Is Melatonin Bad For Your Liver?

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Overview

Melatonin supplementation at 10 mg/day has been shown to significantly increase plasma melatonin levels while reducing liver enzymes, implying benefits in human liver illnesses.1 Melatonin hasn't been connected to liver damage yet, so it's probably safe to consume if you don't have any prior or present liver impairment. The NHS, on the other hand, does not advocate melatonin supplements for persons with hepatic impairments due to a lack of expertise in melatonin usage in patients with liver disease.

About melatonin 

Known as the “hormone of darkness” or “sleep hormone” , melatonin has provided aid for humans for many years. The very nature of its medicinal properties was not identified until it was first discovered in 1958 by Physician Aaron B. Lerner and yet there is still not a clear understanding of the impact the production of melatonin has on our body. 

Melatonin is a neural hormone found in not just humans but animals as well. It is responsible for the secretion indefinitely, present at night: when activity levels are low in humans and the body’s physiological system, the main objective is to rest and recover. Animals like rats and bats with nocturnal characteristics will also secrete melatonin during the night, contrarily, when these animals are exceedingly active. Melatonin is mostly produced in the pineal gland in humans.

Melatonin follows biological rhythms. Melatonin has a circadian rhythm, with a high concentration at night and a low concentration throughout the day. Melatonin has a cyclical pattern as well – the shorter the day the longer the night – longer secretion of melatonin. In contrast, the longer the day, the shorter the night, and the shorter the length of melatonin release.

Biological rhythms are the natural cycles of change in our bodies' substances or activities. It is made up of nerve cells that help sync your body's operations and activities. The circadian clock is a physical, mental, and behavioural clock that responds to light and dark. This clock assists in the regulation of processes such as sleep schedule, appetite, body temperature, hormone levels, alertness, daily performance, blood pressure, and reaction times. External variables can influence your biological rhythms. For example, sunlight, medications, and caffeine can all disrupt sleep patterns.

In addition to our body’s natural production of melatonin, melatonin supplements add to your body’s natural supply of the hormone. It is often distributed to treat those with delayed sleep phase, insomnia, and circadian rhythm sleep disorders in non-seeing people. However, access to melatonin supplements varies from country to country. 

In the US melatonin has been approved for public use. It is available over the counter throughout the country.2 Although, there is currently an absence of knowledge on the toxicity of melatonin, especially with long-term use. Much research is still needed to be carried out. While melatonin has an entirely different status in Europe, where it cannot be purchased over the counter. Even though administration of melatonin in humans and animals has not demonstrated evidence of toxicological effects. 

Melatonin supplements

How much melatonin is optimal?

Officially there is not a melatonin dosage recommendation for adults, however, a range of 0.5 mg to 5 milligrams appears to be safe and beneficial. 3 Melatonin can be taken by adults one hour before going to bed. Melatonin should not be used by pregnant or lactating women without first seeing their doctor. There hasn't been enough study done on the safety of melatonin in this population. Melatonin dosage is calculated depending on your age, weight, and personal sensitivity.3

Researchers recommend that older persons begin with the lowest possible dose of melatonin. Lower doses may help elderly persons sleep better without interfering with their circadian rhythms or producing extended sleepiness.4

Most people take melatonin on a short-term basis to treat sleep problems, such as jet lag. Melatonin can also assist some people, such as shift workers or those suffering from delayed sleep-wake phase disorder, in resetting their internal body clocks to sleep better.5 While melatonin is well recognised as the "sleep hormone," it may perform several vital roles in addition to regulating sleep. It could, for example, aid with nervousness before surgery but this requires further research.6

In the UK, where melatonin can only be prescribed, the NHS suggests adult patients should initially take 2 to 3mg at night and only increase, if necessary, after 1-2 weeks to 6mg at night. Melatonin treatment should be reviewed by the prescriber every 6 months. The treatment should come to a cease for those who experience intolerable side effects or fail to respond to the maximum dose. With paediatric patients, doses will be initiated by a specialist at 2mg at night. They should also be reviewed every 6 months.

Recommended use of melatonin supplements

There are many uses for melatonin supplements. 

Non-24-hour Sleep Wake Disorder – The body clock of most people follows a 24-hour cycle known as the circadian rhythm. This circadian rhythm influences sleep, appetite, and energy levels. Individuals suffering from non-24-hour sleep-wake disorder have a circadian rhythm that is either shorter or slightly longer than 24 hours. Usually prominent with those who are blind. Melatonin is taken orally before bedtime appears to improve sleep in blind children and adults.

