Gluten-free and thyroid disease

I was first diagnosed with Hashimoto’s thyroiditis after 1 year of a gluten free diet. I was quite surprised by this, as I had assumed that a gluten free diet might lessen the symptoms of other autoimmune diseases I had.

Indeed, it made my narcolepsy nearly disappear. Why, then, did I seemingly have continued destruction of my thyroid despite being on what I once considered  an “autoimmune cure-all diet”?

Hashimoto’s has been shown to occur more frequently in individuals with celiac disease, and the opposite (subclinical celiac disease in patients with HT) has also been demonstrated. Currently, there is no good proposed explanation for the association at this time, although some molecular details linking the two are starting to be explained, as described below.

Unfortunately, while a gluten free diet can reverse the effects of subclinical or overt celiac disease and gluten sensitivities, and potentially provide beneficial effects to other autoimmune diseases, a gluten free diet seems to have no effect on Hashimoto’s thyroiditis, and does not affect progression of the disease, either.

In short, while a gluten-free diet may provide relief from the ill-effects of gluten itself, or provide some relief for individuals with other autoimmune diseases, a gluten-free diet does not seem to deter progression of autoimmune thyroid disease once the process has already begun.


Updated September 29, 2012

After several thoughtful comments on this post, I have decided to expand upon some of the concepts originally laid out.  Though familiar with the article, I specifically avoided mentioning “The gluten-thyroid connection” post by Chris Kresser, as well as those by other nutritionists for several reasons detailed below.  However, some really great suggestions were brought up, and it made me really go back and look at the literature again, which I really appreciate!

1. It is clearly demonstrated that celiac disease is associated with several other autoimmune diseases, among them autoimmune thyroid disease, and that undiagnosed celiac disease or gluten sensitivities may have the potential to precipitate other autoimmunities.  I don’t think anyone is saying anything different at this point, so we’ll leave it there.

2. Chris Kresser claims that the immune cells which “see” gluten also make a mistake and “see” thyroid autoantibodies.  This concept is called “molecular mimicry,” and is generally thought of as immune cells being activated by a foreign antigen, see the same antigen in self tissues, and get confused, thereby unintentionally attacking yourself. Molecular mimicry was a pet theory (especially between 1980’s – 1990’s) in the realm of autoimmune research for quite a few years, and still is to a certain degree.

Chris Kresser’s article mentions, but does not cite the reference for his claim that there is molecular mimicry occurring between thyroid tissue and gluten.  

In another post over at “Dr. Karl R.O.S. Johnson’s Chronic Condition Natural Treatment Blog” , Dr. Karl again puts forth the molecular mimicry idea, and even includes a picture as well as a fictitious amino acid sequence (AABCD) supposed to cause the “T cell confusion,” again without reference to any legitimate source.  Enough said.

Leyla Muedin, over at the Dr. Ronald Hoffman Center has a similar article and states:

“In the case of autoimmune thyroiditis, a gluten-free diet can sometimes decrease antithyroid antibodies. It is thought that people with autoimmune disease have a more permeable intestine (leaky gut) and that gluten and/or other undigested substances are leaking into the blood stream and causing autoimmunity through molecular mimicry. This is supported by a recent Italian study which found that individuals with gluten allergy also developed a significant allergy to their own thyroids, which disappeared when gluten grains were removed from the diet. Checking for serum levels of antibodies against gluten as well as thyroid antibodies is standard practice at The Hoffman Center.”

Again, no specific reference is cited, but I believe she is referencing the Italian study shown below, which focuses on pediatric patients with celiac disease prior to onset of overt thyroid disease.

Unfortunately, molecular memory has, in large part, turned out to be a nice idea, but rarely demonstrated for many autoimmune diseases.

“Although there is some evidence that infectious agents play a part in the pathogenesis of multiple sclerosis and many other autoimmune diseases it has not yet been proved that molecular mimicry is the initiating factor in any of these diseases.” [1]

Now, with all of that said, there is some evidence for molecular mechanisms of autoantibody production in celiac disease and off-target (i.e. thyroid) destruction.

In classical celiac disease, autoantibody production to a molecule expressed in the intestine called “tissue transglutaminase” (Ttg) is deemed necessary for progression to celiac disease.  Ttg is expressed in all over the body, including in thyroid tissue.  In context of celiac disease, Ttg becomes upregulated in many tissues as a result of inflammation. Secondary to that, “off-site” targeting of antibodies to Ttg initially generated in the gut is suggested to be part of the cause for inflammation and autoimmunity seen at other sites.   A recent 2009 study has demonstrated that patients with celiac disease have elevated thyroid antibodies which correlates with Ttg antibodies, and that those antibodies may contribute to the development of autoimmune thyroiditis.

Key points:

  • molecular mimicry has not been demonstrated to occur between gluten and thyroid tissue
  • inflammation and oxidative stress can cause upregulation of Ttg in the gut and in other tissues (including the thyroid)
  • “off-target” sites of immune activation for Ttg antibodies can precipitate immunity in the thyroid

Mimicry and mechanism aside, all of this still doesn’t answer the question:

3. Can a gluten free diet reduce thyroid diease?  Because of the clear (and potentially causal) link between celiac disease and thyroid disease, several groups have tracked autoantibody production to thyroid tissues AFTER putting patients on gluten free diets. They have mostly found that gluten free diets do not affect thyroid autoantibody production after over autoimmune thyroid disease has already occured. See: here.

References or legitimate scientific evidence that a gluten free diet can reduce thyroid autoantibodies after overt disease onset is severely lacking, however there seem to be many holistic health practitioners, acupuncturists, and nutritionists quick to quote “studies which show” that a gluten free diet can reduce thyroid autoantibodies.

There is one group from Italy that has demonstrated a reduction in autoantibodies indicative of autoimmune thyroid disease and type-1 diabetes following celiac disease diagnosis and treatment. This paper potentially demonstrates that removal of gluten from the diet of children, who have not yet progressed to overt diabetes or autoimmune thyroiditis, may reduce the risk of developing these complications later on in life. In addition, they mention that nutrient malabsorption due to celiac disease could be at the root of this phenomenon (quoted below). This impressive data, however, does not comment on or suggest that the same process could take place after overt disease (significant tissue destruction) has occurred. A key piece of the data will be to see if some of those children go on to develop disease, or if the protection against developing other autoimmunities following a life-long GF diet is for good.

“Our data, in agreement with data reported by other authors, suggest that the main etiological factor of hypothyroidism at diagnosis may be attributed to a decreased thyroid hormone synthesis as a consequence of isolated malnutrition, and the normalization of thyroid function was obtained by means of gluten withdrawal alone….Therefore, iodide malabsorption could strongly contribute to the etiology of nonautoimmune hypothyroidism in CD. [2]

 Key point: start a GF diet early to ward off other autoimmunities.

That said, there are still several people on-line who say that a gluten-free, casein-free diet have reduced their autoantibody load, and they have had to reduce thyroid medication [3].  What is not clear from these posts, however, is if these people were being treated for subclinical thyroiditis, or whether they had already had significant atropy/destruction of the thyroid.  Clearly research in this area (particularly in adults, and those with advanced thyroid disease) is warranted.

My personal journey: When I was first diagnosed with narcolepsy, I had normal levels of TSH, T3 and T4 (autoantibody production was not checked during this time).  A year after following a strict gluten free diet (about 2 years after my initial narcolepsy diagnosis), I was diagnosed with Hashimoto’s thyroiditis, and had abnormal TSH and T4 levels. At that time my autoantibody production was checked, and it was through the roof (>1500).  Since that time (about 2 years), I have never had my Tpo antibody under 1000, and continue to take desiccated thyroid for keeping my thyroid levels normal.

4. I have no doubt that people with autoimmune thyroiditis feel better on a gluten free diet. In fact, several of the references included within this article note that while their patients to not see a decrease in antibody production, they do note “feeling better” and having “symptomatic” improvement of autoimmune thyroiditis on a gluten free diet.  This makes sense in the context of inflammation and autoimmunity. If you remove gluten from your diet, you remove a significant amount of inflammation.  Lessening inflammation (in whatever form it takes) is bound to have a positive effect on inflammatory conditions, including autoimmune thyroid disease. While symptomatic improvement is clear, it is not necessarily clear that gluten free reduces overt disease after the process has been well established, and there is significant atrophy of the tissue (at least for the thyroid).

Key point: Go gluten free. Reduce inflammation. Feel better.

5. Supplementation: There is a clear connection between selenium and thyroid function. Selenium is a trace mineral that is found in higher concentrations in endocrine tissues (such as the thyroid); therefore it makes sense that decreased intake or absorption of selenium should have a negative effect on the thyroid. I have had both selenium and iodine checked, and have no deficiencies in either, however the papers referenced by Kesser in his selenium article  demonstrate that benefits of supplementation can be seen even in selenium-competent patients (a phenomenon called “saturation”).

I think supplementation prior to disease for underfunctioning thyroids (not already destroyed by autoimmune attack) might be a good option for most, particularly if there is undiagnosed/diagnose celiac disease causing a malabsorptive condition. Please note: I am not recommending individuals with thyroiditis, subclinical thyroid disease or any other disease supplement with selenium. I am not a practitioner.

As was pointed out by Chris Kesser, a study has demonstrated that selenium supplementation may reduce autoantibody titers.  Other groups, however, have demonstrated (using larger cohorts) that selenium supplementation does not improve thyroid antibody production.  Even then, however, selenium supplementation seems to have a positive effect on “well-being” and “mood” in patients, even when autoantibodies do not decrease. It is also noted in the previously reference article that there is good tolerability with few side effects of supplementation.

While selenium does not act on the thyroid directly, it is necessary for the T4 to T3 conversion, and also can take part in NF-kB signaling, by limiting inflammation during the “acute phase” of the inflammatory response. I am all for limiting inflammation in the context of autoimmunity!  

 Key points: 

  • Selenium malabsorption due to celiac disease may precipitate hypothyroid functioning or altered immune signaling, thereby precipitating or maintaining thyroid autoimmunity
  • Selenium supplementation has been shown to reduce thyroid autoantibody titers in some studies, but not in others
  • Even in those studies where autoantibody production was not altered, patients reported having a better “mood”
  • Selenium may act by controlling inflammatory processes; and, again, controlling inflammation is always a good thing.
  • Selenium supplementation seems to fall under the cateogory of “do no harm” with the potential to do good. 
All of that said, stay tuned for a Selenium Supplementation Experiment!  Is anyone taking selenium for thyroid health? Have you noticed a difference? How much do you take?
Thank you for all of the wonderfully thoughtful comments – keep ’em coming!

Narcolepsy, dopamine and tyrosine.

Recently, I have been intrigued by the link between dopamine and narcolepsy.  About a year ago, I had a blood test done for neurotransmitters, which indicated that I had normal serotonin, but low circulating dopamine. Nutritionally, this would indicate a deficiency in intake of L-tyrosine, or maybe a defect in the conversion to dopamine, or some other mechanism of dopamine release in the brain.

I didn’t really appreciate the bloodwork, until I realized there were signs of dopamine deficiency in family members on my mother’s side. My maternal grandfather has long suffered with restless legs syndrome, which can be caused by dopamine deficiency (and, also iron deficiency, which is important for dopamine storage and neurotransmission in the brain). Prior to going gluten free, I often struggled with restless legs, and still cannot take anti-histamines without feeling like my legs are going to dance off my body (anti-histamines are known to aggravate RLS).

I also am a runner, and thrive off of the runner’s high that I get. Running stimulates the release of beta-endorphins, which disinhibit dopamine transmission. In otherwords, running increases dopamine levels in the brain.

In addition, my mother, sister, and I have all struggled with attention deficit disorder (ADD), which has been demonstrated to be connected to low dopamine transmission.

Though not well currently reviewed in the literature, dopamine and narcolepsy appear to have a close association with one another. Orexins act on dopaminergic nuclei, which express orexin receptors, indicating that orexin influences dopamine neurotransmission. In rats, infusion of orexin increases dopamine in the brain. Additionally, increases in orexin (and correspondingly dopamine) increased the time the rats spent awake. For narcoleptics, a deficiency in orexin neurons and orexigenic neurotransmission could cause a secondary dopaminergic neuron transmission deficiency. (i.e. – if orexin isn’t released, dopamine isn’t released).

From a therapeutic perspective, dopamine agonists have long been used to treat cataplexy and excessive daytime sleepiness associated with narcolepsy.  Amphetamines (such as Ritalin) have long been used to reduce daytime sleepiness associated with narcolepsy, and amphetamines have been shown to increase levels of dopamine in the brain. In addition to the traditional stimulants, a more recently adopted wakefull-ness promoting drug, Modafinil, has also been shown to increase dopamine (and histamine) release, potentially by inhibiting the reuptake of dopamine.

In addition to conventional medicinal treatments, administration of the amino acid L-tyrosine, which is a precursor to dopamine, has been shown to positively affect symptom management in narcolepsy.  Patients were administered 100 mg/kg/day (which is about 6 grams of L-tyrosine for the average person) for 6 months, and were reported to have complete remission of symptoms.  Another study found that quantities of about 9 grams/day provided some wakefulness promoting effects, but it was not deemed a suitable alternative for use alone.  There are limited reports of the use of L-tyrosine in scientific literature, however, and no studies have been published on it’s use recently.

Another compelling  piece of the dopamine/narcolepsy connection comes from another neurodegenerative disorder, Parkinson’s disease (PD), whereby individuals lose dopamine-producing neurons in the brain. In fact, PD shares many features with narcolepsy including REM disorder and hallucinations as well as daytime sleep attacks. Indeed, it has been demonstrated that orexin-producing neurons are also lost in individuals with Parkinson’s disease, and narcolepsy has recently been implicated as a potential risk factor for PD, although it is unclear if this is an intrinsic risk factor, or if the treatments associated with  narcolepsy (i.e. long-term amphetamine use) contribute to the deterioration of dopaminergic neurons and development of PD.

Due to the compelling literature evidence that dopamine and narcolepsy are interconnected, I recently began a regimen of 6 grams of L-tyrosine a day. I have had great results so far, and have noticed a significant reduction in daytime sleepiness and  total time spent at night sleeping. I suspect that the effect will gradually wear off (I have been taking L-tyrosine for about 4weeks now), and I am interesting in speaking with others using L-tyrosine for it’s wakefulness-promoting uses; so, anyone out there?

Overcoming MS with diet.

This morning, I found a truly inspiring TedTalk from a woman diagnosed with multiple sclerosis, an autoimmune neurodegenerative disease not completely unlike narcolepsy. Like narcolepsy, which is neurodegenerative and believed to be autoimmune, multiple sclerosis presents as a life-long disability, from which there is “no known cure,” and medications are prescribed only for symptom management.

This life-long disability was not an option for Dr. Wahls, and, like so many of us who receive dissatisfying prognoses and aid from conventional medicine, turned to PubMed to begin searching for her own answer.

What Dr. Wahls found was not only symptom management but reversal of her multiple sclerosis through diet-modification, excluding gluten and grains, and consuming a paleo/hunter-gatherer diet rich in leafy vegetables. Here “cure” came in just 4 short months.

You can find more about Dr. Terry Wahls at her website. Thank you Dr. Wahls for being a outspoken doctor, patient, and advocate of healthy eating for autoimmune disease!