The 23+ Benefits of Melatonin

Support Your Sleep Cycle and Boost Cognition with Melatonin

Melatonin is a hormone produced by the pineal gland used by every cell in the body.



Melatonin has many functions in the body:

  • Regulates circadian rhythm R
  • Influences sleep R
  • Defends against EMF Radiation R R
  • Helps eyesight R
  • An antioxidant R
  • Helps the immune system R
  • Supports cell function R 

Melatonin is more powerful in preventing cell death than vitamin E, glutathione, mannitol and vitamin C. R

Compared to daytime, the body has 10-15x more melatonin in the blood at night. R

Light can decrease melatonin production. R

Age can also decrease melatonin production. R

Rhythmic melatonin production plays a critical role in the regulation of reproduction in seasonally breeding mammals. R R

Melatonin is also a probiotic. R

Melatonin is also called N-Acetyl-5-Methoxytryptamine, Melatonine, Melovine, Melatol, Melatonex, and Circadin.

MT1 and MT2 Receptors

  1. Melatonin is derived from the amino acid tyrptophan. R
  2. Tryptophan is converted to serotonin by AANAT (arylalkylamine N-acetyltransferase), which converts serotonin to N-acetylserotonin.  R
  3. ASMT (Acetylserotonin O-methyltransferase) is an ezyme that is encoded by the ASMT gene and that catalyzes the final reaction in melatonin biosynthesis, converting Normelatonin to melatonin. R
  4. Melatonin is a hormone produced by the pineal gland. R
  5. It is also produced by the gut, among other organs. R
  6. Melatonin release occurs at night and mediates dark adaptation of retina through G-protein MT1 (Mel1a-Mel1b) and MT2 receptor proteins. R R
  7. MT1 and MT2 receptors are encoded by the MTNR1A and MTNR1B genes. R
  8. MT1 and MT2 receptors are active at different stages of sleep. R
  9. MT1 is involved with deep sleep/REM sleep. R
  10. MT1 receptor may be implicated in the pathogenesis of melancholic depression. R
  11. MT2 is involved with pre-dreaming stages of sleep. R
  12. Glucose concentration and the presence of competitive ligands of GLUT1 affect the concentration of melatonin into cells. R


1. Protects the Brain


Melatonin activates BDNF and increases NGF. R R

It strengthens the blood brain barrier. R

Melatonin stops the proteins that activate nerve cell death. R

It helps after TBI and spinal cord injury. R

After stroke, nerve cells die usually from the blocked artery not supplying blood to the brain. In rats, melatonin blocked the activity of IL-1β, TNF-α, BAD, BAX and other proteins that contribute to inflammation and nerve cell death. It did this while increasing protein levels that prevent cell death.  R

In mice:

  • After TBI, melatonin had significantly less swelling various brain regions. R
  • After stroke, it prevented cell death by blocking the release of cytochrome c from mitochondria. R
  • Melatonin prevented cell death from amyloid beta25-35 (similar to the plaques seen in Alzheimer's). R
  • High doses of melatonin can relieve some symptoms of ALS. R
  • Melatonin protected the hippocampus against cognitive deficits from jet lag. R

2. Helps with Depression

Depression is associated with sleep disturbances. R

Melatonin and drugs that bind to MT2 may help with sleep disturbances associated with depression. R

Concentrations of melatonin during the day and night are possible biomarkers for severe depression. R

Depressed patients with delayed sleep phase syndrome improved with supplemental melatonin. R

Depression was prevented with in patients with breast cancer with melatonin supplementation. R

In rats, chronic stress-induced depression symptoms were alleviated with melatonin. R

3. Relieves Tinnitus

Melatonin may protect from tinnitus. R

Low amounts of it has been significant in elderly with tinnitius. R

3mg of melatonin was 150x more effective to treat tinnitus and reduce it's symptoms. R

4. Regulates Cells Mitochondria


Melatonin regulates the expression of genes in the cell cycle, cell/organism defense, protein expression and transport and mitochondrial function. R

The nucleus and mitochondria of cells have the most melatonin. R

Melatonin can repair damaged mitochondria directly. R

1 molecule of melatonin can bind to and neutralize up to 10 toxic reactants. R

Melatonin combats "molecular terrorism" at the mitochondrial level by cleaning up (scavenging) ROS (reactive oxygen species) and RNS (reactive nitrogen species). ROS and RNS can damage DNA and proteins, so melatonin scavenges them while creating new protective molecules. R

It blocks NOS. R

It also activates NRF2. R

Melatonin initiates molecular cleanup in the blood stream. R

It induces the expression of γ-GCS (γ-glutamylcysteine synthetase), the rate-limiting enzyme of glutathione synthesis, which protects cells against oxidative stress and regulates cell proliferation. R

Melatonin not only restores but also prevents the inhibition of the intestinal Ca(2+) absorption caused by glutathione depleting drugs. R

AFMK and AMK produced from melatonin scavenging prevents damage to molecules. R

5. Resets Circadian Rhythm and Sleep Disorders


Melatonin is involved in circadian rhythm. R

It is lower in people with insomnia. R

M1a and M1b receptors activated by melatonin induce sleep. R

Subjects slept quicker, deeper, and longer with melatonin supplementation. R

Melatonin improves sleep quality. R

6. Supports Ocular Health

MT1 and MT2 receptors are found in all layers of the retina. R 

Cells of the eye and retina make melatonin, although the amount of melatonin produced by the retina is small compared to that in the pineal gland. R 

Melatonin is necessary for normal eye development. R

MT receptors disruption can cause cones death. R

Melatonin protects eye pigment cells from cell death. R

It can decrease ocular hypertension. R

Glaucoma has been associated with melatonin dysfunction. R

Treatments for glaucoma (caused by ocular hypertension) include melatonin and 5-MCA-NAT. R

In animal studies:

  • Melatonin prevented optic neuritis. R
  • Mice lacking MT1 had less photoreceptor nuclei. R

Melatonin drops (in infancy and elderly) may prevent ocular damage. R

7. Protects Against Certain Poisons


Poisons can directly effect mitochondria. R

Melatonin can downplay the way poisons interfere with mitochondrial function. R

Melatonin protects against:

  • Rotenone R
  • MPTP R R
  • 3-NPA R
  • Cyanide R R

8. Treats Gut Problems


The gut has 100x more MT receptors than the bloodR

It has 10-100x more melatonin than the blood. R

It also has 400x more melatonin than the brain. R

Gut melatonin is highest during the day, inversely from brain concentration levels. R

Melatonin in the gut reacts to food. R

Melatonin increases gastrin. R R

Melatonin reduced pain during sleep with patients that have IBS (irritable bowel syndrome). R R

When used alone or with omeprezole, melatonin helped GERD (gastro-esophageal reflux disease). R

In animal studies:

  • Melatonin is able to increase Bacteroidetes and reduce the ratio of Firmicutes to Bacteroidetes. R
  • It also increases Akkermansia, which is good for weight loss. R
  • Alistipes, Anaerotruncus and Helicobacter marmotae were all reduced after melatonin treatment. R
  • Melatonin reduces severity of colitis.R
  • It reduces creation of ulcers in the stomach and severity of ulcers from ethanol. R R
  • Ethanal-weekend-guts were strengthened from supplementation of melatonin. R
  • It protected the gut from stress. R
  • It improved the gut lining. R
  • With malaria, it prevented liver cell death. R

9. Combats Metabolic Diseases

Melatonin is important for control of diabetes, obesity, and metabolic syndrome. R

Melatonin can control the change of levels of insulin and also decrease it. R

Melatonin is lower in patients with type 2 diabetes. R

Melatonin is beneficial for refractory central serous chorioretinopathy (affects the eyes of diabetic patients). R

It improves transport of glucose into muscle cells when insulin resistance-inducing poisons are present. R

It restored function and protected the pancreas's insulin-producing cells from cell death. R

Agomelatine (a melatonergic antidepressant) improved diabetic chronic pain. R

It also counteracted depression and controled blood sugar levels in diabetic patients. R

It's probably best to take melatonin at night, since melatonin has shown to educes glucose tolerance and insulin sensitivity in post menopausal women. R

Melatonin can stimulate the browning of fat. R

In animals: 

