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Autism and Vitamin D - Dr. Cannell in Life Extension Mag - Jan 2014

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In 2008, I first published4 and later extended5 epidemiological and animal data connecting vitamin D deficiency with autism.
My second article is open access, discusses some of the autism/vitamin D evidence, and can be fully accessed at: www.lef.org/autism.
In 2009, Life Extensión® Magazine published a detailed description of the theory.6
In 2009, Emily Deans, MD, wrote an extensive piece in Psychology Today outlining the theory of the connection between autism and vitamin D.7
In 2009, Scientific American asked, "What if vitamin D deficiency is a cause of autism?"8
In 2010, Kinney and colleagues at Harvard endorsed the vitamin D connection to autism.9
In 2012, Ko&wská and colleagues, with senior author Professor Christopher Gillberg of the Gillberg Neuropsychiatric Institute in Sweden, reviewed the evidence supporting the vitamin D connection to autism and called for "urgent research" into the connection.10
For the last year, I have been helping parents of autistic children correct their child's vitamin D deficiency. My very preliminary and unscientific impressions are that if the child takes enough vitamin D (as long as they take enough cofactors with the vitamin D), about 25% of the parents report dramatic improvements in their child's autistic symptoms, about 50% of parents report significant improvements, and 25% of parents report no change.
How could vitamin D help autism, a condition that is highly genetic? Research has demonstrated that vitamin D has multiple mechanisms of action, many of which have been demonstrated to play a role in autism. Let's take a look at four:

Anti-Inflammatory Actions

Some believe that autism is a disease of neuro-inflammation.11,12 According to scientific research vitamin D has profound anti-inflammatory actions.13 Experimental models show both direct and indirect anti-inflammatory effects of vitamin D involving both arms of the immune system (innate immunity and adaptive immunity).14,15
Recent research reveals that activated vitamin D exhibits multiple anti-inflammatory effects.16 For example, vitamin D inhibits the synthesis and biological actions of pro-inflammatory prostaglandins, which are elevated in autism.16-18 Vitamin D also exerts anti-inflammatory activity through the inhibition of nuclear factor-kappa B, which is involved in abnormal signaling in autistic brains.19,20

Could vitamin D help autistic children by reducing inflammation?

Autoimmune Actions

There are at least 80 recognized human autoimmune diseases with new diseases frequently added to the list.21 A number of autoantibodies to the brain have been identified in autistic children, causing some to believe that many cases of autism are autoimmune.22,23 Furthermore, the levels of such antibodies are directly associated with the severity of autism.24,25
A recent study found that the level of one antineural autoantibody (anti-MAG) was elevated in 70% of patients with autism.26 The study found that higher levels of anti-Mag were associated with significantly lower levels of vitamin D.26 In the same study, low serum levels of 25-hydroxyvitamin D were significantly associated with higher scores on an autism diagnostic assessment known as the Childhood Autism Rating Scale, indicating increasing severity of autism symptoms.26

Could vitamin D help autistic children by reducing the blood levels of autoantibodies in autistic children?

Neurotrophins

Neurotrophins are the family of proteins that induce the development, function, and survival of nerve and brain cells. Vitamin D upregulates neurotrophins, such as NGF (nerve growth factor) and GDNF (glial-derived neurotropic factor), up to five-fold.27-29

Could vitamin D help autistic children by increasing neurotrophins and thus help a damaged brain develop properly?

Antioxidants

Several research groups report that vitamin D upregulates the antioxidant glutathione in the brain.30,31 Glutathione is involved in the brain detoxification process because it participates in the scavenging of oxidative byproducts and the chelation (capture and excretion) of heavy metals.31-33 Glutathione protects nerve cells and nerve conduction critical to mental processing, especially from toxins such as mercury.33
Other research teams have reported that recent gene profiling has revealed several more antioxidants whose genes are directly upregulated by vitamin D.34 This includes thioredoxin reductase 1 and superoxide dismutase, both of which function as antioxidants and detoxification agents.

Could vitamin D help autistic children by upregulating numerous antioxidants?

