Does melatonin increase liver enzymes?

Does Melatonin Increase Liver Enzymes?

Melatonin generally does not increase liver enzymes; in fact, it may have hepatoprotective effects and has been shown to decrease liver enzymes in patients with fatty liver disease and statin-induced liver injury.

Evidence on Melatonin and Liver Enzymes

Clinical Guidelines Evidence

According to clinical guidelines on REM sleep behavior disorder treatment, melatonin is recommended with few side effects (Level B recommendation). In a Hong Kong Chinese population study cited in these guidelines, only 1 out of 71 patients experienced a "transient and reversible increase in liver enzyme" while taking melatonin 1. This isolated case suggests that liver enzyme elevation with melatonin is rare and typically not persistent.

Hepatoprotective Effects of Melatonin

Melatonin has demonstrated hepatoprotective properties in several clinical contexts:

1. Non-Alcoholic Fatty Liver Disease (NAFLD):

   • A meta-analysis of randomized clinical trials showed that melatonin supplementation significantly improved liver indices in NAFLD patients 2
   • Specifically, melatonin improved:
     • Aspartate aminotransferase (AST)
     • Alkaline phosphatase (ALP)
     • Gamma-glutamyltransferase (GGT)

2. Statin-Induced Liver Injury:

   • In patients with elevated liver enzymes due to statin therapy, melatonin (10mg daily) significantly decreased liver enzymes after 6 months 3:
     • AST: 97.2 ± 19.1 U/L to 52.8 ± 12.3 U/L (p<0.001)
     • ALT: 87.4 ± 15.6 U/L to 49.8 ± 14.5 U/L (p<0.001)
     • GGT: 84.1 ± 14.8 U/L to 59.6 U/L (p<0.001)

3. NAFLD Clinical Trial:

   • A randomized double-blind clinical trial found that 6mg of melatonin daily for 12 weeks improved liver enzymes in NAFLD patients 4:
     • Significant reductions in ALT (p=0.011) and AST (p=0.034)
     • Improvement in fatty liver grade (p=0.020)

Mechanism of Hepatoprotection

Melatonin's liver-protective effects appear to be related to its:

• Potent free radical scavenging properties
• Inhibition of inducible nitric oxide synthase (iNOS)
• Activation of antioxidant enzymes 5

Special Considerations

Liver Cirrhosis

Patients with liver cirrhosis may experience elevated daytime serum levels of melatonin due to decreased clearance, related to:

• Decreased liver blood flow
• Lowered activity of 6β-hydroxylase
• Competition with bilirubin in the intrahepatic transport system 6

This suggests that patients with advanced liver disease may need dose adjustments, though not necessarily due to safety concerns.

Clinical Implications

When prescribing melatonin:

1. Standard monitoring: Routine liver enzyme monitoring is not typically required in patients with normal liver function
2. Liver disease: In patients with pre-existing liver disease, monitoring may be prudent, though evidence suggests melatonin may actually benefit these patients
3. Dosing: Common therapeutic doses range from 3-12mg for sleep disorders 1

Conclusion

The available evidence indicates that melatonin does not typically increase liver enzymes in most patients. The single reported case of transient liver enzyme elevation among 71 patients suggests this is a rare occurrence. More compellingly, multiple studies demonstrate melatonin's hepatoprotective effects, particularly in conditions like NAFLD and statin-induced liver injury.