Melatonin and its Effects: The Truth Behind this Popular Supplement

Lizeth Soto Garcia

B.S. Candidate, Department of Business Administration, California State University Stanislaus, 1 University Circle, Turlock, CA 95382

Received 05 May 2020, Accepted 15 May 2020

Abstract

Melatonin is a significant hormone secreted in the pineal gland of the brain that is primarily known for

regulating the sleep-wake cycle. This sleep-wake cycle is affected by two processes known as process C for circadian

and process S for sleep. Process C work as an endogenous clock driving the cycle’s rhythm, and process S functions

through a homeostatic sleep behavior that keeps up with the sleep and wakefulness acquired. The short-term

consumption of melatonin as a supplement has been successful in treating sleep-related disorders of many kinds such

as jet lag and delayed sleep phase syndrome. It is worth noting, there are many after-effects that can occur with

melatonin consumption, such as short-term depression, dizziness, headaches, and irritability. Easy accessibility to

melatonin supplementation can lead to habit-forming side effects, resulting in dependency. While there is a lack of

information and studies on dependency, it can be underestimated, leading to complications in the side effects

correlating with substance abuse. There is a lack of knowledge in users who do not have a general understanding on

the exact duration of treatment. This can be uncertainty on whether supplements should be taken once for minor cases

such as jet lag, or consistently for a period of time for major sleeping disorders. The goal of this study is to inform

users of the possible effects that can come with taking melatonin supplements, because although already a naturally

produced hormone, melatonin can alter users’ body cycles in the long run.

Keywords: sleep-wake cycle, short-term consumption, lack of information

Methods

The initial interest for this study came from

the constant misinterpretation of melatonin constantly

being considered a drug, and not a hormone. As a

hormone, melatonin is in charge of sending chemical

messengers throughout the body in order to regulate

the sleep-wake cycle. The sleep-wake cycle is a daily

pattern responsible for determining the appropriate

sleep and wake times, affected by physical, mental,

and behavioral changes known as the circadian

rhythms.

For this research, my information was found

through a systematic review. This method allowed me

to select and evaluate evidence in order to assess the

results and derive conclusions. Specific keywords that

were used included the following: “melatonin FDA

banned,” “melatonin supplementation dependency,”

“melatonin overdosage case,” among others.

Regardless of searching through primary, secondary,

academic, and medical sources, there was not enough

research on melatonin supplementation as whole to

find many results on these searches. “Melatonin FDA

banned” was possibly one of the easier searches within

Google Scholar, with a few switches in wording to

“melatonin legality” or “melatonin illegal” and a few

article searches. “Melatonin supplementation

dependency” on the other hand, was quite difficult to

come across. Medical sources such as BioMed Central

and PubMed Central hardly offered, if any,

information on the specific correlation between

melatonin and dependency. It rather cited about the

relationship of melatonin to other sources such as

tobacco, insomnia, and therapy, with information

citing centralized around 2010 for BioMed Central and

around 2015 for PubMed Central. “Melatonin

overdosage case” was also among the easier searches

to find, with many records showing cases of users

overdosing on melatonin supplements. EBSCOhost

was among one of the sources used, but with only three

databases, my information was retrieved from

PubMed, which offered more articles on this topic. On

both sites, information was cited back to 1997. This

was something interesting to note due to the lack of

released information on melatonin supplements.

Looking for specific data, it could be said that

150 databases could have been looked through, but

only about 20 were kept for potential information on

the findings of melatonin and its effects. 150 databases

were looked through for keywords, but not many

actually contained information specific to melatonin,

but rather the mention of the hormone.

Introduction

[Melatonin’s anatomy and physiology] To

understand the effects of melatonin, it is necessary to

first understand what melatonin is and its significance.

Melatonin is a naturally produced hormone in the

body, which is responsible for sending chemical

messengers throughout the body to coordinate specific

functions. In melatonin’s case, specific functions

would be regulating the sleep-wake cycle. Melatonin

is produced right above the center of the brain, in an

area called the pineal gland, which is about the size of

a pea. In order for melatonin to be able to carry out its

functions, there is a process to the way it works.

Melatonin works through the influence of light and

dark detection with the eye retina. Light detection

helps regulate the body’s energy levels produced by

serotonin—a neurotransmitter produced in the

intestines and the brain that contributes to feelings of

well-being and happiness. The circadian rhythm works

as an internal clock scheduling the release of

melatonin, releasing higher levels during dark

detection and lower levels during light detection.

