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Although melatonin is known as a hormone that helps you sleep, it has many other health benefits. Read this post to learn about ways to increase or decrease melatonin levels. If you’re looking for a complete guide on how to get your best night’s sleep every night check out our book Biohacking Insomnia.


Melatonin Part 3 of a 3-Part Series

  • Melatonin Part 1: 24 Surprising Health Benefits of Melatonin – Sleep, Brain, Gut Health, Antiaging, Cancer, Fertility, and more
  • Melatonin Part 2: Surprising Roles of Melatonin in Controlling Inflammation and Preventing Autoimmune Diseases
  • Melatonin Part 3: Ways to Increase and Decrease Melatonin, and Food/Drug/Supplement Interactions

Factors That Increase Melatonin Levels

1) Melatonin Supplements

In a review of 35 studies, researchers found that melatonin supplementation slightly improves sleep quality (R).

Melatonin shows promise in improving insomnia and reducing jet lag. It also does not have any serious side effects (R).

Although the optimal dosage is not yet determined, researchers recommend a lower dosage range. Even at low dosages, there is already a significant increase in melatonin levels after administration (R).

The recommended dosage range for elderly adults is 0.3 – 2 mg, around 1 hour before bedtime (R).

2) Vitamins and Minerals

Folate and vitamin B6 boosts the formation of serotonin from tryptophan. Serotonin is the precursor of melatonin (R).

In rats, vitamin B6 injections strengthen melatonin production. After two months of B6 injections, the blood level of melatonin increased by 35.95% (R).

Additionally, zinc and magnesium enhance the formation of melatonin from serotonin. They bind and activate the AANAT enzyme. This increases the affinity of serotonin for binding to AANAT (R).

Zinc supplementation increases melatonin levels in rats (R).

3) Food and Drinks that Increase Melatonin Levels (R):

  • Tomato (R)
  • Walnuts (R)
  • Barley and rye (R)
  • Strawberries (R)
  • Cherries (R)
  • Olive oil (R)
  • Unprocessed cow milk (R)
  • Grape wine (R)
  • Beer (R)

4) Traditional Chinese Herbs:

  • Periostracum cicadae (Chantui) (R)
  • Babreum coscluea (Shiya Tea-Leaf) (R)
  • Uncaria rhynchophylla (Gouteng) (R)
  • Viola philippica Cav (Diding) (R)
  • Phellodendron amurense (Huangbo) (R)
  • Mori Albae Cortex (Sangbaipi) (R)
  • Coptis chinensis (Huanglian) (R)
  • Angelica sinsensis (Danghui) (R)
  • Ziziphus ujube (Suanzhaoren) (R)
  • Salvia miltiorrhiza (Danshen) (R)
  • Panax notoginseng (Sangqui) (R)
  • Curcuma aeruginosa (Erzhu) (R)
  • Schisandra Chinensis (Wuweizi) (R)

Factors that Decrease Melatonin Levels

1) Drugs

  • Beta blockers: Beta blockers are drugs that help lower blood pressure. Beta blockers decrease melatonin release. They do this by inhibiting specific receptors (R).
  • Non-steroidal anti-inflammatory drugs (NSAIDS): NSAIDs, including aspirin and several other over the counter painkiller drugs, suppress nighttime melatonin levels (R).

2) Blue Light Exposure At Night

Blue light exposure at night can reduce melatonin levels and the time window that melatonin is secreted (R).

3) Other Factors

  • Aging: The pineal gland, which produces melatonin, contains cells called pinealocytes. The number of pinealocytes decreases with age. This then decreases melatonin production (R).
  • Fasting: Fasting reduces the nighttime secretion of melatonin. Short-term fasting from 2 to 7 days reduces blood melatonin levels by 20% (R)
  • Nutrient deficiencies: Folate, magnesium, and zinc deficiencies are linked with lower melatonin levels in rats (R).

Factors that Modify Melatonin Receptors

How to Increase/Activate Melatonin Receptor Activity

Agonists (activators) are agents, usually drugs, which bind and increase the activity of a receptor. The following are melatonin activators.

