Saturday, July 23, 2016

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.

Thursday, July 21, 2016

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.

#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.

Friday, July 15, 2016

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:

Thursday, July 14, 2016

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?

Sunday, July 10, 2016

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 
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.

Wednesday, July 6, 2016

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?

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 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 of manganese in so many hair and skin care products.

Monday, July 4, 2016

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.

Thursday, June 30, 2016

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!

Monday, June 27, 2016

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.

video

Saturday, June 25, 2016

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).

Thursday, June 23, 2016

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.

Tuesday, June 14, 2016

Emigrate?

I have a young adult relative who posted on Facebook yesterday about how the USA is becoming such a terrible place and how she'd like to emigrate. Having lived in a few corners of the world, I can see where she is coming from, but I think she is unaware of just how many problems other countries have, too.

Her major gripes with the USA include having to pay a high price for a college education which isn't even of very good quality (astute of her to have noticed that already), having to pay a large amount of her paycheck into Social Security when there is no guarantee of her receiving anything out of it in a few decades (once young adults start getting substantial paychecks, they get a bit of a reality check about the cost of government), an unfair judicial system, having to work long hours for less pay, shooting sprees (entirely understandable in light of last weekend, but she's apparently forgotten the Bataclan massacre), and the possibility of Donald Trump winning the presidential election (Gary Johnson is looking like a great choice this year...).

She has done some touring in Asia, and I fear that she thinks much of the world is like the beaches of Thailand and the orderly society of Singapore. A little more global education would be helpful, although I don't want her to go in person to many of the places I would like her to be more aware of. The United States of America is still a pretty nice place to live compared to much of the world. People tend to follow the rule of law here more often than not, and rule of law in a country appears to be associated positively with general happiness. The countries with the most rule of law and happiness also have very high tax rates, which she probably wouldn't like. On the other hand, I think people don't mind high taxation as much when they know the taxes are going for services they support instead of lining corrupt politicians' pockets. 

Monday, June 13, 2016

Horrible news from Orlando

Moral approbation or disapprobation of people's noncriminal conduct does not generally disturb me. Everyone approves or disapproves of others' actions to some degree. Because I believe faith and obedience to divine commandments must be freely chosen, I uphold the freedom of all to be religious or to be areligious, to adhere to religious mandates as to one's own behavior or to not adhere. I reserve the right to support or oppose legislation depending on whether it fits my conceptions of how to promote a "good society," yet I recognize the importance of individual liberty and highly value the secular government of the United States of America.

My entire life I have learned and lived the principle of chastity, i.e., no sexual relations outside of marriage, but never have I nor any of my co-religionists picked up a gun and gone to shoot up a nightclub, no matter how unpalatable I found the activities within (and some nightclubs, such as in Berlin, are known for behavior that much of the world's population would likely find distasteful). I reject the idea being pushed right now in media and on the internet that this past weekend's Islamist mass killing is somehow due to a wider failure by everyone to embrace homosexuality. The problem is that an extremist who adhered to a violent, illiberal version of Islam answered the call of ISIS in Orlando, Florida. I can adhere to my religious values and still mourn the evil slaughter that occurred at Pulse, and I do.

Friday, June 10, 2016

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.

Saturday, June 4, 2016

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.

Monday, May 30, 2016

How to not have an autism epidemic, from Poland

While researching some more on autism-folate connections yesterday, I delved into the details of homocysteine transformation into methionine. Elevated homocysteine is correlated with, amongst many bad things, the degree of severity of communication deficits in autism. It turns out that there are two pathways to accomplish the turning of homocysteine into methionine: 1) a pathway that requires methylfolate and can use cobalamin (vitamin B12), and 2) a pathway that requires betaine.

Betaine gets its name from beets, which are a very good source of it. So are wheat bran and quinoa, but rare is the person who drinks wheat bran or quinoa juice.* Beet juice, on the other hand, is regularly consumed in Poland as part of a very typical Polish soup, barszcz, a clear soup made from beets and chicken stock. It's strained at the end, so it is rather more like beet tea than typical borscht. This seems like an highly efficient way to obtain betaine, which is water soluble, from the beets.

