Monday, January 29, 2018

Molybdenum and Diarrhea

This is not a blog about feces. I think about feces as little as I can, as do most humans. A sure way to create a political firestorm appears to be mentioning feces. If you can't stand feces discussions, ignore this post.

When my sister and I first started trying molybdenum in our families and getting successful results in dramatically shortening and averting gastroenteritis symptoms, we did not discuss stools much. It seemed to me that we still had a little diarrhea sometimes in my family, but I didn't care that much about it. Diarrhea gets flushed down the toilet and so is less messy than vomiting, and as a mother of five children, the level of messiness was what I cared about. Well, that and my kids not going through the misery of vomiting.

In fall of December 2016, a friend from church who successfully tried molybdenum for migraines reported that it gave her really bad diarrhea and so she wasn't going to use it very often. But later, she said she'd "fixed her diet" and could now take molybdenum for her migraines and that diarrhea had ceased to be an issue. I don't know what diet changes she made.

Then a few weeks ago, another friend started giving her adult post-traumatic-brain-injury son molybdenum because his medications made him feel sick to his stomach. She was surprised and very pleased to discover that the molybdenum ended his diarrhea; he'd been having diarrhea constantly and required 6-7 clothing changes per day. Now he doesn't require any clothing changes outside the usual.

After I started emailing researchers, one responded back and mentioned that molybdenum, if as effective as I'm reporting, could help many young children. That gave me pause. I'd been thinking of molybdenum as more of a convenience intervention, something to end the gross vomiting. I looked into what he was talking about and realized that each year norovirus kills around 50,000 children < 5 years of age. That is a large, sad number! But the way it kills is dehydration, of which diarrhea is the major cause (although vomiting certainly doesn't help). Can molybdenum help all these little kids not die of diarrhea?

I went back and asked my sister and friends who were using molybdenum for gastrointestinal viruses and had young children whether molybdenum was having an effect on the presence of diarrhea. The answer was a clear "Yes!" Loose stools sometimes still, but the molybdenum is somehow helping them avoid most of the diarrhea which they would normally experience from these viruses. That indicates molybdenum has the potential to be a significant life-saving intervention in poorer countries.

How is molybdenum helping prevent diarrhea? I'd really rather leave that puzzle for the diarrhea experts. If pressed to state a hypothesis, I would suggest that sulfite might induce diarrhea and so molybdenum--by aiding the conversion of sulfite to sulfate--decreases diarrhea. Why? Because of my migraineur friend above. Molybdenum gave her diarrhea until she changed her diet. Why did molybdenum do so? I suspected back when she first reported it that molybdenum was helping her more quickly convert sulfite to sulfate in her stomach and so resulting in more sulfate reaching her small intestine. A sudden increase in sulfate ingestion has been observed to cause diarrhea. (http://www.health.state.mn.us/divs/eh/wells/waterquality/sulfate.html) That indicates to me that she might have had an excess of sulfate-reducing (i.e., changing sulfate to sulfite and then hydrogen sulfide (H2S), which the body can turn around and catabolise, creating sulfite again) bacteria in her small intestine previously and that her diet shift changed her gut microbiome so as to substantially reduce the amount of sulfate-reducing bacteria. But that's just a guess.

One issue though: In poorer countries, they tend to eat a lot of beans and lentils, and yet they still have serious pediatric diarrhea issues. If molybdenum--which is highest in beans and lentils--is helpful against vomiting and diarrhea from gastrointestinal viruses, then shouldn't it already be protecting the people there? I think it does. There is a prevalence of asymptomatic* norovirus in many countries (which also means a lot of people are passing around viruses without knowing it--https://www.news-medical.net/news/20171106/Research-suggests-asymptomatic-infection-as-source-of-norovirus-outbreaks-in-Indonesia.aspx), and those countries seem to be ones where the diet has a higher whole bean and lentil content. Young children may be eating more starch and less of the pulses than are the older children and adults. Also, I've noticed that the effects of molybdenum appear to be dose-dependent. The larger the dose I give, the more dramatic the relief from gastrointestinal virus symptoms. I now often give my family the upper tolerable intake level of molybdenum when viruses come to visit us, and that makes a bigger difference than the smaller doses I used initially.

Naturally, I'd like to know when the doses are too high, and so I really need the professionals to research this and make official recommendations and protocols based on more evidence than I currently have. But my children's lives don't depend on whether I'm using molybdenum properly. That is unfortunately not the case in many poorer countries, so I hope that some researchers will energetically research and then effectively promote molybdenum as a viral gastroenteritis intervention.

* Or mostly asymptomatic. Many taxis in Manila advertise medicines for "LBM," which means "loose bowel movement."

[Edit: My friend with the post-TBI adult son also has a diabetic husband who constantly suffers "digestive issues" and diarrhea. She told me today that she started her husband on 150 mcg molybdenum every other day, and it has greatly alleviated his digestive issues and diarrhea.]

