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Monday, 14 March 2016

Benfotiamine for Autism



by Seth Bittker





In recent decades populations of wild bird species in the Baltic Sea have been dying off in large numbers from a paralytic disease.  When some of the birds with signs of this disease are given thiamine, they rapidly improve.  So it would appear the immediate cause of these large scale population decreases among the birds of the Baltic is thiamine deficiency [1]. The same thing appears to be happening to large mammals like elk [2].

Setting aside the question of underlying cause, could it be another mammal high up the food chain also has many members of its population suffering  from thiamine deficiency?  There is no good standardized test for thiamine deficiency that does not involve supplementing with thiamine.  So whether individual humans are somewhat deficient in thiamine is not obvious.  However, a particular constellation of symptoms was recognized as the disease “beriberi” before it was understood that the underlying cause was thiamine deficiency.  And what are the signs of beriberi?  The symptoms are variable but some that have been observed are mental confusion, irritability, difficulty moving, loss of sensation, loss of muscle function, rashes, involuntary eye movements, digestive issues, abdominal pain, and sometimes lactic acidosis [3].

Many of these symptoms match the symptoms of some with autism.  So one might naturally wonder whether some cases of autism are in fact unrecognized cases of beriberi and perhaps more likely that thiamine deficiency could play a role in other cases of autism depending upon other genetic and environmental factors.  A Dr. Luong and Dr. Nguyen previously noticed this similarity and developed this idea into a paper from 2013 which is available here [4].

Pulling from their Abstract:

“A relationship between thiamine status and the development of autism has been established, with thiamine supplementation exhibiting a beneficial clinical effect on children with autism. Thiamine may involve in autism via apoptotic factors (transcription factor p53, Bcl-2, and caspase-3), neurotransmitter systems (serotonin, acetylcholine, and glutamate), and oxidative stress (prostaglandins, cyclooxygenase-2, reactive oxygen species, nitric oxide synthase, the reduced form of nicotinamide adenine dinucleotide phosphate, and mitochondrial dysfunction). In addition, thiamine has also been implicated in autism via its effects on basic myelin protein, glycogen synthetase kinase-3β, alpha-1 antitrypsin, and glyoxalase 1.”

A researcher named Derrick Lonsdale found in 2003 that a set of 8 of 10 children with autism had clinical improvement on suppositories containing thiamine tetrahydrofurfuryl disulfide (TTFD), a thiamine derivative [5].  There was no control group on this study.  So one should be cautious when interpreting these results.  In addition Lonsdale was interested in metals excretion – TTFD can serve as a chelator.  He found that TTFD increased excretion of such toxic metals but it also would increase thiamine levels as well.

I have not experimented with TTFD, but Lonsdale’s work did get me thinking about oral supplementation of thiamine.  I tried experimenting with my son on regular thiamine hydrochloride.   I thought there may have been a very modest effect in terms of increasing his energy but it was not a sizeable effect.  However, there are other forms of thiamine.  One lipid soluble form that has been used with some modest success in diabetic neuropathy is benfotiamine [6].

There are case reports of neuropathy in cases of autism [7].  In addition one symptom of some with autism that are significantly affected is arm flapping.  It seems to me a person may flap his arms if he is feeling numbness and he is trying to get blood flowing to reduce the discomfort.  For the same reason somebody who is cold may move his limbs rhythmically.  In other words, I think arm flapping may typically be a sign of neuropathy and that neuropathy is an under-recognized and often comorbid condition with autism.

My son does not have neuropathy, but we did try benfotiamine on him.  My experience is that on it he had a significant reduction in irritability, increased cuddliness, and more energy.  I also feel he was mentally sharper initially but this diminished with higher doses.  Another result was he had flatulence some of which was pungent soon after starting supplementation.  In retrospect I take this as a sign that his digestion was beginning to operate more efficiently and relatedly he may have been dumping xenobiotics into his bowel when starting benfotiamine but this is pure speculation on my part.

After about a week on benfotiamine he got a rash and I began to feel that his mental acuity was leveling off.  I found that if I gave him biotin the rash went away and his mental acuity became sharper again.  Biotin and thiamine are both sulfur containing B-vitamins  and there are genetic diseases where both are involved [8].   My experience with my son suggests to me that there may be some common pathways with these nutrients.  In other words, I think befotiamine supplementation may exacerbate biotin deficiency.  As some may be aware, biotin deficiency is also sometimes seen in autism [9].  So for this reason I think they should be taken together when given for autism.

Thus, if you do a trial of benfotiamine, I would include biotin as well.  I am currently giving my son about 120 mg of benfotiamine per day and 5 mg of biotin per day.  He is about 90 pounds.  I give these to him in a juice smoothie because benfotiamine tastes a bit tangy.  You might also consider providing them in something sweet.

In interest of full disclosure when communicating about benfotiamine in the comment section of a separate post, Agnieska Wroczynska mentioned that benfotiamine had a positive effect on her child but increased hyperactivity.  So she found it was not ultimately helpful, and RG reported no positive affect whatsoever.  So it is possible that the experience that I have had with it with my son is highly unusual.

If you do wish to do a trial, as with any other supplement, start with low doses first to avoid risk and increase modestly if you see positive effects.  I am interested in others experiences with it and hope if you try it you will leave a comment here with some color on the results.


I thank Peter Lloyd-Thomas for the opportunity to write this guest blog and for providing a wonderful forum on autism treatment and autism research.




20 comments:

  1. Neuropathy is common with many immune,metabolic,and genetic disorders related to autism.It has only begun to be widely recognized as such in recent years.I have severe polyneuropathy in both arms and legs,that began at the age of ten years.The the pain itself has been severely disabling,on top of everything else.Neuropathy in autism usually starts in older children like this,sometimes triggered by an acute infection.I believe neuropathy has been a big contributing factor to the muscle wasting and atrophy I have that began during puberty.

    I can verify what you say about hand flapping as a way of helping to restore feeling in the arms.

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    1. Roger,
      I am sorry to hear about your pain from neuropathy but thank you for validating its importance in autism. I have some neuropathy myself but not on the order of what it sounds like you have. Mine seems to get somewhat better with benfotiamine and in the past tetracycline antibiotics. Does anything help relieve your neuropathy?

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    2. High dose gabapentin helps.It is widely used by doctors like Richard Frye.

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  2. Hi Seth,

    In your earlier post you mentioned that your son also had low levels of Vitamin D but did not do well on supplementation. How did you treat it? My daughter's recent test again shows low vitamin D. I also have another friend whose son is persistently low in spite of supplementing at 20,000iu per day.

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    1. Hi RG,

      Thank you for asking about vitamin D. I take the low levels of 25,hydroxyvitamin D in blood which typically accompany autism as a sign of vascular inflammation. So as you ask what to do about it? You can try to see if more sun helps your daughter. It helps marginally for me and my son.

      Beyond that I think the objective should be to decrease vascular inflammation. Some supplements can help with this but I believe this has only been proven to raise vitamin D levels in the case of statins. Specfically, I would consider benfotiamine and thiamine as these can improve vascular function. In addition it might make sense to try methylators like methylcobalamin and methylfolate if there is any sign of under methylation. I also give my son carotenoids which are antioxidant pigments and think this helps decrease inflammation. My recollection is you already have tried a number of these without much effect in your daughter.

      I do not know her age or the severity of the issue with respect to vascular dysfunction, but if you think it is severe and her cholesterol is high or high normal, you may also want to investigate statins. I know Peter has a lot of great information on these in the context of autism and indeed taking statins does tend to raise blood levels of vitamin D. In interest of full disclosure I have not used one with my son. See this link for statins effect on blood vitamin D levels though: http://link.springer.com/article/10.1007/s10557-009-6181-8#/page-1

      If you are interested in more details on the supplements mentioned above in the context of autism perhaps with a bit of attitude I have an ebook here: http://www.amazon.com/Autism-Getting-Biomedical-Protocol-Biochemistry-ebook/dp/B00R298YNW/ref=asap_bc?ie=UTF8

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    2. There is a ridiculous amount of evidence out there about low vitamin D levels in autism.I have yet to see any real evidence as to why this is.Is it due to malabsorption? Is it due to a defect of vitamin D metabolism? Is it due to antibodies of some kind?I also have high levels of folate receptor antibodies,that we know are regulated,in part,by dairy consumption.

      When I first started to get any real tests,in 2009,I started with what was then called a DAN! doctor,who only saw autistic children.I was one of the first adults he saw.He told me I had the lowest vitamin D levels he had ever seen at that time.I had rickets or osteomalacia for many years.

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    3. Hi, magnesium is a required cofactor for vitamin D absorption. Rickets and osteomalacia are both associated with magnesium deficiency. Magnesium is also a required cofactor for thiamine.

