Wednesday, May 24, 2017

Vírus zika, placenta e feijoada

Em Uganda, em 1947, o vírus Zika foi isolado pela primeira vez. Zika ocorre em muitas partes distantes do mundo. Há apenas alguns anos, Zika chegou ao Brasil (https://www.usatoday.com/story/news/2016/03/24/study-zika-virus-may-have-arrived-brazil-2013/82210986/), e logo percebeu que Zika estava associada e provavelmente causava microcefalia e outras malformações fetais.(http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30883-2/fulltexthttps://www.nytimes.com/2016/01/22/world/americas/zika-virus-may-be-linked-to-surge-in-rare-syndrome-in-brazil.html).

Por que demorou até Zika chegar ao Brasil para que a conexão Zika-microcefalia se tornasse aparente?

Zika chegou aos EUA, com 40 mil casos confirmados em Porto Rico, mas Puerto Rico viu apenas um pequeno número de casos de microcefalia. (http://www.huffingtonpost.com/entry/zika-puerto-rico_us_5903a419e4b05c39767f8317?t59) Isso reflete a experiência dos países centro-americanos, onde Zika se espalhou, mas os casos de microcefalia não aumentaram dramaticamente de maneira paralela ao que eles fizeram no Brasil. Isso levou a teorias de conspiração sobre pesticidas e água no Brasil.(http://fortune.com/2016/02/16/monsanto-zika-virus-conspiracy/http://www.who.int/emergencies/zika-virus/articles/rumours/en/) Proponho uma explicação mais simples e muito menos controversa:
  • Os brasileiros comem algo regularmente que ajuda o vírus Zika a desenvolver fetos, algo de contrário inócuo.
E que algo parece ser sulfato de condroitina solúvel em água da cartilagem contida em seu prato nacional, feijoada à brasileira. Feijoada é um guisado de feijão preto feito com vários cortes de carne, mais notavelmente orelhas, pés e focinhos de porco (https://pt.wikipedia.org/wiki/Feijoada_(Brasil)http://eatrio.net/2013/06/pig-parts-and-feijoada.html), E a feijoada geralmente é cozida a fogo pequeno por horas, uma excelente maneira de extrair substâncias dessas peças de carne. Como as orelhas de porco são principalmente de cartilagem, elas são uma fonte muito boa de sulfato de condroitina, um suplemento feito de cartilagem de animais e usado por muitos para osteoartrite.(http://www.umm.edu/health/medical/altmed/supplement/chondroitinhttps://link.springer.com/article/10.1007/s10719-016-9665-3http://slism.com/calorie/111173/)

Pouco menos de dois meses atrás, investigadores identificaram o sulfato de condroitina como uma molécula à qual Zika se liga firmemente e qual "pode ser o bilhete do vírus Zika na placenta". (https://www.sciencedaily.com/releases/2017/04/170404084445.htmhttp://pubs.acs.org/doi/abs/10.1021/acs.biochem.6b01056) Se esta descoberta for correta, então, seria imprudente comer sulfato de condroitina extra durante a gravidez e em risco de doença do vírus Zika, pois o sulfato de condroitina administrado por via oral é absorvido e aumenta a quantidade de sulfato de condroitina no plasma sanguíneo. (https://www.ncbi.nlm.nih.gov/pubmed/27108107)

Eu enviei um e-mail para os dois autores correspondentes dos resultados da pesquisa de sulfato de condroitina e Zika para chamar a sua atenção a possível conexão de feijoada com microcefalia. Espero que meu e-mail não acabe em suas pastas "spam." Talvez a conexão que eu desenhe aqui é muito simples e já foi descartada como irrelevante, mas parece ser uma possibilidade que deve ser examinada. Enquanto isso, se você conhece uma mulher grávida que viaja ou reside em áreas onde o vírus Zika é conhecido por ser, você pode querer considerar avisá-la para evitar alimentos e bebidas feitos com quantidades significativas de cartilagem animal.

(Esta é uma versão em português de uma publicação anterior em inglês.)

Tuesday, May 23, 2017

Virus Zika, entrada a la placenta y guiso de feijoada

En Uganda en 1947, el virus Zika fue aislado por primera vez. Zika ocurre en muchas partes lejanas del mundo. Hace apenas unos años, Zika llegó a Brasil (https://www.usatoday.com/story/news/2016/03/24/study-zika-virus-may-have-arrived-brazil-2013/82210986/), y se dio cuenta de que Zika está lanzado con y probablemente causa microcefalia y otras malformaciones fetales. (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30883-2/fulltexthttps://www.nytimes.com/2016/01/22/world/americas/zika-virus-may-be-linked-to-surge-in-rare-syndrome-in-brazil.html).

¿Por qué se tardó hasta Zika llegó a Brasil para que se hiciera evidente la conexión de la microcefalia con Zika?

Zika ha llegado a los Estados Unidos con 40.000 casos confirmados en Puerto Rico, sin embargo, Puerto Rico ha visto sólo un pequeño número de casos de microcefalia. (http://www.huffingtonpost.com/entry/zika-puerto-rico_us_5903a419e4b05c39767f8317?t59) Esto refleja la experiencia de los países centroamericanos, donde Zika se ha extendido pero los casos de microcefalia no se han aumentado de forma espectacular en paralelo como lo hicieron en Brasil. Esto ha llevado a teorías conspirativas sobre pesticidas y agua en Brasil. (http://fortune.com/2016/02/16/monsanto-zika-virus-conspiracy/http://www.who.int/emergencies/zika-virus/articles/rumours/en/) Propongo una explicación más simple, mucho menos controvertible:
  • Los brasileños comen algo (normalmente inocuo) regularmente que ayuda a que el virus Zika llegue a los fetos en desarrollo.
Y esto "algo" parece ser soluble en agua sulfato de condroitina que se obtiene del cartílago contenido en feijoada, el plato nacional de Brazil. Feijoada es un guiso de frijoles negros e incluye varios cortes de carne, especialmente orejas, pies y hocicos de cerdo (http://boliviachef.blogspot.com/2011/03/feijoada-el-sabor-de-brasil.htmlhttp://eatrio.net/2013/06/pig-parts-and-feijoada.html), y la feijoada típicamente se coce por horas--una excelente manera de extraer sustancias de esa carne. Debido a que las orejas de cerdo son principalmente de cartílago, son una muy buena fuente de sulfato de condroitina, un suplemento hecho de cartílago de animales y utilizado para la osteoartritis por mucha gente.(http://www.umm.edu/health/medical/altmed/supplement/chondroitinhttps://link.springer.com/article/10.1007/s10719-016-9665-3http://slism.com/calorie/111173/)

