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Is Low-Dose Naltrexone Safe for Your Liver? Exploring the Evidence: Integrative & Functional Medicine - San Antonio TX Dr. Kim

Often when asked about unlikely event by my patients, my reply is "anything is possible - but that event is improbable."


Low-dose naltrexone (LDN), typically taken at 4.5 mg or less per day, has gained attention for its potential to manage chronic pain, autoimmune conditions, and even alcohol use disorder (AUD). But with any medication, questions about safety arise—especially regarding the liver. Some concerns stem from older studies of high-dose naltrexone. So, what does the evidence say?

Let’s explore the facts, reported cases, and whether LDN truly poses a risk to your liver.


What Is Low-Dose Naltrexone (LDN)?

Naltrexone is an opioid antagonist traditionally used at higher doses (50–300 mg daily) to treat opioid addiction and alcohol dependence. However, LDN uses much smaller doses—typically 1 to 4.5 mg daily—to modulate the immune system and reduce inflammation.

LDN has gained popularity for off-label use in managing conditions such as:

  • Fibromyalgia

  • Multiple sclerosis (MS)

  • Crohn’s disease

  • Chronic fatigue syndrome

  • Autoimmune thyroiditis

But how safe is it for your liver?

Where Did the Concern About Liver Damage Come From?

Concerns over liver toxicity come from early studies using high-dose naltrexone (100–300 mg/day). In a 1986 study, 5 out of 26 obese patients taking 300 mg daily experienced elevated liver enzymes, which reversed after stopping the drug [1]. This led to an FDA black-box warning in the late 1980s.

However, this warning was removed in 2013 after re-evaluation found no strong evidence of liver injury at standard 50 mg doses [2].

But LDN is 1/66th to 1/100th of those doses, raising the question: Do those same risks apply?

What the Research Shows About LDN and Liver Safety

1. LDN Has a Strong Safety Record

Studies consistently show that LDN is well tolerated, even in individuals with mild to moderate liver impairment. A 2014 review emphasized its anti-inflammatory benefits with no significant liver side effects [3].

Interestingly, some research even shows liver function improvements in patients with alcohol use disorder (AUD) using naltrexone [4].

2. Real-World Liver Damage Cases: Almost None

There are no well-documented cases of liver injury directly attributed to LDN (≤4.5 mg). Some key findings:

  • Mild enzyme elevation (ALT/AST) has been reported, but these are:

    • Rare

    • Reversible

    • Usually tied to other causes (e.g., alcohol use, viral hepatitis) [5]

  • Study on Cirrhosis Patients (2022):Of 3,285 cirrhotic patients on naltrexone (most 50 mg), only 2% had elevated enzymes—and no cases were deemed probable drug-induced liver injury (DILI) [6].

  • Mixed Population Study:In a study of 160 patients (with/without liver disease) taking 25–50 mg naltrexone, only 3 showed mild enzyme increases (1.2 events per 1,000 persons/year). Those with liver disease actually showed improvement [7].

3. LDN Might Even Help the Liver

Surprisingly, LDN may have hepatoprotective effects:

  • Animal studies on autoimmune hepatitis showed LDN:

    • Reduced liver inflammation

    • Improved ALT, AST, and bilirubin levels [8]

  • In human studies, LDN used for AUD has been linked to:

    • Lower alcohol intake

    • Reduced liver enzyme levels [4]

Key Takeaways

  • ✅ No evidence links LDN (≤4.5 mg/day) to serious liver injury.

  • ⚠️ Mild enzyme elevations may occur—but they are rare and usually unrelated to LDN.

  • 🚫 Concerns about liver toxicity come from high-dose naltrexone, not LDN.

  • 🧪 For people with pre-existing liver conditions, routine monitoring of liver enzymes is wise.

  • 🌿 Some studies suggest LDN may support liver health in autoimmune or alcohol-related liver conditions.

Bottom Line: Is LDN Safe for the Liver?

Yes—LDN appears to be liver-safe at the typical doses of 1 to 4.5 mg per day. The fears around liver toxicity stem from outdated high-dose studies, not from the low-dose applications used in functional and integrative medicine.

In fact, evidence suggests LDN could even benefit liver function under the right conditions.

Still, if you have a liver condition, it’s best to:

  • Consult your healthcare provider before starting LDN

  • Monitor liver enzymes (ALT/AST) during the first few months

Trusted Resources for Further Reading


📘 Serving San Antonio TX Integrative & Functional Medicine Using LDN for Treatng Neuropathy, Brain Fog, Fatigue


Dr. Yoon Hang Kim, MD is a board-certified physician specializing in integrative functional medicine, dedicated to uncovering root causes and providing personalized healing for chronic and complex conditions. He is a recognized expert in Low Dose Naltrexone (LDN) for treating neuropathy, brain fog, and fatigue. He offers telemedicine services across multiple states—including Quincy, IL and throughout Illinois, San Antonio TX and all of Texas, Missouri, Florida, and Atlanta as well as the rest of Georgia.



References

  1. Pfohl, D. N., et al. (1986). Naltrexone hydrochloride (Trexan): A review of serum transaminase elevations at high dosage. NIDA Res Monogr, 67, 66–72. PubMed

  2. FDA. (2013). Naltrexone label update. Link

  3. Younger, J., et al. (2014). Use of LDN as an anti-inflammatory treatment for chronic pain. Clinical Rheumatology, 33(4), 451–459. DOI

  4. Volpicelli, J. R., et al. (1997). Naltrexone and alcohol dependence: Subject compliance. Arch Gen Psychiatry, 54(8), 737–742. DOI

  5. LiverTox. (2020). Naltrexone. NIH Database

  6. Ayyala, D., et al. (2022). Safety of naltrexone in patients with cirrhosis. Journal of Hepatology, 76(5), 1123–1131. DOI

  7. Mitchell, J. E., et al. (1987). High-dose naltrexone and liver function. J Clin Psychiatry, 48(5), 191–195. PubMed

  8. Wang, H., et al. (2018). LDN and autoimmune hepatitis in mice. J Immunol Res, 2018, 1–10. DOI


 
 
 

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