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) has 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?

Saturday, December 30, 2017

H2S --> sulfite and advances in understanding H2S metabolism

One of the points in my hypotheses about why molybdenum is helping people with nausea and migraines (and apparently "morning sickness," though I have fewer pregnant friends than friends with migraines) is that the molybdenum is enabling higher activity of the sulfite oxidase enzyme--which uses a molybdenum cofactor--in transforming toxic sulfite to excretable sulfate. But where is the sulfite coming from? I think it's a metabolic product of hydrogen sulfide (H2S), which it turns out is important to making new blood vessels from existing ones (angiogenesis), vasodilation, and even keeping uterine muscles from contracting.

The pathways by which H2S is broken down in the body are still being clarified by researchers. Sulfite is often an end result, but sulfite is also used by the catabolism. Therefore, whether there is a net increase in sulfite from H2S catabolism is far from a given. A study published this past year by some Polish* researchers found that there appears to be a non-canonical pathway by which H2S is oxidized in the brain, and that pathway appears to use neuroglobin. (https://www.ncbi.nlm.nih.gov/pubmed/28632164) Guess where neuroglobin shows up besides in the brain? In the stomach and the small intestine! (https://www.ncbi.nlm.nih.gov/pubmed/20828399) The two body regions where I've been observing molybdenum to have an effect on mysterious illnesses--nausea/vomiting and migraines--are also places where an unknown H2S catabolic pathway appears to be occurring. I look forward to more research on neuroglobin's interaction with H2S.

* I love Poland. Lots of easily-utilized glycine betaine in the national diet, and cutting edge research in very interesting fields.

How internal "movies" are shaped depending on who the protagonist is

Many of people's disagreements seem to come from "watching a different movie" in their minds from the one being seen by the people they disagree with. That movie is highly influenced by people's experiences and what they've been told/shown, but it is also shaped by what role the individual person plays in the movie. I think that a fundamental rule of people is that "no one is the villain of his/her own story/movie."

Witness these two music videos done by Alexander Rybak showing the experience of stalking and harassing a love interest. When Alexander is playing the stalker, his actions are cute and kind of funny.



But when he is the one being stalked, he portrays himself as the tortured victim of a person who belongs in a mental institution.



He wrote the second song because he was actually being harassed by a fan, so I know he's not in favor of stalking. That's what makes it even more interesting that he portrayed himself as merely lovably obnoxious when the tables are turned. He undoubtedly had no intention of making stalking look like an OK thing to do, but he apparently can't help avoiding a portrayal of himself as a "bad guy."

Wednesday, December 27, 2017

The fight against rhinovirus is real and continuing

Now that we no longer fear gastrointestinal viruses in our household (see all the previous posts about molybdenum), our current nemesis is the "winter cold," which is usually caused by a rhinovirus. There's no vaccine for rhinovirus, and very little appears to exist in the way of effective treatments; Science-Based Medicine says that only honey seems to help--https://sciencebasedmedicine.org/you-cant-beat-the-common-cold-and-thats-a-fact/. But honey and my current low-simple-sugars way of eating aren't exactly compatible, so I'm still digging.

One promising lead is the finding that warmer temperatures help the body fight off a rhinovirus infection.

The researchers from Yale infected airway cells with a rhinovirus in their lab, and kept some at a normal body temperature (98 degrees Fahrenheit) and others just below it (91.4 degrees). Whether it’s cold or hot, infected cells tend to make little interferons, Tech Times reported — but in the two temperature groups, the virus persisted. In fact, the cells in below-average temps replicated immediately, while the cells in the normal temps died off much quicker and were not able to replicate as quickly.
That’s not all. Researchers used mathematical modeling and genetic approaches to better understand the underlying ways in which a virus grows. The found that not only does the warm temperature kill the infection off faster, but it maximizes the effect of an enzyme, called RNAseL, in the double-stranded RNA. The enzyme is part of the interferon response, and eventually helps to eliminate it. Taken altogether, these findings show that even in the absence of interferons, warm temperatures have profound effects on the body’s antiviral response and the outcomes of the common cold, the researchers wrote.
This also builds upon prior research out of Yale that found cooler temperatures enabled infected airway cells to spread in mice, according to Tech Times. Researchers found that at “several degrees below the normal body temperature, interferons that fought viruses were less able to perform their job.” And in a separate mice study, they found that the rhinovirus spreads to airway cells more quickly in cooler temperatures. So it’s no wonder that peak cold and flu season tends to be in the winter, when temperatures can drop well below zero.
http://www.medicaldaily.com/body-heat-kill-viral-infections-common-cold-391713