Thursday, January 25, 2018

Emailing researchers about molybdenum

In the past week or two, I've sent off around 40 emails about molybdenum's helpfulness with gastrointestinal virus-caused nausea to 60+ researchers/public health officials and cruise lines. I've had one cruise line respond and three researchers so far. I'm actually very pleased with that number of responses because I know how much spam mail I get inviting me to bogus conferences and asking me to submit papers to sketchy journals, and I expect many of my emails go immediately to spam folders due to my lack of an .edu or .gov email address. There are drawbacks to being an independent researcher.

Yesterday, as I was responding to one researcher, I had to laugh a little because I was literally taking a molybdenum tablet as I wrote to him. Remember my complaints about how "stomach bugs" keep circulating in my church and school circles? Monday, I visited a friend whose son was home sick with a vomit-causing virus and helped her wash dishes. Then Tuesday and Wednesday, I didn't feel so great. I think I took around 2000 mcg in 250 mcg doses over the past two days because my stomach kept feeling "wrong," for lack of a better word. I found out Wednesday night that my friend and her daughter were homebound with a "stomach bug," probably the same one her son had on Monday.

It's Thursday now. The weird feeling has moved to my lower abdomen, so I'm apparently nearly done passing this virus. I never threw up. My friend does know about molybdenum and uses it to shorten the duration once the vomiting hits, but I think I'm quicker to take molybdenum than my friend because I've had more experience with it (my 18 months versus her 1 month). If I recall correctly, I took some molybdenum right after leaving her house on Monday because I knew I had likely been exposed to her son's virus.

By taking molybdenum earlier on, I escape vomiting entirely and go merrily on my way, no doubt shedding viruses at some point. So I make a conscious effort to wash my hands thoroughly after using the toilet and before preparing food because I don't want to pass this to the rest of my family or anyone else. So here's a question: Is it better for society for me to stay home vomiting and isolated for a day or two or continually out in society due to being mostly asymptomatic? Considering we let children go back to school a mere 24 hours after vomiting and that viruses are being shed for weeks or more afterward (https://experts.umich.edu/en/publications/heterogeneity-in-norovirus-shedding-duration-affects-community-ri), I don't think it makes a difference as long as I am aware that I am potentially shedding viruses and so practice thorough handwashing.

Friday, January 19, 2018

"First, do no harm"

From wikipedia:
Primum non nocere is a Latin phrase that means "first, do no harm." The phrase is sometimes recorded as primum nil nocere. 
Non-maleficence, which is derived from the maxim, is one of the principal precepts of bioethics that all healthcare students are taught in school and is a fundamental principle throughout the world. Another way to state it is that, "given an existing problem, it may be better not to do something, or even to do nothing, than to risk causing more harm than good." It reminds the health care provider that they must consider the possible harm that any intervention might do. It is invoked when debating the use of an intervention that carries an obvious risk of harm but a less certain chance of benefit.
In October, I reported that my husband's co-worker had seen a 2/3 reduction in her chronic migraines since she started taking a mere 70 mcg of a molybdenum supplement at bedtime. The Recommended Daily Allowance (RDA) for molybdenum is 45 mcg for an adult woman, and she wasn't even doubling that.
For three months she took molybdenum, during which she had only one major headache and only a few little ones. It was a dramatic lessening of migraines from what she had been experiencing before she started taking molybdenum. Then she told her doctor that she was taking supplemental molybdenum. 
The doctor's response was, "That's a metal! Stop taking it." So she stopped taking it. And now her migraines are back. 
This doctor's directive appears to be based on incomplete information, and it manifestly did harm to my husband's co-worker. Molybdenum is an essential trace nutrient. It is included in Pediasure and Centrum multivitamins. It is relatively high--for a micronutrient--in lentils and beans, meaning billions of people eat it regularly. Can molybdenum be harmful in excess? Yes, particularly if inhaling it in an industrial setting. (http://www.imoa.info/HSE/environmental_data/human_health/molybdenum_toxicology.php) Anything--including water and oxygen--is harmful in excess. But not getting any molybdenum at all will put a human in a coma. (https://www.merckmanuals.com/professional/nutritional-disorders/mineral-deficiency-and-toxicity/molybdenum) Blanket restrictions are inappropriate where a nutrient is clearly contributing to better health; at the very least, performing some extra investigation is appropriate before intervening in such a way.
Having experienced three months of substantial relief from migraines due to molybdenum, my husband's co-worker is now going to look into taking the Centrum multivitamin formulations that include 45 mcg molybdenum, as well as increasing her intake of lentils. She says she's "a believer" about molybdenum's effectiveness to decrease migraines.
I wish the researchers I've been emailing about molybdenum for migraines (and nausea/vomiting from gastrointestinal viruses) would take my reports seriously so that news about its effects would spread in the medical community. I'll keep sending out emails until it does. Come on, medical world! Don't let me down!

