Can melatonin supplementation precipitate asthma exacerbations in a patient with a history of asthma, currently taking prednisone (a corticosteroid) for an acute asthma exacerbation?

Melatonin and Asthma Exacerbations: Clinical Recommendation

Melatonin supplementation should be used with significant caution in patients with asthma, as emerging evidence suggests it may potentiate bronchoconstriction and worsen nocturnal asthma symptoms, though it does not appear to cause acute exacerbations in all patients. 1, 2

Mechanism of Concern

Melatonin acts as a bronchoconstrictor through MT2 receptors expressed in airway smooth muscle, directly opposing the bronchodilatory effects of β2-adrenoceptor agonists. 1 This pharmacological interaction is particularly problematic because:

• Peak serum melatonin concentrations are inversely correlated with pulmonary function and are higher in patients with nocturnal asthma compared to healthy individuals 1
• Experimental data demonstrate that melatonin strengthens contraction responses in tracheal smooth muscle preparations exposed to acetylcholine and serotonin 2
• Melatonin attenuates the bronchodilatory effects of β2-adrenoceptor agonists, potentially reducing the efficacy of rescue medications like albuterol 1

Clinical Evidence: Mixed Picture

The evidence presents a paradox that requires careful interpretation:

Sleep improvement without acute harm: One randomized controlled trial in 22 women with mild-to-moderate asthma found that melatonin 3 mg daily for 4 weeks significantly improved subjective sleep quality without causing significant differences in asthma symptoms, relief medication use, or peak expiratory flow rates 3

Theoretical and experimental concerns: Despite the lack of acute exacerbations in the clinical trial, experimental models demonstrate clear bronchoconstrictor effects 2, and mechanistic studies show melatonin potentiates airway smooth muscle contraction 1

Safety profile in general populations: A systematic review of 37 randomized controlled trials found melatonin generally safe and well-tolerated, with the most common adverse events being daytime sleepiness (1.66%), headache (0.74%), and dizziness (0.74%), with no life-threatening events identified 4

Clinical Algorithm for Decision-Making

For patients with well-controlled asthma on stable therapy:

• Melatonin may be considered for sleep disturbances if non-pharmacological interventions have failed 3
• Start with the lowest effective dose (0.5-3 mg) 3
• Monitor peak expiratory flow rates morning and evening for the first 2-4 weeks 3
• Ensure patients have adequate rescue medication available 1

For patients with poorly controlled asthma or frequent nocturnal symptoms:

• Avoid melatonin supplementation entirely 1, 2
• The bronchoconstrictor effects may worsen nocturnal asthma and reduce β2-agonist efficacy 1
• Optimize asthma controller therapy first, including consideration of inhaled corticosteroids at appropriate doses 5

For patients currently taking prednisone for acute exacerbation:

• Defer any melatonin initiation until the exacerbation has fully resolved and lung function has returned to baseline 6
• Complete the corticosteroid course (typically 5-10 days at 40-60 mg daily for adults) before considering any sleep aids 6
• Reassess asthma control 2-4 weeks after exacerbation resolution before introducing melatonin 6

Critical Pitfalls to Avoid

Do not dismiss the bronchoconstrictor mechanism simply because one small trial showed no acute harm 3, 1, 2. The trial was limited to 22 patients with mild-to-moderate asthma over 4 weeks and may not capture:

• Effects in patients with severe asthma 1
• Long-term consequences of chronic melatonin use 4
• Individual variability in MT2 receptor expression or sensitivity 1

Do not assume melatonin is universally safe in asthma based on its general safety profile 4. The systematic review noting melatonin's safety specifically identified insufficient data for "at-risk populations" including patients with asthma 4

Alert patients using over-the-counter melatonin about potential negative effects on asthma control 2. Many patients self-medicate with melatonin without informing their physicians, and clinicians should specifically inquire about its use during asthma evaluations 2

Nuanced Considerations

The evidence reveals a complex relationship where melatonin has both potentially harmful effects (bronchoconstriction, reduced β2-agonist efficacy) and potentially beneficial effects (reduced mucus secretion, anti-inflammatory properties) 1, 7. However, the balance of evidence favors caution, particularly in patients with poorly controlled asthma or those experiencing acute exacerbations 1, 2.

For the specific clinical scenario of a patient on prednisone for an acute exacerbation, the priority is resolving the inflammatory crisis with appropriate corticosteroid therapy (40-60 mg daily until peak expiratory flow reaches 70% of predicted) 6, optimizing controller medications 5, and avoiding any intervention that could theoretically worsen bronchospasm 1, 2.