Hace apenas dos meses, investigadores identificaron el sulfato de condroitina como una molécula a la que Zika se une firmemente y que "puede ser el boleto de entrada del virus Zika a la placenta."(https://www.sciencedaily.com/releases/2017/04/170404084445.htmhttp://pubs.acs.org/doi/abs/10.1021/acs.biochem.6b01056) Si esta identificación es correcta, sería imprudente comer extra sulfato de condroitina durante el embarazo si está en riesgo de Zika virus, debido a que el sulfato de condroitina administrado por vía oral se absorbe y aumenta la cantidad de sulfato de condroitina en el plasma sanguíneo. (https://www.ncbi.nlm.nih.gov/pubmed/27108107)

Envié un mensaje por correo electrónico a los dos autores correspondientes de los hallazgos sobre Zika y sulfato de condroitina de abril para llamar su atención a la posible conexión con feijoada. Espero que mi mensaje no termine en sus "spam" carpetas. Tal vez la conexión que hago aquí es demasiado simple y ya ha sido descartado como irrelevante, pero me parece una conexión posible que debe ser examinado.

Mientras tanto, si conoce a una mujer embarazada que viaja o reside en áreas donde se sabe que el virus Zika está, podría ser beneficioso advertirle que evite los alimentos y bebidas hechas con cantidades considerables de cartílago animal.

(Esta es una versión en español de una publicación anterior en inglés.)

Monday, May 22, 2017

Zika virus, placental entry, and feijoada

In Uganda in 1947, Zika virus was first isolated. Zika occurs in many far-flung parts of the world. Just a few years ago, Zika arrived in Brazil (https://www.usatoday.com/story/news/2016/03/24/study-zika-virus-may-have-arrived-brazil-2013/82210986/), and it was soon realized that Zika was associated with and likely causing microcephaly and other fetal malformations. (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30883-2/fulltext, https://www.nytimes.com/2016/01/22/world/americas/zika-virus-may-be-linked-to-surge-in-rare-syndrome-in-brazil.html).

Why did it take until Zika arrived in Brazil for the Zika-microcephaly connection to become apparent?

Zika has now come to the USA, with 40,000 confirmed cases in Puerto Rico, yet Puerto Rico has seen only a small number of microcephaly cases. (http://www.huffingtonpost.com/entry/zika-puerto-rico_us_5903a419e4b05c39767f8317?t59) This mirrors the experience of Central American countries, where Zika has spread but microcephaly cases have not dramatically jumped in parallel the way they did in Brazil. This has led to conspiracy theories about pesticides and water in Brazil. (http://fortune.com/2016/02/16/monsanto-zika-virus-conspiracy/, http://www.who.int/emergencies/zika-virus/articles/rumours/en/) I propose a simpler, much less controversial explanation:
  • Brazilians eat something regularly that helps Zika virus reach developing fetuses, something otherwise innocuous. 
And that something appears to be water-soluble chondroitin sulfate from cartilage contained in their national dish, feijoada. Feijoada is a black bean stew made with various cuts of meat, most notably pig ears, feet, and snouts (http://eatrio.net/2013/06/pig-parts-and-feijoada.html), and the feijoada is typically simmered for hours, an excellent way to extract substances from those meat pieces. Because pig ears are mostly cartilage, they are a very good source of chondroitin sulfate, a supplement made from animal cartilage and used by many for osteoarthritis. (http://www.umm.edu/health/medical/altmed/supplement/chondroitin, https://link.springer.com/article/10.1007/s10719-016-9665-3, http://slism.com/calorie/111173/)

Just under two months ago, researchers identified chondroitin sulfate as a molecule to which Zika binds tightly and which "may be the Zika virus' ticket into the placenta." (https://www.sciencedaily.com/releases/2017/04/170404084445.htm, http://pubs.acs.org/doi/abs/10.1021/acs.biochem.6b01056) If this finding is correct, then eating extra chondroitin sulfate while pregnant and at risk of Zika virus disease is a terrible idea, for orally-administered chondroitin sulfate is absorbed and increases the amount of chondroitin sulfate in blood plasma. (https://www.ncbi.nlm.nih.gov/pubmed/27108107)

I emailed the two corresponding authors of the Zika-chondroitin sulfate April research findings to bring the possible feijoada connection to their attention. I hope my email doesn't end up in their "spam" folders. Maybe the connection I draw here is too simple and has already been dismissed as irrelevant, but it seems like a possibility that should be looked into. In the meantime, if you know a pregnant woman who travels or resides in areas where Zika virus is known to be, you might want to consider warning her to avoid food and drink made with significant amounts of animal cartilage.

* Fun note for my readers: Almost three years ago, I learned of the existence of feijoada because our family studied Brazil for two weeks, and I learned how to cook it. Who knew it might end up relevant to Zika-caused fetal damage?

Saturday, May 20, 2017

How to get more glycine betaine (trimethylglyicine) in your diet

As discussed earlier this week, we miss out on many dietary sources of glycine betaine (trimethylglycine or TMG) with our western style of eating. Here are easy ways to increase the amount of easily-usable TMG in our diet:

  1. Eat more soups/stews and cooked purees, especially ones that contain spinach, amaranth (greens or seeds), beets (greens or roots), quinoa, rye, and wheat (preferably including the wheat germ).
  2. Eat bulgur pilaf. (Remember not to drain the cooking water.)
  3. Boil pasta in less water and then use the cooking water in your sauce or other recipes.
  4. Put TMG in your beverages. When they refine sugar from sugar beets, one of the things they remove from the sugar is TMG, which can be purchased as a food supplement and easily mixed into juice or milk. If the TMG is used properly in small amounts, no one can taste it.

Because there are other nutrients besides TMG in cooking water, I think the first three are preferable, but not everyone wants to change the way they eat.

Wednesday, May 17, 2017

Soups and glycine betaine

Boiling is a wonderful way to extract glycine betaine (AKA trimethylglycine or TMG) from foods that contain it. Around 60-80% of the TMG in plant material leaches out into the water when it is boiled. For instance, one study found 1472 mg/g of TMG in organic pasta when uncooked; once cooked, the amount of TMG was only 352 mg/g. Where did three-quarters of the TMG go? Into the cooking water, from which most of the TMG can be recovered, as it is fairly heat-stable. Yet what do we do with that cooking water in the USA? We throw it down the drain! All that boiling-extracted TMG, a nutrient that supports our bodies in converting homocysteine--see this article for a partial summary of the health problems that appear associated with having too much homocysteine--and we give it to our sewers. Why?

