Melatonin 101: Dosage, Deficiency, Side Effects and Supplements 2024

 Contents

1. What Is Melatonin
2. How Is Melatonin Made?
3. Melatonin Dosage
4. Melatonin Benefits
5. Melatonin Food
6. Melatonin and Sleep
7. Melatonin and Other Supplements
8. Melatonin Deficiency
9. Melatonin Side Effects
10. Who Should Not Take Melatonin
11. Melatonin and Covid-19
12. Online Shopping Guide

1. What is Melatonin



Melatonin is a naturally occurring hormone that sends a message to our brain that the day is done and it’s time for sleep. Melatonin is an important component of a healthy sleep pattern.

Approximately one-third of Americans, according to the Centers for Disease Control and Prevention (CDC), do not get enough sleep. Others may suffer from insomnia or poor sleep. But melatonin, a widely available supplement , may aid with several sleep issues. According to a study published in 2014, it shows promise in the treatment of insomnia in healthy adults. It’s also used to treat jet lag, delayed sleep-wake phase disorder (DSWPD), and anxiety before or after surgery.

2. How Is Melatonin Made?

Melatonin and sunlight are intimately linked and their relationship is unique in the fact that there are two forms of melatonin, circulatory and subcellular, or that produced by the pineal gland and secreted into the blood, and that produced by your mitochondria and used there locally.

The vast majority of the melatonin your body produces — 95% — is actually made inside your mitochondria in response to near-infrared radiation from the sun. Only 5% of melatonin is produced in your pineal gland.

Both appear to be controlled by either the absence of sunlight or the presence of sunlight. While circulatory melatonin may be the “hormone of darkness,” subcellular melatonin is the “hormone of daylight.”

a. Sunlight and Melatonin Production


Melatonin is produced inside your mitochondria in response to near-infrared radiation, which is part of the infrared spectrum. Because near-infrared has a much longer wavelength than ultraviolet, it can penetrate much deeper into your body, reaching cells in your subcutaneous tissue and not just on your skin. 

Near-infrared is not seen but rather felt as warmth. Its penetrative power (heat) also means it can penetrate lightweight clothing. So, you can cover yourself to prevent sunburn if you’re outside for a longer period of time, while still getting the near-infrared that you need.

It is likely that near-infrared (IR) photons from the sun stimulate subcellular melatonin synthesis in your mitochondria through cyclic adenosine monophosphate (cAMP) or NF-kB activation, or alternatively by stimulating bone marrow stem cells. However, if you fail to expose your skin to sufficient near-IR light from the sun than your mitochondria will have seriously depleted melatonin levels.

b. Melatonin Supplements

Melatonin is available as a supplement. There are two types: natural and synthetic (manmade). Natural melatonin is made from the pineal gland of animals. It is not suggested to use this form since it might be infected with a virus. Melatonin in its synthesized form does not pose this danger. The type of pill should be listed on the label of the pill bottle. Before you take it, see a pharmacist or a doctor if you have any doubts.

In the United States, melatonin is available over-the-counter (OTC) in health food and drug stores. It’s controlled by the US Food and Drug Administration, much like other dietary supplements (FDA).

Melatonin can also be taken sublingually, either in the form of a spray or sublingual tablet. Sublingually, it can enter your blood stream directly and doesn’t have to go through the digestive tract. As a result, its effect will be felt more rapidly.

c. How Melatonin Is Created In The Mitochondria

Melatonin in Mitochondria: Mitigating Clear and Present Dangers,” describes  the mechanism for how melatonin is created within the mitochondria..

“In normal cells, mitochondria account for energy (ATP) production, which results from glucose metabolism (glycolysis) and cellular respiration (oxidative phosphorylation or OXPHOS) in the inner mitochondrial membrane.

Glycolysis, which occurs in the cytosol, generates pyruvate, which is actively transported into the mitochondrial matrix. Here, pyruvate is converted to acetyl-CoA, the latter linking glycolysis with the citric acid cycle in the mitochondrial matrix and thus coupling it to ATP production.

Acetyl-CoA is also an essential co-factor for N-acetyltransferase (AANAT), which converts serotonin to N-acetylserotonin, the precursor of melatonin; AANAT activity rate limits melatonin synthesis.

In contrast to normal cells, many solid tumor cells allow the metabolism of glucose to pyruvate in the cytosol but restricts the transfer of pyruvate into the mitochondria; this is known as the Warburg effect ... The Warburg effect allows cancer cells to rapidly proliferate, avoid apoptosis, and enhance the invasiveness and metastatic processes characteristic of tumors.”

d. When Is Melatonin Released?

The pineal gland produces melatonin in response to darkness, but light causes that production to stop. Melatonin, as a result, aids in the regulation of our circadian rhythm and the synchronization of our sleep-wake cycle with night and day. It helps the transition to sleep and promotes consistent, high-quality sleep as a result.


3. Melatonin Dosage

Melatonin 101 : Dosage / Deficiency / Side Effects / Supplements 2022

Melatonin is a hormone; use it only as needed, not every night. Try the lowest dose that will work for you, starting with about 1 mg or less. If that doesn't work, try 3 mg. Some products contain greater amounts, such as 5 or 10 mg, which may be more than you need and can leave you groggy and have other negative effects. Timed release products may help you not just fall asleep but also stay asleep, but they won't help you stay asleep as well as a prescription sleep medication.

a. How Much Melatonin Is Safe for Adults?

A safe starting dose for adults is between 0.5 milligram and 5 milligrams of melatonin.

Doses of over 5 to 10 mg are likely to draw out heavy metals like mercury which could harm your body. However, Melatonin has been used by adults in doses up to 8 mg by mouth daily for up to 6 months for treatment purposes. 


b. How Much Melatonin Is Safe for Kids?

Melatonin is usually given to children in doses of up to 3 mg by mouth daily for up to 3 months.

However, it would best to start with a lower dosage. Many children will respond to a dose of 0.5mg - 1 mg when taken 30 to 90 minutes before bedtime. 

Medical professionals may recommend melatonin for children with conditions that affect their sleep, such as insomnia, autism spectrum disorder, or attention-deficit hyperactivity disorder. Several studies have shown melatonin supplements can significantly improve overall sleep times by 25 minutes to 48 minutes, on average, for children with these conditions. Children with ADHD may require about 3 - 6 mg of melatonin.

When children experience side effects from taking melatonin, they’re typically mild and may include:
- Agitation
- Bedwetting (more than usual)
- Dizziness
- Drowsiness
- Headaches

Always consult with your pediatrician about the correct melatonin dosage. Melatonin is not a replacement for a proper bedtime routine.

c. Can I Take Melatonin Every Night?

Melatonin supplement is considered safe for short term uses. Because of lack research, the side effect of using melatonin for long period of time still unknown.

d. Is It Ok To Take 30mg of Melatonin?

Doses of Melatonin near the 30mg mark is usually considered to be harmful. Reported side effects, which are usually minor, include dizziness, headache, nausea, upset stomach, rash, and sleepiness. 

e. How Much Melatonin Should I Take For Covid-19

Based on an on-going Spanish study, a 2 mg daily dose protocol is being investigated for prevention of COVID-19. Do take note that the dosage for 'prevention' and 'treatment' is different, For prevention or maintenance, a lower dosage is normally recommended whereas a 'treatment' or 'therapeutic' dosage is normally higher.

Typical doses of 1–10 mg/day melatonin appear to be safe for short-term use (Source)

f. Melatonin for Pregnant and Breastfeeding Women

Pregnant and breastfeeding women should avoid using melatonin without first consulting their doctor. There has not been sufficient research into the safety of melatonin among this population.

g. Is It Safe For Elderly To Take Melatonin?

Older adults may be more sensitive to melatonin and need less melatonin supplementation.

Our melatonin levels naturally decline as we age, disrupting the sleep-wake cycles for many older adults. As a result, older adults may have an increased sensitivity to melatonin. 

In a meta-analysis of 16 studies, melatonin dosages between 0.1 milligram and 50 milligrams per kilogram were administered to older adults aged 55 to 77 years old. In all of the studies, the melatonin levels remained higher among the older adults when compared to younger adults and stayed higher for a longer period of time — leading to increased daytime drowsiness. The more melatonin the person took, the more pronounced these effects.

As a result, researchers recommend older adults start with the lowest dose of melatonin possible. Lower doses may help older adults sleep better without disrupting their circadian rhythms and causing prolonged drowsiness.

h. When Should I Take Melatonin?

The best time to take melatonin is about one hour before your bedtime. Your brain naturally increases melatonin production about one hour to two hours before you sleep, so taking melatonin at this time may help facilitate the process. Melatonin is a hormone; use it only as needed, not every night. 

i. Melatonin for Jet Lag

Melatonin can be effective in relieving jet lag for people who travel across two or more time zones. Adults may take a dose of 0.5 milligram to 5 milligrams one hour before bed for up to four nights after arriving at their destination.

4. Melatonin Benefits

Melatonin is a known cytoprotector and has served in the past to combat several of the comorbidities associated with severe disease, including cardiovascular disease, diabetes and metabolic syndrome. It also..

Helps recharge glutathione. Glutathione is a major detoxification agent and its deficiency has been linked to COVID-19 severity.
- Plays an important role in cancer prevention.
- Boosts immune function
- May improve the treatment of certain bacterial diseases, including tuberculosis
- Helps quell inflammation
- May prevent or improve autoimmune diseases, including Type 1 diabetes
- Is an important energy hormone that can influence your energy level
- Helps regulate the function of the renin-angiotensin system – the hormone system responsible for regulating blood pressure, fluid and electrolyte balance, as well as blood circulation.

a. Melatonin and Sleep



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Melatonin, the hormone secreted by your pineal gland located near the center of the brain, is crucial for the regulation of your sleep cycle. With enough exposure to bright light during the daytime, the gland starts secreting melatonin during the evening darkness.


b. Melatonin for Brain Health

Melatonin is neuroprotective. The brain consumes 20% of the body’s oxygen. All that oxygen passing through the brain makes a toxic byproduct called reactive oxygen species, which can damage nerves and blood vessels. 

i. Melatonin and Seasonal Affective Disorder (SAD)

Seasonal affective disorder (SAD) is a type of depression that’s related to changes in seasons — SAD begins and ends at about the same times every year. (SourceResearch indicates that it could be linked to changes in your circadian rhythm caused by seasonal light changes.

Melatonin has benefits to helps regulate circadian rhythm. As a result, low doses of melatonin may help decrease symptoms of seasonal depression.

According a study, alterations in circadian rhythm were shown to contribute to seasonal depression, but taking melatonin capsules daily was effective at reducing symptoms. However, further research is needed to determine how melatonin may impact symptoms of seasonal depression.

ii. Is Melatonin Good For Anxiety?

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Yes. Melatonin has been shown to improve symptoms of anxiety.


iii. Is Melatonin Good For Alzheimer's?

Your brain uses many different antioxidants, including melatonin, to neutralize the reactive oxygen species before they can cause harm. Therefore, it is not surprising that studies show melatonin seems to provide some protective effect against diseases like Alzheimer’s.

Melatonin also improves sleep, which could theoretically lead to long-term protection against Alzheimer's. A review and meta-analysis on melatonin treatment in Alzheimer's published in Neuroscience & Biobehavioral Reviews (Aug 2021) showed individuals with Alzheimer's improved with more than 12 weeks of treatment.

c. Melatonin for GERD

Gastro-Esophageal Reflux Disease (GERD) ) is a disease that occurs when the reflux of stomach contents causes troublesome symptoms and/or complications.

Melatonin has a role in the improvement of GERD when used alone or in combination with omeprazole. However, further studies are required to confirm the efficacy and long-term safety of melatonin before being recommended for routine clinical use. (Source)

d. Melatonin for Eyes

Melatonin is an effective antioxidant and has a strong antiapoptotic signaling function. Melatonin cytoprotective properties might be useful in the treatment of ocular diseases, like glaucoma and age-related macular degeneration. (Source)

According to research, taking 3 mg of melatonin every day for 6 to 24 months appears to protect the retina and to delay macular degeneration. No significant side effects were observed.

However, evidence on the effects of long-term melatonin supplementation on eye health is limited, and further human studies are needed.


e. Melatonin for Weight Loss

Melatonin 101 : Dosage / Deficiency / Side Effects / Supplements 2022

Melatonin regulates insulin secretion and decreases blood glucose levels. Melatonin also does the following..

- Tips the energy balance in the direction of reducing food intake and increasing brown adipose tissue (also known as brown fat / “good” fat) energy expenditure, thus preventing excessive body weight gain.
- Regulates energy homeostasis and influencing feeding, energy storage and expenditure.
- Regulates glucose metabolism by inducing insulin resistance at night and insulin sensitivity during the day, which is closely associated with nocturnal fasting and daytime feeding.

The protective effect of melatonin on the mitochondria has also been shown to have an impact on diabetes, insulin resistance and obesity.

This study states that melatonin deficiency appears to correlate with obesity. In a human study, melatonin supplementation appeared to regulate adiponectin activity leading to significant weight loss in the treatment group.

When melatonin supplementation was evaluated in 56 postmenopausal women, the researchers found that melatonin supplementation contributed to a significant improvement in the quality of sleep and in body weight reduction.

i. Does Melatonin Cause Weight Gain?

Melatonin is not associated with weight gain. However, poor sleep is associated with weight gain which may be remedied with Melatonin supplements.

f. Melatonin for Immune System

Our immune system works hand-in-hand with melatonin to fight off diseases and infection.

White blood cells have melatonin-specific receptors and the enzymatic machinery required to synthesise melatonin. Melatonin also triggers the production of T-cells, which combats infected host cells, activates other immune cells and helps regulate immune response. In addition, melatonin enhances the phagocytosis process, which removes pathogens and debris from cells.

The protective effects of melatonin due to its antioxidant powers also help in regulating and preventing chronic inflammation. It is also known to inhibit NLRP-3 inflammasomes, which lead to respiratory distress in the lungs.

i. Melatonin for Cancer

Melatonin, a neurohormone produced by your pineal gland, is a master hormone, a potent antioxidant and antioxidant recycler, and a master regulator of inflammation and cell death. These functions are part of what makes melatonin such an important anticancer molecule.

Melatonin both inhibits the proliferation of cancer cells and triggers cancer cell apoptosis (self-destruction). It also interferes with the new blood supply tumors required for their rapid growth (angiogenesis).

As noted in a 2006 paper on melatonin's role in immune system enhancement and its applications in cancer:

"Physiologically, melatonin is associated with T-helper 1 (Th1) cytokines, and its administration favors Th1 priming. In both normal and leukemic mice, melatonin administration results in quantitative and functional enhancement of NK cells, whose role is to mediate defenses against virus-infected and cancer cells.

Melatonin appears to regulate cell dynamics, including the proliferative and maturational stages of virtually all haemopoietic and immune cells lineages involved in host defense — not only NK cells but also T and B lymphocytes, granulocytes and monocytes — in both bone marrow and tissues."
A 2005 paper28 also stressed the importance of NK cells in aging and longevity, noting that "Longer life in centenarians has been associated with increased NK cell number," and, "The cytotoxic capacity of NK cell is well preserved in peripheral blood of the centenarians."

This paper also discusses the immunoregulatory action of melatonin on your innate immune system, and that exogenous melatonin (melatonin supplementation) "augments NK cells and monocytes in both the bone marrow and the spleen with a latency of [seven] to 14 days."

ii. Melatonin and ROS (Reactive Oxygen Species)

As melatonin is released at night, it travels through your circulatory system and is taken up by cells. Once inside, the melatonin mops up excessive ROS.

Melatonin also helps counteract damaging ROS during the day, but through a different pathway. During the day, near-infrared rays from the sun penetrate deep into your body and activate cytochrome c oxidase, which in turn stimulates the production of melatonin inside your mitochondria.

iii. Melatonin and Sepsis

melatonin and sepsis

Sepsis (blood poisoning) is a common outcome of an unhealthy immune response to infection, and melatonin may play an important role in preventing this. Melatonin appears to reverse septic shock symptoms by..
- Decreasing synthesis of proinflammatory cytokines
- Preventing lipopolysaccharide (LPS)-induced oxidative damage, endotoxemia and metabolic alterations
- Suppressing gene expression of the bad form of nitric oxide, inducible nitric oxide synthase (iNOS)
- Preventing apoptosis (cell death)

2019 animal study in the journal Frontiers in Immunology details how melatonin can protect against polymicrobial sepsis, i.e., sepsis caused by more than one microbial organism. A hallmark of polymicrobial sepsis is severe loss of lymphocytes through apoptosis, resulting in a twofold higher lethality than unimicrobial sepsis (sepsis caused by a single microbe).

In this case, melatonin appears to offer protection by having an antibacterial effect on white blood cells called neutrophils. A high neutrophil count is an indicator for infection. According to the authors of the 2019 study:

"Melatonin treatment inhibited peripheral tissue inflammation and tissue damage … consequently reducing the mortality of the mice. We found that macrophages and neutrophils expressed melatonin receptors.

Upon depletion of neutrophils, melatonin-induced protection against polymicrobial infection failed in the mice, but melatonin treatment in macrophage-depleted mice attenuated the mice mortality resulting from polymicrobial sepsis …

The data from this study support previously unexplained antiseptic effects of melatonin during a polymicrobial infection and could be potentially useful for human patients with sepsis."

5. Melatonin Foods



Fruits, vegetables, grains, nuts and seeds, tart cherries, corn, asparagus, tomatoes, pomegranate, olives, grapes, broccoli, cucumber, rice, barley, rolled oats, walnuts, peanuts, sunflower seeds, mustard seeds, flax seeds.

a. Can I Take Melatonin With Alcohol?

It is not considered safe to take melatonin with alcohol. Because alcohol can disrupt your sleep quality and your natural melatonin levels, you should avoid mixing melatonin with alcohol.

Side effects may include drowsiness, which may raise your risk of falling or accidentally injuring yourself.

b. Can I Take Melatonin With Caffeine?

It is not recommended to mix melatonin with caffeine. Caffeine is a stimulant that affects your natural melatonin synthesis and disturbs your sleep-wake cycle.

c. How To Increase Melatonin Production Naturally

i. Sunlight Exposure

The best way to increase mitochondrial melatonin is to optimize your near-IR exposure through regular sunlight exposure. 

You don’t have to be close to naked to benefit, as near-infrared radiation will penetrate lightweight clothing. So, you can cover yourself to prevent sunburn if you’re outside for a longer period of time, while still getting the near-infrared that you need. That said, you will absorb more IR on your bare skin.

Spending time in nature is a good way to increase your IR levels as most green plants and trees reflect IR. This is likely why forest bathing is so healthy.

ii. Avoiding Bright Lights At Night

The other side of the equation is avoiding bright light late at night. To optimize melatonin release in your pineal gland at night, avoid blue light-emitting gadgets at least a couple of hours before bed and keep the lighting in your room dim. Blue-blocking glasses can also be used. Once in bed, makes sure your room is pitch black, as even a small amount of light can interfere with melatonin production.

