The balance between our hypothalamus, pituitary and adrenals (HPA axis) is tightly linked to our health and well being. Many of us live in a hypervigilant state with a chronically activated sympathetic nervous system. An overactive stress response can lead to elevated cortisol, insulin, inflammation, and even autoimmune disease. It’s a complicated connection and it continues to show up in my clinical practice. Just talking about "stress" with patients isn’t enough and it’s not getting to the core issues that throw our body out of balance. In my never-ending desire to understand autoimmune disease I continue to read and learn more about psychoneuroimmunology, the relationship between immunity, the endocrine system, and the central and peripheral nervous systems. A few months ago I came across the concept of "overfunctioning" and it highlights a phenomena I recognize in patients (and myself!) but didn’t have language for. As I read more about overfunctioning I realized it’s a fast track to burnout. Overfunctioning is doing more than is necessary, appropriate and healthy in our lives and relationships. This article in Psychology Today provides a laundry list of behaviors that may indicate a pattern of overfunctioning. I picked a few to share with you: 

• Worrying about other people’s responsibilities.
• Taking over a group project that is coming together slowly.
• Trying to convince someone that your thinking is right.
• Furiously completing tasks for others when you feel bored, anxious, or distressed.
• Updating your friends and family about people they could contact themselves.
• Reminding your spouse or partner to call their family.
• Taking on a task at work because teaching another staff member will be frustrating.
• Doing something for your child that they can do, so it will create less of a mess.
• Giving advice to a distressed friend who hasn’t asked for any.

Dr. Sara Gotfried explains overfunctioning as:

• Doing things for others that they can do for themselves
• Absorbing other people’s feelings
• People-pleasing to avoid disappointing others
• Difficulty saying no and setting boundaries
• Assuming more responsibility than is your share
• Giving advice whether the person asks for it or not
• Fretting about others
• Feeling responsible for others, or knowing what is best for them
• Talking more than listening
• Having goals for others that they don’t have for themselves
• Codependence, or imbalanced relationships, whereby you enable someone else’s immaturity or irresponsibility through caretaking or fixing
• Behaving like a martyr, taking care of everyone else, giving without receiving, and then occasionally feeling like you were taken advantage of
• Overworking and over-scheduling yourself

There can be several core beliefs and coping mechanisms underlying overfunctioning. This article does a really excellent job of summarizing some of the roots of overfunctioning behavior. I also encourage you to work with a therapist if you resonate deeply with this information. This is challenging work. I am a recovering perfectionist and it’s easy for me to fall back into the false belief that if I want something done right, I need to do it myself. This leads me to constantly "do." I often remind myself that I am a human "being" and it’s ok to just "be" sometimes (thanks Tara Brach!)

The following are some ways you can support yourself:  

• Give yourself permission to rest
• Practice saying "no." If that’s a big step for you, consider starting with "let me think about it" and give yourself a few days to make a decision. 
• Creating unstructured time in your schedule
• When you feel the urge to "do" challenge yourself to get grounded first. Take a deep breath, maybe go outside and check in with yourself about your intentions and desired outcome.  
• Evaluate your definition of happiness and wellbeing. Check in with yourself and make sure this is your definition and not influenced by anyone else.

I saved this article as the last one in my autoimmune series because it’s arguably the most important. Autoimmune disease and mind-body medicine are tightly linked. 

Early on in my career I met a patient with mast cell activation disorder and chronic hives. She was so ill that she had been hospitalized a few times with her throat swelling shut. We worked on all sorts of things looking at environmental triggers, using supplements to reduce histamine, changed her diet - you know, the typical naturopathic treatments. She was a little better but nothing dramatic. I lost her to follow-up and out of the blue about 6 months later she sent me a message letting me know she had found a wonderful therapist who had changed her life. Her therapist recognized that my patient had an elevated ACE (Adverse Childhood Experience) score and they had worked extensively on her childhood trauma. Much to my patients' surprise, her very difficult-to-treat condition resolved. This was a turning point for me. I started researching psychoneuroimmunology and reading everything I could about the connection between our mind and our immune system. 

I am going to take a brief pause here to address what mind-body medicine IS NOT before I go on to explain all of the fascinating research. I want to be crystal clear that mind-body medicine is not about blaming the patient. I was surprised to receive an unpleasant message over social media after sharing some research on mindset and health about how unhelpful it is to point out this connection. I was surprised because I think it is incredibly empowering to know that we may be able to use our minds to heal our bodies. In my experience no one is free from the mind-body connection. We are all impacted by our minds. Once we are aware of just how powerful the connection is we are back in the driver's seat. So remember that as you continue reading. If your physical illness is manifesting in part due to emotional wounds, trauma, early childhood experiences, your mindset, etc. this does not mean that your illness is your fault AND there might even be some tools to help you. 

According to the Center for Mind-Body Medicine “Mind-body approaches use the conscious mind to directly affect the workings of the brain and the rest of the body. The techniques exert their effect on the hypothalamus, the switching station in the brain, which exercises control over the autonomic nervous system (which controls heart rate, blood pressure etc.), the endocrine (glandular) system and the immune system.”

The Autonomic Nervous System (ANS) is the part of the nervous system responsible for control of the bodily functions not consciously directed, such as breathing, the heartbeat, and digestive processes. It controls what is going on behind the scenes. You don’t have to think about digesting your food or sending out immune cells to fight off foreign invaders. The ANS has you covered. The ANS has two divisions, the parasympathetic and the sympathetic systems. These two systems oppose each other and ask for different responses from the organs and systems they control. For example the sympathetic nervous system will slow down digestive function while the parasympathetic system will increase digestive function. 

When the sympathetic (fight, flight, or freeze) is dominant we feel more tense and alert. Stress hormones such as cortisol and epinephrine surge through our bodies. Our heart rate and blood pressure increase. Our immune cells secrete inflammatory cytokines such as IL-6 and IL-2. In contrast, when the parasympathetic (rest and digest) system is dominant we feel a sense of relaxation, tranquility and contentment. This is the baseline of balance that our body desires. Our heart rate slows, blood pressure lowers, our muscles relax and we can digest food adequately. Unfortunately, many of us are sympathetic dominant in our daily lives.

There are so many mind-body medicine topics we could cover but I am only going to pick a few since this is a blog not a book. Let’s cover self-criticism, perfectionism and loneliness. While also incredibly important, I am going to leave ACE and trauma to the experts (see the bottom for some good books to read though). 

SELF-CRITICISM
When we are critical of ourselves, it has negative consequences for our health and even impacts our immune system. According to Merriam-Webster self-criticism is "the act of or capacity for criticizing one’s own faults or shortcomings." We have a complex system designed to monitor our environment for threats. When a threat is identified, we are flooded with stress hormones to help us survive. The trouble is, this system can’t differentiate between threats in our environment and threats inside our head. Criticizing ourselves activates our threat system in the same way anxiety does. Chronic stress happens when this system is constantly engaged. 

Chronic stress increases interleukin-6 (IL-6). IL-6 plays an important role in signaling during an active infection. IL-6 increases inflammation and antibody production. Elevated IL-6 actually increases anxiety, alters the immune system, and increases neuro-inflammation. 

We live in a culture that teaches us to be self-critical. We grow up internalizing the ideal that we must push ourselves to achieve greatness. It’s easy to put high expectations on ourselves, which leads to self-criticism when we can’t meet those expectations. Some use self-criticism as a tool to push themselves harder and harder and even fear that without the inner critic they might become "lazy."

A good rule of thumb is to stop and think about whether you would talk to someone you love the way you are talking to yourself. Most people would never speak to another person the way they speak to themselves.

PERFECTIONISM
Perfectionists are often the harshest self critics. Brené Brown, Ph.D defines perfectionism as “a self-destructive and addictive belief system that fuels this primary thought: If I look perfect and do everything perfectly, I can avoid or minimize the painful feelings of blame, judgement, and shame.” 

Self-criticism is used as a way to ensure you are "perfect." The lie perfectionists tell themselves is that constant second guessing means you will not make a mistake. The trouble is you spend so much of your life second-guessing yourself that you don’t get a chance to live in the moment. Instead, you are caught in a constant fight-flight-or-freeze sympathetic loop. 

I noticed a pattern in my practice that patients with autoimmune disease tend to be hard on themselves. I started looking into the research and I found this paper revealing that patients with autoimmune disease are more self-deprecating than controls, which confirmed my suspicions. Years of overwork and stress to prove your worthiness leads to chronic activation of your sympathetic system. Your stress activation system is closely linked with your immune system. The full mechanisms of action for self-criticism and immune activation are not fully worked out yet, but there is a connection. 

Just like Dr. Brown said, perfectionism is a misguided tool to reduce or minimize the painful feelings of blame, judgement and shame. Criticizing yourself and striving for perfection unfortunately do not produce the desired outcome and can harm your health. 

Instead, try holding a hand over your heart and saying to yourself: "I am enough."

LONELINESS
Another aspect to consider is loneliness. Loneliness actually changes how the immune system works. Cellular immunity is impaired, natural killer cells decline, and antibody titers rise. Loneliness triggers the fight/flight/freeze stress response. Humans have spent most of our existence as a species being supported and protected by each other. Loneliness signals to our body that we are in danger, which kicks up levels of inflammation and changes immune response. 

The real kicker for me is that folks who have or develop a chronic illness, such as an autoimmune disease, have a higher risk for becoming socially isolated. So not only does loneliness increase the risk of developing an autoimmune disease, having an autoimmune disease increases your risk of becoming lonely. 


We have so many mind-body medicine techniques at our disposal. Here are some resources I share with patients: 

• Tara Brach has free downloadable talks and meditations on her website and is also available on your podcast app.
• Sharon Salzberg offers meditations for download at no cost on her website. 
• John Makransky teaches a beautiful meditation style based on receiving love downloadable for free from his website.
• The Last Best Cure: My Quest to Awaken the Healing Parts of My Brain and Get Back My Body, My Joy, and My Life by Donna Jackson Nakazawa 
• The Body Keeps the Score: Brain, Mind, and Body in the Healing of Trauma by Bessel van der Kolk

In all honesty it doesn’t matter what tools you pick 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 resilience. 


If you are struggling with an autoimmune disease I recommend working with a naturopathic doctor to help identify the root cause and support your body. It is important to maintain all medications while working on your health from a holistic perspective. Autoimmune disease is serious and tissue destruction is permanent. Our goal with naturopathic treatment is to keep the medication dose stable and slow or stop the autoimmune destruction. I am often asked if patients can expect to stop their medication eventually and that depends on a variety of factors and is a decision made with the prescribing practitioner and patient. 
 

References:
Self compassion as a predictor of interleukin-6 response to psychosocial stress
Compassion meditation reduced stress induced immune changes
Neural concomitants of immunity--focus on the vagus nerve
Personality traits and the immune system
IL-6 Induced by Social Stress
What is Mind Body Medicine

Autoimmune disease occurs when our immune system starts attacking our own tissues. Autoimmune diseases are complex illnesses that develop when there is just the right combination of genetics, epigenetic factors, and environmental triggers (infections, chemicals, stressors, etc). In this article I will focus on a few chemical or xenobiotic exposures that are linked to the development of autoimmune disease.  I want to start by saying it’s very challenging to conduct research trying to link specific chemicals to any disease. Humans are exposed to a myriad of chemicals daily and there is likely a compounding effect happening. There can also be a long delay between exposure and the onset of disease. For example, someone could work in a hair salon touching and inhaling chemicals for 10 years before they finally develop an autoimmune disease. Drug (ie medication) induced autoimmunity is well known and most associated with SLE (lupus) like disease. I will skip that in this article. I want to focus on chemicals in our environment that we can control. 

Endocrine Disruptors
Arguably the most notorious endocrine disruptors we are exposed to are bisphenols with BPA being the most well known. Unfortunately, when the dangers of BPA were brought into public awareness we saw a boom in ‘BPA free’ products that are quite misleading. Many of these products just replaced BPA with it’s cousins BPF and BPS which are also estrogen like compounds. Bisphenols are used in the production of polycarbonate plastics and at this point are ubiquitous in our environment. Research from 2003 found that more than 90% of the US population has detectable levels of BPA in their urine and females BPA levels were at higher concentration than males. Growing concern about the impact on children from bisphenol exposure has caused BPA to be banned in baby products in Canada and the European Union. BPA is a known endocrine disruptor but it’s role in autoimmunity has not been elucidated yet. What happens to our bodies from BPA exposure is quite similar to the autoimmune process. More research is needed but I am concerned that this could be a potential trigger and the people who already have an autoimmune disease may see a worsening in their pathology with higher exposure to bisphenols. 
Some of the products where bisphenols are found include:

• Food packaged in cans or tetra packs
• Beverage cans
• Hard translucent plastic marked #3, 6 or #7
• Cash register receipts
• Plastic food wrap
• Frozen meals in plastic trays
• Heating or microwaving plastic
• Placing plastic in the dishwasher

One relatively easy change is to avoid plastic containers for food or water and opt instead for glass or stainless steel. 

Phthalates are another endocrine and immune disruptor that are ubiquitous in our environment. Phthalates help make plastic soft and to dissolve raw materials when making fragrances. In the US, chemicals such as phthalates are considered safe until they are proven dangerous. Unfortunately, most of the research on phthalates has been done on animals. A 2019 study in rats found that a particular phthalate exacerbates the most common autoimmune disease, an autoimmune thyroiditis called Hashimoto’s. 

Below is an example of products that may contain phthalates. 

• Plastics both PVC and #3
• Children’s toys
• Cosmetics
• Nail polish
• Perfumes
• Almost anything with fragrance
• Detergents
• Solvents
• IV tubing

There is no easy way to tell if a product has added phthalates. There are numerous compounds and are identified on labels often as acronyms (BBP, DBP, DEHP, DEP, etc). Dust may also contain phthalates so consider washing your hands before preparing food and eating, cleaning your floors regularly using a wet mop and using a vacuum with an HEPA filter. 


Solvents
A meta-analysis in 2012 reviewed research studies that explored the potential link between exposure to solvents and autoimmune disease. Common routes of exposure to organic solvents include:

• Nail polish
• Nail polish remover
• Perfumes
• Dry cleaning
• Paint thinners
• Spot removers. 

Many of the studies the authors reviewed look at occupations that have a higher exposure risk such as nurse anesthetists, painters, people who frequently use hair dye and nail polish, and textile workers. Their findings indicate that organic solvent exposure is a risk factor in developing autoimmune disease. The researchers recommended that people with genetic risk factors avoid organic solvents. I think it might be wise for all of us to avoid organic solvents as much as possible.

I find two free apps helpful when trying to avoid chemicals in the products that we use daily,  Think Dirty and ‘Healthy Living’ by The Environmental Working Group. Both apps contain a barcode scanner so you don’t have to memorize the thousands of chemicals that might be a concern for you- you can just scan the barcode and see the product's score. 

There are so many more chemicals we could talk about in relation to autoimmune disease but instead I want to finish this article with some ideas to support healthy detoxification.


Our detoxification system is quite complex and the major players are our liver, kidneys and GI tract. Our liver processes not just the chemicals we are exposed to daily but also things we produce naturally such as hormones and bilirubin. Some of what the liver processes goes back into our bloodstream to be filtered through our kidneys and excreted through our urine. Other substances are deposited into bile to be dumped into the intestines. Our liver produces roughly 3.5 cups of bile every day! Here is an important piece- when that bile binds to fiber it leaves our body through our stool. Regular bowel movements are a very important part of our detoxification system. Laxatives are not the answer, a healthy diet rich in fiber is!
 
Some practical ways to enhance your natural detoxification process include:

• Drink ½ body weight (lbs) in ounces of water daily
• Consume a diet rich in vegetables, especially vegetables in the brassica family such as broccoli, cauliflower, cabbage, and brussels sprouts.
• Get your body moving. Physical activity moves our lymphatic system which helps remove waste. Bonus if you work up a nice sweat!
• Eat 25+ grams of fiber daily. Excellent fiber sources include legumes, avocado, chia, flaxseed, artichoke hearts and oats.
• Have 1 bowel movement per day. If you struggle with constipation consuming adequate fiber and water is a good place to start.

We are all exposed to chemicals on a daily basis. So I recommend taking small steps to both reduce your exposure to chemicals and support your natural detoxification system. 



References:
Toxicology of Autoimmune Diseases
Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis
A Potential Link between Environmental Triggers and Autoimmunity 
Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004
The Potential Roles of Bisphenol A (BPA) Pathogenesis in Autoimmunity
DINP aggravates autoimmune thyroid disease through activation of the Akt/mTOR pathway and suppression of autophagy in Wistar rats

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. 
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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.