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
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?
 Kurtak, K. Dietary and Nutritional Manipulation of the Nuclear Transcription Factors, PPAR’s and SREBP’s,as a Tool for Reversing the Primary Diseases of Premature Death and Aging. Rejuvenation Research 17-2. April 2014. P 140-44.
 D. Bayarsaihan Epigenetic Mechanisms in Inflammation J Dent Res. 2011 Jan; 90(1): 9–17. doi: 10.1177/0022034510378683 PMCID: PMC3144097
 Stephen B Baylin DNA methylation and gene silencing in cancer. Nature Clinical Practice Oncology (2005) 2, S4-S11 doi:10.1038/ncponc0354. Received 16 August 2005 | Accepted 30 August 2005
 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
The Lancet – 11 September 2004 ( Vol. 364, Issue 9438, Pages 937-952 )
 Dariush Mozaffarian, MD, DrPH; Aruna Kamineni, MPH; Mercedes Carnethon, PhD; Luc Djoussé, MD, ScD; Kenneth J. Mukamal, MD; David Siscovick, MD, MPH. Lifestyle Risk Factors and new Onset Diabetes Mellitus in Older Adults. Arch Intern Med. 2009;169(8):798-807. doi:10.1001/archinternmed.2009.21.
 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
 Matsui K1, Kodama N, Nanba H. Effects of maitake (Grifola frondosa) D-Fraction on the carcinoma angiogenesis. Cancer Lett. 2001 Oct 30;172(2):193-8.
 Cheuk-Lun Lee, Xiaotong Yang, Jennifer Man-Fan Wan. The culture duration affects the immunomodulatory and anticancer effect of polysaccharopeptide derived from Coriolus versicolor. Enzyme and Microbial Technology. Volume 38, Issues 1–2, 3 January 2006, Pages 14–21
 Hung-Sen Chena, Yow-Fu Tsaia, Steven Lina, Chia-Ching Lina, Kay-Hooi Khoo, Chun-Hung Lin , , Chi-Huey Won. “Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum (Reishi) polysaccharides”. Bioorganic & Medicinal Chemistry Volume 12, Issue 21, 1 November 2004, Pages 5595–5601
 Sands BE1, Kaplan GG The role of in ulcerative colitis.. J Clin Pharmacol. 2007 Aug;47(8):930-41. Epub 2007 Jun 13.
 VASANTHI, P., NALINI, G. and RAJASEKHAR, G. (2007), Role of tumor necrosis factor-alpha in rheumatoid arthritis: a review. APLAR Journal of Rheumatology, 10: 270–274. doi: 10.1111/j.1479-8077.2007.00305.x
 Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010). “A meta-analysis of cytokines in Alzheimer’s disease”. Biol Psychiatry 68 (10): 930–941. doi:10.1016/j.biopsych.2010.06.012. PMID 20692646.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.
In the temperate zones of the Earth, late summer into autumn has been a time of celebration in many cultures. This is the time when all creatures breathe a sigh of relief as the hard work of growth slows. The cooler air transforms summer’s searing rays of sunshine into loving, golden warmth. Pregnant with sugar, fruits of flowering plants hang heavy from the branches and dapple the landscape in a mosaic of reds, blues and purples from anthocyanins and carotenoids. On the ground, combinations of lutein and zeaxanthin color the winter squashes of the Cucurbita family with the same oranges and yellows that are revealed as chlorophyll relinquishes its dominion over the foliage.
Colorful pigments that once acted as a beacon for pollinators in an array of colors and hormones assume a new form that will serve as this year’s bridge of survival for numerous species of birds and mammals, including humans.
Over these precious few weeks, concentrated glucose and fructose flow in like the ocean tide. With them, the stomach’s master hormones of appetite flip flop. Ghrelin’s waxing and leptin’s waning impose an ever-rising voracity of appetite that has driven successful survival of species over hundreds of millions of years. Inside the sweet goodness lurks even more treasures. Fresh omega-six oils from seeds and grains give a fresh boost to dwindling eicosanoids that are crucial for cell-to-cell communication. Vitamin E, selenium, vitamin C and phytonutrients stand like a levy to ensure the rising tide of inflammation doesn’t breach its banks.
In Traditional Chinese Medicine Theory, this time of year was considered the fifth season associated with the Earth element. Warmth, sunshine, water and Earth have been magically transformed by a billion tiny seeds into a form that passes life’s nourishment unto us. In the Jewish tradition, this season beckons the new year known as Rosh Hashanah.
“Blessed are you, sovereign of the Universe who brings forth bread to the Earth…who has kept us in life, has sustained us and brought us to this season.” Torah
Lurking deep within the cell, all the way down to the nuclear membrane, a sugar-laden surge of insulin nudges a sleeping Goddess from her torpor. 2.1 billion years ago, some of the earliest fungi birthed this goddess and time kindly bequeathed her unto humans. In science she is known as SREBP or sterol regulatory elemental binding proteins. She is the one who, as if by magic, signals that transformation of sugar into a form that can be stored for later use as triglycerides and fat. Without her, most animals in the temperate and arctic zones are unlikely to survive even one winter.
Because of SREBP’s, every cell can make its own LDL cholesterol for membrane repair and vitamin D synthesis. However, without a way to supply basic antioxidants to the cell, LDL quickly oxidizes. This transformation from Dr. Jeckel to Mr. Hide damages everything it touches and is considered to be one of the driving forces of atherosclerosis7. In order to protect her inner world and ensure a constant supply of antioxidants, SREBP must ask for a little help from one of her cousins in the liver, SREBP-1. While most of the cells of the body settle for glucose as an energy source, the liver engages in a more refined taste for fructose. In fact, liver cells are the only ones that can use fructose and its effects are incendiary. Fructose drives rapid production of LDL cholesterol, fats and inflammation in the liver,. This preference for fructose acts as a supply chain for the trillions of cells’ insatiable need for antioxidants during times like these. But without SREBP, these antioxidants are useless. She alone is the key master who permits passage of these antioxidants across the cell membrane. Under the dominion of SREBP, the LDL cholesterol receptor rises to the surface of the cell like a fish rising to feed. If it is lucky, LDL cholesterol will land in its mouth. Along for the ride, precious antioxidants like vitamins A, C, and E are granted access to the cell’s inner world.
As this season wanes, berries hang dried and scant on the branches. Insulin recedes as the sugar festival comes to a close. The Earth cools. SREBP breathes a deep sigh as her hard work comes to an end. As she falls into her winter nap, she brings many of the creatures of the Earth with her. Only one creature has successfully escaped the dominion of this goddess. Humans innovated to store carbohydrates externally. This consistent supply of sugar drives insulin to ensure that SREBP never sleeps. Her unrelenting state of slavery drives disorders like obesity,, fatty liver, insulin resistance and atherosclerosis, . Perhaps this goddess would argue that these are not diseases at all but are phenotypes brought on by depriving her of a proper rest.
 Cutler A.J., Krochko J.E. Formation and breakdown of ABA. Trends Plant. Sci. 1999;4:472–478. doi: 10.1016/S1360-1385(99)01497-1
 Teff KL, Elliott, SS, Tschop M, Kieffer TJ, Rader D., Heiman M., Townsend RR., Keim NL, D’Alesso D, Havel Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. PJ J Clin Endocrinol Metab. 2004 Jun;89(6):2963-72
 Giacomo dugo, Lara La Pera, Donatella Pollicino, marello Saitta. Determination of Selenium Content in Different Types of Seed Oils by Cathodic Stripping Potentiometry (CSP) J. Agric. Food Chem., 2003, 51 (19), pp 5598–5601
 Timothy F. Osborne, Peter J. Espenshade Evolutionary Conservation and Adaptation in the Mechanism that Regulates SREBP Action: What a Long Strange tRIP It’s Been. Genes & Dev. 2009. 23: 2578-2591, doi:10.1101/gad.1854309
 V Laudet Evolution of the Nuclear Receptor Superfamily: Early Diversification from an Ancestral Orphan Receptor. Journal of Molecular Endocrinology Dec. 1, 1997. 19 2-7-226
-  Colleen K. Nye Glyceroneogenesis Is the Dominant Pathway for Triglyceride Glycerol Synthesis in Vivo in the Rat The Journal of Biological Chemistry, 283, 27565-27574. October 10, 2008
 Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621
 Low Density Lipoprotein Can Cause Death of Islet β-Cells by Its Cellular Uptake and Oxidative Modification Miriam Cnop, Jean Claude Hannaert, Annick Y. Grupping, and Daniel G. Pipeleers Endocrinology 2002 143:9 , 3449-3453 http://dx.doi.org/10.1210/en.2002-220273
 Zhang C, Chen X, Zhu RM, Zhang Y, Tu T, Wang H., Zhao H, Zhao M, Ji YL, Chen YH, Meng XH, Wei W, Xu DX. “Endoplasmic reticulum stress is involved in hepatic SREBP-1c activation and lipid accumulation in fructose-fed mice.” 2012 Aug 3;212(3):229-40. doi: 10.1016/j.toxlet.2012.06.002. Epub 2012 Jun 12.
“ER stress contributes, at least in part, to hepatic SREBP-1c activation and lipid accumulation in fructose-evoked NAFLD.”
 Koo HY, Miyashita M, Cho BH, Nakamura MT. Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus. 2009 Dec 11;390(2):285-9. doi: 10.1016/j.bbrc.2009.09.109. Epub 2009 Sep 30.
“Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats.”
 Maret G Traber, Herbert J Kayden “Vitamin E is Delivered to Cells via the High Affinity Receptor for Low-Density Lipoprotein” The American Journal of Clinical Nutrition 40: October 1984, pp 747-51.
 Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621
 Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621
 Moon YA, Liang G, Xie X, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Brown MS, Goldstein JL, Horton JD. The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell Metab. 2012 Feb 8;15(2):240-6
Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. 1998 October 15; 12(20): 3182–3194.
 Karasawa T, Takahashi A, Saito R, Sekiya M, Igarashi M, Iwasaki H, Miyahara S, Koyasu S, Nakagawa Y, Ishii K, Matsuzaka T, Kobayashi K, Yahagi N, Takekoshi K, Sone H, Yatoh S, Suzuki H, Yamada N, Shimano H. Sterol regulatory element-binding protein-1 determines plasma remnant lipoproteins and accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1788-95.
 Kurtak, K. Dietary and Nutritional Manipulation of the Nuclear Transcription Factors, PPAR’s and SREBP’s, as a Tool for Reversing the Primary Diseases of Premature Death and Aging. Rejuvenation Research 17-2. April 2014. P 140-44.
There is never a reason to suffer with self-imposed rigidity to become healthier. When we rely solely on our will, we are at its mercy when it becomes weary. Instead, dissolve addictions and build lasting fortitude by practicing a little bit everyday. Before you know it, your mind and body will become good friends. A recent study in the Journal of Nutrition and Diabetes demonstrated that the brain can learn to eat healthfully. Here is a link to a great article from the BBC discussing the findings.
Eating a little protein as the day winds down helps prevent sugar cravings later in the evening. Replace at least part, or all, of your late afternoon snack with some protein. Instead of sugary fruit, have some nuts, cheese, prosciutto, hummus and veggies, a hard-boiled egg, a nitrate-free cold cut…maybe some tomatoes with mozzarella and basil. 90% of the patients who come to me don’t eat enough protein for all their poor little organs, cells and brain chemicals to function properly.by
A few years ago there was a little-known debate going on in the world of life extension and anti-aging about not eating eggs. Surprisingly this had nothing to do with cholesterol. Instead, the concern was that eggs are high in the amino acid methionine which was shown to accelerate aging…or more precisely, limiting methionine was shown to possibly extend lifespan. Life Extension has a good summary of this research without having to sift through PubMed. At the time I was well into the process of creating the field of Longevity Nutrition. After some investigating, I published this post discussing all of the wonderful health benefits of eggs and the caveats of methionine restriction with regards to life extension. Now that we know that My favorite part of the whole article discusses how the high concentration of methionine likely acts as a signal for fecundity as it travels through the entire food web. Here is a great article that is scientifically accurate discussing the health benefits of eggs that was recently published in Business Insider by Kris Gunnars. Enjoy!
Here is a link to my presentation. SENS6 Karen Kurtak
Hello all! This is my first presentation at a major international conference. It’s very technical but there are pieces that clarify in non-biochemical terminology . Here I present an argument for why the primary diseases of aging are not “diseases” at all but, in fact, phenotypes. I also discuss how the ketogenic diet alters signaling of DNA through nuclear transcription factors to stop, and sometimes reverse, the processes that ultimately lead to the primary “diseases” of aging including diabetes, heart disease, cancer, Alzheimer’s Disease. It was a lot of information to cover in 15 minutes but it offers a rough outline of the biochemical mechanism of action of the ketogenic diet. This took me literally over 1000 hours of sorting through science articles and plugging in the pieces until it all began to make sense. Along the way I found multiple journal articles that were completely wrong that led me down frustrating rabbit holes. Grrrr! For more extensive information please see my article that will be published in Rejuvenation Research Journal. Ultimately, this is just one example of the amount of information we already possess that is independent of clinical trials. Since I was limited to 2000 words in the article, I will be discussing each of these points in more detail in the coming months.
Thanks to Bill Andrews, who in his quest to cure aging or die trying, asked me a question that I couldn’t answer. Thank you to Aubrey de Grey for your vision that has created a firm foundation of understanding of the processes that lead to disease and aging. Thank you to all the humans of the Earth who have dedicated time and money towards uncovering truth and knowledge through science. Thank you to journals who don’t limit access of knowledge by creating pay walls. Elsevier, you guys are self-serving hijackers of knowledge. Thank you Markdavis and mmkroll for your open access photos on Flickr. Thanks to Nick, Robyn, my parents, Doreen, Bob, Michelle, Jordan, Michelle, Cliff, Darcie, Paula, Randi, Sue, Beth and Lara who supported me through multiple meltdowns and temporary possession by the Demon of OCD. Thank you Rozyln, William, Bill, (Bill’s brilliant wife whose name has escaped me), Dr. Cai, and everyone else who cheered for me before or during the conference!!!
In November of 2013 there was a media feeding frenzy when a large study demonstrated that people who ate even small amounts of nuts had an overall “7% reduced risk of dying from any cause during the 30 year study.”(Health Day from Medline © 2013). It also revealed that the more nuts people ate the more they reduced their risk of dying peaking at a 20% reduction for the highest consumers. Previous studies have demonstrated that eating nuts reduces incidence and risk for diabetes, heart disease, memory loss and obesity. (I”m not referencing these because there are too many to sift through).
There are several possible explanations for this but only time will tell. Here are a couple. First, fats, unlike protein and carbohydrates, have a unique ability to signal fullness. Fats do this through a chemical called leptin. It’s possible that simply eating nuts helps to reduce overconsumption of other foods. Second, omega-9 fats, which are predominant in nuts, send signals that talk directly to your DNA to reduce inflammation and cholesterol production, and increase the effectiveness of insulin. As I discuss in my article in Rejuvenation Research Journal, this works through a switch on the cell’s nucleus called PPAR which we know is activated by omega-9 oils. doi:10.1089/rej.2013.1485
In conclusion, eat at least a handful of nuts per day. Not seeds, nuts. Olive oil also contains the same beneficial oils. Try eating nuts before dinner. Since the fats help to signal fullness, it may help to reduce overeating. Later, I will discuss the nuances of deriving maximum benefit from nuts.by