[The sleep-wake cycle] While melatonin has

many functions, one of its most important

contributions is helping regulate the sleep-wake cycle.

This sleep-wake cycle is affected by two processes

known as process C for circadian, working as an

endogenous clock driving the cycle’s rhythm, and

process S for sleep, functioning through a homeostatic

sleep behavior that keeps up with the sleep and

wakefulness acquired. The sleep-wake cycle is

responsible for producing and releasing melatonin at

different rates throughout the day. Melatonin

production tends to increase during the dark, but it is

known to decrease when it is light.

Melatonin and the Sleep-Wake Cycle

[Supplementation] Melatonin has been

studied since the 1950’s, but it did not become a

nutritional supplement until the 1990’s. In 1958,

Aaron B. Learner and his colleagues from Yale

University first isolated this hormone. Melatonin

obtained its name due to their studies in which the

substance had the ability to lighten a frog’s color. With

easier accessibility to melatonin supplements within

the United States than other countries, this supplement

became popularized due to its effects on sleep, cancer,

and other hormones. Melatonin’s availability in

supplement form allows users to treat short-term

disorders. These short-term disorders can include

jetlag and delayed sleep phase syndrome—a condition

where delayed sleep causes difficulty in being able to

wake up at the desired time. Consuming excessive

melatonin can impact the natural circadian rhythm

over time. One should keep in mind that dependency

can arise not from consuming melatonin supplements

itself, but from the side-effects of melatonin

supplements that can be habit-forming. Dependency

varies in definition and is often misinterpreted with

addiction. The difference between them is that

dependency is characterized by symptoms of tolerance

and withdrawal, addiction is the change in behavior

caused by brain biochemical changes due to substance

abuse.

By researching the relationship of melatonin

to its effects, impactful results were found both

mentally and physically. Studies demonstrated that

there is not more than two years’ worth of collected

innovative research. Not finding long-term research

made it harder to identify melatonin’s long-term

impact on users, whether it be beneficial or

detrimental.

Results

Melatonin Availability Chart

United States

•accessibility:

over-the-

counter

•legality:

legal

•form: liquid,

spray,

chewables

and tablets

United

Kingdom

•accessibility:

prescription

needed

•legality:

known as

Circadin,

legal but

with age and

health

requirement

•form:

tablets

Germany

•accessibility:

prescription

needed

•legality:

known as

Circadin,

legal but

must be

over 55

years old

•form:

typically

tablet, but

form can

change

Melatonin supplements are available in

different forms including liquid, spray, chewable and

tablets. Supplementation availability does vary, and

while there is easy access to melatonin supplements in

the United States such as an over-the-counter option

found at local drug stores, there are other countries that

limit it (as seen on the Melatonin Availability Chart

above). Melatonin supplements are classified as

dietary and therefore not FDA approved under the

Dietary Supplementation Health and Education Act of

1994. As mentioned, because of the easy access to

melatonin in some countries, it is necessary to keep in

mind the recommended dosages versus actual dosages.

While studies show that recommended

dosages vary from 0.1 to 5 milligrams, recorded

dosages have shown to greatly exceed this amount. A

case recorded a 66-year old man consuming melatonin

supplements the night before his prostate surgery in

hopes of aiding him in relaxation and a proper night’s

sleep. This case is significant because the user ran the

possibility of affecting or postponing his surgery the

following day due to upping the average dosage of

5mg, to 24mg for relaxation. Another case indicated

that a 4-year old girl accidentally swallowed 39

milligrams of melatonin in liquid form, greatly

surpassing the recommended amount. Sleep routines

are recommended for children as melatonin

supplements are not exactly sleeping pills, but children

with neurodevelopmental disorders among other

children are often found consuming melatonin

supplements. If melatonin supplementation is used, it

is recommended to be taken at extremely low dosages

with the consultation of a pediatrician, for a very short

period of time. While this case resulted in no

symptoms shown on the patient, there are a variety of

factors that may have affected these results, such as

age and lack of brain development.

There were notable differences in both the

brain and blood before melatonin supplementation

consumption. According to ‘“Melatonin the “light of

night” in human biology,”’ the average melatonin in

the brain varies from 10 to 60 pg/ml. It is shown that

melatonin peaks in early childhood but decreases in

older people producing a negligible amount of

melatonin. Due to these statistics, the average

melatonin in the brain for childhood to older people

was considered at 25 pg/ml (as seen on the Melatonin

Dosage Chart above). While studies show that

different tissues or body fluids contain a range of

melatonin concentrations, according to “Significance

of High Levels of Endogenous Melatonin,” the

average melatonin in the blood is about 50pg/ml.

