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Friday, 28 February 2014

Vitamin D in Autism – too much or too little?


Reader’s of this blog will be aware that serotonin plays a major role in autism, and also in many other mental health conditions, like depression.

Vitamin D also regularly raises its head in discussions about autism.  You may recall the Somali autism clusters in Sweden and Minneapolis; researchers suggested that the Somali immigrants were not getting enough sun and therefore lacked vitamin D and so produced children with autism.  I did point out that another large Somali autism cluster exists in sun-drenched San Diego.
Even Martha Herbert talks about vitamin D deficiency and autism.

A while back we had a guest blogger, Seth Bittker, present his opposing view, that too much vitamin D added to food in the American diet may be contributing to the rise in autism there.
In same week that Seth has published his paper on this subject, yet another paper has appeared with the opposing view.  So who is right?

The case for (even) more Vitamin D

The first paper is:- 

 
The authors make the following case:-
Serotonin and vitamin D have been proposed to play a role in autism, however, no causal mechanism has been established. Now, researchers show that serotonin, oxytocin, and vasopressin, three brain hormones that affect social behavior related to autism, are all activated by vitamin D hormone. Supplementation with vitamin D and tryptophan would be a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.

After absorbing L-tryptophan from food, our bodies convert it to 5-HTP (5-hyrdoxytryptophan), and then to serotonin.
The supplements L-tryptophan and 5-HTP are widely available and have been used in ADHD and autism but there is no evidence that they are effective.  All that has been shown is that too little tryptophan is bad; there is nothing to show that abnormally large amounts do any good.
If you read the full paper there is an excellent explanation of the role of serotonin in autism.  It is beyond doubt that in many kids with ASD there is high blood serotonin, but low brain serotonin.
To fully treat autism, one thing to be done is to raise brain serotonin levels, without any nasty side effects.  SSRI drugs like Prozac, used to treat depression, do raise brain serotonin but often cause dependence and side effects (like suicidal thought).
It would be great if some vitamin D and tryptophan could do the job.

If you read the older literature, you will see that there is nothing new about the idea to supplement with Tryptophan in autism.  The results to date have been nothing special.
Here is a paper by Paul Whiteley and Paul Shattock:-
 

“It has been shown that a diet depleted of tryptophan is not beneficial for children with ASDs and that some symptoms are exacerbated. Presumably, the existing lack of available serotonin (and other tryptophan derivatives) was exacerbated under these circumstances. Supplementation with tryptophan would probably not be helpful in the majority of cases because the conversions along the important pathways are inhibited and tryptophan is likely to be converted along the IAG route, which would be unhelpful. Anecdotal clinical reports suggest that some children show benefits and others may get worse but no formal studies have been reported.

For this reason, and because tryptophan is a prescription-only drug*, we have looked at other methodologies. The active transmitter, serotonin, does not cross the blood brain barrier and so would be ineffectual in this respect. However, the precursor molecule 5-HTP does cross the blood brain barrier and reach the appropriate target areas. Some parents have reported impressive consequences, particularly with regard to sleep patterns; some physicians have been able to reduce the doses of e.g. risperidone (an anti-psychotic drug) by supplementing 5-HTP but, on the whole, the results have been less useful than would have been predicted.”


Vitamin D and Children with ASD
Children with autism are probably amongst the most “vitamin-supplemented” of any, since parents tend to give copious amounts of multi-vitamins and also vitamin D rich omega 3 fish oil.  It is hard to imagine that any of these children are deficient in vitamin D.
 

The case for too much vitamin D
In his paper, Bittker seeks to correlate the increase in vitamin D fortification in America with the rise in autism; he highlights groups that do not have vitamin D fortified food and where autism is far less prevalent.

 

Conclusion
So who is right?  Well for sure too little tryptophan or vitamin D is bad for you; but are abnormally high levels good or bad?  In the case of tryptophan, plenty of people have tried supplementation in autism and ADHD and we would probably have heard if it produced a great effect.

Do large amounts of vitamin D help with autism? I very much doubt it, but it would be very easy to do a trial, assuming you found some parents who had not read the Bittker paper.
The good thing is that raising the low level of brain serotonin seems agreed by everyone as a prime target of any autism intervention. For me, vitamin D and tryptophan is not the answer.

 

8 comments:

  1. There are 27 reasons to believe that Autism is due to low vitamin D.
    http://is.gd/DAutism

    ReplyDelete
  2. Dermatoendocrinol. 2013 Jan 1;5(1):159-64. doi: 10.4161/derm.22942.
    Autism prevalence in the United States with respect to solar UV-B doses: An ecological study.
    Grant WB1, Cannell JJ2.
    Author information
    Abstract

    Evidence is mounting that vitamin D deficiency is intimately involved in autism. We report on autism prevalence by US state for those aged 6-17 y in 2010 with respect to indices of solar UV-B (UVB) doses. We calculated autism prevalence rates for white, black and Asian Americans by using total prevalence and relative populations of minors for each ethnic group by state. Analyses omit AK and HI (considered extreme cases), WY (no data), along with AZ and ND for black Americans (low numbers) and DC, ME, MT, ND and SD for Asian Americans (low numbers). For white Americans, the regression coefficient for solar UVB doses and autism prevalence ranged from -0.52 in January to -0.57 in October. For black Americans, the regression coefficient for latitude was 0.61, whereas those for solar UVB ranged from -0.55 to -0.61. For Asian Americans, the values for solar UVB ranged from -0.28 to -0.38. The inverse correlation between solar UVB and autism prevalence is similar to that for many types of cancer in the US. The journal literature indicates that adverse effects on fetal brain development during pregnancy due to vitamin D deficiency can explain these findings. However, we cannot rule out a role of vitamin D deficiency in early life. These results add to the evidence that vitamin D deficiency may be an important risk factor for autism and suggest that pregnant women and autistic individuals raise their serum 25-hydroxyvitamin D concentrations above 30 ng/ml.

    ReplyDelete
  3. Dr. Grant,
    Sunlight may be mildly helpful in many cases without oral supplementation of vitamin D being desirable. I believe in the paper that you mention you exclude Alaska and Hawaii. They both have comparable autism rates according to the LA Times data that I understand the paper was based upon despite having very different levels of sunlight. Both have a rate that is about three times Iowa's rate and Iowa's rate is much lower than states south of it. Also I wonder if those in northern climates are more likely to be given supplemental vitamin D as babies.
    In addition if you examine the effects of oral vitamin D carefully it appears that it would be problematic in many cases of autism. For example autism typically features excessive neuronal growth early in life. Vitamin D supplementation which you cite as important for brain development will upregulate neuronal growth, which will be problematic in some. In addition autism features a Th2 skew to the immune system normally. Vitamin D will make this skew more extreme. As a Th2 skew tends to push the immune system towards allergies, is it a coincidence that those with autism fequently have asthma, eczama, and food allergies?
    In addition vitamin D supplementation among the young has increased significantly since the 1980s and the autism rate has gone up significantly over this time period. This suggests to me that oral supplementation is not the answer.
    The blood levels of vitamin D that you mention as a guide for guaging supplementation may also be misleading. Blood levels of vitamin D are often low in cases of endothelial damage and those with autism often have endothelial damange based on other markers. So it seems you may cause more severe endothelial damage and other damage by supplementing in such cases.

    ReplyDelete
  4. Hi. Sufficient magnesium is required for the absorption of vitamin D, from supplements or sunlight. Human beings have not suddenly lost the ability to get vitamin D from the sun after 3.5 million years. We have lost our sources of magnesium. We are choosing water with no or low magnesium content, plus it's not in our food in the same amounts because acidic soil cannot hold on to organic carbon, including magnesium carbonate - it's still there, just 50 cm under the soil surface where tillers don't reach. If you want to raise your vitamin D levels, throw out the vitamin D pills and take magnesium instead. Start slow and remember magnesium's cofactors, including selenium.

    ReplyDelete
  5. I've got Asperger's syndrome and have recently been diagnosed with adult rickets, a total lack of vitamin D in my body. I took a prescribed megadose of 100,000 UIs and, after initially tripping for 24 hours, now feel wonderful, both physically [so much stronger] and emotionally...I actually feel something, I have passion!

    ReplyDelete
    Replies
    1. Carefull with going too high on the d3 dosing, if you look at my other posts I have included blood tests that shows its actually quite easy to get somewhat toxic levels in your blood.
      I was doing 5000-10000iu per day for a while, felt very good on it and just like you I have aspergers.

      Delete
  6. Hi all.
    This paper shows how D-vitamin inhibits prostaglandins by downregulating the gene expression of COX2-gene (and others). The article is about prostate cancer, but should be relevant in a broader context.

    "Calcitriol, the active form of vitamin D (..) significantly decreases the expression of the PG synthesizing cyclooxygenase-2 (COX-2) gene, while increasing that of PG inactivating 15-prostaglandin dehydrogenase (15-PGDH). Calcitriol also inhibits the expression of the PG receptors EP2 and FP. (..)
    We also propose that calcitriol can be combined with NSAIDs that inhibit COX enzyme activity, as a potential therapeutic strategy in prostate cancer."

    http://ar.iiarjournals.org/content/26/4A/2525.abstract

    This comment might have fitted better under the post of arachidonic acid (https://epiphanyasd.blogspot.se/2016/10/regulation-of-arachidonic-acid-aa.html#comment-form), but I think more people are searching for D-vitamin facts.

    /Ling

    ReplyDelete
    Replies
    1. Hi Ling,

      COX-2 regulation seems very crucial as its highly involved in inflammation, however atleast in some forms of autism, atleast in aspergers, there has also been studies where a dose of arachidonic acid was added in addition to omega3 fatty acids with some success in socializing.
      This highlights the importance of the correct ratios of all important fatty acids.

      Effects of large doses of arachidonic acid added to docosahexaenoic acid on social impairment in individuals with autism spectrum disorders: a double-blind, placebo-controlled, randomized trial.
      https://www.ncbi.nlm.nih.gov/pubmed/22370992

      "The outcome measures were the Social Responsiveness Scale and the Aberrant Behavior Checklist-Community."

      "This preliminary study suggests that supplementation with larger ARA doses added to DHA improves impaired social interaction in individuals with autism spectrum disorder by up-regulating signal transduction."

      "levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (p < 0.001). In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the autistic participants (n = 20) compared to controls.
      Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism."

      This study says HIGH PGE2 and particulary LOW ARACHIDONIC ACID and LOW DHA, this would indeed seem high cox-2 expression.
      However arachidonic acid is also needed for other prostaglandins as arachidonic acid has multiple pathways included some anti-inflammatory prostaglandins.
      The most puzzling thing to me out of all of this is the high pge2 in autism, yet the dramatic improvement in behaviour during fever (where pge2 is increased in the hypothalmus where body temperature/sensing is regulated).

      Now I have allready posted about me somewhat trialing Arachidonic acid in the past.
      I chickened out while using the ARA in addition to my omega3 fatty acids despite noticing that I was leaving the door in the evening far more often to be with friends and others.

      I used this brand and still have most of the bottle left:
      https://ibb.co/ccJ1Lm

      Before re-starting this I need to get a proper protocol set with proper ratios of all the fatty acids. My capsules have 350mg each I think a blood test (if possible?) of my current fatty acid profile would be necesarry.
      Also the addition of a cox2-i with it would promote other pathways including anti-inflammatory prostaglandins?

      Delete

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