When one thinks of food in the USA, one thinks of one word in particular: "convenience." Yesterday, I looked over the breakfast and lunch menus for our local school district and found that there will be no oatmeal mush, stew, soup, or chili offered during the entire month of May. All those high-liquid foods are messy! They require separate bowls and don't come prepackaged like fruit cups. Also, who really wants to clean up soup spills in a school full of young children? I rarely serve my own children soup because 1) they don't initially appreciate it, and 2) they spill it.

US breakfasts have been mostly toast, cold cereal, eggs, Pop-Tarts, etc., and in recent years, we've been moving towards even more portable breakfast choices such as yogurt and breakfast bars. (http://www.bbc.com/news/magazine-28761333) Americans like to eat "on the go." Long ago, when I was a typical multitasking US college student, I was surprised at the reaction I got in Poland when Poles saw me eating my sandwich while strolling down the street at lunchtime; what was normal in the USA definitely wasn't normal in Warsaw.

Polish people have traditionally eaten a large main meal, called "obiad," in the early afternoon, and it customarily includes a soup course. Even though traditional eating habits have had to partially give way before workday requirements, Poles still love their soups. In 2015, Poles ate more soup per capita than every other country in the world, according to a 2016 marketing survey (http://www.euromonitor.com/soup-in-poland/report):

TRENDS
Soup was traditionally always an important part of Polish cuisine, as the consumption of 100 litres per capita recorded in 2015 was the largest in the world. Soup was a part of almost every family dinner, often even being a small meal in and of itself. However due to saturation and shifting preferences towards healthier, home-made soup, the growth of packaged soup in Poland was severely hindered. Polish customers still enjoyed occasional help from dehydrated soup or shelf stable soup, which was often considered to be a relatively good base for soup preparations.
That's over a cup of soup each day. How often do Americans, in contrast, eat soup? Or even stew, chili, or curry? From what I've seen, we in the USA tend not to eat high-liquid cooked foods (eat, not drink--we love our blended beverages) and are far below the Poles when it comes to soup consumption. Canned soup has declined in popularity to the point that the Campbell Soup company had to close two of its soup plants a few years ago. (http://www.cbsnews.com/news/campbell-soup-closing-two-us-plants/) Soup is viewed as "old-fashioned" by younger people and is a struggling market, per a 2017 US market study (http://www.euromonitor.com/soup-in-the-us/report):

Experiencing struggles in recent years, soup experienced a volume decline of 2% over the review period, even as value shot up by a 2% CAGR. The latter was because prices rose from sales of more premium offerings and companies’ struggles to make sales were largely passed on to consumers in the form of higher prices. Shelf stable soup, occupying a 95% volume share of the category, has reflected and fuelled many of these stagnating trends, as much of its products have traditionally been disproportionately popular among older consumers (aged 55-74). For this reason, soup has often been perceived as a largely “old-fashioned” or “conservative” product, making it less popular among influential younger consumer groups, particularly millennials who are increasingly health-conscious and have avoided the high sodium and artificial ingredients contained in many soup products. 
Not only do Poles eat a lot of soup, but their main soups tend to be 1) based on beets, 2) based on rye flour, or 3) thickened with thin wheat noodles, flour, and croutons (Poles are taught from childhood not to waste bread, and croutons are a tasty use for stale bread). If you've been reading my blog, you know that beets, rye, and wheat contain substantial amounts of TMG.*

Since I hypothesize that TMG helps protect against autism spectrum disorders--remember, Poland diagnoses autism at a rate of around 1/2900 while the US rate is 1/68--I think it would be very beneficial if the US population were to increase its intake of TMG-containing soups. Perhaps we could all eat minestrone containing spinach and whole wheat pasta and sold in little disposable cups that can be microwaved; that would be convenient, tasty to the pizza-trained palate of Americans, and a good source of TMG and other important nutrients. (Wouldn't it be nice if someone from Campbell's happened across my blog and used this idea?)

* Based on all the TMG they get in their soup, Poles should be quite healthy, right? Unfortunately, they really like another liquid in that part of the world: vodka. The name means "little water," and too many people (mostly male) in eastern Europe and Poland (now considered "central Europe" by some, but it still shares many diet commonalities with its neighbors to the east) seem to drink it like it is water. Per wikipedia, Polish women have basically the same life expectancy as US women, but Polish men's life expectancy trails Polish women by nearly 8 years. A study of life expectancy in Russia points to alcohol abuse as a major causative factor behind earlier death for Russian men. (http://www.rand.org/pubs/conf_proceedings/CF124/cf124.chap4.html; see also https://www.theguardian.com/world/2014/jan/31/russian-men-losing-years-to-vodka)

Thursday, May 4, 2017

Amaranth greens contain glycine betaine (trimethylglycine)

Several botanical families of plants accumulate betaine (i.e., glycine betaine, trimethyglycine, or TMG). One of the major ones in use for human food purposes is the amaranthaceae family. (https://hungary.pure.elsevier.com/hu/publications/betaine-distribution-in-the-amaranthaceae) Here's the Encyclopaedia Brittanica summary of the primary food species in the amaranthaceae family:
Food crops in the family include the various forms of beet (Beta vulgaris, including garden beets, chardsugar beets, and mangel-wurzel), lamb’s quarters (Chenopodium album), and spinach (Spinacia oleracea). Some species—namely, Inca wheat, or love-lies-bleeding (Amaranthus caudatus), red amaranth (A. cruentus), and quinoa (Chenopodium quinoa)—are high-protein pseudo-grain crops of interest to agricultural researchers. Quinoa in particular, touted as a health food, grew in popularity worldwide during the early 21st century.

https://www.britannica.com/plant/Amaranthaceae

In the past few posts, I've discussed the TMG contribution to various regional diets from inclusion of beet, spinachamaranth seed, and quinoa seed. But I only recently learned of the use of amaranth greens for human consumption. They deserve a post, for they are eaten commonly in several places outside Europe and North America.* The leaves of amaranth are reported to accumulate glycine betaine. (http://www.sciencedirect.com/science/article/pii/S0003986196997313)

Amaranth, despite being once a major foodstuff in southern Mexico, fell into disuse after the arrival of the Spaniards:
Grain amaranth was as important as corn and beans to the Aztecs, who believed that it gave them supernatural powers and used it in ceremonies involving human sacrifice. Some 20,000 tons of the seeds were delivered by Aztec farmers in annual tribute to their emperor, Montezuma.
In Aztec rituals, amaranth was mixed with human blood, formed into cakelike replicas of Aztec gods and fed to the faithful, a practice the Spanish regarded as barbaric and a mockery of Christian communion. Hernan Cortes put a stop to it by condemning to death anyone found growing or possessing amaranth.
http://www.nytimes.com/1984/10/16/science/ancient-forgotten-plant-now-grain-of-the-future.html (The article is from 1984, so we haven't reached the future yet.)

