Melatonin to lessen severity of colds

In my Christmas post, I mentioned using melatonin to lessen the severity of colds. Here's how I got to that idea:

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. To save her, the hospital staff put her in very expensive rotating bed that kept the fluid in her lungs from pooling in any one place in her lungs. (http://www.theindychannel.com/lifestyle/health/rotating-bed-credited-with-saving-lives) 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. (https://www.sciencedaily.com/releases/2006/09/060927201707.htm) 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/8511, http://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:

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 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/26303298, https://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. (http://www.mayoclinic.org/drugs-supplements/melatonin/safety/HRB-20059770)

A work colleague of my husband was telling me recently about his insomnia, for which he takes three kinds of melatonin on a rotating basis. The melatonin hasn't cured his insomnia, but he has had much stronger resistance to colds while taking it.

English translation of "Lulajze, Jezuniu" ("Lullaby, Jesus")

"Lulajze, Jezuniu" is a pretty, haunting Polish Christmas carol that dates back centuries. For Christmas, my church choir sang it. It's been translated into English a few times, but I made a few tweaks to better fit the music and our choir. Our choir accompanist improvised his own arrangement and put in short preludes and interludes. The second verse highlighted the voices of a mother and her two young daughters. It ended up being very nice, even with just an amateur choir performing it. Our music director said it was the loveliest number of the Christmas service.

If you'd like to add a new carol to your Christmas library, here is the version we used.  On the second and third verses, I indicated with all caps which syllables should have two notes sung to them for a pleasing rhythm.

Merry Christmas! Here are some hypotheses for your stockings!

I've had such a fun year doing research on intersections of nutrition, global cuisines, epidemiology, and medical advances. Here are what I consider the most valuable of the hypotheses I formulated in 2016:

1) Molybdenum in large-ish, as-needed doses can help alleviate (or even obliterate) migraines and nausea (at least nausea from travel, migraines, and stomach bugs). 

2) To delay dementia, work to lessen the amount of hydrogen peroxide in your mouth as you age, for the ability of saliva to break down hydrogen peroxide goes down with age. Fresh (or reconstituted dried) horseradish and daikon radish in the mouth help with that because of their high peroxidase content.

3) Some fetal malformations like those resulting from thalidomide might be caused by common vetch or nigella sativa (kalonji) consumption at inopportune moments during early pregnancy, for both of those contain compounds that interfere with angiogenesis (creation of new blood vessels from existing ones).

4) An excess of folic acid and cyanocobalamin disrupts the folate cycle and is linked to autism and ADHD (and who knows what else). Stick to forms of folate and B12 that naturally occur in foods instead of using folic acid and cyanocobalamin. Also include some betaine in your diet.

5) Manganese in skin care products seems like a good idea to fight acne.

6) Addictive behavior, including "falling in love," is the brain forming and working to promote the supremacy of efficient pathways to pleasure. To lessen the strength of unwanted pathways, look at reducing delta-fosB during withdrawal periods via ellagic acid; to form new pathways, look at manipulating c-fos via light at night, MSG, etc.

7) Food allergies seem less likely to occur in the presence of sufficient magnesium chloride, so use sea salt instead of straight NaCl (table salt). Maybe even try some Dead Sea salt, which is half MgCl. Also, look at other ways of supporting and not inhibiting RALDH2.

8) The licorice root in tobacco products might be behind the protective effect smoking has against Parkinson's.

9) Take a melatonin when you first start sneezing with a new cold. It helps neutrophils not dig into the inflamed tissue and live quite so long, which lessens cold symptoms because during neutrophils' lifetimes they pump out lots of histamine. I would only use melatonin for this purpose if you feel your cold is your immune system OVER-reacting to a virus.

10) Vary your diet and your vitamin supplements because of homeostasis, i.e., your body's adaptations over time to high, continuous amounts of any substance.

11) Endogenous hydrogen cyanide in the brain could be connected to seizures, especially epileptic grand mal seizures.

12) Carbon monoxide buildup in the leg muscles could be behind restless legs syndrome.

My two biggest wishes for 2017 research are to 1) help my nine-year-old daughter not be overweight (why her and not my other four daughters? what did I do differently when I was pregnant with her in South America that predisposed her to heaviness? and can I do anything to help her before she reaches puberty?) and 2) figure out a topical way to harness the immune system to fight skin cancers (biopsies and Mohs surgery aren't fun).

