by Datis Kharrazian, PhD, DHSc, DC, MS, MMSc, FACN
(Reprinted with minor revisions from Why Do I Still Have Thyroid Symptoms? by Dr. Datis Kharrazian)
Once the gene for an autoimmune disease has been turned on, it can’t be turned off. The only thing to be done clinically is to turn down the volume on the immune response by restoring balance.
One trick is to discover which side of your immune system is more active — the side that deploys natural killer and cytotoxic T-cells, or the side that deploys B-cell antibodies. Are you producing too many natural killer and cytotoxic T-cells, the ones responsible for killing invaders? If so, you are TH-1 dominant. (TH stands for T-helper cell.)
Or are you producing too many B-cells, the ones in charge of tagging the intruder so it can be readily identified? If so, you are TH-2 dominant.
If you are dominant in one or the other, your immune system is out of balance and autoimmune disease is either highly likely or already underway.
T-helper cells communicate and orchestrate an immune attack. They are the dispatchers that send messengers to fetch natural killer, cytotoxic T-cells, and B-cells. By measuring these messengers, or cytokines, in blood tests, I can find out whether a patient with an autoimmune disease is TH-1 or TH-2 dominant.
Cytokines are like hormones — they are chemical messengers that make things happen. Interestingly, TH-1 and TH-2 cytokines affect thyroid function beyond driving Hashimoto’s disease: Elevated TH-1 or TH-2 cytokines also block thyroid receptor sites, preventing thyroid hormone from getting into the cells, thus causing symptoms of low thyroid activity.
We determine whether someone is TH-1 or TH-2 dominant by measuring cytokines, chemical messengers that stimulate production of natural killer and cytotoxic T-cells or B cells.
The TH-1 cytokines include:
- IL (interleukin) -2
- Tumor necrosis factor alpha (TNFa)
The TH-2 cytokines include:
Although there are exceptions to every rule, I have seen recurring patterns of TH-1 versus TH-2 dominance. For instance, about 90 percent of my patients with Hashimoto’s are TH-1 dominant. Their natural killer and cytotoxic T-cells are over active, thus attacking thyroid tissue. Research not only confirms my experience, but studies also show that Type I diabetes, multiple sclerosis, and chronic viral infections are often associated with a TH-1 dominance.
On the other hand, lupus, dermatitis, asthma, and multiple chemical sensitivities are often associated with a TH-2 dominance.
However, these are generalities, and should not be taken as the rule. Also, it’s important to note that not all autoimmune diseases can be traced to a TH-1 or TH-2 dominance; other possible causes include immune defects and deficiencies. In other words, no cookbook recipes exist to managing an autoimmune disease. Instead, a basic understanding of immunology is key.
How to address a TH-1 or TH-2 dominance
When addressing autoimmune disease, the goal is to restore balance to the immune system. I approach this in several ways. The foundation of care is to support my patient’s overall health. Unstable blood sugar, gut infections, and poor adrenal health (all of which are practically universal in this country) worsen an autoimmune condition. Removing gluten from the diet is also vital, given the studied links between Hashimoto’s and gluten intolerance.
Step one: Support regulatory T-cells
Beyond those basics, however, I use natural medicine to balance the immune system. My first step is to support the T-regulatory cells. At our crime scene, these are the sergeants monitoring the situation from headquarters, sending more T-helper or T-suppressor cells as necessary to boost, slow down, or halt an immune attack. In an autoimmune crime scene, T-regulatory cells start behaving erratically, as if they are drunk or working for the bad guys. As a result, they issue bad commands — dispatching too many or not enough T-helper or T-suppressor cells — that ultimately destroy body tissue. By restoring sanity to their actions, we can restore balance to the immune system and tame an autoimmune response.
Emulsified vitamin D (cholecalciferol) is a powerful immune modulator and best supports the T-regulatory cells when used in therapeutic doses.
Vitamin D supplementation is important for another reason: Studies have found that more than 90 percent of people with autoimmune thyroid disease have a genetic defect affecting their ability to process vitamin D. Therefore, they need higher amounts of vitamin D to maintain health. This can be the case even if a blood test shows sufficient vitamin D: The defect is at the cellular receptor site, so not enough vitamin D can gain entry into the cells. On a lab test, I like to see high-normal vitamin D levels for patients with thyroid disorders.
A powerful nutrient that modulates the immune system and support the T-regulatory cells is glutathione, a powerful antioxidant.Glutathione is an antioxidant made by your body to protect your tissue and it has several key mechanisms to support autoimmunity. Glutathione preserves and protects cells against inflammation, supports TH-3 responses, supports regeneration of the intestinal barrier, and is a natural chelator that can bind to environmental compounds such as heavy metals and pollutants, which may trigger autoimmunity. Although glutathione can be taken as a nutritional supplement, most forms are not absorbed well and do not raise levels within the cells (intracellular). Glutathione can also be taken intravenously, which is effective but can be costly and not easily accessible.
