




































Special Edition: Junior Clinical Research (2022), Vol. 2 No. S2 
 https://doi.org/10.47488/dhrp.v2iS2.70 

 

 

 
DHR Proceedings ǀ http://dhrproceedings.org 100 2022, Vol. 2 No. S2 100-105 

 

COMMENTARY 

Physiological Effects of Melatonin in 

Children 
 

Samantha Lara1,2, Danna Hernandez1,2, Jaime Balli1,2,  Ruby Villa1,3,  Saul Martinez1,3,  David 

Saldana1,3,  Sandy Poy Aguilar1,3,  Krystian Rodriguez1,4,  Clarissa Garza1,4,  Gino Martinez1,4,  

Jessica Cervantes1,4 

 

 
12nd Annual Junior Clinical Research Internship, South Texas Academy for Education & Training in Research, DHR Health 

Institute for Research & Development 
2Progreso Early College High School, Progreso, TX 
3Los Fresnos High School, Los Fresnos, TX 
4La Villa Early College High School, La Villa, TX 

 

All correspondence should be addressed to Program Director, 2nd Annual Junior Clinical Research Internship Program, DHR 

Health Institute for Research & Development, 5323 S McColl Road, Edinburg Texas, 78539 

 
Received 08/04/2022 

Accepted for publication 08/15/2022 

Published 08/15/2022 

 
 

Melatonin Overview  

 

Melatonin is a hormone produced in the body 

that affects when a person sleeps [1]. It contains 16 

hydrogen atoms, 13 carbon atoms, 2 nitrogen atoms, 

and 2 oxygen atoms (C13H16N2O2) [2]. The 

hormone gets produced in the pineal gland located in 

the brain. The hormone is then shot into the 

bloodstream [3]. Depending on whether there is light 

(day) or darkness (night), the levels of melatonin 

increase and decrease [1]. Sometimes, however, the 

melatonin levels at night can be low, making it 

difficult to fall asleep. This causes people to rely on a 

melatonin supplement that helps increase their 

melatonin levels. This supplement comes in various 

forms that can be bought over the counter. For 

instance, you can find them as forms of pills, drops, 

sprays, and gummies. In addition, you can either get 

this supplement natural or synthetic. However, the 

natural form is made in pineal glands from animals 

that can be contaminated by viruses during the 

extraction, while synthetic is manmade and does not 

carry the same risk. [4].  

 

Melatonin Use 

 

Melatonin is utilized by many different 

people for a variety of reasons. According to the CDC, 

a 10-year period study by the American Association of 

Poison Control Centers’ National Poison Data System 

reported that the yearly number of melatonin intake 

increased by 530% with 260,435 pediatric melatonin 

ingestions announced [5]. However, melatonin is not 

only utilized in children; it can also be prescribed and 

used by adults in order to aid in problems involving 

short-term sleep.  

Moreover, in the United States, the purchase 

and intake of melatonin doubled between 2007- 2012, 

making it the 4th most natural product consumed by 

adults and 2nd most natural product consumed by 



Lara, et al  Melatonin in Children 
https://doi.org/10.47488/dhrp.v2iS2.70 

 

 
DHR Proceedings ǀ http://dhrproceedings.org 101 2022, Vol. 2 No. S2 100-105 

children [6]. Melatonin’s popularity is continuously 

growing due to the fact that it can be used to regulate 

sleep cycles where the creation of melatonin is 

influenced by the specific time of day. Melatonin 

supplements can also be utilized to help in withdrawal 

from benzodiazepines and in decrease of blood 

pressure [7].  

 

In addition, there are even specific diseases 

that require melatonin use in order to help the 

individual who has acquired that disease. For instance, 

as stated by the Mayo Clinic, melatonin can be utilized 

to benefit and improve insomnia for older adults by 

decreasing the individual’s ability to fall asleep, 

regulating circadian rhythm sleep disorders in the 

blind in children and adults, and jet lag symptoms by 

enhancing attentiveness and tiredness during the day 

[1]. Furthermore, melatonin is extremely effective and 

can even be used to improve and reduce the pain of a 

uterine disorder known as endometriosis in adults by 

taking melatonin orally [8]. 

 

Melatonin Prescriptions 

 

Melatonin is prescribed by doctors to treat 

circadian rhythm disorders, and to provide relief for 

insomnia [9]. It may also be used to substitute the 

hormone for patients who are 

Melatonin deficient throughout the night [10]. Another 

reason that doctors may be prescribing it is to help with 

anxiety before or after surgery [9]. Researchers have 

found that the prescribing of melatonin for 

hospitalized patients has increased substantially over a 

4-year period, despite limited research on dosing, [11].  

