Rheumatoid Arthritis, Gout, Pseudogout (CPPD) and Related Health Concerns

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

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Systemic manifestations and related diseases in RA

A number of systemic manifestations are commonly seen in Rheumatoid Arthritis. RA may produce a variety of tissue problems in the lungs, including diffuse interstitial pneumonia, pulmonary vasculitis, bronchiectasis, bronchiolitis obliterans, follicular bronchiolitis, and rheumatoid nodules in the lungs. Past studies of RA patients with chest CT scans showed that almost all RA patients exhibited some type of lung lesion or disease, although a small percentage exhibited significant symptoms and were diagnosed with a serious lung disease. Concurrent autoimmune disorder is not uncommon, and dry eyes, occasional inflammation of the conjunctiva or episclera, dry skin, decreased perspiration, dry vaginal membranes, or a chronic nonproductive cough, may be a sign of Sjogren's syndrome, which occurs in approximately 10-15% for RA patients, more predominantly in women. Peripheral neuropathies, with numbness and tingling, or pins and needles sensation is not uncommon with RA, and carpal tunnel syndrome sometimes occurs when swelling affects this area of the wrist.

Anemia is a common manifestation associated with systemic RA. Typically, the anemia is mild, with a reduced red cell production, normocytic-normochromic (normal shape and color to red blood cells), and abnormalities in iron-binding capacity, high or low ferritin, and low iron concentration. RA inflammatory processes often inhibit production of red blood cells (RBC), or erythropoiesis. Destruction of red blood cells is often increased, producing a high ESR, or erythrocyte (RBC) sedimentation rate. Typically, iron supplement is prescribed in standard medicine, which rarely results in a significant benefit, and often exacerbates gastrointestinal complaints. Complementary Medicine offers an effective treatment protocol for this mild anemia, simultaneously stimulating the kidney-adrenal function to produce erythropoietic hormone, spleen function to more effectively clear poor quality red blood cells from circulation, and provide an array of nutrient chemicals and assimilatable iron to dietary supplementation. Acupuncture is also effective in this protocol, acting simultaneously on a variety of systems to increase physiological efficiency.

Leukopenia, or insufficient production of white blood cells, or leukocytes, is also an important problem that must be addressed in RA systemic syndromes. While the severe manifestation is an enlarged spleen, unable to cope with the lymphatic clearing of old or damaged blood cells, the intelligent patient, with a little understanding, can realize that they do not want this problem to proceed that far. The causes of leukopenia are many, with Lupus, lymphoma, viral infection, and folate deficiency commonly involved. These may all be associated with RA and its underlying mechanisms. Essential mineral deficiencies may also be related to both leukopenia and RA. Harsh immunosuppressant drugs used to treat RA may exacerbate the leukopenia. Once again, monitoring and treating sensibly with Integrative and Complementary Medicine is an important consideration for the patient. The body needs a healthy immune system and production of immune mediating blood cells to keep RA in check.

Another systemic problem that has come to light in recent years is the association of osteoporosis with the mechanisms of Rheumatoid Arthritis. Periarticular demineralization, or loss of mineral deposition in the cartilage and other tissue of the bone coverings at joints is a growing concern. Periarticular demineralization often shows a manifestation at early stages of Rheumatoid Arthritis. Standard analysis of osteoporotic bone mineral density utilizes x-ray technology that measure large bone density at the femur and lumbar spine. Newer digital rediogrammetry (DXR) is now used to measure cortical bone mineral density in the bones of the hand. A study at the Friedrich-Schiller University Institute for Diagnostic and Interventional Radiologie in Jena, Germany in 2004 (cited below) showed that DXR digital x-ray studies revealed an average 21% worsening of bone mineral density between stage 1 and stage 5 of Rheumatoid Arthritis in a randomly selected patient study. Standard bone mineral density studies of the femur and lumbar did not reveal this worsening of the condition. The study also noted the corticosteroid medication used to treat RA was responsible for much of the bone mineral density loss, or osteoporosis, in these RA patients. Other studies have demonstrated the prevalence of deficiency of what we call Vitamin D, which is not a vitamin but a hormone produced by the kidney/adrenal gland, and is an integral hormone in the endocrine feedback system. Hormonal imbalance is thus highly associated with RA. This is also obvious when we see that a majority of cases occur with manifestation in women during the premenopausal to postmenopausal age.

