To review, inflammation is not the underlying root of any disease. It is a side effect of a deeper cause. In the previous article I outlined the four core causes of inflammation and discussed some potential problems and benefits of boosting the immune system by stimulating inflammation. Continuing with TNFα as an example, let’s look at the potential problems of taking anti-aging substances to reduce inflammation.
TNFα is an inflammation weapon produced by certain immune cells to protect us from viruses and cancer.
What happens when you take substances that reduce TNFα activty? Several strong pharmaceutical drugs like Humira® and Enbrel® were developed specifically for the purpose of suppressing excess activity of TNFα and relieving the inflammation of many autoimmune diseases. The immune-suppressing side effects of these strong drugs offer glimpse of what happens to the body when TNFα levels are too low. As we would expect, many of side effects revolve around the microbial kingdom gaining the upper hand. These include acute infections of the nose, throat or sinus, cellulitis, fungal infections, reactivated tuberculosis, shingles and bacterial sepsis. For those suffering from autoimmune disorders, this is a calculated risk. By shutting down inflammation, these drugs disarm the immune system so it can no longer effectively fight invaders.
Several herbs and supplements also suppress TNFα. Touted as “anti-inflammatory” or “anti-aging” these include curcumin[i], black cumin seed[ii], Boswellia[iii] and Cat’s Claw[iv]. While nowhere as strong as some of the pharmaceuticals, what happens to the body’s immune defenses when TNFα is artificially lowered? Some pathogens suppress TNFα as a way manipulate and elude the immune system[v]. Over time can moderate suppression of TNFα compromise the body’s natural defenses against overgrowth of pathogens? Since we are turning off the chemicals that cause the symptoms, how would we even know? Our current medical technology has very limited tools for detecting the presence of an invading pathogen. Most of our tools look to the immune system to provide clues about invaders. A simple urinalysis or blood test cannot detect specific pathogens. Instead it looks for high levels of immune cells like neutrophils or lymphocytes to help the physician determine what is causing the infection. By the time these immune cells show up in lab work, there has already been a significant breach of the immune system.
We know that lectins, proteins found in beans and lentils, will raise levels of TNFα. This is not because these foods have mysterious powers. It’s because the immune system mistakes them for an invader and launches an attack against them. Lectins are not inherently dangerous. However, the immune response that they elicit could certainly influence the rate of aging of any tissues participating in the reaction. Perhaps this is why the Indian diet evolved to include so many herbs that suppress this type of inflammation from immune activity. But where is the line? If there are signs of inflammation, how do we know if it is coming from a legitimate invader or if it’s an artifact of our evolution? If someone is experiencing inflammatory symptoms, shouldn’t we identify what is triggering the immune system to act before we suppress it?
An Anti-Aging Regimen Gone Awry
I felt compelled to write this after seeing an extremely healthy patient with recurrent thrush (a yeast infection of the mouth). It was fairly mild but was enough for his doctor to perform an HIV test. It was negative. This gentleman was obsessed with life extension and he was seemingly doing everything right. He was doing intermittent fasting, interval exercise, alkaline water, Paleo Diet, lots of veggies, adequate protein, low sugar and carbs, blackout curtains at night. His labs showed everything as perfect. Even his neutrophils (the immune cells that fight yeast) were on target. As part of his life extension regimen, he was paying a small fortune every month for herbs and supplements. Of interest, these included curcumin, Pterostilbene, green tea extract, fish oil, Boswellia and, when it was still available, Anatobloc®. Unless he took antifungals all the time, the thrush would come back. For awhile, I thought it was microbiome issue. A microbial stool analysis showed only mild yeast overgrowth. This was notable but not remarkable because I see these mild levels in at least 70% of the patients tested. We tried various live-shipped probiotics and fermented foods with no improvement. After a couple of months it finally occurred to me that he may have been going to far with suppressing inflammation. After some negotiating, he finally agreed to stop the Anatobloc, curcumin and Boswellia for a few weeks. Sure enough, within a week, no more thrush!
Perhaps one day we will have amazing assays to instantly identify any immune trigger that is causing inflammation. Until then how do we find that sweet spot where we suppress inflammation while still helping our immune system do what it already knows how to do?