Thursday, January 18, 2018

Unfortunate lack of knowledge about molybdenum in the medical field

Last weekend, I told a group of people about how molybdenum has been preventing nausea and vomiting from gastrointestinal viruses in lots of people. The listeners seemed interested except for one woman. She said, "Isn't that a heavy metal?" (Yes, as are iron, zinc, and selenium.) She reacted with horror when I said I'd given it to my children. "You gave it to your toddler?" (Yes, this oh-so-sketchy substance which is an added ingredient in Pediasure. I gave it to my toddler as-needed and at doses around the established tolerable upper intake level.) My attempts to protest in favor of molybdenum's nutritional value, for it is in many foods and has a set Recommended Daily Allowance (RDA), were ineffective. And here's the strangest part of the story: she is a physician.

Molybdenum is essential--in the right amounts--to human health, and she apparently knew nothing about it except that it was a heavy metal. I thought she might just be an outlier. Surely her lack of information about molybdenum is not representative of what's going on widely in medicine, right? Unfortunately, she appears to have much company in ignorance about molybdenum. I'll tell a similar such story about another doctor (at least, it's statistically unlikely to be the same doctor) in my next post.

I'm not trying to be harsh toward anyone. Ignorance is a normal state of affairs until something has been learned. After all, I was totally ignorant of molybdenum two years ago. I still remember seeing it listed as a nutrient on a webpage about barley and thinking, "Molybdenum? What's that?" (And I definitely didn't know how to pronounce it. It took a couple of months before I could easily say it, which was rather comical when I tried to tell people about it.) I addressed my ignorance by seeking out more information about molybdenum. I clicked on the first webpage's hyperlink to a page on molybdenum, and as I looked at the second page's list of foods considered good sources of molybdenum, I recognized that they were the same foods as those correlated with less "morning sickness."

Rates of nausea and vomiting in pregnancy were correlated with high intake of macronutrients (kilocalories, protein, fat, carbohydrate), as well as sugars, stimulants, meat, milk and eggs, and with low intake of cereals and pulses. 

GV Pepper, SC Roberts. Rates of nausea and vomiting in pregnancy and dietary characteristics across populations. Proc Biol Sci 2006;273(1601):2675-2679.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1635459/

The only reason I knew about the 2006 diet study was because of my prior pregnancies, during which I scoured the internet for information about how to not suffer so much from my "morning sickness." When I saw the list of foods high in molybdenum, my brain made the connection between the 2006 study findings and those foods. It was one of the coolest "Eureka" moments of my life. And given how molybdenum has ended up being helpful for both nausa/vomiting and migraines, it was probably the most impact-making "Eureka" moment I'll ever have. I stumbled on something big because I was willing to learn about something I hadn't known about before. I hope others are also willing to learn. Just because ignorance is a normal state of affairs doesn't mean we have to remain there.

Wednesday, January 17, 2018

Will it ever end?

My kindergartner's classmate threw up at school yesterday. I was really hoping that the Christmas/New Year break would stop the sharing of gastroinestinal viruses that was going on for much of the first half of the school year. Oh, well. At least I can help my own family and friends. I sure wish researchers would get on this.

Monday, January 15, 2018

Profit vs. Nonprofit: And the race is on!

This past week, I emailed two kinds of organizations about the effectiveness of molybdenum supplements to avoid vomiting from gastrointestinal viruses: 1) academic/government researchers who specialize in viral gastroenteritis, and 2) cruise ship lines. I sent them all the information in the past two posts, and told them about the 70+ gastroenteritis-infected people who have thus far experienced relief as a result of taking molybdenum, an overlooked-but-essential micronutrient. (It's now 71+ successes due to yet another friend trying it yesterday, incidentally.)

Now we will see who takes this information seriously and spends the $7/bottle to buy some molybdenum and test it, and who doesn't take it seriously. Will it be the profit-motivated cruise lines who suffer public relations nightmares every time they have a norovirus outbreak sickening hundreds on a voyage? Or will it be the government- and university-paid researchers who the public gives money to in order to find solutions to health problems? I don't know.

I lean towards thinking that the cruise line doctors/nurses will be the first to realize that molybdenum is dramatically effective because I think that, in general, profit is a more powerful motivator than altruism. (I have nothing against altruism, of course; I teach it to my children all the time, and I wish everyone were motivated regularly by it.) However, cruise line medical staff are likely hired for non-research skills more relevant to their jobs, and they probably tend to do everything by their protocols in order to avoid lawsuits. Still, they have a perfect place to look at whether consumption of molybdenum-rich foods is associated with lower nausea and vomiting from viral gastroenteritis infections because their workplace also supplies their patients with nearly all their food. There's nothing controversial about putting more lentils on the menu in a few dining rooms.

On the other hand, what academic/government researcher wouldn't want to be part of a discovery this big? Also if the CDC and Johns Hopkins don't care about a report that there is a cheap, safe way to stop vomiting from norovirus-type infections, then every US taxpayer has a reason to feel sorely let down.

So, we'll see.

