Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men
Abstract
Background Previous studies have suggested that melatonin, a major pineal hormone, possibly modulates the autonomic nervous system in animals. The aim of this study was to examine the effects of melatonin administration on heart rate variability (HRV) in human beings. Methods In 26 healthy men, melatonin (2 mg) or placebo was randomly administered. Power spectral analysis of HRV and blood pressure monitoring were performed in the supine position before and 60 minutes after administration and in the standing position 60 minutes after administration. Plasma catecholamine levels were also assessed. Results No differences in any baseline parameters were found between the two groups. Compared with placebo, melatonin administration within 60 minutes increased R-R interval, the square root of the mean of the squared differences between adjacent normal R-R intervals, high-frequency power, and low-frequency power of HRV and decreased the low-frequency to high-frequency ratio and blood pressure in the supine position (all P Conclusions These findings indicate that melatonin administration increased cardiac vagal tone in the supine position in awake men. Melatonin administration also may exert suppressive effects on sympathetic tone.
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Heart rate variability studies in humans have indicated that melatonin increases cardiac vagal tone.
“Heart rate variability studies in humans have indicated that melatonin increases cardiac vagal tone (Nishiyama et al. 2001).”
From Melatonin attenuates the sympathetic nerve responses to orthostatic stress in humans (2003) · cites this paper as Nishiyama et al. 2001
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Cardiovascular neural regulation explored in the frequency domain.
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Interaction between clock genes, melatonin and cardiovascular outcomes from ICU patients
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Niehoff, J. H., Matzkies, M., Nguemo, F., Hescheler, J., & Reppel, M. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111245 · Cited by 8 · see citing works
Jurado-Guerra, J. A., Flores-Mancha, M. A., Juárez‐Moya, J., Lechuga-Valles, R., Rentería‐Monterrubio, A. L., Sánchez‐Vega, R., Tirado‐Gallegos, J. M., & Chávez‐Martínez, A. (2023) · Journal of Food Processing and Preservation · doi:10.1155/2023/9232447 · Cited by 5 · see citing works
The Multiple Functions of Melatonin: Applications in the Military Setting
Gancitano, G., & Reiter, R. J. (2022) · Biomedicines · doi:10.3390/biomedicines11010005 · Cited by 7 · see citing works
“Melatonin administration also seems to exert suppressive effects on sympathetic tone [65].”
Morning melatonin levels in Prader–Willi syndrome
Butler, M. G., Brandau, D. T., Theodoro, M. F., & Garg, U. C. (2009) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33001 · Cited by 7 · see citing works
“It can affect the autonomic regulation of the cardiovascular system, regulation of the hypothalamic– pituitary–gonadal axis, circadian rhythms and wake-sleep cycles [Cavallo, 1993; Commentz and Helmke, 1995; Nishiyama et al., 2001].”
BackgroundKassab, S., Sachdeva, U., Das, N. S., Al-Shaibani, T., & Nayar, U. (2006) · Sultan Qaboos University Medical Journal · doi:10.18295/2075-0528.2619 · Cited by 6
Endocrine Effects of Dietary Restriction and Aging: The National Institute on Aging Study
Mattison, J. A., Roth, G. S., Ingram, D. K., & Lane, M. A. (2001) · Rejuvenation Research · doi:10.1089/109454501753249984 · Cited by 7 · see citing works
Cell Signaling by Tryptophan Catabolism
Torrelli-Diljohn, A., Kulkarni, B., & Vitturi, D. A. (2026) · Biochemistry · doi:10.1021/acs.biochem.6c00179 · Cited by 7 · see citing works
Influence of Acute Melatonin Administration on Human Physical Performance: A Systematic Review
Faria, V. S., Messias, L. H. D., Pejon, T. M. M., & Beck, W. R. (2023) · Sports Health A Multidisciplinary Approach · doi:10.1177/19417381231155142 · Cited by 4 · see citing works
“15 Compelling evidence has demonstrated the association of melatonin with a depressive effect on the central nervous system, 10,41 reduced alertness, 4,21,32,52 and decreased body temperature.”
BackgroundEo, Y. J., Park, J., Kim, S., Lee, K. N., Lee, S. M., Kim, D. H., Kim, C., & Rag, Y. (2022) · Biological Rhythm Research · doi:10.1080/09291016.2021.2024408 · Cited by 6 · see citing works
“In addition, Nishiyama et al. (2001) reported that exogenous MLT administration increased the RR intervals.”
BackgroundAbulafia, C., Vidal, M. F., Olivar, N., Odzak, A. N., Brusco, I., Guinjoan, S. M., Cardinali, D. P., & Vigo, D. E. (2023) · Clinical Interventions in Aging · doi:10.2147/cia.s394749 · Cited by 5 · see citing works
The role of melatonin in hypertension
Katsi, V. K., Karagiorgi, I., Makris, T. K., Papavasileiou, M. V., Androulakis, A. E., Tsioufis, C. P., Tousoulis, D., Stefanadis, C., & Kallikazaros, I. E. (2012) · Cardiovascular Endocrinology & Metabolism · doi:10.1097/xce.0b013e3283565783 · Cited by 5 · see citing works
Immunoplasticity--triggers of regulatory function.
Moser, A., Salzer, H., & Krause, R. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2011.09.024 · Cited by 3
“Melatonin itself has miscellaneous effects on the immune system and also, interestingly, on cholinergic anti-inflammatory pathways, since Nishiyama and colleagues demonstrated that melatonin administration increased vagal tone in healthy men and elevated heart rate variability [10].”