 

Beneficial and Adverse Outcomes of 

Melatonin Use 

Parents administer melatonin to children 

and/or teenagers to help them get to a more relaxed 

state before bed. However, melatonin is already 

naturally produced. Although there is no real evidence 

of overdosing on melatonin, it is still a risk [12]. 

Anytime a child ingests melatonin, they run the risk of 

experiencing certain side effects. For example, nausea, 

vomiting, headaches, hypotension or hypertension 

[12,13]. A long-term health risk from melatonin has 

not been found since there is a lack of high-quality 

studies in the U.S. However, increased use of 

melatonin at the pediatric stage can lead to multiple 

disorders [13]. For example, cardiac disorders, 

circadian rhythm, delay sexual maturation, and 

depression. Although there are certain downfalls when 

using OTC Melatonin, there are also some positives. 

According to new research, melatonin has been shown 

to synchronize the circadian rhythms, and improve the 

onset, duration and quality of sleep [14]. Every year 

the number of overdoses involved with melatonin have 

increased dramatically [9]. According to a study 

conducted, the number of reports to U.S. poison 

control centers about people 19 years and younger 

who took melatonin increased from 8,337 in 2012 to 

52,563 in 2021 [9].  

Adverse Effects of Melatonin Use  

 

Pulmonary Hypertension 

 

Pulmonary hypertension in children is caused 

by congenital heart defects present at birth [16]. 

Pulmonary hypertension is narrowed, blocked, or 

destroyed blood vessels in the heart which causes high 

blood pressure that affects arteries in the lungs and the 

right side of the heart while simultaneously causing 

blood clots, arrhythmia, and bleeding in the lungs [17].  

It also inhibits the body’s natural production of 

melatonin. Melatonin supplements are shown, in 

recent studies, to have lowered the severity of 

pulmonary hypertension, helping to prevent chronic 

hypoxia caused by Pulmonary Hypertension, and also 

have anti-inflammatory effects, which inhibits 

oxidative stress, restoring nitric oxide production. In a 

study conducted through 2014 - 2019, 64 adult 

patients, 43 patients diagnosed with Pulmonary 

Arterial Hypertension and 21 patients diagnosed with 

Chronic Thromboembolic Pulmonary Hypertension, 

and 111 individuals who reported themselves as 

healthy were used to test the positive and negative 

effects of melatonin in their cardiovascular and 

respiratory health, under the accordance of the 

Declaration of Helsinki. Consistent blood sampling 

was performed during each scheduled visit, between 

the times of 9:00 and 18:00, where the natural 

melatonin levels in the blood were expected to be 

stable. Blood samples would then be frozen and stored 

in aliquots at -80c and then thawed only once for use. 



Lara, et al  Melatonin in Children 
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DHR Proceedings ǀ http://dhrproceedings.org 102 2022, Vol. 2 No. S2 100-105 

Melatonin levels were measured using ultra-

performance liquid chromatography-tandem mass 

spectrometry. The results obtained from these tests 

help show the difference in melatonin levels in the 

patients. Overall, the research came to the conclusion 

that individuals who have been diagnosed with PAH 

or CTEPH have an independent risk factor of PAH in 

logistic regression analysis while individuals who 

have lower levels of melatonin were predicted to have 

a worse long-term survival rate [15].  

 

Valvular Heart Disease 

 

Melatonin inhibits NF-KB/Creb/ Runx2 that 

stimulates and increases aortic valve calcification [18]. 

It causes a high mortality rate. (many deaths) This 

study showed that the use of melatonin signals 

valvular interstitial cell calcification of the aortic 

valve, leading to aortic valve disease.       

Aortic calcification is a disease in which calcium 

deposits form on the aorta and most commonly the 

Aortic valve. This causes narrowing also known as 

stenosis thus causes reduced blood flow, this poor 

blood perfusion and circulation that may often cause 

medical issues and increases the risk of death [19].  

  

Delay in Sexual Maturation 

 

Melatonin may affect the length of one’s 

ovulation cycle and may affect menopause as well 

[20]. The use of long term melatonin (2 or more years) 

will delay one’s sexual maturity. Long term use of 

melatonin delays sexual maturity by interrupting the 

decline in melatonin levels that occur at night and on 

the beginning of puberty [21].  