Upon learning about betaine's role in converting homocysteine into methionine, I remembered that Poles eat barszcz regularly and thought, "I wonder if they have less autism?" The answer to that question appears to be dramatically in the affirmative:

Autism in Poland in comparison to other countries
Received 16 January 2015, Accepted 18 March 2015, Available online 22 April 2015
Material and methods
Statistical data provided by the Polish National Health Fund Headquarters in June 2013 and data pooled from international journal articles were analyzed in detail.
Results and discussion
The National Health Fund reported that 13 261 individuals up to 18 years of age received health services for autism and related disorders in Poland in 2012. This is a prevalence rate of 3.4 cases per 10 000 individuals. Incidence rates vary in different Polish regions, with the highest rates recorded in the following voivodships: warmińsko-mazurskie (6.5 cases per 10 000 individuals), śląskie (5.0), and pomorskie (4.6). The provinces with lowest rates were podlaskie (2.1), małopolskie (1.9), zachodniopomorskie (1.9), and łódzkie (1.8). These rates are far lower than those in European countries (20 per 10 000) and United States (200 per 10 000) epidemiological surveys.
Conclusions
Information on the prevalence of autism in Poland and in the world remains unclear and imprecise. This results from global differences in diagnostic criteria. There is urgent need to develop global standards for the diagnosis of autism in children.
I recognize the possibility that the Poles might be hugely underdiagnosing autism, but it seems unlikely that it is by a factor of 50 compared to the USA. Poland is part of the EU, provides free health care to all young children, and has strong economic and social ties to countries such as Great Britain and Germany.

My nephew is half-Polish, though born and raised in the USA, and he has high functioning autism. Would he have been better off raised in Poland? I look at the statistics above and suspect so. Something environmental--most likely dietary, for Poland has a lot of pollution from Communist days that they're still cleaning up--is causing the USA to see possibly 50 times the autism prevalence of Poland. 

One way or another, homocysteine must get transformed to methionine to support proper DNA methylation. By consuming so much beet juice, it appears the Poles give substantial dietary support to the betaine-dependent pathway.

I suggest, in light of all I've learned over the past few months, that the biggest faults in the US diet with respect to autism are the fortification of food with folic acid (instead of methylfolate or folinic acid) and cyanocobalamin (cobalamin binds more to cyanide than I think it should if we're to get enough useable cobalamin) together with the absence of sufficient dietary betaine and zinc (zinc is part of enzymes in the homocysteine-to-methionine pathways, and zinc levels tend to be lower where there is autism). Making mistakes in facilitating the folate and methionine cycles can cause much else to go wrong with DNA methylation, and we'll never find specific genes at fault for autism because we've then entered the realm of epigenetics.

* Spinach is also a good, juiceable source of betaine, but I can't find any evidence indicating whether spinach consumption is connected to less autism, so I'll pass over spinach for now. Anyone know a spinach lover who avoided folic acid and cyanocobalamin yet has a child with autism? I'd love to hear from them to find problems with my hypotheses. 

Saturday, May 28, 2016

"Everyone is the hero of their own story."

"Everyone is the hero of their own story." That is a maxim I use to better understand why people do as they do and talk about themselves and the world around them as they talk.

Why did people in the Bible so often want to kill prophets? Because the prophets threatened their image of themselves as good people by saying they were sinning.

Why do people get so testy about those who have different political views instead of discussing the merits of different ideas coolly and rationally? Because one tends to feel that one's own views rest upon a higher moral ground. Why? Because otherwise a person might be wrong or mistaken, the villain or fool of one's own story. But that cannot be, for we are the heroes in our minds.