Insomnia – In people with insomnia, taking melatonin orally appears to reduce the time it takes to fall asleep. It also appears to be more beneficial in older adults and those suffering from certain other conditions.

Jet lag – Melatonin can help with certain symptoms of jet lag, such as alertness, as well as reduce daytime sleepiness and tiredness. However, it may not help people suffering from jet lag to fall asleep faster.

High blood pressure - Melatonin appears to reduce blood pressure in patients with high blood pressure when taken before night.

Melatonin may be recommended by a doctor for children who suffer from sleep issues such as insomnia or ADD/ADHD. Several studies have found that melatonin administration can significantly improve total sleep times for children with these problems, increasing them by 25 to 48 minutes on average.3 There hasn't been enough study done on melatonin in children. Because melatonin is a hormone, ingesting it may affect other elements of hormone development in children, but further research is needed.

Side effects of melatonin

Melatonin is probably safe for most individuals to use on a short-term basis. Melatonin may be safe to use long-term. However, it might induce adverse effects such as headache, drowsiness, dizziness, and nausea. Do not drive or operate machinery for at least 4-5 hours after taking melatonin.

Many other sleep drugs can cause dependence, but melatonin is unlikely to. Short-term depression, slight tremor, mild anxiety, stomach cramps, irritability, lower alertness, confusion or disorientation, and unusually low blood pressure are less frequent melatonin adverse effects. Furthermore, melatonin supplements can interact with a variety of drugs. If you're thinking about using melatonin pills, talk to your doctor first, especially if you have any health issues.7

Melatonin and the liver 

Is melatonin bad for your liver?

Melatonin production declines after childhood and is linked to chronic disorders in the elderly, therefore increasing food intake or supplementation may be beneficial for these people. Fibrosis, inflammation, steatosis, and carcinogenesis are the most typical changes in liver disease. Liver fibrosis is a reversible condition, and disease regression at this stage is an essential method for limiting disease progression. Melatonin supplementation at 10 mg/day has been proven to considerably boost plasma melatonin levels while decreasing liver enzymes, suggesting its advantages in human liver disorders.8

Currently melatonin has not been linked with liver damage and is presumably safe to take for those with no previous/current liver damage. The NHS, however, does not recommend the use of melatonin supplements for those with hepatic impairments because there is a lack of experience with the use of melatonin in patients with liver damage. The research also shows that the liver has its own circadian rhythm and those with liver damage have elevated melatonin levels during the day due to decreased clearance.

Instead, other treatments like the antihistamine hydroxyzine will be recommended. It is an effective treatment for restoring normal sleep patterns when liver damage causes chemical pathways in the brain to be disrupted. 

Although more recent studies show that melatonin can decrease the level of elevated liver enzymes. Melatonin can help weight reduction. Melatonin can aid in the treatment of non-alcoholic fatty liver disease by improving the grade of fatty liver. There is a consolation that with longer and greater studies assessing the efficacy and safety, melatonin may be recommended to use for those with hepatic issues.9

Effects of melatonin on liver disease 

The liver is a crucial organ of the human body that performs a variety of essential and critical processes, including digestive and excretory functions, nutrition storage and metabolic functions, molecule synthesis, and harmful chemical purification. Liver injuries and disorders are major public health concerns across the world. Chemical pollutants, narcotics, and alcohol, among other things, can all cause liver damage. Despite all the research, the treatment options for liver injuries and disorders are limited. As a result, finding a novel medication that can safely and effectively stop or cure liver damage and illnesses remains a top focus. The liver has its own circadian rhythms and expressions, as well as its own melatonin production. Previous research has linked circadian rhythms to a variety of liver illnesses, and disturbance of rhythms or clock gene expression may accelerate the development of liver steatosis, inflammation, or cancer.10

Melatonin is a well-known potent antioxidant that has a wide range of bioactivities. Numerous research has been conducted to investigate the impact of melatonin on liver injuries and disorders, and melatonin may influence several molecular pathways in diverse pathophysiological circumstances.8 Melatonin has the potential to be employed in the prevention and treatment of liver damage and disorders. Melatonin and its metabolites have powerful antioxidant/anti-inflammatory capabilities and have been shown to be extremely helpful in a wide range of illnesses associated with inflammation and oxidative stress.8

A study was collected and conducted on the effects of melatonin on liver injuries caused by toxins and other liver injuries. They found that with liver resection, more known as a hepatectomy, patients administered melatonin through a nasogastric tube with a single dose (50 mg/kg) resulted in lower postoperative enzymes and resulted in a shorter intensive care unit stay and overall hospital stay.8 With a toxin like a fluoride inducing a liver injury, melatonin prevents the loss of body and liver weight, as well as the loss of liver enzyme function.

