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Factors that Increase/Decrease Melatonin Levels + Synergies

Written by Aleksa Ristic, MS (Pharmacy) | Last updated:
Nattha Wannissorn
Puya Yazdi
Medically reviewed by
Nattha Wannissorn, PhD, Puya Yazdi, MD | Written by Aleksa Ristic, MS (Pharmacy) | Last updated:

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Melatonin is known for its role in sleep control, but it has a range of other roles and potential benefits. Optimal levels will ensure proper sleep quality, brain and gut health, reduced inflammation, and more. Read on to learn the factors that increase or decrease melatonin levels and discover potential synergies.

Factors That Increase Melatonin Levels

Melatonin levels are a marker of sleep quality and overall health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it. Improving your melatonin levels won’t necessarily cause improvement in sleep quality.

The following is a list of factors that may balance low melatonin levels. Though studies suggest various dietary and lifestyle factors may increase melatonin, additional large-scale studies are needed. Remember to talk to your doctor before making any major changes to your day-to-day routine.

1) Melatonin Supplements

In a review of 35 studies, researchers found that melatonin supplementation slightly improves sleep quality [1].

Melatonin shows promise in improving insomnia and reducing jet lag. It also does not have any serious side effects [1].

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 [2].

The recommended dosage range for elderly adults is 0.3 – 2 mg, around 1 hour before bedtime [2].

2) Vitamins and Minerals

Folate and vitamin B6 boost the formation of serotonin, which is the precursor of melatonin [3].

In rats, vitamin B6 injections enhance melatonin production. After two months of B6 injections, the blood level of melatonin increased by 35.95% [4].

Additionally, zinc and magnesium increase the formation of melatonin from serotonin. They bind and activate the AANAT enzyme. This increases the affinity of serotonin for binding to AANAT [3].

Zinc supplementation increases melatonin levels in rats [5].

3) Food and Drinks

  • Tomato [6]
  • Walnuts [7]
  • Barley and rye [8]
  • Strawberries [6]
  • Cherries [9]
  • Olive oil [10]
  • Unprocessed cow milk [11]
  • Grape wine [6]
  • Beer [12]

4) Traditional Chinese Herbs

  • Periostracum cicadae (Chantui) [13]
  • Babreum coscluea (Shiya Tea-Leaf) [13]
  • Uncaria rhynchophylla (Gouteng) [13]
  • Viola philippica Cav (Diding) [13]
  • Phellodendron amurense (Huangbo) [13]
  • Mori Albae Cortex (Sangbaipi) [13]
  • Coptis chinensis (Huanglian) [13]
  • Angelica sinsensis (Danghui) [13]
  • Ziziphus ujube (Suanzhaoren) [13]
  • Salvia miltiorrhiza (Danshen) [13]
  • Panax notoginseng (Sangqui) [13]
  • Curcuma aeruginosa (Erzhu) [13]
  • Schisandra Chinensis (Wuweizi) [13]

Factors That 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 [14].
  • Tasimelteon also has a high affinity for MT1 and MT2 receptors [14].
  • 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 [14, 15].
  • TIK-301 is a melatonin receptor activator [16].

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 [17].
  • Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs, including aspirin and several other over the counter painkiller drugs, suppress nighttime melatonin levels [18].

2) Blue Light Exposure At Night

Blue light exposure at night can reduce melatonin levels and narrow the time window of melatonin secretion [19].

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 [3].
  • Fasting: Fasting reduces the nighttime secretion of melatonin. Short-term fasting from 2 to 7 days reduces blood melatonin levels by 20% [3].
  • Nutrient deficiencies: Folate, magnesium, and zinc deficiencies are linked with lower melatonin levels in rats [3].

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 [16].
  • Luzindole is a competitive MT2 melatonin receptor antagonist. This means it blocks receptor function [16].
  • P-PDOT blocks the MT2 melatonin receptor [16].
  • S29434 blocks the MT3 receptor [16].
  • Caffeine blocks melatonin signaling/transmission [20].

Melatonin Potential Synergies

1) Vitamins

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 [21, 22, 23].

2) Alpha-Lipoic Acid

In animals, alpha-lipoic acid works to scavenge free radicals. This means that it stops oxidative damage and has antioxidant activity [21].

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 [21].

3) Glutathione

Glutathione is a potent antioxidant that decreases lipid (fat) breakdown [22].

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 [22].

Melatonin also helps stimulate glutathione activity in rat brains. They work together to eliminate peroxides and free radicals that cause oxidative damage [24].

4) Selenium

Selenium has free radical scavenger effects. It protects nerve cells and restores the activity of antioxidant enzymes [25].

Melatonin and selenium work together to improve the treatment of brain ischemia and consequent damage in male rats. This combination helped reduce injury and prevented brain inflammation [25].

5) EGCG

EGCG is responsible for most of the antioxidant effects of green tea. It prevents oxidative damage and protects cellular DNA [21].

However, high doses of EGCG or green tea extracts can cause hepatotoxicity (liver damage). Melatonin reduces toxicity due to EGCG overdose [21].

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 [26].

6) Resveratrol

Resveratrol has both antioxidant and anti-inflammatory activities. However, it can also exhibit pro-oxidant action and contribute to oxidative damage in excessive amounts [27].

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, they do not combine to make a greater (synergistic) antioxidant effect [21].

Learn More

About the Author

Aleksa Ristic

Aleksa Ristic

MS (Pharmacy)
Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets. 
Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

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