Theoretical Only

It's clear that various reasonable 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 blood levels of 50-80 ng/mL of 25-hyroxyvitamin D) may be a potential treatment for some cases of autism.
However, such a claim is entirely theoretical. There are no randomized controlled trials, no open label trials, no case series, and not even one published case report of vitamin D helping autism.
Even though there are no studies proving the benefits of vitamin D in autism specifically, the proven safety and benefits of vitamin D, added together with the fact that vitamin D has been shown to have a beneficial effect on many of the mechanisms of action that underlie autism, make vitamin D a smart option for children with autism.
Parents who want to try it should thoroughly understand that no evidence, other than theoretical, exists for such an effect.

How To Start Your Child On Vitamin D

For parents who want to proceed on their own, the key to success is obtaining high physiological 25-hydroxyvitamin D blood levels around 80 ng/mL (the same levels that are obtained by lifeguards in August).
As all studies show that autistic children are low in vitamin D, getting a 25-hydroxyvitamin D blood test to start is usually unnecessary.
The first step is simply to give your child 50 IU of vitamin D3 per pound of body weight per day. Liquid vitamin D is available from several sources.
So a 25-pound child would be started on 1,250 IU each day of D3, a 50-pound child on 2,500 IU each day, etc. This dose will usually result in mid-range physiological 25-hydroxyvitamin D levels (40-60 ng/mL), although some children may obtain higher physiological levels (60-70 ng/mL) on this dose.
The child should also be started on vitamin D's cofactors, such as vitamin K2 (3 mcg per pound of body weight) and nutrients in a multi-nutrient powder formula. If Life Extension Mix™ powder is used, V a scoop for every 25 pounds of body weight can be blended in juice or a smoothie. The roughly 700 IU of vitamin D3 in one scoop of powder will help raise vitamin D levels.
After three months on the initial vitamin D dose, obtain another 25-hydroxyvitamin D blood test. If the 25-hydroxyvitamin D level is by any chance over 80 ng/mL, then the child's dose is adequate and nothing else needs to be done but to hopefully watch for improvements in core symptoms.
If 25-hydroxyvitamin D levels remain below 80 ng/mL, then a proportional dose increase of 25 IU vitamin D3 per pound of body weight is indicated.
For example, a 25-pound child on 1,250 IU a day would increase to 1,875 IU a day, and a 50 pound child on 2,500 IU a day would increase to 3,750 IU a day.
In three more months, obtain another 25-hydroxyvi-tamin D test and adjust doses accordingly. If 25-hydroxyvitamin D levels exceed 100 ng/mL, simply reduce the dose by 10% for every 10 ng/mL the test is above 100 ng/mL.
Levels above 100 ng/mL do not mean "toxicity" as "toxicity" (asymptomatic hypercalcemia) is rare with 25-hydroxyvitamin D levels below 200 ng/mL, and 200 ng/mL is very difficult to obtain.35 If these high doses make you nervous, have your child's blood calcium level checked, and you will see your child's calcium level is not high (over 10.5 mg/dL).
Keep adjusting the dose every three months based on vitamin D levels. It is important that you test for serum 25-hydroxyvitamin D and not 1,25-dihydroxyvitamin D. For children who do not tolerate venipuncture, an accurate blood spot test requiring only a finger prick is available at www.vitamindcouncil.org.
For optimal absorption, give your child vitamin D during the meal of the day that contains the most fats. This may produce the optimal 25-hydroxyvitamin D levels suggested at the beginning of this section without having to resort to higher dosing.
As I said above, my very rough estimation is that around 75% of autistic children seem to respond at least somewhat to higher doses of vitamin D after levels are around 80 ng/mL.

Role Of Vitamin D In Autism WHAT YOU NEED TO KNOW - sidebar

  • Vitamin D inhibits the synthesis and biological actions of pro-inflammatory prostaglandins, which are elevated in autism.
  • A number of autoantibodies to the brain have been identified in autistic children, causing some to believe that many cases of autism are autoimmune.
  • Research has shown that high levels of certain brain-antibodies are associated with low vitamin D status.
  • Vitamin D upregulates neurotrophins, the family of proteins that induce the develop ment, function, and survival of nerve and brain cells, up to 5-fold.
  • Vitamin D stimulates production of glutathione and several other antioxidant and detoxification enzymes.
  • Even though there are no studies proving the benefits of vitamin D in autism specifically, the proven safety and benefits of vitamin D, added together with the fact that vitamin D has been shown to have a beneficial effect on many of the mechanisms of action that underlie autism, make vitamin D a smart option for children with autism.

