Inflammation is not the underlying root of any disease. It is a side effect of a deeper cause. Tinkering with inflammation is tinkering with the immune system. Buzzwords like “anti-cancer”, “anti-viral”, “anti-inflammation” and “immune-boosting” are misleading and offer no information about how various herbs, supplements and pharmaceuticals actually work. Desperate for relief, ill consumers are constantly duped by the supplement industry as they seek easy answers for complex diseases. When the mechanism of a supplement doesn’t match the underlying cause of the immune imbalance, short-term side effects commonly occur. An understanding the mechanisms of aging offers us a glimpse of the potential short-term and long-term side effects that can result from tinkering with the immune system.
When I began studying functional medicine 18 years ago, I was awakened to the then controversial hypothesis that inflammation was the primary driver of many of the diseases of aging. There were hundreds of studies demonstrating the correlation between inflammation and conditions like heart disease, obesity, diabetes, cancer and even aging. As I developed my practice, it was like having magical powers believing that the cause of heart disease was not cholesterol but, in fact, inflammation. Armed with supplements like fish oil, curcumin and boswellia, I felt like Wonder Woman, striking down interleukin 6, NF-kappa B, TNFα and other inflammatory signals that could lead to disease. It wasn’t until I began treating autoimmune and skin disorders that I came to realize that inflammation is not the underlying root of any of these diseases. It’s a side effect of a deeper cause. In fact, suppressing inflammation without understanding its cause is as insane as turning off the fire alarm and going back to bed while the house fills with smoke.
There are four core mechanisms that drive inflammation. This article will explore the most common; when the immune system recognizes something as an invader and launches an attack using inflammatory chemicals as weapons. In science we call this immune system activation by antigen recognition.
The other three (listed below) will be discussed in future posts.
- Over activation of NFKappaB through dietary signaling. Activity of NFKappa B is highly influenced by the presence or absence of insulin. In general, diet doesn’t cause inflammation; it simply acts like a volume control. It isn’t until grossly pathological changes develop through excessive insulin signaling and ROS production that we begin to see the out-of-control inflammation associated with diseases like obesity and diabetes.
- Deranged methylation and acetylation of DNA,. Basically methyl groups (from SAMe) and acetyl groups are stuck to DNA to turn it on and off.
- The healing response – the redness, pain and swelling that results from an injury is ultimately an immune response that drives healing. However, repeated injuries, like when high blood pressure repeatedly damages the arteries, will lead to thickening and scarring.
Much of inflammation is nothing more than a side effect of immune activity. A fundamental flaw in our current medical approach to inflammation is the false belief that the immune system is creating inflammation for no reason. As a result, we have an entire industry of herbs, supplements and pharmaceuticals built upon the idea that suppressing inflammation is somehow healing the body. All this despite several large studies demonstrating that conditions associated with inflammation like heart disease, diabetes and cancer are mostly driven by external factors. To be clear, unless a true autoimmune condition has developed, the immune system will not act unless there is something triggering it to act. Sometimes we don’t like the results. However, this ancient system that protects us from cancer and invaders is highly intelligent and tightly regulated. The immune system will launch an attack against any critters or substance that it identifies as an invader. These include bacteria, viruses, air pollutants, some metals, environmental contaminants and oxidized LDL cholesterol. It will also attack undigested food proteins like gluten from wheat and lectins from beans. Food sensitivity tests like the ALCAT and Mediator Release Test (MRT) regularly reveal that the immune system will attack virtually any intact food protein or microbe that escapes past the protective gut mucosa (gut lining).
As one example in an ocean of inflammatory immune signals, look at what happens if we tinker with TNFα.
T= “tumor” like cancer
N=“necrosis” like death
Fα=“factor alpha” as a signal category
TNFα is an inflammation weapon produced by certain immune cells to protect us from viruses and cancer. It helps transmit signals from outside a cell to inside a cell’s nucleus where more signals tell the cell to kill itself. In science we call this apoptosis. It is helpful for ensuring that cells that have become cancerous do not survive to divide and grow into a tumor. TNFα also “serve[s] as a first-line defense against influenza virus” and has “strong antiviral activity against many viruses including avian flu and swine flu2”. Upon first glance, it sounds like anything that will increase activity of TNFα can keep you from getting cancer and viruses. Woohoo! In fact, several medicinal mushrooms are promoted as having these anti-cancer and anti-viral properties. Cordyceps,, Maitake, Coriolus and Ganoderma, all contain chemicals that increase activity of TNFα*. While this approach can be transformative for someone with a weak immune response, what effects does artificially increasing TNFα have in a healthy person? We know that in high amounts, TNFα causes considerable collateral damage to tissues. It is one of the main participants in diseases like psoriasis, ulcerative colitis and rheumatoid arthritis. Moderately high levels are associated with Alzheimer’s disease and even cancer10.
*I suspect that these mushrooms cause an increase in TNFα, not because they have magical properties, but because the immune system sees them as invaders and launches an attack.
Over the long term, does artificially raising TNFα activity accelerate the same degenerative problems that we see with any chronic inflammation? Wouldn’t mildly elevated levels still increase cell turnover, damage tissues, accelerate shortening of telomeres, speed aging and ultimately lead to early senescence*?
(*Senescence is a term used in aging research to describe the end stage of the aging process of a cell, tissue or system. When a cell reaches senescence it can no longer function properly or divide to form new cells. As more cells reach senescence in a given tissue, the more that tissue shrinks and becomes dysfunctional.)
Unless there is a specific reason to artificially stimulate TNF-alpha, it is important to weigh the potential effects of taking any herbs or mushrooms that raise it. Other herbs that stimulate inflammation by raising TNFα include Cistanches, Dipsacus, Echinacea and Psoralea. I have personally seen several patients whose autoimmune conditions were severely exacerbated from taking medicinal mushrooms. They were duped by claims and promises that somehow their condition was a result of a “weak” immune system and that these mushrooms were their salvation. On the other hand, with proper diagnosis, these types of mushrooms can be used as an effective tool when the immune response is too weak. Poor wound healing and recurrent viral infections (like shingles and Epstein Barr) are often caused by a weak immune response. Another scenario where these mushrooms may have benefit is with cancer. I have worked with scores of patients who were doing well months after their doctor prescribed Maitake-D as part of a larger protocol to help the immune system kill cancer cells. (Notice I said “part of a protocol”).
In the ocean of herbs and supplements that are supposed to help us live longer and healthier, how do we know which ones are actually helping? With illness, when the mechanism of a supplement doesn’t match the underlying cause of an immune imbalance short-term side effects commonly occur. What are the less detectable the long-term consequences? Is it possible to accelerate the aging process by inappropriately stimulating the immune system?
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 Prof Salim Yusuf DPhil,Steven Hawken MSc,Stephanie Ôunpuu PhD,Tony Dans MD,Alvaro Avezum MD,Fernando Lanas MD,Matthew McQueen FRCP,Andrzej Budaj MD,Prem Pais MD,John Varigos BSc,Liu Lisheng MD,on behalf of the INTERHEART Study Investigators Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study
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 Song Wu, Scott Powers, Wei Zhu & Yusuf A. Hannun. Substantial contribution of extrinsic risk factors to cancer development. Nature (2015) doi:10.1038/nature16166
Received 15 April 2015 Accepted 23 October 2015 Published online 16 December 2015
 From experience I have no doubt that many conditions that are diagnosed as “autoimmune” are nothing more than an appropriate immune reaction to an unidentified trigger that has grown out of control. This is commonly seen with leaky gut syndrome, SIBO and dental infections.
 Although there are hundreds of studies showing that oxidized LDL elicits inflammation from macrophages, it has never been shown whether this is an immune reaction or a healing response.
 Seo SH, Webster RG. Tumor necrosis factor alpha exerts powerful anti-influenza virus effects in lung epithelial cells. J Virol. 2002 Feb;76(3):1071-6.
 Test on mononuclear cells Lymphoproliferative, inhibited NK cell activity, phytohemagglutinin response raises IL2, raises TNF-alpha, IL-2 Kuo YC1, Tsai WJ, Shiao MS, Chen CF, Lin CY. Cordyceps sinensis as an immunomodulatory agent. Am J Chin Med. 1996;24(2):111-25.
