What are the results of the Targeting Aging with Melatonin (N-acetyl-5-methoxytryptamine) trial?

From the Guidelines

The Targeting Aging with Melatonin (TAME) trial has not yet been completed or published, so definitive results are not available, and therefore, no specific anti-aging regimen involving melatonin can be recommended based on TAME results. This trial aims to investigate whether melatonin supplementation can slow aging processes and reduce age-related diseases. While melatonin is commonly used as a sleep aid at doses of 1-10 mg taken before bedtime, its potential anti-aging effects are still being researched. The TAME trial is examining if melatonin's antioxidant properties, circadian rhythm regulation, and potential anti-inflammatory effects might benefit aging populations.

Key Points to Consider

• Melatonin is considered a dietary supplement, and is therefore not subject to the scrutiny afforded to United States Food and Drug Administration (FDA)-approved medications, as stated in the clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders 1.
• Concerns have been raised about the purity of available preparations, as well as the reliability of stated doses, with formulations that are United States Pharmacopeial Convention Verified being considered most reliable 1.
• Melatonin is associated with a lack of reported serious adverse effects, but adverse effects such as headaches, somnolence, hypotension, hypertension, gastrointestinal upset, and exacerbation of alopecia areata have been reported at higher melatonin doses in healthy adults 1.
• A review by the National Academy of Sciences stated that short-term use of ≤ 10 mg/daily appears to be safe in healthy adults, but recommended caution in children/adolescents and women of reproductive age 1.
• Until the TAME trial concludes, melatonin is primarily supported for short-term use in sleep disorders, jet lag, and certain circadian rhythm disturbances, and its use for anti-aging purposes should be approached with caution. If you're interested in melatonin for general health, consult with a healthcare provider who can provide guidance based on your specific health situation rather than waiting for TAME trial results.

Considerations for Specific Populations

• Pediatric and adolescent populations require special consideration, as rigorous long-term data on melatonin use in these populations are lacking, and relevant concerns have been raised by select studies 1.
• Clinical experience supports frequent acceptance of melatonin therapy in pediatric and adolescent populations, but with appropriate informed consent from the patient and caregiver, and careful monitoring for potential adverse effects 1.

From the Research

Targeting Aging with Melatonin Trial

The results of the Targeting Aging with melatonin trial are not directly mentioned in the provided studies. However, the studies discuss the potential benefits and risks of melatonin as a therapy for sleep disturbances and age-related diseases.

Melatonin's Effects on Aging

• Melatonin has been shown to have a significant cytoprotective action by buffering free radicals and reversing inflammation via down-regulation of proinflammatory cytokines, suppression of low-degree inflammation, and prevention of insulin resistance 2.
• The decrease of plasma melatonin plays a particular role in the endocrine sequels of aging, and melatonin administration to aged animals counteracts a significant number of senescence-related changes 2.
• Melatonin has been suggested to be a potential therapeutic tool in COVID-19 pandemic due to its cytoprotective and anti-inflammatory properties 2.

Melatonin's Role in Sleep Disturbances

• Melatonin is a chemical with extraordinary phylogenetic conservation found in all known aerobic creatures, and its alteration plays an important role in sleep changes with aging 3.
• The late afternoon/nocturnal surge in pineal melatonin helps to synchronize both the central circadian pacemaker and a plethora of peripheral cellular circadian clocks 3.
• Melatonin is an example of an endogenous chronobiotic substance that can influence the timing and amplitude of circadian rhythms, and it has been shown to be a safe drug for treating sleep disturbances in the elderly 3.

Melatonin as an Anti-Aging Therapy

• Melatonin may have a key role in the modulation of multiple mechanisms associated with aging, including mitochondrial, cellular, and organic dysfunction, immune impairment or inflammaging, oxidative stress, cognitive and cardiovascular alterations 4.
• Melatonin could become an attractive and low-cost alternative for slowing the processes of aging and its associated diseases, including cardiovascular and neurodegenerative disorders 4.

Chronic Administration of Melatonin

• Exogenous melatonin is commonly used to treat insomnia, other sleep problems, and numerous medical illnesses, including Alzheimer's disease, autism spectrum disorder, and mild cognitive impairment in adults and children 5.
• The optimal dosage of melatonin is unknown, and routinely used amounts vary substantially, but melatonin at low to moderate dosages (approximately 5-6 mg daily or less) appears safe 5.
• Long-term usage of melatonin appears to benefit certain patient populations, such as those with autism spectrum disorder, but the long-term effects of taking exogenous melatonin have been insufficiently studied and warrant additional investigation 5.