(Disclaimer: I do not prescribe the use of pharmaceutical drugs in any way. I am not a physician, and I reject out of hand any attempt to hold me liable for what boils down to a discussion of food. Any use of a molybdenum supplement should be prudent and guided by the tested tolerable upper intake levels for its usage (see http://lpi.oregonstate.edu/mic/minerals/molybdenum for those limits). Any use of an isolated molybdenum supplement during pregnancy should be under the direction of a medical professional as such supplements have apparently not been tested during pregnancy.)

Update on molybdenum for migraines and nausea

Friends and family are starting to spread my hypotheses about molybdenum around. My father-in-law a few states away gave a bottle of molybdenum to a young woman that suffered from migraine-related nausea recently. He emailed me two days ago to say that she used molybdenum twice and it resolved her migraine-related nausea. Unfortunately, he forgot to ask her whether it helped with the migraines, too, although when I asked him, he said that she isn't currently suffering from a migraine. (If you want someone interrogated right, you've got to do it yourself....)

A local friend had her youngest child come down with projectile vomiting from a gastrointestinal virus last week. She gave molybdenum to everyone else in the family, and although others had lower GI tract symptoms, only one other person threw up (it was a teenager, and she stopped vomiting soon after taking more molybdenum). This friend is convinced that molybdenum kept her from ending up with the whole household vomiting.

I should probably keep a running tally of anecdotes of when molybdenum has shown effective for preventing or alleviating nausea and migraines. Here goes:

• 3 women used molybdenum-rich diets and sulfite avoidance to lessen "morning sickness."
• 1 woman used molybdenum (supplement) to end motion sickness-caused headache and nausea.
• 2 women used molybdenum for relief from migraine-related nausea.
• 3 households with multiple young children used molybdenum to stave off the vomiting due to gastrointestinal illnesses (all have found it's most effective to give molybdenum before the vomiting has begun, probably because it's harder to absorb molybdenum once vomiting has started).
• 3 women used molybdenum to lessen or avoid migraine headaches (3 different etiologies of migraine headache: old neck injury, menstruation-related, and unknown trigger).

To be objective, I will also keep a tally of anecdotes where molybdenum has not shown any positive effect:

• 1 teenage girl already suffering from a severe migraine. She took a molybdenum (given to her by a relative of mine), but she still ended up having to go to the hospital a few hours later. (I do not know her or her background, so I have no idea what is causing her headaches.) [Edit on 12/2/2017: My relative says she doesn't know whether the girl actually took the molybdenum. She gave it to the girl's mother and suggested she give it to her for the migraine, but she has no idea if the girl's mother ever gave it to her. So this is not a "no effect" anecdote after all.]

(Disclaimer: I do not prescribe the use of pharmaceutical drugs in any way. I am not a physician, and I reject out of hand any attempt to hold me liable for what boils down to a discussion of food. Any use of a molybdenum supplement should be prudent and guided by the tested tolerable upper intake levels for its usage (see http://lpi.oregonstate.edu/mic/minerals/molybdenum for those limits). Any use of an isolated molybdenum supplement during pregnancy should be under the direction of a medical professional as such supplements have apparently not been tested during pregnancy.)

Nigella sativa (black cumin, czarnuszka, etc.) also helps mice come off morphine addiction

I posted earlier about a study wherein it was observed that ellagic acid helped mice cope with coming off morphine. I came across another study from 2016 finding that thymoquinone, which is found in the spice nigella sativa (also called czarnuszka, kalonji, and black cumin), also helps mice come off morphine addiction:

Abstract
OBJECTIVE:
Dependence and tolerance are major restricting factors in the clinical use of opioid analgesics. In the present study, the effects of thymoquinone, the major constituent of Nigella sativa seeds, on morphine dependence and tolerance were investigated in mice.MATERIALS AND METHODS:
Male adult NMRI mice were made tolerant and dependent by repeated injections of morphine (50, 50, and 75 mg/kg, i.p. on 9 a.m., 1 p.m., and 5 p.m., respectively) during a 3-day administration schedule. The hot-plate test was used to assess tolerance to the analgesic effects of morphine. Naloxone (2 mg/kg, i.p.) was injected to precipitate withdrawal syndrome in order to assess the morphine dependence. To evaluate the effects of thymoquinone on tolerance and dependence to morphine, different single or repeated doses of thymoquinone were administered in mice. Rotarod was used to assess the motor coordination.RESULTS:
Administration of single or repeated doses of thymoquinone (20 and 40 mg/kg, i.p.) significantly decreased the number of jumps in morphine dependent animals. Repeated administration of thymoquinone (20 and 40 mg/kg, for 3 days) and also single injection of thymoquinone (40 mg/kg, on the fourth day) attenuated tolerance to the analgesic effect of morphine. None of the thymoquinone doses (10, 20, and 40 mg/kg) produced any antinociceptive effects on their own. Motor coordination of animals was impaired by the high dose of thymoquinone (40 mg/kg).CONCLUSION:
Based on these results, it can be concluded that thymoquinone prevents the development of tolerance and dependence to morphine.

https://www.ncbi.nlm.nih.gov/pubmed/27247922

Both studies were done in Iran, although in different cities. Why would Iran be so interested in morphine addiction? Because Iran apparently has the highest prevalence of opium addiction in the world. (http://www.irishtimes.com/news/world/middle-east/hooked-in-iran-where-addiction-rates-are-world-s-highest-1.1834386) Iran borders Afghanistan, the world's leading producer of opium. 

Nigella sativa is a peppery spice that is widely used in some of the same areas where opium is grown, so if it turns out to have a compound that can help end opium addiction, that would be convenient.

However, thymoquinone does appear to inhibit angiogenesis (https://www.ncbi.nlm.nih.gov/pubmed/18644991), which appears connected to fetal limb deformities per a prior post of mine, so pregnant women should probably avoid it (sorry, Bengali curry fans - http://www.bongcookbook.com/2007/10/myspice-kalonji.html).

Recent US news headlines on heroin say that overdoses now kill more people in the USA than do gun deaths. Many heroin addicts get started down the road to heroin use by becoming dependent on legitimately-needed prescription opiate medications after an injury or surgery. If ellagic acid and thymoquinone can help these people end their addiction to pain meds, perhaps they'll not go down the heroin road at all. One can hope.

C-fos at night

Being exposed to light during what should be our "night" appears to elevate c-fos levels in the mammalian brain, per a 1990 study:

Photic information entrains a circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the mammalian hypothalamus to environmental light/dark cycles. To determine whether light regulates c-fos gene expression in the SCN, we have measured c-fos mRNA levels in the SCN of the golden hamster. We report that, during the subjective night, light causes a rapid increase in levels of c-fos mRNA in the SCN. Light pulses of 5 min duration are sufficient to induce c-fos mRNA, and the highest mRNA levels occur 30 min following the onset of light. The minimum level of illumination required to induce an increase in c-fos mRNA is indistinguishable from the minimum irradiance that produces a phase shift in the hamster's circadian rhythm of activity. In addition, the induction of c-fos mRNA in the SCN by light is itself under circadian regulation. Light induction of c-fos mRNA occurs only during the subjective night, at circadian times when photic phase shifting of activity occurs. Taken together, these data suggest that c-fos may be a molecular component of the photic pathway for entrainment of mammalian circadian rhythms.

https://www.ncbi.nlm.nih.gov/pubmed/2116813

If elevated c-fos is connected to the creation of addictive neural assemblies in the brain (briefly discussed in the preceding post), then being exposed to light during what should be our sleeping period might increase the possibility of becoming addicted to whatever pleasurable thing we are doing while up at night.

Why do casinos keep the lights on constantly? Is it just so that casino patrons don't notice how much time they've been inside gambling, or have the casinos observed an increase in gambling addiction-like behavior as a result of their exposing their patrons to light when the patrons ought to be in bed?

Why are night owls more prone to addictive disorders than early risers? (https://www.ncbi.nlm.nih.gov/pubmed/26250146) Is it because they are engaged in their addictions when their bodies should be asleep?

Being an evening person, rather than a morning person, was recently found to be linked to a higher risk of becoming addicted to smartphones in German adolescents. (https://www.ncbi.nlm.nih.gov/pubmed/27499228) Is that because the evening people are more likely to have a smartphone shining in their faces when they should be asleep?

All very interesting. It almost makes me want to go to bed earlier. Actually, why don't I? I can read in the early morning just as easily as in the late evening. Perhaps it's time to make my bedtime firm.