Could this help explain why so many people tout hot concoctions as home remedies for winter colds? The steaming hot liquid helps warm their noses and temporarily enables the virus-infected cells to die off more quickly? And why so many of the things they put in their hot concoctions are vasodilators or help enable vasodilation, such as chili peppers, lemon juice, ginger, alcohol (for some), and Vitamin C? I once was coming down with a cold around my birthday, and I wanted to celebrate with Thai food. At the restaurant, I ate much of a steaming tureen of tom ka gai (if you haven't had it before, I highly recommend it), and by the end of our leisurely meal, my cold was gone and didn't come back. I didn't know if it was the chicken, the ginger, the peppers, the lemongrass, or what, but maybe it was that the prolonged consumption of steaming, vasodilating substances enabled my virus-infected cells to die more quickly and replicate more slowly. (Whatever it was, it tasted wonderful.)

Besides lingering over a tureen of spicy soup, what other things can we do to help kill off a cold before it can make us miserable? Perhaps a special nose-warming device like a mini-hair dryer aimed into the nostrils would be a feasible intervention. (Someone beat me to that idea.) Or perhaps using flush-inducing niacin to warm up the facial tissues for a while would help. (Again, I've been beaten to the idea.) Also, when would one first start to use the heating/vasodilating intervention in order to maximize its effect? Right after the first sneeze occurs?

In the meantime, most of the family is "under the weather" because they came down with their colds days ago, and I didn't look all this stuff up until almost everyone was symptomatic. Only the kindergartner hasn't sneezed yet. (But I have a blow dryer handy for when she does. :) ) I did turn up the thermostat, and that seems to help their colds be less severe; I wish I didn't have to turn it down at night, but it's been very cold here and money is a consideration. I won't shrug off people's hot concoctions anymore now that there seems to be a plausible mechanism for their effectiveness at hastening the end of a rhinovirus infection.

[Update on 12/30/2017: The kindergartner sneezed within a day of this post. I quickly sat her in front of the computer with safety goggles over her eyes, instructions to hold her lips inside her mouth to keep them from chapping, and a blow dryer. She aimed the warm air up her nostrils on and off for around half an hour while watching comedy sketches, and that was the end of her possibly incipient rhinovirus cold. Not a sneeze, sniffle, or cough out of her since. An older child who had already been sick a few days let out a wet sneeze later, so she did the blow dryer treatment to herself, too. She also hasn't sneezed since, although she still had to deal with the accumulated mucus from the previous days. She insists the blow dryer treatment helped her, though. These are just anecdotes, I know, but it's nice not to have my children be sick. Next time a rhinovirus comes to call on our family, I'll use a blow dryer or a facial steamer at the first sneezes and report on whether the warm air in the nose seemed to help or was a waste of time.]

Saturday, December 23, 2017

If it took that long to convince him, how long will it take to convince others?

When I first made the connection between molybdenum and less severe morning sickness, I relayed it to a sister who has had very hard pregnancies due to nausea and vomiting. She bought a bottle of molybdenum to have on hand, I suppose in case she became pregnant, though she wasn't planning on it to my knowledge.

Then a "stomach bug" infected her and her husband. She asked me if molybdenum would help with it, and I said I didn't know and she could try it if she wanted to. She hadn't yet begun throwing up, while her husband had. They both took molybdenum (just one tablet each, I think), and she went to bed. The next morning she woke up pleasantly surprised to find that she didn't feel sick after all. She though perhaps she'd been wrong about being infected, but when she ate granola for breakfast, her intestines let her know that all was not normal. Her husband, however, didn't stop vomiting. So naturally he didn't think molybdenum was doing much.