 Jong Seok Lee, Eock Kee Hong. Immunostimulating Activity of the Polysaccharides Isonated from Cordyceps militaris. International Immunopharmacology. Vol 11, Isue 9, September 2011 Pp 1226-1233 doi:10.1016/j.intimp.2011.04.001
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I was first introduced to the concept of Sympathetic Overdrive while attending a lecture about the etiology of autoimmune disease presented by Gary and Rain Klepper D.C. Over ten years later, any skepticism I had regarding the importance of this concept has fully dissolved. There is an array of chronic diseases, including many autoimmune and skin disorders, which are ultimately and intimately related to gut health. Overlooking this single issue can render an otherwise sound treatment protocol slow or ineffective. For successful treatment of gut-related conditions it is imperative that the presence and severity of sympathetic overdrive be assessed and addressed.
Understanding Sympathetic Overdrive
There are two major parts of the nervous system. The parasympathetic, which is activated when we relax, is known as the “rest and digest” part of our nervous system. It stimulates blood flow to the digestive system, brain, extremities and sexual organs. The other part, the sympathetic nervous system, is responsible for the “fight or flight” response. It is activated when our body perceives stress. It reduces blood flow to the extremities, brain and digestive organs in preparation for a perceived survival situation. As we go through our daily lives, our external circumstances and our thoughts stimulate a constant dance between these two aspects of the nervous system. When a person is constantly stressed, their nervous system can be tilted into the state of sympathetic overdrive. The stress can be brought on by various factors including constant worry, skipping meals, not getting adequate rest, not allowing adequate time to carry out tasks and difficult life situations. People who work long hours that involve concentration and active thinking are prone to sympathetic overdrive. This condition is rampant in corporate executives and hedge fund managers. It can also be triggered by situations that remind our subconscious of stressful or scary events from our past.
When a person experiences enough stress to stimulate the sympathetic nervous system, they often experience cold hands and feet. Less noticeable but more serious is the reduced blood flow to the digestive tissues. If this only happens occasionally, the system usually has the resilience to recover. However, if the body is in a state of sympathetic overdrive, tissues of the digestive system constantly experience a state of reduced blood flow and oxygen exchange. Elevated levels of cortisol, the stress hormone, can lead to further damage to these tissues.
The effects of reduced blood flow from sympathetic overdrive interferes with the proper functioning of digestive organs, alters the balance of microbes residing within the gut, reduces the proper functioning of the immune system and interferes with proper filtering of nutrients that are absorbed. Many of the beneficial bacteria and fungi growing in our gut only thrive in an oxygen environment. These bacteria are known as aerobes. As the oxygen supply diminishes with circulation, bacteria that thrive in the absence of oxygen, anaerobes, begin to replace the withering populations of aerobic bacteria. Clostridium Difficile (aka C. Diff), a common infection in hospitals, is a classic anaerobic bacterium. Aside from C. Diff., there are likely hundreds of species of anaerobic bacteria that can or do reside in the human gut. So far, it is estimated that we’ve only been able to culture and identify between 1-5% of these organisms. However, we know they exist because we can test for one of their main waste products, beta-glucuronidase. This little waste product can reap havoc on the body’s detoxification systems and will be discussed in another article.
One would expect significant digestive disturbances in this situation. However, some people never experience any digestive symptoms. In the past 15 years I have seen hundreds of patients who tested positive for overgrowth of C. Diff, numerous pathogens or the presence of beta glucuronidase with no digestive symptoms. On the other hand, most of these patients had other significant chronic diseases including eczema, psoriasis, tyramine intolerance, rheumatoid arthritis, Hashimoto’s thyroiditis and fibromyalgia. I want to be absolutely clear that this scenario is only one piece of the puzzle in healing these diseases.
There are very few possibilities to explain how pathogenic bacteria can thrive in the digestive tract without initiating a proper immune response. The most logical explanation is the disruption of proper immune functioning from gut-associated lymphoid tissue (GALT). I suspect that this system either becomes defective or overloaded. As a result, the constant stream of antigens override this system and they are passed along to other parts of immune system in the mucosa associated lymphoid tissue (MALT). As a result, inflammatory conditions, like eczema and joint stiffness, arise in other parts of the body. This too is a very large subject that I will discuss in another article or in my book.