 

There are many different studies that show 

the correlation in sexual maturation and melatonin use 

in adolescent individuals. In a recent research study 

animal studies showing the exogenous melatonin can 

suppress GnRH secretion [21]. GnRH secretion is 

responsible for sexual development, ovulation cycles, 

and regulating the onset of puberty. Suppression of 

this hormone can produce pubertal disorders 

indicating this may affect a child’s sexual maturation 

[22].  

 

Interactions between Melatonin and Other 

Medications and Herbal Remedies 

 

Through research, the effects of melatonin 

along with other medications and herbal remedies are 

shown to increase the risk of situations to worsen. For 

example, anticoagulants, anti-platelet, and herbs are 

medicines used to reduce blood clotting. However, 

when these drugs combine with melatonin it could 

increase the risk of bleeding. Furthermore, the use of 

melatonin along with blood pressure drugs and 

diabetes medications might affect blood pressure and 

sugar levels. As a result, the adverse effects melatonin 

has with medicine can lead to many problems [1]. 

 

Current Research  

 

Melatonin can be used to help women, who 

have breast cancer, to help slow the growth of cancer 

cells. Several studies have shown it can also increase 

the risk of side effects of chemotherapy drugs (that are 

used to help treat cancer) including loss of appetite, 

nausea, diarrhea, hair loss, a change in the muscles 

(muscle strain and loss of strength), nerve (numbness 

and pain in thumbs and toes), and hearing (loss in 

hearing), and increased risk of infections. However, 

melatonin can also have an opposite effect on 

medication [23]. Although the use of melatonin can 

help benefit people with different problems like breast 

cancer, it could also interfere with medications 

causing them to either “cancel out” the medication or 

to make the medication more “powerful”. For 

instance, in type 2 diabetics, they take a medication 

called metformin that is used to help the body regulate 

blood sugar levels. (NHS) However, when people with 

type 2 diabetes take melatonin, the melatonin levels do 

increase, but the melatonin reduces the ability for the 

insulin to create more insulin causing it hard to 

regulate blood sugar levels. This results in the 

pancreas working harder to produce enough insulin for 

the glucose [25]. A different study shows that 

melatonin can have an effect on diabetes medications. 

In recent studies, melatonin has many effects on 

pancreatic B-cells (cells that release insulin that plays 

a key role in glucose regulation). Non-functional 

pancreatic B-cells lead to uncontrolled blood glucose 

levels and diabetes. Pancreatic B-cells are susceptible 

to oxidative stress which reduces the function or 



Lara, et al  Melatonin in Children 
https://doi.org/10.47488/dhrp.v2iS2.70 

 

 
DHR Proceedings ǀ http://dhrproceedings.org 103 2022, Vol. 2 No. S2 100-105 

survival of B-cells. However, melatonin can provide 

protection against it and help balance the amount of 

insulin produced [24]. 

Conclusion 

Overall, melatonin is used to help children receive the 

recommended amount of sleep and provide parents 

with relief, however, numerous studies have shown 

that the use of melatonin in the pediatric population 

can carry cons such as causing unwanted side effects 

like nausea, loss of appetite, delay in sexual 

maturation, and worsening of chronic disease 

symptoms. On the contrary to the effects melatonin 

has with other medications, it is also shown to help 

improve various medicines to treat diseases. For 

example, the many research studies that have gone into 

finding a proper treatment for Covid-19. As Covid-19 

has been on the watch list for many doctors, 

researchers have found vitamin C and D work efficient 

against Covid-19. Since, vitamin C helps the body 

with its healing process along with increasing the anti-

oxidative (Oxidative damages cells, proteins, and 

DNA function, and vitamin D helps with the immune 

system. Combining them with melatonin, vitamin C 

defense against oxidative and vitamin D immune 

systems improve [28]. 

 

Acknowledgments 

 

Dr. Monica Betancourt-Garcia, MD, Scientific 

Director; Melissa Eddie, MS, Program Manager; 

Xochitl Lopez, BS, Program Coordinator 

 

Funding 

Funded by DHR Health Institute for Research & 

Development; DHR Health; Region One ESC 

GEARUP College Ready, Career Set!; Region One 

ESC GEARUP College Now, Career Connected and 

Region One ESC PATHS 

 

References 

 

1. Melatonin. (n.d.). Mayo Clinic. Retrieved 

July 29, 2022, from 

https://www.mayoclinic.org/drugs-

supplements-melatonin/art-20363071 

2. National Center for Biotechnology 

Information (2022). PubChem Compound 

Summary for CID 896, Melatonin. Retrieved 

August 1, 2022 from 

https://pubchem.ncbi.nlm.nih.gov/compound

/Melatonin. 

