Page 28 - SAM 0625

SAN ANTONIO
MEDICINE

conditions is apropos currently. Humans, for several reasons, are living 4. Reiter, R.J., Mayo, J.C., Tan, D.X., Sainz, R.M., Ala-
longer such that the common aging diseases are becoming increasingly torre-Jimenez, M., Qin, L. Melatonin as an antioxidant:
manifested. For example, the number of individuals suffering with Alz- under promises but over delivers. .J Pineal Res. 2016;61(3):253-
78. doi: 10.1111/jpi.12360
heimer’s or Parkinson’s diseases are predicted to increase substantially 5. Steinbach, M.J., Denburg, N.L. Melatonin in Alzheimer’s Dis-
over the next 25 years. Unless treatments are found to hinder the ini- ease: Literature Review and Therapeutic Trials. .J Alzheimers Dis.
tiation, or the progression of these degenerative conditions, the social 2024;101(s1):S193-S204. doi: 10.3233/JAD-230760
and medical welfare systems will become grossly overtaxed. 6. Lu, X., Yu, S., Chen, G., Zheng, W., Peng, J., Huang, X., Chen, L.
Comments regarding the safety of melatonin have been a feature Insight into the roles of melatonin in bone tissue and bone-relat-
of every clinical trial that has been performed. There is general agree- ed diseases (Review).
Int J Mol Med. 2021;47(5):82. doi: 10.3892/ijmm.2021.4915
ment that melatonin is an uncommonly safe molecule with a wide 7. Jeong, H., Shaia, J.K., Markle, J.C., Talcott, K.E., Singh, R.P.
safety profile. Doses between 1 mg and 1 gram have been given to Melatonin and Risk of Age-Related Macular Degeneration.
humans for prolonged periods without serious side effects being noted. .JAMA Ophthalmol. 2024;142(7):648-654. doi: 10.1001/jama-
ophthalmol.2024.1822
Complaints associated with melatonin ingestion have been mostly 8. Alshahrani, S., Sultan, M.H., Rashid, H., Alam, F., Khan, A.,
subjective and include sleepiness, dizziness and fatigue, like those of Akhter, M.S., Qamri, D., Beigh, S., Riyaz, F. Melatonin Rescues
placebo-treated individuals. While not reported in clinical trials, some Renal Mitochondria From Multiple Stressors-Induced Oxidative
individuals who initially take melatonin report having vivid dreams. In Stress. Basic Clin Pharmacol Toxicol. 2025;136(5):e70031. doi:
animals, a LD50 (lethal dose for 50% of the animals) for melatonin has 10.1111/bcpt.70031
not been defined despite attempts to do so. 9. García-Domínguez, M. Pathological and Inflammatory Conse-
quences of Aging. Biomolecules, 2025,15:404, doi: 10.3390/
Most individuals who use melatonin, especially for sleep, take daily biom15030404’
doses in the range of 1-10 mg at night. While these doses may be suf- 10. Reiter, R.J., Sharma, R., Romero, A., Simko, F., Dominguez-Ro-
ficient for its chronobiologic synchronizing actions, they may not be driguez, A., Cardinali, D.P. Melatonin stabilizes atherosclerotic
adequate for other purposes. A recent detailed statistical analysis of plaques: an association that should be clinically exploited.
currently available data suggested that the optimal anticipated human Front Med (Lausanne). 2024;11:1487971. doi: 10.3389/
fmed.2024.1487971
equivalent doses of melatonin relative to those used in animals are in 11. Gu, P., Wu, Y., Lu, W. New Perspectives on the Role and Thera-
12
the range of 1.0 to 1.5 mg per kg body weight daily. While melatonin peutic Potential of Melatonin in Cardiovascular Diseases. .Am J
is usually recommended to be taken in the early evening, circumstances Cardiovasc Drugs. 2024;24(2):171-195. doi: 10.1007/s40256-
may justify its use at other times during a 24-hour period, e.g., to reduce 024-00631-x. Epub 2024
molecular damage from conventional diagnostic radiation exposure. 12. Qin, J., Wang, G., Han, D. Benefits of melatonin on mortality