Because of a lack of studies, and an unknown

amount of melatonin supplementation users, there was

an inability in calculating the exact amount of

melatonin circulating in the brain and blood once the

supplement was consumed. Results did show that

serum melatonin concentrations in the body were 10

to 100 times higher than the usual nighttime peak.

Melatonin Side Effects Table

While melatonin is a natural compound that

circulates in the body, like a drug, studies show that it

is dependent. Dependency does not arise from the

consumption of melatonin but rather from the habit-

forming side effects of melatonin consumption, which

are viewed as addictive. Melatonin is often considered

a drug, and this is related to the constant

misunderstanding of the differences between

dependency and addiction. Dependency is

characterized by symptoms of tolerance and

withdrawal, but addiction is characterized by changes

in behavior caused by biochemical changes in the

brain due to constant substance abuse. Because

dependency is underestimated, it can result in

complications correlating to melatonin

supplementation due to over-dosage or inability to

correctly measure the body-to-supplement dosage

ratio. It is difficult to calculate the necessary dosage

according to each body type, and it is especially

difficult to self-change the dosage increments

throughout time as the user’s body becomes familiar

Regular Amount CIrculation

without Supplement

Melatonin Dosage Chart

Brain Blood

Short-term side effects

dizziness

headaches

nausea

Long-term side effects

depression

nightmares

low blood pressure

with the supplement. This often leads to dependency

due to the easy accessibility of melatonin supplements,

at least all over the United States, and in other

countries. It is recommended that melatonin dosages

start out small, and as the body becomes more familiar

with it, one can slowly increase the supplement intake.

This will help the body familiarize with the

supplement and help a user rest without obtaining full

side effects. The recommended melatonin dose lasts

about 5 hours in the body, but overuse of this

supplement can cause a disruption in the circadian

rhythm. By disrupting the circadian rhythm, this can

lead to daytime sleeping.

Dose-dependent effects have not been

completely evaluated in users consuming large doses

of melatonin supplementation over long periods of

time, therefore, they cannot be accounted for due to

lack of research. Hypotheses are based on short-term

side effects, which include dizziness, headaches, and

nausea. There is a higher possibility of experiencing

less common side effects if more melatonin

supplementation than recommended is consumed

during a longer period of time. While there is no

specific time frame to define long term, there are only

up to two years’ worth of research in this topic,

displaying the differences between short term and

long-term side effects during this time gap (as seen on

the Melatonin Side Effects chart). The more intense

side effects that can occur during a long-term

consumption include nightmares, depression, and low

blood pressure.

Discussion

When considering taking melatonin as a

supplement, it is important to keep in mind both the

positive and negative effects that could arise. Doctors

are so quick to recommend or prescribe melatonin

supplements for mild uses, compared to other aids.

Other prescribed sleeping aids can be more dependent

and even harmful. Temazepam, for example, is a

sedative treating insomnia, but the user does run the

risk of suffering paranoid or suicidal ideation, and

impaired memory, judgement and coordination, all

effects far more harmful than melatonin

supplementation.

Melatonin supplementation has the

possibility of helping with cell protection. This

includes the involvement of modifying the immune

response and blood cell formation. Melatonin also has

a lot of therapeutic potential. While there are not many

studies to confirm this and it is just a mere possibility,

melatonin supplements are being reinforced into

cancer therapies for therapeutic effects to reduce the

side effects of chemotherapy especially or radiation.

Melatonin supplements are not just used for sleeping,

but also for migraines, attention deficit hyperactivity

disorder known as (ADHD), and irritable bowel

syndrome (IBS).

The lack of long-term research with melatonin

supplementation limits not only researchers’ advances

but also users’ knowledge. Less research leading to

unknown effects in the long run makes it more difficult

to identify on whether effects will be beneficial or

detrimental, among other factors. Supplementation

can also lead to habit forming side effects that result in

dependency. Considering the short-term effects of

melatonin, it leads to consider the detrimental effects

of using melatonin supplements long-term wise.

Concentration from natural foods and varying

dosages are important factors when considering

melatonin supplements. This uneven concentration

leads to an uneven distribution and a difference in the

biophysical dynamic features of the foods. Because

melatonin concentration varies in plants and animal

foods, this leads to unknown amounts circulating in

the body after melatonin consumption. There is not

easy access or enough proven data calculating how

much melatonin is appropriate to take when

considering all health factors. It is necessary to

calculate self-changing dosages as the body becomes

familiar with the supplement.

