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.
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:
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.
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
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.

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.