In my practice I use a mixture of botanicals that have been shown to profoundly impact levels of glutathione inside the cells. These natural compounds include Cordyceps, N-acetylcysteine, gotu kola, milk thistle, L-glutamine, and alpha lipoic acid. These are all TH-1 and TH-2 neutral and because they support TH-3, they have the potential to dampen an overactive TH-1 or TH-2 response in autoimmunity.
Glutathione’s job is to take the bullet
Glutathione is like the bodyguard or Secret Service agent whose loyalty is so deep that she will jump in front of a bullet to save the life of the one she protects. When there is enough of the proper form of glutathione in the body to “take the bullet,” no free radical response occurs. But when glutathione levels drop too low, this triggers a destructive inflammatory process.
When the body is low in glutathione, a person is more likely to become sensitive to foods or chemicals.
Glutathione recycling explained
Supporting glutathione recycling is a little different than just boosting glutathione levels. Glutathione recycling does what the name implies, it recycles existing glutathione for reuse. What’s important about supporting glutathione recycling is that it helps raise levels inside the cells (intracellular).
More common forms of glutathione delivery, such as a liposomal cream or intravenous (IV) glutathione, do not raise levels of glutathione inside the cells, only outside. Intracellular glutathione is important because it is the main antioxidant for mitochondria, the little factories inside each cell that convert nutrients into energy. This is crucial because the degenerative process of an autoimmune disease destroys the mitochondria in affected cells, such as thyroid tissue in autoimmune Hashimoto’s.
Studies have shown that efficient glutathione recycling helps boost regulatory T-cells, which promotes immune balance and helps prevent immune system hyperreactivity. Proper glutathione activity also regulates cell proliferation and immunity, and helps tissues recover from damage.
Maintaining sufficient glutathione levels and glutathione recycling helps buffer the body from the many stressors hurled at us each day and can nutritionally support autoimmunity such as Hashimoto’s.
Supporting glutathione recycling
So how do we support glutathione recycling? The first thing is to reduce the stressors that deplete this vital system. Balancing blood sugar, addressing food intolerances, restoring gut health, balancing hormones, supporting brain health, and so on are some foundational approaches. Of course, lifestyle changes that include getting enough sleep, paring down an over-active schedule, and getting regular physical activity (but not overtraining) are also important. However, nutritional support also may be necessary. Below I cover the basic botanicals and nutritional compounds researchers have found support glutathione recycling pathways.
NAC is a key compound to glutathione activity. It is rapidly metabolized into intracellular glutathione.
Alpha-lipoic acid (ALA)
ALA directly recycles and extends the metabolic life spans of vitamin C, glutathione, and coenzyme Q10, and it indirectly renews vitamin E, all of which are necessary for glutathione recycling.
Research has shown that l-glutamine is important for the generation of glutathione. It is transported into the cell, converted to glutamate, and readily available to intracellular glutathione synthesis.
Selenium is a trace element nutrient that serves as the essential cofactor for the enzyme glutathione peroxidase, which converts GSH to GSSG so glutathione can “take the hit” by free radicals to spare cells.
Cordyceps has been shown to activate both glutathione and peroxidase synthesis in the body and protect cells by engaging the glutathione enzyme cycle. Cordyceps increases glutathione levels in the cells by 300 percent within minutes.
Gotu kola (Centella Asiatica)
Research has clearly demonstrated that oral intake of gotu kola rapidly and dramatically increases the activity and amount of glutathione peroxidase and the quantity of glutathione.54
Milk thistle (Silybum marianum)
Milk thistle has been shown to significantly increase glutathione, increase superoxide dismutase (another powerful antioxidant) activity, and positively influence the ratios of reduced and oxidized glutathione.
Using these compounds together creates a synergistic effect, making them more effective. Start with modest amounts and increase the doses until a positive effect is noticed.
For people with severe leaky gut issues, I suggest they take these compounds as long as they are working on repairing intestinal permeability—glutathione has been shown to protect and regenerate the gut barrier, as well as the brain and lung barriers.
It’s important to use these compounds in conjunction with approaches that boost overall glutathione levels (below). This way the glutathione you take is assured to stay in your body longer and get inside your cells where it can do its best work.
Other practitioners and I have witnessed positive outcomes in patients who build up their glutathione recycling system. As a result, they begin to regain their tolerance to the chemicals around them, they have fewer autoimmune flare-ups, and they recover faster from their flare-ups when they do happen.
Boosting glutathione levels with S-acetyl-glutathione
While you support glutathione recycling, you also want to boost overall glutathione levels.
One method is through a form of glutathione known as S-acetyl-glutathione, which the gastrointestinal tract can efficiently absorb. Oral doses can start at 300 mg per day and go up to several thousand milligrams if necessary with certain inflammatory conditions. However, it is not cheap and the amount used may depend on what you can afford.
I suggest using about 1000 mg a day in most cases, although I suggest much higher doses in certain inflammatory, progressed neurodegenerative, or autoimmune conditions. I still recommend liposomal glutathione cream for use in localized areas, such as an area of pain or inflammation. Examples include over an inflamed joint or over the thyroid of someone with an autoimmune thyroid condition.
You can also purchase liposomal glutathione liquids that you take orally and that work well for many. I even have some patients who even make their own liquid liposomal glutathione with information found online.
Step Two: Balance TH-1 and TH-2
After I establish immune modulation with vitamin D and the glutathione cream, I work directly on taming a dominant TH-1 or TH-2 pathway. I do this is by stimulating the side of the immune system that is not dominant. Imagine your immune system is a seesaw, on which TH-1 and TH-2 are sitting. TH-1, which stimulates production of natural killer and cytotoxic T-cells, is sitting on the ground because it is big and heavy, while TH-2, the B-cell pathway, is way up in the air, waving its skinny little legs in an attempt to come down. To restore balance to that seesaw, I use natural compounds to stimulate TH-2, beefing it up so it can level the seesaw. If TH-2 is the dominant one sitting on the ground, then I support TH-1 to achieve the same balance.
I have put together a short list of compounds that stimulate TH-1 and TH-2. Sometimes, one or more of these nutrients can be used to determine the dominant state. For instance, coffee stimulates the TH-2 pathway. Drinking coffee may worsen a TH-2 dominant person’s autoimmune condition. This is the person who says she can’t drink coffee because it makes her autoimmune condition flare up.
The TH-1 dominant person, however, may find it lessens her symptoms and makes her feel better. Coffee, however, can be a tricky tool for diagnosis. Since it also stimulates the adrenal glands, coffee can cause irritability, insomnia, and other symptoms that resemble an autoimmune thyroid flare-up. I have had cases, however, in which my patients with rheumatoid arthritis have less joint pain when they drink coffee. That’s a clue that they have a TH-1 dominance.
Echinacea, a common component of antiviral remedies, stimulates the TH-1 pathway. It can make the person with TH-1 dominance feel worse and exacerbate autoimmune tissue destruction. The person with TH-2 dominance, in contrast, might feel better using echinacea.
Both the scientific literature and my clinical experience have allowed me to put together a list of botanical and nutritional compounds that affect the TH-1 and TH-2 pathways. Although I list these compounds here, it is important for the person with Hashimoto’s to see a healthcare practitioner trained and qualified in working with autoimmune disease to use these compounds correctly, safely and in the right combinations.
Compounds that stimulate TH-1
(These dampen a TH-2 dominance and will worsen the autoimmune condition of a TH-1 dominant person):
- Beta-glucan mushroom
- Maitake mushroom
- Glycyrrhiza (from licorice)
- Melissa Officinalis (lemon balm)
Compounds that stimulate TH-2
(These dampen a TH-1 dominance and will worsen the autoimmune condition of a TH-2 dominant person):
- Green tea extract
- Grape seed extract
- Pine bark extract
- White willow bark
Compounds that modulate both TH-1 and TH-2
- Vitamin A
- Vitamin E
Compounds that dampen IL-1, activating TH-1 or TH-2
- Pancreatic enzymes
I sometimes use immunological lab tests to determine whether a person is TH-1 or TH-2 dominant so that I know how to properly tame and support her over active and poorly regulated immune system. If a patient is TH-1 dominant, I prescribe compounds that stimulate TH-2, and if she is TH-2 dominant, I recommend compounds that stimulate TH-1.
Because unstable blood sugar, adrenal dysfunction, and poor digestive health exacerbate autoimmune disorders, supporting the entire body is also integral to managing Hashimoto’s. Also, don’t forget that the first priority is to enhance T-regulatory cell function with emulsified vitamin D, fish oil and glutathione. It’s important to add in the right combination of nutritional compounds, as determined by your healthcare practitioner, one at a time every three days to monitor response.
How do I know if the protocol for immune modulation is working? Monitoring symptoms is important of course, but I also use blood tests to monitor cytokines and T and B cell populations along the way, too. They should begin to reach normal levels and antibody tests should become negative. That doesn’t mean the condition is cured, but it is dormant.
Using lab tests to assess immune function
Advancements in technology and testing have given us wonderful tools to assess health. When used in conjunction with these cutting-edge tests, natural medicine is a very effective model of support.
The first thing to establish is whether the person has an autoimmune condition. I use TPO and TGB serum antibody tests to rule out Hashimoto’s. If a test comes back negative but symptoms strongly suggest the disorder, I’ll repeat the test since antibody counts can fluctuate. Sometimes I’ll ask the person to eat gluten-containing foods for two weeks prior to the test, in order to heighten the autoimmune response.
From there, I delve into the immune system mechanics. I measure TH-1 and TH-2 cytokines to determine if the person is TH-1 or TH-2 dominant. When a person is placed on an immune-modulating protocol, I retest these cytokines to see whether the immune system is coming into better balance. When looking at these test results, it is important to look at the percentages of the cytokines and not the totals.
Remember, regardless of whether a person with Hashimoto’s has TH-1 or TH-2 dominance, managing his or her condition requires modulating the immune system with emulsified vitamin D, fish oil, glutathione, a gluten-free and dairy-free diet, and dietary support.