In the intervening 18 months, she and I have learned much more about molybdenum's use for gastrointestinal viruses. It is far more effective at stopping vomiting that hasn't yet occurred, and taking it encapsulated or pressed into a tablet seems to slow down its delivery to where it's needed most in the stomach.

This past week, her husband got another stomach bug. She messaged me last night, saying that I had "made a believer" out of her husband. She pushed him to take molybdenum the day before when he felt like he was getting a stomach bug. "An hour later, he felt pretty good and headed into work. He forgot he started the day thinking it was going to be sulfur and vomits in the next few hours until the afternoon when it crept up on him again, so he took another Mo and he's good to go!"

Approximately eighteen months after his wife was the first one to use molybdenum successfully to prevent nausea from a stomach bug, and he finally believes it. If it took that long for him, I should be patient with everyone else, even if I tire of sounding like a broken record.

Wednesday, December 20, 2017

Could molybdenum end cruise ship norovirus outbreaks?

Just as I was helping my friend's family and my own beat back nausea and vomiting from a severe "stomach bug" (https://petticoatgovernment.blogspot.com/2017/12/another-dramatic-success-for-molybdenum.html) (my turn to host the virus was Monday, and thanks to molybdenum, the worst I experienced was a moderately sore stomach), the news carried a story about a Royal Caribbean ship having a big outbreak of what appears to be a gastrointestinal virus. (http://www.miamiherald.com/living/travel/cruises/article190143054.html) After all I've seen in the past 18 months of molybdenum's effectiveness and apparent safety, I feel like the kid in class who's practically jumping in her seat with hand raised to get the teacher to call on her, "I have an answer, I have an answer, call on me, please!" But, alas, I don't know anyone who works in cruise ship medicine. I live in Colorado. Not a lot of cruises originating out of Denver....

Monday, December 18, 2017

Another dramatic success for molybdenum in treating a gastrointestinal virus

A friend was sick for about five days last week with a bad "stomach bug." Once we were able to get some molybdenum to him, he got better within a day. We saw him at a gathering on Saturday. In fact, we ate next to his family, and dd13 sat beside him. That evening, I pre-dosed all my children with 500-1000 mcg (depending on size) molybdenum after I realized just how easily they could have become infected, too.

Early the next morning, we heard that his wife had come down with the stomach virus. So, I took some molybdenum to her and then came home and asked my children every couple of hours if their stomachs hurt. Dd13 by midmorning reported that her stomach hurt, so I gave her more molybdenum (about 1000 mcg, if I recall correctly). Twice more during the day, her stomach hurt, so I gave her another dose of molybdenum each time. By the third time, she was reporting that the ache had moved down into her intestines. She slept through the night and never vomited. Whew.

I called the friend's wife afterward, and she reported that once she was able to get some molybdenum down, her vomiting ended. Double whew.

Saturday, December 16, 2017

Alexander Rybak

Our family is full of Alexander Rybak fangirls. Our children couldn't tell you the name of a Justin Bieber hit or Lady Gaga song (although they might know parodies of some of hers), but they can sing along with much of Rybak's music, including some of the Russian songs, which shows their great appreciation for him, for they don't speak Russian. Here's one of my favorites:



I'm a violinist but not remotely as good as he is. Here's another great song by him. He recorded it in Belarussian, Russian, and English. Even if you've never been to Europe, he can make a person wish they could see the skies he loves so well.


Friday, December 15, 2017

A bit more on angiogenesis and thymoquinone

Angiogenesis during pregnancy is crucial, for it is the forming of new blood vessels from existing ones. To create a placenta and a baby, this process must be able to go forth properly.

