My updated theory on autism

If you read a couple of my older posts, you'll see that I think there is a link between autism and folic acid supplementation. I started paying attention to this issue because I have a family member who rather demonizes vaccinations. I, on the other hand, believe that the alleged vaccine-autism connection has been quite thoroughly debunked. In fact, a recent study of brains of normal and autistic people found that there were too many neurons (67% more) in the cerebral cortex of the brains of those with autism, neurons which are generated only prenatally and which typically are pruned prenatally and in early infancy through programmed cell death (see this study). Instead of still suspecting vaccines in autism, we should instead pay attention to the prenatal environment.

I'm open to being proved wrong on there being a connection between folic acid supplementation and autism, particularly in light of the 2011 finding by UC Davis that women who took prenatal vitamins were less likely to have autistic children. The researchers postulated that it was because of a protective effect of folic acid. I think they're guessing on that point. Folic acid affects methylation and seems implicated in epigenetic changes, which are connected to autism (see this recent study). Some other vitamin or combination of vitamins appears to me to be more likely as the cause of the protective effect of the prenatal vitamins. Vitamin D seems a very likely candidate, especially since "developmental vitamin D deficiency increase[s] cellular proliferation in the brain and reduce[s] the amount of apoptotic cell death that is normally associated with neuronal differentiation", per this paper.

I imagine this as a possible scenario--folic acid, given with the laudable goal of preventing neural tube defects, also contributes to autism by increasing the number of neurons in the cerebral cortex, then vitamin D deficiency prevents the brain from adequately pruning the neurons to the proper number, resulting in an excess of these neurons, which prevents the brain from functioning in a neurotypical way. Please, any ideas on this? In the meantime, I'm 27 weeks pregnant, and it's nearly winter; I'm going out to buy vitamin D supplements this week.


!! 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 couldn't use folic acid very well.