  • Agomelatine binds MT1 and MT2 receptors (R).
  • Tasimelteon also has a high affinity for MT1 and MT2 receptors (R).
  • Ramelteon is a selective MT1 and MT2 activator. Its binding affinity to melatonin receptors is higher than melatonin itself. It is used to treat insomnia (R, R).
  • TIK-301 is a melatonin receptor activator (R).

Factors that Decrease/Block Melatonin Receptor Activity

  • During aging and Alzheimer’s disease, MT1 receptor expression in the SCN and cortex decreases. MT2 receptor expression is also reduced during Alzheimer’s disease (R).
  • Luzindole is a competitive MT2 melatonin receptor antagonist. This means it blocks receptor function (R).
  • P-PDOT blocks the MT2 melatonin receptor (R).
  • S29434 blocks the MT3 receptor (R).
  • Caffeine blocks melatonin signaling/transmission (R).

Melatonin Supplement and Drug Interactions

1) Melatonin and Various Vitamins Work Together


Vitamin C, Vitamin D3, and Vitamin E are important antioxidants. Melatonin also has antioxidant activity. It can synergize with each vitamin individually to make a more powerful effect (R, R, R).

A combination of vitamin D3 and melatonin can stop human breast cancer cell growth (R).

Additionally, in calf DNA, melatonin and vitamin C worked together to make a powerful antioxidant action (R).

Meanwhile, vitamin E and melatonin combine to stop oxidative damage in rat livers (R).

2) Melatonin Works with Alpha-Lipoic Acid

In animals, alpha-lipoic acid works to scavenge free radicals. This means that it stops oxidative damage and has antioxidant activity. However, its antioxidant effects are weak (R).

When used in combination with melatonin, alpha-lipoic acid stopped DNA damage 3 times more effectively than when it was used alone. Melatonin and alpha-lipoic acid worked together to protect calf DNA from oxidative stress (R).

3) Melatonin Stimulates Glutathione Activity

Glutathione is a potent antioxidant that decreases lipid (fat) breakdown. However, it is less efficient that melatonin in protecting against oxidative stress (R).

Melatonin and glutathione combined had a greater antioxidant effect than when either was given individually. Their antioxidant activity combined to have a greater effect in rat livers (R).

Melatonin also helps stimulates glutathione activity in rat brains. They work together to eliminate peroxides and free radicals that cause oxidative damage (R).

4) Melatonin and Selenium Synergistic Effects

Selenium has free radical scavenger effects. This means that it can stop free radicals from damaging cells and DNA. It protects nerve cells and restores the activity of antioxidant enzymes (R).

Brain ischemia is a condition that occurs when there is not enough blood flow to the brain. It can lead to the death of brain tissue or even stroke. Free radicals and oxidative damage can cause brain ischemia (R).

Melatonin and selenium work together to improve the treatment of ischemia in male rats. This combination helped reduce injury and prevented brain inflammation (R).

5) Melatonin Works with Galantamine

Galantamine is a drug with antioxidant properties. It also helps protect nerve cells in the brain (R).

Human nerve cells treated with a combination of galantamine and melatonin were protected from oxidative damage. Very little concentrations of each substance by themselves did not show any effect. However, a combination of both had antioxidant effects (R).

6) Melatonin and Atorvastatin Combine Effects

Atorvastatin is a cholesterol-lowering (statin) medication. It blocks cholesterol production (R).

The addition of atorvastatin to melatonin therapy can enhance the effects of melatonin. It prevents harmful actions of the medication, reduces inflammatory action, and lowers free radical production (R).

7) Melatonin Interferes with EGCG

EGCG is responsible for most of the antioxidant effects of green tea. It prevents oxidative damage and protects cellular DNA (R).

However, high doses of EGCG or green tea extracts can cause hepatotoxicity (liver damage). Melatonin reduces toxicity due to EGCG overdose (R).

In one study, researchers gave mice toxic and lethal doses of EGCG. Melatonin extended the survival time of mice given toxic doses of EGCG. Meanwhile, it also helped reduce liver injury caused by a nonlethal toxic dose of EGCG (R).

8) Melatonin Reverses Resveratrol’s Pro-Oxidant Activity

Resveratrol has both antioxidant and anti-inflammatory activities. However, it can also exhibit pro-oxidant action. It contributes to oxidative damage of cellular DNA in the presence of transition metal ions (R).

