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In Focus ® I n n o v a t i v e N u t r i t i o n NutriCology® Newsletter March 2008 Herbal Adaptogens For Asthma And Adrenal Function: A Blend of Unique Herbs May Have Wide Clinical Application In This Issue Herbal Adaptogens For Asthma and Adrenal Function: A Blend of Unique Herbs May Have Wide Clinical Application . . . . 2 New CoQH-CFTM Update. Ubiquinone and Ubiquinol: Working Hand in Hand. . . . . . 6 Diagnosis and Treatment of Adrenal Dysfunction: Q&A With James L. Wilson, N.D., D.C., Ph.D. ........................7 "An Extraordinarlily Useful Tool" A Doctor Reviews Garum Armoricum® for Depression, Anxiety, Cognition and Stamina . . . . . . . . . . . . . . . . . . . . . . . 10 How Overactive Membrane Ion Channels Influence Asthma and Other Disorders . . . . . . 12 In 2006 we reported a landmark study from the Mt. Sinai School of Medicine on a novel blend of Chinese herbs that proved statistically as effective as steroids in alleviating asthma symptoms. New evidence suggests these herbs may in fact restore adrenal function and be useful in a wide range of chronic illnesses. Turn to page 2 for more on Herbal Adaptogens. Diagnosis & Treatment of Adrenal Dysfunction: Q&A with James L. Wilson, N.D., D.C., Ph.D. The bestselling author of Adrenal Fatigue distills thirty years of experience in diagnosing and treating hypoadrenia, which he calls a problem of "monstrous proportions largely unrecognized by the medical establishment...recovery from adrenal fatigue is highly likely with proper treatment." Turn to page 7 for more on Diagnosis and Treatment of Adrenal Dysfunction. "An Extraordinarily Useful Tool" A Doctor Reviews Garum Armoricum® for Depression, Anxiety, Cognition and Stamina Dr. Tom Dorman reviews the concentrated whole food supplement, Garum Armoricum®: "I take it, my son takes it, and I'd have no hesitation to recommend it to every practitioner from M.D.'s to naturopaths." Turn to page 10 for more on Garum Armoricum®. How Overactive Membrane Ion Channels Influence Asthma and Other Disorders NutriCology® 2300 North Loop Road, Alameda CA 94502 Phone: 800-545-9960/510-263-2000 Fax: 800-688-7426/510-263-2100 www.nutricology.com A new model of excitation and inhibition helps us understand chronic inflammatory conditions like asthma, and perhaps even the bioenergetics of cancer. Turn to page 12 for more on Overactive Membrane Ion Channels. Herbal Adaptogens For Asthma and Adrenal Function: A Blend of Unique Herbs May Have Wide Clinical Application In 2006 we reported a landmark study member, who suffered from severe, refrom the Mt. Sinai School of Medicine in fractory asthma, has been off all mediNew York, the Weifang Asthma Hospi- cations, on twice daily doses of these tal and the Weifang School of Medicine herbs, and has had no asthma sympin China, on a novel blend of Chinese toms at all.” (see page 4) herbs (named ASHMI) that proved statistically as effective as steroids in • “My own experience is equally realleviating asthma symptoms. Now markable,” she continues, noting that we report more fully on these unique these herbs have also improved her adaptogenic herbs, which may have far stamina, substantially decreased her wider application than asthma alone. need for sleep, helped her shed exThere were preliminary indications cess weight, and reduced her frequent that this formula may in fact restore nocturia. “This formula may be an imadrenal function, and thus be useful in portant key to supporting the hyporelationship to many chronic illnesses thalamus-pituitary-adrenal axis,” she suggests. (see page 4) associated with adrenal fatigue. Highlights of the new information we inThese unique adaptogenic herbs clude in this article: study in which an anti-asthma Chinese herbal medicine has been found to be as effective as a corticosteroid drug. The mechanisms underlying the remarkable effects…are likely a result of synergistic or additive effects of the complex nature of its constituents.” In this article, we review the entire scope of published work on this herbal formula and theorize as to how and why these herbs might restore adrenal function in a wide range of disorders in which adrenal function is compromised. In a companion article, one of the world experts on adrenal fatigue, James Wilson, N.D., Ph.D., distills a lifetime of experience diagnosmay ing and treating hypoa• This formula is now restore adrenal function. The latest findings drenia, which is, he says the subject of a new, “monstrously underalso suggest strong immunotherapeutic NIH-sponsored study at diagnosed.” Finally, in effects of these Chinese herbals. Mt. Sinai investigating a related article, we prowhether steroid-depenpose a completely novel dent asthma sufferers can theory on the pathogenwean off their medications while taking • A single, stunning herb in this for- esis of asthma—a theory which also these herbs. In the original study, this mula, Sophora flavescens proved effec- has implications for the pathogenesis herbal formula not only significantly tive and potent in an open, recently of cancer—and suggest that hyperimproved lung function and clinical published 3-year study of fourteen excitability of cellular membranes symptoms, but increased cortisol pro- chronic, refractory asthmatics, by Ba (due to ion channel activity) may be duction. In contrast, the study found Hoang, M.D., Ph.D., and colleagues, an important trigger of chronic disthat steroids suppressed cortisol levels. in Phytotherapy Research. All fourteen ease. This novel theory gives us a repatients had improved lung function, markable new way of thinking about • According to Dr. Stephen Feig, D.O., clinical symptoms and quality of life, chronic illness, and may explain why who utilizes these herbs in his practice, while reducing or even eliminating at least one of the herbs in this for“In a subset of patients, these herbs their use of inhaled steroids and beta- mula, Sophora flavescens, is so powseems to provide enhanced adrenal agonists without any significant ad- erful and well-tolerated. support that synergizes with more verse reactions. commonly used adrenal glandular Asthma Is a Model for products and with the use of cortisol.” Such a wide spectrum of clinical efficacy suggests that the synergistic Adrenal Dysfunction • “Since February of 2007,” writes power of this formula may help reclinical nutritionist and chiropractor store healthy adrenal function. As the The rate of asthma has tripled in the Linda Li, DC, MS, CCN, who has been Mt. Sinai researchers wrote of these last quarter century. Twenty million in practice for thirty years, “my family herbs, “This is the first well-controlled Americans suffer from the condition, 2 In Focus March 2008 according to the CDC. Asthma is the This formula, dubbed MSSM-002, was ers concluded that the herbal formula third leading cause of hospitaliza- based on a TCM formula used in the was as effective as the potent corticostion among those under 18, reports a pediatric department of the China-Ja- teroid, dexamethasone—without the 2006 article in the New England Jour- pan Friendship Hospital in Beijing to harmful side effects. nal of Medicine. Asthma accounts for treat asthma and bronchitis in children. $16 billion in annual health care costs, Unlike many asthma formulas, this The researchers then “used the conand there are 5,000 visits to the emer- one contained no Ma-Huang, a source cept of traditional Chinese medicine to gency room a day in the United States of ephedrine that has been reported to reformulate several herbal blends into for asthma. At the same time, chronic cause central nervous system stimula- simplified formulas, and tested these use of asthma drugs may be harmful tory activity, increased blood pressure, new formulas,” says senior study researcher Xiu-Min Li, M.D., Associate or even fatal. Steroids are well known and heart palpitations. Professor, Pediatrics and Assistant Proto suppress cortisol and immune funcThe researchers first tested this blend fessor, Center For Immunobiology, at tion. Other asthma drugs, such as Serof herbs in a mouse model of allergic the