Sulfite could be behind migraines, too

As noted in my last post, I recently published a theory of excess sulfite accumulation being behind nausea and vomiting in pregnancy (NPV) (online now at http://www.sciencedirect.com/science/article/pii/S0306987716300986).

It has so far proven very effective for myself and a friend to ameliorate nausea in pregnancy by avoiding sulfite compounds in/on food and increasing molybdenum intake. Molybdenum is used by the body in sulfite oxidase, an enzyme that catalyzes the conversion of toxic sulfite to excretable sulfate. But our bodies can only make so much sulfite oxidase, so it's important to limit intake of sulfites. Molybdenum isn't a "now eat whatever you want" cure.

As I was putting together this theory, I started seeing similarities between morning sickness and migraines, specifically

1) both are quite involved with hormones,

2) both appear to be associated with similar food intake, and 

3) they share similar patterns of gradual onset and varied duration and intensity.

I realized that just as sulfite accumulation in the gastrointestinal tract could lead to nausea and vomiting, similarly sulfite accumulation in the brain could lead to migraine headaches. The brain damage experienced over time from migraine headaches lends support to the idea that migraines are caused by a toxic chemical in the brain. Because of recent research on endogenous hydrogen sulfide, we now know that hydrogen sulfide--a catabolite of which is sulfite--is a neuromodulator in the brain. 

A friend in her early 40s has been suffering terribly from migraines and, realizing that that all her migraine medications only made her feel worse, weaned herself off of the medications. Then about 3 weeks ago I told her of my theory's possible application to migraines and gave her some capsules of a 500 mcg molybdenum supplement (it was this one). She informed me this week that she takes molybdenum when a migraine starts coming on, and the migraine goes away. She feels better now than she has for a while.

If someone suffers from migraines, I think avoiding heavily-sulfite-treated grapes and other sulfite-containing foods would be a very good idea. It might also be a good idea to look at whether one's molybdenum intake might be too low. Molybdenum is highest in pulses, some whole grains (especially barley and oats), and liver (I'm not a fan of long-term high liver intake, though, due to its high retinol content); molybdenum naturally occurs in milk, too, but it's mostly found in the cream, which in large amounts poses its own health-related risks.

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

+ Molybdenum - Sulfites = Less Morning Sickness

Here's the link to my published theory on "morning sickness," published online at the end of last week:

http://www.sciencedirect.com/science/article/pii/S0306987716300986

And here's the abstract if you don't want to follow the link:

Medical Hypotheses

Volume 95, October 2016, Pages 31–33

A novel treatment for “morning sickness”: Nausea of pregnancy could be induced by excess sulfite which molybdenum can help alleviate

Abstract

Nausea and vomiting of pregnancy (NVP) remains difficult to treat. Last century, thalidomide was used to alleviate NVP, but it caused teratogenesis by interfering with angiogenesis. The gasotransmitters hydrogen sulfide (H2S) and nitric oxide are mutually dependent on each other for their angiogenesis-related functions. Pregnancy-related requirements for increased endogenous H2S could create a temporary excess of sulfite, an H2S catabolite, which is toxic and can induce nausea. Sulfite oxidase, a molybdenum-containing enzyme, catalyzes oxidation of sulfite to sulfate, which can then be excreted or reused by the body. Supplementation with molybdenum should facilitate enhanced sulfite oxidase activity, thus lowering gestationally-elevated sulfite levels in the gastrointestinal tract and easing NVP.

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

Excess Endogenous Hydrogen Cyanide and Epileptic Seizures

I have an acquaintance with epilepsy (i.e., repeated seizure disorder), a consequence of encephalitis around eight years ago. Because of his illness--which has yet to respond to the usual medications--I looked into epilepsy over the past couple of months to see if there was anything diet-related that he could do to lessen his seizures. This is a result of that research. (If it's wrong, please let me know how and where, and I'll note that or scrap the hypothesis entirely.):

Here is a description of grand mal seizures (also known as generalized tonic-clonic seizures), a common manifestation of epilepsy:

Generalised Tonic Clonic Seizures Generalised tonic-clonic seizures are sometimes called a fit or convulsion. They are the most universally recognised seizures.
They often begin with a sudden cry. If standing, the person will fall to the ground and lose consciousness.
The body becomes quite stiff (tonic) shortly followed by jerking of the muscles (clonic). Breathing is shallow or temporarily suspended causing the lips and complexion to look grey/bluish. Saliva (sometimes also blood if the tongue has been bitten) may come out of the mouth, and there may be loss of bladder control.
The seizure usually lasts approximately two minutes and is followed by a period of confusion, agitation and extreme tiredness. Headaches and soreness are also common afterwards.

And here is the CDC's description of what happens in a case of poisoning by sodium cyanide, which releases hydrogen cyanide gas:

• EFFECTS OF SHORT-TERM (LESS THAN 8-HOURS) EXPOSURE: Early symptoms of cyanide poisoning include lightheadedness, giddiness, rapid breathing, nausea, vomiting (emesis), feeling of neck constriction and suffocation, confusion, restlessness, and anxiety. Accumulation of fluid in the lungs (pulmonary edema) may complicate severe intoxications. Rapid breathing is soon followed by respiratory depression/respiratory arrest (cessation of breathing). Severe cyanide poisonings progress to stupor, coma, muscle spasms (in which head, neck, and spine are arched backwards), convulsions (seizures), fixed and dilated pupils, and death. The CNS is the most sensitive target organ of cyanide poisoning. Cardiovascular effects require higher cyanide doses than those necessary for CNS effects. In serious poisonings, the skin is cold, clammy, and diaphoretic. Blue discoloration of the skin may be a late finding. Severe signs of oxygen deprivation in the absence of blue discoloration of the skin suggest cyanide poisoning.

INHALATION EXPOSURE:

• Mild to moderate: CNS effects: headache, confusion, anxiety, dizziness, weakness (malaise), and loss of consciousness. Cardiovascular effects: palpitations. Respiratory effects: respiratory tract irritation, difficulty breathing or shortness of breath (dyspnea), and transient increase in rate and depth of breathing (hyperpnea). GI effects: nausea and vomiting (emesis).

• Severe: CNS effects: coma, seizures, and dilated pupils (mydriasis). Cardiovascular effects: shock, abnormal or disordered heart rhythms (dysrhythmias), critically low blood pressure, and cardiac arrest. Respiratory effects: abnormally rapid, followed by abnormally slow respirations; accumulation of fluid in the lungs (pulmonary edema); and respiratory arrest. Eye effects: dilated pupils, inflammation of the surface of the eye, and temporary blindness.

