Comparison
Berberine vs Low-Dose Naltrexone
Side-by-side of Berberine 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.
Berberine
Berberine supplement guide: 1500 mg/day lowers fasting glucose and HbA1c, AMPK activation, metformin parity in RCTs, dihydroberberine absorption.
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
Berberine
- •Lowers HbA1c by ~0.7% versus placebo at 1500 mg/day across 27-trial meta-analysis (Lan 2015)
- •Roughly comparable to metformin on fasting glucose and HbA1c in small head-to-head RCTs (Yin 2008)
- •Reduces LDL cholesterol 10-20% and triglycerides 15-25% via PCSK9 inhibition
- •Activates AMPK, the cellular energy sensor that drives insulin-independent glucose uptake
- •Oral bioavailability under 1%; dihydroberberine is the higher-absorption alternative at lower doses
- •GI side effects affect 10-30% at 1500 mg/day; split dosing with meals reduces incidence
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 | Berberine | Low-Dose Naltrexone |
|---|---|---|
| Category | natural | pharmaceutical |
| Also known as | berberine HCl, berberine hydrochloride | LDN, naltrexone (low dose) |
| Half-life (hr) ↗ | 3 | 4 |
| Typical dose (mg) ↗ | 1500 | 4.5 |
| Dosing frequency | 3x daily with meals | once daily, typically at bedtime |
| Routes | oral | oral |
| Onset (hr) | 2 | 1 |
| Peak (hr) | 3 | 1.5 |
| Molecular weight | 336.36 | 341.4 |
| Molecular formula | C20H18NO4+ | C20H23NO4 |
| Mechanism | Activates AMP-activated protein kinase (AMPK), suppressing hepatic gluconeogenesis and lipogenesis while increasing peripheral glucose uptake. Inhibits PCSK9 transcription, modulates bile acid signaling, and shifts gut microbiome composition. | 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 | Dietary supplement (US, EU, UK, Canada); Rx in some Asian jurisdictions | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) |
| WADA status | allowed | allowed |
| DEA / Rx | Not scheduled | Rx only (not a controlled substance) |
| Pregnancy | Contraindicated (kernicterus risk in neonates) | Insufficient data; not routinely recommended |
| CAS | 2086-83-1 | 16590-41-3 |
| PubChem CID | 2353 | 5360515 |
| Wikidata | Q411435 | Q426444 |
Safety profile
Berberine
Common side effects
- constipation
- diarrhea
- abdominal cramping
- flatulence
- nausea
Contraindications
- pregnancy
- lactation
- neonatal jaundice
- severe liver disease
Interactions
- metformin: additive HbA1c reduction; additive GI side effects(moderate)
- insulin or sulfonylureas: additive hypoglycemia risk; dose adjustment may be required(major)
- statins (simvastatin, atorvastatin): CYP3A4 inhibition raises statin plasma levels(moderate)
- cyclosporine: raises cyclosporine levels through CYP3A4 and P-gp inhibition(major)
- calcium channel blockers (amlodipine): elevated plasma levels via CYP3A4 inhibition(moderate)
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?
Berberine comes out ahead for most readers on the criteria we weight: 3 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 metabolic health and glucose control, pick Berberine.
- → If your priority is healthspan extension, pick Berberine.
- → 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, Berberine is the more accessible choice.
Default choice: Berberine. 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 Berberine and Low-Dose Naltrexone?
Berberine and Low-Dose Naltrexone differ in category (natural vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Berberine or Low-Dose Naltrexone?
Berberine half-life is 3 hours; Low-Dose Naltrexone half-life is 4 hours.
Can you stack Berberine 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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