Is melatonin linked to cardiovascular (CV) disease?

Melatonin and Cardiovascular Disease: Evidence Summary

Yes, melatonin is linked to cardiovascular disease, with substantial research evidence suggesting protective effects against multiple cardiovascular pathologies including hypertension, atherosclerosis, myocardial ischemia-reperfusion injury, and metabolic syndrome. 1, 2, 3, 4, 5

Mechanisms of Cardiovascular Protection

Melatonin exerts cardioprotective effects through multiple pathways:

• Direct antioxidant activity: Melatonin functions as a free radical scavenger, efficiently interacting with reactive oxygen species through receptor-independent mechanisms 2, 4
• Receptor-mediated effects: MT1 and MT2 melatonin receptors are present in vascular tissue and cardiac cells, mediating anti-inflammatory, antioxidant, and anti-hypertensive functions 2, 3
• Sirtuin pathway modulation: Melatonin activates Sirt signaling pathways, preserving mitochondrial function, reducing oxidative stress, decreasing inflammation, preventing cell death, and regulating autophagy in cardiac cells 5

Clinical Evidence for Specific Cardiovascular Conditions

Hypertension

• Patients with hypertension have lower melatonin levels than those with normal blood pressure 1
• Melatonin administration (even 1 mg doses) reduced blood pressure to normal range and decreased catecholamine levels after 90 minutes in human subjects 1
• Blood pressure reduction occurs through: direct hypothalamic effects, antioxidant mechanisms, decreased catecholamine levels, and smooth muscle relaxation in the aorta wall 1

Coronary Heart Disease

• Patients with coronary heart disease demonstrate low melatonin production rates, particularly those at higher risk of cardiac infarction and sudden death 1
• Melatonin concentrations in serum and urinary 6-sulphatoxymelatonin decrease with age, correlating with increased frequency of heart diseases 1
• Clinical data report alterations of melatonin in human stroke and coronary heart disease 1

Cholesterol and Atherosclerosis

• People with high LDL-cholesterol levels have low melatonin levels 1
• Melatonin suppresses cholesterol formation by 38% and reduces LDL accumulation by 42% 1
• A 10-20% reduction in cholesterol concentration has been observed with melatonin administration, which translates to a 20-30% decrease in coronary heart disease risk 1

Myocardial Ischemia-Reperfusion Injury

• Melatonin contributes to cardioprotection following myocardial ischemia in animal models 1
• Recent studies demonstrate significant protective effects on ischemia-reperfusion injury and myocardial chronic intermittent hypoxia injury 3, 4

Therapeutic Implications

Melatonin represents an inexpensive, well-tolerated therapeutic option for cardiovascular disease prevention and management 3, 4:

• Beneficial effects demonstrated in: myocardial ischemia-reperfusion injury, pulmonary hypertension, hypertension, atherosclerosis, valvular heart diseases, diabetic cardiomyopathy, and sepsis-induced cardiac injury 3, 4, 5
• Multi-target molecule with pleotropic effects acting through receptor-mediated and non-receptor-mediated mechanisms 4

Important Clinical Considerations

Dosing for Cardiovascular Effects

• Lower doses (1-3 mg) have demonstrated cardiovascular benefits in clinical studies 1
• The American Academy of Sleep Medicine recommends starting with 3 mg for sleep disorders, which may also provide cardiovascular benefits 6
• Higher doses (10 mg) may cause receptor desensitization or saturation, potentially reducing effectiveness 6

Safety Profile

• Melatonin is well-tolerated with minimal adverse effects 3, 4
• Most frequently reported adverse events are headache (0.74%) and dizziness (0.74%) 6
• Melatonin is regulated as a dietary supplement in the US, raising concerns about purity and reliability of stated doses 6, 7
• Choose United States Pharmacopeial Convention Verified formulations for reliable dosing 6, 7

Potential Risks

• Melatonin has been associated with impaired glucose tolerance in healthy women after acute administration 7
• Both hypotension and hypertension have been reported at higher doses 7
• Use with caution in patients taking warfarin or those with epilepsy due to potential interactions 6

Clinical Algorithm for Cardiovascular Risk Reduction

For patients with cardiovascular disease or risk factors:

1. Assess baseline melatonin status: Consider that patients with hypertension, coronary disease, or hyperlipidemia likely have reduced endogenous melatonin 1

2. Initiate low-dose melatonin: Start with 1-3 mg taken 1.5-2 hours before bedtime 6, 1

3. Monitor cardiovascular parameters: Track blood pressure, lipid profiles, and cardiovascular symptoms over 4-12 weeks 1, 3

4. Dose adjustment if needed: If no benefit after 1-2 weeks and no adverse effects, consider increasing by 3 mg increments, but avoid exceeding 5-6 mg to prevent receptor desensitization 6

5. Long-term management: Periodic reassessment every 3-6 months to determine lowest effective dose and continued need 6