I highlighted the parts of these two descriptions that appear to overlap. Whether there are dilated pupils (mydriasis) in a grand mal seizure isn't clear, for apparently the eyes roll back into the head during such a seizure. Also, I couldn't find much information about whether cyanide poisoning causes a sudden cry; it can cause gasping, though, when injected into the brainstems of cats (the study cats were anesthetized), and abrupt onset gasping is sometimes seen in severe cyanide poisoning cases.

Why am I pointing out these similarities? Our bodies make endogenous hydrogen cyanide ("HCN"). Yes, the same poisonous gas used in the Nazi death camps. HCN is a little molecule--just one hydrogen, one carbon, and one nitrogen together in a linear bond--so it's not surprising that it would be a product of some of the many chemical reactions that occur in a body. When dissolved in water, HCN releases a cyanide ion that halts cellular respiration. Fortunately we have internal methods of detoxifying cyanide, the primary mechanism being the rhodanese-catalyzed conversion of cyanide to thiocyanate; these methods can, however, be overwhelmed by acute cyanide poisoning.

Cyanide is generated in neuronal tissue. So could epileptic seizures be the result of cyanide poisoning, localized in the brain, that is caused by the body’s own production of hydrogen cyanide? That is my hypothesis.

A seizure is defined as "a temporary dysfunction of the brain consisting of an excessive synchronous neuronal discharge." Cyanide appears to dramatically (by 300%) increase the spontaneous discharge of a type of neuron found in the brainstem, which is where grand mal seizures are suspected to originate. A 1997 study documented that endogenous cyanide generation in neuronal tissue was increased significantly by mu opiate receptor agonists (the 1997 study was confirmed per this 2004 article), and per this 2012 study mu opiate receptors are known to be involved in seizures and are enhanced in the hippocampus (located in the medial temporal lobe) of patients with drug-resistant temporal lobe epilepsy (this 1988 study also seems to connect mu opiate receptors with epileptic seizures). And this might be too big a stretch, but a very recent study found that 3-MST, an enzyme which helps detoxify cyanide and is required for biosynthesis of thiosulfate (which rhodanese uses to convert cyanide into thiocyanate), was mainly located in living, not dead, neurons after traumatic brain injury (TBI), which suggests the possibility that cyanide accumulation in a TBI-caused lesion might be implicated in post-TBI epilepsy.

If this cyanide-epilepsy theory has merit, then does it point to something a person can do diet-wise to decrease the risk of experiencing seizures? I haven't come across any medical websites citing trigger foods that are clearly associated with the occurrence of epileptic grand mal seizures, although such websites do sometimes warn against caffeine, especially if it interferes with sleep patterns. Cyanide is found in several foods, including almonds, soy, cereal grains, tapioca (also known as cassava or yuca), lima beans, cherry juice, and bamboo shoots. Interestingly, a study last year in Ghana linked cassava consumption to active convulsive epilepsy. Also, a couple years ago a UW-A seizure researcher found that replacing soy protein mouse chow with a casein-based chow resulted in a 50% decrease in seizures; she suspected the component of soy that might be causing the increased seizures is phytoestrogens, but perhaps cyanide could be partially to blame. Further, since cereal grains contain cyanide, perhaps avoiding them is one reason why ketogenic diets have been observed to alleviate epilepsy. I therefore conclude that decreasing consumption of cyanide-containing foods will likely help diminish the occurrence of epileptic seizures.

Another thing that might be helpful--if this theory has merit, of course--is taking multivitamins that contain the hydroxocobalamin form of B12 instead of the cyanocobalamin form of B12 and avoiding cyanocobalamin-fortified foods. Rather than ingest extra cyanide, it makes sense instead to supplement with hydroxocobalamin, for hydroxocobalamin is a form of B12 that just happens to be an approved, effective treatment for cyanide poisoning.

More on chloride ions and allergies

My Aged P ("aged parent") was here visiting last night. He is a retired family practice physician, so I told him about my recent research on retinol metabolism pathways, immune tolerance, and diet differences that appear implicated in various undesirable immune and autoimmune reactions. Specifically, we discussed the Israeli peanut snack, Bamba and its ability to help keep at-risk children from developing peanut allergies. As I talked about the chloride ions provided by the dissolved salt in Bamba, my father pointed out that people already have chloride ions in their stomachs because gastric acid's most important constituent is hydrochloric acid, which dissociates into hydronium and chloride ions.

Not having gone to medical school, I appreciated his insight. And then I thought, well, then people with low hydrochloric acid, i.e., "hypochlorhydria," should be more likely to suffer from food allergies than people with adequate stomach acid. I did a little research, and found that over 80 years ago, researchers were noticing an association between low gastric acidity and various allergic conditions. Recent research still finds this association. For example, a study published three years ago found that children with GERD who were given gastric acid suppressing medications were more likely to develop food allergies than children with GERD who were not given gastric acid suppressing medications.

I grew up hearing from TV ads that stomach acid is a bad thing that must be neutralized. I don't think that's generally true. It's bad to have the acid get into the esophagus--we call that "heartburn"--but stomach acid performs many important functions, including perhaps helping our bodies not become allergic to foods.

Another publication

It's been months since I submitted the article to the journal, but that's apparently how long it takes to get peer reviews back. My theory about how to alleviate morning sickness has been approved for publication. When it becomes available online, I'll post a link to it together with a summary of the theory.

It has begun

For years, I've told my husband, "Our girls will have crushes on boys starting as early as fourth or fifth grade. They'll dream about them. They'll write their initials plus the boys' initials in secretive places. It's just part of being a girl."

And my husband with a glower would say, "We're moving three hours away from the nearest boys! Three hours!"

I would laugh and hope he wasn't even a tiny bit serious. I love my home, and I don't want to move to Montana or Alaska.

Today my oldest (dd11) was pulling out school notebooks from last year to get ready for the new school year and showing them to me when I noticed on the last page of a notebook an elaborate drawing pairing her first initial with a letter that doesn't match anyone in the family. I called attention to it, asking whose it was, and she blushed and ran away with her notebook. Hello, puberty, I don't know if we adults are ready for you yet.

The salt of the earth...might help prevent allergies from developing?

There is a much lower rate of peanut allergies in children in Israel than is seen in genetically similar Jewish children in the USA and UK. The main theory to explain the difference is early exposure to peanuts in the form of a favorite snack food called Bamba.

A study was done in the UK where some parents were instructed to give their babies peanuts, preferably in the form of Bamba snacks, 3 times a week, while other parents were instructed to have their babies avoid peanuts.

Of the children who avoided peanut, 17% developed peanut allergy by the age of 5 years. Remarkably, only 3% of the children who were randomized to eating the peanut snack developed allergy by age 5.   Therefore, in high-risk infants, sustained consumption of peanut beginning in the first 11 months of life was highly effective in preventing the development of peanut allergy.
“For decades allergists have been recommending that young infants avoid consuming allergenic foods such as peanut to prevent food allergies,” notes Professor Lack, the lead investigator for the LEAP study. “Our findings suggest that this advice was incorrect and may have contributed to the rise in the peanut and other food allergies.”

http://www.leapstudy.com/leap-study-results#.V6uC8VQrIdU

I don't think it's just the early exposure to peanuts. Many parents can tell you how their children developed allergies to foods given in infancy. I think it's specifically the ingredients of Bamba: peanuts, corn, palm oil, and salt. 

As discussed below, food allergies appear more likely to develop when we do not promote optimal expression of an enzyme called RALDH2. Optimal expression of RALDH2 is key to developing oral tolerance of foods. This enzyme is activated by magnesium chloride. Bamba includes both magnesium (in peanuts and pulverized corn) and chloride (in table salt, i.e., sodium chloride). Both sodium chloride and magnesium chloride are ionic compounds that dissolve easily and dissociate in water, raising the possibility that Bamba, in the process of being digested, essentially provides dissociated magnesium chloride. Thus every time an Israeli child eats Bamba, they could be activating RALDH2 and promoting oral tolerance of peanuts. Osem, the maker of Bamba, recently promised to lower the salt content in Bamba by 15% over the next 2 years. It will be interesting to see if Israeli children start developing more peanut allergies over the next 2 years, as well.

One allergy that is common in Israeli children is sesame, which they eat in halvah (a sweet snack) and tahini (sesame paste used in hummus). Sesame contains a small amount of Vitamin E, but sesame lignans enhance Vitamin E activity. From the recipes and products I'm finding on the internet, Israeli halvah is typically just sesame seeds and sweeteners with no added salt. When tahini is used in hummus, it is combined with salt, but hummus also contains lemon juice, which if bottled likely has added lemon oil, which means it has citral, a RALDH2 inhibitor. If I were an Israeli parent trying to head off sesame allergies, I think I'd begin putting a little Dead Sea salt--it's half magnesium chloride--into my halvah and check my lemon juice to be sure I'm not putting extra lemon oil into my hummus.

So now I'll raise the question that would get me shunned in many nutritionist circles: Is it possible that the low-sodium push is partly responsible for the increase in allergies? And perhaps autoimmune diseases? Good thing I have no professional career in the field to be damaged. :)

Anecdotes about developing quinoa allergies

As seen in the preceding post, I've got a theory about what might be behind the rise in food allergies. 

I was surprised to learn today that quinoa is considered a low-allergenic food, despite it being a good source of tocopherols (Vitamin E) like wheat. According to my theory, quinoa should be likely to trigger an allergy when eaten together with Vitamin C and beta carotene (non-meat form of Vitamin A), especially if a lemony oil is also eaten. 

I was fascinated to come across this blog post and see that quinoa allergies have been triggered under many conditions that accord with my theory. The original poster developed a quinoa allergy after eating a quinoa/bean/raw pepper dish; raw pepper is a good source of both beta carotene and Vitamin C. Then a commenter reports developing the allergy upon eating quinoa with turkey after Thanksgiving Dinner; while the comment doesn't say whether sweet potatoes--a very good source of beta carotene and Vitamin C--were eaten as part of the Thanksgiving Dinner, they're considered a standard part of a US Thanksgiving meal. Another commenter mentions ending up in the hospital overnight with a horrific allergic reaction (memory loss can result from an allergic reaction?!) after eating a quinoa-stuffed pepper. Another commenter reports starting to notice a quinoa allergy when eating quinoa with tomatoes, which contain the entire triad mentioned below, Vitamins A, C, and E! (Maybe this vitamin richness of tomatoes is why my mother-in-law was allergic to tomatoes for a decade or so, although she seems to be over it now.) A later commenter links developing an allergy to quinoa to eating it in a Mexican salad with tomato and lime juice (citral!). 

The only comment not connecting development of a quinoa allergy to a food item in alignment with my theory is from a woman who was eating it with rice milk, but she does mention that she was breastfeeding at the time, so maybe she was taking postnatal multivitamins steadily. I know that I'm far more attentive to my vitamin needs when I'm pregnant or breastfeeding.

I wonder if quinoa just got labeled as unlikely to be allergenic because it used to be primarily eaten boiled in water or chicken stock, the way it has been traditionally eaten in the Andes. There is not a lot of Vitamin A and C in porridge or chicken soup. (Also, both the porridge and soup are likely to have added salt, but more on the salt aspect in a later post....) Will we see an increase in quinoa allergies as people going gluten-free eat it regularly in their bread, crackers, salads, tabouleh, etc.?

Celiac & Food Allergies Connected to Retinol Pathways

The only allergy I suffer from is one to cat dander, and considering what my children do to the house and furniture already, I'm probably better off without a cat. But I know many people with food allergies and/or celiac disease. They are all conscientious people who try to eat healthily. Many people are wondering what is causing the rise in celiac disease, an autoimmune disease where the body damages itself after ingestion of gluten and which is related to certain genes and can be triggered by various events, including childbirth, pregnancy, viral infections, and stress. I also wonder, hence this hypothesis.

On p. 236 of a 2013 review of celiac disease (CD) epidemiology, there is a map that shows graphically the reported prevalence of CD by country. Two countries jumped out at me: Finland, with a high prevalence (more than 1 in 100), and Estonia, with a significantly lower prevalence (and apparently not increasing, per this study). Genetically, the Finns and Estonians are reported to be very similar. Their traditional cuisines and geographical situations are also very similar. Why would they have dramatically different rates of developing celiac disease?

The first difference I found between Finland and Estonia concerned Vitamin D fortification. Estonia does not fortify dairy products with Vitamin D at all; Finland puts Vitamin D not just in milk, but also other food products. Also, Estonians, unlike Scandinavia in general, appear to not go in for cod-liver oil or other Vitamin D supplements.

Why would differences in Vitamin D supplementation have an effect on who develops CD? Our bodies make molecules called Vitamin D receptors (VDRs) that are also important in maintaining the health and barrier function of the intestines (see this, this, this, this, this, and this). Perhaps by adding Vitamin D to our milk we are overexposing our intestines to Vitamin D—most Vitamin D is supposed to come from our skin’s production of it, not from our food—and causing our bodies, in line with homeostasis principles, to decrease expression of VDRs in our intestines over time. Something similar does appear to happen with excess folic acid ingestion and folate receptors in the intestines, but there is only one study out there hinting that this might happen with Vitamin D and VDRs.

This Vitamin D receptor hypothesis might be helpful in explaining intestinal permeability problems, but it doesn’t explain the increase in CD seen in many other countries that don’t fortify with Vitamin D or take cod liver oil. As I looked further into CD incidence, I started to see a pattern of correlation between dairy intake and CD. Milkfat is a rich source of Vitamin A, which is also high (rather dangerously so) in cod liver oil. In the US, lowfat and skim milk are now fortified with Vitamin A to supply a higher amount than naturally occurs in whole milk.

Why would high Vitamin A intake cause a hyperimmune reaction to ingested gluten? Well, first off, it’s necessary to point out that CD apparently involves hyperimmune reactions to more than just gluten; one study found that half of CD patients had the same reaction to cow’s milk protein as they did to gluten, indicating that the immune system’s dysfunction is the culprit, not an unavoidable genetic incompatibility with gluten. After all, people typically eat wheat fairly happily before CD is triggered. That hyperimmune reaction, it turns out, is connected to Vitamin A-related processes, for signaling related to retinoic acid—a metabolite of retinol, the storage form of Vitamin A—is a “keystone in the development of oral tolerance” (oral tolerance means “the capacity of the immune system to recognize substances taken in through the digestive system and to weaken or suppress the immune response to them”).

At this point, I feel I must widen the discussion a bit to include all hyperimmune reactions to dietary gluten and other highly allergenic foods, although I will still occasionally address CD specifically.

Several enzymes are involved in transforming retinol into retinoic acid. Retinol is first transformed into retinal, catalyzed by retinol dehydrogenases and alcohol dehydrogenases. Retinal is then transformed into retinoic acid, catalyzed by retinal dehydrogenases (RALDHs) and retinal oxidases. RALDH2, one of the RALDHs, apparently needs to be optimally expressed in order for intestinal dendritic cells to properly carry out their oral tolerance function. (This is a very complex field of study that I won’t pretend to fully comprehend or adequately summarize, so I’ll direct you here, here, here, here, here, here, here, here, here, and here for more information on the subject.) But retinoic acid, the product of RALDH2, can make inflammation worse, not better. This study, in particular, is interesting in that it finds that retinoic acid promotes an inflammatory immune response to dietary antigens in connection with a cytokine that is greatly upregulated in the gut of CD patients; to me, this indicates that 1) retinoic acid might be interfering with RALDH2 expression in a way that negatively affects oral tolerance (it is not unusual for the product of an enzyme to inhibit an enzyme through a process called feedback inhibition), and 2) RALDH2 might have an important immunity-related function besides catalyzing the transformation of retinal into retinoic acid.

My key point in the paragraph above is that we want to optimize expression of RALDH2 in order to avoid hyperimmune reactions to our food. I have come across four ways to do that:

1)      Promote RALDH2 activity with magnesium chloride, which has been found to activate RALDH2.

2)      Don’t inhibit RALDH2 activity with too much citral, which has been found to inhibit RALDH2.

3)      Be cautious about consuming common dietary allergens in conjunction with elevated endogenous or exogenous prostaglandin E2, for prostaglandin E2 inhibits RALDH expression.

4)      Avoid excess retinoic acid by not ingesting too much Vitamin A. We have multiple metabolic pathways that make retinoic acid out of forms of Vitamin A, and there is evidence indicating that retinoic acid and other retinoids suppress expression of RALDH2. Retinoic acid also suppresses IL-12, which is apparently absent during allergic responses, per this study.

#1 Magnesium Chloride –

Magnesium Chloride (MgCl2) is a salt that naturally occurs in the ocean and briny lakes, most notably the Dead Sea, the salt content of which is fully half MgCl2. Until recent times, the salt people ingested typically contained some magnesium chloride, but we now commonly consume nearly pure sodium chloride as our regular table salt. Perhaps, in light of MgCl2’s ability to activate RALDH2, this shift to pure sodium chloride has been detrimental to our ability to orally tolerate some common allergens. It is interesting to note that Japanese people still consume magnesium chloride widely, both in sea salt and as a tofu coagulant, and that celiac disease is nearly unknown in Japan even though Japanese cuisine today includes regular consumption of wheat noodles. There is at least one study finding an apparently protective role for magnesium in acute allergic reactions. Also, a little magnesium chloride looks like it might help bring down abnormally high triglycerides, so it seems a good idea to sometimes use sea salt or drink mineral water containing magnesium chloride. The push to lower salt intake is just to lower sodium intake, not all forms of culinary salt.

#2 Citral –

Citral is present in many lemony oils—per wikipedia, in lemon myrtle (90-98%), Litsea citrata (90%), Litsea cubeba (70-85%), lemongrass (65-85%), lemon tea-tree (70-80%), Ocimum gratissimum (66.5%), Lindera citriodora (about 65%), Calypranthes parriculata (about 62%), petitgrain (36%), lemon verbena (30-35%), lemon ironbark (26%), lemon balm (11%), lime rind (6-9%), lemon rind (2-5%), and orange rind—and used as an additive in flavorings (including as a “natural flavor” in soda pop) and perfumes. Citral is recognized to be a highly sensitizing substance.

#3 Prostaglandin E2 –

In light of prostaglandin E2’s connection to childbirth and fever initiation, it is intriguing that it inhibits RALDH2. Birth and viral infections are both associated with onset of CD. Perhaps we really should “starve a fever” a bit, at least at the beginning. And it probably wouldn’t hurt to give women who are genetically-susceptible to CD a hypoallergenic diet around childbirth, especially if prostaglandin E2 (Cervidil) is being used to soften the cervix.

#4 Excess Vitamin A –

And we end back on Vitamin A, which is easy to overdose on over the long-term because it is a fat-soluble vitamin that our bodies store. A mere teaspoon of cod liver oil contains the daily RDA of Vitamin A. Beef liver is even higher in Vitamin A, and it does appear to be a significant part of the cuisine in many places that are notable for CD prevalence.

There are 8 major food allergens—shellfish, eggs, cow milk, fish, peanuts, tree nuts, wheat, and soy—the first four of which are amongst the highest food sources of retinol (pre-formed Vitamin A, found in animal products). Retinol is what the body breaks down in the enzymatic pathway that includes the RALDH enyzmes.

The other four major allergens—at least if one means wheat to include whole wheat, which still has the germ—are all sources of Vitamin E (tocopherols), which appear to increase the synthesis of retinal and retinoic acid from beta-carotene, especially if there is also Vitamin C present. If someone is eating lots of beta-carotene (orange and yellow fruits and vegetables) and Vitamin C along with whole wheat, soy, peanuts, or tree nuts, that appears to have a similar effect on retinol metabolism as eating animal products that are high in retinol. Unfairly, it would thus appear that many people trying to eat healthily and get all their vitamins regularly are more likely to develop food allergies from RALDH disturbances than someone who consumes a diet that is sometimes deficient in Vitamin A, C, or E.

In support of a retinol-celiac link, I note that China has long eaten wheat in noodles, dumplings, and buns. Yet as China grows wealthier and increases its intake of dairy and other animal products, it is seeing an increase in CD.

Even if Vitamin A doesn’t turn out to be associated with CD, it’s always a good idea to keep pre-formed Vitamin A (i.e., retinol, not beta-carotene) intake within reasonable bounds. Oh, and definitely always consume it with fat, for consuming too much Vitamin A without dietary fatty acids leads to excessive production of retinol, retinoic acid, and other retinoids (the linked article describes this finding). US-sold skim milk with 12% of the RDA of Vitamin A in one cup doesn’t seem like such a great idea.

When did that happen to my blog?

I promise, this is a blog about education/geography/books/basic life of a homeschooling mom who has had the chance to live in several parts of the world. When did it turn into a nutrition/biomedical studies blog? (I take one little online course....) I have a couple more theories I've been working on (food allergies and seizure disorders), but I think I'm mostly done. After all, school starts up again in less than a month!

In the meantime, I need to order math books for my children, I'm learning Arabic (one line a night, but I'm already starting to recognize some words), my favorite fun reads for the summer have been books by Traci Hunter Abramson, and life has been great this summer, as we've learned about Bangladesh, Japan, Austria, Chile, and Senegal. The best part of our country studies is having a reason to invite people to our home to tell about their countries or countries they lived in; they love revisiting their memories and sharing them with us, and we all feel happier as we learn together and make friendships warmer.

Botox and depression

That last post was pretty technical. Time to lighten it up a bit with a fun theory I just came up with yesterday after a friend asked me to send her any recent studies connecting depression/anxiety with nutrition.

A few weeks after receiving botox treatment for wrinkles, around half of patients find relief from depression. (See https://www.ncbi.nlm.nih.gov/pubmed/24910934.) The obvious conclusion is they're simply happier with how they look. But what if it's more than that?

#1 - Botox suppresses the release of acetylcholine.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1192367/

#2 – Nicotinic acetylcholine receptors (nAChRs) respond to acetylcholine. https://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptor

#3 -  nAChRs in the brain can become desensitized after repeated exposure to stimulants. http://web.as.uky.edu/Biology/faculty/cooper/Bio401G/nicotineDesen.pdf

#4 - Recent drug research on new antidepressants has been targeting nAChRs: http://www.hindawi.com/journals/tswj/2012/104105/

So here's the basic theory:

We in the west eat a large amount of choline-rich food, so we can easily synthesize lots of acetylcholine. The constant exposure to plentiful acetylcholine in conjunction with other internal and external stimulators of nAChRs can result in desensitization of the nicotinic acetylcholine receptors in our brains, dysfunction of which receptors is associated with depression. Botox allows a "reboot" of the system by cutting the acetylcholine supply for a while, and the nAChRs become more sensitive again.

And here's how to test it (beside getting botox treatments): Go on a low-choline diet (unless you're pregnant) for a 3-4 days, during which it would probably be good to also avoid anything that would mess with nAChRs (esp. nicotine, alcohol, and recreational drugs). Here’s a link to the choline content of foods. See if you feel different a couple weeks later. Don't do the low-choline diet for an extended period, though. We need choline, just maybe not quite as constantly as we get it.

Perhaps the non-constant supply of choline-rich animal products (which are relatively expensive) in the diet of people in poor countries is part of the reason why it is sometimes found that rates of depression are higher in richer countries. Also intriguing is the connection between gardening (soil is full of the bacteria that makes botox) and less severe depression.

Carbon monoxide and restless legs syndrome (RLS)

As part of the research I've been doing in nutrition, I have come across studies and information giving rise to a theory in a very different area. Here's the theory:

Restless legs syndrome (RLS) appears to possibly be caused by carbon monoxide buildup in leg muscles. Here's why I think that could be the case:

1) Everyone's body makes endogenous carbon monoxide in small amounts. The endogenous carbon monoxide is a product of the breakdown of heme, a cofactor containing iron that is found primarily in animal products.
2) There appears to be a weak association between a heme oxygenase (which produces carbon monoxide) gene and RLS.
3) When we rest in a horizontal position, we are lowering arterial O2 (oxygen) pressure in the legs, which can cause more carbon monoxide to move from blood to the muscles. This effect should be even more pronounced during pregnancy due to the temporarily increased weight on the legs when standing; pregnancy is associated with increased risk of RLS. Compression stockings would help keep arterial pressure high; many RLS sufferers find that using compression stockings lessens their symptoms.
4) Carbon monoxide binds to myoglobin--"The oxygen carrying and storage protein of muscle, resembling hemoglobin but containing only one subunit and one heme as part of the molecule (rather than the four of hemoglobin), and with a molecular weight approximately one quarter that of hemoglobin," per an online medical dictionary--in the muscles. Thus, those who are already deficient in iron would tend to suffer more from higher levels of carbon monoxide interfering with myoglobin in the muscles. RLS has long been found associated with low stores of iron in the body.
5) The primary (and almost only) treatment for carbon monoxide poisoning is oxygen therapy. Peripheral hypoxia in the legs is associated and correlated in degree with RLS.
6) The most well-known symptom related to RLS is involuntary movement of the leg muscles. This movement could be the body trying to get more oxygen to the leg muscles in order to alleviate carbon monoxide buildup in the legs. Moving muscles take in more oxygen than resting ones.
7) Severe RLS and ischemic stroke are correlated. Carbon monoxide poisoning also correlates with an increased risk of ischemic stroke. This is a point in support of the hypothesis that endogenous carbon monoxide poisoning is behind RLS.
8) Dopamine agonists lessen RLS symptoms. Dopamine is also used to increase arterial pressure in patients with hypotension (low blood pressure). This is another point in support of the hypothesis, for increasing arterial pressure can be expected to help prevent the movement of carbon monoxide from blood into muscles.

Does my theory point to ways to treat RLS? I see a few, many of which have already been studied and shown positive effects:

• Increase oxygen inhalation at night. RLS is associated with reduced oxygen saturation and sleep-related breathing disorders.
• Look into ways to increase arterial pressure at night. Obviously, compression stockings can help do that. Also, progressive exercise programs that increase overall strength help with RLS, perhaps because having stronger cardiac and rib-cage-connected muscles increases arterial pressure and/or oxygen inhalation.
• Massage leg muscles. It can contribute to an increase in muscle blood volume. 
• Dopamine agonists, as mentioned above in #8.
• Don't be deficient in iron.
• Don't over-consume heme, a form of iron from animal products that is the primary source of endogenous carbon monoxide.
• Don't be deficient in vitamin E, which in the form of d, alpha-tocopheryl acetate, appears to relieve RLS leg cramps. I suspect this is partially due to alpha-tocopherol's inhibition of lipid peroxidation, which results in production of endogenous carbon monoxide.
• Perhaps acizol, a new zinc-containing medication for acute carbon monoxide poisoning, would be helpful for RLS. No research has been done on this, though.
• Hydroxocobalamin combined with Vitamin C shows promise as a treatment for carbon monoxide poisoning, per a rat study published last year. If carbon monoxide is connected to RLS, then hydroxocobalamin and Vitamin C supplements together might help with RLS.

Cyanocobalamin - a very poor choice, part 3

Some researchers feel that cyanocobalamin is probably just as good a B12 supplement as other forms of cobalamin. Others prefer methylcobalamin and hydroxocobalamin to cyanocobalamin for purposes of preventing dementia and stroke.

Dr. Dale Bredesen, a doctor and researcher in California, made the news recently for reversing cognitive decline in some Alzheimer's patients. He reported similar results in 2014 in the journal Aging. The full text of the 2014 article lists the details of his treatment protocol in Table 1:

Table 1 - Therapeutic System 1.0

Goal	Rationale and References
Optimize diet: minimize simple CHO, minimize inflammation. Enhance autophagy, ketogenesis Reduce stress Optimize sleep Exercise Brain stimulation Homocysteine under 7 Serum B12 over 500 Etc.*	Patients given choice of several low glycemic, low inflammatory, low grain diets. Fast 12 hr each night, including 3 hr prior to bedtime. Personalized—yoga or meditation or music, etc. 8 hr sleep per night; melatonin 0.5mg po qhs; Trp 500mg po 3x/wk if awakening. Exclude sleep apnea. 30-60′ per day, 4-6 days/wk Posit or related Me-B12, MTHF, P5P; TMG if necessary Me-B12 Etc.*

*Full table found online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221920/table/T1/.

Notice the use of methylcobalamin ("Me-B12") both to lower homocysteine and to increase the serum B12 level. Dr. Bredesen is getting results in preventing and reversing dementia, and he's using methylcobalamin as part of his treatment strategy. Why would I use a form of B12 that is tightly bound together, i.e., cyanocobalamin, when methylcobalamin appears to help prevent dementia?

Diet and obsessive thoughts

I have an Aspberger's nephew who exhibits the same tendency to fixate as his father. His father's fixations have been terrible for family relationships for the past few years, and the son really, really doesn't want to fixate, too. So I've been delving into the PubMed database for findings related to obsessive thoughts.

The research repeatedly shows apparent connections between lower levels of GABA & GABA receptors and OCD. See this, this, this, this, this, and this. The GABA(A) receptor is decreased when homocysteine is elevated (which fits with MTHFR defects being associated with autism, for MTHFR defects negatively impact conversion of homocysteine to methionine). Myo-inositol has been shown to help protect subunits of GABA(A) receptors in the hippocampus, and some people on Amazon are reporting that it helps them with OCD thoughts. 

The research thus supports a two-pronged dietary approach to lessening fixations that consists of 

• supporting homocysteine conversion by making sure to consume enough betaine, zinc, B12 (but not the cyanocobalamin form), and folate (definitely avoid folic acid, though; too much of it apparently causes pseudo-MTHFR deficiencies)
• protecting GABA(A) receptors from internal or external antagonists by consuming enough myo-inositol (it seems prudent to limit caffeine consumption, as caffeine appears to interfere with at least one inositol-related function)

What we eat can't change our genetics, but it definitely affects our phenotypes. Fresh fruits and vegetables, whole grains, and moderate intake of animal products (at least after childhood--babies need milk!), combined with avoidance of excess intake of anything, keep popping up as keys to long-term health.

Skin care and manganese

I've become a fan of barley water recently. It is made by boiling a little barley in water for a while until the barley splits and all its soluble fiber and nutrients start dissolving into the water. And barley has a lot of soluble fiber and helpful nutrients! (And for the LDS people out there, I would add that barley is the only beverage grain approvingly mentioned by name in D&C 89.)

In looking for news articles mentioning barley water, I came across one saying that the Queen of England reportedly drank it everyday for her complexion. She really does have a remarkably good complexion for her age. Why would barley water help with skin? It was a traditional acne remedy in the British Isles; what component(s) of it might have been helping acne sufferers?

Acne is correlated with the presence of androgens. See this, this, and this. Apparently, androgens stimulate production of sebum, an oily secretion made in our skin pores. But there are substances that can partially inhibit production of androgens, such as the ones mentioned in this study abstract:

The effects of various calcium-channel blockers on androgen production by collagenase-dispersed mouse testicular interstitial cells were investigated. Cobalt caused a dose-dependent inhibition of the maximum rate of luteinizing hormone (LH)-stimulated androgen production without altering the concentration of LH required for half maximum stimulation (EC50). Nickel and manganese also inhibited LH-stimulated steroidogenesis but were less potent than cobalt. The major site at which cobalt treatment inhibited steroidogenesis was beyond cAMP formation and before 3 beta-hydroxysteroid dehydrogenase. This conclusion was based on the observation that cobalt inhibited dibutyryl cAMP-stimulated androgen production but did not affect protein synthesis and pregnenolone-supported androgen production. Androgen production was unaffected by the organic calcium-channel blockers verapamil and the (+) and (-) enantiomers of D600 at concentrations less than 0.1 mM. At a concentration of 0.1 mM the organic calcium-channel blockers inhibited LH- and dibutyryl cAMP-stimulated androgen production. Unlike cobalt, the organic calcium-channel blockers also inhibited pregnenolone-supported androgen production and reduced the rate of protein synthesis. Similarities between the effects of cobalt in the present study and previous reports of the effects of reduced extracellular calcium concentrations on androgen production suggest that cobalt inhibits androgen production as a result of its ability to block calcium influx. The calcium channels involved in the steroidogenic process appear, however, to be relatively insensitive to the organic calcium-channel blockers.

Two things jump out at me from these findings and conclusions:

1) Blocking influx of calcium might inhibit androgen production in some cells. Perhaps this would in part explain the recurring observations of high dairy intake and acne correlation. See this, this, this, this, this, this, and this. Dairy products are rich natural sources of calcium.

2) Cobalt, nickel, and manganese can inhibit androgen production. I have a nickel allergy, which is quite common, and a little research on cobalt quickly convinced me that I don't want to mess around with it as a supplement.

But manganese...now there's a lead. In small amounts (and small amounts only), manganese is necessary for our bodies. And it is highest in two foods: clove (the spice) and oats. Barley is also a very good source of manganese. Queen Elizabeth II, I salute you for your regular consumption of barley water, which I'm sure provides you with a steady supply of manganese.

Do you know how long oats have been used in skin care? One personal care website claims oats have been used for skin care for 4000 years. The skin and hair care company Aveeno takes its name from the Latin name for oats, avena sativa, and centers its products on oats.

Cloves don't have quite as wide usage as oats in skin care, but anecdotal accounts of clove oil use support its efficacy for some people in clearing up acne. But clove oil often causes a numbing or burning sensation that makes it problematic for widespread use in therapeutic quantities. If the acne-fighting ingredient in clove is manganese, though, perhaps we can just put a little manganese in our acne creams and face lotion. Why fill the body with manganese when we just want a little extra affecting our facial pores? (But don't inhale manganese. That's known to lead to neurological damage.)

Manganese seems a beneficial component of cosmetic creams for other reasons. For instance, it helps protect skin from UVA and hydrogen peroxide damage. A manganese enzyme appears to be involved in helping protect connective tissue from age associated abnormalities. And a manganese peptide complex showed promising results in improving the appearance (especially hyperpigmentation) of photodamaged skin, per a 2007 article.

Chronic exposure to excessive manganese leads to manganism, which resembles Parkinson's disease. One of the ways manganism is treated is with chelation using a salt of EDTA to lower blood manganese levels. Check every chemical product you own that touches your face, and it probably has EDTA in it as a stabilizer unless you purposely avoid EDTA. If we want some manganese in our skin, I wonder whether we are unwise to use a known chelator in so many hair and skin care products.

[Update on June 16, 2018: I saw a few people had been reading this old post, so I thought I'd let anyone reading this know that topical manganese didn't help my teenager in 2018 when she was getting some acne. Oh, well, maybe manganese is good for other things.]

Happy Fourth of July!

A family tradition is to watch National Treasure on Independence Day. The film combines a fun treasure hunt, adventure, and respect for family, freedom, and history. My favorite line from it is the protagonist's speech about the risks that the Founding Fathers* took to establish this nation:

Ben Gates: A toast? Yeah. To high treason. That's what these men were committing when they signed the Declaration. Had we lost the war, they would have been hanged, beheaded, drawn and quartered, and-Oh! Oh, my personal favorite-and had their entrails cut out and *burned*! So... Here's to the men who did what was considered wrong, in order to do what they knew was right...what they knew was right.

* They were men, so I'll call them "Founding Fathers." The word "Founders" calls up images of ships going down at sea and introduces ambivalence towards the brave patriots of 1776.

Egg for breakfast

We're going to be learning about Austria for the first two weeks of July. A typical Austrian breakfast is a roll with butter/cheese/jam/etc., a cup of coffee or hot cocoa, and an egg. I look forward to breakfasts that include egg for a while. Typically, we just have cold cereal (the kind without cyanocobalamin and folic acid these days) and milk because it's convenient. But it really doesn't seem to be the best way to start every single day, especially if one is trying to avoid weight gain and Type II diabetes. A recent study shows some clear advantages from including an egg as part of one's breakfast.

This study evaluated appetite and glycemic effects of egg-based breakfasts, containing high and moderate protein (30 g protein and 20 g protein +7 g fiber, respectively) compared to a low-protein cereal breakfast (10 g protein) examined in healthy adults (N = 48; age 24 ± 1 yr; BMI 23 ± 1 kg/m²; mean ± SE). Meals provided 390 kcal/serving and equal fat content. Food intake was measured at an ad libitum lunch meal and blood glucose response was measured. Visual analog scales (VAS) were used to assess hunger, satisfaction, fullness, and prospective food intake. The egg-based breakfast meal with high protein produced greater overall satiety (p < 0.0001), and both high protein and moderate protein with fiber egg-based breakfasts reduced postprandial glycemic response (p < 0.005) and food intake (p < 0.05) at subsequent meal (by 135 kcal and 69 kcal; effect sizes 0.44 and 0.23, respectively) compared to a cereal-based breakfast with low protein and fiber.

"The effects of the combination of egg and fiber on appetite, glycemic response and food intake in normal weight adults – a randomized, controlled, crossover trial," [Abstract], http://www.tandfonline.com/doi/full/10.1080/09637486.2016.1196654

Eggs are a bit messy to prepare, especially in comparison with a bowl of cereal and milk, but it's time my older children learn to fry them!

Published!

Here's a link to the letter to the editor that my friend and I submitted to the International Journal of Food Sciences and Nutrition. The gist of it is that research, especially over the past 10 years or so, points to mechanisms explaining how a rise in folic acid intake could have caused increases in autism spectrum disorders and inattentive-type ADHD and that we would be prudent to consider using folate supplements that don't inhibit the enzyme dihydrofolate reductase the way folic acid does.

http://www.tandfonline.com/eprint/E4IhDdijbZIMRfYh4T28/full

Published!

Here's a link to the letter to the editor that my friend and I submitted to the International Journal of Food Sciences and Nutrition. The gist of it is that research, especially over the past 10 years or so, points to mechanisms explaining how a rise in folic acid intake could have caused increases in autism spectrum disorders and inattentive-type ADHD and that we would be prudent to consider using folate supplements that don't inhibit the enzyme dihydrofolate reductase the way folic acid does.

http://www.tandfonline.com/eprint/E4IhDdijbZIMRfYh4T28/full

Update: All 50 of the free downloads from the publisher are already gone, so here's a 30-second slide show video I made from part of the letter and its supporting references.

Cyanocobalamin - a very poor choice, part 2

When the body has to detoxify cyanide, the most well-known pathway is facilitated by the enzyme rhodanese, which converts cyanide to thiocyanate, which is then excreted via the kidneys. But what does thiocyanate do to us before it's excreted? I'm sure there are other things I haven't come across yet, but my early research has turned up studies showing that thiocyanate induces hypothyroidism in weaned mice and is associated with neurological diseases. Then there's a website for anesthesiologists saying

Thiocyanate toxicity causes anorexia, fatigue, and mental status changes, including psychosis, weakness, seizures, tinnitus, and hyperreflexia. Thiocyanate is usually excreted in the urine. Toxicity can be minimized by avoiding prolonged administration of nitroprusside and by limiting drug use in patients with renal insufficiency. If necessary, thiocyanate can be removed by dialysis.