And it wasn't just human blood they were mixing into the little amaranth figurines, it was purportedly blood from human sacrifices--at least according to a video program called Ancient Grains Series: Amaranth (https://www.amazon.com/Amaranth/dp/B00VZ4A8D4) that I just watched--which would explain the Spaniards' revulsion. But humans no longer eat amaranth seeds in conjunction with murder victim blood, so it seems like amaranth should be poised to become a major foodstuff again.

Amaranth greens are popular in many parts of Asia, Africa, and the Caribbean, where they are usually eaten stewed, which is a great way to coax TMG out of its leaves. For some reasons, people in the USA just want to use amaranth greens in salads, though. (http://www.appalachianfeet.com/2010/05/10/how-to-grow-and-use-amaranth-greens-wrecipes-sources/, http://www.today.com/food/sick-kale-amaranth-next-super-green-try-6C10658383) (Why don't Americans like to consume liquid from boiled food? That subject calls for its own post.)

In Jamaica, they call amaranth greens "callaloo," which can get confusing because callaloo is also used as an appellation for other greens as well as for the dish made with amaranth and/or other greens. (https://realjamaica.org/what-on-earth-is-callaloo, http://www.africanbites.com/callaloo-jamaican-style/) Despite multiple research papers on autism epidemiology out of Jamaica in the past few years, I can't find any estimates of autism prevalence there, so I can't say whether high Jamaican consumption of amaranth greens is protecting them to any extent from autism spectrum disorders (per my hypothesis).

* According to various wikipedia articles, kañiwasessile joyweedchenopodium album (i.e., lamb's quarters or bathua; popular in north India), celosia argentea var. argentea (Lagos spinach, soko yokoto, or cresta de gallo; popular in India), and epazote are also food/herb crops within the amaranthaceae family and so are likely to be good dietary sources of TMG. I have no experience with eating any of them, and all seem to be relatively unknown in most of the more economically developed countries. I list them in hopes that some researchers will read this and investigate how much glycine betaine these foods might be contributing to the diets of the people who eat them, but I won't do individual posts on them.

Wednesday, April 26, 2017

Non-wheat grains that are high in glycine betaine (trimethylgycine)

Cereals and pseudocereals (i.e., edible grains) are typically the main source of glycine betaine (trimethylgycine or TMG) in human diets. (http://www.sciencedirect.com/science/article/pii/S0308814613012247)  (Whether we can easily use that TMG appears to depend on food preparation methods, as discussed here.) Wheat germ and bran have especially high TMG content. Unfortunately, many people now avoid eating wheat due to concerns about gluten or a desire to lose weight via a low-carbohydrate diet. Some Serbian researchers realized avoidance of wheat might cause a deficiency in dietary TMG and investigated the TMG content of other grains. They posted their results in a paper available online here.

Here's the abstract:

In this study, betaine [TMG] content in cereal grains, cereal-based products, gluten-free grains and products of mainly local origin was surveyed. Estimates of betaine are currently a topic of considerable interest. The principal physiologic role of betaine is as an osmolyte and methyl donor. Inadequate dietary intake of methyl groups causes hypomethylation in many metabolic pathways which leads to alterations in liver metabolism and consequently, may contribute to numerous diseases such as coronary, cerebral, hepatic and vascular. Cereals are the main sources of betaine in human diet. Results showed that betaine content in grains is variable. Spelt grain was found to be a richer source of betaine (1848 mg/g DM) than that of common wheat (532 mg/g DM). Gluten-free ingredients and products were mainly low in betaine (less than 150 mg/g DM). Amaranth grain is a remarkable gluten-free source of betaine (5215 mg/g DM). Beet molasses is an ingredient which may increase betaine content in both cereal-based and gluten-free products.

http://fins.uns.ac.rs/e-journal/index.php?mact=Magazines,cntnt01,details,0&cntnt01hierarchyid=35&cntnt01sortby=magazine_id&cntnt01sortorder=asc&cntnt01summarytemplate=current&cntnt01detailtemplate=detaljno&cntnt01cd_origpage=178&cntnt01magazineid=174&cntnt01returnid=188

I highly recommend reading the entire paper if you're at all interested in this topic. I'll pull out what I consider the highlights:

Rice contains no TMG. Corn, millet, and buckwheat have a little TMG, and oats and barley have a little more. Good sources of TMG include wheat (spelt wheat is best, and bread wheat has more than durum) and rye. Amaranth and quinoa have very high levels of TMG, as does beet molasses.

I pestered a Belarussian relative recently to find out whether she eats a lot of borscht and beet greens. She said, no, that's more her mom and aunt who do that, but she drinks kvass often. Kvass is a rye bread-based beverage popular in eastern Europe. Rye has about two-to-four times the amount of TMG as wheat. Sadly for me, kvass is mildly alcoholic, and I don't drink alcohol for religious reasons. (I'd love to play with a reverse osmosis filter that could allow me to make my own de-alcoholized drinks, but from what I read online, such an apparatus is hard to come by.)

Amaranth seed used to be a very popular grain in Guatemala, Mexico, and Peru. Amaranth has been becoming a regularly-consumed pseudocereal again in the past couple decades, but it's happening very, very slowly. I started putting a tablespoon full of amaranth in with my batch of rice in the rice cooker in order to get more TMG in our family diet; my family doesn't notice the addition. (Update: I spoke too soon. One of the children noticed it in the rice tonight. But they didn't mind it.)

I've liked quinoa since I was sixteen. I think my dad was introduced to quinoa while on a trip to Machu Picchu, and he ate it like it was couscous, complete with canned spaghetti sauce over it. It tastes quite good that way, especially with some grated cheese on top. In the Andes, quinoa is mostly eaten in soups and porridges. I think it's unfortunate that we tend to drain our quinoa here in the USA, for that disposes of the TMG that leaches out into the cooking water.

Beet molasses is marketed as a bread topping in Germany. A German friend brought me some a couple of weeks ago, and it is quite tasty. I'll have to look for it in our local German deli/market after I run out. Which will be in about 2-3 more weeks, based on how quickly we're eating it. It's rather like pancake syrup, but one feels healthier eating it due to the knowledge that it is high in TMG.

Tuesday, April 18, 2017

Wheat as a source of trimethylglycine (glycine betaine)

As referenced earlier, here is a post on bulgur. I'll also talk a little about steamed buns and boiled wheat generally.

