Comparison
Low-Dose Naltrexone vs Omega-3 (EPA/DHA)
Side-by-side of Low-Dose Naltrexone and Omega-3 (EPA/DHA). 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.
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.
Omega-3 (EPA/DHA)
Omega 3 fish oil profile: EPA/DHA marine fatty acids, 2-4 g/day cuts triglycerides 20-30%, REDUCE-IT showed 25% cardiovascular risk reduction on icosapent eth.
Effects at a glance
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
Omega-3 (EPA/DHA)
- •Reduces fasting triglycerides 20-50% at 2-4 g/day in hypertriglyceridemic patients
- •REDUCE-IT showed 25% relative risk reduction in major CV events at 4 g/day icosapent ethyl
- •Modest antidepressant effect (SMD ~0.40) for EPA-dominant formulations at 1-2 g/day
- •Atrial fibrillation incidence rises ~30-50% at 4 g/day; relevant for older patients with pre-existing CV disease
- •Tissue omega-3 index (RBC EPA + DHA) target ~8%; Western baseline typically 4-5%
- •Triglyceride and re-esterified triglyceride forms absorb ~70% better than ethyl esters in fasted state
Side-by-side
| Attribute | Low-Dose Naltrexone | Omega-3 (EPA/DHA) |
|---|---|---|
| Category | pharmaceutical | supplement |
| Also known as | LDN, naltrexone (low dose) | fish oil, EPA, DHA, marine omega-3 |
| Half-life (hr) ↗ | 4 | 48 |
| Typical dose (mg) ↗ | 4.5 | 2000 |
| Dosing frequency | once daily, typically at bedtime | 1 to 2 times daily with food |
| Routes | oral | oral |
| Onset (hr) | 1 | 4 |
| Peak (hr) | 1.5 | 12 |
| Molecular weight | 341.4 | 302.45 |
| Molecular formula | C20H23NO4 | C20H30O2 (EPA); C22H32O2 (DHA) |
| Mechanism | 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. | Substitutes arachidonic acid in membrane phospholipids, shifting eicosanoid production toward less-inflammatory 3-series prostaglandins and 5-series leukotrienes. Activates PPAR-alpha to lower hepatic VLDL/triglyceride synthesis. DHA modulates synaptic membrane fluidity and neuronal function. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | Dietary supplement; prescription forms (icosapent ethyl, omega-3 acid ethyl esters) for severe hypertriglyceridemia |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Not scheduled |
| Pregnancy | Insufficient data; not routinely recommended | Recommended at 200 to 600 mg DHA/day for fetal development |
| CAS | 16590-41-3 | 10417-94-4 |
| PubChem CID | 5360515 | 446284 |
| Wikidata | Q426444 | Q207688 |
Safety profile
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)
Omega-3 (EPA/DHA)
Common side effects
- fishy aftertaste
- eructation (fish burps)
- mild dyspepsia
- loose stools at high doses
Contraindications
- fish allergy (use algal omega-3 alternative)
- active bleeding disorders
- scheduled surgery (discontinue 5-7 days prior)
Interactions
- warfarin and DOACs: additive antiplatelet effect at 2+ g/day; meaningful bleeding risk(moderate)
- aspirin and antiplatelet agents: additive bleeding risk at high doses(moderate)
- statins: complementary cardiovascular effects; no pharmacokinetic interaction(minor)
- antiarrhythmics: high-dose omega-3 increases AF risk; relevant in pre-existing arrhythmia(moderate)
Which Should You Take?
Omega-3 (EPA/DHA) comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-A outcome catalogued. Low-Dose Naltrexone is the right call when one of the conditionals below applies.
- → If your priority is immune support, pick Low-Dose Naltrexone.
- → If your priority is pain modulation, pick Low-Dose Naltrexone.
- → If your priority is cardiovascular health, pick Omega-3 (EPA/DHA).
- → If your priority is healthspan extension, pick Omega-3 (EPA/DHA).
Edge case: If you want to avoid prescription-only, Omega-3 (EPA/DHA) is the more accessible choice.
Default choice: Omega-3 (EPA/DHA). Lower friction to source, a Tier-A evidence outcome catalogued, 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 Low-Dose Naltrexone and Omega-3 (EPA/DHA)?
Low-Dose Naltrexone and Omega-3 (EPA/DHA) differ in category (pharmaceutical vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Low-Dose Naltrexone or Omega-3 (EPA/DHA)?
Low-Dose Naltrexone half-life is 4 hours; Omega-3 (EPA/DHA) half-life is 48 hours.
Can you stack Low-Dose Naltrexone with Omega-3 (EPA/DHA)?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper