Melatonin – a Possible Treatment for MS

Research shows that supplementing with melatonin promotes a restful sleep and immune modulation, improves balance and muscle strength and lessens pain and fatigue in MS. These significant symptom improvements are why melatonin is being considered a promising new treatment for multiple sclerosis.

 

Melatonin

Melatonin is hormone and an antioxidant that is produced in the mitochondria of all cells in the body that contain mitochondria and by the pineal gland in the center of the brain. The amount of melatonin produced by the pineal gland is less than 5% of the total melatonin present in the body.[i]

Melatonin concentrations in the spinal fluid of humans are substantially higher than those in the peripheral circulation to protect neurons and glia from oxidative stress.[ii]

Because the pineal gland produces the highest amounts of melatonin when it is dark, peak levels of melatonin are found in the blood during the night and lower levels are present in the blood during daylight hours.

Melatonin has many functions in the body, including influencing glucose metabolism in all cells, enhancing mitochondrial function, modulating immune function, ensuring adequate ATP (energy) production under stress[iii], regulating the circadian rhythm, sleep and blood pressure, blocking the detection of pain and suppressing demyelination while increasing the remyelination of nerve cells.[iv]

While melatonin is a powerful immune modulator, it also increases antimicrobial peptides which could be helpful in controlling the microbes that live in the body.[v]

Seasonality and MS

Several studies have suggested that a higher risk of an MS attack in the spring and summer is due to lower amounts of melatonin in the blood during those times of the year.[vi] [vii] [viii]

One study found that at 8am, blood melatonin levels were significantly lower in MS patients than in control subjects.[ix]

Another study found a 32% reduction in the number of MS relapses during fall and winter months when melatonin levels are higher due to less hours of daily sunlight.[x]

Other researchers reported that disruptions in circadian melatonin rhythms commonly seen in shift workers has been associated with an increased risk for MS[xi] and MS patients who did shift work for 3 years or longer before the age of 20, significantly increased their risk of multiple sclerosis.[xii]

Melatonin and immune modulation

The activation of the immune response in MS flares reflects changes in the balance between the actions of proinflammatory T helper (Th) immune cells and modulatory T regulatory (Tregs) immune cells in lymphatic organs, brain and other tissues.[xiii]

Melatonin blocks the production of proinflammatory T immune cells and slows the production of proinflammatory IL-17 cytokines.

Melatonin also boosts the production of immune modulatory T cells and cytokine IL-10.

To confirm the importance of melatonin’s effects on T immune cells and their cytokines in human MS patients, researchers assessed the blood of MS patients and discovered that higher serum melatonin levels were associated with lower levels of the proinflammatory cytokine IL-17, and higher levels of IL-10, the immune modulating cytokine.[xiv]

A 2017 study evaluated the effects of giving melatonin to MS patients and how this affected immune cells in the blood of relapsing remitting MS subjects vs healthy controls. Melatonin decreased the responses in two types of proinflammatory Th immune cells but did not lower immune regulatory Treg cells. Melatonin also promoted the more protective cytokines because of the increased anti-inflammatory to proinflammatory T cell ratio. They concluded that melatonin may be an effective treatment for MS.[xv]

MS patients that have decreased nighttime melatonin, have an increased severity of the disease and symptoms such as fatigue, insomnia and depression.[xvi]

Larger pineal gland sizes linked to decreased risk of multiple sclerosis

A 2016 study found that a larger sized pineal gland was related to a lower risk of multiple sclerosis.[xvii]

In a 2024 study, researchers reported that the pineal gland volume in female MS patients was significantly lower than in healthy females. There was little difference in males with MS. They also concluded that pineal gland volume was not age dependant and the smaller pineal gland in MS female patients could be reliably attributed to the disease itself. Also, a large pineal gland size when compared to a specific lower pineal gland volume was associated with a greater than 200% or doubled increased risk of multiple sclerosis.[xviii]

Safety and benefits of melatonin supplementation

Melatonin has been commonly used at small doses to promote sleep and as a treatment for jetlag. It is also used in the treatment of cancer and more recently COVID-19 prevention and treatment.

Four studies that were suitable for a meta-analysis reported that melatonin did not cause a detectable increase in severe adverse effects or withdrawals due to adverse effects, but did appear to increase the risk of drowsiness, headache and dizziness.  Based on these studies, it was concluded that melatonin appears to have a good safety profile.

In a 12 week study, MS patients were given 3 mg of melatonin / night for 12 weeks. Posture balance, walking performance, sleep quality and fatigue all improved.[xix]

Will melatonin supplementation decrease the body’s production of melatonin?