3. Melatonin and Sleep. (2022, April 8). Sleep 

Foundation. Retrieved July 29, 2022, from 

https://www.sleepfoundation.org/melatonin 

4. What Is Melatonin? - Can't Sleep | 

familydoctor.org. (2000, September 1). 

FamilyDoctor.org. Retrieved August 1, 2022, 

from https://familydoctor.org/melatonin/ 

5. Lelak, K. (2022, June 2). Pediatric Melatonin 

Ingestions — United States. . . Centers for 

Disease Control and Prevention, from 

https://www.cdc.gov/mmwr/volumes/71/wr/

mm7122a1.htm 

6. Grigg-Damberger, M. M., & Ianakieva, D. 

(2017). Poor Quality Control of Over-the-

Counter Melatonin: What They Say Is Often 

Not What You Get. Journal of clinical sleep 

medicine: JCSM : official publication of the 

American Academy of Sleep Medicine, 

13(2), 163–165. 

https://doi.org/10.5664/jcsm.6434 

7. Encyclopædia Britannica. (n.d.). Melatonin. 

Britannica Academic. Retrieved August 1, 

2022, from    https://academic-eb-

com.ezproxy.southtexascollege.edu/levels/c

ollegiate/article/melatonin/51873 

8. MELATONIN: Overview, Uses, Side 

Effects, Precautions, Interactions, Dosing 

and Reviews. (2005). WebMD. Retrieved 

August 2, 2022, from 

https://www.webmd.com/vitamins/ai/ingredi

entmono-

940/melatonin#:%7E:text=People%20most

%20 commonly%20use%20 melatonin, 

support%20best%20of%20these%20 uses 

9. Melatonin: What You Need to know. (n.d.). 

National Center for Complementary and 

Integrative Health. Retrieved August 1, 2022, 

from 

https://www.nccih.nih.gov/health/melatonin-

what-you-need-to-know 

10. Hardeland R. (2012). Neurobiology, 

pathophysiology, and treatment of melatonin 

deficiency and dysfunction. 

TheScientificWorldJournal, 2012, 640389.   

https://doi.org/10.1100/2012/640389 

11. Procaccini, D. E., & Kudchadkar, S. R. 

(2021). Melatonin Administration Patterns 

for Pediatric Inpatients in a Tertiary 

Children's Hospital. Hospital pediatrics, 

https://www.cdc.gov/mmwr/volumes/71/wr/mm7122a1.htm
https://www.cdc.gov/mmwr/volumes/71/wr/mm7122a1.htm
https://doi.org/10.5664/jcsm.6434
https://academic-eb-com.ezproxy.southtexascollege.edu/levels/collegiate/article/melatonin/51873
https://academic-eb-com.ezproxy.southtexascollege.edu/levels/collegiate/article/melatonin/51873
https://academic-eb-com.ezproxy.southtexascollege.edu/levels/collegiate/article/melatonin/51873


Lara, et al  Melatonin in Children 
https://doi.org/10.47488/dhrp.v2iS2.70 

 

 
DHR Proceedings ǀ http://dhrproceedings.org 104 2022, Vol. 2 No. S2 100-105 

11(11), e308–e312. 

https://doi.org/10.1542/hpeds.2021-006117 

12. What Are the Dangers of Taking Too Much 

Melatonin? (2022, April 12). Verywell 

Health. Retrieved August 3, 2022, from 

https://www.verywellhealth.com/melatonin-

overdose-5219376 

13. https://www.mayoclinic.org/drugs-

supplements-melatonin/art-

20363071#:~:text=Less%20 common%20 

melatonin%20side%20effects,hours%20of%

20making%20the%20 supplement 

14. Xie, Z., Chen, F., Li, W. A., Geng, X., Li, C., 

Meng, X., Feng, Y., Liu, W., & Yu, F. 

(2017). A review of sleep disorders and 

melatonin. Neurological research, 39(6), 

559–565. 

https://doi.org/10.1080/01616412.2017.1315

864 

15. Cai, Z., Klein, T., Geenen, L. W., Tu, L., 

Tian, S., van den Bosch, A. E., de Rijke, Y. 