Instabilities of the cervical spine are a growing concern in the medical community with RA patients as well. A 2014 multi-cohort study in Japan, at Kobe University Graduate School of Medicine and various hospitals (see study link below in additional information) showed that over 5 years, accelerated cervical spine instability and compression on the nerve roots and spinal cord (compressive myelopathy) was common, especially when subluxation was noted prior to onset of moderate to severe RA symptoms, and corticosteroid treatment incorporated into drug protocol was an indicator for poor prognosis. Obviously, treatment of the cervical spine, with such therapies as soft tissue mobilization, myofascial release, neuromuscular reeducation, chiropractic treatment, targeted stretch and exercise, and acupuncture, could greatly reduce the risk for this serious consequence of Rheumatoid Arthritis. A prior study of this problem at Kobe University Graduate School of Medicine (PMID: 22895480) found that 43.6 percent of patients followed over 5 years developed cervical instabilities, that severe symptoms occurred in 12.9 percent of patients, and decreased spinal cord canal space (SAC) was seen in 4.3 percent of patients. Conservative care of the cervical spine is shown to be very important in the treatment protocol.

The biggest worry in systemic disease associated with RA, though, is cardiovascular health. Numerous studies show that life expectancy for patients with RA is reduced, primarily due to deteriorating cardiovascular health. Pericarditis and pulmonary vasculitis is the manifestation of a systemic vascular inflammatory state, which creates atherosclerosis, or stiffening and thickening of arterial walls. This problem should be addressed with Complementary and Integrative Medicine, which offers a wide variety of treatment protocols to both address underlying causes and improve current cardiovascular health. Standard medicine utilizes drugs to control hypertension and high cholesterol, but these measures are not the key to cardiovascular health, as more recent research demonstrates. More important cardiovascular markers include C-reactive protein and high homocysteine levels in circulation, which indicate that the body is struggling to cope with excess systemic inflammatory processes and oxidant stress. The only successful way to treat these problems is with a comprehensive holistic treatment protocol, and much research in recent years has delivered the objective data for the Complementary Medicine physician to utilize an array of herbal and nutritional chemistry to achieve realistic goals.

An array of therapeutics supported by sound research is now utilized in the treatment of Rheumatoid Arthritis in Complementary and Integrative Medicine

The various herbal and nutrient medicines utilized by the Licensed Acupuncturist and herbalist today in the treatment of Rheumatoid Arthritis is more extensive than this article can handle. The key therapeutic products are introduced and explained here. Of course, a disease like RA is complex, and a full understanding of the medicines is thus also complex. Trust in the knowledge of the physician is thus important. A variety of effective therapeutics is also available to the Licensed Acupuncturist to help with the health problems associated with Rheumatoid Arthritis, and an individualized protocol which integrates various therapeutics, especially acupuncture and physiotherapy, in a synergistic and comprehensive strategy will produce superior outcomes.

Various chemicals in Chinese herbs are shown in scientific study to reduce the inflammatory cytokines that are known to be in excess in RA. Scopoletin is a chemical found in various Chinese herbs (e.g. Ding gong teng, Bai zhi) that is shown to reduce excess cytokines IL-6, VEGF, and FGF-2 in synovial tissues. Traditional Chinese formulas formulated to treat Rheumatoid Arthritis utilize these herbs and combine them with various support herbs to achieve a broad effect. Numerous studies of various Chinese herbs have affirmed the physiological mechanisms that explain the beneficial effects in the treatment or RA and other autoimmune inflammatory diseases. Research is advancing to human clinical trials worldwide with a number of these herbs.

Triptolyde in the Chinese herb Lei gong teng, or Trypterygium wilfordii, has been proven effective in the treatment of Rheumatoid Arthritis in human clinical trials in the United States and Europe. Some of the extensive studies of these herbal chemicals is cited below in additinal information at the end of this article, with links to the study summaries on the NIH database PubMed. Triptolide has been found to inhibit collagen degradation induced by excess fibroblasts in RA synovial tissues, by downregulation of the expression of key inflammatory enzymes called matrix metalloproteinases. An array of physiological effects of such herbal chemicals is proven to have positive effects on controlling the many disease mechanisms in RA. By combining herbs in therapy, the overall effects provide the patient with not just one allopathic effect to curb disease expression, but with an array of effects that can successfully address the many pathophysiological aspects of the disease.

