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.

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)

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

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 item	Betaine content
	mg/100 g
Wheat bran	1339
Wheat germ	1241
Spinach	600-645
Beets	114-297
Pretzels	237
Shrimp	219
Wheat bread	201
Crackers	49-199

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. Here's a post about the topic.)

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.

• Ukraine - 1 in 2074. (https://crupp.org/autism/)
• Israel - 1 in 208. (http://www.timesofisrael.com/low-prevalence-of-autism-seen-among-israels-minorities/: "Broken down into population groups, though, minorities in Israel have even lower prevalence rates: 1 out of 833 for Israeli Arabs [who utilize chard heavily in popular stews] living in rural populations, and 1 out of 386 for ultra-Orthodox Jews, compared to 1 out of 182 for the general Jewish Israeli population.")
• Amish in the USA - 1 in 271.(https://imfar.confex.com/imfar/2010/webprogram/Paper7336.html)
• Germany - 1 in 263 (http://journals.sagepub.com/doi/abs/10.1177/1362361316673977?journalCode=auta).

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