Mt. Sinai School of Medicine. The event and Advair, have “black box” asthma. Mice were sensitized to an eggformula the researchers found most warning labels because of the higher white protein and then challenged with effective in mice contained three Chirate of deaths tied to exacerbations of it. The mice reacted with allergic asthnese herbal extracts—Ling-Zhi (Ganasthma in patients taking them. And ma including pulmonary eosinophilia, oderma lucidum), Ku-Shen (Sophora according to a 2004 article in the Annals airway hyperreactivity (AHR), and inflavescens) and Gan-Cao (Glycyrrhiza of Internal Medicine, regular use of betauralensis), also known as agonist drugs for asthma Reishi, Shrubby Sophora not only causes tolerance and Chinese Licorice— to the drugs themselves, and was dubbed ASHPatients in the ASHMI group showed but increases airway inMI (anti-asthma herbal flammation compared to increased levels of serum cortisol into medicine intervention). placebo use. The ASHMI formula the normal range demonstrated the same The entire picture of broad spectrum of theraasthma, its soaring numbers, the dangers of drug treatment, creased antigen-specific IgE associated peutic effects on the major pathogenic and the efficacy of selected herbs for with inflammatory cytokines, including mechanisms of asthma. “This formula this condition, may serve as a model IL-4 and IL-5 in bronchial lavage fluids. was almost as effective as the original fourteen herbs, and was the simplest,” for a wide host of conditions marked by low cortisol, adrenal fatigue and In the Journal of Allergy and Clinical Li explains. All three herbs have a long Immunology, they report that treat- history of human use in China and are chronic inflammation. ing mice with this formula “virtually considered to be safe when used acIf we take a closer look at the Mt. Sinai eliminated airway hyperreactivity and cording to TCM practice either alone research, it becomes apparent that it is markedly reduced the total number or in formulas. remarkable for how thorough and ro- of cells and the percent eosinophils in bust its design has been all along. Chi- bronchoalveolar fluid compared with The next Mt. Sinai, NIH-sponsored nese herbs have a long tradition of use the sham-treated group.” Inflammation study was on ASHMI in humans, and in asthma, but well-controlled clinical and mucus were reduced in the lungs was published in the Journal of Allergy trials using herbs for the treatment of as well. Treatment with MSSM-002 and Clinical Immunology in Septemasthma are rare. That is one reason this twenty-four hours after intratracheal ber of 2005. It reported the remarkable antigen challenge of sensitized mice finding that ASHMI was as effective Mt. Sinai research is so notable. virtually eliminated airway hyperreac- as steroids, without suppressing corOf Mice and Men: The tivity and this effect was equivalent to tisol or immune function. This study dexamethasone. MSSM-002 down-reg- included thirteen researchers—eleven Remarkable Research ulated inflammatory cytokines includ- of them physicians—from the Weifang Behind ASHMI ing IL-4, IL-5 and IL-13, all involved in Asthma Hospital, the Weifang School chronic asthma. of Medicine, and the Mt. Sinai School The Mt. Sinai study is remarkable beof Medicine, and was remarkable for cause the researchers followed an un- In comparison, “one of the most poits methodical, careful design. Fortyusually thorough and meticulous de- tent corticosteroids, dexamethasone, five non-steroid dependent individusign over a period of many years. Their also suppressed antigen-induced airals received oral ASHMI capsules and first study, published in 2000, tested a way hyperreactivity and eosinophilic prednisone placebo tablets, and fortyblend of fourteen herbal extracts com- inflammation in this model. However, six non-steroid dependent individuals monly used in traditional Chinese unlike MSSM-002, dexamethasone supreceived oral prednisone tablets (20 milherbal medicine for allergic asthma. pressed Th1 responses.” The research- For more information call 800-545-9960 or visit www.nutricology.com 3 ligrams) and ASHMI placebo capsules for four weeks. Serum cortisol, cytokine and IgE levels were evaluated before and after treatment, as well as symptom scores, side effects and spirometry measurements. Spirometry literally means “the measuring of breath” and is the most common pulmonary function test. The study began with a week-long “run-in period” before initiating treatment. Average daily symptom scores were evaluated during this period to establish a baseline. Beta-agonist inhalation was allowed as needed during the study, but all other medications, such as leukotriene modifiers, antihis- tamines, and either inhaled or intravenous steroids, were prohibited. Symptom scores rated cough, chest tightness, wheezing, dyspnea, night awakening or early morning awakening caused by dyspnea, allergic rhinitis, and beta-agonist use. Lung function was evaluated with a spirometer, Field Report: An Interview with Dr. Linda M. Li on The Ability of Adaptogenic Herbs To Restore Health Note: Dr. Linda M. Li, DC, MS, DABCN, CCN, is a chiropractor and Certified Clinical Nutritionist who has been in practice for thirty years. She has a Masters in Nutrition and is a Diplomate from the American Board of Clinical Nutrition. She practices in both New York City and Boulder, Colorado. Q: Tell us about your experience with the adaptogenic herbs discussed in the Mt. Sinai School of Medicine 2005 study in the Journal of Allergy and Clinical Immunology. A: After I read the study, I was compelled to try the herbs. My experience, both with a close family member and myself, is astonishing. Surprisingly, I soon realized these herbs have a much broader spectrum of application in addition to asthma. Specifically, this formula seems to help support adrenal, kidney, thyroid, liver, female hormone function and overall general metabolism. Q: What was your family member’s experience? A: My relative has suffered from severe adult asthma for over fifteen years. There have been times her attacks were so severe she could barely climb up a flight of stairs. She has been dependent on prednisone, inhaled steroids and bronchodilators to function. Even these medications didn’t always ease her symptoms, and one medication even caused a severe anaphylactic reaction requiring emergency room care. Last year her asthma became refractory and worsened in spite of medication. In fact, she was having undiagnosed allergic reactions to all of her medications, which were causing paroxysmal bronchial spasms that left her choking and gasping for air. Her spirometry tests—a very accurate indication of lung function—were 50% at best. When I read about this herbal formula, I passed along the information immediately. She began to take the herbs, steadily increase the dose, while weaning off her medications. Since February of 2007 she has been off all medications, on twice daily doses of these herbs, and has had no asthma symptoms at all. Q: That’s remarkable. A: My own experience with these herbs is equally remarkable. Over the thirty years that I have been in practice, I have used almost every type of nutritional support for adrenal and associated chronic fatigue symptoms. I suffered from childhood asthma, and in my twenties, a serum blood cortisol test revealed that even then my adrenals were exhausted and my cortisol level was low. I have practices in both New York City and Boulder, Colorado, which requires constant traveling. I have felt exhausted for years and know that my serum cortisol levels are still clinically low. Previously, I needed ten hours of sleep a night in order to function. I have been taking these herbs for ten months now and noticed the energy that I had in my thirties is starting to return. I can now easily get by with eight hours of sleep. No other supplement—from ribose to adrenal extract to adaptogenic herbs—has helped me in this way. I also have had frequent nocturnal urination (every two hours) since my early twenties. I am now able to get five to seven hours of restful sleep without getting up to urinate. For the last fifteen years, after a long day on my feet, my ankles would be so swollen and edematous that I literally could not see my ankle bones. They are now normal even after standing all day. These herbs have clearly helped my adrenal/kidney balance. For the first time in twenty-five years, my weight has decreased (eight pounds lost) even though my exercise program and diet have not changed. In the past, no matter what I ate or how I exercised, my weight always remained the same. Furthermore, the symptoms of my functional hypoglycemia are over 85% improved. Q: Do you have any final thoughts about these particular herbs? A: Adrenal dysfunction is associated with many problems. Health professionals are rightly concerned about the axis of the hypothalamus, pituitary and adrenal glands. These herbs may be an important key to supporting that HPA axis. I truly want to thank you for making such high quality information about quality herbal compounds available. 