  • Obese rats given melatonin lost weight. R
  • They were genetically altered to not produce insulin. This increased their melatonin. R
  • Melatonin treatment improved diabetes symptoms (possibly through calcium regulation). R
  • It improved liver activity in obese diabetes. R
  • It improved rats and mice with NAFLD. R R
  • Melaxen and Epifamin (melatonin level correcting drugs) improved diabetes. R

10. Regulates Immune System

Melatonin improves states of immunity. R

It enhances TH2. R

Melatonin encouraged the proliferation of Th cells and improved their ability to secrete IL-4, but down-regulated the levels of IL-2 and IFN-gamma (interferon-gamma). R

11. Prevents and Fights Cancer


Melatonin prevents cancer development. R

It also blocks cancer cell growth. R

Melatonin interferes the energy process of cancer cells. R

It reduces the uptake of glucose and modifies the expression of GLUT1 transporter in prostate cancer cells. R

Blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities by amplifying nighttime melatonin levels. R

In an artificial sphere, melatonin blocked cancer growth of breast cancer cells by binding to estrogen receptors. R

It increases e-cadherin, a protein used in tumor suppression. R

Melatonin decreased OCT4 and N-cadherin, proteins used in tumor survival. R

It protects against CSC (cancer stem cells). R

In combination with flavone, melatonin increased cancer cell death by 80, when flavone alone only killed 40%. R

It suppresses inflammation, thus preventing the spread of cancer. R

Melatonin stops the growth of cholangiocarcinoma. R

It causes ovarian cancer cell death. R

In mice:

  • Melatonin suppresses tumor progression by reducing angiogenesis stimulated by HIF-1. R
  • Melatonin suppresses regulatory T cell activity, which led to cancer cell death. R
  • In combination with retinoic acid, breast tumors growth reduced by up to 20%. R
  • (In rats) melatonin suppressed tumor development in the liver. R

12. Helps with Alzheimer's Disease

Elderly Alzheimer's patients have both low MT1 and MT2 levels. R R

Bright light therapy and supplemental melatonin improved Alzheimer's patients sleep. R

This same treatment had been used long term Netherlands study showing benefits to rest and mental problems. R

In mice and rats, melatonin alleviated symptoms of Alzheimer's. R

13. Increases Longevity

In fruit flies, mice and rats, melatonin increased longevity. R

14. Helps Lungs Repair


Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome. R

15. Regulates Bipolar Disorder

Bipolar disorder has been associated with dysregulation of sleep and mood. R

Melatonin can be beneficial for bipolar disorder. R

16. Helps with Parkinson's Disease

Parkinson's disease often disrupts sleep. R

In mice and rats, melatonin alleviated symptoms of Parkinson's. R

It significantly improved PD patient's quality of sleep, but not motor function. R R

Melatonin was able to blocked the loss of dopamine neurons, and may be beneficial long term for PD. R

17. Reduces Drug Dependency


Melatonin helped patients reduce side effects and dependency of certain drugs. R

It also helped patients with benzodiazepines withdrawal. R

Melatonin can attenuate methamphetamine-induced neurotoxicity. R

18. Helps with ADHD and Autism

Melatonin supplementation helped ADHD children sleep better and earlier. R

Abnormalities in fatty acid metabolism and membrane fatty acid composition may play a part in autism spectrum disorders. Altered brain lipid composition and neurotoxicity related to autism spectrum disorders in propionic acid had restored levels of fatty acids when supplementing melatonin and CoQ10. R

19. Increases Ghrelin

Supplementation of 10mg of melatonin (2x 5mg/day) in H. Pylori patients with stomach ulcers, increased gastrin and ghrelin. R

20. Reduces Blood Pressure

5mg of melatonin for 2 months decreased blood pressure. R

1mg of melatonin depressed blood pressure and reduced noradrenaline levels in healthy men. R

Blood pressure and noradrenaline were both decreased in healthy women. R

21. Increases Leptin


After melatonin treatment, leptin levels rose significantly by 33%. R

22. Increases Growth Hormone

500mcg and 5mg of melatonin activated the pituitary gland increasing serum growth hormone. R R

23. Reduces Exercise-Induced Inflammation

Supplementation of melatonin suppressed exercise-induce inflammation and oxidation. R

24. Helps With Psoriasis

Low melatonin is usually found in psoriasis patients. R

This may be due to high CRH or MSH levels. R

Regulating melatonin levels has shown to have an effect on reducing psoriasis. R

My Experience

I use melatonin when I'm traveling to a different time zone. I'll use it to reset my circadian rhythm. I'll take about 250mcg (0.25mg) of melatonin. If I take too much I wake up in the middle of the night or feel hungover the next day.