Our minds are very supportive in allowing us to maintain the illusion of being heroes. For instance, they muddle our memories of past unethical behavior so that we forget how badly we acted. Scientists call this "unethical amnesia." Here is an excerpt from a recent study on this phenomenon:
Significance
We identify a consistent reduction in the clarity and vividness of people’s memory of their past unethical actions, which explains why they behave dishonestly repeatedly over time. Across nine studies using diverse sample populations and more than 2,100 participants, we find that, as compared with people who engaged in ethical behavior and those who engaged in positive or negative actions, people who acted unethically are the least likely to remember the details of their actions. That is, people experience unethical amnesia: unethical actions tend to be forgotten and, when remembered, memories of unethical behavior become less clear and vivid over time than memories of other types of behaviors. Our findings advance the science of dishonesty, memory, and decision making.
Abstract
Despite our optimistic belief that we would behave honestly when facing the temptation to act unethically, we often cross ethical boundaries. This paper explores one possibility of why people engage in unethical behavior over time by suggesting that their memory for their past unethical actions is impaired. We propose that, after engaging in unethical behavior, individuals’ memories of their actions become more obfuscated over time because of the psychological distress and discomfort such misdeeds cause. In nine studies (n = 2,109), we show that engaging in unethical behavior produces changes in memory so that memories of unethical actions gradually become less clear and vivid than memories of ethical actions or other types of actions that are either positive or negative in valence. We term this memory obfuscation of one’s unethical acts over time “unethical amnesia.” Because of unethical amnesia, people are more likely to act dishonestly repeatedly over time.
From the weighing of one's heart by Anubis to the life review that shows up so frequently in near-death experiences, most beliefs in an afterlife include a time of reckoning for all, a moment when they will see clearly all their deeds, both good and evil, and be judged for them. No unethical amnesia allowed then. But we'll also know the whole story then: the limitations we lived with, the biochemistry issues that made it harder to have empathy or wisdom, etc. I think we will find that we all had some moments of heroism and some of foolishness or evil. I think some of the most heroic moments will be the ones where we accepted the existence of our faults and chose to overcome them rather than pretend their absence.

Wednesday, May 18, 2016

"Why does Washington (state) have unusually high Alzheimer's mortality rates?"

A friend of mine asked this question on Facebook two days ago, so I looked into it. How could I resist?

Here's the article she shared with her question:
Washington state has the highest mortality rate for Alzheimer’s disease in the U.S., according to data released this week by the National Vital Statistics System.
At 46.3 deaths per 100,000 people, the state’s death rate for the year 2010 far exceeded the national rate of 25.1 deaths per 100,000.

A bit flippantly, I shot off a comment, "It's probably due to coffee." After all, two of the states with the lowest Alzheimer's rates are Utah and Nevada, where there are large numbers of coffee-avoiding LDS people. And everyone knows that Starbucks and rain are the two things that Seattle has in the most abundance.


As I mentioned in another post below, coffee contains salicylates, which are basically really mild aspirin, so it does have a protective effect against regular age-related dementia. But Alzheimer's? That mysterious tau tangle ailment? What's causing that? Look at the countries with the highest Alzheimer's rates. Finland, Italy, Switzerland, other Scandinavian countries, the Netherlands, the USA, Canada, are at the top. Some suggest that it's due to Vitamin D deficiency, but that doesn't really explain things. Minnesota is full of Scandinavian-descent people who don't get enough sunlight during their harsh winter, yet they just have an average (for the USA) Alzheimer's mortality rate there.

Then look at the countries with the highest coffee intake per capita. Finland tops the list again, followed by the Netherlands, Switzerland, and other Scandinavian countries. The USA is a bit lower down on the coffee list, but Washington state alone is probably quite a bit higher than the US average, what with all the coffee bars that manage to turn a profit there.

Maybe it's only coincidence. But I found some hints of what could be a connection between coffee and Alzheimer's. Tau protein tangles appear to be a result of hyperphosphorylation. Chlorogenic acid, apparently consumed mostly via coffee and tea, inhibits DNA methylation by increasing SAH:

The presence of caffeic acid or chlorogenic acid inhibited DNA methylation predominantly through a non-competitive mechanism, and this inhibition was largely due to the increased formation of S-adenosyl-L-homocysteine (SAH, a potent inhibitor of DNA methylation), resulting from the catechol-O-methyltransferase (COMT)-mediated O-methylation of these dietary catechols.

But we don't want to increase SAH if it decreases the SAM/SAH ratio, for that is associated with hyperphosphorylation of the tau protein and the tangles that correlate with cognitive impairment in Alzheimer's.

