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.

A protocol for treatment of common autism phenotype(s)

This is a guest post written by Seth Bittker, who previously wrote about Vitamin D in Autsim.

Your child has just been diagnosed with autism.  Now what?  Start some form of behavioral therapy and research autism biochemistry.  You will soon realize by reading blogs like Peter’s that biochemical dysfunction is fundamental to most cases of autism.   For example, some biochemical characteristics that are common in autism are:

1)       Immune dysfunction.  Often this shows up as comorbidity with allergic or autoimmune diseases. http://europepmc.org/abstract/med/16512356

2)       Elevations in monoamine neurotransmitters in the young.  http://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.1994.tb11911.x/abstract

3)       Methylation deficits.  Often the oxidized to reduced glutathione ratios are high. http://www.ncbi.nlm.nih.gov/pubmed/15585776

4)       Low plasma cysteine and higher sulfate excretion than controls.  This means there is a functional sulfation deficit. http://informahealthcare.com/doi/abs/10.1080/13590840050000861

5)       Lower levels of fatty acids in blood plasma than controls. http://www.lipidworld.com/content/10/1/62

6)       Higher testosterone than controls. http://www.nature.com/srep/2014/140926/srep06478/full/srep06478.html

7)       Oxidative stress as demonstrated by markers.

http://www.ncbi.nlm.nih.gov/pubmed/22005342

8)       Vascular damage as demonstrated by markers. http://archneur.jamanetwork.com/article.aspx?articleid=792009

9)       Intestinal dysbiosis.  http://www.biomedcentral.com/1471-230X/11/22  

Given this background, it makes sense to determine whether there are issues in your child’s biochemistry that may be involved in inducing autism and how his biochemistry compares to others with autism.  After all if his biochemistry is similar to what is common it may be that therapies that have proven useful in others with autism will prove useful in the case of your child as well.

How can you get an understanding of your child’s biochemistry?  You can have tests run on your child’s urine and blood.  This typically involves finding a medical doctor who can order such tests and has the inclination to do so.  One test that I believe everybody with autism of an unknown cause should have done is a quantitative urine organic acid test.  A good organic acid test will provide information on fatty acid and carbohydrate metabolism, Krebs cycle function, B vitamin deficiencies, neurotransmitter metabolism, oxidative stress, detoxification, and bacterial and fungal activity in the digestive tract, as well as methylation and sulfation processes.  In short it will provide information on a lot of the biochemistry that is often dysfunctional in autism.  Different providers of organic acid tests include different compounds and provide different information on them.  I recommend Genova’s comprehensive test because it includes a number of metabolites that are of interest in autism, it is quantitative, and the data is displayed in a logical manner.  Here is a link: https://www.gdx.net/product/organix-comprehensive-profile-metabolic-function-test-urine.  To be clear I have no relationship to Genova and I do not recommend that you follow the supplementation guidelines that they typically include with test results.  After reviewing the information from your child’s organic acid test and googling various metabolites, you may have some leads on whether the biochemistry of your child is similar to the biochemistry that is common with autism as described above.

What to do next?  The next step especially if there are indications that your child’s autism is similar to what is common in the medical literature is to develop a food and supplement protocol for your child by experimentation.  To mitigate risk you should find a physician who you can collaborate with, experiment with one therapy at a time, use your child’s biochemistry as determined by tests as a guide, use supplements that have generally found to be helpful in others with autism, and carefully control any experiments.  Always use low doses of any supplements at first.  In fact to obtain positive effects with most supplements, you need not provide large doses and in my view the amounts used in supplement trials are often excessive.

Below are some supplements and experiments and a reasonable order in which to try them.  I recommend that you try these (or some subset of them) if your child’s biochemistry suggests they may be helpful.  If you find significant issues in your child’s biochemistry that may be ameliorated with a single supplement, you should certainly consider trying that supplement first.  Also if something does not work well for your child, leave it out of the protocol that you are developing independent of biologic rationale.  The objective is to improve the functional level and health of your child.  If something does not work, discard it.  You need not do everything.

