Autism Research Connections #3: A Conversation with Dr. Derrick Lonsdale

Dr. Derrick Lonsdale was interviewed by Seth Bittker on April 12, 2016 on autism, thiamine deficiency, thiamine supplementation, and TTFD. Dr. Lonsdale observed that thiamine deficiency is often present in autism. He sees autism as typically a metabolic disease that combines genetic risk with environmental stress and in some cases marginal malnutrition. © 2016

A podcast of the interview is available here.  A transcript of the interview appears below.

SB: This is Autism Research Connections #3.  It is April 12, 2016.  I am your host, Seth Bittker, and our guest today is Dr. Derrick Lonsdale.  Dr. Lonsdale has had a long and productive career in medicine.  At one point Dr. Lonsdale was head of Biochemical Genetics at the Cleveland Clinic, but he gave up this position and decided to become a pediatrician focused on nutrient based therapies at the Preventive Medicine Group.  Dr. Lonsdale is arguably the world expert on thiamine deficiency and supplementation of thiamine analogs in those with autism and other conditions.  He has written a number of papers on these topics, and in many cases he has significantly improved the lives of his patients in circumstances when other physicians had given up.  Dr. Lonsdale, welcome to Autism Research Connections.  Thank you for being here.

DL: Thank you for asking me.

SB: Dr. Lonsdale, as I alluded to in the introduction, I understand that you were head of Biochemical Genetics at the Cleveland Clinic, a very prestigious position, but you left there in 1982 to join the Preventive Medicine Group specializing in nutrient based therapies.  What drove you to make this decision?

DL: Well it’s an interesting question.  I was a pediatric oncologist for six years, and I gave that up to study the inborn errors of metabolism.  Those that could be treated could only be treated by dietary means.  So I was interested in picking up these metabolic disorders, and one day a six year old child came to my attention because he had had episodes of cerebellar ataxia.  That is just sort of like being drunk if you will, and he had had every test under the sun with the question of whether it was encephalitis or whether it was a tumor.  All the tests had been negative.  Well to cut a long story short, we found out that he was suffering from what became the first published case of vitamin thiamine dependency – not deficiency.  This is a situation where the linkage or bonding of the cofactor thiamine to the enzyme is disturbed genetically speaking.  So the bonding requires enormous doses of the cofactor, and he required as much as 600 milligrams a day of thiamine whereas the recommended daily allowance of it is between 1 and 1.5 milligrams.  So it was a humongous dose, but what was so interesting about him was that he never got an attack of ataxia unless there was some kind of stress factor – an infection like a cold, on one occasion a light head injury, and on another occasion even an inoculation.  So that the stress factor was an important part of the initiation of these attacks, and that case drove me on a research way of going.  I spent a great deal of time in the library and studied thiamine in all its different aspects and that went on right through my career, and I am still studying it after retirement.  So that is about the answer to your question.

SB: I mean that is terrific.  We are sure glad you embarked on that journey.  So if we were to look at somebody with thiamine deficiency, what are some of the macroscopic symptoms of thiamine deficiency when you see them?

DL: Well thiamine deficiency causes the well-known disease called beriberi.  It is one of the standard vitamin deficiency diseases and it is a disturbance of glucose metabolism.  So that if we take our cue from beriberi, we have known for many many years – from the very earliest discovery made in this disease that if the patient had a normal blood sugar, the patient would respond to doses of thiamine.  If he had an elevated blood sugar, he responded poorly, and if he had a low blood sugar, sometimes he did not respond at all.  So this probably represents the staging of the disease – the seriousness of the disease – as it progresses.  Also we find that the triglycerides in the lipid profile are usually elevated.  It is almost diagnostic of sugar intake.  It is sort of interesting that in 1973 a book was written called “Sweet and Dangerous” and in that book a professor of nutrition at one of the major London hospitals had discovered that cardiovascular disease was due to sugar and not due to cholesterol.  So he was way way way ahead of his time and he found that many diseases were due to intake of sugar, but never came to a conclusion as to why sugar caused so much disease, and I think the answer to it is that because sugar has been known since 1936 to induce thiamine deficiency.  So it may be that thiamine deficiency is an extremely common phenomenon in America because of the high intake of sugar.

SB: That is a fascinating connection.  So you mentioned this issue with sugar and the high triglycerides.  What are some of the other metabolic markers that people would see in cases thiamine deficiency – and maybe not the most extreme cases of true beriberi but maybe more modest deficiency?

DL: Well the trouble is that you get some of the standard laboratory tests such for example as CRP – C-reactive protein and other inflammatory markers are increased because thiamine deficiency does produce inflammation, and I think that what is happening is that because thiamine deficiency simply does not exist in the lexicon of the American physician for many reasons.  Particularly because they say well the food industry has been using vitamin enrichment.  So we don’t have to worry about vitamin deficiency diseases.  So when these inflammatory markers are elevated, it is ascribed to some other cause.  For example we now know that rheumatoid arthritis is as much of a mental disease as a physical disease, and the inflammation is conducted from the brain, and the brain is defective in thiamine deficiency.  So you keep getting back thiamine deficiency as a cause of many different conditions.

SB: That is an excellent summary.  From some of your papers I also understand that thiamine deficiency is involved in you mentioned inflammation, maybe relatedly things like oxidative stress.  You mentioned the high triglycerides.  It looks like there is an issue with fatty acid metabolism when you have thiamine deficiency.  Is that correct?

DL: Yes and even worse than that, it has recently been found that it is absolutely essential for alpha oxidation.  Now alpha oxidation is a preparation for what is called beta oxidation and beta oxidation is one of the ways in which energy is produced in the energy producing mechanism.  So we now know that thiamine presides over sugar metabolism.  We have known for a long time that it presides over aspects of protein metabolism because it is necessary for the oxidation of the three branched chain amino acids – leucine, isoleucine, and valine.  So it actually presides over diet in general because carbohydrate, protein, and fat make up the entire diet.

SB: That is great color, and just to highlight for some of our listeners there probably [are] some parallels between what you are saying is common biochemical indicators of thiamine deficiency and autism.  Would you like to comment on that Dr. Lonsdale?

DL: Well as you know I did a pilot study in which I studied ten autistic children and eight of them improved as a result of giving a derivative of thiamine known as thiamine tetrahydrofurfurl disulfide and this is actually a prescription item in Japan by the name of Alinamin.  It is also referred to as Fursultiamine and Allithiamine, and it has got various trade names, but they are all the same substance, and I gave these children big doses of it by rectal suppository because of the taste factor.  The taste is so horrible that I couldn’t get them to take it by mouth.  Well when we finished the study – and the whole idea of the study was as a pilot study to go on and then we wanted do an interinstitutional study, but the FDA wouldn’t let us do it because we had to get a separate IND if the TTFD was given by suppository, and we couldn’t do that.  It was just impossible.  So all I can say is that this needs to be further researched because if TTFD is a valuable nutrient in autism, then it certainly should be researched further.

SB: Right.  That is outrageous, and your study as far as I could see was very impressive.  It was just as you mentioned it is not like a double blinded trial.  It is just a case series, but it did highlight that many of these kids did have thiamine deficiency as you mentioned and many of them improved.  When you are looking at measuring thiamine deficiency what measure are you using, and what is the standard criteria that you would use for determining whether somebody does have thiamine deficiency?

DL: Well there is a very accurate study called red cell transketolase.  Thiamine and magnesium are cofactors to a very important to a very important enzyme known as transketolase, and transketolase occurs in the brain.  It occurs in red cells.  So you can measure the enzyme activity in the laboratory and then you come out with a baseline figure of how active that enzyme is, and then you add thiamine pyrophosphate to the reaction and repeat the reaction, and if you find that activity of the enzyme accelerates it is simply saying OK this is what we needed thank you.  Now we can reach our maximum efficiency.  So it is an excellent test for thiamine deficiency.  The trouble is that the Mayo clinic for example has published a statement that the only way of measuring thiamine is the level in the blood and that is totally inaccurate because that level can be completely normal in the presence of thiamine deficiency.  The baseline transketolase activity can also be normal with thiamine deficiency.  So you can be hoodwinked.  You can miss a fairly severe case of thiamine deficiency by doing the test improperly.

SB: This is a really important point.  So to actually measure it properly is sounds like you do this reading and then you need to provide it, is that correct?  And then you do the reading again to see if there is a difference?

DL: Yes.  Exactly.  If it accelerates, then the enzyme was not saturated with the cofactor.

SB: It sounds like you may have already answered this, but just to be clear is there possibly some other biomarker that you think people should look at to see oh this person likely has thiamine deficiency, and then later on you could do the confirmatory test to provide the thiamine?

DL: Well you don’t need any other test.  This is a definitive test.  It is absolutely the most accurate test that you could possibly imagine.  I have literally done thousands of these tests and when I have given the patient thiamine or TTFD or magnesium or whatever, the transketolase activity becomes normal and the patient’s symptoms disappear.

SB: That’s terrific.

DL: It’s very very accurate and very very closely relates to the clinical situation.

SB: That’s great.  So there [are] various forms of thiamine and you have already described the TTFD form.  What other forms of thiamine are there, and what are their advantages and disadvantages in your view as supplements?

DL: Well that is a good question, and about mid-century Japanese investigators were looking at the biochemicals that are in garlic, and they found that there is an enzyme in garlic which acts on thiamine, and converts it into a disulfide derivative of the vitamin, and because it was found in garlic which is a member of the allium species it was referred to as allithiamine – A-L-L-thiamine – all one word.  They thought originally that it had lost its biologic value, but when they used it in animal studies they found it had a biologic activity, which was increased over the biologic activity of the original thiamine from which it had been derived.  And they did many many studies in animals and in human studies, and showed that I really had extraordinary therapeutic value.  For example they were able to show if they pretreated mice with TTFD which is the most modern of the disulfide derivatives, the mice were partially protected from cyanide poisoning.  They also found that it could prevent carbon tetrachloride poisoning of the liver.  These are amazing experiments which we had ignored.  So the Japanese went on to study these many different disulfide derivatives, and they found that the tetrahydrofurfuryl was by far and away the best, because the previous ones had made the patients smell very strongly of garlic which made it very very unpleasant.  They also made a whole series of what are called acyl (A-C-Y-L) derivatives and these are nondisulfide derivatives and in order to process them they require an enzyme in the body whereas the disulfides are automatically reduced at the cell membrane and they pile the thiamine into the cell where it is needed.

SB: That is great.  I also recall from your search that TTFD in animals…

DL: Well we know it crosses the blood brain barrier.  Benfotiamine which is has become quite a popular one is an acyl derivative and it does not cross the blood brain barrier.  That’s been proved by basic studies done in Belgium – in Liege University, Belgium.

SB: That’s great, and I also recall that TTFD I believe there were some studies you mentioned – or in some of your research where it had protective capabilities against lead and some heavy metals if I am recalling correctly?

DL: That’s correct.  Yes.  It’s interesting because thiamine actually the mechanism is not by any means clear, but it clears the lead through the liver.  It goes through the bialary system.  So the lead comes out in the stool.  Not in the urine, and what people are looking for is lead in the urine and they should be looking for it in the stool if they use thiamine.  Well of course nobody is using thiamine because they don’t know about it, but I would have loved to have got in touch with the people in Flint and tell them that the kids that have lead poisoning all they need is 100 milligrams of thiamine a day and that will ease the lead out of their systems.

SB: That’s well said.  In our discussion a moment ago of the various forms of thiamine I know there are the standard water soluble forms, there is the TTFD form, there is benfotiamine.  Am I correct in thinking that you favor the TTFD based on your research?

DL: Oh absolutely.  I think it is the most superior product.

SB: And also when we look at autism and thiamine – well frequently in autism as you know often times there is a sulfur deficit, and by this I mean often time we see excess sulfur compounds in the urine and too little – or deficit – in the blood.  Is there a connection between thiamine supplementation…

DL: Well that is an interesting question.  I know the researcher in Britain who reported that.  We were unable to repeat it when we did it ourselves.  We were unable to repeat it when we did it ourselves, but I think that the work that was done in Britain is authentic.  I think the answer is this.  If you take an example of a machine like a car, it has an engine. Well in the human body mitochondria are the equivalent of an engine.  Well a car has to make energy and then has to transfer it to the wheels, and that is through a transmission.  So the citric acid cycle and the electron transfer chain represent the mechanism of the engine.  That is where the energy is produced, but then transsulfuration which is what you were talking about about the sulfur – transsufluration – represents the transmission.  It is an energy consuming device.  The citric acid cycle produces the energy and the traunssulfuration, transmethylation mechanism consumes energy, and that enables us to what we call function.  In other words, cells function.  So we function.  Does that make sense?

SB:  It makes complete sense.  And I thought it was interesting the way you have tied this in with the mitochondria.  So when you do have thiamine deficiency – or close to it, is it accurate to say you have some sort of mitochondrial dysfunction or at least it appears that way?

DL: It has been actually proved that autism is a mitochondrial disease.  It has also been shown by Bettendorff in Belgium that thiamine deficiency will damage the mitochondria, and in the early stages – these are in vitro experiments.  In the early stages of thiamine deficiency in the mitochondria they can be repaired simply be reinstating the thiamine.  So thiamine is in an inherently essential component to mitochondrial function.  Of course it is not the only one, but it has a dominating influence.

SB: That is well said.  What percentage of those with autism do you think could have their functional level improved with some form of thiamine supplementation?

DL: Well our pilot study showed eight of ten had improvement.  It is interesting that only – I think either only two or three of them had evidence through an abnormal transketolase, but in spite of that eight of those children improved significantly.  Now we used computer read forms in the study that had been invented by the Autism Research [Institute] that Rimland ran and they had been tested over time as being extraordinarily accurate.  As you know there is actually no biologic marker that identifies autism per se.  So this symptom reporting device was used in the study and even though it wasn’t a controlled study it showed a definite advantage in the use of TTFD in those kids.  We’d have loved to have done a complete study after that between the institutions but as I say we weren’t allowed to do that.

SB: It is really unfortunate that you weren’t allowed to do it.  Why…

DL: They said that we had to take out a new IND if the thiamine was given by rectal suppository or on the skin or whatever.  It is typical FDA.

SB: It is an outrage.  So why do you think there are so many individuals with autism who seem to be thiamine deficit?

DL: Well the only thing that I can do is to guess that it’s the sugar intake because it starts in pregnancy.  Now I came across a case just recently where I was asked to give some help to a boy that has become a screwball like so many of these kids are today.

And so I said to his mother, “Did you have nausea and vomiting in pregnancy?”

“Oh yes,” she said, “Yes.”

I said, “Hyperemesis?”

“Yes.”  Hyperemesis that has actually been shown to be a thiamine deficiency disease.”

I said, “Did your son have jaundice at birth?”

She said, “Yes he did.”

And I said, “Did he have colic?”

She said, “Yes he did.”

Both of those – jaundice and colic – have been shown to be because of oxidative inefficiency.  Actually it is free oxygen radical pathology.  So you start the ball rolling right at the beginning of life, and the mitochondria are injured at birth.

SB: Thank for that additional information.  When you provide TTFD or supplemental thiamine do you ever see cases of it inducing other deficiencies?

DL: Oh yes.  I think we have to remember that when you are talking about something like thiamine that it is a member of a team.  Magnesium is its first cousin.  I never give thiamine without magnesium because they are double cofactors to the enzymes that are represented, and I think that what we call the noncaloric nutrients – the vitamins and essential minerals – really have to be regarded as a team.  And so what I have done for many of these situations, I give large doses of thiamine and magnesium, and then back it up with a well-rounded multivitamin.

SB: That makes a lot of sense.  When you are giving the magnesium what form would you normally give?

DL: My favorite is magnesium potassium aspartate.  Potassium is a very important noncaloric nutrient and aspartate actually enables the ingredients to pass through the cell membrane.  It sort of helps to load the magnesium into the cell.  So it is a very useful way of giving it.

SB: That is very interesting.  So aspartate as I recall is an amino acid, but you are not concerned that would somehow overload that particular amino acid?

DL: Right.  Right.

SB: So you have mentioned magnesium, a multivitamin, and thiamine.  Are there any other supplements that you think are underutilized?

DL: No. I don’t think you can pick on any one in particular.  The research that is needed is to identify which of the nutrients is apt to be missing, but the commonest way in which these nutrients are deficient is through poor nutrition.  Nutrition in the United States is absolutely awful because so many people are eating junk food as a staple.  Good food and good nutrition is at a premium.  It is hard for people to buy it.  So they dodge it by getting cheaper stuff which then causes them to have illnesses which are then being treated as various different diseases.  For example allergy.  And I think that what happens is that a patient goes to his physician and goes, “I have got these palpitations of the heart.”

So you go back in a week later, “Well the palpitations are all right, but now I can’t sleep.”  So now he gives you another prescription to help you sleep and so on.

Well really the palpitations of the heart and the diarrhea alternating with constipation and the abdominal pain and the headaches and the emotional disturbances are all due to the fact that oxidative metabolism in the brain is in poor shape.  And when that happens the brain becomes very very hyperirritable.  So that any impulse coming in like a change in the weather or something like that can impact in the brain and fire off an autonomic nervous system response which is exaggerated in volume.  Am I making sense?

SB: Absolutely.  This is a beautiful – well not a beautiful – a portrait of disease.  So it makes complete sense.  Let’s say there is a kid that is brought into see a practitioner.  I understand you are retired I believe?

DL: Yes.

SB: But when somebody comes in what sort of labs would you think that should be ordered?  When a child comes in and they have autism, what are labs that should be ordered?

DL: Well I think the standard labs you do, but it is the interpretation that matters.  I mean the interpretation of laboratory markers is very misaligned.  For example if I see a cholesterol that is too low, I think that is more dangerous than a cholesterol that is too high, and yet we are being told constantly by physicians get your cholesterol down its dangerous.  Let me tell you a story just for an example.  I knew the laboratory director at the Cleveland Clinic and he told me that patients would come in for surgery and their cholesterol would be normal before surgery, or maybe high, or whatever, and after surgery and they would get complications and they would do repeated lab studies and the cholesterol would go down down down down down, and they would die.  So what was really going was that the stress of the surgery caused them to use their steroid hormones released by the adrenal gland and the adrenal gland requires cholesterol in order to make the steroid hormones.  Because their energy level – their cellular energy level was inefficient – they couldn’t make the cholesterol to make the steroid hormones.  So as the cholesterol ran low, the steroid hormones could no longer be made, and that is when they died.  It is a different way of looking at it.  You have to think in terms of energy metabolism being the background of health and consequently its loss is the cause of disease.

SB: I mean given your views that are well summarized there, I’m almost afraid to ask but I’ll ask anyways, are there any pharmaceuticals that you feel are useful in treatment of autism?

DL: No.  I never used any pharmaceuticals.  They are unpredictable.  They often have paradoxical effects, and you just can’t tell what is going to happen with a pharmaceutical.

SB: OK.  In terms of autism research there does seem to be a lot of exciting autism research going on.  Is there anybody extending the research you have done on thiamine in autism?

DL: Not that I know of.  No.

SB: Well that’s disappointing.  Of course that is not your fault.

DL: I tried to get… Did you ever go to Defeat Autism Now – DAN?

SB: I’m familiar with the group.  I’m very familiar with the group.

DL: Well I tried to present this to their group, and I don’t think they even listened.

SB: I’m very sorry to hear that.  Are there other areas of autism research that you find are promising?  Interesting?

DL: Well not really because I’m out of the swim now, but I do think that we have to understand that autism is not a psychological disease.  It is a biochemical disease, and it is fundamentally due to mitochondrial dysfunction.  I think that what we are looking at is genetic risk – not genetically determined disease – but genetic risk.  And I think that these minor genetic risks can be made to initiate disease when there is a stress factor imposed on the individual who has perhaps marginal malnutrition.

Let me illustrate that in a case that I had many years ago.  A six year old boy had a head injury.  His skull was fractured.  When he went back to school the school nurse said, “I want you to come down and get your eyes tested every two weeks because” – open quotes “people go blind with this kind of injury” – closed quotes.  Where she got that information I don’t know, but it happened to be proverbial, because three months later there was a major change in his vision, and she referred him to an ophthalmologist who found cataracts in both eyes.  Well the ophthalmologist knew of my interest in metabolism, and there is a disease which occurs in children called galactosemia.  And galactose is a sugar that is formed from lactose, and the galactose then has to be broken down to glucose, and it is under genetic control, and if you don’t have the gene then you accumulate galactose, and it causes cataracts in children.  So the question was does he have galactosemia?  He only had actually one allele.  This is a recessive gene, and he only had one of them.  So he was a carrier of the gene. And so I sat down with mom to find out what his diet was like, and she had been giving him lots and lots of milk to drink as a health drink.  That is quite common with many people pushing milk as a health drink.  Now the milk contains lactose which was then converted to galactose and overwhelmed his single gene.  So he got the cataracts.  Now the point is this, if he had never had the head injury, he wouldn’t have had the cataracts.  If he hadn’t had the milk, he probably wouldn’t have had cataracts, and if he hadn’t had the carrier gene, he definitely wouldn’t have got cataracts.  All three had to be represented.

SB: That is very well said.  So we have many different risk factors and they can work in combinations.

DL: Yes.

SB: It’s very well said.  Dr. Lonsdale is there anything else you would like our audience to know?

DL: Well I think anybody with a child with autism has to think in terms of biological phenomena.  It has got nothing to do with Dr. Freud.  It has got nothing to do with traditional psychology.  It is very much of a biochemical disorder, and I think that ADD and ADHD and O[C]D and all of these conditions that we are seeing in children today are really nothing more than variations on a symphonic theme.  Even obesity is related to dysfunction of the brain and that is published material too. We are damaging ourselves wholesale in this country and in Western Civilization in general.  That is the take home message I think.

SB: Thank you for that sobering point and thank you for taking the time with us.  Thank you for being with us on Autism Research Connections, Dr. Lonsdale.

DL: Well thank you for asking me.  I’ve enjoyed being with you.

5 thoughts on “Autism Research Connections #3: A Conversation with Dr. Derrick Lonsdale

    1. Thanks Susan. You can find it on amazon in capsule form here, but I don’t like this version as it includes calcium and phosphate. A blogger friend of mine, Peter Lloyd-Thomas, noticed that tablets are available from a Japanese pharmacy here:


    1. Shyamala,
      According to Dr. Lonsdale’s 2002 study, he was providing 50 mg twice a day to children via suppositories. I am not a doctor, but I think it makes sense with any supplement to start low and gradually increase to the desired dose over a number of days to reduce risk.

      Liked by 1 person

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