[i] Cho, J., Lee, K., & Kim, C. (2007). Curcumin attenuates the expression of IL-1β, IL-6, and TNF-α as well as cyclin E in TNF-α-treated HaCaT cells; NF-κB and MAPKs as potential upstream targets. International Journal of Molecular Medicine, 19, 469-474. http://dx.doi.org/10.3892/ijmm.19.3.469
[ii] Aftab Ahmad, Asif Husain, Mohd Mujeeb, Shah Alam Khan, Abul Kalam Najmi, Nasir Ali Siddique, Zoheir A. Damanhouri, and Firoz Anwar A review on therapeutic potential of Nigella sativa: A miracle herb Asian Pac J Trop Biomed. 2013 May; 3(5): 337–352. doi: 10.1016/S2221-1691(13)60075-1 PMCID: PMC3642442
[iii] B. Gayathria, N. Manjulaa, K.S. Vinaykumara, B.S. Lakshmia, , , A. Balakrishnanb Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNFα, IL-1β, NO and MAP kinases. International Immunopharmacology Volume 7, Issue 4, April 2007, Pages 473–482
[iv] Sandoval M1, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection.
Free Radic Biol Med. 2000 Jul 1;29(1):71-8.
[v] Bosio CM. The Subversion of the Immune System by Francisella Tularensis. Frontiers in Microbiology. 2011;2:9. doi:10.3389/fmicb.2011.00009.by
This article is not intended to diagnose or treat any diseases.
Due diligence is a necessary part of the healing process. If you believe you are worth the effort, then seek the knowledge you need to reveal the truth.
In the world of functional medicine and nutrition we use a large array of herbs, vitamins, minerals, amino acids and other biological substances to restore function and support healing. Most of the supplements we use are fairly safe. Even when the diagnosis is incorrect or if a side effect occurs, most reactions will resolve quickly with no permanent harm. However, there is a handful of supplements that can cause, at best, a setback and, on occasion, significant side effects. Betaine hydrochloride (HCl) is one of them. When used appropriately and under the correct diagnosis, Betaine HCl can have seemingly magical effects on conditions like acne, eczema, asthma, idiopathic malnutrition, GERD and other digestive issues. However, a visit to most mainstream medical websites will advise you, “Do not take Betaine HCL”. This is with good reason. Betaine HCL can exacerbate several underlying health conditions and, in rare instances, can cause life-threatening health issues.
Betaine HCL is used to treat a condition called hypochlorhydria (insufficiently strong stomach acid). Although it hasn’t been subject to rigorous clinical trials, here is the simplified hypothesis; when acid is the stomach is not strong enough (pH between 1.5 and 3.5) animal protein cannot be effectively digested into amino acids and smaller protein fragments. As a result, the stomach somehow detects this problem and continues to produce weak acid. The weak acid fills up past the stomach and into the esophagus. Unlike the iron-clad lining of the stomach, the esophagus is easily damaged by acid. The thinking is that Betaine HCl works by restoring the correct pH (increasing the acidity) of stomach acid. When the correct dosage achieved, the excess production of weak acid stops and normal digestion of protein and minerals resumes. If the correct dose is not achieved, supplementing with Betaine HCl has little value. Practitioners, here is a link to a method that was originally presented by Jonathan Wright M.D. on how to figure out the correct dose of Betaine HCl. As the author describes, most cases require no more than 2500mg for reestablishing adequate acid levels. I have seen a few cases where the replacement dose was over 6000mg per meal.
Accurate Diagnosis is Crucial
There are many downstream health issues that can arise from inadequate digestion of protein. These include IBS, excessive flatulence, leaky gut syndrome, asthma, acne, allergies, eczema, acid reflux, idiopathic malnutrition, premature osteoporosis etc. There are scientifically sound explanations for each of these that we will discuss another time. However, any of these conditions can be caused by other factors and, none of them is a defining symptom of low stomach acid (hypochlorhydria).