1)       Fatty acids.  As mentioned previously fatty acids are often low in autism.  You could get a fatty acid panel on your child to determine if they are low in your child.  Two double blinded trials have been done with fish oil (omega 3 fatty acids) in the context of autism with generally positive results.   http://www.ncbi.nlm.nih.gov/pubmed/16920077  Interestingly it seems some omega 6 and omega 9 fatty acids are often more deficient than omega 3s in autism.  As omega 6s like omega 3s are essential fatty acids, deficiency can be problematic.  While controlled trials have not been done with omega 6s or omega 9s in the context of autism, it makes sense to experiment with borage oil (omega 6) and olive oil (omega 9) if deficiency is suggested based on a fatty acid panel.

2)       Methylation cofactors.  Are there elevations (even mild ones) of methylmalonic acid or forminoglutamic acid from your child’s organic acid test?  Does your child have a high ratio of oxidized to reduced glutathione (a test by the European Laboratory of Nutrients can measure this)?  If so, then your child may have a methylation deficit.  Jill James among others has found that shots of methylB12 and oral supplementation of folinic acid can help normalize this biochemistry.  http://ajcn.nutrition.org/content/89/1/425.long  MethylB12 is absorbed well orally even in those with dysbiosis.  In addition the methylfolate form of folate is absorbed well and is the active form used in the body.  Also it is methylated which is a plus for those with methylation deficits.  Therefore, if there is any indication of need, I recommend supplementation with oral methylB12 and oral methylfolate rather than the forms that were used by James.  In my experience high doses of methylcobalamin can cause insomnia but low doses are therapeutic.  So be wary of inducing insomnia.

3)       Thiamine.  Deficiencies of this vitamin lead to a disease known as beriberi.  If you set aside the rashes that typically characterize it, there is significant overlap between the symptoms of beriberi and those that are common in autism.  In fact some with autism have rashes as well.  The word thiamine means sulfur containing vitamin and thiamine does indeed contain sulfur.  Sulfur deficits are common in autism as previously noted.  So this is another hint in my view that thiamine may be helpful in general in autism.  Indeed a trial from 2002 of thiamine suppositories found that thiamine deficiency was fairly common in autism and supplementation even in those without obvious signs of deficiency could lead to improvement in behavior.  http://www.ncbi.nlm.nih.gov/pubmed/12195231 It is my belief that this vitamin is significantly underutilized in treatment of autism.  Some signs that thiamine may be warranted include high levels of lactate or pyruvate, issues of fatty acid or carbohydrate metabolism and rashes.

4)       Vitamin C.  A double blinded placebo controlled trial from 1993 found some improvement in behavior could be attributed to supplementing vitamin C in the context of autism.  http://www.ncbi.nlm.nih.gov/pubmed/8255984  This is not surprising given that oxidative stress is common in autism.  Are there indications of oxidative stress from your child’s organic acid test or other sources such as high levels of 8-Hydroxy-2’-deoxyguanosine?  Then a trial of vitamin C is warranted.  I think low doses are preferable to high doses as high doses have effects on digestion as well as neurotransmitters that may be undesirable.  In addition high doses can induce copper deficiency.  Too much copper is not uncommon with autism but copper deficiency can be as problematic as too much copper.

5)       Removal of supplementary and fortified sources of fat soluble vitamins and particularly vitamin D.  This is controversial and the vast majority of practitioners would recommend supplementation with vitamin D.  I believe getting rid of supplemental and fortified sources of vitamin D was vital to improving my son’s biochemistry.  In addition processing oral vitamin D requires sulfation and sulfation deficits are common in autism.  Also many of the biochemical characteristics of autism including excessive levels of neurotransmitters, excessive levels of hormones, and a Th2 skew to the immune system are exacerbated by significant supplementation of oral vitamin D.  I wrote a paper on this available here: http://omicsgroup.org/journals/infant-exposure-to-excessive-vitamin-d-a-risk-factor-for-autism-2165-7890.1000125.pdf If you think there is merit to this view, some indications that excessive fat soluble vitamins could be a problem for your child include elevation in glucarate and sulfate on an organic acid test.  Please note sun exposure is positive for those with autism.  My concern is only with significant supplemental oral sources of fat soluble vitamins and particularly vitamin D.

6)       Probiotics.  A number of excellent studies support the notion that dysbiosis is common in autism.  In addition a double blinded trial from 2010 found marginal improvement in those with autism from supplementation with a probiotic.  http://centaur.reading.ac.uk/17353/  If your child has elevations in dysbiosis markers, this is worth a try.  I recommend a trial of a probiotic that is high in bifidobacteria and lactobacilli as there are indications that these are typically lower than controls in the digestive tracts of those with autism.  In addition if there are indications that your child may have clostridia from an organic acid test or other test, it probably makes sense to try the probiotic yeast saccharomyces boulardii as it has proven helpful in cases of clostridia.  Clostridia is common in autism and can lead to dysfunction.

7)       Carnitine.  One study found that about 17% of those with autism have abnormal carnitine metabolism.  In addition a double blinded placebo controlled trial found significant improvements in behavior from carnitine supplementation in the context of autism.  http://www.ncbi.nlm.nih.gov/pubmed/21629200  One indication carnitine may be useful is a high lactate to pyruvate ratio.  In addition one can measure the level of carnitine in the blood and low carnitine is an indication that supplementation could be benefical.  I do not use carnitine in supplementation with my son as I have not found it to be helpful but the trial mentioned suggests it will be helpful to a number of others.

8)        Removal of milk from the diet.  I do not believe there have been double-blinded trials showing efficacy for this treatment.  However some open label trials have resulted in positive results and I attest to the importance of this intervention in the case of my son.  Issues of digestion such as diarrhea and especially constipation are indicators that a trial of this may be beneficial.

9)       Removal of gluten from the diet.  As with milk free diets, I do not believe there have been double blinded trials showing efficacy.  However some open label trials have resulted in positive results and it seems helpful to my child.  In addition there does appear to be some comorbidity between celiac (autoimmune disease of the small intestine initiated by reaction to gluten) and autism. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884520/ Again issues of digestion such as diarrhea or constipation can be good indicators that a trial may be beneficial.

10)   Cruciferous vegetables.  Sulfur deficits are common in autism as previously noted.  In addition a number of trials with sulfur containing compounds have had tantalizingly positive results in the context of autism.  Such trials include: NAC, DMSA, and sulforaphane as well as thiamine (mentioned above).  We have tried small doses of all of these with my son and with the exception of thiamine I have not felt the long term results were positive.  NAC and DMSA both tend to exacerbate dysbiosis in some cases as well.  As dysbiosis can be such a huge issue in those with autism, I am hesitant to recommend them.   We also tried a tiny dose of a sulforaphane supplement with my son and I believe it induced a temporary verbal tick, which was awful.  In fact the researchers who conducted the sulforaphane trial acknowledgement that it might raise the risk of seizures in some.  http://www.pnas.org/content/111/43/15550.short?rss=1&ssource=mfr  Seeing the results in my son, I think this caution is warranted and for this reason I feel sulforaphane supplementation can be dangerous despite the positive results that many have seen.  Cruciferous vegetables such as broccoli (which contain sulforaphane) seem to have a marginally positive effect on my son.  As these are foods I also have less fear of negative side effects.  Thus, I recommend inclusion of a trial of cruciferous vegetables  in your child’s diet if there are any indications of sulfation deficits (low cysteine) or high sulfur excretion (high sulfate in urine).

Some other supplements that I believe are useful in autism include biotin, riboflavin, milk thistle, melatonin (for sleep), and prunes (for constipation).  One could write a book about treatment protocols for those with autism and a number of good books have already been written on this topic.  What appears above is a summary of an ebook that I wrote describing this protocol which is available here:  http://www.amazon.com/Autism-Getting-Biomedical-Protocol-Biochemistry-ebook/dp/B00R298YNW/.  If you have any interest, please feel to preview it on amazon.

In interest of full disclosure, I am not a doctor, I do not consider my son “recovered” from autism, the autism literature I have consulted as well as my own views may later be shown to be incorrect, and independent of what is true generally your child may have negative reactions to the supplements mentioned above.  I thank Peter for the opportunity to describe this protocol here and for his wonderful blog on cutting edge treatments for autism and the science behind them.  I wish you success in your efforts to improve the health of your child.