Authored by Dr. Barrett

This is part five in a series covering autoimmune disease. Don’t miss upcoming articles covering environmental medicine and mind body medicine. Check out previous articles covering Loneliness, GI health, nutrition part 1 and nutrition part 2, and hormones.

Autoimmune disease develops when the immune system starts attacking your own tissues. In addition to genetic factors environmental triggers including viruses, bacteria and other infectious agents play a major role in the development of autoimmune diseases. There are several mechanisms behind these triggers that include but are not limited to molecular mimicry, bystander activation and epitope spreading. If you scroll to the bottom of this blog there are some citations that go into great detail about how these mechanisms work if you are interested. In an oversimplified nutshell there can be cases of mistaken identity, our immune system getting overexcited, and chronic inflammation. 

What is a chronic infection? All of us are likely familiar with an acute infection: you become briefly ill such as from a cold or the flu and then you recover. Acute infections give our immune system practice. I don’t know about you but it’s now been over 12 months since I’ve had an acute infection (thanks physical distancing!)  While this is a nice perk of the pandemic it’s not great for our immune systems. A chronic infection happens when the body can’t seem to muster enough of a defense to adequately resolve the infection. Some examples include hepatitis C and HIV. HIV is treatable but at the time I am writing this there is no way to completely resolve the viral infection. Hepatitis C used to be a lifelong infection but with recent advances in drug therapy it’s now possible to be virus free! Some infections can be latent which means you become ill when initially exposed but then the infectious agent remains in the body dormant only to reactivate at a later time. The classic example is the virus that causes chickenpox will remain latent for decades only to emerge during a time of stress as shingles. Another example of a latent virus is the herpes simplex virus which can cause cold sores or ‘fever blisters’. The herpes family of viruses actually ‘sense’ when stress hormone levels rise and activate to come out of latency. Then the virus triggers a hormone cascade to actually further raise the levels of stress hormones. It’s genius and of course not great for us. There are many pathogens that can be latent or chronic. 

When treating autoimmune disease we are always looking for the root cause(s). We can use symptoms as clues that there may be a chronic infection to deal with. Some of those symptoms include; low grade fevers, migratory joint pain, recurrent hives, muscle pain, crawling sensation, as well as exacerbation and remission of symptoms. We can also use the knowledge of which pathogens are commonly associated with particular autoimmune diseases. For example, the bacteria klebsiella is implicated in the development of ankylosing spondylitis (AS), an autoimmune joint disease impacting the spine. Antibodies against klebsiella are found in AS patients. AS patients tend to have elevated levels of klebsiella in their stool and reduction of this bacteria can reduce the severity of AS. A combination of signs, symptoms and empirical knowledge will lead us to suspect chronic infections. 

Unfortunately, testing for chronic infections is challenging. Sometimes standard lab work can provide clues. We can see chronically low or high white blood cells and/or a chronically low/low normal RDW on a CBC. When testing for specific infections we must look for antibodies specific to that infection. This requires running several tests for each infection you are looking for. Let’s use Epstein-Bar (EBV) as an example. When looking for this infection we will often run: EBV viral capsid IgM, EBV viral capsid IgG, EBV nuclear antigen, and EBV early antigen IgG. If we want to test for other viral infections we will need a similar list of labs. You can see the list of labs gets very long and it can become incredibly expensive. 

Once I suspect a chronic infection the first steps I take are to support the person as a whole. All of us are exposed to infectious agents that can cause chronic infections. Instead of jumping to herbs/medications that can eradicate the infection I first want to identify what about this patient is allowing this infection to persist. In Naturopathic medicine we use the language ‘terrain’ to describe the environment in the host (patient). We need to make the terrain more inhospitable, strengthen the patient, and then go after the infection. 

The following are some avenues we explore together in strengthening the patient and creating an inhospitable terrain: 

• Getting blood sugar in check
• Optimize nutrition
• Making sure stressors and more importantly the stress response is under control
• Prioritizing rest
• Ensuring adequate sleep
• Optimize GI health and the microbiome

​
I will leave you with an example from Hashimoto’s disease, a condition I treat frequently. People with Hashimoto’s Thyroiditis (HT) have higher levels of EBV viral capsid IgG and early antigen IgG. In one study researchers looked at surgical specimens of thyroid tissue and found that 34.5% of the tissue from HT patients contained signs of EBV etiology. Does this mean that I test every Hashimoto’s patient for EBV during the first visit? No. We start with the list above while monitoring thyroid function and antibodies. Remember it’s not about the bug, we must work on the ‘terrain’ first and then go after chronic infections. 




References:
Infectious diseases and autoimmunity
Molecular Mimicry, Bystander Activation, or Viral Persistence: Infections and Autoimmune Disease
Virus infection, antiviral immunity, and autoimmunity
Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1 and Part 2
Social stress and the reactivation of latent herpes simplex virus type 1
The relationship between Klebsiella infection and ankylosing spondylitis
Study of Epstein–Barr virus serological profile in Egyptian patients with Hashimoto’s thyroiditis: A case-control study
The role of Epstein-Barr virus infection in the development of autoimmune thyroid diseases

Myo-inostiol and Selenium for Hashimoto's (2017)
You might already know that selenium can be very helpful for Hashimoto’s. It’s an antioxidant that supports the production of glutathione. Selenium is helpful in reducing anti TPO antibodies. This study compared patients using selenium alone and selenium with myo-inositol. 

Inositol is involved in cell signaling specifically around TSH, FSH and insulin. You may be familiar with inositol’s benefit for some patients with polycystic ovarian syndrome (PCOS) and it turns out, it’s helpful for patients with Hashimoto’s as well. 

This study found that using 600mg of inositol in combination with selenium was superior to selenium alone in reducing TSH levels and improving thyroid hormone concentration. TPOAb concentration decreased in both groups as expected. TgAb doesn’t tend to reduce with selenium supplementation alone and this study found that when adding myo-inositol there is a reduction in TgAb concentration! Patient’s also reported more symptom improvement when using a combination of selenium and myo-inositol. 

Bottom line: consider talking to your provider about using a combination of selenium and inositol to support your thyroid health.  


Nutraceuticals for Thyroid Health (2020)
This article is a review article which means the authors scoured the literature looking for all the information they could find on the topic. As the title indicates, most studies they looked at and discussed were done in animals. This article is full of great information about nutrients and their role in thyroid health. I am going to summarize some high points-
Vitamin D: Likely plays a protective role in preventing thyroiditis 

Zinc: Positively impacts thyroid function

Selenium: Improves immune regulation

Inositol: This was the topic of last month’s review article, these authors reviewed that study among others that concluded inositol is beneficial in autoimmune thyroid disease. 

Resveratrol: I’ve previously reviewed research exploring the mental health implications of Hashimoto’s disease and it appears that resveratrol might be useful. It improved BDNF and had antidepressant activity in hypothyroid mice. In addition, resveratrol appears to prevent the metabolic toxicity caused by fluoride exposure (drinking water) and restored the functional status of the thyroid. 

Soy: There is no easy answer here. Soy likely has different impacts on human health during various life stages (ie the effects on a baby fed soy formula are different from a perimenopausal person) making animal models unreliable for humans. It also appears that the potential goitrogenic effect of soy is made worse with low iodine in the diet. (My opinion- deciding soy is ‘bad’ for the thyroid and completely avoiding it is a little bit like throwing the baby out with the bathwater. If we took ever food/nutrients that may inhibit thyroid function out of the diet we would have very little left to eat.)

They also reviewed several synergistic reactions which really interests me. It’s not often we find THE ONE nutrient that the body needs to function better. We are complex creatures and nothing works in isolation. They found melatonin’s benefits were improved with zinc, selenium’s benefits were improved with inositol, and vitamin E’s benefit was improved with curcumin. 

There is much more to the article than what I summarized. It’s an open-access article available free online so check it out if you want more details :)


Cognitive functioning in Hashimoto's Patients (2018)
Something I hear at least weekly in practice is, “I am on levothyroxine/synthroid and my doctor says my thyroid is fine but I still have symptoms”. Well that is exactly the outcome from this study. They compared 139 patients with Hashimoto’s Thyroiditis (HT)  who were properly treated with medication and 111 people who do not have thyroid disease. The TSH, FT3 and FT4 were no different between the thyroid patients and controls. You know what was different between the two groups? Symptoms. Global cognitive function, anxiety and depression scores were all significantly worse in the adequately treated HT patients. This isn’t surprising to those of us that treat thyroid disease holistically. Just replacing thyroid hormone doesn’t get to the root of the problem. 

If you have Hashimoto’s and you’ve asked your conventional provider to check your antibodies (TPOAb and TGAb) you have likely been told that antibodies levels don’t matter. Well this study also helps disprove that long-held theory. The researchers found that TPOAb levels correlated with a lower quality of life in hypothyroid patients. 

Bottomline: Just replacing thyroid hormone often doesn’t improve symptoms in Hashimoto’s patients and checking antibody levels is an important part of your care. If your provider isn’t on board, might be time to look for a new one. 


Differences in food consumption between patients with Hashimoto’s thyroiditis and healthy individuals (2020)
I am pleased to see another study evaluating the relationship with food and Hashimoto’s Thyroiditis (HT) but unfortunately this study doesn’t give us very much clinically useful information. 

The most statistically significant results were that folks with HT consumed more animal fat and processed meat that controls. Controls consumed more red meat, grains, plant oils and non-alcoholic beverages. 

There was an association with elevated T3 levels in those who consumed more plant oil. The questionnaire used offered 3 options for fat intake: plant oil, olive oil and animal fat. So unfortunately, ‘plant oil’ covers a variety of oils and this nugget isn’t very helpful. 

This study isn’t clinically useful for a variety of reasons. This is a cross sectional, observational study that is not designed to give a causal connection between the consumption of food groups and HT development. It is also very challenging to accurately measure food intake via questionnaires. Anyone who has filled out or reviewed a diet diary understands this! The questionnaire used in the study was not designed to collect quantitative data on dietary intake, only frequency of intake. If someone eats 1 TBS of animal fat vs 5 TBS of animal fat 3x per week, that’s a big difference and isn’t taken into account in this study. 

Bottomline: Really nothing helpful here to incorporate into practice unfortunately. Again, still happy to see more research on diet and Hashimoto’s disease though!



References

1. ​Nordio M, Basciani S. Myo-inositol plus selenium supplementation restores euthyroid state in Hashimoto's patients with subclinical hypothyroidism. Eur Rev Med Pharmacol Sci. 2017 Jun;21(2 Suppl):51-59. PMID: 28724185.
2. Benvenga S, Ferrari SM, Elia G, Ragusa F, Patrizio A, Paparo SR, Camastra S, Bonofiglio D, Antonelli A, Fallahi P. Nutraceuticals in Thyroidology: A Review of in Vitro, and in Vivo Animal Studies. Nutrients. 2020 May 8;12(5):1337. doi: 10.3390/nu12051337. PMID: 32397091; PMCID: PMC7285044.
   
3. Djurovic M, Pereira AM, Smit JWA, Vasovic O, Damjanovic S, Jemuovic Z, Pavlovic D, Miljic D, Pekic S, Stojanovic M, Asanin M, Krljanac G, Petakov M. Cognitive functioning and quality of life in patients with Hashimoto thyroiditis on long-term levothyroxine replacement. Endocrine. 2018 Oct;62(1):136-143. doi: 10.1007/s12020-018-1649-6. Epub 2018 Jun 29. PMID: 29959689.
   
4. Kaličanin, Dean & Brčić, Luka & Ljubetić, Katija & Barić, Ana & Gračan, Sanda & Brekalo, Marko & Lovrić, Vesela & Kolcic, Ivana & Polasek, Ozren & Zemunik, Tatijana & Punda, Ante & Perica, Vesna. (2020). Differences in food consumption between patients with Hashimoto’s thyroiditis and healthy individuals. Scientific Reports. 10. 10670. 10.1038/s41598-020-67719-7. ​

This part three in a series covering autoimmune disease. Don’t miss upcoming articles covering chronic infections, environmental medicine and mind body medicine. Check out previous articles covering GI health, nutrition part 1 and nutrition part 2. ​

Hormone balance can often be an overlooked part of autoimmunity. I see a lot of emphasis on GI health (rightfully so) but autoimmune diseases are complex so it makes sense that the etiology is also complex.

A hormone is a signaling molecule released into circulation to target distant organs and regular physiology or behavior. In layman’s terms hormones are tiny middle managers running around the body bossing organs and tissues around. Hormones are involved in most of the activities of our bodies including digestion, sleep, stress, growth, reproduction and mood - just to name a few. We have somewhere upwards of 50 different hormones in the body with varying degrees of relationship to autoimmune disease. I am going to pick a few to highlight for you. 

Estrogen
Autoimmune disease in general tends to target people with ovaries.* A current hypothesis is that estrogen might actually enhance the inflammatory process of the immune system (1). Interestingly, even the joint fluid in RA patients contains higher levels of estrogen regardless of sex (2). I will cover this more extensively in the upcoming article on autoimmune disease and environmental medicine but I want to note that we are exposed to many chemicals that are ‘estrogen-like’ (xenoestrogens) such as BPA. So it’s important to test your individual hormones as well as look at what endocrine disrupting chemicals you are exposed to in your environment. 


Prolactin
Prolactin’s major role in the body is to stimulate lactation and suppress reproduction. Prolactin also stimulates the immune system as well as enhances the production of immunoglobulins and autoantibodies (3). Elevated levels of prolactin have been noted in Lupus (SLE), Rheumatoid arthritis (RA), Sjogren’s, Hashimoto’s and Multiple Sclerosis (MS) (4). Prolactin levels tend to be higher in folks with ovaries. Prolactin also elevates during chronic stress (5). Prolactin is an inexpensive blood test.

Testosterone 
Testosterone levels are naturally higher in folks with testes, which might have a protective effect against autoimmune disease. The effects of estrogens on immunity have been extensively studied but less is known currently about how androgens such as testosterone impact the immune system. We do know that mice with autoimmune disease have an increase in disease activity when they are castrated (ouch!) and androgen treatment improves survival in mice with Lupus (6).

It’s important to look at the pathways. If you have a patient with low testosterone and elevated estrogen they might be converting their testosterone into estrogen via aromatase. So reducing aromatase activity is a better treatment plan than just replacing testosterone. 

Cortisol
I will cover cortisol extensively in an upcoming article on mind-body medicine and autoimmune disease. In a nutshell, cortisol is supposed to be released in short bursts when we are under acute stress (running from a bear for example). Our bodies were not designed to be bathed in cortisol which is all too common these days. We have pesky chronic infections lurking behind the scenes just waiting for our immune system to be suppressed. Epstein-Barr Virus (EBV), varicella and herpes all contain stretches of DNA that sense cortisol levels and when these levels are elevated, the viruses reactivate (7). These viruses are implicated in autoimmune disease, especially EBV (8). 


I like to use a combination of blood, saliva and dried urine (DUTCH) hormone testing to get an overall picture of hormone balance. Hormone pathways are complicated as you can see by this chart below. Just looking at a blood estrogen level isn’t enough. You can have a ‘normal’ estrogen level but if you are converting most of your estrogen into 16-OH that can make autoimmune disease worse. Testing is key. 
​

Is stress slowly killing you? It feels that way right now and surprisingly the answer might be yes! Lately I’ve been focusing my continuing education and reading on Psychoneuroimmunology defined by Merriam Webster as “a branch of medicine that deals with the influence of emotional states (such as stress) and nervous system activities on immune function especially in relation to the onset and progression of disease”. I had been noticing a significant relationship between mental/emotional stress and immune function since I started specializing in autoimmune disease but I had no idea there was an entire field of medicine devoted to this topic. I was reading an article and I noticed the author’s bio included psychoneuroimmunology and from then on I have been reading as much as I can about this fascinating topic. 

Unfortunately the word ‘stress’ has become such a commonly used term and normalized in our society that when I try to broach this topic with patients I often hear, ‘I know stress is bad but let’s talk about XYZ diet and why I should follow it to fix my autoimmune disease’. Digging into the stress response is not a place many of us want to explore. I wonder if it’s because it feels too overwhelming and out of our control? Or maybe we just think that stress can’t possibly be the root cause of such significant illness? Why is it easier to blame food? Humans are poor reporters of their stress levels. It’s so indoctrinated in us that high levels of stress are normal that we no longer do a good job even recognizing that we are under high stress. 

The work of Emily and Amelia Nagoski was helpful for me in breaking apart the stressors from the stress. Often we can’t control the stressors (work, kids, family) but we can control how we manage the stress in our body. Here are some clues that you might be struggling with stress (this is not a comprehensive list):

• Depression/anxiety
• Anger, irritability
• Trouble sleeping or sleeping too much
• Problems with memory/concentration
• Feeling overwhelmed or unmotivated
• Digestive distress (constipation, diarrhea, bloating)
• Appetite changes
• Pain/tension in your head, chest, abdomen or muscles
• Lowered sex drive
• Irregular or painful menses
• Increase in blood pressure and/or heart rate

If you want to hear more about stressors vs stress and how to manage this check out the Nagoski sisters book-  Burnout: The Secret to Unlocking the Stress Cycle. If you prefer to ‘cliff notes’ version check out this podcast episode interviewing the authors. 

So how does this relate to our immune system? Well, our stress response system was designed to be activated in short bursts when we need to survive. Unfortunately, it’s activated much more often and we are feeling the consequences. When I talk to patients about stress many are familiar with the hormones adrenaline and cortisol. These two are our major players in the stress response but many other hormones are impacted when our stress response system is activated. 

When we are under stress the following hormones are released: 

• Glucagon (increase blood sugar)
• Prolactin (decrease reproduction)
• Endorphins and enkephalins (decrease pain)
• Cortisol (a major stress hormone)

When we are under stress the following hormones are suppressed: 

• Estrogen
• Progesterone
• Testosterone
• Insulin
• Growth hormone

We could deep dive into each of these hormones and how the changes impact you but this is a blog not a book. I will give you a few nuggets to get you thinking. 

Cortisol suppresses our immune response, if you are under threat of bodily harm you don’t have time to waste resources fighting that pesky cold. The trouble is chronic infections are often lurking behind the scenes just waiting for your immune system to check out. EBV, varicella and herpes all contain stretches of DNA that sense glucocorticoid (cortisol) levels. When levels are higher these viruses reactivate. Isn’t that incredible (and also scary?) 

Each of us process stress hormones differently for a variety of reasons. We are all biochemically unique  and a great example of this is the COMT SNP. That’s quite the acronym huh? It stands for catechol-o-methyltransferase (COMT) single nucleotide polymorphism (SNP) and what it means is that there are some of us whose enzymes that process catechols a little differently. This can lead to higher levels of catechols such as adrenaline and noradrenaline staying in our system for longer. Folks with COMT mutations tend to have a bigger stress response to stressors than the average person. 

Each of us processes stressors differently. As we grow up our brains learn how to appropriately respond to stress. When the young brain is constantly in a state of ‘fight or flight’ it causes lasting changes. The original research on how stressors in childhood impact long term health was called the ACE (Adverse Childhood Experiences) study. The results were profound. There is a direct association with the number of adverse events in childhood and risk of illnesses as an adult such as heart disease, IBS, diabetes, migraines, insomnia and more.  This is after they controlled for diet, socioeconomic status, smoking, etc. Over 60% of us have experienced at least one significant adverse childhood experience. 

In summary, chronic stressors lead to an overactive stress response that causes lasting damage. Each of us are unique in how we process these hormones and how easily we are triggered by stressful events. We are not great at recognizing and reporting how much stressors are causing an increase in the stress response. This is a really important piece in managing chronic illness. 

Now that we understand how incredibly impactful our stress response is on our immune system what can we do about it?

Physical activity is probably one of the best tools that we have to combat the ever increasing levels of stress. Moving your body is a non-negotiable. We need 30 minutes of movement daily and this can be as simple as a walk outside. 

Some other ideas for reducing the stress response include:  

• Singing
• Dancing
• Creative outlets
• Nurturing healthy relationships
• Breathwork
• Formal exercise
• Meditation/Mindfulness
• Spending time in nature

In all honesty it doesn’t matter what tools you pick for stress management as long as you actually do it. Don’t wait until it’s convenient, you have to incorporate relaxing activities into your daily routine. I find myself falling into the same trap I hear from patients- I can manage the tools on days that aren’t too busy but sometimes (read most of the time) I am ‘too busy’ to get in that exercise/meditation/coloring etc. These are the days that you need it most. Creating new habits takes time and I hope that learning just how important stress management is for your health will help inspire you to take the time to cultivate new habits to build stress resilience. 

I often hear patients express a desire to ‘health their gut’ as a means for achieving their health goals. In naturopathic medical school I often heard the phrase ‘health starts in the gut’ or ‘treat the gut first’. Treating gut health has become popular, but what does it really mean? According to online ‘experts’, it can mean many things ranging from drinking cups of bone broth daily to downing special ‘gut healing’ powders. Let’s break this down a little bit and start with why digestive health is so important.

The main function of our digestive system is the breakdown and assimilation of nutrients. We use these nutrients as the building blocks for our tissues, as cofactors for reactions, and as the fuel we run on. I am sure you have heard several tired analogies around nutrition and your health. But food really is the gas we put in our tank. If that gas is full of preservatives, sugar, highly refined carbohydrates, dyes, etc., it can seriously clog your engine (I couldn’t help myself!). 

Another aspect of digestive health is that the majority of our immune system resides in our gut. This is a major training ground for our immune system. Our immune cells are learning how to fight and what to fight. If they are trained well by the beneficial flora (microbiome), they can better recognize self and non-self tissue. This is a big deal for folks predisposed to allergies and autoimmune disease. 

Which leads me to another important aspect of your ‘gut’, the microbiome. I could spend an entire article singing the praises of a healthy microbiome. In short, these little guys make short chain fatty acids that keep your colon healthy, make vitamin K, likely ‘talk’ with your central nervous system, play a role in keeping pathogenic flora out of your gut, keep the lining of your gut intact, and the list goes on. 

Once I ask a few more questions of the patients inquiring about ‘healing their gut’, they often follow it up with an explanation that they suspect ‘leaky gut’. The technical term for leaky gut is intestinal permeability and it’s still not recognized by most conventional gastroenterologists. The official test used in research is to drink a large sugar molecule, too large to be absorbed by your intestines, and then check the urine for presence of this sugar. The test isn’t very helpful in clinical practice because it just tells you that intestinal permeability is present and that’s it. The biggest misconception I hear is that it takes months to heal a leaky gut. The cells that make up our intestines turn over often, every three days in fact. My approach is to reduce or eliminate the culprits damaging the lining rather than flooding your GI with nutrients/supplements to ‘heal’ the gut.  We’ve been a little brainwashed into thinking we need to take things to make use better. 

When your intention is to work on your digestive health, you want to consider a few things before you jump on the supplement train:

• What are you putting in your gut? This includes food, alcohol, NSAIDS, antibiotics…
  
• Are you taking time to chew your food?
  
• Are you consuming the right blend of fibers/prebiotics to support a healthy microbiome?
  
• How is your current stress and past stress impacting your microbiome and digestive capability?
  
• What is your breathing pattern and posture like? Are you using your diaphragm and giving your body the space it needs to do its job?
  
• How often are you physically active? Fun fact: physical activity can beneficially alter your microbiome.

Most folks who make their way to my office have complex and complicated digestive concerns. That does not mean we skip the basics listed above. If you don’t have a strong foundation, it’s very challenging to heal. Often the root causes of even the most complicated conditions can be an issue with one of the basics. For example, a sluggish gallbladder can put you on the path to SIBO especially when combined with chronic stress. Don’t even get me started on how strong the connection is between chronic stress and IBD. Holistic medicine incorporates all of the lifestyle basics with the most current research on nutrients, botanicals, and functional testing to help guide a person back to wellness. For digestive health, this may include functional stool testing, prescribed diets, targeted probiotics, specific nutrients/herbs and more. With so much information at our fingertips, it’s tempting to try and tackle your health challenges alone, but I highly recommend working with an experienced provider. In addition to providing you guidance from education and experience, you gain a cheerleader in your corner. 

​I am starting up a new blog series to highlight research updates for Hashimoto’s Thyroiditis (HT). My intention is to review recent literature every 6 months. I am starting by pulling together a variety of research articles until I feel ‘caught up’ (will I ever feel caught up?!) and will then focus solely on new research. My plan  is to publish an update every January and July. 

For this first installment I have pulled together a variety of research articles. 

Gluten and Hashimoto’s (2019)

Krysiak R, Szkróbka W, Okopień B. The Effect of Gluten-Free Diet on Thyroid Autoimmunity in Drug-Naïve Women with Hashimoto's Thyroiditis: A Pilot Study. Exp Clin Endocrinol Diabetes. 2019;127(7):417-422. doi:10.1055/a-0653-7108

I read this article in 2019 when it came out and was excited to see that research is starting to support what we have known clinically for years. Many patients with Hashimoto’s Thyroiditis (HT) benefit from a gluten free diet. The sample size was small and it wasn’t randomized, patients were allowed to choose the gluten free group or the control group. That said, even with the small sample size there was an improvement in both TPO and TG antibodies in the gluten free group as well as a slight increase in thyroid hormone output. 

The authors hypothesize that the improvement in autoimmunity may be due in part to an increase in vitamin D that was seen in the gluten free group. The participants did not increase their vitamin D intake and it’s unknown why a gluten free diet would have improved their vitamin D status. 

This study is very interesting and I hope it’s the first of many exploring the important connection between a gluten free diet and HT. 


Vitamin D and Hashimoto’s (2016 + 2018)

Sahin, M., Corapcioglu, D. The effect of vitamin D on thyroid autoimmunity in non-lactating women with postpartum thyroiditis. Eur J Clin Nutr 70, 864 (2016). https://doi.org/10.1038/ejcn.2016.56

Xu J, Zhu XY, Sun H, et al. Low vitamin D levels are associated with cognitive impairment in patients with Hashimoto thyroiditis. BMC Endocr Disord. 2018;18(1):87. Published 2018 Nov 26. doi:10.1186/s12902-018-0314-7

We know from observational studies that low vitamin D status seems to contribute to thyroid autoimmunity. What sets this research apart is that they looked at women post partum to see what impact vitamin D supplementation has on antibodies. ⁠If you are familiar with Hashimoto's you probably know post partum is a common time for the condition to flare. ⁠
⁠
The investigators found that the women with post partum thyroiditis (PPT) had lower levels of vitamin D than post partum women without thyroiditis. Giving vitamin D (either 2,000IU or 4,000IU depending on the patient's vitamin D blood level) to the PPT women significantly lowered their antibodies without any side effects. Between 20-40% of women with PPT go on to develop permanent hypothyroidism and lowering antibodies is an important step to prevent that outcome.

The second study looks at the relationship between vitamin D, Hashimoto's Thyroiditis (HT), and  cognitive impairment. 
⁠
We already know that low vitamin D is correlated with cognitive impairment in the general population and that there is a high prevalence of low vitamin D in patients with HT. It wasn't surprising that they found low vitamin D is associated with cognitive impairment in patients with HT. ⁠

The authors  also found that vitamin D levels were inversely related to TPO antibody levels.

Bottom line study #1 and #2:  If you have Hashimoto's I highly recommend talking to your provider about your vitamin D level. ⁠
⁠
Depression and Hashimoto’s (2011 + 2014)

Giynas Ayhan M, Uguz F, Askin R, Gonen MS. The prevalence of depression and anxiety disorders in patients with euthyroid Hashimoto's thyroiditis: a comparative study. Gen Hosp Psychiatry. 2014;36(1):95-98. doi:10.1016/j.genhosppsych.2013.10.002

Hardoy MC, Cadeddu M, Serra A, et al. A pattern of cerebral perfusion anomalies between major depressive disorder and Hashimoto thyroiditis. BMC Psychiatry. 2011;11:148. Published 2011 Sep 13. doi:10.1186/1471-244X-11-148

The first study looked at the prevalence of depression and anxiety in euthyroid Hashimoto’s thyroiditis. Euthyroid Hashimotos’ is when a patient has Hashimoto’s but their thyroid hormones are not abnormal (yet!). They looked at patients who have a normal FT3, FT4 and TSH but also have thyroid antibodies and an abnormal thyroid ultrasound. There are already several studies that show a higher prevalence of psychiatric disorders in patients with Hashimoto’s but this study is unique in that they only included HT patients who had ‘normal’ thyroid function based on thyroid hormone testing. Surprise! They found there was a higher prevalence of anxiety and depression in these patients than in the general population or control. There are many theories as to why HT patients have a higher incidence of psychiatric disorders and many center around imbalanced levels of TSH, FT3 and FT4. There is likely more to the story. This study might be the first to find a relationship between OCD and HT. The prevalence of OCD in the HT group was 15.7% and the prevalence in the general population is around 0.8% to 3.2%. 

Bottom line study #1 - If you have anxiety or depression and your thyroid has been screened with just a TSH make sure to talk to your provider about a comprehensive screen that includes antibody or ultrasound testing  especially if you have a family history of thyroid disorders. 

The authors summarized the second study very well so I am going to quote the authors directly “The debate on the pathogenesis of depression in thyroid autoimmunity involves two hypothesis, it is suggested that the neuronal tissue is hypersensitive to hormonal deficiencies and are more vulnerable to possible subclinical hormonal deficiencies not detectable with routine laboratory tests. In the second hypothesis, a possible pathogenic factor linked to inflammation is postulated, consequent to cytokine activation or extraglandular lesions similar to vasculitis induced effects.” 
In other words it could be that our brains are hypersensitive to fluctuations in thyroid hormone so even when the levels are ‘normal’ our brains might suffer and/or there is likely a role of inflammation in altering blood flow. 

Bottom line study #2: Depression and brain blood flow changes happen with HT (both euthyroid and hypothyroid) and patients with depression, especially atypical depression, need comprehensive thyroid screening. 

For more frequent research updates check out my Instagram account.