Together, sun exposure during the day and keeping it dark at night, will ensure your mitochondria are being bathed — day and night — in melatonin.

iii. Sleep

Another way of making sure your body produces enough melatonin is to get good sleep on a regular basis. You will need a good dose of natural sunlight around midday to synchronize your circadian clock so that your body produces melatonin at the appropriate time (i.e., in late evening). 

iv. Melatonin Supplements

It is important to note that melatonin supplements, contrary to what you might expect, do not wind up in your mitochondria where they are needed most to quench the damage from oxidative stress produced in the electron transport chain.

6. Melatonin and Sleep

Melatonin, the hormone secreted by your pineal gland located near the center of the brain, is crucial for the regulation of your sleep cycle. With enough exposure to bright light during the daytime, the gland starts secreting melatonin during the evening darkness.

As this amount increases the body prepares for sleep. When you stay up past dark using artificial light, especially light emitted by electronic devices, it inhibits melatonin production. Ideally, you would stop using electronics at least an hour or two before bedtime. This helps to raise your melatonin production and maintain a steady circadian rhythm.

In children, melatonin is typically used to treat difficulties with going to sleep or staying asleep. It may be beneficial to children who are developing normally as well as those who have ADHD, autism, other developmental disorders, or visual impairment.

a. Does Melatonin Help Adults Sleep?

According to the Centers for Disease Control and Prevention (CDC), about 1 in 3 Americans don’t get enough sleep. Others may experience poor sleep or insomnia. But melatonin, a widely available supplement, may help with several sleep issues. Research from 2014 reported that it shows promise in the treatment of insomnia among healthy adults. Some people also use it for jet lag, delayed sleep-wake phase disorder (DSWPD), and anxiety before or after surgery.

Supplementing with 1 mg of melatonin at bedtime might also benefit those whose sleep–wake cycles have become dys­regulated with long COVID.

When taken in gummy form, these sleep aid supplements increase melatonin in the body while also encouraging overall mental calmness and relaxation, which will help you feel tired faster and support your body’s natural sleep rhythm.

b. How Many Hours Of Sleep Do I Need?

According to a scientific review of more than 300 studies published between 2004 and 2014 to ascertain how many hours of sleep most people need in order to maintain their health, a panel of experts came up with the following recommendations.

Keep in mind that if you're sick, injured or pregnant, you may need a bit more than normal.

Age GroupHours of sleep needed for health
Newborns (0 to 3 months)14 to 17 hours
Infants (4 to 11 months)12 to 15 hours
Toddlers (1 to 2 years)11 to 14 hours
Preschoolers (3 to 5)10 to 13 hours
School-age children (6 to 13)9 to 11 hours
Teenagers (14 to 17)8 to 10 hours
Adults (18 to 64)7 to 9 hours
Seniors (65 and older)7 to 8 hours

c. How To Know If You Slept Well

One of the easiest ways to gauge whether you've slept enough is to assess your level of sleepiness the next day. For example, if you had the opportunity, would you be able to take a nap? Do you need caffeine to keep you going?

The following three factors, in combination, influence how restorative your sleep is:

i. Duration 
This is the number of hours you sleep. Sleep requirements are highly individual and can change from one day to the next, depending on factors like stress, physical exertion, illness and pregnancy, just to name a few. But, on average, most people need about eight hours of sleep per night.

ii. Timing 
This is the habit of going to bed at approximately the same time each night. When you go to bed and wake up at the same times, your body becomes accustomed to the routine. This helps regulate your circadian clock so you fall asleep and stay asleep all night. 

Keep this routine, even on the weekends, because even if the duration of sleep is the same, when the timing of your sleep is shifted, it's not going to be as restorative.

iii. Intensity 
This has to do with the different stages your brain and body go through over the course of the night; the sequence of them, and how those stages are linked. 

Some medications will suppress certain phases of sleep, and certain conditions like sleep apnea will lead to fragmented sleep. With these scenarios, even if you're sleeping for an adequate duration and have consistent timing, your sleep will not be as restorative.

c. How To Improve Sleep Quality

i. Sleep in complete darkness, or as close to it as possible - Light can disrupt your pineal gland's production of melatonin and serotonin, thereby disrupting your sleep cycle. So, close your bedroom door, get rid of night lights and use blackout shades, an eye mask or thick drapes. If you absolutely have to have some sort of night light, use a red bulb.

ii. Keep the temperature in your bedroom no higher than 70 degrees F
iii. Sleep in silence - A pair of earplugs can eliminate most noise.
iv. Shut down your Wi-Fi at night
v. Move alarm clocks and other electrical devices away from your bed
vi. Take magnesium malate or glycinate before bed
vii. Avoid watching TV or doing work in your bed. Reserve your bed for sleeping only.
viii. Get to bed as early as possible, ideally between 9 and 10 p.m.
ix. Go to bed and wake up at the same times each day, even on the weekends.

x. Establish a relaxing bedtime routine - Find something that makes you feel relaxed, then repeat it each night to help you release the tensions of the day. This could include meditating, deep breathing, using aromatherapy or essential oils or indulging in a massage from your partner. 