The main purpose of learning about the uses of

melatonin along with the possible side effects that can

be either beneficial or detrimental in the long run is for

the reader or user to gain awareness when it comes to

consuming melatonin supplementation. There is very

little information and studies, with so many possible

unknown risks that can come with melatonin

consumption if consumed long-term. While there is

not a lot of long-term research to consider, it is

necessary to keep in mind both the positive and

negative side effects that can be found affecting users

both physically and mentally.

Acknowledgements

I would like to thank the Honors Program at

California State University, Stanislaus for offering me

this opportunity to excel in research. I am thankful for

all the knowledge and assistance that this program

provided me. I would also like to thank my mentor, Dr.

Jamila Newton, for inspiring and continuously

supporting me.

References

“Addiction vs. Dependence: Differences In Drug

Abuse Terms.” Addiction Center,

www.addictioncenter.com/addiction/addiction

-vs-dependence/.

“Circadian Rhythms.” National Institute of General

Medical Sciences, U.S. Department of Health

and Human Services,

www.nigms.nih.gov/education/fact-

sheets/Pages/circadian-rhythms.aspx.

Cox, Lauren. “What Is Melatonin?” LiveScience,

Purch, 18 Dec. 2013,

www.livescience.com/42066-melatonin-

supplement-facts.html.

Denise, and Sebastian Mueller. “How I Sleep On a

Plane & Conquer My Jet Lag.” Tourist Is a

Dirty Word Travel Blog,

www.touristisadirtyword.com/index.php?post

_id=53.

The Editors of Encyclopaedia Britannica.

“Melatonin.” Encyclopædia Britannica,

Encyclopædia Britannica, Inc., 31 Oct. 2019,

www.britannica.com/science/melatonin

Grivas, Theodoros B, and Olga D Savvidou.

“Melatonin the ‘Light of Night’ in Human

Biology and Adolescent Idiopathic

Scoliosis.” Scoliosis, BioMed Central, 4 Apr.

2007,

www.ncbi.nlm.nih.gov/pmc/articles/PMC185

5314/

Holliman, B J, and P A Chyka. “Problems in

Assessment of Acute Melatonin

Overdose.” Southern Medical Journal, U.S.

National Library of Medicine, Apr. 1997,

www.ncbi.nlm.nih.gov/pubmed/9114843

Holliman, B J, and P A Chyka. “Problems in

Assessment of Acute Melatonin

Overdose.” Southern Medical Journal, U.S.

National Library of Medicine, Apr. 1997,

www.ncbi.nlm.nih.gov/pubmed/9114843

“How Do Hormones Work? | Fooling With Nature |

FRONTLINE.” PBS, Public Broadcasting

Service,

www.pbs.org/wgbh/pages/frontline/shows/nat

ure/etc/hormones.html.

“How Your Body's Circadian Rhythm (or

Sleep/Wake Cycle) Helps You

Sleep.” Sleep.org,

www.sleep.org/articles/sleepwake-cycle/

Li, Ya, et al. “Melatonin for the Prevention and

Treatment of Cancer.” Oncotarget, Impact

Journals LLC, 13 June 2017,

www.ncbi.nlm.nih.gov/pmc/articles/PMC550

3661/

“Melatonin and Children's

Sleep.” HealthyChildren.org,

www.healthychildren.org/English/healthy-

living/sleep/Pages/Melatonin-and-Childrens-

Sleep.aspx.

Meng, Xiao, et al. “Dietary Sources and Bioactivities

of Melatonin.” Nutrients, MDPI, 7 Apr. 2017,

www.ncbi.nlm.nih.gov/pmc/articles/PMC540

9706/

Nunez, Kirsten. “How Long Melatonin Remains in

Your Body, Efficacy, and Dosage

Tips.” Healthline, 11 Sept. 2019,

www.healthline.com/health/how-long-does-

melatonin-last.

Ratini, Melinda. “Melatonin Sleep Aid Supplement:

Effectiveness, Dosage, & Side

Effects.” WebMD, WebMD, 18 Mar. 2020,

www.webmd.com/sleep-disorders/what-is-

melatonin.

Tan, Dun-Xian, et al. “Significance of High Levels of

Endogenous Melatonin in Mammalian

Cerebrospinal Fluid and in the Central

Nervous System.” Current

Neuropharmacology, Bentham Science

Publishers Ltd, Sept. 2010,

www.ncbi.nlm.nih.gov/pmc/articles/PMC300

1210/