4 In Focus March 2008 and serum levels of IgE, eosinophils, cortisol and cytokines including IL-5, IL-13 and IFN-gamma were measured. After four weeks both groups showed an equal, significant improvement in symptom scores, pulmonary function and eosinophil levels. In both groups, pre-treatment cortisol levels were slightly below normal, as is common in asthma. However, after treatment, the corticosteroid group showed suppression of the hypothalamic-pituitary-adrenal axis, marked by even more depressed cortisol levels. In contrast, patients in the ASHMI formula group showed increased levels of serum cortisol into the normal range. After four weeks, the prednisone group had significant weight gain, while the ASHMI group did not. The difference between the two groups was statistically significant. were not steroid dependent. In this study our patients are steroid dependent, and we are trying to wean them off their steroids. They really don’t want to be on steroids anymore, and our results will be more significant if, with the use of ASHMI, we can reduce or replace steroids. We are almost finished with our Phase I trial, which included 18 patients, and we will begin our Phase II trial with 60 patients.” How Do These Herbs Work? Individually, these herbs all have a long history of use in asthma and other allergic, autoimmune and immune disorders, allergic rhinitis, hepatitis B, jaundice, adrenal insufficiency, peptic ulcers, and many other conditions. The researchers speculate that these herbs work both individually and synergistically. For instance, the increase in serum cortisol into the normal range was retrospective and all patients gave written informed consent. The quality of life, clinical symptoms and respiratory function improved during all periods of measurement. The use of inhaled corticosteroid and betaagonists were reduced or eliminated. There were no significant adverse reactions reported. It appears that the extract of S. flavescens as an excitatory modulator may be safe and effective for chronic refractory asthma. Within two weeks of starting therapy with Ku-Shen, the patients had reduced daytime and nighttime symptoms of asthma, and had begun to reduce their beta-agonist doses. By three years, all patients were off their corticosteroid medication, had almost entirely eliminated beta-agonist medications, and their symptoms of asthma were significantly reduced. How does Ku-Shen “The relationship between work? Though the plant cytokine imbalance and contains a rich cornuthe expression of both atopy and asthma is of Illnesses treated with corticosteroids would copia of chemicals, the has been on two considerable interest and theoretically benefit from herbal formulas focus principle alkaloids, maimportance,” the researchtrine and oxymatrine, ers note. “A Th1-Th2 imlike that of ASHMI which have been the subbalance has been hypothject of research for years. esized in asthma, with a shift in immune responses away from could be in part due to the glycyrrhizin The toxicity of both alkaloids is very Th1 (IFN-gamma) toward Th2 (IL-4, in Chinese licorice, “which affects the low, and Ku-Shen may contain about IL-5 and IL-13). In a cohort study, pa- conversion of cortisol to cortisone by 2% of these two alkaloids. According to tients with severe asthma exhibited sig- inhibition of 11-beta-hydroxysteroid Dr. Ba Hoang’s theory, these alkaloids nificantly reduced IFN-gamma produc- dehydrogenase enzyme activity.” “act as modulators of membrane excittion in response to allergen compared In addition, previous research has ability…they can decrease body temwith control subjects and subjects with shown that Chinese licorice decreases perature, have a significant analgesic resolved asthma. In addition, all pa- IgE levels. Chinese licorice is a staple effect, have a tranquilizing effect, and tients with asthma…showed increased botanical in TCM for asthma and al- an inhibitory action on glutamate-induced excitatory nerve impulses. They generation of IL-5." Numerous studies lergic rhinitis. confirm that IL-4, IL-5 and IL-13 secre- Ku-Shen, in turn, has been widely can also have an antiarrhythmic effect.” tion is the major driving force behind used for eczema, pruritus and asthma. Glutamate receptors have been found persistent asthma. Ku-Shen is particularly interesting. It in the lungs and airways, and the activation of glutamate receptors has led ASHMI significantly reduced IL-3 and is proving to have therapeutic value to increased airway submucosal glanfor a surprisingly wide range of conIL-5 levels. It also increased human dular secretion. Activation of the gluinterferon-gamma (IFN-gamma), a po- ditions. The impact of Ku-Shen, which tamate receptor might be an important, has excitatory modulator activity, was tent antiviral and immunomodulator, unrecognized mechanism of airway inwhile cortisone suppressed IFN-gam- studied by Ba Hoang and colleagues. flammation and hyper-reactivity, and An open and selective 3-year followma. These findings suggest strong immight explain one of the ways that Kumunotherapeutic effects of the Chinese up of 14 chronic refractory asthmatics Shen helps in asthma. aged between 22 and 70 was used. Parherbal. Now, says Li, “we have an ongoing FDA-approved clinical trial us- ticipants received an extract of Sopho- In fact, Dr. Ba and Dr. Levine proing ASHMI as an investigational new ra flavescens. Medication use, a diary pose a novel mechanism for asthma drug. In the last study our patients card of symptoms, and respiratory in a 2006 article in Medical Hypothfunction were recorded. The study For more information call 800-545-9960 or visit www.nutricology.com 5 eses entitled, “Bronchial epilepsy or broncho-pulmonary hyperexcitability as a model of asthma pathogenesis.” In this separate paper, Ba and Levine have hypothesized that membrane hyperexcitability may reflect a more generalized disease mechanism. In sum, not only are the herbs in ASHMI remarkably effective in asthma, but the increase in cortisol levels and the shift away from inflammatory cytokines toward a balanced immune response, suggests that adrenal and immune function are being restored. This would argue for a far wider use of herbal formulas like ASHMI, in conditions associated with low cortisol, chronic inflammation and adrenal fatigue. Illnesses treated with corticosteroids would theoretically benefit from herbal formulas like that of ASHMI. References: Wen MC, Wei CH, Hu ZQ, Srivastava K, Ko J, Xi ST, Mu DZ, Du JB, Li GH, Wallenstein S, Sampson H, Kattan M, Li XM. Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma. J Allergy Clin Immunol. 2005 Sep;116(3):517-24 Li XM, Huang CK, Zhang TF, Teper AA, Srivastava, K, Schofield BH, Sampson HA. The Chinese herbal medicine formula MSSM-002 suppresses allergic airway hyperreactivity and modulates Th1/Th2 responses in a murine model of allergic asthma. J Allergy Clin Imunol. 2000 Oct; 106(4):660-8. Hoang BX, Shaw DG, Levine S, Hoang C, Pham P. New approach in asthma treatment using excitatory modulator. Phytotherapy Research 2007 Jun:21(6): 554-7 Hoang BX, Levine SA, Shaw DG, Pham P, Hoang C. Bronchial epilepsy or bronchopulmonary hyper-excitability as a model of asthma pathogenesis. Med Hypotheses. 2006 Jun;67(5):1042-51 New CoQH-CF Update TM Ubiquinone and Ubiquinol: Working Hand in Hand S ince we published the article on the new reduced CoQ10-Ubiquinol in our last newsletter (In Focus, November 2007), we have seen some negative, confusing and erroneous reports about Ubiquinol. Because these articles could discourage the use of this breakthrough product by some who might greatly benefit from it, we would like to address a few important points. It’s true that the Ubiquinone form of CoQ10 has more human studies –three decades worth. But this is hardly surprising, as Ubiquinol in stable, oral form is a recent breakthrough. FDA registration as a New Dietary Ingredient was completed just two years ago. Preclinical toxicity studies and clinical studies on Ubiquinol were done in Japan, and initial human and animal studies show that properly formulated oral Ubiquinol is stable and well absorbed, and can remarkably increase plasma levels of CoQ10. Clinicians are already confirming these results, and further studies are underway. Questions have been raised about bioavailability. Given the short time that oral Ubiquinol has been available for study, it is remarkable how much evidence already suggests that Ubiquinol may produce a higher level of bioavailability than Ubiquinone. In fact, studies published in refereed scientific journals indicate that Ubiquinol may provide up to eleven times greater absorption based on resulting plasma levels. As we said in our article, “This is an extremely strong indication that the body needs and wants to assimilate Ubiquinol.” We did confirm that regular CoQ10 is also a significant nutrient, saying: “The importance of CoQ10 (Ubiquinone) should not be disqualified and has nearly 30 years of research and clinical evaluation demonstrating its considerable health benefits and excellent safety profile…”. Each of the forms of Q10 have important metabolic functions. Ubiquinol is an active lipid soluble antioxidant, whereas both Ubiquinone and Ubiquinol are needed for mitochondrial electron transport (cellular respiration). Without the reversible transfer of electrons between Ubiquinone and Ubiquinol, there would be no electron transport in the mitochondrial Electron Transport Chain. Cellular respiration is essential for the maintenance of energy homeostasis, cell growth and development and cell viability. It’s not true that only Ubiquinone is biosynthesized, and Ubiquinol is not. Both are generated naturally in our bodies. Like other redox active cofactors (FAD, NAD), the oxidized forms are biosynthesized first, and the reduced forms (Ubiquinol, NADH, FADH) are biosynthesized via reversible cellular enzymatic systems. In a healthy individual the predominant form of CoQ10 in the plasma and tissues is the reduced Ubiquinol form. Ubiquinone or New Ubiquinol: Which Supplement is Best for Me? In young, healthy individuals, supplemental Ubiquinone follows the digestive path of most lipids; it is first incorporated into chylomicrons, reduced in the small intestine and (Continued on page 11) 6 In Focus March 2008 Diagnosis and Treatment of Adrenal Dysfunction Q&A with James L. Wilson, N.D., D.C., Ph.D. Introduction: Dr. James L. Wilson is as a primary cause, or as secondary to glands (HPA axis). In experimental the bestselling author of Adrenal Fa- the stress of illness itself. It is often the psychology, there is a saying: “The tigue: The 21st Century Stress Syndrome. missing link for the chronically ill pa- hypothalamus rules the world.” This He received his Ph.D. in Human Nu- tient who, no matter what intervention gland is really the four-star-general of trition from the University of Arizona, is made, cannot seem to fully recover. the endocrine system. As the keeper with research in Cellular Immunol- The good news is that recovery from of physiological balance, it regulates ogy, is one of the original founders of adrenal fatigue is not only possible, sleep, weight, satiation, hunger, thirst, the Canadian College of Naturopathic but highly likely with proper treat- and the stress response. The hypothalaMedicine, currently serves as President ment, which includes a sophisticated mus must sense the stress and signal a of Future Formulations, LLC and is on and targeted program of glandulars, response through the pituitary, but the adrenals must provide the hormones the Advisory Board of the American adaptogenic herbs, and nutrients. for adaptation to the Chiropractic Association Council on Nutrition. "Adrenal fatigue is a problem of monstrous stress. Cortisol and the other hormones secreted proportions largely unrecognized by In your book you by the adrenal glands state that hypoadrenia— go to every tissue, gland the medical establishment" or adrenal fatigue—is and organ in the body, in – Dr. James L. Wilson a problem of monstrous direct proportion to the proportions that is total amount of stress largely unrecognized by the medi- Even in illnesses as common as the flu, sensed by the hypothalamus. cal establishment. Even enlightened, if symptoms linger, low adrenal funccomplementary medicine practitio- tion should be considered. For exam- As clinicians, we have seen again and ners often overlook the role of the ple, during the Spanish flu epidemic again the impact stress has on the imin 1919, according to the Archives of mune system. Immune function is proadrenals. Why is that? Internal Medicine, doctors autopsied foundly affected by adrenal activity. One of the major functions of the 126 patients who had died in the flu All white blood cells of the immune adrenal glands is to respond to stress epidemic. Of these, 103 showed adre- system have cortisol receptors that and maintain physiological homeo- nal gland atrophy and shriveling con- modulate the immune response when stasis so that the body can continue to sistent with adrenal exhaustion, and activated. This means that when levels function in a healthy way. These “glands another 3 cases had adrenal hyper- of cortisol are too low or too high, imof stress” must react to every kind of trophy and swelling consistent with mune competence is impaired. stress, including those of physical, emo- a state of extreme stress. The adrenals What are some common tional, psychological, biochemical, hor- were exhausted in their effort to reclinical and laboratory indicators monal, thermal, chemical and biologi- store balance to the body during overof adrenal fatigue? cal origins, and the functioning of every whelming infection, to the point that tissue, organ and gland in the body is their depleted state was physically The daily energy pattern is a key significantly affected by adrenal activ- detectable upon autopsy and signifiindicator. Morning fatigue is one of the ity. But practitioners all too often don’t cantly contributed to their death. That most common symptoms of adrenal is quite remarkable. think seriously about the adrenals. fatigue. People with adrenal fatigue wake up tired despite sleeping for 8 What endocrine glands are When should practitioners look or more hours. Even after they get up involved in the stress response? at adrenal function? they often do not feel fully awake until The major players are the hy- later in the morning, or until they have Adrenal function should be investigated in any chronic illness, either pothalamus, pituitary and adrenal had a caffeinated beverage or some Q: A: Q: A: Q: Q: A: A: For more information call 800-545-9960 or visit www.nutricology.com 7 other stimulant. They usually experience an afternoon low between 2-5 PM, but by about 6 PM or with their evening meal they get a new burst of energy. They may even experience a second wind at about 11 PM and cannot go to sleep until 1-2 AM. Although there are many causes of fatigue, I know of no other cause that produces a fatigue pattern like this. Other common indicators include symptoms of hypoglycemia, a need for caffeine, decreasing ability to bounce back from stress or illness, decreased focus or concentration, decreased libido, and delayed recovery from an acute illness, especially respiratory illnesses. Q: What other markers do you see most commonly in hypoadrenia? A: however, blood levels of circulating cortisol are excessively broad and often do not detect low adrenal function. The ACTH challenge test also misses adrenal fatigue in most cases except those that are very, very severe. in the stress response to achieve deep healing. In contrast, synthetic hormones tend to suppress the function of glands over time, since they override the normal feedback loops that the body uses to regulate hormone levels. The best laboratory test to use is the salivary cortisol test. I recommend a 1 day collection, taken at 4 different times, as a baseline. There are several laboratories that do salivary cortisol testing and it is covered under Plan B of Medicare. During the salivary cortisol test, I also ask the patient to record the date and time of each saliva sample on a separate sheet, what signs and symptoms they were experiencing at the time they gave each sample, their food and beverage intake for that day, as well as any events that may have occurred during that day that might affect their cortisol levels. This information is very useful When I began combining dried glandular extracts I was able to start achieving positive outcomes I had never achieved using them singly. A combination of glandulars that support all the glands involved in the stress response (hypothalamus, gonads, adrenals, pituitary and thyroid) seems to work best. This combination is usually taken 2-3 or more times per day in conjunction with the nutrients and herbs that facilitate proper, healthy adrenal response. Q: What are the key vitamins, minerals and nutrients? I often see recurrent lung and bronchial infections when there is adIt’s important to provide all the renal fatigue. Because nutrients that are used the adrenal glands help in the adrenal cascade of regulate the sodium and Adrenal fatigue is common in fibromyalgia, hormone production. For potassium balance, esinstance, the adrenals use chronic fatigue syndrome, rheumatoid pecially during stress, a vitamin C than any arthritis, autoimmune disorders, asthma, more craving for salt is often a other organ or gland in clue to low adrenal functhe body. It is the only tisand other serious illnesses tion. People with adresue I know of that can acnal fatigue have difficulty producing tually store small amounts of vitamin to help me to more accurately interpret adequate cortisol levels, and as a result C for short periods of time. During any the test results. they also often suffer more from allerstress, the demand for vitamin C skygies, chemical intolerances, environ- I also test for the other steroid hor- rockets. The problem for people with mental sensitivities, and poor wound mones with the same test kit, including hypoadrenia is that they tend to be too healing. Patients also often complain DHEAS, progesterone, estrogen and acidic, and regular vitamin C (ascorbic of a general feeling of unwellness. testosterone in order to more compre- acid) is also acidic. So when people sufhensively interpret the test and provide fering from adrenal fatigue take ascorAdrenal fatigue is often associated with bic acid, their bodies try to neutralize adequate treatment. chronic illnesses. The chronic illness the acidity by drawing on the circulatitself is a large stress physically, emoWhat are the mainstays of treatment? ing magnesium or calcium stores. This tionally and psychologically, and is ofreduces the amount of magnesium and The combined use of certain dried ten accompanied by social and somecalcium available to the tissues of the times lifestyle changes that contribute glandular extracts, and highly targeted, body. This is especially bad for people additional stress. Not surprisingly specific vitamins, minerals and herbs with adrenal fatigue because they are then, I find adrenal fatigue common in the correct form and amount, accom- almost universally deficient in magnein patients suffering from chronic ill- panied by lifestyle improvements, has sium and often deficient in calcium. I nesses such as fibromyalgia, chronic fa- been the best way I have found to help suggest a buffered vitamin C, prefertigue syndrome, rheumatoid arthritis, patients with adrenal fatigue. Glandu- ably one using mineral ascorbates. autoimmune disorders, asthma, cancer, lar extracts contain nucleic acids and nutrients in a concentrated form that Pantothenic acid is another nutrient AIDS, and other serious illnesses. provides all the proper building blocks critical to the conversion of glucose into Can you tell us about a few of needed by the glands for healthy func- energy and is needed in abundance as the tests you recommend? tion and hormone production. These a part of acetyl CoA at the beginning of extracts can be utilized by the adrenals the Krebs cycle to make ATP (cellular Laboratory tests are helpful to conand other endocrine glands involved energy). Magnesium is also involved firm the presence of adrenal fatigue, Q: A: Q: A: 8 In Focus March 2008 A: in this process and is often consid- effect on the HPA axis. The ones I have Other herbs such as Ginger and Ginkgo ered to be the “sparkplug” of the cell. found to be most clinically effective in- biloba are also sometimes helpful as Niacin is necessary to many reactions clude the Ayurvedic herb, Ashwagand- ancillary herbs. Ginger root is another that are important in helping the body ha; the Chinese herb, Eleuthero (for- adrenal adaptogen that helps modumake energy. Large amounts of niacin merly called Siberian ginseng); Licorice late cortisol levels, increase energy, and are necessary because niacin is a cofac- root; and Maca. Although there has not stimulate digestive enzyme secretions tor for all NAD and NADPH reactions been a lot of scientific study on Maca for proteins and fatty acids. Ginkgo leaf critical for several steps in the adrenal in adrenal function, the other three is a powerful antioxidant that sequescascade. Up to 150 milligrams of nia- herbs are well known adaptogens. Lic- ters free radical production, protecting cin may be needed the adrenal glands daily. The entire B which suffer tremencomplex is essential dous oxidative stress Recovery from adrenal fatigue is not only in varying quantities when producing exthroughout the adre- possible, but highly likely with proper treatment cess cortisol during nal cascade, but they the stress response. must be balanced Ginkgo also contains with each other properly in order to orice, in particular, helps keep cortisol several bioflavonoids that improve adequately support adrenal function. in its active form. Ashwagandha is an blood flow, and it has been shown to Organic trace minerals, such as man- ancient Indian herb with a history of lessen tissue damage from inflammaganese, zinc, selenium, molybdenum, therapeutic use dating back to at least tion and shock. Its unique qualities ofchromium, copper and iodine are also 1000 BC, probably because of its di- ten make it useful in an adrenal recovneeded, and typically have a calming rect beneficial effects on adrenal tissue ery program. effect on the body which can help al- and function. It has been prescribed What else do you recommend? leviate the jittery, exhausted state that as a tonic, is anti-inflammatory, and is some people with adrenal fatigue expe- an Ayurvedic treatment of choice for Lifestyle is important. Try to get rience. The best sources of trace miner- joint inflammation. Some studies have to sleep early, before 10 PM, and sleep als are sprouts, young plants, algae and shown Ashwagandha to be capable of until 8 or 9 AM, if possible. Minimize sea vegetables, and the trace mineral normalizing cortisol levels. Eleuthero stress in your life. Take breaks in which supplements made directly from them. is good for both sexes, and has a wide you lie down, not just sit down – berange of activities that support and re- ing horizontal is more restorative than Use sea salt liberally. juvenate adrenal function. It has been resting upright. Proper nutrition is also You emphasize special herbs in used by Russian deep-sea divers and very important. In every meal or snack supporting adrenal function. Olympic athletes, and