I fear I'm going to sound like a broken record before I'm done with researching cyanocobalamin, but we should really be using other forms of cobalamin (B12) in our breakfast cereal and vitamin supplements. Instead of adding to the body's cyanide load, we could be decreasing our suffering from cyanide and its metabolites if we used hydroxocobalamin. Hydroxocobalamin and cyanocobalamin are both synthetic, but at least hydroxocobalamin dissociates more easily and helps reduce the body's cyanide and thiocyanate loads. I'll have to do more research later on methylcobalamin and adenosylcobalamin, the forms of B12 that naturally occur in food (mostly animal products).

Cyanocobalamin - a very poor choice, part 1

We humans have cyanide in our bodies. It's a fairly simple, small molecule, so that's not surprising. Not only are we exposed to it from some foods (especially cassava), smoking, combustion of some materials, and some poisons and medications, but it turns out that our bodies make it! Who knew? The research on endogenous (i.e., made in the body) hydrogen cyanide (a poisonous cyanide compound) focuses on mammalian brain tissue:

Cyanide is generated in neurons and this report examines the two different receptors which mediate cyanide formation in neuronal tissue. An opiate receptor blocked by naloxone increases cyanide production both in rat brain and in rat pheochromocytoma (PC12) cells. A muscarinic receptor in PC12 cells releases cyanide and the effect is blocked by atropine. In rat brain, in vivo, a muscarinic agonist inhibits cyanide generation, possibly by acting on receptor subtypes different from those in PC12 cells. Cyanide generation by a muscarinic agonist in PC12 cells is blocked by pertussis toxin but that caused by an opiate is not. Thus, two different receptors and two different second messenger systems can mediate cyanide generation in PC12 cells. In parallel with the in vivo data, cultured primary rat cortical cells also show decreased cyanide release following muscarinic stimulation. Both blockade of cyanide generation by muscarinic receptor activation and cyanide release by opiate agonists from cortical cells are pertussis toxin insensitive. Similarly, little cyanide generation was seen following cholera toxin treatment. These data indicate that opiate receptors increase and muscarinic receptors decrease cyanide production in rat brain tissue by G-protein independent mechanisms. This work supports the suggestion that the powerful actions of cyanide may be important for neuromodulation in the CNS.

Abstract from https://www.ncbi.nlm.nih.gov/pubmed/15099699.

In very small amounts, it looks like our body finds cyanide useful. Too much cyanide is to be avoided, though, for it can cause seizures, coma, and death. Among other detoxification pathways, our body has an enzyme called rhodanese that helps us convert cyanide to thiocyanate (which apparently causes hypothyroidism, which is a problem, but not as big a problem as cyanide). Too high a cyanide load overwhelms the body's ability to detoxify cyanide before it can cause harm. However, even low-level exposure to cyanide over a long period of time apparently can harm us, so it's important to minimize our intake of cyanide-containing substances.

Chronic exposure to cyanide has been associated with development of pancreatic diabetes, hypothyroidism, and several neurological diseases in both humans and animals. However, there is a limited number of experimental models for these pathologies. Thus, in the present study 0, 0.15, 0.3, or 0.6 mg KCN/kg body weight/day was administered for 3 months to 26 rats. On the last day, plasma samples were obtained for glucose, cholesterol, and thyroidal hormone measurement, and the pancreas, thyroids, and whole central nervous system were collected for histopathologic study. There were no significant difference in plasma concentrations of the substances measured between groups, and no lesions were found in the pancrease or thyroid. The CNS of experimental animals revealed the presence of spheroids on the ventral horn of the spinal cord, neuron loss in the hippocampus, damaged Purkinje cells, and loss of cerebellar white matter. In conclusion, cyanide administration could promote neuropathological lesions in rats without affecting pancreas or thyroid gland metabolism.

Abstract from "Effects of low-dose long-term cyanide administration to rats," https://www.ncbi.nlm.nih.gov/pubmed/12481854.

Because it's stable (and so cheaper), the form of vitamin B12 that is typically put into fortified foods and vitamins is cyanocobalamin. "Cyano" stands for "cyanide." It seems to be generally assumed that 1) the cyanocobalamin will dissociate into cyanide and cobalamin (useable B12) during digestion, and 2) the cyanide dose from cyanocobalamin is too low to harm us. However, a recent study of brain tissue found that cyanocobalamin is present in the brain. If it dissociates in the brain--which is kind of the point of supplementing with cyanocobalamin in the first place as we want the benefit of the cobalamin--the cyanide will be added to that from endogenous hydrogen cyanide in the central nervous system. And if it doesn't dissociate in the brain, then it isn't helping us meet our brain's cobalamin needs.

I believe cyanocobalamin is a very poor choice of B12 supplement. The evidence clearly indicates that cyanide and its less toxic metabolite, thiocyanate, could exacerbate or even cause hypothyroidism and cyanide-related neurological problems. Cyanocobalamin is far from the only form of B12 available. There is even one form of B12, hydroxocobalamin, that is used to treat cyanide poisoning because the cobalamin binds more tightly to the "cyano" than to the "hydroxo" (hydroxyl), and our bodies can excrete the resulting cyanocobalamin.

Learning about Bangladesh

It's summer, and that means learning about other countries!

Right now, we're learning about Bangladesh, a country that has only existed in its current form since 1971. Despite being only the size of Iowa, it has around 160 million people, making it the 8th most populous country in the world. Yet because of its poverty, it has little influence on the world, apart from its clothing manufacturing industry. It also seems like a very unpleasant place to be female.

Bangladesh appears to be taking an unfortunate turn to radicalism, as the hacking deaths of late indicate. As a former State Department employee, I grieve at the death of Xulhaz Mannan.

All that research wasn't in vain

For several months a high school friend, who happens to be an RN and have MTHFR mutations, and I have been researching medical science and nutrition, with an emphasis on MTHFR-related processes. We drafted a letter to the editor on some important connections we made and submitted it to three different journals. It has been under review for some time, but we found out today that the third journal will accept it for publication after we make a few changes.

Truly, science is for everyone. My friend and I are both currently housewives taking care of several children. Well-educated housewives, to be sure, with a definite STEM bent. We were the two girls our high school sent to an area conference on "Women in Math and Science" one year. But I could never have been the person in the lab coat, slicing and dicing mouse brains. Emotionally, I would have a very hard time doing that. But I can see patterns, use logic, and follow where the data lead. As can anyone now, thanks to the people in the lab coats who create research data and the PubMed database. I am very grateful to live in a time and place where scientific knowledge is so readily accessible to all.