Nitric oxide modulation for autoimmune disease

In the thyroid book I introduced the concepts of TH-1 and TH-2 and their role in autoimmune diseases, such as Hashimoto’s. It turns out another key player in the autoimmune scenario is TH-17, and that we can work with nitric oxide and glutathione (which I wrote about earlier) to tame autoimmune destruction caused by TH-17.

TH-17: The new kid on the block

There are many TH (again, TH means T helper cell) players actually, but TH-17 is one worth turning the spotlight on for a moment.

When the immune system triggers an autoimmune response, the autoimmune reaction expresses predominantly through either the TH-1 or TH-2 system, as explained in chapter three of Why Do I Still Have Thyroid Symptoms?.

When activated, the TH-1 and TH-2 systems release cytokines, or immune messenger cells, called IL-17. These cytokines in turn promote tissue destruction at the site of the autoimmune attacks, which for our purposes is the thyroid gland.

TH-17 cells are a fairly recent discovery, and believed to be connected with autoimmune destruction when found in abundance. TH-17 is the system that adds fuel to the autoimmune fire and determines the severity of tissue destruction.

It’s important to understand that TH-17 isn’t all bad—it also plays an anti-microbial role in the body’s mucous linings, preventing infection from microbes such as candida or staphylococcus. But when it comes to the immune system, too much of a good thing ends up creating an imbalance with bad results.[1]

Using nitric oxide to modulate autoimmune activity

IL-17 does its dirty work of destroying tissue by activating a compound called inducible nitric oxide.

Nitric oxide is a gas in the body that acts as a signaling compound, triggering things to happen. It plays a role in many normal physiological processes, but also in disease. There are three forms of nitric oxide, two of which are beneficial, and one of which is destructive.

Exercise enthusiasts take an amino acid supplement called arginine to boost nitric oxide, as the beneficial forms of nitric oxide promote blood flow and the dilation of blood vessels. Bodybuilders like this because increasing blood flow to their muscles enables them to lift heavier weights, work out longer, and recover faster, thus building more muscle. Good nitric oxide activity has also been shown to lower the risk of cardiovascular disease. [2]

The good and the bad of nitric oxide

Unfortunately, arginine may also increase a very pro-inflammatory and damaging form of nitric oxide called inducible nitric oxide.

Researchers have found that when an autoimmune reaction creates a surge in TH-17 activity, it stimulates an enzyme called inducible nitric oxide synthase (iNOS) to produce more inducible nitric oxide. When TH-17 goes up, iNOS goes up, and inducible nitric oxide sets about destroying body tissue, such as the thyroid gland, erroneously targeted by the dysregulated immune system.[3] [4] [5]

In other words, TH-17 gives the orders to attack, but inducible nitric oxide is the perpetrator that carries out the dirty work. Unfortunately, people who take arginine may be subjecting themselves to unnecessary increases in iNOS activity, and hence more inflammation.

Like TH-17, iNOS isn’t all bad. It’s pro-inflammatory role comes in handy to combat viruses, bacteria, and other pathogens.[6] But the health imbalances that lead to autoimmune disease are the same ones that over stimulate the production of iNOS that destroy body tissue.[7]

We can test TH-17 levels just as we can test for TH-1 and TH-2. This is helpful because if a lab panel shows TH-17 cytokines to be elevated, this tells us tissue is actively being destroyed and it’s vital to quench that process.

The good news and the bad news about nitric oxide

Body builders who take arginine think nitric oxide is good. A practitioner seeking to tame the destruction of an autoimmune process may look upon nitric oxide as bad. Which is it? It depends on the form of nitric oxide the body is producing.

So far I have talked about inducible nitric oxide, which a TH-1 or TH-2 triggered autoimmune attack activates via TH-17 to destroy tissue. For people experiencing autoimmune flare-ups, this system is in overdrive.

