Comparison
Low-Dose Naltrexone vs Vitamin D3 + K2
Side-by-side of Low-Dose Naltrexone and Vitamin D3 + K2. 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.
Vitamin D3 + K2
Vitamin D3 K2 supplement profile: cholecalciferol at 1000-4000 IU/day corrects deficiency, MK-7 directs calcium to bone, away from arteries.
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
Vitamin D3 + K2
- •Reduces non-vertebral fractures 10-20% in older adults at 800 IU/day or above when combined with calcium
- •VITAL trial showed neutral results on primary CV and cancer endpoints at 2000 IU/day over 5 years
- •Vitamin D supplementation reduces respiratory infection incidence ~10-20% in deficient populations
- •K2 MK-7 has 72-hour plasma half-life vs 1-2 hours for MK-4; once-daily dosing is sufficient
- •Synergy hypothesis is largely preclinical; dedicated combination RCTs are limited
- •Daily dosing outperforms bolus dosing for immune and infection outcomes
Side-by-side
| Attribute | Low-Dose Naltrexone | Vitamin D3 + K2 |
|---|---|---|
| Category | pharmaceutical | supplement |
| Also known as | LDN, naltrexone (low dose) | cholecalciferol + menaquinone, D3/K2, vitamin D3 with MK-7 |
| Half-life (hr) ↗ | 4 | 360 |
| Typical dose (mg) ↗ | 4.5 | 0.05 |
| Dosing frequency | once daily, typically at bedtime | daily with a fat-containing meal |
| Routes | oral | oral |
| Onset (hr) | 1 | 24 |
| Peak (hr) | 1.5 | 168 |
| Molecular weight | 341.4 | 384.64 |
| Molecular formula | C20H23NO4 | C27H44O (D3); C46H64O2 (MK-7) |
| 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. | D3 converts to calcidiol then calcitriol, activating the vitamin D receptor (VDR) to increase intestinal calcium absorption and modulate immune and bone gene transcription. K2 carboxylates osteocalcin and matrix Gla protein, directing calcium toward bone and inhibiting vascular calcification. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | Dietary supplement (global) |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Not scheduled |
| Pregnancy | Insufficient data; not routinely recommended | Recommended at standard doses for fetal bone development; consult clinician at higher doses |
| CAS | 16590-41-3 | 67-97-0 |
| PubChem CID | 5360515 | 5280795 |
| Wikidata | Q426444 | Q139347 |
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)
Vitamin D3 + K2
Common side effects
- GI upset at high doses
- headache (rare)
- hypercalcemia (only at sustained very high D3 doses)
Contraindications
- hypercalcemia
- sarcoidosis
- active hyperparathyroidism
- warfarin therapy (K2 component requires stable intake)
Interactions
- warfarin: K2 component can affect anticoagulation; maintain stable intake and inform anticoagulation clinic(moderate)
- thiazide diuretics: additive calcium retention; hypercalcemia risk with high-dose D3(moderate)
- digoxin and calcium channel blockers: additive effects from D3-induced hypercalcemia(moderate)
- glucocorticoids: reduced vitamin D efficacy and bone effects(moderate)
- cholestyramine and orlistat: bind fat-soluble vitamins; separate dosing by 2 to 4 hours(moderate)
Which Should You Take?
Vitamin D3 + K2 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 bone density, pick Vitamin D3 + K2.
- → If your priority is healthspan extension, pick Vitamin D3 + K2.
Edge case: If you want to avoid prescription-only, Vitamin D3 + K2 is the more accessible choice.
Default choice: Vitamin D3 + K2. 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 Vitamin D3 + K2?
Low-Dose Naltrexone and Vitamin D3 + K2 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 Vitamin D3 + K2?
Low-Dose Naltrexone half-life is 4 hours; Vitamin D3 + K2 half-life is 360 hours.
Can you stack Low-Dose Naltrexone with Vitamin D3 + K2?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper