Autism-Folic Acid Supplementation Link "Highly Likely"

For years now, I've suspected that the rise in autism, at least the higher-functioning kind, is connected to the increase in folic acid. The vaccine-autism connection theory never seemed very credible to me--the statistics didn't fit--and it's been debunked repeatedly, though it remains controversial. What I've read of folate's role in brain development, the larger than normal number of neural connections in autistic children, and the efficacy in some autism cases of folic acid supplementation has caused me to think that the global increase in prenatal folic acid intake can plausibly be tied to the increase in autism cases.

Because I have a nephew with autism who is now mainstreamed and no history of neural tube defects, I have consciously chosen to take prenatal vitamins sporadically to lessen my suspected risk for autism in my children. I already consume orange juice; folic acid fortified breakfast cereal, flour, bread, pasta, and tortillas; and a variety of fruits, vegetables, meats and nuts. It just seems like overkill to give my body 800 mcg (seriously, that's how much folic acid is in my Kroger prenatal vitamins) more folic acid everyday when 400 mcg is the amount deemed necessary to cut the risk of a neural tube defects (600 mcg for pregnant women). However, if I lived off diet soda and fish and chips, I don't doubt that I would need a prenatal vitamin everyday to have a chance at growing a healthy baby in me.

Because of the proof that folate lessens the chances of a neural tube defect, I do sometimes wonder if I'm doing the right thing by not popping a vitamin pill every day. Then I come across a scientific article like this one in Medical Hypotheses showing that I'm not completely off my rocker. Here is an excerpt from the article's summary:

Summary The inverse association between maternal folate status and incidence of infants born with neural tube defects (NTD’s) was recognized over twenty years ago and led the US health agencies in the early 1990s to recommend that women of childbearing age consume 400 mcg of folic acid each day. The FDA followed by mandating that certain foods be fortified with folic acid and this has resulted in a significant enhancement of maternal folate status to levels that are often difficult to otherwise achieve naturally. At least one study indicates that this has decreased the incidence of NTD’s. However, this same time period directly coincides with what many feel is the apparent beginning and continuous increase in the prevalence of Autism and related Autism Spectrum Disorders (ASD’s) in the US. [I wasn't just imagining the coincidence!] Are these similar time frames of changes in maternal folate status and possible Autism prevalence a random event or has improved maternal (and fetal) folate status during pregnancy played a role? It is not only plausible but highly likely. A particular polymorphic form to a key enzyme required to activate folate for methylation in neurodevelopment, 5- methylenetetrahydrofolate reductase (MTHFR), demonstrates reduced activity under low or normal folate levels but normal activity under conditions of higher folate nutritional status. A consequence of the presence of the polymorphic form of this enzyme during normal or reduced folate status are higher plasma homocysteine levels than noncarriers and the combination of these factors have been shown in several studies to result in an increase rate of miscarriage via thrombotic events. However, the incidence of hyperhomocysteinemia in the presence of the polymorphism is reduced under the common condition of enhanced folate status and thereby masks the latent adverse effects of the presence of this enzyme form during pregnancy. Of great importance is that this polymorphism, although common in the normal population, is found in significantly higher frequency in Autisic individuals. It is hypothesized here that the enhancement of maternal folate status before and during pregnancy in the last 15 years has altered natural selection by increasing survival rates during pregnancy of infants possessing the MTHFR C677T polymorphism, via reduction in hyperhomocysteinemia associated with this genotype and thereby miscarriage rates. ["Natural selection" is certainly sad in this context.] This also points directly to an increased rate of births of infants with higher postnatal requirements for folic acid needed for normal methylation during this critical neurodevelopmental period. If these numbers have increased then so have the absolute number of infants that after birth fail to maintain the higher folate status experienced in utero thus leading to an increased number of cases of developmental disorders such as Autism. [Intriguing--had my nephew been on large doses of folate as a toddler, would he have not developed an autism spectrum disorder?]

I am emphatically not saying that women should never take prenatal vitamins. And if they have had a child already with a neural tube defect, I'm all for them taking lots of folic acid! On the other hand, if a woman is already getting needed nutrients from her diet, she might want to consider whether she's willing to mess around with nature by taking regular vitamin megadoses. After all, up to 50% of pregnancies end in miscarriage--there's got to be a good reason for that.

Update: Please see my updated post on this subject at http://petticoatgovernment.blogspot.com/2011/11/my-updated-theory-on-autism.html.

!! Further update!! : A recent study out of Norway, where they do not enrich the food supply with folate, indicates that taking folic acid just before and after conception markedly decreases the probability that the child will have autism. In light of it, I revise everything I've ever said on this issue to include a recommendation that women trying to conceive take folic acid supplements from 4 weeks pre-conception to 8-weeks post-conception. Here's the abstract for the Norway study on the JAMA website:

ABSTRACT

ABSTRACT | METHODS | RESULTS | COMMENT | AUTHOR INFORMATION | REFERENCES

Importance  Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders.

Objective  To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder–not otherwise specified [PDD-NOS]) in children.

Design, Setting, and Patients  The study sample of 85 176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity.

Main Outcome Measure  Specialist-confirmed diagnosis of ASDs.

Results  At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61 042) had autistic disorder, compared with 0.21% (50/24 134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use.

Conclusions and Relevance  Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.

ADDENDUM: I've recently discovered that around half the USA has a genetic mutation that makes it hard for them to actually use the folic acid that is put in white flour, breakfast cereal, and most multivitamins. To bypass the problem, it's better to ingest L-methylfolate, which is exactly the form that our bodies use. On average, it is better for increasing our blood folate status and doesn't mask B-12 deficiency. And get the word out so that food producers will start putting L-methylfolate in their products instead of plain folic acid.

Notice that in the Norway study above, autism went down by half in the group that took folic acid. Maybe it would have gone away almost completely if they'd given all the mothers L-methylfolate, seeing as around half the women likely couldn't use folic acid very well.

Final Update: Here's a link to a letter to the editor that a friend and I co-authored where we discuss the possible connections between folic acid overuse, inattentive-type ADHD, and autism spectrum disorders. It was published in the International Journal of Food Sciences and Nutrition in June of 2016.

[Edited Jan. 11, 2018: OK, not fully finished with this topic. I think that proper nutritional support of the two enzymatic pathways from homocysteine to methionine is crucial in helping with autism spectrum disorders. The first pathway uses folate and vitamin B12; unfortunately the folic acid and cyanocobalamin forms of those vitamins appear to be counterproductive in excess, so avoid ingesting them regularly in high amounts, instead eating the forms of B12 and folate that occur naturally in foods. The second pathway uses glycine betaine and zinc; glycine betaine is easy to get out of plant cells by boiling it out, so I suggest regularly eating soup made with foods high in glycine betaine. My family now puts some glycine betaine in with the family beverages and it appears to have had a calming effect in our children who showed signs of Asperger's and ODD.]