From: Guy R. Schenker, D.C. October, 1997 Dear Doctor, In last month's Letter you learned that with the magical ... ABRACADABRA ZAP ... you give your patients with Oxy A-Plus and Oxy D-Plus, along with the unique combination of ingredients in Oxy A and Oxy D, there is no anaerobic/dysaerobic clinical challenge you cannot meet. But, believe it or not, THERE IS EVEN MORE YOU CAN DO FOR YOUR ANAEROBIC/DYSAEROBIC PATIENTS. Your QRG lists several amino acids which can take your clinical results from excellent to spectacular. On the dysaerobic side of your QRG you will note that it is often beneficial to give your patients the amino acids histidine and glutamine above and beyond what is already contained in their Oxygenic D. We already covered histidine in our discussion several months ago of electrolyte stress imbalance. Histidine was recommended for those patients who have a dysaerobic oxidative stress as a major part of their cardiovascular disease. We noted in that Letter that histidine has a specific protective effect on the arterial intima. It is also a vaso-dilator and thus decreases blood pressure. We also noted that Histidine has been shown to decrease angina pain. These and all the other beneficial effects of histidine are associated with its unique antioxidant activity. Histidine is the most effective naturally occurring singlet oxygen scavenger. That makes it the most important antioxidant found in our diets. - 2 - What exactly does it mean to be a singlet oxygen scavenger? A classic free radical contains an unpaired electron which makes it highly reactive. There is, however, a reactive, highly unstable oxygen species called singlet oxygen that contains a pair of electrons (and so technically cannot be classified as a free radial itself). But since the two electrons exist in unstable form, this molecule participates in reactions that generate free radicals. One example is the super oxide radical. Deactivating singlet oxygen with histidine prevents the formation of the super oxide radical. (The other common singlet oxygen quencher in our diet is beta carotene, though it is not nearly as powerful as histidine.) Histidine has been found to be particularly effective in the following conditions (frequently found in dysaerobic patients): rheumatoid arthritis, anemia, allergies, and nausea (including nausea of pregnancy), and upper GI ulcers. Regarding rheumatoid arthritis, it has been shown that both NSAIDS and steroids lower plasma histidine. So, while affording temporary relief, they actually exacerbate the condition. Aging is largely a cumulative effect of excessive oxidative free radical damage in the body. A chronic dysaerobic imbalance is always associated with tissue destruction and premature aging. It is interesting to note that low histidine levels are strongly correlated with aging. Your other powerfully anti-dysaerobic amino acid is glutamine. There is so much to be said about this amazing amino acid and its anti-dysaerobic effects that I don't know how I can cover it in less than 10 pages. But here goes: The specialized biological activities of glutamine can all be attributed to two distinctive qualities it possesses: 1. It is the one amino acid that contains two nitrogens, not just one. Therefore, it functions throughout the body as a nitrogen shuttle. Its role as a nitrogen shuttle is the basis of all glutamine's metabolic effects outside the GI tract. 2. In the GI tract glutamine is used directly by the cells of the GI lining for food. Glutamine is absorbed by enterocytes where it is broken down to eventually yield 5 ATP for every glutamine molecule. You must understand (and this is important because almost no other clinicians understand this) that almost no glucose is utilized by enterocytes for energy. In other words, glutamine is the source of fuel which the intestinal tract uses to perform its functions and to maintain itself structurally. - 3 - Let us talk about the GI functions of glutamine first. You note that ulcerative colitis, mucus colitis and certain other GI ulcers are typical of your dysaerobic patients. Glutamine is even more essential for the GI tract of the dysaerobic patient than for the rest of us. Glutamine is essential for the maintenance of GI cell metabolism, for the maintenance of its structure and for the maintenance of GI epithelial function. Leaky gut syndrome (which is associated with chronic allergic symptoms as well as absorption of bacterial and viral toxins) can be reversed with glutamine supplementation. The negative impact of disease/stress is far greater and occurs far earlier in the GI tract than any other organ. Further- more, the recovery time from disease or stress is much longer in the GI tract than in other organs. (Fibromyalgia is one example of a stress-related disease that has a GI component and is always associated with leaky gut syndrome.) Secretory IgA is the most abundant immunoglobulin in the intestinal immune barrier. The synthesis and expression of secretory IgA requires adequate glutamine. Regarding GI ulcers, glutamine supplementation results in complete healing within four weeks of 92% of ulcer patients. Glutamine supplementation has been shown to be beneficial in patients with inflammatory bowel disease. The glutamine helps decrease inflammation, helps repair the epithelial tissue, and helps decrease the excess mucosal permeability, thus decreasing the absorption of enterotoxins. Glutamine supplementation is therefore indicated in therapeutic doses for all your dysaerobic patients with irritable bowel syndrome and inflammatory bowel disease and chronic diarrhea. (It is also beneficial for viral diarrhea for any patient.) Glutamine has also been shown to prevent and eliminate gall stones. Glutamine achieves this by increasing bile flow and by decreasing the ionized calcium concentration of the bile. Consider now the other unique biological activity of glutamine -- its ubiquitous presence as a nitrogen shuttle. As part of the body's stress reaction, muscle tissue breaks down and amino acids are liberated. (This catabolic state is exaggerated in your dysaerobic patients.) Glutamine comprises 33% of the amino acids liberated from muscle breakdown during stress. What is more, 60% of the free amino acids in the intracellular amino acid pool (mostly found in muscles) consists of glutamine. This amino acid pool is reserved to be mobilized into plasma when amino acids (particularly - 4 - glutamine) are needed at other organ sites. So we see that muscle tissue is first a storage depot for glutamine, and second, a synthesizer of glutamine. In response to stress (either emotional or disease related) glutamine synthesis increases by 200 to 400%, yet the glutamine level in muscles decreases by 50% and the glutamine level in the blood decreases by 30%. How is it that glutamine levels decrease while synthesis is actually increased by two to four times? It is decreased simply because glutamine is utilized for tissue repair throughout the body and especially to maintain the GI mucosa. The muscle wasting that occurs when a person is sick or under chronic stress is virtually 100% due to a glutamine deficiency. Following is a list of other glutamine functions related to its nitrogen shuttle capacity, and which are particularly relevant to your dysaerobic patients: 1. Low glutamine levels decrease the activity of lymphocytes, decrease phagocytosis, and decrease the levels of immunoglobulin A, thus crippling immune function. One study showed that among animals made septic with massive doses of bacteria, 21 of 38 died, yet when given glutamine for one week prior only 3 out of 38 died. Another study showed that when animals were given an enzyme to destroy glutamine they all became rapidly immuno-suppressed; all developed necrotizing enterocolitis and died. 2. In burn patients glutamine levels were shown to drop by 58% and remained far below normal for 21 days. This relates to the immuno-suppression that occurs in burn patients. It was further found that the chance of infection in a burn is inversely proportional to the glutamine levels. From a NUTRI-SPEC perspective, burns are a dysaerobic lesion. (Note that Oxygenic D-Plus is extremely effective when used topically on burns for the first three days. The effect on healing is unbelievable until you have seen it yourself.) 3. Auto-immune diseases are typified by the presence of excess cytokines. (Rheumatoid arthritis patients have 50% more than normal.) Glutamine has a dramatic impact on decreasing cytokine production. (NOTE: On the DYSAEROBIC page of your QRG, add rheumatoid arthritis to the conditions for which glutamine supplementation is indicated.) 4. When an athlete over-trains (and they all do) glutamine levels decrease 9% below normal. This is due to muscle catabolism that exceeds the anabolic rebuilding capacity. The glutamine is also pulled out of muscles to be sent to the kidneys to help eliminate the acids produced during exercise. - 5 - The low glutamine levels from over-training decrease the athlete's resistance to infection and decreases the healing of wounds and athletic injuries. Many athletes supplement with substances purported to be anabolic aids. Most of them are an ineffective waste of money. If there is one anabolic aid that would really work for athletes it would be glutamine. Glutamine has been shown to stimulate human muscle glycogen synthesis following exercise. Glutamine administration has been shown to increase circulating plasma growth hormone concentration. Also note that glutamine is extremely heat labile and is thus destroyed in over-cooked foods. Note further that glutamine is not a part of the protein powders taken as supplements by many athletes, yet it is the one component of protein that they really may need in supplement form. 5. Glutamine is the most abundant amino acid in the cerebro- spinal fluid. Glutamine is a precursor to glutamic acid (an excitory neuro transmitter which does not cross the blood/brain barrier), and, glutamine is a precursor to GABA (an inhibitory neuro transmitter). Supplementation with only 250-1000 milligrams per day of glutamine has been shown effective as an antidepressant and a mood elevator. Keep this in mind for your dysaerobic patients. (In fact, you may add this to your QRG page as a dysaerobic condition for which you give additional glutamine.) Other brain effects of glutamine include improved problem solving on continuous performance tests -- and the effect here was immediate. Glutamine has also been shown to decrease anger and decrease fatigue. 6. Glutamine reverses the catabolic effect on muscles due to glucocorticoids. Glutamine thus eliminates the muscle atrophy typical in patients taking glucocorticoids. 7. Glutamine is effective in treating impotence. 8. Low levels of glutamine (like histidine) are strongly correlated with aging. How's that for an impressive list of credentials? Certainly you see the many uses you have for histidine and glutamine supplementation in your dysaerobic patients. Now look at the anaerobic side of your anaerobic/ dysaerobic QRG page. Three amino acids are listed as frequently beneficial for your anaerobic patients -- tyrosine, methionine and taurine. We covered the benefits of tyrosine in our discussion of electrolyte insufficiency imbalance in our March Letter. Rather than repeat that discussion, suffice - 6 - it to say that tyrosine is compatible with an anaerobic body chemistry. It elevates depressed levels of certain brain transmitters. Tyrosine also has specific antihistamine activity and specifically strengthens thyroid function. In terms of symptoms, it can be used for all your anaerobic patients with somnolence, fatigue, allergies or depression. Methionine is an essential amino acid that is powerfully anti-anaerobic by virtue of its sulfhydril group. (Also note that methionine is the most heat labile of the amino acids and therefore is easily destroyed in over-cooked food.) Via its active sulfur group methionine assists in detoxification. Methionine facilitates liver function and increases the production of lecithin in the liver. Methionine is lipotrophic -- helping the liver process and eliminate cholesterol and other fat. Methionine also decreases histamine levels and is thus beneficial for your anaerobic patients with allergies. Methionine has also been found beneficial in many cases of schizophrenia (and this is speculated to perhaps be due to its anti-histamine effect). Methionine also shows its anti-anaerobic activity in its effect on anaerobic cancers. According to a study published in Nutrition and Cancer, it may prevent and even reverse certain cancers by permitting the remethylation of DNA methylation inhibited by a carcinogen. Our final anti-anaerobic amino acid is taurine, which you read about extensively in our May Letter regarding its use for your electrolyte stress patients. The only clinical effect of taurine we did not cover in that discussion is its effect on the nervous system. Taurine enhances brain function in many ways and has demonstrated a particular beneficial effect on seizure disorders. It is important to note that virtually all seizure patients are anaerobic. In summary: The majority of your patients have an anaerobic/dysaerobic component to their health problem. (If the imbalance doesn't show up on initial testing it often will on a follow-up.) With Oxy A & A+, Oxy D & D+, and the amino acids histidine, glutamine, tyrosine, methionine and taurine, you are equipped to empower these patients like no other clinician can. Sincerely, Guy R. Schenker, D.C.