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

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

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Information Resources and Additional Information with Links to Scientific Studies

  1. The standard theories on the pathophysiology of Rheumatoid Arthritis is well presented in this overview by John Hopkins University: http://www.hopkins-arthritis.org/arthritis-info/rheumatoid-arthritis/rheum_clin_path.html
  2. A 2006 evaluation of Complement Immune testing to better evaluate and define the various stages and progression of Rheumatoid Arthritis, by experts at Sanquin Research at CLB in Amsterdam, The Netherlands, described how specific complement proteins are important biomarkers for disease progression, especially comparisons between the expression of these complement proteins in both the synovial fluid and the circulating blood: http://onlinelibrary.wiley.com/doi/10.1002/art.21729/pdf
  3. Recent scientific study is finally finding key biological mechanisms that cause Rheumatoid Arthritis, such as the overexpression of the protein CCL28 during periods of mild hypoxia, or low oxygen conditions, and subsequent overexpression of CCL28 protein receptors on the membranes of RA joints. C-C motif chemokine ligand 28 is a mucosal epithelial chemokine that is related to complement regulation and activation of both the adaptive and innate immune response, especially with IgA and IL-17, and may be an important link between problems with intestinal mucosal immunity and joint pathologies such as RA. Such study as this, in 2014 at the University of Illinois at Chicago, show the potential for both creation of new biologic drugs to block aspects of this pathological process, as well as new insights into how Complementary and Integrative Medicine can perhaps stop this pathological mechanism holistically: http://www.sciencedaily.com/releases/2014/05/140516111003.htm
  4. A 2014 study at the INRA Centre de Val de Loire, in Nousilly, France, found that the protein CCL28, linked to Rheumatoid Arthritis, is widely distributed in mucosal tissues as part of the innate immune protection in response to various anaerobic bacteria and fungi in the gut, explaining the link between hypoxia and overexpression of CCL28. Such study demonstrates that a holistic medical approach that clears parasitic overgrowth and restores a healthy Biota could be integral to preventing and reversing RA: http://www.ncbi.nlm.nih.gov/pubmed/24445014
  5. The U.S. National Institutes of Health in 2013 revealed that early stages of Rheumatoid Arthritis are highly linked to specific pathological bacteria that overgrow in the intestinal tract, Prevatella capri, indicating that an imbalance in the gut Biome may lead to the cascade of autoimmune dysfunctions that result in RA, and links RA cause to Psoriatic arthritis and other chronic inflammatory conditions. Such findings indicate that the holistic approach with Complementary and Integrative Medicine could be invaluable in reversing these diseases: http://www.nih.gov/researchmatters/november2013/11252013arthritis.htm
  6. Over 15 types of joint disease can be mistaken for Rheumatoid Arthritis, which depends on subjective analysis to really diagnose. Often, a patient is thus not diagnosed until later stages of RA occur to fully define the illness. A 2014 study in Japan examined over 600 cadavers to see what the incidence of pseudogout, or CPPD, in knee cartilage really was, a diagnosis rarely considered. The findings showed that 13 percent of randomly chosen cadavers with an average age of 78 could have been diagnosed with CPPD in the knee cartilage, and that this was correlated with the severity of the cartilage degeneration: http://www.ncbi.nlm.nih.gov/pubmed/24814686
  7. A 2015 randomized controlled study in France, at the Hospital Bichat of the University Paris Diderot, showed that ultrasonography was able to accurately diagnose CPPD in knee cartilage in 100 percent of cases, while the standard X-ray testing identified CPPD only in 64 percent of cases: http://www.ncbi.nlm.nih.gov/pubmed/26077407
  8. In 2015, a review of studies of the standard prescription of Methotrexate to treat CPPD, by the University Miguel Hernandez de Elche, in Spain, shows that studies indicate that supposed benefits from this treatment have not been confirmed in follow-up studies, and that the adverse side effects are significant. A better treatment protocol for CPPD is needed, not just the same prescription as is given to patients with Rheumatoid arthritis: http://www.ncbi.nlm.nih.gov/pubmed/25885915
  9. A wide variety of diseases may mimic Rheumatoid Arthritis, which is very difficult to diagnose definitively. Health on the Net Foundation provides a succinct differential description of 15 diseases that are often mistake for RA: http://www.healthcentral.com/rheumatoid-arthritis/cf/slideshows/conditions-that-mimic-rheumatoid-arthritis?ap=104
  10. The U.S. National Institutes of Health has expanded to include an institute devoted to Complementary and Integrative Medicine, but it is still presenting the most conservative and cautious advice to the public. This website does show that there is standard evidence of efficacy of a wide array of therapies currently, and larger studies awaiting: http://www.nih.gov/about/almanac/organization/NCCIH.htm
  11. A 2016 review of current treatment for Rheumatoid Arthritis at the Bharathidasan University School of Medicine, in Tamil nadu, India, points out that diagnosis and treatment of RA is still problematic, with corticosteroids, Biologic immune modulating or suppressing drugs, and some work with targeted gene therapy commonly used, but with evidence now supporting integration of acupuncture, physiotherapy, yoga and Tai chi as well: http://www.ncbi.nlm.nih.gov/pu...
  12. The American Academy of Orthopaedic Surgeons states that Rheumatoid Arthritis manifests with foot symptoms in about 90% of cases, and that the first signs and symptoms occasionally occur in the foot with common foot deformities such as flat feet, claw or hammer toe. Sometimes, the first signs are systemic, such as episodic flush or feverishness, easy fatigue, and loss of appetite: http://orthoinfo.aaos.org/topic.cfm?topic=A00163
  13. A number of inflammatory mediators, or cytokines, are central to the tissue destruction seen in Rheumatoid arthritis, and research into specific immune mediators that are key to the pathology are creating new biologic drugs for treatment, but are also elucidating the efficacy of key herbal chemicals that modulate these immune responses effectively. Hopefully, a sensible integration of evidence-based herbal/nutrient medicine combined with acupuncture will allow patients to reduce dosage and combination of harsh pharmaceutical immune suppressants to achieve a protocol with fewer adverse effects: http://www.ncbi.nlm.nih.gov/pubmed/8717520
  14. A 2011 study at Birmingham VA Medical Center, in Birmingham, Alabama, found that the array of new biologic drugs that target specific immune pathways to treat Rheumatoid Arthritis come with significantly higher rates of total adverse events and withdrawals from therapy due to adverse events, as well as serious risks of infection due to suppression of immune pathways, such as the reactivation of latent TB, much of which is now antibiotic resistant: http://www.ncbi.nlm.nih.gov/pubmed/21328309
  15. A 2014 meta-review of treatment strategies in standard medicine for Rheumatoid Arthritis, at the Sint Maarten Clinic in The Netherlands, a renowned Orthopedic and Rheumatic Hospital, found only 6 randomized controlled human clinical trials assessing the long-term use of anti-TNF biologics such as Etanercept (Enbrel) in the treatment protocol for RA, despite significant dose-dependent adverse effects and high cost. These studies revealed that with the evidence available, that lowering the dose by half, to 25 mg weekly, after 12 months of low disease activity, seemed the best course with respect to control of disease remission and lower chronic adverse effects. The researchers noted, though, that there were no published trials of discontinuation of Etanercept (Enbrel) and Adalimumab (Humira), or disease-activity-guided dose reduction of these drugs, despite reports of a sizable percentage of patients choosing this course with long-term disease remission, making it difficult to assess such strategies in guidelines: http://www.ncbi.nlm.nih.gov/pubmed/25264908
  16. A 2014 meta-review of standard treatment for Rheumatoid Arthritis, at the University of Texas M.D. Anderson Cancer Center, showed that about 16 percent of patients prescribed Methotrexate, an immune suppressant folic acid antagonist, discontinued use due to serious adverse effects, and 45 percent reported significant adverse effects at 12 weeks. The therapy with a range of 5-25 mg weekly doses, provided significant improvement in symptoms and function over placebo for about 15 percent of patients, although no significant differences over placebo were noted in radiographic scores, but progression rates were improved. The total published randomized controlled human clinical trials as of 2013 only totalled 7, with only 732 patients included, though, and one study found no notable remission of disease with either Methotrexate or placebo at 52 weeks. Clearly, integration of Complementary Medicine could improve outcomes, as well as lowered dosage for many patients to achieve fewer adverse effects. While meta-reviews of acupuncture with only 7 randomized controlled trials and 732 patients would conclude that there was insufficient proof of efficacy based on absence of larger studies, this meta-review concluded that the standard drug therapy was proven safe and effective: http://www.ncbi.nlm.nih.gov/pubmed/24916606