BackgroundDiurnal body temperature rise is reduced in diabetes with autonomic neuropathy
Amiya, E., Watanabe, M., Takata, M., Nakao, T., Hosoya, Y., Watanabe, S., Nagai, R., & Komuro, I. (2014) · Clinical Autonomic Research · doi:10.1007/s10286-013-0223-9 · Cited by 2 · see citing works
“For example, melatonin is a key regulatory peptide of body temperature rhythm and sleep, and it also affects autonomic vagal activity [5].”
BackgroundAlterations in Heart rate Variability in Blind PatientsPreprint
Moreno, R. D., Moreno-Mantilla, N. P., de Lima, M. V. M., Morais, M. J. D. D., Valenti, V. E., de Abreu, L. C., Raimundo, R. D., & Sato, M. A. (2021) · Research Square · doi:10.21203/rs.3.rs-820334/v1 · Cited by 2 · see citing works
Плисс, М. Г., Владимировна, К. Н., Rubanova, N. S., & Tsyrlin, V. A. (2019) · Advances in Gerontology · doi:10.1134/s2079057019030111 · Cited by 6 · see citing works
Neuropathy Detection, Quality of Life Tools & Treatment for Type 2 Diabetes
Brown, J. J. (2016) · doi:10.25777/q2my-6b79 · Cited by 2
“administration, measured norepinephrine and dopamine levels were lower (Nishiyama et al., 2001), suggesting that melatonin administration influences cardiac vagal tone, potentially exerting suppressive effects on sympathetic influences from the ANS.”
BackgroundD’Aurea, C. V. R., Gusmão, W. D. P., Saraiva, S. P., Luz, C. S. D. S., Zucchi, E. M., do Amaral, F. G., Cipolla‐Neto, J., Moreno, C. R., & Marqueze, E. C. (2026) · Biological Rhythm Research · doi:10.1080/09291016.2026.2622303 · Cited by 1 · see citing works
“Some studies using doses of 2 mg and 3 mg of melatonin obtained similar results, with significant improvement in sympathetic activity, heart rate, and blood pressure reduction (Nishiyama et al. 2001; Ray 2003).”
Pharmacological modulation of MRAP2 protein on murine melatonin receptor signaling
Song, W., Li, Y., Xu, H., Zhang, Y., Liu, L., Li, Y., Wang, X., Du, Y., Chen, Y., Lyu, J., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1593345 · Cited by 1 · see citing works
Vegetative Funktionsdiagnostik mittels Analyse der Herzratenvariabiltät
Lohninger, A. (2013) · Erfahrungsheilkunde · doi:10.1055/s-0033-1334374 · Cited by 1 · see citing works
“Clin Physiol Funct Imaging 2004; 24: 10–8 [30] Nishiyama K, Yasue H, Moriyama Y et al.”
BackgroundMelatonina y aterosclerosis coronaria
Domínguez-Rodríguez, A., Samimi-Fard, S., Abreu-González, P., & Kaski, J. (2009) · doi:10.1016/s0214-9168(09)72688-9 · Cited by 1
Brito, L. C., Jones, M. L., Garcês, C. P., Shea, S. A., & Thosar, S. S. (2026) · Physiological Reports · doi:10.14814/phy2.71145
“In young healthy adults, a single ingestion of 2–3 mg melatonin tablet attenuated the muscle sympathetic nerve response to orthostatic stress and increased cardiac parasympathetic modulation when administered in the morning ( ~ 10 a.m.) (Nishiyama et al., 2001).”
Lauritzen, E. S., Støy, J., Møller, N., Poulsen, P. L., & Kampmann, U. (2026) · Acta Diabetologica · doi:10.1007/s00592-026-02750-0
“Previous research has indicated that melatonin increases the vagal tone on the heart and that it may have suppressive effects on the sympathetic tone [ 8].”
Ma, C.-C., Yang, C.-Y., Chang, W., Sack, A. T., Chang, C.-C., & Chang, H. (2025) · Medicina · doi:10.3390/medicina61091522
“Supporting evidence includes findings that a single 2 mg melatonin dose increased vagal tone and decreased sympathetic tone in healthy men [47], and animal studies showing that chronic melatonin reduces heart rate via sympathetic inhibition [48].”
Protective Effects of Melatonin and Its Supplements on the Arterial Mechanics
Yıldız, M., & Yıldız, B. Ş. (2022) · Koşuyolu Heart Journal · doi:10.51645/khj.2022.m291
“Melatonin administration also may exert suppressive effects on sympathetic tone as evidenced by a decrease in catecholamine and dopamine levels(25).”
BackgroundDOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ
Özgen, Z. E. (2021) · Izmir Democracy University Health Sciences Journal · doi:10.52538/iduhes.827754 · Cited by 1 · see citing works
- Authors
- Nishiyama, K., Yasue, H., Moriyama, Y., Tsunoda, R., Ogawa, H., Yoshimura, M., & Kugiyama, K.
- Affiliations
- Kumamoto University (JP)
- Kumamoto University Hospital (JP)
- ORCID
- Venue
- American Heart Journal
- Publisher
- Elsevier BV
- Published
- 2001-05
- Volume
- 141
- Issue
- 5
- Pages
- 13A-17A
- ISSN
- 0002-8703 (ISSN-L)
- OpenAlex
- W2136100283
- Cited by
- 113
- References
- 0
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 7 · 2013: 2 · 2012: 3
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- melatonin, heart rate variability, cardiovascular autonomic regulation, cardiac vagal tone, sympathetic tone, blood pressure, norepinephrine, dopamine, catecholamines, postural changes, healthy men
- MeSH terms
- Blood Pressure, Cardiovascular System, Circadian Rhythm, Dopamine, Dose-Response Relationship, Drug, Electrocardiography, Heart Rate, Humans, Male, Melatonin, Norepinephrine, Posture, Reference Values, Vagus Nerve, Free Radical Scavengers
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