Comparison
Fisetin vs Low-Dose Naltrexone
Side-by-side of Fisetin and Low-Dose Naltrexone. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Fisetin
Fisetin is a flavonoid found in strawberries with senolytic activity in mouse models. Hickson 2019 confirmed senescent-cell clearance in human adipose tissue.
Low-Dose Naltrexone
Low dose naltrexone at 1.5 to 4.5 mg, one-tenth the 50 mg addiction dose. Compounded Rx. Small trials in fibromyalgia, Crohn's, Hashimoto's.
Effects at a glance
Fisetin
- •Flavonoid found in strawberries; most potent natural senolytic in screening assays (Yousefzadeh 2018)
- •Hickson 2019 confirmed reduced senescent-cell burden in human adipose tissue at 20 mg/kg pulsed for 2 days
- •Pulsed Mayo protocol (20 mg/kg/day x 2 days monthly) is the only dose with human biomarker evidence
- •Daily low-dose (100-500 mg) is mechanistically weaker but commonly used
- •Low oral bioavailability; with-fat dosing modestly improves absorption
- •Active cancer is a relative contraindication pending clearer polyphenol-treatment data
Low-Dose Naltrexone
- •Off-label use at 1.5 to 4.5 mg, roughly one-tenth the FDA-approved 50 mg addiction-treatment dose
- •Proposed mechanisms include brief opioid receptor blockade triggering rebound endogenous opioid release, plus TLR4 antagonism
- •Compounded prescription only; insurance rarely covers; cash prices 20 to 80 USD per month
- •Younger 2013 reported ~30% pain reduction in fibromyalgia at 4.5 mg in a small crossover trial
- •Smith 2011 reported endoscopic improvement in active Crohn's disease (n=40 placebo-controlled)
- •Vivid dreams affect 20 to 40% in first 2 weeks; manageable by switching to morning dosing
Side-by-side
| Attribute | Fisetin | Low-Dose Naltrexone |
|---|---|---|
| Category | supplement | pharmaceutical |
| Also known as | 3,7,3',4'-tetrahydroxyflavone | LDN, naltrexone (low dose) |
| Half-life (hr) ↗ | 2 | 4 |
| Typical dose (mg) ↗ | 500 | 4.5 |
| Dosing frequency | pulsed 2 days/month (Mayo protocol) or daily continuous (empirical) | once daily, typically at bedtime |
| Routes | oral | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 4 | 1.5 |
| Molecular weight | 286.24 | 341.4 |
| Molecular formula | C15H10O6 | C20H23NO4 |
| Mechanism | Senolytic via Bcl-2 family inhibition (Bcl-xL, Bcl-w); broad polyphenol with Nrf2 activation, mTOR inhibition at high concentrations, and antioxidant effects. | Brief mu-opioid receptor antagonism proposed to trigger compensatory upregulation of endogenous opioids; secondary TLR4 antagonism on microglia and immune cells contributes to anti-inflammatory effect. |
| Legal status | OTC dietary supplement | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement | Rx only (not a controlled substance) |
| Pregnancy | Insufficient data | Insufficient data; not routinely recommended |
| CAS | 528-48-3 | 16590-41-3 |
| PubChem CID | 5281614 | 5360515 |
| Wikidata | Q230614 | Q426444 |
Safety profile
Fisetin
Common side effects
- mild GI upset
- headache (rare)
Contraindications
- active cancer (theoretical, polyphenol interactions)
- pregnancy and lactation (insufficient data)
- concurrent CYP3A4-sensitive medications
Interactions
- statins (CYP3A4 substrates): theoretical reduction in statin clearance at high fisetin doses(minor)
- warfarin: theoretical CYP-mediated interaction; monitor INR if combining(moderate)
- other senolytics (rapamycin, dasatinib + quercetin): additive senolytic effect; pairing is investigational(minor)
Low-Dose Naltrexone
Common side effects
- vivid dreams
- sleep disruption
- headache
- mild GI upset
- fatigue (early)
Contraindications
- concurrent opioid use
- acute hepatitis or liver failure
- opioid dependence
- pregnancy (insufficient data)
Interactions
- opioid analgesics (oxycodone, morphine, codeine): blocks analgesic effect; precipitates withdrawal in dependent users(major)
- tramadol: blocks opioid component of analgesia(major)
- thyroid hormone replacement: may alter dose requirements after immune modulation; monitor TSH(minor)
Which Should You Take?
Fisetin comes out ahead for most readers on the criteria we weight: 2 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-B outcome catalogued. Low-Dose Naltrexone is the right call when one of the conditionals below applies.
- → If your priority is healthspan extension, pick Fisetin.
- → If your priority is focus or working memory, pick Fisetin.
- → If your priority is immune support, pick Low-Dose Naltrexone.
- → If your priority is pain modulation, pick Low-Dose Naltrexone.
Edge case: If you want to avoid prescription-only, Fisetin is the more accessible choice.
Default choice: Fisetin. Lower friction to source, and broader goal coverage. Reach for Low-Dose Naltrexone only if your priority sits squarely in the goals it owns above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Fisetin and Low-Dose Naltrexone?
Fisetin and Low-Dose Naltrexone differ in category (supplement vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Fisetin or Low-Dose Naltrexone?
Fisetin half-life is 2 hours; Low-Dose Naltrexone half-life is 4 hours.
Can you stack Fisetin with Low-Dose Naltrexone?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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