 2012 Jul 4;32(27):9173-81. doi: 10.1523/JNEUROSCI.0125-12.2012.
Acute administration of L-DOPA induces changes in methylation metabolites, reduced protein phosphatase 2Amethylation, and hyperphosphorylation of Tau protein in mouse brain.
Bottiglieri T1Arning EWasek BNunbhakdi-Craig VSontag JMSontag E
Abstract
Folate deficiency and hypomethylation have been implicated in a number of age-related neurodegenerative disorders including dementia and Parkinson's disease (PD). Levodopa (L-dopa) therapy in PD patients has been shown to cause an increase in plasma total homocysteine as well as depleting cellular concentrations of the methyl donor, S-adenosylmethionine (SAM), and increasing the demethylated product S-adenosylhomocysteine (SAH). Modulation of the cellular SAM/SAH ratio can influence activity of methyltransferase enzymes, including leucine carboxyl methyltransferase that specifically methylates Ser/Thr protein phosphatase 2A (PP2A), a major Tau phosphatase. Here we show in human SH-SY5Y cells, in dopaminergic neurons, and in wild-type mice that l-dopa results in a reduced SAM/SAH ratio that is associated with hypomethylation of PP2A and increased phosphorylation of Tau (p-Tau) at the Alzheimer's disease-like PHF-1 phospho-epitope. The effect of L-dopa on PP2A and p-Tau was exacerbated in cells exposed to folate deficiency. In the folate-deficient mouse model, L-dopa resulted in a marked depletion of SAM and an increase in SAH in various brain regions with parallel downregulation of PP2A methylation and increased Tauphosphorylation. L-Dopa also enhanced demethylated PP2A amounts in the liver. These findings reveal a novel mechanism involving methylation-dependent pathways in L-dopa induces PP2A hypomethylation and increases Tau phosphorylation, which may be potentially detrimental to neuronal cells.

It's far too little to turn into a publishable hypothesis. Association doesn't equal causation. However, I think it's enough to induce coffee drinkers to consider limiting their intake.

Eurovision 2016

For a non-political song contest, Eurovision's winner this year was a very political choice. I didn't enjoy the winning song, a Ukrainian of Crimean ancestry singing about Stalin's killing of her ancestors back in the 1940s.



My favorite song was "Loin d'ici" from an Austrian singer named Zoe.



And our family's favorite performance for visual effects was "You're my only one" from Russia.




And the song that left us all laughing for sheer fun and humor was done by the Swedish presenters and paid homage to the quirky things about Eurovision entries. We were delighted to see them invite Alexander Rybak back for it. I really do love a good violin song.

Despite (and also because of) the politics, we'll be watching Eurovision again next year. Maybe someday they'll invite the USA to send an entry. After all, they've invited Australia twice in a row. But I bet they invite Canada next, as long as Canada promises not to send Justin Bieber.

Wednesday, May 11, 2016

Yes, too much folic acid during pregnancy really is connected to autism in the offspring

If you've been following this blog for a few years, you know that I've been concerned that folic acid was in part responsible for the rise in autism. I backed off from expressing that worry because of studies showing that folic acid supplementation decreased autism. But it looks like my initial concern was valid.

Johns Hopkins today announced that women with high levels of folic acid and B12 just after giving birth had a much higher chance of having children with autism. Here's an excerpt of the Science Daily article about it:

The researchers found that if a new mother has a very high level of folate right after giving birth -- more than four times what is considered adequate -- the risk that her child will develop an autism spectrum disorder doubles. Very high vitamin B12 levels in new moms are also potentially harmful, tripling the risk that her offspring will develop an autism spectrum disorder. If both levels are extremely high, the risk that a child develops the disorder increases 17.6 times. Folate, a B vitamin, is found naturally in fruits and vegetables, while the synthetic version, folic acid, is used to fortify cereals and breads in the United States and in vitamin supplements.
The findings will be presented May 13 at the 2016 International Meeting for Autism Research in Baltimore.
"Adequate supplementation is protective: That's still the story with folic acid," says one of the study's senior authors M. Daniele Fallin, PhD, director of the Bloomberg School's Wendy Klag Center for Autism and Developmental Disabilities. "We have long known that a folate deficiency in pregnant mothers is detrimental to her child's development. But what this tells us is that excessive amounts may also cause harm. We must aim for optimal levels of this important nutrient."

Because of the research I've done during the past few months, we already limit folic acid in our family diet. I gave away the "enriched pasta" in my food supply, and we only buy cereals without added folic acid. I also tossed the regular multivitamins into the garbage. We eat green salad nearly every day and frequently consume oranges and orange juice, so we get lots of folate in our food. I also take methylfolate and plant-derived folate supplements sometimes because I hope to try to become pregnant again in a few months.