A 1997 study reported that giving 50 mg daily at bedtime for 37 days to a group of subjects that did not know that they were receiving melatonin, resulted in no change in the body’s production of melatonin. These researchers concluded that circulating melatonin does not change the amount of pineal melatonin secretion.[xx]

The results from a 2011 study supported the efficacy and safety of 2 mg prolonged release melatonin in primary insomnia patients aged 20-80 for 6-12 months of continuous therapy. The prolonged release melatonin was discontinued after 12 months and was not associated with adverse events, withdrawal symptoms, or suppression of endogenous melatonin production.[xxi]

Vitamin D and Melatonin

Vitamin D is produced by the skin when exposed to sunshine, whereas melatonin is produced by the pineal gland when it is dark.

Research shows that a one year treatment of MS patients with high dosage vitamin D daily significantly suppressed nighttime secretion of melatonin.[xxii]

In a randomized, double blind study, 21 MS patients were given 800 IU of vitamin D3 per day (low dose) and 19 patients received 4,370 IU vitamin D3 per day (high dose) for one year. Vitamin D and melatonin levels were measured at the start of the study, at 3 months and at one year from enrolment into this study. The researchers found that after 3 months of supplementation, vitamin D levels increased and nighttime melatonin secretion decreased significantly in the high dose group, but not in the low dose group.

These results showed that after a year of daily treatment of MS patients, high doses of vitamin D significantly suppressed the nighttime melatonin and that there is a negative correlation between vitamin D and melatonin.[xxiii]

Summary

Although supplementing with melatonin appears to be safe and may promote immune modulation and significant symptom improvements while recovering from MS or other disease, it is important to work with a health care professional when taking melatonin, especially in higher amounts. It is always best practice to use the minimal amount of any therapy to support healing.

Melatonin may be a promising candidate as an MS treatment but more research is needed to help understand the possible interaction between melatonin and other hormones in the body and to know the potential therapeutic efficacy in both men and women.

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References:

[i] https://pmc.ncbi.nlm.nih.gov/articles/PMC8621753/#:~:text=Since%20melatonin%20is%20produced%20in,glucose%20metabolism%20in%20all%20cells.

[ii] https://pmc.ncbi.nlm.nih.gov/articles/PMC3001210/

[iii] https://www.sciencedirect.com/science/article/pii/S2590279224000075#:~:text=The%20presence%20of%20melatonin%20in,maintain%20condensate%20stability%20and%20solubility.

[iv] https://pubmed.ncbi.nlm.nih.gov/25787187

[v] https://pmc.ncbi.nlm.nih.gov/articles/PMC9167428/

[vi] https://pmc.ncbi.nlm.nih.gov/articles/PMC4570563/

[vii] https://pubmed.ncbi.nlm.nih.gov/539790/

[viii] https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=Melatonin%20in%20humans&author=A%20Brzezinski&volume=338&publication_year=1997&pages=185-95&pmid=8988899&doi=10.1056/NEJM199701163360306&

[ix] https://pubmed.ncbi.nlm.nih.gov/24732664/

[x] https://pmc.ncbi.nlm.nih.gov/articles/PMC4570563/

[xi] https://pubmed.ncbi.nlm.nih.gov/22006815/

[xii] https://pmc.ncbi.nlm.nih.gov/articles/PMC5660121/#:~:text=Disturbances%20in%20circadian%20melatonin%20rhythms,%3B%2095%25%20CI%2C%201.2%E2%80%93

[xiii] https://pubmed.ncbi.nlm.nih.gov/26359987/

[xiv] https://pmc.ncbi.nlm.nih.gov/articles/PMC4570563/

[xv] https://pubmed.ncbi.nlm.nih.gov/28793364/

[xvi] https://www.sciencedirect.com/science/article/pii/S2211034822000359#bib0005

[xvii] https://www.neurology.org/doi/10.1212/WNL.86.16_supplement.P4.182

[xviii] https://pubmed.ncbi.nlm.nih.gov/38813079/#:~:text=Results%3A%20Pineal%20gland%20volume%20of,there%20is%20not%20such%20difference.

[xix] https://pubmed.ncbi.nlm.nih.gov/39122092/#:~:text=Conclusion%3A%2012%2Dweek%20melatonin%20supplementation,its%20benefits%20on%20sleep%20quality.

[xx] https://pubmed.ncbi.nlm.nih.gov/9062869/

[xxi] https://pubmed.ncbi.nlm.nih.gov/21845053/

[xxii] https://pubmed.ncbi.nlm.nih.gov/23665342

[xxiii] https://www.pnas.org/doi/10.1073/pnas.2219334120#:~:text=Results%20showed%20that%20after%20a,between%20vitamin%20D%20and%20melatonin.

Melatonin: Miracle Molecule: Transform your life with ‘high dose’ Melatonin. Benefits beyond sleep as the bodies master stress resilience molecule for healing & longevity. by Dr John Andrew Lieurance ND, DC (Author)