Resveratrol, in the presence of other antioxidants, loses its pro-oxidant action and acts as an antioxidant. Melatonin was highly effective in reversing resveratrol’s pro-oxidant DNA damage in calf DNA. However, melatonin and resveratrol’s combined actions do not combine to make a greater (synergistic) antioxidant effect (R).

Buy Melatonin

Melatonin Part 3 of a 3-Part Series

  • Melatonin Part 1: 24 Surprising Health Benefits of Melatonin – Sleep, Brain, Gut Health, Antiaging, Cancer, Fertility, and more
  • Melatonin Part 2: Surprising Roles of Melatonin in Controlling Inflammation and Preventing Autoimmune Diseases
  • Melatonin Part 3: Ways to Increase and Decrease Melatonin, and Food/Drug/Supplement Interactions


  • Under the control of the AANAT gene, the stomach makes melatonin (R).
  • Melatonin also protected the liver from damage in an experimental setting (R).
  • Results for melatonin are better than those for ascorbic acid and β-carotene (R).
  • It also increases the efficacy of chemotherapy drugs such as doxorubicin (R).
  • There is about 100 times more MT in the stomach than blood (R).
  • Mice that had their MT1 receptors knocked out not only had severe sleep disturbances, they also had melancholic-like behavior similar to depression in humans (R).
  • In mouse mitochondria, directly incubating mitochondria with MT improves various parameters of their activity; it also improves production of the main energy molecule – ATP (R).
  • There are a lot of cells that have suprachiasmatic nucleus, or SCN receptors, in an area of the brain called that is responsible for controlling day-night cycles and sleep (R).
  • The MT2 receptor is lower in the eyes of Alzheimer’s patients (R).
  • Agomelatine is an MT analogue that is able to activate both MT receptors in the same time block where the 5-HT2c receptor binds with serotonin (R).
  • Melatonin prevents cell death more effectively than other antioxidants, like vitamin E, glutathione, mannitol, and vitamin C (R).
  • Recently, several combination therapies containing melatonin and a chemical associated with the MT3 receptor, 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT), decreased eye pressure in rabbits (R).Melatonin also increases the efficacy of treatment with IL-2 in patients with stomach cancers (R).

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
  • SelfDecode – a software tool that will help you analyze your genetic data from companies such as 23andme and ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

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  • Gerald

    Ive been taking SSRI’s for 24yrs (Paxil) is it possible to take Melatonin with an SSRI, one affects Melatonin and the other Serotonin could one get Serotonin Syndrome?

  • Martha Ray

    Took Melatonin for many years 25+ with no issue. But a few years ago it began causing me eye pain within 15 min of taking. Over those years I took everything from tiny doses to very large but mostly too 3 mg. When this eye pain (both eyes) first happened I tried cutting down my mcg dose and also tried different brands even an herbal brand and still got the side effect. Very strange. I was questioning taking hormones for years but was hooked on the sleep help. I now do not believe it is good to take any hormones and even most supplements long term. No functional or conventional doctors have any ideas why this reaction happened to me. I am also gluten, nightshade, caffeine and MSG sensitive as well as some other supplement fillers bother me. But nothing else has ever caused me eye pain in short order like the Melatonin did. I have not tested it for a year or so but it was painful enough for me not to risk it again. If anyone seeing this has had a similar reaction or any ideas please reply. I would like to brainstorm this with someone to help me get to the root cause.

  • K M Rao

    I feel terribly sleepy by 12 AM if I am not working. The urge to sleep is very great. If I sleep for one to two hours I get refreshed. Is the sleepiness due to excess Melatonin .There is lot of discomfort in the eyelids (you may call it heaviness). I posed this problem to many doctors but they have no answer. I am a patient of Sleep Apnea and have rest less leg syndrome.

  • Cindi

    Interesting series. I have virtually no MSH due to decades of mold illness. For years I have taken a lot of melatonin but have cut back because some say it suppresses any normal production. And according to the Oura Ring I don’t get much deep sleep and some suggested the melatonin could be a cause. What are your thoughts on this? (I was taking 12-16mg most nights, and now am at 6-9mg.)

    The stomach issues are interesting too because I have had a lot of issues from ulcer to chronic gastritis for which a cause was never found (control symptoms with low dose doxepin). Perhaps melatonin is a factor there.

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