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    4. Hi Roger,
      I don't think the vitamin D issue in autism is malabsorption. Supposedly what comes in through the sun dwarfs what comes in through the diet. As mentioned I think it has to do with vascular inflammation.
      Another way to look at it is with respect to calcium. After all when one is inflammed one is at risk of tissue destruction through calcification and related processes. Diseases such as kidney disease and cardiovascular disease often feature low levels of vitamin D in the blood as well. I would hypothesize this is connected with lowering the calcium load. In other words, the body naturally decreases the vitamin D level to decrease calcium absorption. Does this make sense?

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  3. Hi
    Thanks for this very interesting post. Coincidentally I’ve spent last few days (or nights) reading on thiamine.I have some update with regard to benfotiamine. My son has just recovered from the worst febrile infection that he had in years. When his fever decreased after a week he was extremely fatigued, much more than usually expected and suddenly his stuttering got much worse. He used to stutter before, but it was minor problem.

    I looked at medical treatments used for stuttering and for issues that may be related to prolonged fever and found one common thing: thiamine. Excess use of thiamine during fever is suggested to cause B1 deficiency (http://emedicine.medscape.com/article/116930-overview) and anecdotally high dose of B1 helps some one third of adults stuttering. A double blind study more than 50 years old about preschool kids speech fluency improvement on thiamine seems to be often discussed with relation to stuttering: :
    http://www.casafuturatech.com/should-stutterers-take-vitamin-b-1/

    So I gave my son benfotiamine 50 mg and stuttering improved the same afternoon. It might be just due to recovery from illness, but his fatigue got better before benfotiamine treatment while stuttering did not until that day. Changes are easy to check as our speech therapist advised us to monitor which words are most challenging for him.

    There is no problem with hyperactivity at the moment. For last few weeks I’ve been giving my son also Mitospectra increasing the dose without that issue. My previous trials with B1 and carnitine were done in “pre-PolyPill“ times and I think that now with some abnormal processes corrected resulting in more awareness and improved cognition (on bumetanide + acetazolamide) it is easier for him to manage the energy boost than in the past, when stimming was in fact the only thing he was able to do.

    Seth, how did you establishe benfotiamine dose for your son? How long has he been taking it?

    I also found some old studies on acetazolamide + thiamine treatment:

    “18 chronic, treatment-resistant psychiatric inpatients (aged 25–86 yrs) were administered acetazolamide and thiamine (A + T) in addition to their maintenance therapy. Ss showed decreased hallucinatory and delusional thought, improved social alertness and interpersonal responsiveness, and increased purposeful behavior. Ss relapsed within a few months after A + T withdrawal.”
    http://www.ncbi.nlm.nih.gov/pubmed/3280618
    http://www.ncbi.nlm.nih.gov/pubmed/2669002

    I also stumbled upon something odd about thiamine and carbonic anhydrase:
    http://www.ncbi.nlm.nih.gov/pubmed/22145674

    Diuretics are suggested to increase thiamine urinary loss. While as far as I know there are no reports of that problem in children treated with bumetanide, I think this might be something to consider on long-term treatment with more than one diuretic:
    http://www.ncbi.nlm.nih.gov/pubmed/?term=10482307
    Peter do you continue with bumetanide + acetazolamide?

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    1. Agnieszka, for the first time ever, Monty started to have reflux and I think this may have been a side effect of acetazolamide. It may have been a coincidence, but there are reports of acetazolamide causing reflux. So quite shortly after starting using it in combination with bumetanide, I stopped. Bumetanide has been completely trouble free for us.

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    2. Hello Agnieszka,
      I think the discovery you have made regarding stuttering and thiamine deficiency is very interesting. This seems very relevant to autism as well given how issues of speech and verbal communication often play into it.
      Regarding the dose for my son, it was determined using experimentation. I started low and moved up. Lower doses seem to help in general. At a dose of 180 mg, I started to feel there was a leveling off in the positive and in particular this seemed to occur with respect to memory. I.e. at a high dose he seemed pleasant, conversational, but a bit forgetful. I am not sure what it means, but 120 mg seems to be about right for him.
      With respect to how long he has been on it, it has only been about 6 weeks. He was also on thiamine for a while for about a year before.

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    3. Have a look at this:

      'Biotin-thiamine-responsive basal ganglia disease'

      "... Typically, the neurological symptoms occur as increasingly severe episodes, which may be triggered by fever, injury, or other stresses on the body. Less commonly, the signs and symptoms persist at the same level or slowly increase in severity over time rather than occurring as episodes that come and go. In these individuals, the neurological problems are usually limited to dystonia, seizure disorders, and delay in the development of mental and motor skills ..."