Most importantly, acid reflux, often diagnosed as GERD, is NOT a pathognomonic symptom of hypochlorhydria. The exact same symptoms can be caused by overgrowth of bacteria and in small intestine, excess production of acid, stagnation of the motor migrating complex and, more commonly, by excess histamine. This is why decades of research produced two classes of drugs to treat GERD. These are the proton pump inhibitors (PPI’s) and H2 blockers (Histamine receptor blockers). It can be implied that the effectiveness of these two categories of drugs in treating symptoms can shed some clarity on the root of the problem. In more complex cases, hypochlorhydria and excess histamine will occur simultaneously.
The Big Cautions With Betaine HCl
Esophageal Damage and Strictures
Pills of Betaine HCl can get lodged in areas where the esophagus has narrowed from scar tissue or has shrunk from old age. This usually causes a strong, sharp pain. If the pill remains for more than a couple of minutes, it can literally burn the area. If this happens, the irritation can last several days and it is best to discontinue the course of Betaine HCl therapy until it is completely healed. To prevent damage to the esophagus in cases like these, it is crucial to flush the area until the pill is small enough to move on. This can be done by sipping a weak solution of baking soda in warm water (1/4 tsp per 12 oz of water) OR by diluting a full dose of a liquid antacid in warm water. DO NOT use baking soda if the patient has high blood pressure. This scenario is more common in elderly patients and it is better to break up the Betaine HCl capsules before swallowing them. As a general rule, if this happens, don’t hesitate to seek medical attention.
Exacerbation of Gastritis
Gastritis is inflammation of the stomach lining. It has many causes but ultimately occurs because the cells lining the stomach cannot replace themselves quickly enough to maintain the integrity of the tissue. When this happens, any small amount of acid can quickly damage the lining. This is a potentially dangerous situation as ulcers can form. Possible causes include excessive alcohol consumption, use of corticosteroids and NSAIDS, stress, excess acid production, nutritional deficiencies, excess levels of histamine and infection.
Combine a stomach that is severely irritated by excess histamine and add Betaine HCl and you have yourself a new condition that can take several weeks to fully heal.
Symptoms of gastritis can easily go unnoticed. This is especially true for people who are busy, overwhelmed and/or highly driven. I meet people all the time in my practice who have had low to mid-grade symptoms of gastritis for years without giving it a single consideration that something could be wrong. This can also happen because some people have an altered perception of pain in their digestive tract. Nerve blocks and cauterizations as well as medications, like antidepressants, narcotics and opioids, can reduce pain sensations. Practitioners! Confirm your diagnosis before prescribing Betaine HCl and proceed cautiously with the dose. DO NOT assume that patients will notice side effects immediately.
A True Story of a Gastritis Nightmare
More than a decade ago, I had a nutrition consultation with a gentleman who had clear signs of gastritis. Although he didn’t think so, his lifestyle was extremely stressful. He was founder and CEO of a very successful chain of stores. He worked long hours and traveled frequently. Drinking too much alcohol was one way he compensated for the stress. His symptoms manifested as a dull ache (fairly mild) above his naval that was worse on an empty stomach, with water, with spicy food and about 20 minutes after eating (food usually absorbs acid for a few minutes before the stomach makes more). He denied any sign of dark, tarry pieces in his stool (a sign of bleeding in the digestive system). At the time of our meeting, he was preparing to leave for a big game hunting trip in east Africa. I insisted that he consult a physician before departing. His first week in the African bush he developed anemia as a result of a bleeding ulcer. It took several days for him to reach a facility with adequate medical care. He ended up having to have surgery and, more unfortunately, a blood transfusion that left him with a lifelong disease.
Healing gut disorders is often one of the most complicated, daunting and challenging aspect of all health issues. There are multiple systems that all have to work in harmony and one tiny defect can affect everything downstream. If you are lucky, sometimes a simple probiotic, glutamine or digestive enzyme will fix the issue. However more often than not, simply diagnosing the root cause is buried underneath a pile of confusing symptoms. Because many gut disorders heal much faster with the assistance of glutamine it is important to understand the side effects that it can cause and what they mean.
When you read about glutamine on the various online resources (some being more accurate than others) it sounds like a miracle for treating anything from leaky gut to Crohn’s disease. Generally speaking, glutamine is absolutely lovely for two specific problems.
- Supplying energy for the cells of the small intestine. The cells of the small intestine use glutamine instead of glucose as an energy source.