by cosmonauts eat a generous amount of protein comfor stress and increased vitality. bined with non-hydrogenated oil or A few herbs have a very beneficial fat and an unrefined starchy carbohydrate. These three together provide the best energy for people with adrenal fatigue. Avoid fruit in the mornings, emphasize alkaline foods, including five or six servings of vegetables daily. Additional salt is usually necessary. Q: A: Q: A: HORMONE Some form of mild, noncompetitive exercise is very useful, even walking. In one study, people in their eighties who simply walked up and down a hall four times a day improved all their physiological functions. ACTION Epinephrine (Adrenalin) Norepinephrine (Noradrenalin) Responds to "Fight or Flight" Situations HORMONE ACTION DHEA; Pregnenolone; Progesterone; Estrogen; Testosterone; Androstenedione Antioxidant; Tissue Repair; Sex Hormone; Balancer of Cortisol; Anti-Aging Function HORMONE Blood Sugar Regulation; Anti-Inflammatory Actions; Immune Response Modification; Heart & Blood Vessel Toning; Central Nervous System Stimulation; Stress Reaction Normalization Cortisol HORMONE Aldosterone ACTION ACTION Regulation of Sodium, Potassium & Fluid Volume Q. Do you have any final thoughts about adrenal fatigue? A. Sure. Successful treatment includes changes in diet, lifestyle, and proper dietary supplements. The most exciting fact is that recovery from adrenal fatigue is not only possible, but highly likely with proper treatment. For more information call 800-545-9960 or visit www.nutricology.com 9 Garum Armoricum : “An Extraordinarily Useful Tool” ® A Doctor Reviews Garum Armoricum® for Depression, Anxiety, Cognition and Stamina “I simply burst out laughing,” recalls in the ocean depths of the Armorican by students who wanted to do a study Thomas Dorman, M.D., board-certified Peninsula in France, as deep as 3000 on nutrition, which coincided with my in internal medicine in both the U.S. feet. These unusual fish have devel- increasing interest in Garum.” and Canada, and author of the classic oped a unique metabolism well suited textbook for physicians on prolothera- to the extreme and stressful conditions Dr. Dorman and researchers at Califorpy, Diagnosis and Injection Techniques in in which they live—a dark, cold, high- nia Polytechnic State University carried Orthopedic Medicine, of the afternoon pressure, oxygen-depleted environ- out a crossover, double-blind study on when a friend told him of the mood- ment. This nutraceutical was originally Garum that was published in 1995 in boosting properties of a supplement discovered by the ancient Celts, thou- The Journal of Advancement in Medicine. made from the fermented entrails of sands of years ago, to improve mood, The study looked at fifty four college fish. “It was called Garum Armori- energy and stamina. It was given to Ro- students between the ages of 18 and 25 cum®.” I said, “That is a funny story man soldiers before long marches into on the assumption that they are an exand of course that’s impossible.” Then battle, and was also used by children, cellent test group because of the anxiDr. Dorman tried the extract, felt much pregnant women and the elderly. Un- ety associated with academic stress. calmer, ran out of his supply, and for- like benzodiazepine drugs, which have Anxiety levels were measured by the Speilberger State Trait Anxiety Invengot about it. “A lady tory (STAI) test, and then who worked for me and the college students were who’d become a friend “I’d have no hesitation to recommend this randomly divided into over the years said to me two groups. Group one supplement to every practitioner from one day, “Dorman, what received three weeks of has happened to you? naturopaths to regular M.D.’s” Garum followed by three You were so nice to work weeks of placebo. Group with and now everytwo received three weeks thing makes you angry.” I realized I’d a dramatic, short-term, anxiolytic efof placebo followed by three weeks stopped taking Garum, and I started fect, Garum, is gentle and without any of Garum. Each three week treatment taking it again. A few weeks later she known side effects, and its nutritional period was followed by a week long said, “Dorman, welcome back, your constituents include proteins, antiwashout. Garum markedly reduced temperament is sunny again.” Now, oxidant nutrients, omega-3 fatty acids, anxiety. However, as Dr. Dorman notes: she had no idea I was taking Garum, at and micropeptides including hypotha“Garum works slowly, you build up to all. I’ve been taking it ever since and I lamic-releasing factors and opioid pepan effective level in about three weeks, often recommend it to anxious or mild- tides. It is a wonderful concentrated and it takes several weeks to wash out. ly depressed patients. For those who whole food supplement. We learned that from our study. Our are chronic worriers, it almost always “I had a private practice physically very washout period was not long enough, works. It’s an extraordinarily useful close to California Polytechnic State so that the group who received Garum tool, and I’d have no hesitation to recUniversity in San Luis Obispo,” recalls first continued to have lower anxiety ommend it to every practitioner from Dr. Dorman, “and was conducting a even on the placebo, because of a slownaturopaths to regular M.D.’s. My own number of research projects in conjuncly declining, residual effect of Garum.” son takes it. He operates a big production with the university. This particular tion line at a factory and his colleagues A second crossover, double-blind report he is the coolest, calmest produc- branch requires that pre-med students study followed, to test the effectiveness complete a research project, and I was tion line engineer they’ve ever had.” already guiding a number of groups of of Garum on weakness and fatigueGarum Armoricum® is an extract from students in research on spinal and ortho- related depression and anxiety, as well a giant blue fish that can only be found pedic medical issues. I was approached as memory and cognitive performance. It was published in The Journal of the 10 In Focus March 2008 European College of Neuropsychopharmacology in 1996. This study clearly demonstrated that Garum could enhance memory and mental clarity, as demonstrated by Wechsler’s Test of Memorization, and Rey’s Test. A positive impact on memory and cognition was particularly apparent in the 45-55 age group. Garum was also beneficial in chronic fatigue. “My patients rave about it,” concludes Dr. Dorman. “Many of my patients come to me with a multitude of health New CoQH-CFTM Update (Continued from page 6) shuttled through the lymphatic system to the circulation. Efficient reduction of Ubiquinone to Ubiquinol occurs during absorption or rapidly after the appearance of Ubiquinone in the blood. As we get older, the ability of our bodies to produce and metabolize CoQ10 declines. We do not biosynthesize as much Ubiquinone, and the ability to efficiently produce the reduced Ubiquinol form also declines. The reasons for this include: increased metabolic demand, diseases, insufficient dietary CoQ10 intake, deficiency of factors required for biosynthesis, gene mutation, oxidative insult, or any combination of these factors. Some reports say this decline becomes apparent around 40 years of age, some as early as 20 with issues, and naturally they worry about these issues. It’s not possible to turn them around and restore their health instantly. My strong clinical impression over the last twenty years is that Garum can help these chronically anxious individuals become people who are able to cope in a rational, calm way with their health issues. Where benzodiazepines have serious side effects, are addicting, and lead to significant withdrawal issues, Garum works better and serves as a useful, safe substitute. I have switched many patients off benzodiazepines successfully by tapering them slowly over six to eight weeks while they take Garum.” slow but continuous decline. The result is less cellular energy, slower conversion to the reduced form and subsequently diminished protection against oxidative insult. ease, neurodegenerative disease, diabetes, cancer, fatigue, metabolic syndrome and many others. Research also shows that conditions of ill health result in decreased ability to reduce ingested Ubiquinone to Ubiquinol. Plasma concentration ratios of Ubiquinol to Ubiquinone are significantly decreased in patients with various pathological conditions (e.g., hyperlipidemia, hepatitis, cirrhosis, hepatoma, coronary artery disease, diabetes mellitus) compared to healthy subjects. Not surprisingly, more and more scientific reports indicate that dramatic decreases in CoQ10 concentrations, mitochondrial dysfunction and increased oxidative stress are associated with the aging process and many age related diseases such as cardiovascular dis- References: 1. Le Poncin M. Experimental Study: Stress and Memory. The Journal of the European College of Neuropsychopharmacology. 