Below result from other studies based on the functional roles and therapeutic potentials of melatonin and circadian rhythms in liver diseases. 

Alcoholic liver disease – Another research gave pregnant rats alcohol by gavage with or without melatonin. Melatonin therapy reduced levels of alcohol-induced liver damage not only in mums but also in newborn pups in this paradigm. Although further research is needed to discover innovative therapies for ALD that target circadian rhythms and clock gene expression, prior studies have revealed that melatonin administration has promised therapeutic benefits.8

Non-alcoholic fatty liver disease – Effects such as decreased oxidative stress, an increase of brown adipose tissue mass and activity, restored mitochondria functions and improved gut microbiota are results from melatonin dosage given to patients/rats with non-alcoholic fatty liver disease.8

Cholangiopathies – Cholangiopathies are distinguished by the presence of cholestasis, ductular reaction, biliary inflammation, and liver fibrosis. These illnesses advance slowly but steadily, and liver problems can be severe and cirrhotic, particularly in the latter stages. Circadian rhythm and melatonin production has been linked to the aetiology of cholangiopathies and liver cirrhosis. A recent study discovered that individuals with primary biliary cholangitis (PBC) or cirrhosis have significantly delayed sleep time, and that delayed sleep timing is related to poor sleep quality in PB patients. Melatonin supplementation might be a potential strategy for regulating cholangiocyte activities and maintaining liver homeostasis. 8

Liver transplantation and ischemia-reperfusion injury – Melatonin protects the liver from ischemia and reperfusion damage by blocking the toll-like receptor signalling cascade.10

Although the precise processes are yet unknown, alterations in clock gene expression and circadian rhythms may contribute to melatonin's therapeutic benefits. It is unclear if melatonin has therapeutic benefits independent of circadian rhythms or whether rhythmic melatonin administration restores broken rhythms and has greater effects.8 More research is needed to understand the functions of melatonin and circadian rhythms in liver illnesses and to create effective and practical melatonin therapy for liver disease patients. Fundamentally, melatonin has been shown to protect against a variety of liver disorders, and circadian rhythms and clock gene expression are interesting therapeutic targets for the treatment of liver ailments.

Reducing melatonin supplement use

Melatonin use is only intended for the short term. If after 1 or 2 months and you are still struggling to get a goodnight’s rest, the issue may be something else – poor sleeping habits.

To ensure good sleeping habits, it is recommended to apply certain practices.

Exercising – Exercising has been proved to aid sleep. Light exercise before bed is more advised than strenuous exercise. 

Bathing – A warm relaxing bath before sleeping is helpful as it raises the body temperature making you feel sleepy. A similar effect taking melanin supplements provides.

Sleep Environment – The bed should only be used for sleeping. The mind could associate the bed with other activities if it was used for tasks like reading, watching movies or eating.  A quieter bedroom, a pleasant temperature, and a well-made bed promote better sleep. Melatonin secretion is suppressed by bright light and shorter wavelength light It is better to avoid using technology that emits blue light.11 A less bright bedroom and longer wavelength lighting will help you sleep.

Food/Drugs – Sleep deprivation is caused by hunger. A large dinner before bedtime can cause sleep disruption. A light snack may be beneficial. Melatonin-containing foods and tryptophan-containing foods can work as natural sleep inducers. For at least 4-6 hours before going to bed, avoid caffeine, nicotine (cigarettes), and alcohol (fragments and lower total sleep time).11 Certain drugs, such as stimulants, can have a negative impact on sleep either directly or through interfering with melatonin synthesis (e.g.aspirin, ibuprofen etc).11

Sleep schedule - Try to stick to a consistent bedtime and wake-up routine, even on weekends. Most critical, regardless of how bad the previous night's sleep was, waking up at the same time every morning. Rather than spending too much time in bed awake, sleep when you are weary and asleep. If you haven't slept after 20-30 minutes in bed, get out of bed, and do something relaxing. Avoid taking naps during the day. Naps, on the other hand, are essential for young children, ideally in the early afternoon.