Alkaloids in the Chinese herb Han fang ji, or Stephania tetrandra, have been shown to inhibit key pro-inflammatory cytokines involved in Rheumatoid arthritis, such as IL-1, IL-6, and TNF-alpha. Alkaloids are best extracted with alcohol, and a tincture may be the best form of this herbal medicine.

Study in recent years is proving that specific acupuncture and electroacupuncture treatments also significantly modulate the key inflammatory pathways in Rheumatoid Arthritis, and a number of scientific studies are cited and linked in additional information. Short courses of electroacupuncture and acupuncture, with 2-3 treatments per week for 4 weeks, is proven to modulate a number of immune pathways to improve treatment efficacy. Such therapy combined with studies herbal and nutrient medicine delivers a proven safe and effective treatment protocol to enhance the effects of standard therapy. For patients unable to tolerate standard drugs, or that have not yet reached a severity of disease warranting these harsh drug therapies, this type of TCM therapy could be especially effective. The only side effect to such treatment is better overall health, and when combined with direct soft tissue mobilization, or Tui na, could provide amazing benefits with only short courses of therapy repeated every few months.

With the advance of sound research into herbal chemicals, a wide variety of articles are produced by the pharmaceutical industry to warn of potential drug interactions and ill effects. One notes in these articles the use of the word theoretical in all of these warnings, and the lack of substantive clinical ill effects and problems with drug interactions. So far, some herbs are found with measured toxicities at higher dosage, but these problems are integral to the professional study of herbal medicine. The science of toxicities, potential problems with herb-herb and herb-drug interactions, etc. are, of course, an important part of professional herbal study. The Licensed Acupuncturist is one of the only medical professionals that receives a thorough herbal medical training in the United States in approved medical colleges. The safety of such professional herbal prescription is demonstrated in the lack of malpractice cases against the profession, and the very low cost of malpractice insurance. Such professional herbal prescription is very dependable.

Nutrient needs are great as the body tries to control of reverse the tissue degeneration in Rheumatoid Arthritis. A decade of study at Harvard Medical College has produced a usable source of Collagen Type 2 that was proven in clinical trials to increase tissue repair in human trials with both Rheumatoid and Osteoarthritis. This patented extract is unlike standard collagen supplements or the glucosamine and chrondrotin supplements now widely used. It is available in the patented form as Collagenex2, from Health Concerns, a professional herbal and nutrient supplier of TCM physicians in clinical practice. This specific type of coated natural collagen extract was proven in studies at Harvard to eventually supplant the collagen in the joint tissues of Rheumatoid arthritis patients that the autoimmune reaction targeted, and significantly benefited patients in human clinical trials after 3 months of use. The patient must be aware that relief of symptoms are not expected soon after taking this supplement, but after extended use.

Serratiopeptidase, or Serrapeptase, is one of the super enzymes discovered in Asia shown to effectively clear protein fragments from tissues in the body. It is derived from the gut of the Chinese silkworm and has undergone extensive human clinical trials in Japan and China. Proteolytic enzymes have long been studied and found to be effective to reduce arthritic pain. European studies long ago showed that the effects of proteolytic enzymes over time produced more effective pain relief than standard pharmaceutical pain medications, even opiates. These enzymes are combined with herbal tree resins, such as boswellia and olibanum, from the Frankincense and Myrrh trees, which have long been prized for there tissue repairing effects, in Chinese herbal formulas. Nattokinase is another potent proteolytic enzyme from treated soy bean that is often combined with serrapeptase to treat blood clotting and fibrin accumulation. Since these medicines are blood thinning, professional herbal guidance is important in therapy. The use of short courses of serratiopeptidase and natto kinase may not only aid the joint tissues in RA, but treat associated health problems, such as fibrosis in the lungs and other organs.

Sea cucumber is an ocean vegetable long prized in China for the treatment of Rheumatoid arthritis. Extensive studies have shown that quality sea cucumber species contain collagenase inhibitors (chemicals to inhibit the enzymatic breakdown of joint tissue collagens), EPA (an important omega-3 essential fatty acid useful to improve inflammatory modulation), proanthocyandidins, and other beneficial fatty acids to help treatment of inflammatory dysfunction.

Nutrient chemicals found to help the body reduce advanced glycation endproducts (AGEs) and the receptors for AGEs, may also be an important therapeutic tool to prevent and treat Rheumatoid Arthritis. These chemicals are combined in various nutrient formulas, such as AGEBlock from Vitamin Research. A full explanation of this strategy is given next in this article.

Inositol hexaphosphate (IP6) is another nutrient chemical that may be important as an adjunct treatment in Rheumatoid arthritis. This chemical was discovered to reduce excess angiogenesis in cancerous tumors, and this was applied as a potentially effective therapy in RA. In addition, IP6 has been found to reduce microbial parasites that infect red blood cells in various diseases, a subject that is being explored as one of the explanations of the autoimmune reaction in RA. Studies cited below also show that IP6 reduces VEGF and bFGF, 2 significant growth factors that are found to be overexpressed in synovial tissues of RA patients. VEGF, a signal protein produced by cells, stimulates increased growth of blood vessels, which is directly related to the degree of tissue and bone degeneration in joints affected by RA. While stimulation of VEGF in adherent cells is due to decreased oxygen, studies have shown that hypoxia was not responsible for stimulation of excess VEGF from platelets and the white blood cells, neutrophils, eosinophils and basophils, which is stimulated by increased heat and acidosis. IP6 in conjunction with a clearing of blood heat (indicated by CRP on blood tests) and systemic acidosis, may be the most effective treatment for reducing angiogenesis in RA.

Curcumin is an herbal chemical found in a variety of Chinese herbs that inhibits IL-18, a key cytokine that stimulates VEGF, the growth factor responsible for the excess angiogenesis associated with the degree of synovial degeneration in RA. Curcumin is found in the herbs E Zhu (Curcuma zedoaria) and Yu Jin (Curcuma aromatica), as well as in JIang Huang, or Turmeric. Optimized curcumin is a product discovered in research that utilizes a lipid membrane to keep the curcuminoids from breaking down too quickly in the digestive process, delivering an optimized dosage to blood circulation.

Omega-3 essential fatty acids, found in high concentration and balance in krill oil, have been shown to be helpful in treating Rheumatoid Arthritis by affecting excess of antigen-presenting cells by the Major Hisotcompatibility Complex (MHC) and Human Leukocyte Antigen (HLA) portions of the complement immune system. These genetic codes largely determine what the immune system needs to attack and what is normal to the body. Studies in 2000 at the Institute of Food Research in the United Kingdom found that key fatty acids EPA and DHA in krill oil modulate the expression of HLA-DR, and inhibit expression, but only on activated monocytes, explaining the positive effects in controlling symptoms of Rheumatoid Arthritis.

Of course, as this article implies, there are a variety of actual health concerns in Rheumatoid Arthritis, and these may also be treated by the Complementary Medicine phsyician with various treatment strategies and products. Not all of these treatments need to be used for each individual, and many of these treatment protocols can be used over time. The patient can discuss these treatment options with the physician and come up with a mutual proactive treatment strategy that fits individual needs and cases. Treatment over time can utilize a number of helpful herbs, nutrient medicines, acupuncture, physiotherapies, and even helpful advice on self-administered therapies, dietary changes and stress reducing activities. The holistic therapy in Traditional Chinese Medicine has much to offer.

Research into systemic or holistic pathological processes reveals both the need for holistic Complementary and Integrative Medicine (CIM), and provides the Complementary physician access to new specifics to aid therapy. Evidence-based therapies in Traditional Chinese Medicine have increased dramatically each year in the last decade.

The pathophysiological roots of chronic disease is an important subject for integrative Complementary Medicine. In Traditional Chinese Medicine, ancient physicians formulated many theories of the roots of disease, and emphasized that both the root and the branch, or symptomatic manifestation, of these diseases must be addressed in therapy. Translation of this concept into modern integrative models is a complex and difficult task, but one that is vitally important to the progress of TCM as an integrative medicine. The most important research advance to this task is the discovery of AGEs (advanced glycation endproducts) and the way that excess AGE in our bodies will generate excess receptors (RAGEs) that react to a host of chemical ligands, immunomodulators, hormones, neuropeptides, etc. This excess accumulation is a key factor in aging processes, neurodegenerative disease, atherosclerosis, diabetes, metabolic syndrome, chronic kidney failure, heart disease, cancer, etc.