1996;6(3): 110. 2. Dorman, T. et al. The Effectiveness of Garum Amoricum (Stabilium) on Reducing Anxiety in College Students. Journal of Advancement in Medicine. 1995; Vol 8(3):193-200. People who are sick or older often need to ingest very large amounts of regular CoQ10 to get benefits, likely because less and less is being converted to Ubiquinol. If such a person is given already reduced CoQ10 (Ubiquinol), then they will also easily get all the Ubiquinone they need. We are confident that as more studies are completed, including studies now underway, more data will further confirm what clinicians are already telling us – the new CoQ10-Ubiquinol is truly a CoQ10 breakthrough. References in November 2007 NutriCology In Focus Newsletter. Questions? Contact NutriCology at 1-800-545-9960. Buy 3 Get One FREE! Contains SEANOL-F extract of Ecklonia Cava • • • • Fibronol & FibroBoost ® ™ Super Antioxidant Packs a Powerful Punch Contains a patent-pending extract (SEANOL-F) derived from a specific species of brown seaweed Ecklonia cava. The polyphenols in SEANOL-F have been found to have antioxidant properties approximately 10 times stronger than green tea polyphenols.* Phlorotannins support the cardiovascular system, brain, metabolism and general health.* May be beneficial for a wide range of health applications because of its powerful antioxidant properties.* * These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. For more information call 800-545-9960 or visit www.nutricology.com 11 + -+-+-+- +-+-+-++-- -+-+ - - -+++ + + - - + + +- + + + How Overactive Membrane + Ion Channels + Influence + Asthma+and Other + Disorders - + -+ + -- It May Be Time To Change: Treat Excitation Not Inflammation + + At first glance, asthma and epilepsy don’t seem to have much in common: one is a neurological disorder, the other a breathing problem. But according to a new model of asthma by Ba Hoang, MD, PhD, Stephen Levine, PhD and colleagues, published in Medical Hypotheses in 2006, asthma symptoms may be viewed as a hyper-excitability condition of the airway that is actually kindled in a manner similar to epilepsy, and can be triggered by a variety of endogenous and environmental factors. This new model goes beyond descriptive studies of inflammatory immune mediators or abnormalities in smooth muscle function, and looks deeper—at dysfunction in the electrical potential of the cell membrane. If this view proves correct, it might provide a novel way of explaining asthma, as well as suggesting new therapeutic approaches. It also may offer insight into the runaway cascade of ill health we see in other chronic conditions. Chronic membrane hyper-excitability leads to its exact opposite, depletion of cellular energy that results in pathology. By reversing cell membrane hyper- excitability, Ba and colleagues suggest, we can reverse chronic inflammation and pathology, and restore cellular health. We already know that ion channels exist in the brain, that when hyperactive can cause neurons to fire abnormally, resulting in, for instance, the seizures of epilepsy. It turns out that these ion channels also exist in the lungs. In fact, a receptor once thought only to belong to the central nervous system—called the N-methyl-D-aspartate (NMDA) glutamate receptor—is present in our lungs and bronchial tubes. 12 In Focus March 2008 + The electrical potential of a cell membrane is a fascinating topic, one that bridges both biology and physics. All cell membranes have electrical potential, activated through ion channels that open and close constantly, letting thousands to millions of ions diffuse down their electrochemical gradient. When a channel switches between a conducting and nonconducting state, this is called gating. These gated channels can be responsive to sodium, potassium, magnesium, chloride, and other molecules. The electrical signal spreads rapidly over the cell and allows almost instantaneous communication to occur. Membrane channels can bind or reject an ion in the most astoundingly brief time intervals—10 to 100 nanoseconds. A nanosecond is only one-billionth of a second. According to Ba & Levine, sodium voltage-gated channels may be involved in the pathogenesis of asthma, and may offer us a deeper understanding of this condition that will help us ultimately provide novel, therapeutic interventions to modify the disease or even achieve a cure. Salt of the Earth: How Sodium and Glutamate Trigger Asthma Sodium-gated ion channels may play a major role in membrane excitability. An influx of sodium is linked to release of the acetylcholine, which results in smooth muscle contraction. Not surprisingly, two sodium channel blockers—lidocaine and phenytoin—have been proven already to be effective anti-asthma agents. Lidocaine is a local anesthetic, anticonvulsive and antiar- rhythmic agent that works primarily by blocking sodium channels and decreasing membrane excitability. Phenytoin is an anticonvulsant and cardiac depressant used to treat epilepsy and arrhythmias. It blocks repetitive firing of neurons by acting on sensitive sodium channels. Ba and colleagues believe that sodium channels contribute to asthma by modulating the neurotransmitters acetylcholine, glutamate, and GABA. In particular, they believe that asthma occurs as a result of hyperactivity of the NMDA glutamate receptors in the airways. Glutamate is an excitotoxin and its action in rat lungs looks very much like asthma. Glutamate increases the release of acetylcholine. Excess glutamate is well known to be linked to loss of neuronal function in diseases as wide ranging as Huntington's, Parkinson’s, ALS, and epilepsy. Excess glutamate has also been shown to directly lead to cell proliferation via inflammation. GABA, in turn, is the main inhibitory neurotransmitter, and like glutamate is also found in the lung. GABA agonists (chemicals that increase activation of GABA receptors) inhibit smooth muscle contraction, anaphylactic bronchospasm, and cough. That means that, just as in the brain, glutamate (excitatory) and GABA (calming and inhibitory) are in flux and move in tandem, so they do in the lung. The hypothesis: the cell membrane is induced into a hyper-excitable state via sodium ion channels, which activates the NMDA glutamate receptor. When it is overactive this provokes hyperexcitability, leading to cell injury and cellular proliferation. In the short run this + + triggers reversible bronchoconstriction and inflammation. In chronic cases, this might lead to thickening of the airway wall and inflammation. This excitotoxic process does much of its damage by triggering excessive production of inflammatory chemicals, and creating a constant high-energy demand and drain that ultimately depletes the cell. This hypothesis may explain why some asthma is so refractory and severe, and unresponsive to beta-agonists or steroids. Are We Treating Inflammation or Excitation? Ba and colleagues believe we should be using an excitatory modulator to calm overexcited cells that may be at the root of asthma. The nutrients magnesium, taurine and glycine, and the ketogenic (high protein) diet are known to be beneficial in epilepsy; for the same reason, they may benefit asthmatics. Magnesium may work by inhibiting calcium, since it has been shown that the