However, we can combat this destruction by activating the two beneficial forms (technically called isomers) of nitric oxide called endothelial nitric oxide and neuronal nitric oxide.

Endothelial nitric oxide

Endothelial nitric oxide is found in the lining of blood vessels. It aids in tissue recovery and regeneration, enhances blood flow, dissolves plaques, and dilates blood vessels. One thing that dramatically activates endothelial nitric oxide is exercise. When you exercise, the increase in blood flow turns on the endothelial nitric oxide system, which helps dissolve plaque in the arteries.

Unfortunately, autoimmune disease often compromises this system, thus hindering the delivery of blood to body tissue.[8] This not only makes body tissue, such as the thyroid gland, more vulnerable to inflammation and destruction, but it also makes it more difficult for these tissues to recover and heal.

A weak endothelial nitric oxide system helps explain cold hands and feet, the loss of hair, weak nails prone to fungal infections, and other symptoms frequently found in conjunction with autoimmune diseases.

Poor blood flow robs the brain of blood, and hence oxygen and nutrients, and brain function deteriorates.

Poor blood flow to the digestive tract is one cause of leaky gut and poor gut function. Coupled with inflammation and poor glutathione activity, the person with a chronically activated autoimmune disease can never seem to repair her gut. This is why a strict autoimmune diet to protect the gut is necessary in these cases.

Overall, the research shows endothelial nitric oxide plays a big role in preventing and taming autoimmune disease, due to its inhibition of over activity of both the TH-1 and TH-2 systems.

Neuronal nitric oxide

Neuronal nitric oxide acts on the brain and nervous system, enhancing the ability of the brain and nervous system to adapt to change, communicate between neurons, and recover. Because good brain health is vital to absolutely every organ and system in the body, we want neuronal nitric oxide levels to be sufficient and active.

How to boost the good nitric oxide and dampen the bad

So we know endothelial nitric oxide helps tame the autoimmune response and aids in tissue recovery. We know we have a “bad” nitric oxide, inducible nitric oxide, which is over active during TH-17-stimulated autoimmune attacks. We also know that taking arginine is not desirable, because although it might boost endothelial and neuronal nitric oxide, it may also boost the destructive inducible nitric oxide. These are the facts I considered as a practitioner when I began exploring these mechanisms and how to further help my autoimmune patients.

The clinical goal is to modulate the TH-1, TH-2, TH-3, and TH-17 systems (by modulate, I mean influence them to behave appropriately), increase endothelial nitric oxide, and dampen the inducible nitric oxide response.

Eventually, after my ongoing review of the research and clinical experience, it became apparent glutathione pathway integrity and nitric oxide modulation (boosting the good and dampening the harmful) offered profound responses.

Nutritional compounds for nitric oxide modulation

Through reading published studies, I found a variety of nutritional compounds that have been shown to boost endothelial nitric oxide without also boosting the pro-inflammatory inducible nitric oxide. I use these nutrients together as I find they have the best effects when working synergistically:

• Adenosine
• Huperzine A
• Vinpocetine
• Alpha Glycerylphosphorylcholine (Alpha GPC)
• Xanthinol niacinate
• L-Acetylcarnitine

In my practice the use of these compounds together in an emulsified liquid formula has had profound effects in managing some of my most severe autoimmune cases, and, together with glutathione recycling, has been an exciting discovery for me as a practitioner.

For the best results take these compounds before exercise, even if it’s a walk around the block. Exercise will get the blood flowing and enhance the effects of the endothelial and neuronal nitric oxide activation.

Glutathione recycling and nitric oxide modulation—a beautiful partnership

A nitric oxide modulating and glutathione recycling approach is available through a qualified health care practitioner trained in these approaches.

The nice thing about supporting glutathione recycling and nitric oxide is that it doesn’t matter whether you are TH-1 or TH-2 dominant.

I find these approaches have been successful with my very fragile patients who react to so many foods and supplements and can’t handle the TH-1 or TH-2 stimulating compounds.