I also used melatonin for a 3 weeks after I had a concussion. This is the longest I have chronically used it.

Increase Melatonin


Decrease Melatonin

Side Effects

Insecticides can mimic melatonin in the body and cause circadian rhythm disruption. R

Not really a side effect, but melatonin suppresses GDNFR

Melatonin also suppresses dopamine (and dopamine suppresses melatonin). R

Hungover the next day (anecdotally)

Other side effects: R

  • Daytime sleepiness
  • Headaches
  • Dizziness

It may interact with medications such as: R

  • Blood-thinning medications (anticoagulants)
  • Medications that suppress the immune system (immunosuppressants)
  • Diabetes medications
  • Birth control pills

Mechanism of Action in the Body

Overview of Melatonin Biosynthesis R and more in depth

Overview of Melatonin Biosynthesis R and more in depth

  1. BH4 reacts with oxygen and the active site of iron of tryptophan hydroxylase. 
  2. It may either:
    • There is a transfer of 1 electron of pterin to O2, creating superoxide.
    • The superoxide combines with the pterin radical to create 4a-peroxypterin.
    • Along with the active site iron (II), it creates iron-peroxypterin intermediate, directly transfering an O atom to Fe.
    • O2 produces iron (III) superoxide by reacting with the active site iron (II).
    • Iron (III) superoxide reacts with pterin to create an iron-peroxypterin intermediate. 
  3. There is a double bond of iron oxide (from the iron-peroxypterin) to give a carbocation at the C5 position of the indole ring.
  4. Hydrogen loses 1 of its 2 atoms to create 5-hydroxy-L-tryptophan. R
  5. PLP along with a decarboxylase removes CO2 from 5-hydroxy-L-tryptophan to create 5-hydroxytryptamine. R
  6. PLP forms an imine with 5-hydroxytryptamine.
  7. The pyridine amine breaks the C-C bond, releasing CO2 by pronating and acting as an electron sink.
  8. By pronating the amine from tryptophan, it restores the aromaticity of the pyridine ring.
  9. The imine is then hydrolyzed to produce 5-hydroxytryptamine and PLP. R
  10. His122 of serotonin N-acetyl transferase catalyzes 5-hydroxytryptamine.
  11. This allows a lone pair on the amine to attack acetyl-CoA, forming a tetraherdral intermediate.
  12. The thiol from coenzyme A leaves allowing N-acetyl-serotonin to form. R
  13. SAM (S-adenosyl methionine) methylates N-acetyl-serotonin at the hydroxyl position producing SAH (S-adenosyl homocysteine) and melatonin. R


  • Browns adipose tissue R
  • Decreases ROS R
  • Decreased LPS, TNFα, and IL-6 R
  • Increases BDNF and NGF R R
  • Lowers IL-1β, BAD, BAX R
  • Protects NF-kB activation in liver R
  • Water and fat soluble R

More Research

  • Melatonin is found in tears. R
  • The combination of myo-Ins plus melatonin seems to affect positively glucose metabolism, while myo-Ins only seems to improve thyroid function. R
  • Nonmammalian species have a third high-affinity melatonin receptor subtype, the Mel1c receptor. R
  • Melatonin can prolong coma duration. R
  • Retinal melatonin may contribute to the levels of the hormone in the blood. R
  • The genes Pgc-1α and Nr4a1 are linked to circadian neurohormone release with functional adaptation and healthiness of retina and photoreceptor cells. R
  • Melatonin upregulates the activity of AMPK. R R R
  • When combined with galantamine, it supports neuronal protection. R R
  • The amount of light preschool-age children are exposed to in the 2 hours before bedtime predicts variance in circadian phase over and above bedtime alone. R
  • Melatonin Effects on the Brain, Sleep, Mitochondria, Vision/Eyes and Hearing (Part 1) and (Part 2) R R