      ".. It is unclear how biotin is related to this disorder. Some researchers suggest that the excess biotin given along with thiamine as treatment for the disorder may increase the amount of thiamine transporter that is produced, partially compensating for the impaired efficiency of the abnormal protein. Others propose that biotin transporter proteins may interact with thiamine transporters in such a way that biotin levels influence the course of the disease."

      Even is the disorder (caused by mutations in the SLC19A3 gene) is not directly relevant to most autism the mechanisms behind it might well be!!

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    4. Peter, I am sorry to hear about reflux and hope Monty is better with that problem now.

      Thanks Seth for comment about the dose, I will continue further with this treatment and let you know.

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  4. When I was studying the connection between thiamine and autism, I found out that gestational low thiamine (often concurrent with low magnesium) results in an underdeveloped temporal lobe, and the more underdeveloped the temporal lobe, the more severe the autism symptoms. Slightly low magnesium and thiamine would result in very subtle changes to the temporal lobe which would only result in reduced sociality and increased concentration. Interesting that today's children with autism are more likely to have an engineer for a father, as well as more educated mothers - I would guess that engineers and educated mothers would have needed to concentrate to complete their education, so maybe they have underdeveloped temporal lobes as well. This is a bit of a stereotype - but - when I conjure up an engineer, I do not imagine a social butterfly, although there are exceptions I'm sure. Anyway I see this as very much a thiamine / temporal lobe issue caused by insufficient sulfur / magnesium and its cofactors. Temple Grandin quote: “In an ideal world the scientist should find a method to prevent the most severe forms of autism but allow the milder forms to survive. After all, the really social people did not invent the first stone spear. It was probably invented by an Aspie who chipped away at rocks while the other people socialized around the campfire. Without autism traits we might still be living in caves.”

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  5. Feel free to delete this post as it is obviously off topic but I thought you (Peter) would be very interested in this paper that came out today (if you have not seen it already) which is another study on low dose clonazepram in another mouse model of autism that successfully rescued the mice from autistic behaviors.

    http://www.nature.com/ncomms/2016/160316/ncomms10861/full/ncomms10861.html

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  6. Thanks Seth/Peter - this is very interesting.

    Our son has shown significant benefit from transdermal thiamine patches which are usually used for preventing insect bites: https://www.amazon.co.uk/Vie-Patch-Insect-Repellent-Patches/dp/B004ZGZVCW/ref=sr_1_1_a_it?ie=UTF8&qid=1472044050&sr=8-1&keywords=thiamine+patches

    I guess by keeping the blood thiamine level constantly high, they may be allowing some more to pass through to cells without needing active transport mechanisms, which are possibly not working properly. We have seen the initial improvements level off however, so your biotin suggestion may be helpful. The urine tests we've had don't suggest a need for biotin though, so perhaps not, but could be worth a try.

    Are you still the using biotin/thiamine combination Seth? We have just started using benfotiamine now, as our son does tend to develop a shin rash from using the transdermal patches, so we don't want to continue for long if possible.

    I'm very interested in talking to people who may be dealing with similar phenotypes.

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    1. Hi Anonymous,

      Sorry for not responding previously. We continue to use benfotiamine and biotin but admittedly at smaller doses. See reply to Melanie below.

      For my son I needed to lower the doses. It maybe initially he was very deficient and we built up the stores or maybe I just was less sensitive to signs than I should have been.

      Good luck with your son.

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  7. Seth,

    I have two sons who have autism. They are ages 8 and 6 and basically non verbal. We all have "low vitamin D levels" but cannot supplement because of a reaction that seems like increased inflammation. The best biomedical interventions for us have been benfotiamine, biotin, magnesium and selenium. I am curious as to whether you have found other nutritional interventions that have helped your son. We are of German European descent and have had occurrences in our family of Tourette's, OCD among males and autoimmune hyperthyroid among females. Always looking for additional info. Thanks, Melanie

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  8. Hi Melanie,

    Thanks for mentioning this.

    Many of the things that help your sons seem to help my son as well. In addition to benfotiamine and biotin, I also give my son the following daily: 1.6 mg of methylfolate, 5 mg of methylcobalamin, a carotenoid supplement, and 2 capsules of olive oil. I also try to get him to take baths with Epsom salts. I think each of these help him at the margin.

    With respect to benfotiamine and biotin in interest of full disclosure I am giving less now than I used to of these. Too much biotin and he becomes angry. Too much benfotiamine and he becomes spacey. I would speculate there is some kind of issue of balance in sulfur containing compounds. However, I continue to think some supplementation of these is very important for him, but I think smaller doses than what I was giving are better for him. I give him about 70 mcg of biotin a day which is a very small dose and about 5 mg of benfotiamine.

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