Recent research has linked AGE accumulation to chronic inflammatory diseases such as Rheumatoid Arthritis. AGEs, RAGE, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin are expressed in an overlapping manner in human inflamed rheumatoid synovia according to researchers at Columbia University, the University of Siena in Italy, and the G. d'Annunzio University in Italy, who jointly researched this important disease mechanism under the guidance of the CNR Institute of Clinical Physiology in Pisa, Italy (see study link below). Since atherosclerosis and diabetes, two common diseases also highly associated with Rheumatoid Arthritis, are also explained by the mechanisms of AGE accumulation and excess AGE receptors, this may be an important discovery in explaining the elusive pathophysiology of Rheumatoid Arthritis. E-selectin is an adhesion molecule that is associated with the large population of macrophages in the synovial joint tissues in RA. E-selectin is also enhanced in vascular linings (endothelium) in atherosclerosis, and may be the link between RA and atherosclerosis. Numerous studies have linked E-selectin to vascular risk factors in all subjects, and activation of endothelial cells that produce this excess of E-selectin is thought to be stimulated by excess AGEs and RAGE. Excess E-selectin is also noted with atherosclerosis related to pregnancy and insulin resistance, implying that hormonal changes are involved. Vascular cell adhesion molecule-1 (VCAM-1) is also highly associated with the formation of atherosclerosis, and exposure of human cells to AGEs has been shown to induce VCAM-1. Such research presents a definitive link between excess AGEs and RAGE and the onset of RA.

Glycosylation is the enzymatic process that links saccharides to produce glycans, or polysaccharides (carbohydrates), to proteins, lipids, or other organic molecules. This process produces many of the essential cellular components in our bodies. The majority of proteins synthesized in the cell endoplasmic reticulum, which regulate our cellular processes, undergo glycosylation. Proteins are the large products of RNA expression, combining amino acids in such a way as to express the functional commands and produce the products that our bodies need to function in a healthy homeostasis. The glycosylation products insure that these proteins fold and unfold properly, are stable, adhere to other cells, etc. AGEs are glycosylation endproducts that are not properly regulated by enzymatic regulation, and may be a key component of disease processes. Our modern world has changed the fundamental nature of our foods with technology, and our bodies have a long way to go to adapt to these changes.

Research has also uncovered the fact that a number of modern stressors have been created that increases the pathological effects of excess AGE and RAGE in our bodies. These include the increases in oxidants from both physiological stress and our environment. As the array of common chronic diseases advance in our bodies, so too does the ill effects of AGE accumulation and RAGE expression. This is the catch-22 of chronic disease. What we need to discover is a holistic plan to reverse this pathological process that incorporates improved public dietary health, decreases in environmental stressors, prevention of chronic common disease processes, and restoration of a healthier and more natural physiology. A simple plan of inventing new allopathic pharmaceuticals to block the production of AGE and negate RAGE expression will not be effective enough. Medical doctors must look outside the box and incorporate an integrative and holistic approach to have an appreciable effect on this root process of common chronic disease.

AGEs are one example of a pathological process that can be reversed and prevented effectively with a medical protocol that is inclusive of Complementary Medicine. The first significant attention to these metabolites occurred with the pharmaceutical focus on new diabetic or metabolic therapy and testing. The A1C index is now a universal test to accompany circulating blood sugar and triglyceride levels to evaluate and treat Metabolic Syndrome, which is still unfortunately referred to as type 2 diabetes. A1C is the nonenzymated glycated product of the hemoglobin beta-chain at the valine terminal residue, and excess indicates a complex metabolic dysfunction of unregulated sugar and protein coupling that leads to many of the health risks in metabolic syndrome. While a pharmacological allopathic approach has produced the glitazones Actos and Avandia to lower the A1C index, these drugs have produced alarming systemic side effects that have prompted stern FDA warnings in 2007 of increased cardiovascular risk. The drugs also produce weight gain, water retention, anemia, inhibition of steroidogenesis and androgen production, and in a 5 year efficacy study, the various metabolic drugs failed in 15-34% of cases.

The research that has resulted from these pharmacological studies has opened a pandora's box of information related to unhealthy metabolism and its consequences on public health issues. AGEs are now implicated as a root disorder in the etiology of diabetes, metabolic syndrome, atherosclerosis, heart failure, age-related diseases, neuroendocrine disorders, and possibly cancer. These metabolic endproducts appear to relate to neuroendocrine receptors in most organ systems in our bodies, and require a robust oxidative and immune metabolism to counter ill effects of excess. The food industry has gravitated toward processed foods that are high in these AGEs, and also stimulate endogenous production, while inhibiting the essential nutrients needed to counter the ill effects. What we see here is a scientific explanation of a holistic approach to pathology.

"Advanced glycation end-products (AGEs) are molecules formed during a non-enzymatic reaction between proteins and sugar residues, called the Maillard reaction. AGEs accumulate in the human body with age, and accumulation is accelerated in the presence of diabetes mellitus. In patients with diabetes, AGE accumulation is associated with the development of cardiac dysfunction. Enhanced AGE accumulation is not restricted to patients with diabetes, but can also occur in renal failure, enhanced states of oxidative stress, and by an increased intake of AGEs. Several lines of evidence suggest that AGEs are related to the development and progression of heart failure in non-diabetic patients as well." Department of Cardiology, Thoraxcenter, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands. j.w.l.hartog@thorax.umcg.nl

Scientific study of advanced glycosolation endproducts represents a field of research that points to a need for a holistic approach to a number of serious health problems. Not only age and diabetes associated heart failure, but atherosclerosis itself has been linked to excess AGE and AGE receptor stimulation. Complementary medicine must play a large role in the standard of care devoted to normalizing homeostasis and decreasing excess production of AGEs, as well as providing reliable dietary information to decrease excess intake in the diet, reducing oxidative stress, and insulin resistance. Simply applying pharmaceutical drug therapy to block excess production of these endproducts of normal sugar metabolism is unwise and may engender excess health risk greater than benefit for many patients. Use of Complementary Medicine has shown promise as an adjunct therapy to pharmaceutical drugs in this realm, as a reducer of risks from side effects, and as a first line conservative care for patients with less risk.

AGEs have been implicated in the formation of atherosclerotic plaque independant from a diabetic state. AGEs have also been implicated in health problems associated with aging, and probably future research will implicate this unhealthy metabolic mechanism in many chronic diseases affecting our population. The problem involves a combination of dietary habits, unregulated processed foods, environmental stresses, increased oxidative stress in the population, decreased immune efficiency, metabolic dysfunction, insulin resistance, hepatic and renal dysfunction, and normal aging, all of which may contribute to a significant cause of the most threatening chronic health problems in the United States today.

"The normal aging process is often accompanied by arterial wall stiffening and by a decrease in myocardial compliance. These processes contribute to isolated systolic hypertension and diastolic heart failure, which lead to substantial morbidity and mortality among older individuals. Patients with diabetes manifest arterial stiffening and diastolic dysfunction at a younger age. This leads to the concept that the mechanism that underlies changes in vascular mechanical properties during aging is accelerated in diabetes. The Maillard reaction or advanced glycation of proteins occurs slowly in vivo with normal aging and at an accelerated rate in diabetes. Advanced glycation end-products (AGEs) that form during the Maillard reaction are implicated in the complications of aging and diabetes. The formation of AGEs on vascular wall and myocardial collagen causes cross-linking of collagen molecules to each other. This leads to the loss of collagen elasticity, and subsequently a reduction in arterial and myocardial compliance. Aminoguanidine, an inhibitor of AGE formation, is effective in slowing or preventing arterial stiffening and myocardial diastolic dysfunction in aging and diabetic animals. In aged and diabetic animals, agents that can chemically break pre-existing cross-linking of collagen molecules are capable of reverting indices of vascular and myocardial compliance to levels seen in younger or non-diabetic animals. These studies suggest that collagen cross-linking is a major mechanism that governs aging and diabetes-associated loss of vascular and cardiac compliance. The development of AGE cross-link breakers may have important role for future therapy of isolated systolic hypertension and diastolic heart failure in these conditions." Department of Cardiology, Rambam Medical Center, POB 9602, Haifa 31096, Israel. d_aronson@rambam.health.gov.il

Aminoguanidine is a chemical inhibitor of nitric oxide synthase. Recent research has shown that this pharmaceutical does not inhibit AGE formation, as was believed. Scientific data is available at the end of this artilce in additional information, with links to study summaries. Herbal chemicals that achieve this same inhibition of inducible nitrix oxide synthase include wogonin, baicalin, and baicalein from the Chinese herb Huang qin, berberine from Huang bai, and polydatin from Hu zhang. Studies at Taipei Medical University found that these herbal chemicals effectively inhibited nitric oxide production without directly effecting the inducible nitric oxide synthase enzyme activity, and without noticeable cytotoxic effects on the cell. Alone, or as complement to chemical iNOS, Huang qin presents a dose-dependant treatment to effectively block the effects of excess AGE on arteries and heart muscle. Fang feng is another studied herb found to inhibit nitrite production. Imperatorin and deltoin from this herb were found to be potent NO production inhibitors via inhibition of nitrite production, as well as inhibition of the expression of iNOS protein.

These herbs not only inhibit excess nitric oxide production, one of the harmful endproducts of AGEs, but exert potent antioxidant activity, lower cholesterol, inhibit harmful prostaglandins and COX-2 enzyme, and lower blood sugar. The herbs, unlike synthetic pharmaceuticals, often have a modulatory effect, with a host of chemicals in the herb that protects the body from excess effects. These modulatory approaches are important, as inducible nitric oxide synthase has beneficial effects as well as toxic effects in our bodies, inducing healing of skin and intestinal mucosa, killing of certain bacteria, regulating of T-cell proliferation and differentiation, and control of leukocyte recruitment.

A host of Chinese herbal chemicals have been studied as potent inhbitors of nitric oxide synthase. Nitric oxide production by inhibition of nitrites was found to be an activity of angelicin, pimpinellin, sphondin, byakangelicol, oxypeucedanin, oxypeucedanin hydrate, xanthotoxin, and cnidilin, from the Chinese herbs Bu gu zhi, Bai zhi, Bai xian pi, and Chuan xiong.

When clearing bitter herbs, or circulatory herbs, are not used, scientific research has found tonic herbs that also inhibit excess AGE formation. Huang qi, astragalus, was found to inhbit AGE formation and exert significant antioxidant activity.

Such research as cited in this article points to importance of using a variety of treatment modalities in Complementary Medicine to prevent disease associated with AGEs. Research shows that metabolic syndrome, commonly called type 2 diabetes, which now affects a high percentage of our youth, and accounts for more than 60% of health care expenditure on patients under the age of 15, accelerates the effects of harm from excess AGEs. The first step in reducing harm from excess advanced glycation endproducts, and preventing harm from cardiovascular problems, diabetes and metabolic syndrome, is to decrease dietary intake of these molecules.

These herbs and herbal mechanisms are also useful in the treatment of Rheumatoid Arthritis. As stated, one of the key biomarkers recently discovered for diagnosis of RA is an autoimmune antibody to citrinullated protein peptides (ACPA). These peptides in citrinullation occur when the amino acid arginine is broken down. Arginine is a key amino acid in the triggering of nitric oxide production in the inflammatory process. There is a strong link between the COX-2 inflammatory stimulation, excess nitric oxide production, and reduced clearing of excess oxidants and protein fragments and the mechanisms of Rheumatoid Arthritis. The science is confirming the efficacy of traditional herbal strategies in the treatment of autoimmune arthritis.

Nutritional medicine to reduce excess AGEs

Scientific study has found that a number of healthy nutritional supplements and herbal chemicals help to reduce AGE (advanced glycoylation endproducts). P5P, the active form of Vitamin B6, helps inhibit AGE formation and platelet clumping. Vitamin B1 thiamine, and the metabolite of thiamine, benfotiamine, both protect cells from excess AGE, and inhibit superoxide radicals and excess inflammatory mediators called nuclear factors (NFKbeta). There are many different antioxidants, and some of them are particularly effective in inhibiting AGE formation and accumulation. These include L-Carnosine, N-acetyl cystine, and alpha-lipoic acid (ALA). Of course, dietary changes, such as eating less simple carbohydrates, or refined foods, and more real whole grains, fresh vegetables and whole beans and legumes, will also help.

Dietary sources of advanced glycation endproducts or AGEs

The most significant source of these harmful AGE molecules is found in processed foods. High fructose corn syrup is the most common commercial sweetener and contributes heavily to AGE in the diet. This is because high fructose corn syrup is a more reactive acyclic form of fructose that induces greater AGE fluorescence compared to glucose. Commercial baked goods, snacks, and many processed foods are also a big dietary source of AGEs. A variety of baked goods and processed foods are made with proteins cooked with sugars in the abscence of water. Proteins are found in most food sources, not just meat, and when the cooking or preparation of these foods is accomplished with little water, the sugars bind to the proteins and form excess AGEs. This type of processing is used in commercial food production to save money and extend shelf life, as well as to produce sweeter foods. Carmelized foods are one example, as are grilled and charred commercial meats, such as hamburgers. Fastfood that is grilled or barbecued with a commercial sauce is particularly high in AGEs, as is meat that is breaded and fried. French fries would be a good example of a mixture of potato protein with added commercial sugar, fried in the abscence of water. Often commercially processed, or cooked, foods will utilize fructose or dairy sugar (galactose), which undergoes glycation at a rate of about 10 times that of glucose. Products made in small quality bakeries and restaurants often use old fashioned sugar, honey or maple syrup, and food preparation is often natural and healthy. Investing a little more money in your food may save your life down the road. Avoidance of commercially prepared foods or attention to the label contents will help reduce dietary AGEs drastically.

Healthy and intelligent choices in your diet help in three ways. One, you take in less of these harmful AGEs, two, the healthier dietary choices help insure that your body, especially your liver, does not produce an excess of AGEs, and three, your body is nourished properly with essential nutrients needed to clean up these excess endproducts of glycosolation. In times of increased oxidative stress, healthy foods that help with antioxidant cleaning are important. Diet is not the only concern here, though, improved function of the liver and kidney systems, improved metabolism, and reversal of diabetic or metabolic dysfunction is also important. Acupuncture, herbal formulas, and nutrient medicine may all help in this regard. Today, scientific evidence helps the physician choose the right evidence-based medicine to take care of these specific problems.

Many patients may make healthy choices in diet changes and tell themselves that they are now immune from dietary harm. This is not necessarily the case, and attention to healthy dietary education is always valuable. Vegetarian diets do not guarantee health in this regard. Vegetarian diets with high fructose intake, or chronic deficiency of lysine and lack of balanced protein may also lead to excess AGE production and accumulation. AGEs are produced in the body as an endproduct of a non-enzymatic reduction of carbohydrates with lysine side chain molecules and N-terminal amino groups of macromolecules, and a lack of lysine, poor and unvaried sources of protein, and a problem with enzyme metabolism may contribute to excess AGE accumulation. As stated, fructose is a carbohydrate that is more difficult to process in AGE metabolism. Excess intake of sweeter fruits, sweet fruit juices, and dried fruits in the diet may also contribute to an excess fructose intake. Apples, for instance, are often very high in fructose compared to glucose content. A choice of fruits that are less sweet, and care in controlling excess consumption of sweet fruits, especially with juices and dried fruit is important. Even though our palates are trained in the United States to desire sweet foods, acquiring a taste for foods that are sour, pungent and bitter are important to a healthy balanced diet. These various tastes occur in foods because they are high in various important nutrients. A person concerned with health will work to change their appetite by acquiring a natural desire for these types of foods.

Some helpful tips in your diet to reduce excess AGEs include increased comsumption of slightly bitter green leafy vegetables, boiling, steaming, lightly sauteing, or braising, instead of using high heat and dry frying. Cooking meats slower, as in stews and soups, and eating broiled or grilled meats rare or medium rare, will help. Experimentation with recipes that steam fish etc. is helpful. Barbecuing with sweet commercial sauces and charring the meats will produce the most AGEs. Avoidance of commercially prepared barbecued meats is helpful. Sometimes, our choices of food at lunch or on the go are particularly unhealthy. Commercial snack foods are often prepared by combining proteins and sugars without water in the cooking process, such as with corn chips, etc. Be careful of excess consumption of these foods as snacks. If your like to drink juices and eat dried fruit, choose fruits that are less sweet. Many people just drink orange and apple juice, and avoid less sweet fruit choices. Start eating sour cherries, apricots, tart apples, berries, etc. and experiment with and acquire the taste for more varied foods. Raw vegetable juicing is one healthy choice, but beware of juices that are again too sweet. Excess consumption of sweet carrot juice, and commercial vegetable juices with a high content of sweet apple or banana should be avoided.