Tuesday, May 10, 2016

Submission completed

I finished the article proposing a theory of nausea during pregnancy and how to ameliorate it. I submitted it to an appropriate journal today. This is one of the biggest independent projects I have ever undertaken, possibly the biggest since law school. It feels good to have it done.

As I posted about previously, the nausea remedy worked when I had nausea during my recent anembryonic pregnancy. I did not take the remedy until after the point at which the pregnancy ceased to progress, so I have no reason to suspect the remedy caused the pregnancy to fail. However, my HCG levels were high enough that I experienced nausea and was able to test the remedy (successfully!).

Also, the nausea remedy has been tested--for fun--by my husband, my sister, her friend, and one of my friends. It has shown itself useful in lessening nausea or avoiding it altogether in situations involving gastrointestinal bugs and migraine. I wonder if it would help with chemotherapy nausea? Because that would be wonderful.

Friday, May 6, 2016

Labeling One's Self

In a society that exhorts us not to judge others, we certainly are presented with many opportunities to process people's statements about themselves.

I can't drive down the road without seeing bumper stickers and decals about all kinds of topics. They convey messages like: "I'm a fan of dinosaurs eating Christian fishes." "We have exactly 1 son and 3 daughters." "My grandchildren are dogs." "I vote Republican and like to keep really old election stickers on my car." "I love Tolkien and hiking...and maybe telling the world that I abandoned my parent's religion." "I'm so funny, and I don't care if I expose barely literate children to vulgarity/profanity." "People who use disposable diapers hate the planet and their babies." "My child is really smart/talented." "Whew! I ran 13.1 miles without dying." "I once visited a really cool tourist town/European country and bought a little oval sticker for my car to show you how cool I am for having been there."

Did ever so many complete strangers have the way to share their opinions so widely before the automobile? Twitter and Facebook aren't the same because you have to actually follow someone to see what they think, and we can always block people when we don't want to see what they share (or overshare). But there's no way to stop seeing bumper stickers, at least not until we get self-driving cars and can use time on the road for a good snooze.

Then there is clothing, which has always sent messages about one's values, sometimes wrongly read or inaccurate, but still there. Now people label themselves in ways that go beyond mere appearance. Here in Colorado, Amsterdam of the Rockies, where we see rising rental rates from all the out-of-state pot fans who want to move here and use legally, many people wear clothing adorned with marijuana leaves and pan-African colors. They might as well be advertising to potential employers, "I will never not have THC in my system."

I've always been wary of name brand clothing. Why should I pay extra to wear an advertisement for a clothing brand? What makes a shirt with "Hollister" written across the front something I would want to wear except for its current popularity? That's not my last name. I remember being worried, back when dating my current husband, because he wore a Tommy Hilfiger jacket. I didn't want to get financially tied to someone who would pay extra for a label. He greatly relieved my mind when he told me that the jacket was a castoff from a roommate.

We grew up running road races because my dad was a runner. We usually got free race shirts that said the name of the race and helped expand our wardrobe. Free shirts had a way of making the race experience last. They told the world, "I ran this race!" without also telling the world that I barely beat the ambulance. I still like free shirts, of which my husband gets a lot on the job from companies who are using our torsos to advertise their products. They make great yardwork shirts or nightgowns for the littles. But if I'm looking to impress people, I don't wear those shirts. That would be like slapping a bumper sticker on my forehead.

Tattoos used to mean "I served in the military." Now they are in vogue and send all kinds of messages. If someone's knuckles say "thug life," they are labelling themselves as someone who, at the least, doesn't mind being taken for a criminal. What am I supposed to do when presented with such a label? Pretend that battery and drug dealing are A-OK? Sorry, but sometimes judgments must be made.

I think we should not be hasty in accepting labels on others, whether given by others or taken upon one's self. People don't always know what message is implied by that specific piercing or a striped pair of socks. However, symbols are real. Part of the education we should give our children as they grow up is that they visually tell other people about themselves and what they stand for by how they adorn their bodies and their cars.