  17. A 2015 meta-review of current studies of new therapeutic drugs for the treatment of Rheumatoid arthritis, by the Nanjing Medical University, in Nanjing, China, noted that in China, the largest number of published patent applications for new anti-rheumatic drugs used research concerning herbal chemistry in Traditional Chinese Medicine (TCM), showing that the obvious efficacy of these chemicals cannot be denied. While synthesized drugs containing herbal chemicals or analogues may be stronger and more specific, traditional use of herbal medicine is obviously effective, and very safe: http://www.ncbi.nlm.nih.gov/pubmed/26066366a
  18. A short explanation of the scientific research of just one of the well used herbal extracts to treat Rheumatoid Arthritis (RA) in Asia, Celastrus aculeatus, at the University of Maryland, U.S.A. by Shannadora Hollis, a doctoral student at the University of Maryland in 2012, reveals just how this herbal extract benefits treatment of RA. The herbal extract, either derived from Celastrus as Trypterygium wlfordii, or Lei gong teng, or Celastrus as Nan she teng, C. orbiculatus, is just part of a holistic protocol that can be integrated into care to improve outcomes and prevent RA exacerbations: http://www.asbmb.org/asbmbtoday/asbmbtoday_article.aspx?id=18165
  19. The original study at the University of Maryland School of Medicine exploring the effects of the Chinese rheumatic herb Celastrus aculeatus, also called Trypterygium wilfordii, or Lei gong teng, shows how this herbal extract, here captured in alcohol extraction, benefits the treatment in a number of ways, mainly by potentiating the immune effects to regulate inflammation in autoimmune disorder. Such treatment is usually combined with other herbal protocols and enhanced by acupuncture stimulation, and is easily integrated with standard pharmaceutical treatment without problems: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2206370/
  20. A 2015 large study of the patient population in Taiwan noted that a growing percentage of patients utilized CIM/TCM in the integrated treatment protocol for their Rheumatoid Arthritis, with regular TCM users generally younger, and the most used treatment being herbal medicine, used by about 75 percent of TCM patients, with 21 percent combining acupuncture and herbal medicine. The reasons, or aspects of the disease and related disorders, that the TCM therapy was used for varied considerably and is listed, as well as the most used herbs and formulas: http://www.ncbi.nlm.nih.gov/pubmed/26481605
  21. A 2015 study by the University of Maryland School of Medicine, in Baltimore, Maryland, U.S.A. confirmed that the herbal drug Celastrol, developed in China to treat autoimmune disorders such as Rheumatoid Arthritis, and derived from the herb Celastrus, commonly called Trypterygium wilfordii, or Lei Gong Teng, was very effective. The research showed that this herbal remedy achieved a balance of Th1/Th2 expressions, reduced Th17 in the synovial tissues of affected joints, and increased T-regulatory expression in the tissues. Celastrol was found to suppress autoimmune RA by modulating the immune effects in inflamed joints, and the recommendation was "it should be tested as a potential adjunct/alternative for RA therapy": http://www.ncbi.nlm.nih.gov/pubmed/25660987
  22. A 2015 meta-review of herbal medicines used to treat and prevent Rheumatoid Arthritis, by experts at the Griffith University School of Natural Sciences, in Nathan, Queensland, Australia, found that 65 of the 106 Australian herbal extracts from 40 indigenous plants studied showed the ability to inhibit a variety of low-grade bacterial endotoxins that are found to trigger onset of Rheumatoid Arthritis. Both alcohol tinctures and water extracts were studied. Species of Eucalyptus, Leptospermum, Datura, Melaleuca, Petolostigma, Szygium, Tasmannia lanceolata fruit, and herbs containing resveratrol were found most effective. Such study confirms that efficacy of common and traditional herbal medicine in the prevention of RA, and indicates that increased utilization of professional herbal medicines around the world would have a dramatic effect in disease prevention: http://www.ncbi.nlm.nih.gov/pubmed/26109767