Sunday, January 14, 2018

Molybdenum for Gastroenteritis Nausea and Vomiting, part 2

(continued from the previous post)

Gastrointestinal infections, Hydrogen Sulfide, and Sulfite 

A typical part of a viral gastroenteritis infection is damage to the mucosa (lining) of the proximal small intestine (the part of the small intestine closest to the stomach).[1] Our bodies make and use hydrogen sulfide (H2S) while working to protect the gastric[2] [3] and intestinal mucosa.[4]

It is still being investigated exactly how H2S is afterward transformed in the body, but one of its catabolic products is known to be sulfite. Moreover, it was recently discovered that there appears to be a previously-unknown H2S oxidation pathway using neuroglobin.[5] Neuroglobin has been discovered to be expressed in the cells of the stomach fundus and the small intestine after hypoxia.[6] I suspect that neuroglobin-assisted H2S catabolism results in more net sulfite than the better known sulfide:quinone oxidoreductase catabolic pathway and that it could be a major contributor to the presence of sulfite in the stomach and small intestine at levels high enough to trigger vomiting.

In most people, sulfite oxidase typically seems able to handle the amount of sulfite resulting from endogenous hydrogen sulfide metabolism. However, in the absence of sufficient molybdenum, magnesium,[7] or P5P (active vitamin B6 is involved in making heme, which is part of sulfite oxidase),[8] sulfite oxidase might not reach necessary levels of activity, for those three nutrients are needed to form sulfite oxidase and the molybdenum cofactor. The main result of insufficient sulfite oxidase activity is a buildup of nausea-inducing sulfite. It thus follows that supplemental molybdenum can reduce nausea.

mARC 1 and mARC 2

Two relatively recently discovered molybdenum-utilizing enzymes are the mARC 1 and mARC 2 enzymes. They appear to be involved with nitric oxide (NO) production,[9] and NO and H2S cooperatively interact in many ways.[10] [11] Thus mARC1 and mARC2 might also be involved in the pathophysiology of nausea and vomiting.

Conclusion

I have written this because I have seen molybdenum dramatically prevent nausea and vomiting from gastrointestinal viruses, as well as shorten the duration of gastrointestinal virus symptoms even after vomiting has already begun. I think current research supports a hypothesis that molybdenum does so by supporting optimal activity of the molybdenum-utilizing enzymes sulfite oxidase and possibly mARC1 and mARC2.

Because this discovery has great potential for improvement of public health, I think it urgent for professional researchers to explore molybdenum’s effect in alleviating gastrointestinal virus-caused nausea and vomiting and establish appropriate dosage guidelines for its use.

- CT

References



[1] Widerlite L, Trier JS, Blacklow NR, Schreiber DS. Structure of the gastric mucosa in acute infectious bacterial gastroenteritis. Gastroenterology 1975;68(3):425-430.
[2] Bronowicka-Adamska P, Wróbel M, Magierowski M, Magierowska K, Kwiecień S, Brzozowski T. Hydrogen sulphide production in healthy and ulcerated gastric mucosa of rats. Molecules 2017;22(4). pii: E530.
[3] Souza LK, Araújo TS, Sousa NA, Sousa FB, Nogueira KM, Nicolau LA, Medeiros JV. Evidence that d-cysteine protects mice from gastric damage via hydrogen sulfide produced by d-amino acid oxidase. Nitric Oxide 2017;64:1-6.
[4] Wallace JL, Caliendo G, Santagada V, Cirino G, Fiorucci S. Gastrointestinal safety and anti-inflammatory effects of a hydrogen sulfide-releasing diclofenac derivative in the rat. Gastroenterology 2007;132(1):261-271.
[5] Bilska-Wilkosz A, Iciek M, Górny M, Kowalczyk-Pachel D. The Role of Hemoproteins: Hemoglobin, Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes. Int J Mol Sci 2017;18(6). pii: E1315. doi: 10.3390/ijms18061315.
[6] Emara M, Turner AR, Allalunis-Turner J. Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues. Cancer Cell Int 2010;10:33.
[7] Mendel RR. The Molybdenum Cofactor. J Bio Chem 2013;288:13165-13172.
[8] Heinemann IU, Jahn M, Jahn D. Arch. The biochemistry of heme biosynthesis. Biochem Biophys 2008;474(2):238-251.
[9] Sparacino-Watkins CE, Tejero J, Sun B, Gauthier MC, Thomas J, Ragireddy V, Merchant BA, Wang J, Azarov I, Basu P, Gladwin MT. Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. J Biol Chem 2014; 289(15):10345-10358.
[10] Farrugia G, Szurszewski JH. Carbon Monoxide, Hydrogen Sulfide, and Nitric Oxide as Signaling Molecules in the Gastrointestinal Tract. Gastroenterology 2014;147(2): 303–313.
[11] Szabo C. Hydrogen sulfide, an enhancer of vascular nitric oxide signaling: mechanisms and implications. Am J Physiol Cell Physiol 2017 Jan 1;312(1):C3-C15.

Molybdenum for Gastroenteritis Nausea and Vomiting, part 1

Molybdenum supplements for nausea and vomiting from gastrointestinal viruses

During the first part of 2016, I authored a medical hypothesis connecting less severe “morning sickness”—nausea and vomiting of pregnancy (NVP)—with high regional intake of foods containing relatively high levels of the essential micronutrient molybdenum.[i]

My sister purchased a bottle of the molybdenum supplement “Moly-B” to have on hand in case she became pregnant. She did not get pregnant, but she and a friend contracted a gastrointestinal virus, and she decided to try the molybdenum for the nausea and vomiting caused by the virus (her husband was already vomiting from it). As a result of taking the molybdenum early in the course of the infection, she and her friend completely avoided any vomiting and passed the virus quickly.

