Image credit: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151498/

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.

Factors That Increase Melatonin Levels

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 boosts the formation of serotonin from tryptophan. Serotonin is the precursor of melatonin [3].

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

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 [3].

Zinc supplementation increases melatonin levels in rats [5].

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

  • 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 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 [14].
  • Non-steroidal anti-inflammatory drugs (NSAIDS): NSAIDs, including aspirin and several other over the counter painkiller drugs, suppress nighttime melatonin levels [15].

2) Blue Light Exposure At Night

Blue light exposure at night can reduce melatonin levels and the time window that melatonin is secreted [16].

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 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 [17].
  • Tasimelteon also has a high affinity for MT1 and MT2 receptors [17].
  • 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 [17, 18].
  • TIK-301 is a melatonin receptor activator [19].

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 [19].
  • Luzindole is a competitive MT2 melatonin receptor antagonist. This means it blocks receptor function [19].
  • P-PDOT blocks the MT2 melatonin receptor [19].
  • S29434 blocks the MT3 receptor [19].
  • Caffeine blocks melatonin signaling/transmission [20].

Melatonin Supplement and Drug Interactions

1) Various 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].

A combination of vitamin D3 and melatonin can stop human breast cancer cell growth [24].

Additionally, in calf DNA, melatonin and vitamin C worked together to make a powerful antioxidant action [21].

Meanwhile, vitamin E and melatonin combine to stop oxidative damage in rat livers [22].

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. However, its antioxidant effects are weak [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. However, it is less efficient that melatonin in protecting against oxidative stress [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 stimulates glutathione activity in rat brains. They work together to eliminate peroxides and free radicals that cause oxidative damage [25].

4) Selenium

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 [26].

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 [26].

Melatonin and selenium work together to improve the treatment of ischemia in male rats. This combination helped reduce injury and prevented brain inflammation [26].

5) Galantamine

Galantamine is a drug with antioxidant properties. It also helps protect nerve cells in the brain [27].

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 [27].

6) Atorvastatin

Atorvastatin is a cholesterol-lowering (statin) medication. It blocks cholesterol production [28].

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 [28].

7) Interferes with 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 [29].

8) 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 [30].

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 [21].

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