Supplements That Support Melatonin Cofactors as Alternatives to Melatonin
L-tryptophan is the most effective supplement to support melatonin production as it is the essential amino acid precursor from which melatonin is synthesized. 1, 2
Key Melatonin Cofactor Supplements
L-tryptophan: As an essential amino acid and direct precursor to melatonin, L-tryptophan supplementation can support the body's natural melatonin synthesis pathway. However, it should be held 24 hours before surgery due to potential risk of serotonin syndrome when combined with certain medications. 1
Vitamin B6: Acts as a cofactor in the conversion of tryptophan to serotonin, which is then converted to melatonin. Adequate B6 levels are necessary for optimal melatonin synthesis. 2
Magnesium: Functions as a cofactor in the enzymatic reactions that convert serotonin to melatonin. Magnesium deficiency has been associated with reduced melatonin production. 2
Zinc: Serves as a cofactor for several enzymes involved in melatonin synthesis and has been shown to enhance melatonin production. 2
Folate (Vitamin B9): Supports methylation processes necessary for melatonin synthesis. 2
Vitamin B12: Works with folate in methylation reactions required for melatonin production. 2
Alternative Sleep-Supporting Supplements
For those seeking alternatives to direct melatonin supplementation, several evidence-based options exist:
Passionflower: Can be safely continued even in perioperative settings due to its anxiolytic effects and good safety profile. 1
Valerian: May be continued as it appears to be a safe supplement for sleep support, though evidence shows no objective benefit for sleep latency or quality. 1
Lavender: Consider continuing as supplementation has shown efficacy and safety in treating anxiety, including preoperatively, with no clinical evidence suggesting it potentiates anesthetic effects. 1
German chamomile: Can be continued as it may provide benefit in the perioperative period due to its anxiolytic effects. 1
Cautions and Considerations
Melatonin supplement quality concerns: Commercial melatonin supplements show significant variability in actual melatonin content (ranging from -83% to +478% of labeled amounts) and lot-to-lot variability up to 465%. Additionally, 26% of tested supplements contained serotonin as a contaminant. 3
Serotonin-affecting supplements: S-adenosylmethionine (SAM-e) should be held 24 hours before surgery as it increases serotonin turnover and norepinephrine and dopamine activity. 1
Limited efficacy of melatonin: Recent evidence suggests melatonin supplements may not significantly improve sleep duration or quality, and treatment effects show little heterogeneity among individuals. 4
Lemon balm caution: Hold for 2 weeks before surgery as there is evidence suggesting potential additive CNS depression when combined with sedatives or alcohol. 1
Special Populations
Beta-blocker patients: Night-time exogenous melatonin administration may be particularly beneficial for patients on beta blockers, as these medications reduce endogenous melatonin production via inhibition of adrenergic beta1-receptors. 5
Elderly patients: Melatonin may decrease delirium in hospitalized elderly patients and has been found safe in the perioperative period. 1
Cancer patients: While melatonin has been studied for cancer-related fatigue, evidence is insufficient to support its routine use for this indication. 1
Antioxidant Support for Melatonin Function
N-acetylcysteine: As a precursor of glutathione, it supports melatonin's antioxidant functions, though it should be held 24 hours before surgery due to potential increases in NO synthase production. 1, 6
Vitamin E: Has complementary antioxidant effects to melatonin but should be held 2 weeks before surgery due to potential antiplatelet effects. 1, 6