Controlled-release oral melatonin supplementation for Hypertension and nocturnal Hypertension: A systematic review and meta-analysis
Open accessAbstract
Abstract Oral melatonin is a potential alternative treatment for hypertension and nocturnal hypertension. However, high‐quality and relevant meta‐analyses are lacking. This meta‐analysis aimed to investigate whether oral melatonin supplementation reduces daytime/asleep blood pressure and cardiovascular risk, improves sleep quality, and is well‐tolerated compared with placebo. Relevant articles were searched in multiple databases, including MEDLINE, EMBASE, CINAHL Complete, and the Cochrane Library, from their inception to June 2021. The included studies were randomized controlled trials recruiting patients with hypertension, using oral melatonin as the sole intervention, and investigating its effect on blood pressure. The mean out‐of‐office (including 24‐h, daytime, and asleep) systolic and diastolic blood pressures, sleep quality, and side effects were compared between the melatonin and placebo arms using pairwise random‐effect meta‐analyses. A risk of bias assessment was performed using the Cochrane risk‐of‐bias tool. Four studies were included in the analysis and only one study was considered to have a low risk of bias. No study reported on cardiovascular risk or outcomes. Only controlled‐release melatonin (not an immediate‐release preparation) reduced asleep systolic blood pressure by 3.57 mm Hg (95% confidence interval: –7.88 to .73; I2 = 0%). It also reduced asleep and awake diastolic blood pressure, but these differences were not statistically significant. Melatonin improves sleep efficacy and total sleep time and is safe and well‐tolerated. Due to the limited number of high‐quality trials, the quality of evidence was low to very low. Therefore, adequately powered randomized controlled trials on melatonin are warranted.
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Controlled-release oral melatonin reduced asleep systolic blood pressure by 3.57 mm Hg in a meta-analysis.
“A recent meta-analysis and systematic review by researchers at The Chinese University in Hong Kong concluded that a controlled-release oral melatonin supplement reduced asleep systolic blood pressure by 3.57 mm Hg [120].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [120]
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Cites
2020 International Society of Hypertension Global Hypertension Practice Guidelines
Unger, T., Borghi, C., Charchar, F., Khan, N. A., Poulter, N. R., Prabhakaran, D., Ramirez, A., Schlaich, M., Stergiou, G. S., Tomaszewski, M., et al. (2020) · Hypertension · doi:10.1161/hypertensionaha.120.15026 · Cited by 4,132 · see citing works
Mills, K. T., Bundy, J. D., Kelly, T. N., Reed, J. E., Kearney, P. M., Reynolds, K., Chen, J., & He, J. (2016) · Circulation · doi:10.1161/circulationaha.115.018912 · Cited by 3,531 · see citing works
Analysing data and undertaking meta‐analyses
Deeks, J. J., Higgins, J. P., Altman, D. G., & on behalf of the Cochrane Statistical Methods Group (2019) · Cochrane Handbook for Systematic Reviews of Interventions · doi:10.1002/9781119536604.ch10 · Cited by 2,672 · see citing works
Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015
Forouzanfar, M. H., Liu, P., Roth, G. A., Ng, M., Biryukov, S., Marczak, L., Alexander, L., Estep, K., Hassen Abate, K., Akinyemiju, T. F., et al. (2017) · JAMA · doi:10.1001/jama.2016.19043 · Cited by 2,381 · see citing works
Ohkuma, T., Ninomiya, T., Tomiyama, H., Kario, K., Hoshide, S., Kita, Y., Inoguchi, T., Maeda, Y., Kohara, K., Tabara, Y., et al. (2017) · Hypertension · doi:10.1161/hypertensionaha.117.09097 · Cited by 541 · see citing works
Association of office and ambulatory blood pressure with mortality and cardiovascular outcomes
Yang, W.-Y., Melgarejo, J. D., Thijs, L., Zhang, Z.-Y., Boggia, J., Wei, F.-F., Hansen, T. W., Asayama, K., Ohkubo, T., Jeppesen, J., et al. (2019) · JAMA · doi:10.1001/jama.2019.9811 · Cited by 491 · see citing works
Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension
Scheer, F. A. J. L., Van Montfrans, G. A., van Someren, E. J. W., Mairuhu, G., & Buijs, R. M. (2004) · Hypertension · doi:10.1161/01.hyp.0000113293.15186.3b · Cited by 451 · see citing works
Clinical pharmacokinetics of melatonin: a systematic review
Harpsøe, N. G., Andersen, L. P. H., Gögenür, I., & Rosenberg, J. (2015) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-015-1873-4 · Cited by 329 · see citing works
Individual Differences in the Amount and Timing of Salivary Melatonin Secretion
Burgess, H. J., & Fogg, L. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003055 · Cited by 270 · see citing works
Melatonin mediates two distinct responses in vascular smooth muscle
Doolen, S., Krause, D. N., Dubocovich, M. L., & Duckles, S. P. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00064-8 · Cited by 229 · see citing works
Gholami, F., Sajjad, M., Rasaei, N., Soveid, N., Setayesh, L., & Mirzaei, K. (2021) · Journal of Neurology · doi:10.1007/s00415-020-10381-w · Cited by 182 · see citing works
Melatonin reduces night blood pressure in patients with nocturnal hypertension