excitotoxic action of glutamate may often involve abnormal uptake or intracellular mobilization of calcium ions. The herb Sophora flavescens may be an effective treatment for asthma. Two alkaloids found in the herb—matrine and oxymatrine—are excitatory modulators. Recent research suggests Sophora may neutralize excessive build-up of glutamate and reduce the sensitivity of the excitatory NMDA receptor, potentially inhibiting an important cause of membrane hyper-excitability. The alkaloids in this herb have been found to inhibit glutamate action in a study in crayfish. So perhaps when we think of asthma, we should not think of calming inflammation, but of looking deeper, and calming hyper-excitability of the cell membrane itself, providing an effective, safe treatment that may even allow the cells to heal over time. What About Ion Channels and Cancer? Could the pathogenic changes and uncontrolled proliferation of cancer be linked to cellular hyper-excitability mediated by voltage-gated ion chan- nels? This is what Ba and colleagues suggest in a 2007 paper in the European Journal of Cancer Prevention. In fact, notes Ba, “It has been reported that glutamate antagonists at…glutamate receptor/ion channel complexes limit growth of human cancers….the antiproliferative effect of glutamate antagonists is calcium dependent… the proliferative effect of cancer varies directly with the intracellular calcium levels.” Expression of a specific NMDA receptor and its involvement in cellular proliferation is well known in tumors of neuronal tissues, such as glioma and neuroblastoma. Excessive expression of this receptor has also been seen in prostate, breast and colon cancers. Is it surprising then, that toxic chemicals like formaldehyde and other organic solvents increase NMDA sensitization and stimulate glutamate release? Formaldehyde has already been classified as a human carcinogen by the US Environmental Protection Agency. Exposure to organic solvents also has been associated with a high risk of cancer. If we follow this remarkable line of thought, it becomes evident that channel inhibitory agents like GABA, glycine, magnesium, and essential fatty acids, as well as glutamate-inhibiting herbs like Sophora flavescens, may have a role to play in combating cancer. Perhaps, as Ba speculates, “The most important targets to combat and prevent cancer are eliminating excitatory factors and creating favorable conditions for the body to restore the resting membrane potential.” When normal cells are subjected to the constant stress of membrane hyper-excitability, we may have the preconditions for cancer. The stage may be set by chronic infections, ionizing radiation, toxic agents like solvents and pesticides, and dietary excitotoxins. In addition, nutritional deficiencies in inhibitory nutrients such as magnesium, glycine, and taurine, among others, add to the cellular load. The up-regulation of the cell membrane hyper-excitability triggers a cascade of adaptations that may lead to pathological changes. These might include cell dysplasia, fibrosis, cell death, or cellular proliferation. In fact, according to a 2005 paper in the Journal of Membrane Biology, the last two decades have brought a remarkable increase of published evidence for the role of ion channels in tumor progression. The role of ion channels in both cell proliferation and cell death is extremely complex, say researchers at the University of Tubingen and the University of Salzburg: “Considerable further experimental effort is required to fully understand the complex interplay between ion channels, cell proliferation, and apoptosis.” In sum, if we look beyond tissue inflammation to the cell membrane itself, we may discover that a new model of excitation and inhibition helps us create a powerful and elegant framework for chronic inflammatory conditions like asthma, and perhaps even cancer. In 2005, at the annual meeting of the American Association of Cancer Research, scientist Eyal Gottlieb claimed he had found a hallmark of cancer: bioenergetics. If the bioenergetics of the cell lies at the heart of malignant transformation, ion channel hyperexcitability may be a mechanism. It is with such frameworks and insights, that we begin the journey to truly effective therapeutic breakthroughs. References: Cocco P, Kazerouni N, Zahm SH. Cancer mortality and environmental exposure to DDE in the United States. Environ Health Perspect 2000;108:1-4. Hoang BX, Graeme Shaw D, Pham P, Levine SA. Neuro-bioenergetic concepts in cancer prevention and treatment. Med Hypotheses. 2007; 68(4):832-43. Hoang BX, Shaw DG, Levine S, Hoang C, Pham P. New approach in asthma treatment using excitatory modulator. Phytotherapy Research 2007 Jun:21(6): 554-7 Hoang BX, Levine SA, Graeme Shaw D, Pham P, Hoang C. Bronchial epilepsy or broncho-pulmonary hyper-excitability as a model of asthma pathogenesis. Med Hypotheses. 2006 Jun;67(5):1042-51. Hoang, B. X. Levine, S. A. Pham, P. Shaw, For more information call 800-545-9960 or visit www.nutricology.com 13 D. G. Hypothesis of the cause and development of neoplasms. European Journal of Cancer Prevention. 2007; 16(1):55-61. Ishida M, Shinozaki H. Glutamate inhibitory action of matrine at the crayfish neuromuscular junction. Brit Journal Pharmacology. 1984; 82:523-533. Lang F, Foller M, Lang KS, Lang PA, Ritter M, Gulbins E, Vereninov A, Huber SM. Ion channels in cell proliferation and apoptotic cell death. J. Membrane Biol. 2005; 205(3):147-57. Lynge E, Anttila A, Hemminki K. Organic solvents and cancer. Cancer Causes Control. 1997;8(3):406-19. and Complementary Medicine 2004; 10 (2): 345-8. Rzeski W, Turski L, Ikonomidou C. Glutamate antagonists limit tumor growth. Proc Natl Acad Sci USA. 2001;98:6372-7. 2. Faloona GR, Levine SA.The Use of Organic Germanium in Chronic EpsteinBarr Virus Syndrome (CEBVS): An Example of Interferon Modulation of Herpes Reactivation. Journal of Orthomolecular Medicine. 1988; 3 (1): 29-31. Schonherr R, . Clinical relevance of ion channels for diagnosis and therapy of cancer. J. Membrane Biol. 2005;205:175-184. Energy deregulation: licensing tumors to grow: Science, May 2006;312:1158-1159. Germane Facts About Germanium Sesquioxide: II. Scientific Error and Misrepresentation. The Journal of Alternative 3. Asai K. Miracle Cure: Organic Germanium. Japan Publications, 1980. 171 p. 4. Kumar V, Abbas A, Fausto N. Robbins and Cotran Pathologic Basis of Disease.7th ed. Elsevier; 2004.1552 p. Russian Choice Immune® Superior Immune Support* Developed as an immunobiotic by top Russian scientists in 1980’s. This special strain of Lactobacillus rhamnosus cell wall fragments has demonstrated consistent efficacy over the years as a powerful modulator and booster of the immune system.* Russian Choice GI® A formula with Lactobacllus rhamnousus cell wall fragments with the added benefits of synergistic Chinese herbal extracts to boost energy and support the GI system’s health and integrity.* * These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. In Focus on NutriCology® Editor-in-Chief: Stephen A. Levine, Ph.D. Executive Editor: Jill Neimark Medical Editor: Jeffry L. Anderson, M.D. Assistant Editors: Daniel Milosevich, CN, Diane Raile, CNC and Luba Voloshko, Ph.D. Graphic Design & Layout: Christian Northcott IN FOCUS publishes emerging nutritional science and scientific theories that should not be construed to be conclusive scientific proof of any specific cause, effect, or relationship. The publication is for the educational use of healthcare practitioners and physicians. The articles in the publication are the independent scientific views and theories of the authors. FOCUS takes no position on the views and theories expressed but offers them for candid inquiry and debate. The articles are not intended for use in support of the sale of any commercial product and should not be construed as indicative of the use or efficacy of any commercial product. Emerging science and scientific theories do not constitute scientific proof of any specific cause, effect, or relationship. Copyright © 2007. Allergy Research Group®. 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