- Supporting fast healing of almost any damaged tissue of the digestive lining.
These make glutamine a keystone remedy for repairing conditions like burning mouth syndrome, gastritis, stomach and duodenal ulcers, leaky gut syndrome of both the small and large intestine, damage from chemotherapy, food poisoning and irritants like gluten. However, if you haven’t identified the cause of the damage, then taking glutamine is like trying to patch a crack in a dam that is expanding everyday. Although it can produce noticeable improvement, glutamine deficiency is rarely the core cause of digestive problems. Interestingly, unexpected side effects to glutamine can help guide you to the root of the problem. Here are the main ones I’ve seen in my practice.
#1 Increased bloating with glutamine:
There are only two possible things that can cause increased bloating with glutamine. First, and more common, is constipation or undigested food that is stagnant in the digestive system. Many patients may not even be aware that they are constipated. A simple way to find out is to do the beet test. Simply eat some red beets and see how long it takes for them to come out. Believe me, the blood-red color is unmistakable. Anything over 24 hours is quite suspicious.
Glutamine can sometimes improve normal churning movements in the gut known as peristalsis. If the patient is constipated the churning movement can move undigested food that is in the stool or trapped behind it into new areas where bacteria are waiting for their next meal. The bacteria produce various gasses as a byproduct of digesting these foods.
The second cause is glutamine-eating bacteria. The first time I saw this was in a patient with a severe case of SIBO. None of my other colleagues had ever seen it before and it took me quite a while to figure out what it was. It turns out that there are some bacteria that are happy to use glutamine as a food source. In this patient’s case she had glutamine-eating bacteria in her small intestine where no bacteria should have been growing. They would produce extreme bloating within 30 minutes of taking glutamine.
#2 Glutamate-type effect:
Some bacteria convert harmless glutamine into glutamate. Glutamate is most commonly known in monosodium glutamate (MSG). It has excitatory effects on the nervous system and is a known “excitotoxin”.
Common side effects include dialation of pupils, feeling wound up or anxious, headaches or aggravation of migraines, a tight sensation in the diaphragm and, if severe, heart palpitations. In this case it is important to identify and diminish the populations of the offending bacteria before continuing the use of glutamine.
*It took me 15 years to understand why some patients had this reaction to glutamine. Dr. Katherine Pollard’s talk at the 2015 American Association for the Advancement of Science finally revealed the missing piece.
#3 Allergies or other immune reactions to glutamine:
Any immune reactions to glutamine are ALWAYS due to either to added ingredients or to residues from the source of the glutamine (usually an animal source). It is not possible to have an immune reaction (allergy or otherwise) to glutamine by itself. The immune system is not capable of recognizing individual amino acids as a threat. Pure glutamine does not clump or cake and will homogenize quickly in liquids. If the glutamine you are using does not have these properties then it probably contains fillers.
Aside from classic histamine-type allergies that produce itching, swelling and nausea, it is possible to have other types of immune reactions to a substance that have nothing to do with an actual allergy. This is very common in leaky gut syndrome where various types of immune cells are recruited to deal with different substances that have breached past the intestinal lining. For example, neutrophils normally attack bacteria. However they are known to react to some food proteins that mimic antigens (proteins) on the surface of bacteria. Lectins from beans are a common example. An immune reaction after taking glutamine can manifest as an allergy or an exacerbation of the existing symptoms. For example, if acne, joint aches or interstitial cystitis has developed from leaky gut syndrome (this is not the only cause of these conditions), there will be a very obvious flare within 4 hours of taking the glutamine. In this case consider trying an alternative brand or a pharmaceutical-grade, synthetic glutamine that has no residues. Although there are hundreds of supplement manufacturers, most obtain their ingredients from a handful of bulk suppliers. Therefore, even an alternate brand can produce the exact same effect if they get their glutamine from the same bulk supplier. There is one way to avoid getting the same bulk glutamine from a different brand. Contact the company from whom you obtained the glutamine. Nicely explain that you have had a reaction to it. Ask them what the source is of the glutamine (so you can identify the offending residue) and the name of their bulk supplier. Once you have this information, you can contact other supplement companies and identify ones that don’t use the same bulk supplier or source. If you want to help others, feel free to post your discoveries here.