In the USA and western Europe, we eat a lot of wheat (although western Asia surpasses even our high consumption - http://www.fao.org/docrep/006/Y4011E/y4011e04.htm). We eat our wheat primarily in two forms: 1) moderately-wet dough baked at relatively high temperatures over/in dry heat and 2) boiled-then-drained noodles. The first method of preparation lacks long periods of significant amounts of water molecules energetically vibrating in and around and breaking down plant cell walls, which would mean less TMG becomes freed. The second method obviously includes boiling water, but the trimethylglycine (TMG) dissolved into the boiling water (typically around 60-80% of food's TMG content - http://www.sciencedirect.com/science/article/pii/S0308814603000633) is subsequently drained away.

Why do we like our wheat products so dry in the USA? Bread, buns, crackers, cookies, pizza, drained pasta, bran flakes, and so forth are convenient, less messy, and store well. In medieval times, the countries of western Europe used to eat gruel and porridge made of high TMG grains like wheat and rye, however, except for oats, porridge has mostly fallen out of favor in those regions.

Yet in other--usually much poorer--parts of the world, wheat is still prepared in ways that allow for consumption of easily-absorbed TMG. Bulgur wheat is a parboiled-then-dried cracked-wheat product that is prepared at home for consumption by being placed in very hot/boiling water until the water has been absorbed. The water is sometimes drained away afterward, but it is not drained away when bulgur is utilized in pilaf dishes, which are intentionally made so as to absorb all the cooking liquid. The parboiling, or partial cooking, process is often carried out with steam rather than actual boiling. Parboiling retains enough nutrients that bulgur is classified as a whole grain product. Thus bulgur is twice treated with steam/hot water, which helps release TMG from the bulgur's cell walls without carrying it all away, while the nutrients in the water used to prepare bulgur are usually retained and ingested.

Look at which countries and cultures are eating large amounts of bulgur. They're the ones all around the Mediterranean, especially Turkey and the region called "the Levant." These countries also don't seem to have much of a societal burden from autism. Other societal burdens, they have aplenty. But not autism. Remember the low autism prevalence in Israel and how it was lowest of all for rural Israeli Arabs? And over in Turkey, despite evidence that medical and nursing schools there are doing a good job of teaching their students about autism (https://www.ncbi.nlm.nih.gov/pubmed/27524519), Turkey simply is not dealing with the same levels of autism as the US and western Europe (http://www.tpfund.org/2013/03/lets-talk-about-autism-in-turkey/).

Eastern Asia generally eats less wheat than Europe and western Asia, but in Chinese-influenced cuisines, it's normal to eat that wheat in steamed buns, dumplings, and noodle soup. Western-style bread, while becoming more popular, is not normally a staple of eastern Asian diets. (https://chinafoodingredients.wordpress.com/2014/05/19/bread-in-china-from-snack-to-staple-though-for-the-young-urban/) The steaming process seems as it if would help break down cell walls to allow the egress of TMG while not carrying it away as full-on boiling would do. Where dumplings and noodles have been cooked in soup, TMG leaching from them into the soup broth will end up being ingested. China also consumes a lot of stewed spinach and other greens, so I suspect that its traditional cuisines include enough easily absorbed TMG to protect to some degree against autism. Unfortunately, data about autism in China are currently considered inadequate. (https://molecularautism.biomedcentral.com/articles/10.1186/2040-2392-4-7) (I wouldn't be surprised if the Chinese data turn out to be pretty accurate in the end. I've never understood why autism-awareness advocates online insist that the other countries of the world are all misdiagnosing children if they don't find the same rate of autism as the USA. That seems arrogant.)

My takeaway from this? Ingest liquids in which wheat was cooked. To quote an online cooking writer, "when you dump the remaining pasta water down the drain, that's where you make the pasta gods cry." (http://www.cookinglight.com/cooking-101/your-pasta-water-is-liquid-gold)

Sunday, April 2, 2017

It's time to end the autism epidemic (Conclusion)

I didn't intentionally set out to end this blog series on Autism Awareness Day. These ideas have been percolating in me for over a year, but it is fitting that I finish on a day when the world's attention is turned to autism spectrum disorders (ASD).

Some have begun turning Autism Awareness movements into a celebration of being neurodiverse and so deflected attention from finding what is causing the rise in autism in order to stop the "epidemic." (I use quote marks because epidemics are of infectious diseases, and autism spectrum disorders are not contagious.) I'm what I would consider a mild case of "Asperger syndrome," and I experience both the good and bad of being on the autism spectrum: the ability to focus (obsess even) and shut out people around me, the bent towards abstract subjects like math and linguistics, and the delay in social skills that made me an easy target as a child for bullying peers. This form of high-functioning autism runs in my family and affects the males more than the females, often disrupting their ability to have productive relationships. Autism-connected disruption in social skill development is not something to celebrate; it's something to address, ameliorate, and prevent if possible.

The evidence I have cited in this series indicates that we can prevent a large percentage of cases of ASD in the USA by 1) replacing cyanocobalamin and folic acid with other forms of vitamin B12 and folate, and 2) consuming more glycine betaine (TMG) in easily absorbed ways during pregnancy and early childhood.

Thank you for reading. If you think the research and connections I have presented have merit, please spread the word. 

C. Taylor, JD

**This is one of a series of posts. Here are the links to each entry in the series.**

Introduction
Part 1
Part 2
Part 3
Part 4
Conclusion

Saturday, April 1, 2017

It's time to end the autism epidemic (part 4)

In part 1 of this blog series, I approached the problem of autism spectrum disorders (ASD) like a computer programmer looking for a programming glitch. The best output data available point to a problem in the homocysteine-methionine cycle being involved in approximately 95% of autism cases. (Because autism diagnoses criteria are still subject to some debate, I wouldn't expect us to ever find a 100% correlation between any one physical process and autism.) Recent findings, outlined in parts 2 and 3, indicate that autism development is more specifically linked to the methionine synthase (MS) homocysteine-to-methionine pathway. Having formulated a hypothesis that methinone synthase dysfunction is involved in autism, I next developed a testable prediction based on the existence of an alternative homocysteine-to-methionine pathway catalyzed by the enzyme betaine-homocysteine methyltransferase (BHMT). My prediction is that nutritional support of BHMT activity will partially make up for MS dysfunctions and in that way protect against developing an autism spectrum disorder. Let's examine whether the data support that prediction.