B., Reiss, I., Boersma, E., Duncker, D. J., 

Boomars, K. A., Guignabert, C., & Merkus, 

D. (2020). Lower Plasma Melatonin Levels 

Predict Worse Long-Term Survival in 

Pulmonary Arterial Hypertension. Journal of 

clinical medicine, 9(5), 1248. 

https://doi.org/10.3390/jcm9051248 

16. Pulmonary Hypertension in Children. (n.d.). 

Johns Hopkins Medicine. Retrieved August 

1, 2022, from 

https://www.hopkinsmedicine.org/health/co

nditions-and-diseases/high-blood-pressure-

hypertension/pulmonary-hypertension-in-

children  

17. Pulmonary hypertension - Symptoms and 

causes. (2022, April 13). Mayo Clinic. 

Retrieved August 1, 2022, from 

https://www.mayoclinic.org/diseases-

conditions/pulmonary-

hypertension/symptoms-causes/syc-

20350697 

18.    Li SJ, Cheng WL, Kao YH, Chung CC, 

Trang NN, Chen YJ. Melatonin Inhibits NF-

κB/CREB/Runx2 Signaling and Alleviates 

Aortic Valve Calcification. Front Cardiovasc 

Med. 2022 Jun 20;9:885293. doi: 10.   

.2022.885293. PMID: 35795373; PMCID: 

PMC9251177 

             https://pubmed.ncbi.nlm.nih.gov/35795373/   

19. Shah SY, Higgins A, Desai MY. Bicuspid 

aortic valve: Basics and beyond. Cleve Clin J 

Med. 2018 Oct;85(10):779-784. doi: 

10.3949/ccjm.85a.17069. PMID: 30289756. 

https://pubmed.ncbi.nlm.nih.gov/30289756 

20. Greendale, G. A., Witt-Enderby, P., 

Karlamangla, A. S., Munmun, F., Crawford, 

S., Huang, M., & Santoro, N. (2020). 

Melatonin Patterns and Levels During the 

Human Menstrual Cycle and After 

Menopause. Journal of the Endocrine 

Society, 4(11), bvaa115. 

https://doi.org/10.1210/jendso/bvaa115 

21. Boafo, A., Greenham, S., Alenezi, S., 

Robillard, R., Pajer, K., Tavakoli, P., & de 

Koninck, J. (2019). <p>Could long-term 

administration of melatonin to prepubertal 

children affect timing of puberty? A 

clinician&rsquo;s perspective</p> Nature 

and Science of Sleep, Volume 11, 1–10. 

https://doi.org/10.2147/nss.s181365 

22. Marques P, Skorupskaite K, Rozario KS, et 

al. Physiology of GnRH and Gonadotropin 

Secretion. [Updated 2022 Jan 5]. In: Feingold 

KR, Anawalt B, Boyce A, et al., editors. 

Endotext [Internet]. South Dartmouth (MA): 

MDText.com, Inc.; 2000-. Available from: 

https://www.ncbi.nlm.nih.gov/books/NBK2

79070/ 

23. Melatonin Information. (n.d.). Mount Sinai. 

Retrieved August 3, 2022, from 

https://www.mountsinai.org/health-

library/supplement/melatonin 

24. Espino, J., Pariente, J. A., & Rodríguez, A. B. 

(2011). Role of melatonin on diabetes-related 

metabolic disorders. World journal of 

diabetes, 2(6), 82–91. 

https://doi.org/10.4239/wjd.v2.i6.82 

25. Garaulet, M., Qian, J., Florez, J. C., Arendt, 

J., Saxena, R., & Scheer, F. (2020). 

Melatonin Effects on Glucose Metabolism: 

Time To Unlock the Controversy. Trends in 

endocrinology and metabolism: TEM, 31(3), 

192–204. 

https://doi.org/10.1016/j.tem.2019.11.011 

26. Type 2 diabetes - Understanding medicine. 

(n.d.). NHS. Retrieved August 2, 2022, from 

https://www.nhs.uk/conditions/type-2-

diabetes/understanding-medication/ 

27. Gavin, M. L. (n.d.). What Is Type 2 Diabetes? 

(for Teens) - Nemours KidsHealth. Kids 

Health. Retrieved August 2, 2022, from 

https://kidshealth.org/en/teens/type2.html 

28. Does Evidence Exist to Blunt Inflammatory 

Response by Nutraceutical Supplementation 

during COVID-19 Pandemic? An Overview 



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DHR Proceedings ǀ http://dhrproceedings.org 105 2022, Vol. 2 No. S2 100-105 

of Systematic Reviews of Vitamin D, 

Vitamin C, Melatonin, and Zinc. (2021, April 

12). NCBI. Retrieved August 3, 2022, from 

https://www.ncbi.nlm.nih.gov/pmc/articles/P

MC8069903/ 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


