Section 1 of Part 2: How Could A Gluten Intolerance Cause Amyotrophic Lateral Sclerosis (ALS) Or Lou Gehrig’s Disease?

March 9, 2011 · Filed Under ALS 

This is part 2 of a 5 part series discussing how ALS could be caused by a gluten intolerance, other types of allergies, and/or by a reaction to lectins. In this part of the series, the possible association between ALS and a gluten intolerance is discussed. Due to the length of this part, I will need to break it into 8 posts/sections. At the end of this post, I have outlined the series for you. Today, section one will discuss how reactions against transglutaminases may contribute to symptoms.

Section 1: How Could Antibody Reactions Against Transglutaminases Contribute To ALS

Transglutaminases are very important enzymes. These enzymes are involved in many functions, such as tissue repair, signalling processes, cellular differentiation (cells become more specialized), matrix stabilization (tissue that provides support to cells), and apoptosis (biochemical change that causes death in cells that are not needed). Without it, tissue repair is hindered, unfavourable cellular changes can occur, abnormal cells could grow uncontrollably leading to cancer and signalling between cells (including nerve cells) could be negatively affected. These changes could occur in any area of the body where the enzyme is not available.

You may be wondering why I’m so interested in transglutaminases and what does this have to do with ALS. Well, with a gluten intolerance, antibody attacks against tissue transglutaminase can cause many problems. Since I have celiac disease and have experienced the result of this reaction, I am intrigued by this enzyme. With celiac disease (CD), tissue transglutaminase 2 is damaged by antibodies in the bowel, antibodies against tissue transglutaminase 3 occur in dermatitis herpetiformis (another form of gluten intolerance) and antibodies attack tissue transglutaminase 6 in gluten ataxia (form of gluten intolerance causing neurological disease). Since many neurological symptoms can occur with gluten intolerance (due to immune reactions against transglutaminase and nerve tissue),  it seems reasonable to suspect that cross reactions to transglutaminases could occur in patients with ALS.

Like celiac disease, dermatitis herpetiformis and gluten ataxia, perhaps, immune responses to gluten and transglutaminase in the gut leads to autoimmune activity against various forms of transglutaminases throughout the body (in this case, the central and peripheral nervous system). This could result in different types of neurological diseases, such as ALS. IgA and IgG antibodies against transglutaminase (and nerve tissue) could lead to inflammation and autoimmune damage in the central and peripheral nervous system. This type of damage could interrupt the neuronal impulses and lead to the neurodegenerative disease process seen in ALS. I believe this type of reaction is very likely to occur considering that neuronal impulses can be negatively affected with a gluten intolerance.

In studies, researchers found that transglutaminase levels were higher in the initial stages of ALS. However, as the ALS progressed, abnormally low levels of transglutaminase was found in the cerebral spinal fluid of patients with clinical motor dysfunction. In autopsies (from 5 patients with ALS), tissue (transverse sections) taken from the human spinal cord (lumbar and thoracic) showed very low transglutaminase activity (in the ventral, dorsal, and lateral regions). The researchers theorize that the transglutaminase enzyme is low because the supply is exhausted due to the demand for tissue repair with ALS. The researchers in another study suggested that the enzyme may leak out of the spinal cord into the CSF and then into the bloodstream leaving low levels in the CSF and spinal cord [1,2].

I think that it is reasonable to suspect that IgA and IgG antibodies may initially react to gluten, then cross react against tissue transglutaminase in the central and peripheral nervous system of patients with ALS. Tissue transglutaminase has an affinity for undigested gluten so a cross reaction could easily occur. The reaction to gluten could initially increase levels, then as the antibodies identify and attack transglutaminase, levels would be depleted (like in the studies). Cross reactions against neuronal tissue could also occur, just as it does against endomysial tissue in celiac disease and brain plus nerve tissue in gluten ataxia. This autoimmune reaction could be the culprit underlying the damage found in the brain and spinal cord of patients with ALS.