First, BHMT is a zinc-containing enzyme, so having enough zinc in one's body should correlate with a lower ASD risk. That does indeed appear to be the case. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100031/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563033/, https://www.ncbi.nlm.nih.gov/pubmed/26218250)

Second, BHMT requires glycine betaine (trimethylglycine or TMG) as a substrate. What is TMG?
Betaine is found in microorganisms, plants, and animals and is a significant component of many foods, including wheat, shellfish, spinach, and sugar beets. Betaine is a zwitterionic quaternary ammonium compound that is also known as trimethylglycine, glycine betaine, lycine, and oxyneurine. It is a methyl derivative of the amino acid glycine with a formula of (CH3)3N+CH2COO and a molecular weight of 117.2, and it has been characterized as a methylamine because of its 3 chemically reactive methyl groups. Betaine was first discovered in the juice of sugar beets (Beta vulgaris) in the 19th century and was subsequently found in several other organisms. The physiologic function of betaine is either as an organic osmolyte to protect cells under stress or as a catabolic source of methyl groups via transmethylation for use in many biochemical pathways.

http://ajcn.nutrition.org/content/80/3/539.full; Craig SAS. "Betaine in human nutrition." Am J Clin Nutr 2004;80(3):539-549.

Here's a listing of the some of the best sources of TMG:

Food itemBetaine content
mg/100 g
Wheat bran1339
Wheat germ1241
Spinach600-645
Beets114-297
Pretzels237
Shrimp219
Wheat bread201
Crackers49-199
http://ajcn.nutrition.org/content/80/3/539/T1.expansion.html

The very best sources of TMG are mussels, clams, oysters, and scallops, but due to cost and convenience factors they tend not to be commonly-eaten components of cuisines in areas with reported statistics for autism prevalence. Moreover, it is not clear just how much TMG is actually available during digestion from unpulverized mussels, oysters, clams, and scallops, all of which when cooked whole are too often rubbery and difficult to chew. So I will have to pass shellfish by and look at plant sources of TMG.

Inside plant cells, TMG functions as an osmoprotectant (https://academic.oup.com/jxb/article/51/342/81/485733/Genetic-engineering-of-glycinebetaine-synthesis-in), and in onions TMG has been demonstrated to protect cell membranes against NaCl-induced membrane permeability. (http://cat.inist.fr/?aModele=afficheN&cpsidt=2422100) Hence, it is to be expected that methods of vegetables and grain preparation which rupture plant cell membranes would be more effective at freeing TMG for human dietary absorption than would other food preparation methods that tend to leave TMG-protected plant cell membranes intact. It has been found that boiling is highly effective at removing TMG from foods and that the TMG is largely recoverable from the liquid that the food was boiled in (http://www.sciencedirect.com/science/article/pii/S0308814603000633). Free TMG in an aqueous solution and liberated from its original plant cells should be the most easily-absorbed of all TMG dietary sources. The highest levels of TMG in plant sources are found in wheat bran and germ, spinach, and Beta vulgaris (beetroot and chard). (Update 4/26/2017: I just learned today that amaranth is also a betaine-accumulating plant and that amaranth greens are widely eaten in many parts of the world. I'll write a post about it later.)

Which regional cuisines have high amounts of boiled wheat bran and wheat germ? Wheat gruel has fallen out of popularity in the wheat-eating parts of the world in the past couple of centuries. We do boil pasta, but the pasta is often manufactured so as to be mostly devoid of wheat germ and bran. Also, during the boiling of pasta, most of its TMG content leaches into the water and is subsequently dumped down the drain instead of being ingested. (Update 4/8/2017: I overlooked the use of cracked wheat--or bulgur--in many countries and cuisines, so here's a post about it. And here's a post discussing non-wheat grains that are high in TMG.)

What about spinach? I know of only one major regional cuisine that frequently utilizes boiled spinach together with the liquid in which it was boiled. That region is that of northern India and Pakistan, where they often eat palak (spinach) puree dishes; in the USA, this puree can be found in the Punjabi dish palak paneer. Due to poverty and health care issues, autism statistics in all of India are not clear. But a recent study out of the Punjab region (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943381/) found an ASD prevalence of merely 0.9/1000 (1 in 1,111). In comparison, the ASD rate in the USA is 14.6/1000 (1 in 68) (https://www.cdc.gov/mmwr/volumes/65/ss/ss6503a1.htm).

And what about beets? Beets are actually what brought me to see the importance of TMG in preventing autism. I lived in Poland, and I know how important a part of their cuisine beetroot is, especially cooked into a strained borscht-like soup called "barszcz cerwony." Did you catch that? Strained. That means barszcz czerwony is simply full of TMG and doesn't include any plant fiber to decrease the TMG percentage of the soup. If my hypothesis is correct, then Poland should have a very low autism prevalence. And Poland apparently does, per a 2015 study of health records:
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.

http://www.sciencedirect.com/science/article/pii/S1230801315000119

Despite having guaranteed health care for all Polish children, Poland appears to be diagnosing ASD in only .34/1000, or 1 in 2941, children. Can the USA really have approximately 40 times more children with ASD than Poland? Perhaps the Polish people, due to language and training differences, just don't know about autism? That is highly unlikely. There have been Polish universities offering English-language medical school programs for over twenty years. And Poles themselves, including Polish doctors, have been working in the United Kingdom (UK)--where autism is certainly well-known--in large numbers since Poland joined the European Union (EU), which enabled its citizens easily to work in other EU countries.

If the beetroot soup and other beet consumption is protecting the Polish children from developing ASD, then other countries and cultures that often eat borscht and the juice of boiled beets should have lower rates of ASD. And they do.


Other countries that eat borscht as part of their traditional cuisines include Russia, Belarus, Romania, and Lithuania, for all of which we lack clear statistics about ASD prevalence. Based on my interactions with people from eastern Europe, autism seems to be be much less of a problem for their societies than it is for western Europe and the USA currently (https://www.autismspeaks.org/science/science-news/europe-gets-active-autism).

The evidence above bears out my prediction that high levels of free TMG in the diet will protect against development of autism spectrum disorders. One counterclaim that could be made, though, is that genetics might actually be behind the lower rates of ASD in the above-cited regions and cultures, but I do not consider that a strong argument because much of the US population is of partial or full Germanic ancestry, either from Germany or via English heritage. Moreover, I have two young male relatives of half-Slavic background, and only the one born and raised in the USA exhibits ASD symptoms.

In short, I consider the evidence convincing that 1) a dysfunction involving methionine synthase is causally connected to autism spectrum disorders, and 2) high consumption of easily-absorbed glycine betaine protects against developing autism spectrum disorders.