Sunday, May 1, 2016

May Day

This is a day to herald springtime! Yet we have snow on the ground still. We are having a very late spring this year in our part of Colorado. Our heater is running right now, and I'm heading off to get a blanket soon to curl up under while I read. I've been feeling guilty about not turning on our sprinklers yet (our grass shows the lack of water), but it's supposed to snow again tonight. Grrr. Fortunately, this current rainy/snowy weather is supposed to move away by the middle of the week.

Soon maybe I can sing, as Julie Andrews in the stage version of Camelot, "Tra la, it's May!" while romping over the green.


What a sublime voice. Even if I can't like Guenevere's character, the song is simply lovely.

Thursday, April 21, 2016

Faith is Voluntary

In English we get a bit confused sometimes because we have two words, belief and faith, for the same thing. Especially because we also use the word "faith" to mean a religious institution. Lost in the vocabulary confusion is the idea that the definition of a religion is believing in and worshiping a superhuman power. Did you see that those are both verbs? Action verbs, in fact? Things you can do or not do and so the products of free will.

Because you can believe or not believe, worship or not worship, faith is a choice. Any claim that a faith can be "involuntary" is anti-faith. If you can't freely choose to believe and worship, you are trapped in a "mind prison"* and have no ability to exercise faith.

Recent efforts in some strains of Islam to approve and promote death to apostates from Islam is destructive of Islam itself. The first pillar of Islam is faith. A shahada, declaration of faith and trust in Allah, is empty words if not freely chosen. The coercion of a death sentence basically takes away free choice. God doesn't want slaves; he wants faithful servants.

Those who preach death to apostates are destroying Islam as a religion. Those who love Islam need to stand up for it being voluntary. Until they do so, they can't expect those who value real faith to respect Islam. All its practices (esp. obvious ones like the hijab) will seem like trappings of slavery as long as Islam is difficult to leave. Indeed, the western world cannot respect Islam if it resembles slavery, for the western world has abandoned slavery almost entirely over the past three centuries.

Asserting the voluntary nature of Islam would also help decrease sectarian violence within Islam, for different sects often consider each other apostates worthy of death, which tends to make peace harder to restore. Christianity had its period of forced religiosity. It led to horrible conflicts and injustices, and the result is that many in Europe and European-influenced countries turn away from God altogether. I hope the Islamic world can learn from Europe's past and abandon coercion in matters of faith.

* As opposed to Sherlock's "mind palace."

Wednesday, April 20, 2016

Restaurant Food Serving Sizes

A decade or so ago, while living in the Philippines, I noticed that serving sizes were much smaller than in the USA. I recall approx. 8 and 12 oz beverage cups being quite common. Filipinos would laugh at how one of the first culture shock moments they experienced upon visiting the USA was the enormous soda pop cups that they would be given at fast food restaurants.

Why do we have such huge plates of food and huge bottomless mugs of beverages at restaurants in the USA? I think it's because food is cheaper than labor here.

The Philippines has a high rate of population growth; its primary product seems to be its people, who go abroad as maids, nurses, teachers, seafarers, nannies, and manual laborers to the US, UK, and Middle East. Security guards and salespeople abound at commercial establishments. While one can sometimes feel at a US store that it's impossible to find an employee, in the Philippines we were once nearly mobbed by around ten salespeople anxious to sell us bedsheets in which we had expressed some interest.

When labor is relatively cheap, employers can more easily dip into their margins to hire more employees to attract customers with better service. But when food is inexpensive compared to labor costs--such as where there is high minimum pay and employment taxes--restaurant operators can more easily offer generous serving portions to try to entice customers.

I know I'm not an economist, but this article made me think that my idea is not silly. They're going to automate parts of McDonald's food production at a new restaurant in the Midwest but still hire many employees, and a new attraction will be "all-you-can-eat fries." That doesn't sound necessary or healthy to me. However, while potatoes, salt, and oil aren't free, they probably cost a lot less than new kiosks and employees whose minimum wage is likely to go up in the near future. Without customers, there's no way to pay labor and automation costs, so increasing food amounts beyond that offered by the competition is a logical way to try to stay afloat financially.

I like fries, I really do. But I also like not feeling guilty after eating an extra large serving of them. I'm OK with small portions of oil-drenched starches.