Unfortunately, this damage would increase the demand for tissue transglutaminase (for tissue repair) and this would deplete the supply further (may help explain the low levels in the studies). This type of reaction occurs with gluten ataxia (a neurological condition that results from antibody reactions to gluten and transglutaminase). It isn’t a far stretch to suspect that immune reactions to gluten and cross reactions against tissue transglutaminase could be the underlying culprit in ALS.

I believe researchers need to conduct further research to look at the role and types of transglutaminases that are present in the the brain, spinal cord (and CSF), how the transglutaminases are affected with ALS, and how the ingestion of gluten may be promoting a cross reaction against tissue transglutaminase and nerve/brain tissue in this illness. If a gluten intolerance is responsible, a gluten-free diet may take a year or longer to work, but is a nice alternative to the current prognosis associated with ALS.

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The rest of Part 2, along with parts, 3, 4, and 5 will follow in the next 2-3 months.

5 Part Series

Part 1 Of 5 Part Series : Could A Gluten Intolerance Cause Amyotrophic Lateral Sclerosis (ALS) Or Lou Gehrig’s Disease?

Part 2 Of 5 Part ALS Series: How Could A Gluten Intolerance Cause Amyotrophic Lateral Sclerosis (ALS) Or Lou Gehrig’s Disease? (see 8 sections of Part 2 below)

Section 1 of Part 2: How Could Antibody Reactions Against Transglutaminases Contribute To ALS

Section 2 of Part 2: Could IgA and IgG Mediated reactions To Foods Contribute To ALS Symptoms

Section 3 of Part 2: Could Glutamic Acid And Aspartic Acid Contribute To ALS Symptoms

Section 4 of Part 2: Abnormal Neurological Findings With A Gluten Intolerance

Section 5 of Part 2: Can Nutrient Deficiencies Contribute And How is This Associated With A Gluten intolerance?

Section 6 of Part 2: Are There studies Showing An Association Between Gluten And ALS?

Part 3 Of 5 Part Series: How Could A Gluten Intolerance Cause ALS In Various Age Groups

Part 4 Of 5 Part Series: How could A Lectin Intolerance Contribute To ALS

Part 5 Of 5 Part Series: Some Final Thoughts About ALS And Gluten

References

1. Kimikazu Fujita, Masato Ando, Masamitsu Yamauchi, Yutaka Nagata and Masao Honda. Alteration of transglutaminase activity in rat and human spinal cord after neuronal degeneration. Biomedical and Life Sciences Neurochemical Research, Volume 20, Number 10, 1195-1201.

2. Kimikazu Fujita, Masao Honda, Ryuichiro Hayashi, Kazuhito Ogawa, Masato Ando, Masamitsu Yamauchi, Yutaka Nagata. Transglutaminase activity in serum and cerebrospinal fluid in sporadic amyotrophic lateral sclerosis: A possible use as an indicator of extent of the motor neuron loss. Journal of the Neurological Sciences Volume 158, Issue 1 , Pages 53-57, 11 June 1998.

3. Hasegawa G, Suwa M, Ichikawa Y, Ohtsuka T, Kumagai S, Kikuchi M, Sato Y, Saito Y. A novel function of tissue-type transglutaminase: protein disulphide isomerase. Biochem J 2003; 373:793-803.

4. Kamaeva OI, Reznikov IP, Pimenova NS, Dobritsyna LV. Antigliadin antibodies in the absense of celiac disease. Klinicheskaia Meditsina, 1998; 76 (2):33-5.

6. Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature’s biological glues. Biochem J 2002;368:377-96

7. Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S, Hoffenberg EJ, Horvath K, Murray JA, Pivor M, Seidman EG. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005 Jan;40(1):1-19.

8. Shane M. Devlin, MD, FRCPC, Christopher N. Andrews, MD, FRCPC, Paul L. Beck, MD, PHD, FRCPC. Celiac Disease. Canadian Family Physician, CME update for family physicians. May, 2004

9. Mishra S, Murphy LJ. Tissue transglutaminase has intrinsic kinase activity: identification of transglutaminase 2 as an insulin-like growth factor-binding protein-3 kinase. J Biol Chem 2004;279:23863-8.

10. Fesus L, Piacentini M. Transglutaminase 2: an enigmatic enzyme with diverse functions. Trends Biochem Sci 2002;27:534-9.

11. Sakly W, Thomas V, Quash G and El Alaoui S. A role for tissue transglutaminase in alpha-gliadin peptide cytotoxicity. Clin Exp Immunol 2006;146:550-8.

12. M Hadjivassiliou, RA Grünwald, GAB Davies-Jones. Gluten Sensitivity As A Neurological Illness. J Neurol Neurosurg Psychiatry 2002:72: 560-563.

13. Sardy M, Karpati S, Merkl B, Paulsson M, Smyth N.Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J Exp Med.Mar 18 2002;195(6):747-57.

14. Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders DS, Woodroofe N, Aeschlimann D. Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol 2008 Sep;64(3):332-43.

15. Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D. Gluten sensitivity: from gut to brain. Lancet Neurol. 2010 Mar;9(3):318-30.

Comments

7 Responses to “Section 1 of Part 2: How Could A Gluten Intolerance Cause Amyotrophic Lateral Sclerosis (ALS) Or Lou Gehrig’s Disease?”

  1. Ket Brian on March 15th, 2011 10:43 am

    Thanks for your post! I have learned new things now! Gluten really can’t help :( I was been diagnosed once with celiac! Now I am so care of my foods to eat. A selection foods for a healthy diet :)

  2. Greg Malby on April 14th, 2011 4:37 am

    Shelly,
    Great article, thanks so much. I am a 61 year old male that has suffered from seizure activity since I was 12. Two year ago I lost about 60 pounds and noticed that my seizure activity decreased while I was using the Medifast foods to loose weight. The short version is that I had DNA testing done and found markers that indicated gluten intolerance. After a 6 month purge I am seizure free as long as I stay away from gluten. I use a supplement called GlutenFlam (K-52) whenever I suspect I may have ingested gluten. I have never had a celiac problem.
    I just recently had a friend diagnosed with ALS and found your site while doing some research. I will sign up for your newsletter. Thanks so much for work, I look forward to sharing this information with my friend.
    Sincerely,
    Greg

  3. John L on June 15th, 2011 11:11 am

    I like the way your hypothesis is developing. I think a lot of the odd reactions to gluten may be caused by the damage done the small intestine and the resultant problems with nutrient absorption. Specifically vitamin D and magnesium. Both nutrients are sometimes mentioned in natural treatments for ALS and MS. I hope more research is done on this nutrient absorption issue.

    I am also curious has anyone looked at Mr. Gehrig’s family history? I know he was first generation Norwegian. It would be interesting to know if there was a family history with gluten.

    John

  4. Shelly on August 9th, 2011 10:08 pm

    Thank you John:)

    Yes, it would be interesting to look at Mr. Gehrig’s family history. If I see anything, I’ll post a link to it.

    Best regards,
    Shelly

  5. Dana Carpender on September 3rd, 2011 2:05 pm

    Thank you for this. My BIL has been suffering increasing ataxia, tremors, and spasticity; neurologists have been clueless. I just read Wheat Belly by Dr. William Davis, and realized he sounds like a very possible case of gluten-caused cerebellar ataxia. Then I remembered that his mother died of ALS, and started googling. Very good to find this.

    Now — do you know anything about Lewy Body Dementia and gluten?

  6. Shelly on October 7th, 2011 10:27 am

    Hi Dana,

    Thank you for your comment. It is great that you are considering gluten intolerance as one contributing factor since there could be an association.

    With regards to Lewy Body Dementia, I haven’t seen any research, but would not be surprised if there was a connection.

    You may find my other post about Alzheimers interesting and also the neurology chapter in my book, “Gluten Toxicity”. Both discuss how immune reactions to gluten (and immune reactions to other foods) can affect the brain and the neurological system.

  7. Cherie Litton on January 17th, 2012 11:03 am

    I have trigeminal neuralgia and my daughter, found out I need to be on an gluten-free diet. I have had allergies all my life, since a child. I have used different allergiest. I also have a vitamin D deficiency for years. Cherie Litton

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