Seth Bittker, a regular reader of this blog and our occasional guest blogger, is creating an excellent interview series with leading autism researchers.
These interviews will be of interest to all readers of this blog. There is something for everyone, whether you are the type that reads the literature in detail, or is more interested in the lay summary.
There are three interviews, all with podcasts, and more will be added later.
3) Dr. Derrick Lonsdale on thiamine deficiency and supplementation of thiamine derivatives in autism.
Good work Seth! I am sure he will be interested in your suggestions for future interview candidates.
By the way, in the third interview, Dr Lonsdale refers to his preferred thiamine supplement called TTFD, this has been used for decades in Japan. It is also called Fursultiamine and the Japanese brand name is Alinamin, which is made by Takeda, a major Japanese company. The Japanese website (in English) is here.
Takeda have various combinations with other B vitamins and some are sold on Amazon/eBay. Some with very high amounts of B12.
In interview number two above, Dr Hendrenon clearly does believe in the merits of extra B12 in autism. His trial did inject the vitamin, rather than take it orally.
It is best to only supplement at high doses the B vitamins that really help in your specific case; there are known negative reactions to some B vitamins, so best to go through them one by one.
There is also a version of TTFD sold as Allithiamine by a small US company, Ecological Formulas, which Seth is investigating.
So as long as swallowing pills is possible, you have the opportunity to replicate Dr Lonsdale's trial and see if you have a responder or not.
Side Effects of high dose B vitamins
According to the University of Maryland taking any one of the B vitamins for a long period of time can result in an imbalance of other important B vitamins, they suggest taking a B-complex vitamin which includes all B vitamins.
This might explain why some people who initially respond well to high doses of biotin, vitamin B7, later experience a negative response.
Many people do not respond well to high doses of multiple B vitamins as prescribed by some DAN-type doctors.
Dr Frye, from interview number one, is also a big believer in B vitamin supplementation.
Clearly B vitamin supplementation needs to be much better thought out, to keep any good effects, without developing any bad effects.
Takeda have various combinations with other B vitamins and some are sold on Amazon/eBay. Some with very high amounts of B12.
In interview number two above, Dr Hendrenon clearly does believe in the merits of extra B12 in autism. His trial did inject the vitamin, rather than take it orally.
It is best to only supplement at high doses the B vitamins that really help in your specific case; there are known negative reactions to some B vitamins, so best to go through them one by one.
There is also a version of TTFD sold as Allithiamine by a small US company, Ecological Formulas, which Seth is investigating.
So as long as swallowing pills is possible, you have the opportunity to replicate Dr Lonsdale's trial and see if you have a responder or not.
Side Effects of high dose B vitamins
According to the University of Maryland taking any one of the B vitamins for a long period of time can result in an imbalance of other important B vitamins, they suggest taking a B-complex vitamin which includes all B vitamins.
This might explain why some people who initially respond well to high doses of biotin, vitamin B7, later experience a negative response.
Many people do not respond well to high doses of multiple B vitamins as prescribed by some DAN-type doctors.
Dr Frye, from interview number one, is also a big believer in B vitamin supplementation.
Clearly B vitamin supplementation needs to be much better thought out, to keep any good effects, without developing any bad effects.
Hi Peter and Seth
ReplyDeleteAll about B vitamins is very interesting. We have been giving our son methyl and hydroxy B12 shots for over 2 years without any really good or bad effects. I kept giving them to support methylation. However, recently I came across this paper about Methylcobalamin increasing MTOR. As my son has a PTEN mutation, the last thing we want is to stimulate MTOR further.
What are your thoughts on this? Here is the link:
http://www.ncbi.nlm.nih.gov/m/pubmed/21458538/
I look forward for your comments.
Thank you!
Laura
If you have nerve damage, stimulating MTOR with methylcobalamin would be a good idea, like after an accident in sport. As you say Methylcobalamin would not be a good idea in someone with too much MTOR. Most important is that if there are no positive effects after two years, it might be time to stop. If you then notice a deterioration you can always start again.
DeleteHi Laura,
DeleteThanks for highlighting this. I agree with both Peter and Roger. I am unaware of any connection regarding methyl B12 and PTEN and had not appreciated methyl B12's effect on mTOR until you highlighted it. As Roger mentioned it may make sense to get some metabolic testing done to see if this can give some clues regarding what might be helpful.
There are some biochemical analyses of PTEN in the medical literature that I find interesting and that may give us some ideas. Specifically see http://www.ncbi.nlm.nih.gov/pubmed/23695273 and http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019996/. The first reference shows among other things that PTEN often features modest deficits of cysteine in the blood. The second says succinate is often high. The next step of the citric acid cycle requires iron sulfur clusters. So what I take from this latter reference is that there are not enough iron sulfur clusters which probably means insufficient sulfur. As cysteine is also a sulfur containing amino acid, these references together suggest to me that PTEN like many other types of autism often features sulfur deficits. Some potential ways to approach this deficit are Epsom salt baths and n-acetyl-cysteine supplementation. Peter has commented on the beneficial effect of the latter and there is good literature on it. If you have not tried these, they might be good prospects for therapy. In interest of full disclosure my son did not do well on n-acetyl-cysteine even though I think he has a sulfur deficit.
In addition my understanding is that those with PTEN often have high oxidative stress. So therapies that reduce oxidative stress may be helpful in general. The thiamine derivative TTFD that Dr. Lonsdale highlighted could help if there is a functional thiamine deficit (it also contains sulfur). Another idea is a mixed carotenoid supplement. This would lower oxidative stress, but I know of no human trials in autism. However in my experience it can be helpful. One caveat on this is there are indications that carotenoids increase the risk of some forms of cancer in former smokers and I understand there are increased risks of some cancers in PTEN. Peter has also highlighted a number of other great ideas around reducing oxidative stress in his blog.
The latest research which I am sure many people here are aware of is that B-12 levels peripherally seem to be about normal in controls and those with autism, but in the brain B-12 levels are about a third of what they should be relative to controls. Why this is the case is an open question but an obvious consideration is that the B-12 is being consumed faster in the brain than it is allowed in by the BBB due to oxidative stress and other metabolic reactions that use a lot of B-12 as a cofactor.
DeleteNevertheless, a big breakthrough in understanding how to open the blood brain barrier was accomplished in the last couple weeks where researchers found out that an adenosine A2A receptor agonist would open up the BBB enough for large molecules to get through. Caffeine remember is an adenosine A2A antagonist which is interesting considering it is considered canon that those with severe autism have a leaky BBB, likely for inflammatory reasons, so caffeine or other adenosine A2A antagonists could be used to help promote the integrity of the BBB, while on the other hand adenosine A2A agonists can be used selectively to get substances/drugs such as B-12 into the brain acutely.
We have stopped the shots as per last week and so far nothing has changed.
ReplyDeleteRoger, I agree we should treat based on lab results. I put my son on leucovorin as per our MAPS Doctor as well as on B12 shots basically just to see if we saw any gains.
I certainly hope I didn't do more harm than good.
Roger, are regular biochemical tests for homocysteine, folic acid and B12 of any credibility?
ReplyDeleteMy son has 6,5 homocysteine (5,4-16,5 normal means) and his folic acid and B12 look very normal in the blood.
Doctor says we don't know what happens in the brain.
So Peter, are you saying that if mTOR is upergulated... you would not want to use B12? We see mTOR is upergulated is TS. I'm wondering if it's the same for Pitt. Each time I have tried to give my son B12... he becomes agitated and hyper...
ReplyDeleteIt may be that, or there may be another reason. If you have a negative reaction it would be prudent not to use it.
ReplyDeleteSeth, I have been following your thorough research on B vitamins and autism through Peter's blog and would like to express my appreciation and respect on your work.
ReplyDeleteI have used B complex 50 many times for my Asperger's young adult son and each time my results were similar.
During the first two days we had improvement in his autistic symptoms but on the third day we had anxiety, distress, aggressiveness and finally depression.
The last time the tense was so high that it lasted for many hours and almost nothing seemed to help. At that time, it suddenly struck me and used 5mg of Baclofen, which I had put aside for some time, while trialling Verapamil.
Baclofen really helped a lot with this crisis and my question is if B vitamins work as antagonists to hypo NMDA hypothesis and neurological disorders.
I have also used spirulina several times. Spirulina has good amounts of B vitamins together with amino acids. My son's response seemed better with it and we didn't have the consequences mentioned.
I was wondering if you have any ideas/explanation about this matter.
Hi Peter & Roger,
ReplyDeleteI am giving my son B12 shots and Folinic acid, actually my genetics doctor recommnded folinic acid ( without testing for mutation, he said we can just figure out by doing a trial).
We have seen good results from B12 shots.
Q: Do you know the exact name of test for MTHFR mutation and folate receptor issue, we have an upcoming appt with genetics and wanted to know if I can specifically request them.
Thanks, this was a really good post
BK
Hi Bhaskar, I am not an expert on these tests. Roger would know more.
DeleteIf you are using methylcobalamin, a very specific form of B12, you may be seeing an effect that is rarely connected to B12. It has a specific effect on mTOR and Akt.
Many people with autism features dysfunctions in mTOR and Akt pathways.
http://www.pubfacts.com/detail/21458538/Aktmammalian-target-of-rapamycin-signaling-pathway-regulates-neurite-outgrowth-in-cerebellar-granule
I know that all about discus are way of solution as you are discussing about autism so good for every all"
ReplyDeletehttp://www.luminousmom.com/autism-series-part-1-my-child-has-autism/
Hi Peter,
ReplyDeleteThis is from 2016 (and there's a similar one from the same group in molecularautism from 2018) but I thought I'd point it out since the markers sound interesting. Lower thiamine pyrophospate and higher dityrosine in plasma in autism https://www.tandfonline.com/doi/pdf/10.1080/10715762.2016.1239821
Aspie2
PS Maybe you could add a label for thiamine?
B12 and might help with memory retention.
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107735/
Stephen
The impact of magnesium biotinate and arginine silicate complexes on metabolic dysfunctions, antioxidant activity, inflammation, and neuromodulation in high-fat diet-fed rats
ReplyDeletehttps://link.springer.com/article/10.1007/s10238-024-01434-9
I've been using magnesium biotinate for a couple of days with the Leucovorin. They seem to do a good job with each other. A lot more spontaneous sentences for my son with both the blocking and binding folate auto-antibodies.
Stephen