**This is one of a series of posts. Here are the links to each entry in the series.**

Introduction
Part 1
Part 2
Part 3
Part 4
Conclusion

Friday, March 31, 2017

It's time to end the autism epidemic (part 3)

Besides 5-MTHF, we need a sufficient supply of methylcobalamin (MeCbl), a form of cobalamin (vitamin B12), in order to support methionine synthase (MS) function. There are four kinds of vitamin B12 available as supplements: methylcobalamin, adenosylcobalamin, hydroxocobalamin, and cyanocobalamin (CnCbl). Only methylcobalamin and adenosylcobalamin occur naturally in our bodies, and we normally get them from animal products. Hydroxocobalamin is produced by bacteria and then is made stable synthetically by using cyanide to change it from hydroxocobalamin to cyanocobalamin. Cyanocobalamin is the form of B12 typically put into multivitamins and fortified foods.

What happens when we ingest methylcobalamin? Unfortunately, it doesn't seem to go straight to where it might be needed in the body. A complex processing of B12, which is still the subject of investigation, happens in the cells first. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692085/, https://www.ncbi.nlm.nih.gov/pubmed/27771510) Methylcobalamin, adenosylcobalamin, and cyanocobalamin all undergo separation of the non-cobalamin part from the cobalamin part by the protein MMACHC. MMACHC catalyzes the decyanation of cyanocobalamin and the dealkylation of methylcobalamin and adenosylcobalamin, after which the cobalamin is chaperoned (cobalamin is very volatile on its own) and changed to adenosylcobalamin and methylcobalamin. The transformation of cobalamin to methylcobalamin, based on recent findings, appears to be part of an interplay of several proteins, including both MMACHC and methionine synthase (MS). (https://www.ncbi.nlm.nih.gov/pubmed/27771510) In other words, a problem with MS could not only affect MS in its homocysteine-salvaging function but could also make MeCbl less available to due to MS interacting with MMACHC, which decyanizes cyanocobalamin.

If you've ever read about chaos theory, you probably saw a mention of feedback loops. Feedback loops are an important principle to understand when dealing with systems of complex interactions such as those involving MS and B12 transport, conversion, and use.
The term feedback refers to a situation in which two (or more) dynamical systems are connected together such that each system influences the other and their dynamics are thus strongly coupled. Simple causal reasoning about a feedback system is difficult because the first system influences the second and the second system influences the first, leading to a circular argument. This makes reasoning based on cause and effect tricky, and it is necessary to analyze the system as a whole. A consequence of this is that the behavior of feedback systems is often counterintuitive.

http://authors.library.caltech.edu/25062/1/Feedback08.pdf (Feedback Systems: An Introduction for Scientists and Engineers. Karl Johan Åström; Richard M. Murray (2010). "§1.1: What is feedback?" Princeton University Press, p. 1).

I'm not going to try to untangle exactly what is happening between cyanocobalamin, MMACHC, and MS in the human brain, for we lack the necessary knowledge to do so at present. But we have evidence from a paper published last year that the fetal brain, for whatever reason, doesn't break down cyanocobalamin as well as expected.
We found CNCbl to be 15-fold higher in fetal samples, as compared to 0–20 yr old subjects, suggesting unique Cbl metabolism during fetal development. However, the underlying cause of this higher CNCbl level remains unclear, as does the biological origin CNCbl. Maternal folate and vitamin B12 supplementation is a common recommendation during pregnancy, which could be a source of the elevated CNCbl we observed, although Cbl levels in placenta were comparatively low. Conversion of CNCbl to active cofactors MeCbl and AdoCbl requires NADPH- or GSH-dependent decyanation by MMACHC and it is possible that the developing fetal brain has diminished decyanation capacity. The markedly higher level of inactive CNCbl could potentially have functional consequences by competing with MeCbl and AdoCbl, restricting their cofactor activity.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146797 (references omitted).

An excess of CnCbl in the developing fetal brain could be restricting MeCbl activity? Which would negatively affect MS activity? That's exactly what we don't want to have happen if MS dysfunction is behind autism spectrum disorders.

Too little B12 in the brain has been linked to autism. (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146797) And so has an excess of B12, according to the Johns Hopkins findings last year that I mentioned in a previous blog post: "Very high vitamin B12 levels in new moms are also potentially harmful, tripling the risk that her offspring will develop an autism spectrum disorder." (http://www.jhsph.edu/news/news-releases/2016/too-much-folate-in-pregnant-women-increases-risk-for-autism-study-suggests.html) The high B12 levels in the Johns Hopkins study population were almost certainly a result of cyanocobalamin in prenatal vitamins and fortified foods, for naturally occurring B12 forms are unlikely to be consumed at sustained excessively high levels unless one frequently eats clams and liver. (https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/).

Here's the worst part of the finding from the Johns Hopkins study: "If both levels [folate and B12] are extremely high, the risk that a child develops the disorder increases 17.6 times." (http://www.jhsph.edu/news/news-releases/2016/too-much-folate-in-pregnant-women-increases-risk-for-autism-study-suggests.html)

Talk about synergy! Yes, that said 17.6 times the risk of an autism spectrum disorders for children of women who had blood containing too much folate and B12, which almost certainly came from folic acid and cyanocobalamin in their prenatal vitamins and their fortified foods. Both the conscientious mothers who take their prenatal vitamins dutifully and economically disadvantaged mothers who rely on WIC--which generally limits their cereal choices to those that are highly fortified with folic acid and cyanocobalamin--are at risk of having excessive folate and B12, so their children end up at much greater risk of autism spectrum disorders, which are disorders of development, meaning it will be difficult or impossible to fully repair the damage later in life.

The heavy use of folic acid and cyanocobalamin, especially in conjunction, appears to have helped cause the dramatic rise in autism spectrum disorders in the last three decades. Folic acid and cyanocobalamin should be replaced with other forms of folate and B12 that are bioidentical to naturally, commonly occurring forms in order to minimize the hazard of causing unintended problems as has apparently happened with autism spectrum disorders. (I think ADHD is related to this mess, too--https://www.ncbi.nlm.nih.gov/pubmed/27346490--but I'll stay focused on autism for now.)