xi. Avoid drinking fluids within two hours of going to bed
xii. Avoid eating at least three hours before bedtime, particularly grains and sugars
xiii. Take a hot bath or shower before bed
xiv. Install blue-blocking software on your electronic screen devices
xv. Reduce or avoid as many drugs as possible, including caffeine and alcohol
xvi. Exercise regularly, but not within three hours of bedtime
xvii. Chamomile tea
xviii. Limit daytime naps, and avoid napping after 5 p.m.
xix. Use a sleep tracker

7. Melatonin and Other Supplements

a. Melatonin and Vitamin B6

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B6 vitamin injections increase melatonin biosynthesis, which promotes good therapeutic effects. Reduced endogen melatonin production is one of the causes for pathological processes that arise in the body as a result of B6 vitamin deficiency. (Source)

b. Melatonin and Vitamin C

Natrol Sleep+ Immune Health Sleep Aid Gummies > Melatonin Gummies with Vitamin C and Vitamin D

Melatonin and vitamin C are involved with ACE2, the receptor that SARS-CoV-2 uses to gain entry into the cell. Together, melatonin and vitamin C help reduce SARS-CoV-2 virulence by inhibiting NLRP3 inflammasomes, which in turn inhibits cytokine storms.

c. Melatonin and Vitamin D

i. Melatonin and Vitamin D Together
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Melatonin enhances vitamin D signaling and the two work synergistically to enhance your mitochondrial function. Vitamin D is involved in the pathways that produce melatonin in the pineal gland. Meanwhile, Melatonin is also involved with dictating our circadian rhythm (SourceSource).

ii. Deficiency
A deficiency in either vitamin D or melatonin has been associated with the pathogenesis of several chronic diseases, including high blood pressure, cardiovascular disease, metabolic syndrome and diabetes, just to name a few.

These conditions have also emerged as co-morbidities that significantly raise your risk of death from COVID-19. Synthesis of both vitamin D and melatonin is also dramatically reduced with advancing age, and old age is a primary risk factor for COVID-19 death. So, while vitamin D3 and melatonin supplementation may be beneficial for most people, it’s particularly important for the elderly.

iii. Sleep
An evaluation of clinical trials and correlation studies have shown that “Vitamin D has both a direct and indirect role in the regulation of sleep.”

iv. Raising Melatonin and Vitamin D Levels
Vitamin D and Melatonin levels can both be increased by sufficient sunlight exposure.

d.  Melatonin and Niacin / Vitamin B3

Niacin and melatonin are antioxidants that help prevent release of inflammatory cytokines. Like niacin, melatonin also increases adiponectin levels.

i. Can Melatonin Reduce a Niacin Flush?

Taking melatonin with niacin helps to reduce, and in some cases eliminate, the symptoms of a niacin flush. Those with long-haul symptoms may find relief by supplementing with melatonin and those who have had an injury or reaction from the shot may find relief using the combination of niacin and melatonin.

Although there are many variations of COVID-19 vaccine detox protocols, here are the common recommendations for flush niacin and melatonin (aka niatonin protocol).

Flush Niacin (nicotinic acid form)
  • Take 2-3 times per day with melatonin
  • Start with 500 mg dose, work up to 1,500 mg – 2,000 mg per dose as tolerated*
  • Ex. 500 mg 3 times a day on Day 1, 1,000 mg 3 times a day on Day 2, etc.
*It’s called flush niacin for a reason. The flushing is a warm, prickly sensation in the face and upper body that starts 15-30 minutes after taking niacin and lasts 1-2 hours. The flush is not harmful but is an unusual sensation at first. Taking melatonin at the same time will help reduce flush symptoms.

Melatonin
  • Take 2-3 times per day with flush niacin
  • Start with 10 mg dose, work up to 20 mg per dose^
  • Ex. 10 mg 3 times a day on Day 1, 15 mg 3 times a day on Day 2, etc.
^Some protocols go up to 40 mg per dose. Although there is no theoretical maximum melatonin dose, the higher the dose the more drowsy you will feel.

Also key:
  • Do not drink alcohol during any of this (or ingest other intoxicating substances)
  • Get plenty of sunlight for natural vitamin D, but feel free to add a vitamin D supplement, especially if you live in cold, dark climates
  • Consider adding a vitamin C supplement, but no sooner than two weeks after your last vaccine dose. In the meantime, get vitamin C from natural food sources. The theoretical reason to wait two weeks to supplement vitamin C is to avoid your immune system going into overdrive and activating those destructive cytokines.
Issues & Precautions:
  • There is great ambiguity on the timing of niacin and melatonin related to vaccination. Some discuss using this protocol before going for a vaccine, others immediately afterwards, and others only if side effects develop.
  • There are not many FDA / academic peer reviewed studies related to this.
  • Avoid taking melatonin with any SSRIs like fluvoxamine. If you are on a SSRI then take a lower dose of melatonin.
  • Long-term use of high dose melatonin causes habituation, meaning your body builds up a tolerance to that dose, and may also decrease your body’s natural production of melatonin.

ii. Weight Loss

This animal study found the effects of melatonin and niacin supplementation, in addition to treadmill exercise, resulted in weight loss after just 10 days. Weight loss was greater in the melatonin and niacin group than in the niacin only group and these two groups experienced greater weight loss than the control group.

e. Melatonin and Fluvoxamine

Both inflammation and blood clots are known to be features of severe COVID-19. Meanwhile, fluvoxamine is also known to raise melatonin, which might also help. That said, combining fluvoxamine and melatonin may significantly increase the blood levels and effects of melatonin (Drugs.com). 