Since my sister’s serendipitous discovery, approximately 70 people (at least that I know of) have  used molybdenum supplements to either completely avoid vomiting from “stomach bugs” or to cut short the duration of vomiting from “stomach bugs” after it had already begun. The effects are clear and dramatic and go far beyond what one would expect from a placebo effect. Molybdenum, if taken during the early stomach cramping stage of a gastrointestinal virus infection, has been to my knowledge uniformly successful at preventing vomiting. Furthermore, molybdenum taken during the vomiting stage has also shown itself effective to shorten the duration of the vomiting stage, although larger doses seem to be required than if molybdenum had been taken earlier.

The dosages people have been taking for this purpose are typically 10-20 times larger than the established RDA for molybdenum, yet still below the established tolerable upper intake level. Moreover, the molybdenum is only used on as “as-needed” basis, not chronically. Two other brands of molybdenum supplements have also been used by people I know, and all three molybdenum supplement brands show approximately the same effectiveness.

How is molybdenum having this effect? Correlation argues best for causation where there is a plausible causative mechanism, and below is a suggestion of how I think molybdenum might be alleviating nausea and vomiting from gastrointestinal viruses.

The Molybdoenzyme Sulfite Oxidase and Sulfite

There are only five known enzymes in the human body that incorporate element #42, molybdenum,[ii] an essential trace mineral in the human diet. The most interesting of these molybdenum enzymes to my research on NVP was sulfite oxidase. Sulfite oxidase catalyzes the conversion of sulfite to sulfate, which is then recycled or excreted from the body. Sulfite is toxic to humans; it was formerly used in salad bars to keep cut produce fresh-looking until it sent many restaurant patrons to the hospital with severe symptoms that included anaphylactic shock, nausea, abdominal pain, seizures, and death.[iii]

Feeding rats in such a way as to make them deficient in molybdenum results in a loss of sulfite oxidase activity.[iv] Supplementing them with molybdenum, on the other hand, increases sulfite oxidase activity up to a plateau.[v] Molybdenum is essential for human health, as was discovered when a man kept on molybdenum-less total parenteral nutrition developed headaches, vomiting, and heart rhythm abnormalities, and then became comatose; his condition was reversed when he was given molybdenum.[vi]

(To be continued in a second post.)

References



[i] Taylor CE. A novel treatment for “morning sickness”: Nausea of pregnancy could be induced by excess sulfite which molybdenum can help alleviate. Med Hypotheses 2016;95:31-33.
[ii] Mendel RR. Cell biology of molybdenum. Biochim Biophys Acta - Mol Cell Res 2006;1763(7):621-635.
[iii] Yang WH, Purchase EC. Adverse reactions to sulfites. CMAJ 1985;133(9):865-867, 880.
[iv] Cohen HJ, Drew RT, Johnson JL, Rajagopalan KV. Molecular Basis of the Biological Function of Molybdenum. The Relationship between Sulfite Oxidase and the Acute Toxicity of Bisulfite and SO2. Proc Natl Acad Sci USA 1973;70(12 Pt 1-2):3655-3659.
[v] Wang X, Oberleas D, Yang MT, Yang SP. Molybdenum requirement of female rats. J Nutr 1992;122(4):1036-1041.
[vi] Abumrad NN, Schneider AJ, Steel D, Rogers LS. Amino acid intolerance during prolonged total parenteral nutrition reversed by molybdate therapy. Am J Clin Nutr 1981;34(11):2551-2559.

Friday, January 12, 2018

Is molybdenum "snake oil"?

The vocabulary term for today is "snake oil." From wikipedia:
Snake oil is a fraudulent liniment without snake extract. Currently, it has come to refer to any product with questionable or unverifiable quality or benefit. By extension, a snake oil salesman is someone who knowingly sells fraudulent goods or who is a fraud, quack, or charlatan.
A snake oil recipe from 1719/1751 (Juan de Loeches, Tyrocinium Pharmaceticum), printed in Spain: "The viper oil of Mesues. Take 2 pounds of live snakes and 2 pounds 3 ounces of sesame oil. Cook slowly, covered in a glazed pot, until meat pulls away from bone. Strain and store. Uses: Cleans the skin, removes pimples, impetigo and other defects."
The use of snake oil long predates the 19th century. In Europe, viper oil had been commonly recommended for many afflictions, including the ones for which rattlesnake oil was subsequently favored (e.g., rheumatism and skin diseases). In China, oil made from Chinese water snake (Enhydris chinensis) fat is a traditional liniment used for treating joint pain. Chinese water-snake oil contains 20 percent eicosapentaenoic acid (EPA), which has strong analgetic and anti-inflammatory properties.

I can tell that many think I am selling snake oil when I tell them about what I've seen of molybdenum's effect on alleviating nausea/vomiting and migraines. But I'm not selling it. I'm actually often giving it away for free in order to help people not suffer. And then it works. 

