There is a proverb, said by the famous British historical literary critic, who published the first English Dictionary. “The road to hell is paved with good intentions.” – Samuel Johnson (1709-1784)
Today is the last day of April, which has been autism awareness month. I think it’s fitting to point out a provocative hypothesis of autism causation. Studies of folic acid metabolism and autism have been published over the past several years, by various authors. This recent paper King CR. A novel embryological theory of autism causation involving endogenous biochemicals capable of initiating cellular gene transcription. A possible link between twelve autism risk factors and the autism ‘epidemic’ Med hypotheses (2011) is interesting, since it presents a hypotheses that autism is an epigenetics disorder.
Is it possible that excessive folic acid is a teratogenic environmental factor for susceptible populations? Is epigenetics the basis of autism? Here are a few of the tidbits which the author ties together as evidence for a Retinoic Acid/Estradiol Causation model.
- Folic acid is converted to 5′-methyltetrahydrofolate, (5′-MTHF) in the folate cycle. 5′-MTHF is a methyl donor to homocysteine, creating methionine. Methionine activates to S-adenosylmethionine (SAM), which has a significant role in de novo methylation/imprinting.
- Since the late 1980s, expectant mothers are advised to take 600mcg of folic acid per day, as a harmless way to prevent birth defects and prevent miscarriages. Also, folic acid supplementation of enriched grain products, has been required in the USA since 1988. This time line fits with the uptick in Autism spectrum diagnoses.
- Autistic brain stems are shortened, due to the lack of a transient embryological structure which has shown to be dependent in mice, on one of the Hox gene transcription factors.
- Retinoic acid signaling initiates expression of the developmental master regulator Hox genes – mutations in Hoxa-1 cause autism.
- Excess folic acid might temporarily compensate in utero, for genetic mutations to methylation cycle related proteins, which would normally be terminally disruptive to early central nervous system development.
- Higher functioning autism may be caused by folic acid promoting estrogen sensitive growth responses.
- Testosterone is converted in the brain to estadiol. Male embryos could be overexposed to maternal estradiol during sexual differentiation, hence the high male to female ratio in high functioning autism.
- Aspergers may be caused by overexposure to self produced testosterone. Most of the affected areas of the brain would be converting that testosterone to estradiol. However, the brain region for speech development might lack the enzyme to catalyze that conversion, and be developmentally unaffected.
- Autism symptoms which have also been shown to be functions affected by estrogen, include motor coordination, epilepsy, attentiveness, pain regulation, memory, spatial ability, etc.
Now, I hate to distract from this author’s critical scientific thinking applied to the controversial problem of increasing incidences of autism. However, if this hypothesis gets proven with data – prenatal folic acid supplementation will end up being an outrageous example of how broad medical recommendations, can fail us! I prefer to view this hypotheses as an opportunity to concretely apply epigenetics to prove or disprove a simple solution for combating the rising incidence of autism spectrum disorders.