Also worth noting is that your brain synthesizes melatonin from serotonin. That is why many believe fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), appears to be beneficial for COVID-19 infection. If you inhibit the reuptake (aka clearance) of serotonin, then there is more serotonin floating around in the brain that can be converted into beneficial melatonin.

8. Melatonin Deficiency

Melatonin 101 : Dosage / Deficiency / Side Effects / Supplements 2022

Melatonin levels decrease throughout time and may be linked to decreased sleep effectiveness, which is frequently connected with aging, as well as to deterioration of many circadian rhythms.

For most people, peak melatonin production is between the hours of 2 am to 3 am. The maximum melatonin levels measured in healthy adults between the ages of 65 to 70 years appeared to be around 49.3 picograms/ml (pg/ml). Adults more than 75 years of age only have maximum production levels of 27.8 pg/ml.

Young children, on the other hand, have extremely high melatonin levels, compared to adults. The maximum levels recorded for children showed a decline as age increased. Children between the ages of 1 to 5 had peak melatonin at 325 pg/ml, while those between the ages of 5 to 11 already declined to 133 pg/ml.

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Moreover, melatonin production is affected by stress, smoking, exposure to too much light at night (especially blue light), and not obtaining enough natural light during the day.

9. Melatonin Side Effects

Reported side effects are usually minor, include dizziness, headache, nausea, upset stomach, rash, and sleepiness. However, some other reports have linked high blood levels of melatonin with delayed puberty and hypogonadism.

Do not drive or operate equipment within five hours of taking melatonin since it might induce daytime sleepiness.

a. Melatonin Overdose

Short-term use of melatonin supplements appears to be generally safe for adults. However, melatonin can potentially affect blood pressure as well as testosterone and estrogen levels. Melatonin can also interact with certain foods and medications. Long-term use is associated with an increased risk of bone fracture. It is probably best to use melatonin "as needed" rather than on a regular basis.

Too much melatonin might have the reverse impact of what it’s supposed to do. Because your natural circadian cycles will be interrupted, it may make sleeping more difficult.

An overdose can also make you drowsy and sleepy throughout the day, as well as cause you nightmares or unusually vivid dreams at night. You can also have the following experiences:
– nausea
– dizziness / headaches
– irritability or anxiety
– diarrhea
– joint pain

10. Who Should Not Take Melatonin

To ensure safe usage, it is always a good idea to consult your doctor before taking any over-the-counter sleep aid, including melatonin. They know your personal medical history and can best advise you on the appropriate melatonin dosage for your needs. They will also know whether melatonin might interact with any other medications you may currently be taking.

Certain health conditions and medications may increase your risk of side effects when taking melatonin. If you take any of the following medications, be sure to talk to your doctor before taking melatonin..

Birth control or oral contraceptives : Birth control pills increase the melatonin levels in your body. When used in combination with melatonin, your melatonin levels may become too high.
- Blood thinners
Immunosuppressants or corticosteroids
Medications that lower blood pressure
- Warfarin or other anticoagulants
- Seizure Threshold Lowering Drugs

a. Pregnancy and Breastfeeding

Studies have not evaluated melatonin supplementation during pregnancy and breastfeeding, but some research suggests that these supplements might inhibit ovarian function (Source). Therefore, some experts recommend that women who are pregnant or breastfeeding avoid taking melatonin.

b. Depression

study found a higher serum melatonin values in patients suffering from endogenous depression. Melatonin aids in the preparation of your body for sleep. It makes you feel less energetic, which is a symptom of depression. 


11. Melatonin and Covid-19



Melatonin is a hormone synthesized in your pineal gland and many other organs. While it is most well-known as a natural sleep regulator, it also has many other important functions. For example, melatonin is a potent antioxidant (Antioxidants, 2020) with the rare ability to enter your mitochondria, where it helps “prevent mitochondrial impairment, energy failure and apoptosis of mitochondria damaged by oxidation.” It also helps recharge glutathione and glutathione deficiency has been linked to COVID-19 severity.

The Frontline COVID-19 Critical Care Alliance (FLCCC) also recommends the use of melatonin in their outpatient and inpatient treatment protocols.

a. Melatonin's Role in Covid-19 Treatment

Melatonin has also been shown to play a role in viral infections and according to a June 2020 research paper in Life Sciences journal, it may be an important adjunct to COVID-19 treatment. 