Also, I'm not saying it works for many afflictions. As far as I've seen, molybdenum clearly helps with only two things: 1) nausea and vomiting, and 2) migraines. Both of these ailments are affected by diet in what (till now) have been mysterious ways, and molybdenum is in some foods. If you read my other blog posts, you'll see that current research supports plausible explanations for how molybdenum could help with both of these two ailments.

The answer to the post title is "No." Molybdenum is proving itself by repeated observations in different people to actually be a genuine help. I think that, far from being a placebo, molybdenum acts on a molecular level to relieve a physiological cause of migraines and nausea/vomiting.

Wednesday, January 10, 2018

Molybdenum and Migraines, part 2

(continued from yesterday)

The Migraine Connection to Sulfite

The air pollutant sulfur dioxide, a sulfiting agent, appears linked to migraine occurrence.[1] [2] Chemically induced sulfite oxidase deficiency is toxic to the brain, primarily to the cerebral cortex and striatum,[3] which first area is connected to migraine susceptibility.[4] Sulfite is a catabolic product of hydrogen sulfide (H2S), an gasotransmitter found in the brain[5] that is connected to vasodilation,[6] and vasodilation has been repeatedly observed in connection with migraines. It is still unclear exactly how  H2S is broken down in the body; it was recently discovered that there appears to be a previously-unknown H2S catabolic pathway using neuroglobin.[7]

In most people, sulfite oxidase typically seems able to handle the amount of sulfite resulting from endogenous hydrogen sulfide production. However, in the absence of molybdenum, magnesium,[8] or P5P (active vitamin B6 is involved in making heme, which is part of sulfite oxidase),[9] sulfite oxidase might not reach necessary levels of activity, as those three nutrients are needed to form sulfite oxidase and its component, the molybdenum cofactor. Moreover, when sulfite oxidase is dealing with a high level of sulfite, nitrites also are substrates of the enzyme;[10] the connection between nitrites and migraines has much evidence behind it.[11] There is also evidence connecting sulfite consumption to migraines.[12]

mARC 1 and mARC 2

Two relatively recently discovered molybdenum-utilizing enzymes are the mARC 1 and mARC 2 enzymes. They appear to be involved with nitric oxide (NO) production,[13] and nitric oxide has long been reported to be involved with headaches, including migraines.[14] Molybdenum supplementation might, by facilitating optimal functioning of the mARC1 and mARC2 enzymes, contribute to appropriate NO production and possibly less migraine incidence. There is also evidence that interaction of NO and H2S is connected to migraine pathophysiology,[15] and NO and H2S cooperatively interact in many ways.[16]

Conclusion

I have written this because I have seen molybdenum help with migraines in several women with different etiologies (for example, one connected to hormonal fluctuation, one connected to neck injury and exacerbated by air pressure changes, and one of unknown causation), and I think current research supports a hypothesis that molybdenum does so by supporting optimal activity of the molybdenum-utilizing enzymes sulfite oxidase, mARC 1, and mARC 2. Because chronic migraines could be causing brain damage,[17] I think it urgent to explore whether molybdenum has potential to alleviate migraines.


References



[1] Szyszkowicz M, Rowe BH, Kaplan GG. Ambient sulphur dioxide exposure and emergency department visits for migraine in Vancouver, Canada. Int J Occup Med Environ Health 2009;22(1):7-12.
[2] Szyszkowicz M, Porada E. Ambient Sulphur Dioxide and Female ED Visits for Migraine. ISRN Neurology 2012;2012:279051.
[3] Grings M, Moura AP, Parmeggiani B, Motta MM, Boldrini RM, August PM, Matté C, Wyse AT, Wajner M, Leipnitz G. Higher susceptibility of cerebral cortex and striatum to sulfite neurotoxicity in sulfite oxidase-deficient rats. Biochim Biophys Acta 2016;1862(11):2063-2074.
[4] Lang E, Kaltenhäuser M, Neundörfer B, Seidler S. Hyperexcitability of the primary somatosensory cortex in migraine--a magnetoencephalographic study. Brain 2004;127(Pt 11):2459-2469.
[5] Gheibi S, Aboutaleb N, Khaksari M, Kalalian-Moghaddam H, Vakili A, Asadi Y, Mehrjerdi FZ, Gheibi A. Hydrogen sulfide protects the brain against ischemic reperfusion injury in a transient model of focal cerebral ischemia. J Mol Neurosci 2014;54(2):264-70.
[6] Bhatia, M. Hydrogen sulfide as a vasodilator. IUBMB Life 2005;57:603–606.
[7] Bilska-Wilkosz A, Iciek M, Górny M, Kowalczyk-Pachel D. The Role of Hemoproteins: Hemoglobin, Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes. Int J Mol Sci 2017;18(6). pii: E1315. doi: 10.3390/ijms18061315.
[8] Mendel RR. The Molybdenum Cofactor. J Bio Chem 2013;288:13165-13172.
[9] Heinemann IU, Jahn M, Jahn D. Arch. The biochemistry of heme biosynthesis. Biochem Biophys 2008;474(2):238-251.
[10] Wang J, Krizowski S, Fischer-Schrader K, et al. Sulfite Oxidase Catalyzes Single-Electron Transfer at Molybdenum Domain to Reduce Nitrite to Nitric Oxide. Antioxidants & Redox Signaling 2015;23(4):283-294.
[11] D'Amico D, Ferraris A, Leone M, Catania A, Carlin A, Grazzi L, Bussone G. Increased plasma nitrites in migraine and cluster headache patients in interictal period: basal hyperactivity of L-arginine-NO pathway? Cephalalgia 2002 Feb;22(1):33-6.

