[Update: 10 October 2017. Melatonin has not lived up to my hopes with some kinds of respiratory illnesses so far. I’ll keep trying it as the occasion arises, and if it continues to disappoint, I’ll likely delete this post. Part of playing sudoku is being willing to erase a number if it doesn’t work out. In the meantime, I have seen positive results from chewable vitamin C (I think that by chewing it we aerosolize some of the vitamin C and enable faster delivery of it throughout the respiratory tract where it is actually needed) and drinking pomegranate juice (punicalagin, a compound in pomegranates, can greatly reduce virus replication).]

I have found that melatonin seems to do more to help me get over a viral respiratory infection than over-the-counter cold medicines. Below is my explanation of how I came to try it and why I think it could help:

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Three years ago my older sister, a health-conscious woman who was only in her forties, came close to dying from acute respiratory distress syndrome (ARDS) after coming down with the flu over Christmas break, during which she overtaxed herself playing hostess despite being sick. Why did she get so ill? How do we prevent such illness in the future?

In the near-century since the 1918 flu epidemic, which killed many otherwise healthy younger adults, researchers have come to realize that an immune system overreaction was a probable cause of many of those flu deaths. Many touted cures for colds (especially vitamin C) are promised to “boost the immune system,” but when it comes to otherwise healthy people, they might be feeling terrible due to an already vigorous immune response.

A study a few years ago found that inoculating 17 healthy people with the flu virus resulted in only around half of them “getting sick” even though all of them showed some kind of immune response to the flu virus. (http://ns.umich.edu/new/releases/8511http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002234) Apparently, healthy people can sometimes fight off a virus without suffering from a week or two of the sniffles, sneezing, and coughing. So then my question became how? Because if I can forgo a week or two of Kleenex, I want to!

I looked into runny noses (rhinorrhea), the excess nasal discharge that generally starts clear then becomes nasty, thick stuff that messes with the sinuses. Histamine often causes runny noses, which is why people take anti-histamines for colds. Anti-histamines do help lessen severity of cold symptoms for a short time but not in the longer term:

In adults, there is a short-term beneficial effect on severity of overall symptoms on the first or second day of treatment (45% felt better versus 38% with placebo), but there was no difference between antihistamines and placebo in the mid to long term. The effect of sedating antihistamines on rhinorrhoea and sneezing is too small to be relevant to the patient and involves a risk of side effects such as sedation (9% versus 5.2% with placebo). Trials in children were smaller and of lower quality and lacked evidence of effectiveness.
http://www.cochrane.org/CD009345/ARI_antihistamines-common-cold

There has got to be a longer term way to lessen severity of colds. I kept digging to see where the histamine was coming from, and came up with the unexpected culprit of neutrophils, a kind of white blood cell. Neutrophils have been connected to exacerbation of allergy and bacterial lung infection:

In both models, depletion of neutrophils or neutrophil FcγRs protects mice from anaphylaxis. Amazingly, adoptive transfer of human neutrophils into the FcγR-deficient mice restored the response, suggesting that human cells can induce systemic anaphylactic reactions in response to IgG. In this model, anaphylaxis is mediated not by histamine but by neutrophil-derived platelet-activating factor, a known vasoactive lipid. By contrast, neutrophil-derived histamine is the major contributor to pulmonary allergic inflammation in chronic mycoplasma infection (223). Neutrophils may also contribute to the sensitization phase of allergic skin diseases. This idea is suggested by the surprising finding that depletion of neutrophils protects mice from the development of contact dermatitis, which suggests that these cells are important in facilitating the development of allergen-specific T cell responses (224).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277181/. Also see “Neutrophil histamine contributes to inflammation in mycoplasma pneumonia” at http://jem.rupress.org/content/203/13/2907.

A 2013 study found that influenza fatality could be prevented by reducing, but not removing, neutrophils. (http://www.cell.com/abstract/S0092-8674(13)00715-0) So how do we keep the number of neutrophils from getting too high without messing with the immune system as it carries out its necessary function of killing enemy bacteria and viruses? An answer appears to lie in preventing some of the neutrophils from having the extended lifespan they tend to have once burrowed into inflamed tissue. (http://isites.harvard.edu/fs/docs/icb.topic1445350.files/Neutrophil%20functions%20review.pdf, http://rheumatology.oxfordjournals.org/content/49/9/1618.full) It turns out that melatonin–made by the body and used regularly as an over-the-counter sleep aid–helps keep neutrophils from migrating into areas of tissue injury. (https://www.ncbi.nlm.nih.gov/pubmed/26031343) Giving melatonin appears to attenuate neutrophil inflammation and mucus secretion. (https://www.ncbi.nlm.nih.gov/pubmed/26303298https://www.ncbi.nlm.nih.gov/pubmed/25388990)

How do we help the body get more melatonin? The easiest way is to be in the dark, which stimulates the body’s synthesis of melatonin; this is usually done by sleeping. Getting too little sleep is definitively connected to susceptibility to colds and respiratory illnesses. (http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/414701, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899278/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115328/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242683/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548567/) Exposure to light, especially blue light, suppresses melatonin production. (https://www.ncbi.nlm.nih.gov/pubmed/26017927) (This is why computers and phones now offer settings that block blue light at nighttime; I utilize those settings on my primary desktop and tablet.)

What if a person can’t go hide in a dark cave the next time they sneeze a couple of times? Perhaps they have work, small children, or other pressing commitments that force them to stay awake. Taking a melatonin supplement would logically give part of the benefit of a good nap, in that it would lessen the lifespan of some neutrophils and decrease overall histamine production. Of course, it would probably be unwise to purposely take melatonin for this purpose if one already has a depressed immune system (e.g., patients going through AIDS, cancer treatment, etc.) However, melatonin is widely used and seems to be quite safe for most people.

I think going to bed and getting enough rest is the best option of all, but if melatonin is part of the healing process, we should know that. Otherwise we might be on our phones while in bed, and the blue light from the phone would suppress the needed melatonin production.

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