  23. A 2010 randomized controlled human clinical trial at Suzhou municipal hospital in Jiangsu Province, China, found that both acupuncture and electroacupuncture had significant effects on reduction of key pro-inflammatory cytokines in patients with Rheumatoid arthritis, but the electroacupuncture showed significantly improved reduction of the key pro-inflammatory cytokine in the disesase, IL-1 (interleukin-1). The points used were DU20, GB20, LI11, SJ5, Ren4, and ST36, with electroacupuncture used at local trigger points near diseased joints, followed by electroacupuncture at the paraspinal points called back-shu: http://www.ncbi.nlm.nih.gov/pubmed/21058483
  24. A 2010 review of the use of Complementary Medicine and TCM therapies for Rheumatoid Arthritis by the Chinese Academy of Science, Shenzhen, China, found that there is both scientific proof and ample clinical evidence that an array of TCM therapies are effective to both improve symptoms and quality of life of patients, combining acupuncture, electroacupuncture, herbal and nutrient medicine, and medical massage (Tui na) to relieve pain, expand joint motion, modulate emotion, modulate immune responses, and improve the function of the neuroendocrine system. These experts stated that there are virtually no reliable systematic reviews of scientific study of this protocol: http://www.ncbi.nlm.nih.gov/pubmed/20204371
  25. A 2009 study at Zhejiang Chinese Medical University, in Hangzhou, China, found that electroacupuncture at just 2 points, ST36 and SP6, effectively decreased joint swelling, pain, prostaglandin E2, and the pro-inflammatory cytokines TNF-alpha and IL-1beta in studies of laboratory animals with collagen-induced Rheumatoid arthritis: http://www.ncbi.nlm.nih.gov/pubmed/19685721
  26. A 2009 study at the Hokkaido University Graduate School of Medicine, in Sapporo, Japan, conducted a 12 month study of Rheumatoid Arthritis patients, who received a mere 10 treatments of acupuncture in this time. Pain and function were improved significantly from treatment, but the chemical measurements were limited to ESR, CRP, and maximum standard uptake value of PET scan, not the levels of inflammatory cytokines or other clear signs of treatment benefit. Such studies appear to be designed to easily discount the acupuncture effects, as ESR, CRP and uptake value of radiological emissions in PET scan are markers for rheumatoid disease, but not accurate values to judge improvement in the condition of the patient. Nonetheless, even this too infrequent and simplistic treatment showed success in reducing pain and increasing joint mobility: http://www.ncbi.nlm.nih.gov/pubmed/19337783
  27. A 2012 randomized controlled laboratory trial of acupuncture to treat chronic inflammatory arthritis, at the Beijing University of Chinese Medicine, in China, found that electroacupuncture at ST36, significantly downregulated the expression of key inflammatory cytokines TNF-alpha, IL-1beta, IL-4 and IL-10, which are integral to the disease expression in Rheumatoid Arthritis and the focus of biologic immune suppressing drugs used to treat RA: http://www.ncbi.nlm.nih.gov/pubmed/23140046
  28. A 2015 study at the Hubei University of Chinese Medicine and the Tongji Medical College, in China, showed with a randomized controlled animal study that acupuncture at ST36, GB39 and UB23 mediates the NK-kB pathway to reduce the disease expression in Rheumatoid Arthritis and presents as a significant adjunct therapy: http://www.ncbi.nlm.nih.gov/pubmed/26030114
  29. A 2015 randomized controlled animal study at Shanghai University of Traditional Chinese Medicine showed that electroacupuncture at ST36 and ST39, in a short course of 3 treatments per week for 4 weeks, exerted significant anti-inflammatory effects in collagen-induced Rheumatoid Arthritis by activating the vasoactive intestinal peptide-dependent signaling cascade to modulate the T-helper T-reg cell balance: http://www.ncbi.nlm.nih.gov/pubmed/25979865
  30. A 2009 study at China Pharmaceutical University in Nanjing found that the main active chemical in the herb Erycibe obtusifolia, or Ding gong teng, scopolin, significantly reduced the cytokines found in excess in synovial tissues of Rheumatoid Arthritis patients, IL-6, VEGF and FGF-2, thus able to reduce clinical symptoms by both inhibiting inflammatory mechanisms and reducing angiogenesis in the joint tissues: http://www.ncbi.nlm.nih.gov/pubmed/19327410
