autism thiamine folate B12

Are High Folate and Vitamin B12 Linked to Low Thiamine in Autism and Other Disorders?

Autism is now classified as an epidemic in the United States. It can only be understood by first recognizing that it is caused by biochemical changes in the brain. There are only two ways in which these changes are brought about. One is genetics. The other is nutrition. The focus of research has been almost exclusively in terms of genetics. Very little has been said about nutrition. A recent epidemiological study found elevated concentrations of folate and vitamin B12 during pregnancy associated with autism. In this post I want to discuss the potential relationship of autism with B vitamins. In order to introduce the subject, I must digress.

High Folate and Vitamin B12 in the Face of Other Vitamin Deficiencies

Many years ago I was confronted by the case of a six-year-old child who had been suffering from an extraordinarily common problem for approximately two years. He would develop a sore throat, fever and swollen glands in the neck. Of course, these episodes had always been treated with antibiotics as infections but there was no valid explanation of why they were repeated. His case had been reviewed at prestigious medical institutions and he had been admitted to a hospital when, during a febrile episode, a gland in the neck was removed for biopsy. The report arrested my attention, because it was described as “a swollen gland whose architecture was otherwise normal”. Another part that arrested my attention was that his diet was appalling, full of sugar, so I had a blood test performed that showed that he was vitamin B1 deficient. But there was another strange association. Folate, a B vitamin and vitamin B12, also a B vitamin, both had very high concentrations in the blood. This had been discovered at the same hospital where the gland had been removed.

The doctor had told the child’s mother about this and accused her of giving the child too many vitamins. She was very perplexed because she denied that she had been giving any vitamins, but they would not believe her. Because of this history, I performed the same tests and both these vitamins were indeed elevated in the blood. Because of the sugar association and the finding of vitamin B1 deficiency, I treated the child with megadoses of thiamine (vitamin B1) and sent him home. To my great surprise, not only did his health improve drastically, his feverish episodes ceased and the repeat of the blood tests showed that the levels of folate and vitamin B12 had fallen into the normal range.

I asked the mother to stop the vitamin B1 which she did reluctantly. Three or four weeks later the child had another episode of swollen glands in the neck with fever. The mother also reported that he had sleep walked and, going downstairs, he had urinated spontaneously. Of course, this implicated a mechanism in the brain. I readmitted him to the hospital and I found that the folate and B12 levels had again shot up. I treated him with thiamine again. The fever and swollen glands remitted and the levels of folate and B 12 dropped again into the normal range. Well, of course, this was a natural experiment that sent me to the library to try to come up with an explanation of the relationship between these three B vitamins. It appears to be an important phenomenon because recently, a paper has been produced in which folate and B 12 have both been found to be increased over the normal range in autism.

The Engines in the Body

First of all, I had to try to explain why there was a very obvious response to the megadose thiamine. One thing that I had learned is that the part of the brain that deals with a defense against stress becomes very irritable when cellular metabolism becomes inefficient. Thiamine deficiency in that part of the brain produces the same action as a mild to moderate lack of oxygen, because both spell “danger”. When a bacterial or viral infection attacks us, we go into a defensive mode. This is, of course, the illness. The fever makes the action of the microorganism less efficient. Swollen glands are created to catch the dead microorganisms as they are washed into the lymphatic system. My hypothetical explanation is that the thiamine deficiency created brain irritability that repeatedly went into a defensive mode under the false impression that the child was being attacked by a microorganism.

The Transmission in the Body

This again is a hypothesis and I must digress again. Let us take a car as an example of a machine. The engine produces energy and that energy is passed through a transmission that enables the car to go into action. Bewildering as it may seem, the human body is a chemical machine and we can only understand how it functions by understanding the chemistry. As I have said many times in this forum, thiamine has the responsibility of producing energy. It is exactly like a spark plug in a car engine. But because the human body is also a machine, it has to have the equivalent of a transmission. To put it simply, energy is produced by thiamine and stored in the form of a chemical substance known as ATP. Without going into the technological details, ATP is consumed by releasing energy used to drive the transmission that enables bodily functions. The transmission is an energy consuming series of chemical changes known as transmethylation. These chemical changes require folic acid and vitamin B12. Because of thiamine deficiency the ability to produce ATP was compromised. This resulted in lack of energy that affected the transmission. Folic acid and vitamin B12 simply collected in the blood because because they were not being used. As soon as thiamine restoration took place, the transmission became more efficient and the folate and B12 were consumed in the action.

What Has This to Do with Autism ?

The present disease model states that each disease has a unique cause that demands a unique treatment. Genetic research has revealed thousands of possible gene mutations involved in the underlying cause of autism and I have no doubt that this produces variations on a common theme, perhaps explaining why each child with autism is unique in his own right. Thiamine deficiency can express itself in many different ways, depending on which part of the brain is affected. If it can express itself in repeated episodes that exactly imitate a throat infection in one individual and autism in another, we surely have to change how we see health and disease. Both thiamine and vitamin D deficiency have been described in the medical literature as a cause of autism. I have concluded that anything that interferes with an efficient use of oxygen in the brain creates symptoms that may well be interpreted as “psychological”. Most gene mutations don’t have an effect on their own. Serious prolonged stress and/or vitamin deficient malnutrition may have to be present for the disease to be expressed.

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Derrick Lonsdale MD, FACN, CNS

Derrick Lonsdale M.D., is a Fellow of the American College of Nutrition (FACN), Fellow of the American College for Advancement in Medicine (FACAM). Though now retired, Dr. Lonsdale was a practitioner in pediatrics at the Cleveland Clinic for 20 years and was Head of the Section of Biochemical Genetics at the Clinic. In 1982, Lonsdale joined the Preventive Medicine Group to specialize in nutrient-based therapy. Dr. Lonsdale has written over 100 published papers and the conclusions support the idea that healing comes from the body itself rather than from external medical interventions.


  1. Eighteen years ago, years ago Rosemary Waring found that in autism that there was very
    strong evidence of rhodanese dysfunction. Rhodanese is the mitochondrial
    enzyme that detoxifies cyanide by forming thiocyanate from thiosulfate.

    Here is some data from her paper, “Sulphur metabolism in Autism” from the
    Journal of Nutritional and Environmental Medicine (2000) 10, 25-32:

    Autism(n=232) Controls (n=68)

    Protein 103.2 64.5
    Sulphite 106.9 7.1
    Thiosulphate 130.8 18.6
    Thiocyanate 6.4 44.0
    Sulphate 6819.0 3030.8

    In the paper, she discusses the role of rhodanese and why it could be

    Rhodanese converts thiosulphate to thiocyanate, so the ratio of these two
    compounds helps to assess the function of rhodanese. In autism, that ratio
    is 20.4. In her control population, the ratio was 0.42. That means the
    ratio was 49 times normal in autism….a strong indication that this enzyme
    was inhibited in this very large sample population.

    When this enzyme isn’t working, the burden is put upon methyl or
    hydroxycobalamin to detoxify the cyanide by forming cyanocobalamin. This
    conversion that becomes necessary with depressed rhodanese activity might
    raise serum cyanocobalamin levels, but it would also deplete
    methylcobalamin. Those relationships are nicely illustrated

    How do we tie in the thiamine? Well, this is a bit curious:

    Format: Abstract

    Send to
    J Neurol Sci. 2010 Sep 15;296(1-2):30-3. doi: 10.1016/j.jns.2010.06.016.
    Etiology of Konzo, epidemic spastic paraparesis associated with cyanogenic glycosides in cassava: role of thiamine deficiency?
    Adamolekun B1.
    Author information

    Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Memphis, TN 38163, USA.


    Konzo is a syndrome of symmetrical, non-progressive, non-remitting spastic paraparesis occurring in epidemic and endemic forms in several countries in Africa, invariably associated with monotonous consumption of inadequately processed bitter cassava roots (Manihot esculenta) with very minimal protein supplementation. Despite numerous epidemiological, clinical and biochemical studies by authors in several countries aimed at elucidating the etiological mechanisms of Konzo, the etiology remains unknown. High cyanide consumption with low dietary sulfur intake due to almost exclusive consumption of insufficiently processed bitter cassava roots was proposed as the cause of Konzo, but there has been no evidence of a causal association between cyanide consumption and Konzo. In this paper a new etiological mechanism of thiamine deficiency is presented, based on detailed review of the epidemiological, clinical and biochemical features of Konzo. It is postulated that in Konzo patients, a severe exacerbation of thiamine deficiency results from the inactivation of thiamine that occurs when, in the absence of dietary sulfur-containing amino acids; the sulfur in thiamine is utilized for the detoxification of cyanide consumed in improperly processed bitter cassava. Thiamine is known to be rendered inactive when the sulfur in its thiazole moiety is combined with hydrogen cyanide. This hypothesis may stimulate studies examining the role of thiamine in the etiology of Konzo, and may lead to the formulation of strategies for the prevention and treatment of this debilitating disease.
    Comment in

    The role of thiamine deficiency in konzo. [J Neurol Sci. 2011]


    I have also wondered if oxalate may itself impair rhodanese activity, but nobody seems to have studied that. We do know that oxalate seems to have a role in autism: Dr. Waring did not figure out what caused the inhbition of rhodanese activity in autism, but she just found the evidence that the inhibition was there. It was only years later that we discovered the high oxalate levels in autism.

      • Dr. Lonsdale; Thank you for this article and for your informative book. I wish I knew about this Thiamine connection years ago. My son is 8 and considered on the spectrum with a high IQ . His symptoms are muscle weakness , coordination problems, low verbal, some memory problems, fevers that come and go, chronic sinus congestion and fine motor delays and insomnia. I gave him 100mg Thiamin 2 days in a row and have seen improvements in daytime energy and he slept amazingly for the first time in 7 years 2 nights in a row. Right away these two things are amazing and he does have high arsenic in his past urine tests. I do not give him rice and I no longer give him apple juice since that can be a source of arsenic. I just ordered the brand of Lipothiamine that you recommend and I will give that with magnesium citrate. do you have any further advice for me? Also did you see that Dr. Constantini in Italy is using Thiamine for Parkinson’s disease?

        • Is there a family history of alcoholism? Get rid of all forms of sugar in his diet. Yes I am aware of Constantini’s work. A high IQ is a dietary risk because it requires a lot of brain energy. Energy cannot be synthesized in the body/brain without thiamin

          • Yes grandparents on one side did drink. Ok I have gotten rid of sugar. He is still very calm since starting the Thiamine and happier about everything. His teacher mentioned that he happily worked in fine motor skills in art class (weaving) and it was easier for him! Fine motor has been difficult for him. He is eight and normal size, a little thin, I have the Lipothiamine being delivered tomorrow. I plan on starting that Saturday at 50mg. Do I then stop using the regular Thiamine. I Thank you for your professional advice!

        • Is there a family history of alcoholism? Get rid of all forms of sugar and stick to any and all forms of God made food including fresh fruit (but not canned).Yes I am aware of Constantini’s work but very few physicians are aware

        • Rosemary showed that the enzyme rhodanese was the clue but you have to read the paper to understand the connetion. Japanese scientists showed many years ago that the thiamin derivative known as thiamin propyl disulfide (one of the many disulfide derivatives) stimulated rhodanese and gave partial protection from cyanide poisoning in mice.

  2. A final comment on this post. I have tried to give an explanation for why folate and B 12 levels are increased in autism. But they were also increased in a child who had repeated episodes of sore throat and swollen glands! In both conditions (autism/febrile lymphadenopathy) the underlying causative factor has been shown to be thiamin deficiency, both reported in the medial literature. Does that mean that we have conquered autism and febrile lymphadenopathy? Of course not. However, thiamin deficiency results in a decay of energy metabolism so perhaps we can draw the conclusion that anything that interferes with energy metabolism will cause these diseases. Perhaps all illness is related to a compromise in energy metabolism and it is the “biochemical lesion” that must be found in order to secure a proper diagnosis. Descriptive terms to make a diagnosis, e.g.rheumatoid arthritis, Parkinson’s disease, etc. are no longer valid without knowing the chemical underpinning. This requires a knowledge of the genetic mechanisms that may be at fault, Including the genes in the mitochondria, coupled with the degree of lifestyle stress and places nutrition at front and center as the ONLY source of prevention and treatment.We can regard a bacterial or viral infection as a form of attack. It became the paradigm for medical treatment and gave rise to the idea of killing the bacteria, the virus or even the cancer cell (the enemy). We gave little thought to the normal defenses of the body conducted by the brain as the “conductor of the body orchestra”. Even Louis Pasteur admitted on his deathbed that he was wrong. He said that it is the defenses of the body that must be supported. By all means kill the enemy as long as it is safe to do so but do not neglect the defenses. The only thing that we can do is attend to the details of nutrition, filling in the gaps where micronutrient deficiency is at fault.

    • HI my child spontaneously urinates and looses control of her bowel within an hour of eating a food product with Thiamine in, she also gets extremely itchy around the bum and down the backs of her legs. Is this normal reaction of Thiamine consumption? We are not talking excess we are talking a couple of biscuits, using flour in her food to make a rue sauce, eating a sausage. My daughter is still young but feeding her is difficult. and the loss of control upsets her. Any help would be really appreciated as anyone we tell thinks were crazy!

      • State child’s age, nature of diet, i.e sugar intake and “food with thiamin in it” . Give details of pregnancy, birth and neonatal history of child.

  3. Dr Lonsdale, can you break the lipothiamine up into smaller pieces while you are working up? I started taking 100mg doses of benfotiamine and had chest pains. I ordered lipothiamine and have broken the tablet up into 1/8ths for 2 days and haven’t had any chest pains, but wondering if breaking the tablets affects efficacy. Also, will thiamine improve thyroid function? My dr has prescribed me thyroid medication but I am curious if thiamine alone with solve this.

    • Lipothiamin is enteric coated to ensure that it gets through the acid environment of the stomach to the next part of the bowel, the jejunum. Here, the enteric coating is removed and thiamin is absorbed. The best way to start taking thiamin is to begin with small doses of thiamine hydrochloride and gradually increase until you can accept the 50 mg Lipothiamin. For those coming to this website new, this response applies to people who have been severely deficient in thiamin for a long time without it being recognized.

  4. Dear Dr. Lonsdale.

    I had been reading your blogs posts and learning about thiamine. My son started getting fevers when exposed to cold weather ie even few minutes exposure will result in fever . No drs have helped. He is a special needs kid (nonverbal ASD) . He has severe oxalate issues which started after his abx dose .

    Since then I have learnt that short course of abx can flare lyme. I am also suspecting Babesia infection and soon we will be testing for it . Lyme seems to deplete thiamine and maganese. We tried adding all the B vitamins as per his biomed dr’s recommendation. Adding B1 in big doses caused severe oxalate dump which triggersed/worsened his MCAS and resulted in clonic /tonic seizures.

    Do you have any advise for patients with glutamate/oxalate/MCAS issues on adding thiamine. I love to hear your thoughts on this issue. Please help.

    • Does your son have a high level of folate and B 12 in the blood? I was fascinated by your report that he developed fever when the environmental temperature decreases. Let me try to explain this. The lower part of the brain computes all our defensive actions as a response to what you might call environmental stress. A bacterium or virus can be thought of as an attacking agent or a form of stress. When that part of the brain becomes hypersensitive to any form of stress, it will automatically overreact to the low temperature as a stress effect, as though it were an infecting organism. Hypersensitivity is caused by any form of oxygen depletion or its equivalent and thiamin deficiency is causing that kind of hypersensitivity in his brain. It is also interesting that his burden was increased after his abx dose. That also acted as a stressor. Support for thiamin deficiency comes from oxalate issues. Oxalate comes from a defect in an enzyme that is dependent upon thiamin. We now know that immunity is controlled by the brain and thiamin deficiency will derail this mechanism. If I were in control of your case I would start him on 5 mg doses of thiamin and gradually increase. By starting on high doses you induced a paradoxical reaction, known to occur when a deficiency has been prolonged and is the forerunner to improvement. The trouble with this is that length of the paradox can never be forecast and may be several weeks. When you get up to about 50 mg of thiamin a day, switch to Lipothiamine that can be obtained on line from Ecological Formulas. You MUST act under the care of your physician who can research it by getting my paper (Lonsdale D. Thiamine and magnesium deficiencies: keys to disease. Medical Hypotheses,2015, 84(2):129-134.

    • It is not surprising that your son’s fever response to cold weather Is not understood by your physician, because there is no explanation in the present medical model. Thiamin deficiency makes the brain very irritable. Since it is responsible for initiating a defensive reaction to any form of stress it is treating the exposure to cold weather as a stress phenomenon that requires a response, even though it is unnecessary.Oxalate is an endpoint of metabolism and has no chemical function in the body. We know that oxalate can be manufactured because of thiamin deficiency. I would strongly suspect that your son’s diagnosis, whatever the name given to it, is a result of thiamin deficiency, beginning perhaps even before he was born. Even though it may have a genetic origin, it is likely to respond to pharmacologic doses of thiamin. Ask your physician to do a little research on his own and see if this is just my imagination or whether it has substance in scientific evidence. You can get lots of information by obtaining one of my several books that are available on Amazon, the latest being co-authored with me by Dr. Chandler Marrs

  5. Really interesting article, as am currently looking into this area for myself. Please could you give me the reference for the paper you refer to in your article as below ;

    “recently, a paper has been produced in which folate and B 12 have both been found to be increased over the normal range in autism”.

    Thank you in advance!

  6. What an excellent article. I appreciate the simple manner you use to explain this biochemical process. I believe this applies to my 12 year old daughter. It lines up with her lab work and symptoms. Thank you!

  7. Fascinating article. I’m an autistic adult whose sensory challenges were greatly exacerbated in response to certain medical treatments. My b12 levels have been elevated every time they’ve been tested. They’re usually around 1080-1200 pg/mL with a reference range of 213-816 pg/mL. I don’t take b12 supplements or get b12 injections. At the times my levels were tested I followed a plant based diet. None of the physicians I’ve seen have been able to explain the elevated b12, so they dismiss it as a clinically insignificant anomaly or alternately insist I must be lying about supplementation. I’m curious as to whether elevated b12 might have something to do mast cells. There’s a doctor at Tufts, Dr. Theoharides, who thinks mast cell activation is behind some types of autism. Thoughts?

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