Assessing the Presence and Severity of Sympathetic Overdrive
There are several key signs that suggest a patient is experiencing Sympathetic Overdrive. Many of these were originally observed in the Traditional Chinese Medicine literature under the concepts of Liver Qi Stagnation, Liver overacting on Spleen and/or Stomach. Obviously, there are variations but here are some basic guidelines.
- Cold hands and feet – This symptom can arises when the stress response is fairly pronounced. Of course, it can be caused by other conditions that affect circulation. However, as a general rule, if the patient is experiencing both cold hands and feet, it is usually a symptom of sympathetic overdrive.
- Constipation or sluggish bowel movements without dry stools – the reduction of circulation to the digestive system slows churning in the intestinal tract and can lead to mild constipation or sluggish movement. It is possible to have constipation with dry stools along with this condition but it will not be caused by it.
- Overgrowth of anaerobic bacteria or elevated beta-glucuronidase on a stool and digestive analysis.
- Any symptom that is generally worse with stress is often related to sympathetic overdrive.
Treating Sympathetic Overdrive
There are multiple ways of treating this problem. However, tools that the patient can use several times per day will accelerate progress. The most powerful remedy for this situation is a variation of abdominal breathing that originated from the ancient practice of Qi Gong. This exercise, acts as a pump to restore circulation to the digestive tissues and directly stimulate the parasympathetic nervous system.
Instructions: Stand with your feet shoulder width apart and your knees slightly bent. Place your hands on the lower abdomen below the naval bringing your attention to this area. Inhaling deeply, extend your abdomen out as if it is a balloon filling with air. Exhale and squeeze the lower abdomen in imagining that you are trying to touch your naval to your spine. The repetitions can be done fairly quickly averaging about 1 every 3-4 seconds or slowly for a deeper meditative effect. You can also do this exercise while driving or lying down. Repeat 5-10 times several times per day or whenever symptoms appear. For amazing abdominal muscles repeat 100-200x per day.
You can find other meditative and breathing exercises in my previous post “Finding Inspiration Through Respiration”
Abdominal heat packs – simply applying heat to the abdominal area can stimulate circulation to these tissues and stimulate the parasympathetic nervous system.
Acupuncture is powerfully effective for “resetting” the nervous system and reducing stress. It has been demonstrated to treat the most extreme version of sympathetic overdrive, which we call post-traumatic stress disorder or PTSD. It is so effective that a few years ago, the U.S Department of Defense funded The Air Force Acupuncture Center. This is a clinic dedicated to treating military personnel who suffer from PTSD. It is used as a practice and training facility for physicians and medical professionals for “battlefield acupuncture”.
Herbs and Homeopathic Remedies that Really Work
Please note that all of these recommendations should be administered under the guidance of a qualified health care provider.
Rescue Remedy – This is available in all health food stores and online. Its intended use was originally for stress and traumatic experiences. I have found it to be incredibly helpful for treatment of gut disorders that involve sympathetic overdrive. Just follow the instuctions.
Psy-Stabil by Pekana – This is another remedy that falls under the practice of homotoxicology, which is slightly different from homeopathy. Its effects are similar to Rescue Remedy but may be a bit stronger. It is also very helpful for relieving anxiety.
Rhodiola – This herb is literally miraculous for restoring circulation to the digestive system and also balancing the nervous system. It is also helpful for treating addiction and some causes of depression. Be careful! It has some interactions with medications. Practitioners, be sure to take the time to inform yourself before prescribing it.
Lactobacillus Rhamanosus – This beneficial bacterium is one of the few that generates hydrogen peroxide. It is very helpful for reintroducing oxygen to the digestive tract and reducing overgrowth of C. Diff and other obligate anaerobes.
Other tips for preventing stimulation of the sympathetic nervous system:
- Don’t skip meals! Every time your body has to accommodate a drop in blood sugar, it stimulates the production of cortisol and initiates a stress response
- Take time everyday to do nothing
- Give yourself the gift of extra time to complete tasks. Cramming more and more tasks into your day increases stress and reduces creativity and the possibility of spontaneity.
- Pay attention to the situations and people in your life who make you feel stressed. Reflect on why they trigger these feelings in you and decide if there are ways of managing your exposure to them.
- Spend time in Nature. This is proven to reduce stress levels.
“Healing is a matter of time, but it is sometimes also a matter of opportunity.” – Hippocrates