Is Thiamine Deficiency the Beginning of Celiac Disease?

[knitty kitty]

I've been researching Celiac disease and Thiamine deficiency for a long time.  Recently I found information that shows a relationship between the lack of Thiamine and Celiac Disease pathogenesis.  What do you think?

Thiamine is used in the mitochondria to produce energy (ATP) in the body for cells use as they go about their various functions.  Various chemical reactions take place as the glucose moves through the transport chain in the mitochondria.  Oxygen is needed at the end of the transport chain to pick up electrons leftover from the chemical reactions of ATP production and combines with Hydrogen electrons to form water.  One molecule of glucose results in 32-36 ATP. 

If there is not enough Thiamine for the mitochondria to produce ATP using Oxygen to mop up the spare electrons, the mitochondria switches to anaerobic (without oxygen) production of energy.  Only 2 ATP are produced in this manner from one glucose molecule.  Anaerobic production of ATP leaves lactic acid as a byproduct.  Oxygen delivered to the cell passes through unused or is ignored since it's not capable of being used.  This induces a state of hypoxia.  Thiamine deficiency causes hypoxia.

Hypoxia-Inducible Factor 1 alpha (HIF-1a) is part of a checks and balances system within cells.  HIF-1a is degraded (turned off) by byproducts from aerobic production of energy using thiamine.  However, if the byproducts build up too much, HIF-1a is stimulated.  During low oxygen levels and anaerobic production of ATP, a build up of lactic acid stimulates HIF-1a.  

Hypoxia-Inducible Factor 1α binds to thiamine transporter SLC19A3 and activates it to increase thiamine uptake.

HIF-1a affects genes in the nucleus, entering through micro-pores.  HIF-1α signaling triggers the release of inflammatory cytokines and increases inflammatory cell proliferation.  It can also cause cell death. 

Hypoxia and high levels of HIF-1a are found in many autoimmune diseases and cancer. 

Thiamine attenuates HIF-1a signaling.  Thiamine restores ATP production to aerobic production. 

Here's an excerpt...

"HIF-1α shows its functions through translocating into the nucleus, dimerizing with HIF-1β and binding to hypoxia-responsive elements of the HIF-1α target genes. Recent data have also suggested that HIF-1α plays a role in maintaining intestinal epithelial barrier functions [37,38]. Accumulating evidence has also shown that HIF-1 α plays an essential role in cells via interaction with the NF-kB p65 pathway in the pathogenesis of inflammation [17]. In addition, previous research has further reported that HIF-1α expression is increased in the duodenal tissue of celiac disease patients [19,39]. It has been pointed out that activated HIF-1α is involved in celiac disease pathogenesis.".  

https://pmc.ncbi.nlm.nih.gov/articles/PMC9954839/

References:

Increased Expression of Hypoxia-Inducible Factor 1α in Coeliac Disease

https://www.nature.com/articles/pr2010143

Intestinal parameters of oxidative imbalance in celiac adults with extraintestinal manifestations

https://pmc.ncbi.nlm.nih.gov/articles/PMC5703914/

Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1073971/full

Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes

https://pmc.ncbi.nlm.nih.gov/articles/PMC5646851/

Stabilization of the hypoxia-inducible transcription Factor-1 alpha (HIF-1α) in thiamine deficiency is mediated by pyruvate accumulation

https://pubmed.ncbi.nlm.nih.gov/30008376/

Thiamine (Vitamin B1)-An Essential Health Regulator

https://pmc.ncbi.nlm.nih.gov/articles/PMC12251314/

https://pubmed.ncbi.nlm.nih.gov/40647310/

Role of HIF-1α in the Hypoxia Inducible Expression of the Thiamine Transporter, SLC19A3

https://pmc.ncbi.nlm.nih.gov/articles/PMC5097002/

https://pubmed.ncbi.nlm.nih.gov/27743994/

Thiamine insufficiency induces Hypoxia Inducible Factor-1α as an upstream mediator for neurotoxicity and AD-like pathology

https://pubmed.ncbi.nlm.nih.gov/36241022/

Mito-Nuclear Communication by Mitochondrial Metabolites and Its Regulation by B-Vitamins

https://pmc.ncbi.nlm.nih.gov/articles/PMC6379835/

The role of hypoxic microenvironment in autoimmune diseases

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1435306/full

Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1073971/full

Increased Expression of Hypoxia-Inducible Factor 1α in Coeliac Disease

https://www.nature.com/articles/pr2010143

Peroxiredoxins and Hypoxia-Inducible Factor-1α in Duodenal Tissue: Emerging Factors in the Pathophysiology of Pediatric Celiac Disease Patients

https://pmc.ncbi.nlm.nih.gov/articles/PMC9954839/

Edited March 21 by knitty kitty
Typo correction

[knitty kitty]

References about Thiamine:

Thiamine (Vitamin B1)—An Essential Health Regulator

https://pmc.ncbi.nlm.nih.gov/articles/PMC12251314/

Thiamine and benfotiamine: Focus on their therapeutic potential

https://pmc.ncbi.nlm.nih.gov/articles/PMC10682628/

The importance of thiamine (vitamin B1) in humans

https://pmc.ncbi.nlm.nih.gov/articles/PMC10568373/

[Scott Adams]

You’re definitely connecting some real dots here, and your thinking isn’t off base—but it’s important to separate what’s established from what’s still theoretical.

There is good evidence that HIF-1α and hypoxia-related pathways are involved in inflammation and are elevated in celiac disease tissue . And separately, thiamine deficiency can push cells toward anaerobic metabolism, increase lactate, and influence HIF-1α signaling. So biologically, your chain of reasoning—thiamine → energy metabolism → hypoxia signaling → inflammation—is plausible.

Where it gets less certain is causation. Right now, the research doesn’t show that thiamine deficiency drives celiac disease. It’s more likely that:

• celiac-related intestinal damage → malabsorption of nutrients (including thiamine)
• inflammation → changes in metabolic and hypoxia pathways

So thiamine deficiency may be more of a downstream effect or contributing factor, rather than a root cause.

That said, your idea still has value. Even if it’s not causing celiac, low thiamine could:

• worsen fatigue and brain fog
• impact energy production
• potentially amplify inflammatory signaling

So optimizing thiamine status in people with celiac (especially untreated or newly diagnosed) could absolutely be beneficial—even if it’s supportive, not curative.

The current evidence supports association and modulation, not direct causation of celiac disease.

[Mari]

It is rather amazing to me that I was able to follow, in a general way, your reasoning in this scientific  thesis. It is very good work on your part taking different research papers and tying the information together if not for a cure for celiac disease, the ability to decrease the symptoms of celiac disease and other autoimmune conditions. Now if you can get this into the scientific conversation about autoimmune  problems. I hope so.

On a more practical level please give me the name of the thiamine that you recommend. I forgot to copy it the last time you shared it.   

Thanks

[knitty kitty]

I've got them listed in my blog...

Benfotiamine and TTFD-B1 Max by Maxlife Naturals, or Ecological Formulas Allthiamine (TTFD), or Thiamax by EO Nutrition are my favorites.

[knitty kitty]

@Mari, 

I found Dr. Derrick Lonsdale and Dr. Chandler Marrs' website hormonesmatter.com most helpful in learning about thiamine.

https://hormonesmatter.com/talking-about-thiamine/

I thought these might interest you...

New insights on genes, gluten and immunopathogenesis of celiac disease

https://pmc.ncbi.nlm.nih.gov/articles/PMC11283582/

Celiac disease: From genetics to epigenetics

https://pmc.ncbi.nlm.nih.gov/articles/PMC8790554/

Keep me posted on your progress!