Evidence that vitamin D is involved in the autism epidemic is mounting. In 2009, Life Extension Magazine published a detailed description of the vitamin D deficiency as it pertains to autism theory, and in 2010, a Scientific American article asked, “What if vitamin D deficiency is a cause of autism?” In 2009, Emily Deans, MD, wrote an extensive piece in Psychology Today outlining the theory; and in 2010, Dennis Kinney, PhD, and colleagues at Harvard, endorsed the vitamin D connection to autism. In 2012, Eva Kočovská, PhD, and colleagues, with senior author professor Christopher Gillberg of the Gillberg Neuropsychiatric Institute in Sweden, reviewed the evidence supporting the vitamin D link to autism and called for “urgent research” into the connection.
I first became interested in vitamin D when I learned that it is not a vitamin. Instead, it is the only known substrate of a seco-steroid neuro-hormone that functions, like all steroids, by turning genes on and off.
That means it has as many different mechanisms of action as the genes it regulates. Moreover, vitamin D directly regulates hundreds, if not thousands, of the 21,000 coding genes of the human genome. Genes are responsible for making the proteins and enzymes the human body relies on for normal development and function.
I myself first published, and later extended, epidemiological and animal data connecting vitamin D deficiency with autism. My second article discusses some of the autism/vitamin D evidence, such as the devastating effect gestational vitamin D deficiency has on developing brains.
For the last three years, I have been helping parents of autistic children correct their children’s vitamin D deficiencies. My very preliminary and unscientific impressions are that if the child takes enough vitamin D, along with the correct co-factors, about 25 percent of the parents report dramatic improvements in their child’s autistic symptoms; about 50 percent of parents report significant improvements; and 25 percent of parents report no change.
But how can vitamin D help autism—a condition that is highly heritable?
Autism may be a genetic disease that isn’t inherited, but how can that be? It appears that many small, new genetic mutations, such as those seen in autism, occur either in the womb or during early childhood. This theory explains the genetics of autism very nicely: These mutations are the most common genetic findings in autistic children.
Scientists have identified at least five vitamin D-dependent genes that direct DNA repair proteins. These proteins have only one job: to fix your broken DNA. James Fleet and colleagues at Purdue University wrote an excellent article on how vitamin D helps prevent cancer, and he almost offhandedly mentioned DNA repair as one of vitamin D’s mechanisms of action in cancer. Likewise, other research has shown that vitamin D is responsible for protecting the genome from genetic damage.
Repairing the genome is just another one of vitamin D’s repair and maintenance functions. Once the body has enough vitamin D, including enough to overcome any inherited defect of the vitamin D system, all those little genetic repair train cars can chug happily along, fixing the multiple genetic variations—including, perhaps, those associated with autism.
DNA protection differs from DNA repair because preventing DNA damage is preferable to repairing the damage once it has occurred. In 2001, researchers reported that vitamin D stabilizes chromosomal structure and prevents DNA double-stranded breaks. They concluded that the role of vitamin D in repairing gene mutation and DNA strand breaks is much more important than we originally thought.
Because some scientists think that vitamin D helps repair DNA, it’s not outlandish to think that vitamin D has a role in protecting DNA as well. Three scientists from the University of Sydney Medical School in Australia recently reviewed test tube animal and human studies in detail, concluding that vitamin D does appear to protect DNA from mutations. They went so far as to say that vitamin D deficiency is associated with DNA damage from various cellular stresses and that obtaining adequate vitamin D is important in preventing DNA damage.
This research supports my theory that the tiny, widespread mutations and DNA damage in those with autism are the effects of a genetically impaired vitamin D system interacting with inadequate amounts of vitamin D building blocks. This interaction causes DNA injury not to be repaired. These differences in DNA have confused geneticists for years because they assumed that any genetic abnormality in those with autism was a cause rather than an effect.
Some researchers believe that autism is a disease of neuro-inflammation and that vitamin D’s anti-inflammatory actions may profoundly counter that inflammation. Studies in animals show both direct and indirect anti-inflammatory effects of vitamin D involving both arms—adaptive and innate—of the immune system.
Recent research reveals that activated vitamin D exhibits multiple anti-inflammatory effects, such as inhibiting the synthesis and biological actions of pro-inflammatory prostaglandins—unsaturated fatty acids that cause inflammation—the levels of which are elevated in those with autism. Vitamin D also exerts anti-inflammatory activity through the inhibition of nuclear factor-kappa B—NF-KB, a protein complex that is involved in abnormal, pro-inflammatory signaling in autistic brains.
There are more than 160 human autoimmune diseases, and some people believe that many cases of autism are, in fact, autoimmune; a number of autoantibodies in the brain have been identified in autistic children. Furthermore, levels of such antibodies are directly associated with the severity of autism.
A recent study found that the level of one particular anti-neural autoantibody was inversely correlated with vitamin D levels. In the same study, 25-hydroxy vitamin D—a pre-hormone produced by the liver—had significant negative correlations with the Childhood Autism Rating Scale. These findings beg the question: Would vitamin D help autism by reducing the blood levels of autoantibodies in autistic children?
Neurotrophins are the family of proteins that induce the development, function, and survival of nerve and brain cells. Vitamin D upregulates neurotrophins, such as the nerve growth factor (NGF) and the glial cell-line derived neurotrophic factor (GDNF), up to a fivefold. Could vitamin D help autistic children by increasing neurotrophins, thus helping a damaged brain develop properly?
Several research groups report that vitamin D upregulates the antioxidant glutathione in the brain. Because glutathione participates in the scavenging of oxidative byproducts and the chelation (capture and excretion) of heavy metals, it is involved in the brain detoxification process. Thus, in addition to functioning as a master antioxidant, glutathione acts to remove heavy metals such as mercury. Glutathione protects nerve cells and nerve conduction that is critical to mental processing. In this regard, its protective effects on toxins are particularly important.
Scientists have reported that recent gene-profiling has revealed several more antioxidants whose genes are directly upregulated by vitamin D. This includes thioredoxin reductase and superoxide dismutase, both of which, among other things, function as antioxidants and detoxification agents. Thus, extra vitamin D may upregulate a suite of antioxidants.
Various tenable mechanisms exist for how vitamin D could help children with autism. Be it via anti-inflammatory actions, anti-autoimmune activities, upregulation of neurotrophins, or stimulation of antioxidant pathways, adequate doses of vitamin D (enough to obtain natural levels of 50 to 80 ng/ml) may be a potential treatment for some cases of autism.
Mitochondria are the power plants of the cells; every human cell has them. When they work properly, they transform sugar into an energy molecule called adenosine triphosphate (ATP). With autism, something is wrong with the mitochondria: About 1 in 20 people with autism have obvious mitochondrial disease. Perhaps as many as 1 in 3 are in the gray zone; their mitochondria are not fully working. However, the numbers could be even higher—mild mitochondrial dysfunction is hard to document.
Recently, scientists tested an activated vitamin D-like drug, paricalcitol, to see if it could protect mitochondria. Scientists purposefully injured mitochondria in two groups of lab animals—one group given a placebo and the other given activated vitamin D—by tying off the ureter (the tube connecting the kidney to the bladder). In the non-vitamin D group, the mitochondria were larger and misshapen in their interiors, indicating serious damage; these changes did not occur in the vitamin D group. Additionally, markers of mitochondrial damage reverted back to normal in paricalcitol-treated animals several hours after the ureter was untied, but not in the control group.
These results suggest that vitamin D may have a protective effect at the mitochondrial level. Because vitamin D is turned into activated vitamin D in the tissues, it seems likely that vitamin D could protect mitochondria in people with autism.
No Randomized Controlled Trials
There have been no randomized controlled trials, and just one open label trial, concerning the role of vitamin D in preventing or treating autism spectrum disorder (ASD). Parents who want to try it should do their research and thoroughly understand that other than a single open label clinical trial, as well as test tube, epidemiological, and animal studies, no randomized controlled trials exist showing such an effect. However, a well-designed randomized controlled trial of vitamin D in autism is currently waiting for funding in Australia.
As I said previously, my very rough estimation is that around 75 percent of autistic children seem to respond at least somewhat to higher doses of vitamin D if given with the correct dose of co-factors, such as magnesium, zinc, boron, and vitamin K2. To date, I have noticed the following things predict a positive response:
- Reported seasonality of autistic symptoms for children with summer access to a swimming pool, or similar extensive outdoor activities with few clothes and without using sunblock, in which the child is much better in late summer than he or she is in late winter, usually respond.
- Children who had a period of early normal development, compared with those who seem affected even as infants, seem to respond better.
- Children with mild or moderate autism seem to respond better.
- Children younger than 8 seem to respond better than older children do.
None of these, except perhaps a very distinct seasonality of symptoms, clearly predicts a response to vitamin D. In the same vein, some parents have told me that children with infantile onset of symptoms, more severe autism, or children older than 8 have responded.
Unfortunately, my experience is that the 10 to 20 percent of children with known genetic causes of autism—such as Rett syndrome, fragile X syndrome, tuberous sclerosis, clear mitochondrial defects, submicroscopic deletions or duplications in DNA sequences, or deletions or duplications of chromosome regions—do not respond.
Parents can get the full story by reading my book, Autism Causes, Prevention and Treatment.
By John Cannell, MD, the founder of the Vitamin D Council. He has written many peer-reviewed papers on vitamin D and speaks frequently across the United States on the subject. He has served the medical field as a general practitioner, emergency physician, and psychiatrist.