An overlooked dietary source of an angiogenesis inhibitor is thymoquinone (https://www.ncbi.nlm.nih.gov/pubmed/18644991, https://www.spandidos-publications.com/10.3892/or.2012.2165, https://www.sciencedirect.com/science/article/pii/S1567576916302053), one of the most active constituents of Nigella sativa (AKA black cumin, czarnuszka, black seed, etc.). (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387228/) In 2013, it was shown that thymoquinone has a potentially disruptive effect on embryonic development in the middle of rat pregnancy (http://www.tandfonline.com/doi/full/10.3109/01480545.2011.648326); specifically, thymoquinone caused fetal death and resorption:

Results showed that TQ [thymoquinone] induces maternal and embryonic toxicities in a dose- and time-dependent manner. With a dose of 50 mg/kg, treated rats experienced a significant decrease in maternal body weight and complete fetal resorption when the dose was given on day 11 of gestation. On the other hand, 46.2% of implants were resorbed and the viable fetuses showed no TQ-related malformations when the dose was given on day 14 of gestation. At a lower TQ dose of 35 mg/kg, maternal and embryonic toxicities were observed only when it was given on day 11 of gestation.


As in the rodent studies of thalidomide, thymoquinone does not appear to cause to cause any morphological abnormalities in rat fetuses. Just fetal resorption. This is striking to me because it resembles the only early indication that thalidomide is harmful to developing embryos. Thalidomide has a different effect on developing rodents than on humans. Thalidomide was initially approved for human use partly because the rodent tests done with it appeared to be showing that it was safe for developing embryos.

A 1962 study titled "Thalidomide and Congenital Abnormalities," by Victor Knapp, George Christie, and Mary Seller, all working in the UK, looked at the teratogenic effects of Thalidomide on rats, mice, and rabbits, and the study reported no abnormalities in the offspring of these animals after researchers had exposed the pregnant females to the drug. The authors noted that the study provided no grounds to think that drugs containing Thalidomide were safe for human use, and they argued that the only method guaranteed to safely deal with drugs of unknown teratogenicity would be to completely refrain from using them unless absolutely necessary. In 1963, Joseph A. DiPaolo, working in the US, discussed various birth defects found in mice fetuses whose mothers were fed Thalidomide daily, but he found only one kind of anamoly [sic] called fetal resorption, or the partial or complete dissolution of fetal tissues after some embryos had died in utero.

Black cumin is much praised by some Islamic researchers. (https://www.ncbi.nlm.nih.gov/pubmed/28603137https://www.ncbi.nlm.nih.gov/pubmed/26396361https://www.ncbi.nlm.nih.gov/pubmed/27247928) I think this is because they have a "hadith" (post-Quran saying attributed to Muhammed) in which Muhammed was reported to have said that black cumin is good for all diseases except death. 

Narrated Khalid bin Sa`d: We went out and Ghalib bin Abjar was accompanying us. He fell ill on the way and when we arrived at Medina he was still sick. Ibn Abi 'Atiq came to visit him and said to us, "Treat him with black cumin. Take five or seven seeds and crush them (mix the powder with oil) and drop the resulting mixture into both nostrils, for `Aisha has narrated to me that she heard the Prophet (ﷺ) saying, 'This black cumin is healing for all diseases except As-Sam.' Aisha said, 'What is As-Sam?' He said, 'Death."

https://sunnah.com/bukhari/76 (Might Khalid bin Sa'd, Aisha, or Ibn Abi 'Atiq have heard wrong or unintentionally exaggerated?)

It appears to me from the way some researchers in Islamic countries talk about black cumin, they seem frightened to admit that, like all medicinal substances, black cumin might have some negative side effects, too. Which is irrational. Now, I totally get where they're coming from. After all, in the middle of a "Wheat Belly" trend, I refuse to dump wheat because D&C 89 (the Mormon Word of Wisdom) says that wheat is "for man." But lots of LDS people who believe that D&C 89 is a revelation from God have celiac disease and so don't eat wheat. It's important to find out where a particular substance helps and where it harms in order to utilize it wisely and for optimal effects.

