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
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).
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.
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.**