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Mechanism of action in autism?

Posted on: May 7, 2012   by  John Cannell, MD


A paper came out last week that supported, at least to me, the mechanism of action in autism that I proposed in 2007. As you know, some of us are tall, some are short, and science can usually display that and so many other things in nature in some sort of a normal or Gaussian distribution. In what appears to me to be unique research, Dr. Peter Schnatz and his team from Jefferson Medical College wanted to know if some of us have lots of vitamin D receptors (VDR) and some of us only a few. His team also wanted to know if that variation was associated with atherosclerosis.

Schnatz PF, Nudy M, O’Sullivan DM, Jiang X, Cline JM, Kaplan JR, Clarkson TB, Appt SE. The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis. Maturitas. 2012 Apr 26. [Epub ahead of print]

He took 39 monkeys, kept them out of sunlight and gave them 1,000 IU of vitamin D/day and a plaque building (atherogenic) diet for three years. He then sacrificed them to count the number of VDRs inside their arteries as above the 50th percentile or below, and then measured the height of the atherosclerotic plaque in those arteries. To his surprise a strong negative association exists (p<0.001) between the two.

That is, if you are unlucky enough to be born with only a few VDRs, your atherosclerosis may get bad early, at least according to this animal model. However, he also pointed out that vitamin D itself increases the number of VDRs present. So just taking vitamin D can shift you over to having more VDRS.

This study was of interest to me because it is exactly the mechanism I proposed for the autism epidemic four years ago. In my 2007 paper on autism and vitamin D, I proposed that a quantitative and/or qualitative genetic mechanism was at work in autism. That is, low quantity and/or quality of the inherited vitamin D system have met with declining vitamin D levels over the last 30 years leading to damage to the most sensitive of the vitamin D organs, the developing brain.

Cannell JJ. Autism and vitamin D.Med Hypotheses. 2008;70(4):750-9. Epub 2007 Oct 24

If your genetics deals you low numbers of VDRs and you have to deal with vitamin D deficiency as well, your developing brain loses. The autism geneticists have been looking for mutations. It is not a mutation; the small de novo mutations they do find (in all 23 pairs of chromosomes) are effects, not causes, of autism because vitamin D deficiency impairs DNA repair mechanisms.

Other components of the vitamin D system, such as the amount and activity of the enzyme that makes activated vitamin D, the one-hydroxylase, is also inherited. You get either a little or a lot with most getting somewhere in between, for both quantity and quality, a normal or Gaussian distribution of each. The same is true of the vitamin D breakdown enzyme, the 24-hydroxylase, but here, high amounts are detrimental. More than 70% of your vitamin D level is heritable when levels are low.

Karohl C, Su S, Kumari M, Tangpricha V, Veledar E, Vaccarino V, Raggi P. Heritability and seasonal variability of vitamin D concentrations in male twins. Am J Clin Nutr. 2010 Dec;92(6):1393-8. Epub 2010 Oct 13.

Say you are unlucky enough to inherit low VDRs and low one-hydroxylase enzyme activity both together, and your mother believes in strict sun avoidance and sunblock. She breast feeds you (if mother is below 40 ng/ml, and most are, there is no vitamin D in breast milk) and then weans you on vitamin D-less 100% pure fruit juice and not vitamin D fortified cow’s milk. To boot, you will not eat cold-water fatty fish, reindeer meat, or sea gull eggs (all with some vitamin D). By the time you are 12 months, you literally have no source of vitamin D and your inherited vitamin D physiology will interact with your low vitamin D level to injure your developing brain, as it injures the arteries of monkeys. Exactly the same mechanism can happen in utero.

Presto, you have a brand new “genetic” disease, as autism is, interacting with the environment, as autism is, to create an unfathomable new epidemic, as autism is. While these genetics have always been around, the low amount of substrate is brand new, thus a new “genetic” epidemic. The 1-hydroxylase may be involved because it explains the now 5:1 male to female ratio in autism. Estrogen increases expression of the 1-hydroxylase, but testosterone does not and may inhibit it. In addition, Liel et al reports estrogen does the same to the VDR.

Liel Y, Shany S, Smirnoff P, Schwartz B  Estrogen increases 1,25-dihydroxyvitamin D receptors expression and bioresponse in the rat duodenal mucosa. Endocrinology. 1999 Jan;140(1):280-5.

If I’m right, what do autistic children need? They need enough vitamin D (adult doses) to upregulate their VDRs and their one-hydroxylases in order to stop the autoimmune inflammatory brain damage that is ongoing. If I’m wrong, what will happen? Children will have high-normal vitamin D levels, stronger bones, fewer infections, less asthma, fewer autoimmune disorders, and better physical performance.

Remember, this year, according to the CDC, if you have a male child, he will have a 1 in 54 chance of developing autism by age 8, and the epidemic is growing at almost 20% per year. Couples with an autistic child are under more stress than are couples with a child with a fatal illness. The divorce rate is double. Besides the meltdowns, the parent’s main worry is who is going to care for my child when I’m gone. No person of good heart can ignore this epidemic.

2 Responses to Mechanism of action in autism?

  1. [email protected]

    Many times my late father sadly commented on who would take care of “retarded” children after their parents were gone. My father was a real “tough guy” but very sentimental (of course, that being the best possible of combinations!).

  2. pcolquet

    Another mechanism may be that D3 protects against the neurotoxic effects of glutamate. Autistic kids are said to have excess glutamate (and not enough GABA to balance it out), which explains the stimming, and sensory issues, among other symptoms. Vitamin D3 may help protect against neuronal cell death upon exposure to glutamate.


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