Summary

Melatonin is a naturally occurring hormone generated by the pineal gland (located in your brain). It helps to regulate your sleep pattern. Melatonin is produced by the body shortly after it becomes dark, increasing in the early hours of the morning and decreasing during the day. Melatonin stimulates sleep by acting on receptors in your body. Although there is no official melatonin dose guideline for people, a range of 0.5 mg to 5 milligrams appears to be both safe and helpful. Melatonin is used to treat insomnia, jet lag, and other sleep problems such as non-24-hour sleep-wake disorder. Melatonin supplements appear to enhance sleep and are safe for short-term usage, according to research. There are no substantial adverse effects or hazards connected with taking a tiny dosage of melatonin before bed on an irregular or short-term basis. Irritability, sleepiness, nausea, diarrhoea, and headaches are among the mild side effects. Melatonin pills cause your body to grow sleepier progressively until you fall asleep. It might take up to two hours after taking melatonin for you to fall asleep. As a result, you should take the supplement one to two hours before going to bed. Melatonin hasn't been connected to liver damage yet, so it's probably safe to consume if you don't have any prior or present liver impairment. The NHS, on the other hand, does not advocate melatonin supplements for persons with hepatic impairments due to a lack of expertise with melatonin usage in patients with liver disease. Numerous studies have been undertaken to study the effect of melatonin on liver injuries and illnesses, and melatonin may alter numerous cellular pathways in a variety of pathophysiological situations. Melatonin and its metabolites have potent antioxidant/anti-inflammatory properties and have been demonstrated to be particularly beneficial in a variety of diseases related to inflammation and oxidative stress. As melatonin is only intended to be used for the short term, once reducing melatonin supplement intake, establishing a healthy environment will promote good sleep. You may assure excellent sleeping patterns by keeping to a consistent bedtime and wake-up schedule, especially on weekends. Bright light and shorter wavelength light also decrease melatonin release. It is preferable to avoid using blue-light emitting technologies. You will sleep better if your bedroom is less bright and has longer wavelength illumination.

References

  1. Zhang J-J, Meng X, Li Y, Zhou Y, Xu D-P, Li S, et al. Effects of Melatonin on Liver Injuries and Diseases. International Journal of Molecular Sciences [Internet]. 2017 Mar 23;18(4). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412268/
  2.  Melatonin Pharmacy Compounding Advisory Committee Meeting [Internet]. 2021. Available from: https://www.fda.gov/media/150006/download
  3. Summer J. Melatonin Dosage by Age and Weight [Internet]. Sleep Foundation. 2021. Available from: https://www.sleepfoundation.org/melatonin/melatonin-dosage-how-much-should-you-take
  4. Should Melatonin Be Used as a Sleeping Aid for Elderly People? The Canadian Journal of Hospital Pharmacy [Internet]. 2019;72(4):327–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699865/
  5. NHS. Melatonin: a man-made hormone used for short-term sleep problems [Internet]. nhs.uk. 2019. Available from: https://www.nhs.uk/medicines/melatonin/
  6. Chaudhry SR, Stadlbauer A, Buchfelder M, Kinfe TM. Melatonin Moderates the Triangle of Chronic Pain, Sleep Architecture and Immunometabolic Traffic. Biomedicines [Internet]. 2021 Aug 9 [cited 2022 Aug 4];9(8):984. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392406/
  7. Bauer B. Pros and cons of melatonin [Internet]. Mayo Clinic. 2017. Available from: https://www.mayoclinic.org/healthy-lifestyle/adult-health/expert-answers/melatonin-side-effects/faq-20057874
  8. Sato K, Meng F, Francis H, Wu N, Chen L, Kennedy L, et al. Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies. Journal of Pineal Research. 2020 Apr;68(3).
  9.  Pakravan H, Ahmadian M, Fani A, Aghaee D, Brumanad S, Pakzad B. The Effects of Melatonin in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial. Advanced Biomedical Research [Internet]. 2017 Apr 17 [cited 2021 Dec 29];6:40. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414412/
  10.  Li Y, Yang Y, Feng Y, Yan J, Fan C, Jiang S, et al. A review of melatonin in hepatic ischemia/reperfusion injury and clinical liver disease. Annals of Medicine. 2014 Jul 18;46(7):503–11.
  11.  Stein MA, Weiss M, Hlavaty L. ADHD Treatments, Sleep, and Sleep Problems: Complex Associations. Neurotherapeutics [Internet]. 2012 Jun 21;9(3):509–17. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441938/

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Ambria Pearce

Bachelor of Science - BSc, Neuroscience, University of Sussex, England

Ambria is currently a BSCs Neuroscience student at the University of Sussex. She has a particular interest in the brain-gut connection; where the brain has a direct influence on the stomach and intestines and the neural processes of mental disorders. She intends to further study neuroscience at a Masters's level.

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