Melatonin may combat SARS-CoV-2 infection by..
  • Suppressing oxidative stress
  • Regulating blood pressure (a risk factor for severe COVID-19)
  • Improving metabolic defects associated with diabetes and insulin resistance (risk factors for severe COVID-19) via inhibition of the renin-angiotensin system (RAS)
  • Protecting mesenchymal stem cells (MSCs, which have been shown to ameliorate severe SARS-CoV-2 infection) against injuries and improving their biological activities
  • Promoting both cell-mediated and humoral immunity
  • Promoting synthesis of progenitor cells for macrophages and granulocytes, natural killer (NK) cells and T-helper cells, specifically CD4+ cells
  • Inhibiting NLRP3 inflammasomes

They point out that melatonin is also “effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes.

The scientific review paper, “Melatonin Potentials Against Viral Infections Including COVID-19: Current Evidence and New Findings,” published October 2020 in Virus Research journal, also summarizes the many potential mechanisms by which melatonin can protect against and ameliorate viral infections.

The authors review research looking at melatonin’s beneficial effects against a variety of viruses, including respiratory syncytial virus, Venezuelan equine encephalitis virus, viral hepatitis, viral myocarditis, Ebola, West Nile virus and dengue virus. Based on these collective findings, they believe melatonin may offer similar protection against SARS-CoV-2.

i. Melatonin and Cytokine Storms

Cytokine storm is one of the reasons why sepsis (blood poisoning) is so lethal, and studies have confirmed melatonin has a favorable influence on sepsis. (Sepsis is also a feature of severe COVID-19.) As reported in a 2010 study in the Journal of Critical Care:

Melatonin is an effective anti-inflammatory agent … Its anti-inflammatory action has been attributed to inhibition of nitric oxide synthase with consequent reduction of peroxynitrite formation, to the stimulation of various antioxidant enzymes thus contributing to enhance the antioxidant defense, and to protective effects on mitochondrial function and in preventing apoptosis.

In a number of animal models of septic shock, as well as in patients with septic disease, melatonin reportedly exerts beneficial effects to arrest cellular damage and multiorgan failure …

Apart from action on the local sites of inflammation, melatonin also exerts its beneficial actions through a multifactorial pathway including its effects as immunomodulatory, antioxidant and antiapoptotic agent.

b. Hypoxic Damage from Covid and Melatonin

With severe COVID-19, hypoxic damage is mediated by hypoxia-inducible factor (HIF)-1α, a marker of increased mortality. In fact, the rise HIF-1α in diabetics is a key contributor to the severity of COVID-19 in this subset of patients, as high glucose levels stimulate glycolysis within the inflammatory macrophage-monocyte cell subset.

The activity of HIF-1α is suppressed by melatonin, which reverses the Warburg metabolic shift while also inhibiting the inflammasome and macrophage changes. This prevents the cytokine storm, inhibits pro-inflammatory enzymes cyclo-oxygenase and myeloperoxidase, and suppresses the inflammatory signaling molecule nuclear factor κB (NF-κB). This leads to increased cell survival, lower levels of lung damage, less mitochondrial damage, and higher levels of transcription factors and of superoxide dismutase 2 (SOD2).            

c. Melatonin and Covid Studies

Melatonin has been the focus of much research throughout the COVID-19 pandemic, as it is a safe molecule with many clinical actions that could be beneficial to humans. Moreover, melatonin is a biomolecule that is naturally produced in the human body and is associated with a broad spectrum of antiviral activity.

The potential utility of melatonin in treating COVID patients has not gone unnoticed, with a PubMed search combining melatonin and COVID producing more than 50 citations. Check out the evidence tracker on melatonin and COVID-19 from c19melatonin.com (constantly updated).

As of January 2024, there are more than 12 published clinical studies of melatonin for treatment and prevention in COVID-19 and the results are promising even when it's given as a late treatment.

12. Online Shopping Guide

1. Nature's Bounty Melatonin 5mg > Best Melatonin To Take For Sleep


3. Nature Made Melatonin 3mg Tablets > Melatonin Tablets To Help Sleep

4. Natrol Liquid Melatonin Tincture > Liquid Melatonin for Adults

5. Benevolent Natural Melatonin Liquid 3mg > Melatonin Sublingual Drops


7. OLLY Sleep Gummies > Best Melatonin Gummies for Adults


9. Nature's Craft Melatonin Gummies 5mg > Melatonin Gummies for Adults

10. Natrol Melatonin Sleep Tablets > Melatonin with Vitamin B6 Supplement

11. Natrol Sleep+ Immune Health Sleep Aid Gummies > Melatonin Gummies with Vitamin C and Vitamin D

12. Purefinity Melatonin Gummies > Melatonin for Anxiety

13. OLLY Muscle Recovery Sleep Gummies > Best Melatonin with Vitamin D


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