[12] Millichap JG, Yee MM. The diet factor in pediatric and adolescent migraine. Ped Neurology 2003;28(1):9-15.

[13] Sparacino-Watkins CE, Tejero J, Sun B, Gauthier MC, Thomas J, Ragireddy V, Merchant BA, Wang J, Azarov I, Basu P, Gladwin MT. Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. J Biol Chem 2014; 289(15):10345-10358.
[14] Thomsen LL, Olesen J. A pivotal role of nitric oxide in migraine pain. Ann N Y Acad Sci 1997;835:363-372.
[15] Wild V, Messlinger K, Fischer MJ. Hydrogen sulfide determines HNO-induced stimulation of trigeminal afferents. Neurosci Lett 2015; 602:104-109.
[16] Szabo C. Hydrogen sulfide, an enhancer of vascular nitric oxide signaling: mechanisms and implications. Am J Physiol Cell Physiol 2017 Jan 1;312(1):C3-C15.
[17] Asma Bashir, Richard B. Lipton, Sait Ashina, Messoud Ashina. Migraine and structural changes in the brain: A systematic review and meta-analysis. Neurology 2013;81(14):1260–1268.

Tuesday, January 9, 2018

Molybdenum and Migraines, part 1

During the summer of 2016, I was working on a hypothesis connected to “morning sickness” when I started noticing that trigger food categories for nausea and vomiting of pregnancy (NVP) often overlapped with reported migraine trigger foods.

One day I was talking with a friend who informed me that she often had horrible, disabling migraine headaches that medications did not relieve; the medications made her feel even worse than the migraines, so she had stopped taking the medications. As part of my research on NVP, I had formulated a hypothesis that dietary molybdenum intake in various regions was inversely correlated with the NVP burden observed in those locales.[i] So I suggested to my friend that she try molybdenum supplements for her migraines. She did try them, taking a capsule of 500 mcg of chelated molybdenum glycinate when a migraine first started coming on; it worked dramatically. She has since found molybdenum effective to not only stop a migraine as it starts but to help relieve a migraine after it has already become quite painful.

Why did it work for her? And for several other friends and friends-of-friends who have since used it to ameliorate or end their migraine suffering? (Molybdenum has also resolved migraine-related nausea in at least two other women, which could be due to the same mechanism behind molybdenum alleviating NVP, as mentioned above.) Below is an explanation of how I think molybdenum intake might help alleviate migraines.

The Molybdoenzyme Sulfite Oxidase

There are only a handful of known enzymes in the human body that incorporate element #42, molybdenum,[ii] an essential trace mineral in the human diet. The most interesting of these molybdenum enzymes to my research on NVP was sulfite oxidase. Sulfite oxidase catalyzes the conversion of sulfite to sulfate, which is then recycled or excreted from the body. Sulfite is toxic to humans; it was formerly used in salad bars to keep cut produce fresh-looking until it sent many restaurant patrons to the hospital with severe symptoms that included anaphylactic shock, nausea, abdominal pain, seizures, and death.[iii]

Feeding rats in such a way as to make them deficient in molybdenum results in a loss of sulfite oxidase activity.[iv] Supplementing them with molybdenum in turn increases sulfite oxidase activity up to a plateau.[v] Molybdenum is essential for human health, as was discovered when a man kept on molybdenum-less total parenteral nutrition developed headaches, vomiting, and heart rhythm abnormalities, and then became comatose; his condition was reversed when he was given molybdenum.[vi] A lack of sulfite oxidase in infants causes severe neurological damage and early death.[vii] [viii]

(to be continued)


References



[i] Taylor CE. A novel treatment for “morning sickness”: Nausea of pregnancy could be induced by excess sulfite which molybdenum can help alleviate. Med Hypotheses 2016;95:31-33.
[ii] Mendel RR. Cell biology of molybdenum. Biochim Biophys Acta - Mol Cell Res 2006;1763(7):621-635.
[iii] Yang WH, Purchase EC. Adverse reactions to sulfites. CMAJ 1985;133(9):865-867, 880.
[iv] Cohen HJ, Drew RT, Johnson JL, Rajagopalan KV. Molecular Basis of the Biological Function of Molybdenum. The Relationship between Sulfite Oxidase and the Acute Toxicity of Bisulfite and SO2. Proc Natl Acad Sci USA 1973;70(12 Pt 1-2):3655-3659.