in severe-to-critical COVID-19 patients: A systematic review
Pathological processes are often highly complex and involve more and meta-analysis of randomized controlled trials. Clinics (Sao
than oxidatively mutilated critical molecules which thereafter contrib- Paulo). 2025;80:100638. doi: 10.1016/j.clinsp.2025.100638
ute to pathophysiology. While the radial scavenging actions of mela- 13. Cardinali, D.P. Melatonin as a chronobiotic/cytoprotective agent
tonin are emphasized in the current article, the actions of melatonin are in bone. Doses involved. J Pineal Res. 2024;76(1):e12931. doi:
10.1111/jpi.12931
extraordinary and uncommonly diverse as noted. These varied actions 14. Zhang, B., Tang, M., Li, X.A. narrative review of sleep
are currently under intensive investigation, including in some ongoing and breast cancer: from epidemiology to mechanisms. Cancer
clinical trials, to further define melatonin’s worthiness in disease pre- Causes Control. 2024. doi: 10.1007/s10552-024-01951-8
vention and treatment. The extensive positive accumulated data engen- 15. Reiter, R.J., Sharma, R., Bai, Y., Chuffa, L.G.A., Loh, D., Fan,
ders confidence that the experimental findings from animal and human L. Cardinali DP Function of intramitochondrial melatonin and
studies will support the expanded use of melatonin in a variety of clin- its association with Warburg metabolism.Cell Signal. 2025
21;131:111754. doi: 10.1016/j.cellsig.2025.111754
ical disorders as a sole treatment or in combination with other medica-
tions. Trials using melatonin as a treatment should have high priority.
Russel J. Reiter, PhD, is Professor of Cell Biology in the
Department of Cell Systems and Anatomy at the UT Health
References: San Antonio. In addition to his PhD, Dr. Reiter has received
The majority of the references cited are to recent review articles, so the
reader is given a broad perspective and ready access to the field as a whole. four honorary MD degrees and one honorary DSc degree from
1. Lian, X., Liu, Z., Gan, Z., Yan, Q., Tong, L., Qiu, L., Liu, Y., international universities. He has received many awards for his research
Chen, J.F., Li, Z. Targeting the glymphatic system to promote including the A. Ross McIntyre Gold Metal (USA), US Senior Scientist
alpha-synuclein clearance: a novel therapeutic strategy for Par- Award (Germany), Lizoni Lincee Award (Italy), Inaugural Aaron B.
kinson’s disease. Neural Regen Res. 2025. doi: 10.4103/NRR. Lerner Pioneer Award (USA), Chulabhorn Royal Academy Medal
NRR-D-24-00764
2. Bjørklund, G., Oleshchuk, O., Ivankiv, Y., Venger, O., Liuta, O., (Thailand), etc. He has published numerous research papers, reviews and
Mocherniuk, K., Lukanyuk, M., Shanaida, M. Melatonin Inter- chapters and he has written or edited 25 books. Based on Google Scholar,
ventions in Autism Spectrum Disorder: Sleep Regulation, his papers have been cited in scientific literature more than 222,000
Behavioral Outcomes, and Challenges Across the Lifespan. Mol times and his h-index is 227. Thomson Reuters/Clarivate Analytics
Neurobiol. 2025. doi: 10.1007/s12035-025-04809-5 has identified Dr. Reiter as a Highly Cited Scientist (top 1%) and listed
3. Zhao, D., Yu, Y., Shen, Y., Liu, Q., Zhao, Z., Sharma, R., Reiter,
R.J. Melatonin Synthesis and Function: Evolutionary History him as one of the World’s Most Influential Scientific Minds in 2014.
in Animals and Plants. .Front Endocrinol (Lausanne). 2019 He is ranked in the top 200 list of Best Scientists in the World-2024 by
7;10:249. doi: 10.3389/fendo.2019.00249 Research.com.

28 SAN ANTONIO MEDICINE • June 2025