Response Rates

To date, I have noticed that children who fall in one of the following categories tend to respond positively to vitamin D:

  • 1. Children with reported seasonality of autistic symptoms (such as those with summer access to a swimming pool or similar extensive outdoor activities, in which the child is much better in late summer than he or she is in late winter) usually respond better.
  • 2. Children who had a period of early normal development (as opposed to those who seem affected even as infants) seem to respond better.
  • 3. Children with mild or moderate autism seem to respond better.
  • 4. Children under the age of eight seem to respond better than older children do.

However, none of these, except perhaps a very distinct seasonality of symptoms, clearly predicts a response to vitamin D. In the same vein, some parents tell me that children with infantile onset of symptoms, children with more severe autism, or children older than eight have responded.
Unfortunately, my experience is that the 10-20% 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 to vitamin D.
Parents who want me to participate in the diagnosis and treatment of their autistic child should contact my office in San Luis Obispo, California, for an appointment. There I will fully assess your child and give treatment recommendations to the parents. I will also be available for a limited number of tele-educational sessions via Skype, in which I will educate parents about vitamin D and its cofactors.

Summary

Over the past few years evidence has been mounting that vitamin D is involved in the autism epidemic. Research has demonstrated that vitamin D has multiple mechanisms of action, many of which have been demonstrated to play a role in autism. Scientific data have made it clear that various reasonable mechanisms exist for how vitamin D could help children with autism. Be it via anti-inflammatory actions, anti-auto-immune activities, upregulation of neurotrophins, or stimulation of antioxidant pathways, adequate doses of vitamin D (enough to obtain natural levels of 50-80 ng/mL) may be a potential treatment for some cases of autism. •
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
For further information, please contact: John Cannell, MD 1411 Marsh Street, Suite 203 San Luis Obispo, CA 93401


Especially noted by VitaminDWiki

  1. 50 IU of vitamin D / pound, with a goal of 80 ng/ml.
  2. vitamin K2 3 microgram/ pound
  3. best results before age 8

See also VitaminDWiki

  1. Both have strong inheritance features – Vitamin D about 60%
  2. Both have gotten substantially worse in last 30 years
  3. Vitamin D is known to be involved in brain development
  4. All autistic children are vitamin D deficient, but not all children who are deficient are autistic: since genes are involved as well
  5. When giving vitamin D to cure children of rickets “mental dullness” decreases as well
  6. Children with genes which give them too much (Williams Syndrome) have to reverse of autism – too sociable
  7. Mothers having lots of fish (and thus more vitamin D) give birth to kids with less autistic symptoms
  8. Both associated with weak bones
  9. Both worse around the age of weaning
  10. Autism is more common in rich families – more likely to apply sun screen and stay indoors
  11. Autism increases with drugs which lower levels of vitamin D
  12. Seizures are common with Autism - Vitamin D has been shown to reduce seizures
  13. Fewer autistic symptoms (such as sleep problems) during summer: when child gets more vitamin D from the sun
  14. Both worse with latitude
  15. Both vary with Ultraviolet light
  16. Both vary with time of year (more birth of autistics in March in Northern hemisphere)
  17. 2X more urban autism – less UVB in urban environments
  18. Both worse with pollution
  19. Both worse with increased clouds and rain
  20. Both worse with closely spaced pregnancies
  21. Autistics have abnormal immune response – similar to that of vitamin D deficiency
  22. Low levels of vitamin D in mother animals reduces brain function in offspring
  23. Vitamin deficient rat pups have similar brain abnormalities to that of human autistic children
  24. Autistic children get less vitamin D in their blood for the same amount of sun exposure
  25. The 4 males/1female autism ratio can be explain by the observation that estrogen increases vitamin D in the brain (testosterone does not)
  26. Both worse in African Americans (A-A 2-3 increased autism rate)
  27. Both worse in Dark-skinned immigrants in Europe


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Health Problems and D

  # of studies as of 9/30/14