It's been repeatedly noted that Muslim cultures/countries tend to top the global charts for birth defects (http://english.alarabiya.net/en/life-style/healthy-living/2015/03/10/Saudis-unaware-of-high-birth-defect-rate-.html), including congenital blindness (http://jalili.co/covi/07_cbmena.htm) and deafness (https://link.springer.com/article/10.1007/s00439-001-0674-2?no-access=true), which were also results of thalidomide exposure during gestation (http://www.thalidomide.ca/recognition-of-thalidomide-defects/), interestingly enough. Researchers appear to almost unanimously conclude that consanguinity (marrying close relatives) is the main factor behind this higher rate of birth defects. (https://reproductive-health-journal.biomedcentral.com/articles/10.1186/1742-4755-6-17, http://www.journalrmc.com/volumes/2_Association%20of%20Consanguineous%20Marriages%20%20with%20Congenital%20Birth%20Defects%20(1).pdf) But what if the least secular Muslims--the ones marrying cousins despite all the data about the higher risk of the practice because clerics tell them that Muhammed's approval of cousin marriages 14 centuries ago makes it evil to question them now--are also using black cumin during pregnancy because of the hadith recommending it? What if the black cumin is contributing to birth defects, too? How would we ever tease out evidence of such an effect while both cousin marriage and black seed use are promoted within the hadith-accepting sects of Islam? Ideas?

Thursday, December 14, 2017

GDF15, "morning sickness," and angiogenesis

Last month, researchers at Cambridge announced that they had found a correlation between the protein GDF15 and nausea and vomiting in pregnancy. (http://www.newsweek.com/sick-pregnancy-protein-your-placenta-could-be-blame-723716) Here's the abstract from their prepublication paper:

Nausea and vomiting in pregnancy (NVP) affects 70-90% of all pregnant women, but its pathogenesis is unknown. Growth and Differentiation Factor 15 (GDF15), secreted from the trophoblast and decidual stromal cells, is present at high levels in the blood of pregnant women. The receptor for GDF15 has recently been identified and is specifically expressed in the hindbrain where it transmits aversive signals including nausea and conditioned taste aversion. We explored the relationship between GDF15 concentrations in maternal serum during pregnancy and self-reported NVP. In a study of 791 women from the Cambridge Baby Growth Study maternal GDF15 concentrations were higher in women who reported vomiting in the 2nd trimester (geometric mean: 11,670 pg/mL; 95% confidence interval 11,056-12,318) and were even higher in the eleven women who reported taking anti-emetics during pregnancy (13,376 (10,821-16,535) compared to those who reported no nausea or vomiting during pregnancy (10,657 (10,121-11,222); P=0.02 and P=0.04, respectively, adjusted for gestational age at sampling and maternal BMI). In conclusion serum GDF concentrations early in the second trimester are significantly and positively associated with second trimester vomiting and with maternal anti-emetic use. In the context of the recently revealed biology of GDF15 this data suggests that antagonism of GDF15 may have some potential for therapeutic benefit in NVP.

https://www.biorxiv.org/content/early/2017/11/17/221267.full.pdf+html

I am both delighted and worried by this paper, and the cause for both feelings is the same: GDF15 promotes (https://link.springer.com/article/10.1007/s11033-011-1182-7) and has an essential role in angiogenesis (https://www.ncbi.nlm.nih.gov/pubmed/28831101), the creation of new blood vessels from existing ones. Around 18 months ago, I published my hypothesis that sulfite, a metabolic product of endogenous H2S used in angiogenesis, is the primary culprit behind NVP and that molybdenum supplementation can help the body more quickly break down that sulfite to sulfate via sulfite oxidase.* (http://www.medical-hypotheses.com/article/S0306-9877(16)30098-6/fulltext) So naturally I'm very pleased to see this recent finding that connects an angiogenesis promoter to NVP. What worries me is the paper's suggestion that antagonism of GDF15 might be a therapy to treat NVP.

We do not want to interfere with angiogenesis during early pregnancy. That's exactly what went wrong with thalidomide. Thalidomide inhibits angiogenesis, leading to truncated limbs and other awful consequences.

I found the lead author's professional Facebook page and posted my appreciation of his findings and concern about the proposal to antagonize GDF15. I hope he takes it seriously despite my lack of biology credentials. Whether I have a piece of paper from the proper college is irrelevant to the copious evidence of the necessity of proper angiogenesis in pregnancy.

* And if you've been reading my blog, you know that molybdenum ended up surprising me by being good for more than just NVP!