Grossman, E., Laudon, M., Yalcin, R., Zengil, H., Peleg, E., Sharabi, Y., Kamari, Y., Shen-Orr, Z., & Zisapel, N. (2006) · The American Journal of Medicine · doi:10.1016/j.amjmed.2006.02.002 · Cited by 168 · see citing works
Kario, K., Kanegae, H., Tomitani, N., Okawara, Y., Fujiwara, T., Yano, Y., Hoshide, S., & on behalf of the J-HOP Study Group (2019) · Hypertension · doi:10.1161/hypertensionaha.118.12740 · Cited by 167 · see citing works
Peripheral and Central Effects of Melatonin on Blood Pressure Regulation
Pecháňová, O., Paulis, L., & Šimko, F. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151017920 · Cited by 158 · see citing works
Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials
Laudon, M., Grossman, & Zisapel, N. (2011) · Vascular Health and Risk Management · doi:10.2147/vhrm.s24603 · Cited by 147 · see citing works
Li, T. X., Jiang, S., Han, M., Yang, Z. Z., Lv, J., Deng, C., Reiter, R. J., & Yang, Y. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.004 · Cited by 121 · see citing works
Lusardi, P., Piazza, E., & Fogari, R. (2000) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2000.00195.x · Cited by 115 · see citing works
Role of melatonin in blood pressure regulation: An adjunct anti‐hypertensive agent
Baker, J. R., & Kimpinski, K. (2018) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12942 · Cited by 111 · see citing works
Vural, E. M. S., van Munster, B. C., & de Rooij, S. E. (2014) · Drugs & Aging · doi:10.1007/s40266-014-0178-0 · Cited by 92 · see citing works
Bo, Y., Kwok, K. O., Chung, V. C., Yu, C., Tsoi, K. K., Wong, S. Y. S., & Lee, E. K. P. (2020) · Journal of Hypertension · doi:10.1097/hjh.0000000000002522 · Cited by 73 · see citing works
Self-citationGavriilaki, M., Anyfanti, P., Nikolaidou, B., Lazaridis, A. A., Gavriilaki, E., Δούμα, Σ., & Gkaliagkousi, Ε. (2020) · Journal of Clinical Hypertension · doi:10.1111/jch.14039 · Cited by 69 · see citing works
Loloei, S., Sepidarkish, M., Heydarian, A., Tahvilian, N., Khazdouz, M., Heshmati, J., & Pouraram, H. (2019) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2019.04.043 · Cited by 58 · see citing works
Doosti-Irani, A., Ostadmohammadi, V., Mirhosseini, N., Mansournia, M., Reiter, R., Kashanian, M., Rahimi, M., Razavi, M., & Asemi, Z. (2018) · Hormone and Metabolic Research · doi:10.1055/a-0752-8462 · Cited by 52 · see citing works
Hadi, A., Ghaedi, E., Moradi, S., Pourmasoumi, M., Ghavami, A., & Kafeshani, M. (2019) · Hormone and Metabolic Research · doi:10.1055/a-0841-6638 · Cited by 45 · see citing works
Wood, S., Greenfield, S. M., Sayeed Haque, M., Martin, U., Gill, P. S., Mant, J., Mohammed, M. A., Heer, G., Johal, A., Kaur, R., et al. (2016) · British Journal of General Practice · doi:10.3399/bjgp16x685717 · Cited by 44 · see citing works
Katz, A., Lemoine, Wade, Nir, & Zisapel (2012) · Integrated Blood Pressure Control · doi:10.2147/ibpc.s27240 · Cited by 39 · see citing works
Blood pressure reducing effects of piromelatine and melatonin in spontaneously hypertensive rats.
Huang, L., Zhang, C., Hou, Y., Laudon, M., She, M., Yang, S., Ding, L., Wang, H., Wang, Z., He, P., et al. (2013) · PubMed · Cited by 36 · see citing works
Akbari, M., Ostadmohammadi, V., Mirhosseini, N. Z., Lankarani, K. B., Tabrizi, R., Keshtkaran, Z., Reiter, R. J., & Asemi, Z. (2019) · Journal of Human Hypertension · doi:10.1038/s41371-019-0166-2 · Cited by 27 · see citing works
Cuspidi, C., Tadic, M. V., Sala, C., Gherbesi, E., Grassi, G. M., & Mancia, G. (2019) · Journal of Hypertension · doi:10.1097/hjh.0000000000002099 · Cited by 24 · see citing works
Rahbari-Oskoui, F. F., Abramson, J. L., Bruckman, A. M., Chapman, A. B., Cotsonis, G., Johnson, S., & Bliwise, D. L. (2019) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2019.01.026 · Cited by 15 · see citing works
Vecchis, R. D., Paccone, A., & Maio, M. D. (2019) · International Journal of Statistics in Medical Research · doi:10.6000/1929-6029.2019.08.09 · Cited by 3 · see citing works
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Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022) · Nutrients · doi:10.3390/nu14193934 · Cited by 176 · see citing works
- Authors
- Lee, E. K., Poon, P., Yu, C., Lee, V. W., Chung, V. C., & Wong, S. Y.
- Affiliations
- Chinese University of Hong Kong (HK)
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine The Chinese University of Hong Kong Hong Kong
- Corresponding author
- Lee, Eric Kam‐Pui
- Venue
- The Journal of Clinical Hypertension
- Publisher
- Wiley
- Published
- 2022-04-07
- Volume
- 24
- Issue
- 5
- Pages
- 529-535
- ISSN
- 1524-6175 (ISSN-L)
- 1751-7176
- PMC
- PMC9106086
- OpenAlex
- W4225677985
- Cited by
- 38
- References
- 31
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 14 · 2023: 6 · 2022: 3 · 2014: 1
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Hypertension (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- melatonin, hypertension, nocturnal hypertension, blood pressure, sleep quality, cardiovascular risk, tolerability, total sleep time
- MeSH terms
- Blood Pressure, Delayed-Action Preparations, Humans, Hypertension, Melatonin, Randomized Controlled Trials as Topic, Dietary Supplements
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