**This is one of a series of posts. Here are the links to each entry in the series.**

Introduction
Part 1
Part 2
Part 3
Part 4
Conclusion

Thursday, March 30, 2017

It's time to end the autism epidemic (part 2)

In order to carry out the conversion of homocysteine back to methionine, the enzyme methione synthase (MS or MTR) is dependent on cobalamin (vitamin B12 or Cbl) and folate, specifically in the forms of methylcobalamin (CH3-Clb or MeCbl) and L-methylfolate (5-MTHF, 5-methyltetrahydrofolate, or levomefolic acid). Here's an illustration, showing how the 5-MTHF essentially gives up its methyl group and ends up as plain tetrahydrofolate (THF, another form of folate) while homocysteine is converted to methionine:
https://www.researchgate.net/figure/6580050_fig4_Figure-1-The-cobalamin-dependent-methionine-synthase-catalysed-reaction-CblI

We need sufficient 5-MTHF to keep methionine synthase operating. Where does 5-MTHF come from? It's a form of folate that is produced by the enzyme methylene tetrahydrofolate reductase (MTHFR), and the gene that produces MTHFR has the same name. The body cycles through different forms of folate. Here's an illustration of that "folate cycle":
Folate metabolism gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with ADHD in myelomeningocele patients.
Spellicy CJ, Northrup H, Fletcher JM, Cirino PT, Dennis M, Morrison AC, Martinez CA, Au KS - PLoS ONE (2012) https://openi.nlm.nih.gov/detailedresult.php?img=PMC3515551_pone.0051330.g001&req=4
A deficiency in 5-MTHF can apparently be caused by at least three things:

1 - A deficiency in total folate diminishes the amount of 5-MTHF that can be made from other forms of folate.
  • Defective folate transport can result in autism spectrum disorders and other developmental disorders, and treatment with folinic acid (a form of folate) has been effective in in many children to reverse some autism symptoms. (https://www.ncbi.nlm.nih.gov/pubmed/26924398)
2 - MTHFR gene polymorphisms can decrease the ability of the body to produce 5-MTHF, production of which is catalyzed by the MTHFR enzyme, because the variant genes result in MTHFR enzymes that are more prone to being inactivated by heat. (https://www.ncbi.nlm.nih.gov/pubmed/10201405)
3 - High folic acid consumption causes a pseudo-MTHFR deficiency in mice and so might do the same in humans. (http://ajcn.nutrition.org/content/early/2015/01/07/ajcn.114.086603) Folic acid thus appears highly likely to be a sub-optimal form of folate for preventing 5-MTHF deficiency.
The third point is still controversial because there is research that has found folic acid prenatal supplements help prevent autism specifically where the MTHFR polymorphism associated with autism is present. (https://www.ucdmc.ucdavis.edu/publish/news/newsroom/6677). How does this square with the research I cited that finds autism risk appears to go up when there is excess folic acid? The key word is "excess." Our bodies can handle a little folic acid, but too much can get in the way of making 5-MTHF. I suspect folic acid does this by partially inhibiting the enzyme dihydrofolate reductase (DHFR), leaving more dihydrofolic acid (DHF) to get in the way of the MTHFR enzyme and thus cause a pseudo-MTHFR deficiency. 

Are we getting too much folic acid in the USA? I've come across articles about north American study populations that found unmetabolized folic acid in 40-95% of fasting study participants. (http://ajcn.nutrition.org/content/92/2/383.longhttp://jn.nutrition.org/content/145/3/520.short) From that, I conclude that many in north America are definitely getting more folic acid than they need.

Am I anti-folate? Not at all. Every woman should take measures to ingest enough folate if she thinks she could become pregnant in order to lessen the risk of neural tube disorders such as spina bifida. But I think folic acid is a terrible form of folate to be putting in everyone's food and multivitamins. Folate is available in many foods naturally and in other supplement forms, including actual 5-MTHF.

**This is one of a series of posts. Here are the links to each entry in the series.**

Introduction
Part 1
Part 2
Part 3
Part 4
Conclusion

Wednesday, March 29, 2017

It's time to end the autism epidemic (part 1)

Two weeks ago, a group of researchers published their findings about biological markers that can be used to a high degree of accuracy to predict the presence or absence of autism. In other words, they have deduced and tested a highly accurate "blood test" for autism. Here is the link to the entire report: http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1005385.

Here is the abstract:

The number of diagnosed cases of Autism Spectrum Disorders (ASD) has increased dramatically over the last four decades; however, there is still considerable debate regarding the underlying pathophysiology of ASD. This lack of biological knowledge restricts diagnoses to be made based on behavioral observations and psychometric tools. However, physiological measurements should support these behavioral diagnoses in the future in order to enable earlier and more accurate diagnoses. Stepping towards this goal of incorporating biochemical data into ASD diagnosis, this paper analyzes measurements of metabolite concentrations of the folate-dependent one-carbon metabolism and transulfuration pathways taken from blood samples of 83 participants with ASD and 76 age-matched neurotypical peers. Fisher Discriminant Analysis enables multivariate classification of the participants as on the spectrum or neurotypical which results in 96.1% of all neurotypical participants being correctly identified as such while still correctly identifying 97.6% of the ASD cohort. Furthermore, kernel partial least squares is used to predict adaptive behavior, as measured by the Vineland Adaptive Behavior Composite score, where measurement of five metabolites of the pathways was sufficient to predict the Vineland score with an R2 of 0.45 after cross-validation. This level of accuracy for classification as well as severity prediction far exceeds any other approach in this field and is a strong indicator that the metabolites under consideration are strongly correlated with an ASD diagnosis but also that the statistical analysis used here offers tremendous potential for extracting important information from complex biochemical data sets.

Here is a pictorial summary of folate-dependent one-carbon metabolism:


http://journal.frontiersin.org/article/10.3389/fgene.2011.00036/full
And here is an illustration of the transsulfuration pathway:

https://www.researchgate.net/figure/261328951_fig2_The-methionine-cycle-and-transsulfuration-pathwayNotes-Glutathione-synthesis-begins
Do you see where the two connect? It's at the part where methionine is converted in steps to homocysteine and then the homocysteine is recycled to methionine. The major homocysteine-to-methionine pathway is via the enzyme methionine synthase (MS).

In 2013, preliminary findings (due to the small study size) were reported that clearly indicated prematurely low levels of methionine synthase mRNA in autistic subjects' brains during their early years. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577685/) I highly recommend viewing the findings as graphically represented (here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577685/figure/pone-0056927-g005/) as they make it clear just how dramatic the difference is during crucial years in child development.

Why is the methionine-homocysteine cycle important in autism? Autism spectrum disorders are pervasive developmental disorders that are characterized by delays in multiple areas of development, and candidate genes for autism seem to constitute an ever-lengthening list. An influential theory currently is that epigenetic mechanisms are involved, particularly DNA methylation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955092/), which ties directly into the s-adenosylmethionine (AdoMet or SAMe) made from methionine (as illustrated above).

If a methionine synthase transcription deficiency can cause autism via epigenetic mechanisms, that suggests we need to efficiently and vigorously support the activity of whatever MS-associated activity is present. That is where getting the proper forms of folate and cobalamin (B12) comes in. I'll go more into detail on that tomorrow.

**This is one of a series of posts. Here are the links to each entry in the series.**

Introduction
Part 1
Part 2
Part 3
Part 4
Conclusion