[v] Wang X, Oberleas D, Yang MT, Yang SP. Molybdenum requirement of female rats. J Nutr 1992;122(4):1036-1041.
[vi] Abumrad NN, Schneider AJ, Steel D, Rogers LS. Amino acid intolerance during prolonged total parenteral nutrition reversed by molybdate therapy. Am J Clin Nutr 1981;34(11):2551-2559.
[vii] Johnson-Winters K, Tollin G, Enemark JH. Elucidating the Catalytic Mechanism of Sulfite Oxidizing Enzymes using Structural, Spectroscopic and Kinetic Analyses. Biochem 2010;49(34):7242-7254.

[viii] Dublin AB, Hald JK, Wootton-Gorges SL. Isolated Sulfite Oxidase Deficiency: MR Imaging Features. AJNR 2002;23:484-485.

Sunday, January 7, 2018

Short video on observations about molybdenum preventing vomiting from "stomach bugs"

I've seen and heard enough instances and anecdotes to convince me that molybdenum is very effective for preventing nausea/vomiting from "stomach bugs" (i.e., gastrointestinal viruses), especially if taken before vomiting begins. So I made a video to tell others. It's probably one of the most visually-boring videos in the history of YouTube, but I think the content is quite exciting. Hopefully that makes up for my lack of graphic design skills. Please feel free to share. Here it is:


Friday, January 5, 2018

Some other locations of neuroglobin

Two posts ago, I mentioned that there appears to be a non-canonical H2S oxidation pathway involving human ferric neuroglobin. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486136/) Neuroglobin is high in the brain and also might be upregulated by hypoxia in the stomach fundus and the small intestine. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945342/) As I was looking into neuroglobin, I noticed that it is also highly expressed in the adrenal glands, pancreas, and testis. (https://www.ncbi.nlm.nih.gov/gene/58157)

If my idea is correct about neuroglobin being involved in causing an excess amount of sulfite to result from H2S catabolism--which sulfite then causes migraine symptoms in the brain and nausea/vomiting in the stomach/proximal small intestine--then there could also be hard-to-explain, individually-varying, molybdenum-deficiency-linked illnesses involving those other parts of the body, similar to migraine and "morning sickness." There certainly is a weird illness happening for some in their pancreases: idiopathic chronic pancreatitis (https://www.medscape.com/viewarticle/487185). Maybe molybdenum could help with idiopathic chronic pancreatitis; at the very least, it wouldn't hurt to try it for the nausea and vomiting that often occur during episodes of pain. (https://www.medicalnewstoday.com/articles/160459.php) I have no idea about the adrenal glands and the testis, though. I don't know anyone who has issues with those body parts (at least openly), and I usually confine my research to something I can ask a friend/relative about in order to ground my hypothesizing to reality.

Tuesday, January 2, 2018

A cartilage study that should be redone with modern imaging technology

Back in 1973, Florida and Pennsylvania researchers published findings in which they unexpectedly discovered that rabbit cartilage cells (synovial cells and chondrocytes) could become infected by Influenza A2 viruses. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC422866/) However, using "light microscopy" to look at the cells, they were unable to detect any cytopathology in the infected cells, even after a period of 18 days. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC422866/?page=4)

But a lack of effect in cartilage cells from influenza doesn't make any sense, for influenza is known to often cause aches and pains in joints. (https://www.express.co.uk/life-style/health/864122/flu-symptoms-aussie-cold-virus-arthritis-joint-pain) Further, chondrocytes infected with influenza A might have the ability to tell T-cells to destroy them. (http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2567.2003.01621.x/full: "The ability of chondrocytes to process and present both endogenous and viral antigens also confirms them as possible target cells for [cytotoxic T cells] in the enthesis or joint during localized inflammation or infection.")

Something must be occurring within the influenza A-infected chondrocytes. We need more than 1970s microscopes on the job. Something like this:
             
Using sheets of light to scan cells, a new microscope can capture real-time 3D videos of what's happening inside cells down to the molecular level—feat once thought impossible.  

***

This new microscope, outlined today in the journal Science, builds on advances in what's called light-sheet microscopy, in which sheets of light scan the targets. Conventional light sheets are too thick to illuminate details smaller than cells, though. So Betzig and his colleagues used ultra-thin sheets as little as 250 nanometers (billionths of a meter) wide.
The new microscope can achieve resolutions of up to 230 nanometers and record at up to 1,000 frames per second, Betzig says. And crucially, the light sheets spread light energy in such a way to minimize damage to any single point in a specimen.
Scientists have used the new microscope to study embryonic development in nematodes and fruit flies, trace the pathways of nerve cells that form synapses in the brain, and follow the progress of proteins that clump together to cause disease.
"This really lets you look at the dynamic processes in cells in 3-D non-invasively," says Betzig, an engineering physicist at the Howard Hughes Medical Institute's Janelia Research Campus in Ashburn, Va.
http://www.popularmechanics.com/science/health/a11487/using-sheets-of-light-this-new-microscope-sees-inside-a-cell-17345685/

The invention of the microscope was a huge advance in medicine. Can you imagine how far imaging down to the molecular level will take medical science?