostable myrosinase that converts cooked broccoli's glucoraphanin. This works and is well-validated (Saha 2012; Okunade 2018, PMID 29806738).

Quality tips

• Sprouts at home: Use organic broccoli seeds rated for sprouting (e.g., Sproutman, True Leaf Market, Mumm's). Avoid commercial sprouting-supply rinses unless rated food-safe (E. coli/Salmonella risk on raw sprouts is real but manageable — 3× daily water rinse + airflow keeps it controlled). Look for "BroccoSprouts" branded glucoraphanin-rich cultivar seeds for highest density.
• Capsules: Buy from manufacturers reporting third-party assay of SFN-yield-per-cap (Avmacol does this; most generics do not).
• Cost-per-effective-dose: Home sprouts $5/month, Avmacol $50/month, generic "broccoli seed extract" $20/month for effectively nothing.

Dylan's recommended sourcing: Home-grow sprouts as the cheapest, most data-aligned route ($25 starter kit, $10 seeds, 3 days germination, infinite resupply). Avmacol Extra Strength as backup for travel days. Skip every other product in the category until they prove active myrosinase content.

Baseline (before starting)

• CBC, CMP, ALT/AST, lipids, fasting glucose, HbA1c — standard annual panel
• TSH, free T4 — confirm euthyroid baseline (rules out iodine-deficient hypothyroid that could confound goitrogen narrative)
• 25(OH)D and ferritin — covered in Dylan's June 2026 panel
• Genotyping: GSTM1, GSTT1, GSTP1, NQO1, NFE2L2 — Dylan's 23andMe upload (June 2026) covers these; interpret via Promethease.

During use

• 3-6 months: Repeat lipids, fasting glucose, ALT/AST — sulforaphane shouldn't move any of these in a 20yo healthy adult, but baseline + monitoring catches confounds.
• Annual: TSH check — paranoia-level surveillance, expected to be unchanged.
• Subjective sleep, training recovery, allergic-symptom diary — week-on/week-off comparison if Dylan wants to test his own n=1 response (sulforaphane is one of the harder compounds to feel acutely, so this self-blind test is honest).

Optional / advanced

• Urinary sulforaphane-mercapturate (SFN-NAC) excretion — only available in research labs (Hopkins, Oregon State) but is the direct biomarker of sulforaphane absorption + Phase II conjugation.
• Lymphocyte NQO1 enzyme activity — research-grade biomarker of NRF2-target gene induction. Available only academically.
• Plasma GSH:GSSG ratio — feasible commercially (e.g., Genova, Doctor's Data); shifts toward reduced (GSH) state on chronic sulforaphane.
• 8-OHdG, F2-isoprostanes — oxidative stress biomarkers expected to drop modestly. Commercially available; useful for longevity-oriented n=1 tracking.
• Urinary aflatoxin-N7-guanine, benzene-mercapturate — only relevant for users with documented high pollutant exposure; not standard.