  31. A 2010 study at China Pharmaceutical University in Nanjing found that another active chemical in the herb Erycibe obtusifolia, or Ding gong teng, scopoletin, significantly reduced the cytokines found in excess in synovial tissues of Rheumatoid Arthritis patients, IL-6, VEGF and FGF-2, and reduced symptoms of joint swelling, and the pathological processes of excess capillary formation and tissue hypertrophy in animal studies of inflammatory arthritis: http://www.ncbi.nlm.nih.gov/pubmed/19845767
  32. A 2008 study at Fujian Medical University found that the Chinese herb Trypterygium wilfordii, widely used in China to treat Rheumatoid Arthritis, exhibits a wide array of beneficial therapeutic effects, such as immunomodulation, and blocking of genetic expression of pro-inflammatory cytokines: http://www.ncbi.nlm.nih.gov/pubmed/19244746
  33. A 2007 study at Rutgers University in New Jersey, found that the main active chemical in Trypterygium wilfordii, or Lei gong teng, could be attributed to triptolide, and was shown to produce significant anti-inflammatory and immunosuppressive activities in human clinical trials for rheumatoid arthritis: http://www.ncbi.nlm.nih.gov/pubmed/17399748
  34. A 2003 study in Japan found that Triptolide, a key chemical in the Chinese herb Lei gong teng, significantly inhbited collagen degradation by inducing downregulation or the production of metalloproteinases by fibroblasts: http://www.iovs.org/content/44/12/5082.abstract
  35. A 2012 study at the Second Military Medical University in Shanghai, China, found that the Chinese herb Paeonia lactiflora Pallas, or Chi shao, exerts a wide array of beneficial effects for the treatment of Rheumatoid arthritis, with the main chemical paeoniflorin reducing pro-inflammatory cytokines, prostaglandin E2, leukotriene B4, nitric oxide (swelling), reactive oxygen species (oxidants), formation of pathological blood vessels, and matrix metalloproteinases: http://www.ncbi.nlm.nih.gov/pubmed/22705050
  36. Studies in 2011 at the University of Kebangsaan, Malaysia, showed that the Chinese herbal chemical curcumin reduced ESR (erythrocyte sedimentation rate), and arrested degenerative changes in joints of collagen-induced arthritis in laboratory animals, reversing degeneration in Rheumatoid Arthritis: http://www.ncbi.nlm.nih.gov/pubmed/21717043
  37. Studies in 2012 at Kyung Hee University, in Seoul, South Korea, showed that the Chinese medicinal herb Polygonum cuspidatum, or Hu zhang, the source of resveratrol, effectively decreases joint swelling in rheumatoid arthritis, inhibits CRP effects, and rheumatoid factor: http://www.ncbi.nlm.nih.gov/pubmed/21711083
  38. A 2014 randomized controlled study of herbal treatment for Rheumatoid Arthritis, at Zhengzhou University First Affiliated Hospital, in China, found that the herbal extract called Horsetail Mixture, or Equisetum arvense (Wen jing), long-used to treat osteoporosis, kidney stones, and urinary tract infections, significantly downregulated TNF-alpha and IL-10, and lowered the ESR and RF, demonstrating how this Chinese herbal medicine could treat RA effectively within herbal formulas: http://www.ncbi.nlm.nih.gov/pubmed/25410066
  39. Studies in 2010 at the University of Maryland School of Medicine found that methanol tincture of the Chinese and Indian herb Celastrus aculeatus, 拉丁名, (La Ding Ming) and the product Celastrol, both effectively attenuated inflammatory responses to significantly improve rheumatoid arthritis. Celastrol is a sapogenin compound from the Chinese herb Trypterygium wilfordii, as well, much studied in Asia and Europe for the treatment of various autoimmune pathologies: http://www.jbc.org/content/286/17/15138.abstract
  40. The full study report of the effects of Celastrol, a Chinese herbal alcohol tincture, at the University of Maryland School of Medicine, in 2010, and the recommendation to proceed to human clinical trials of this herbal medicine to treat RA and other autoimmune diseases, is found here: http://link.springer.com/article/10.1186%2Far2268#page-1
  41. Further studies in 2015 of the Chinese herbal compound Celastrol, at the University of Maryland School of Medicine, in Baltimore, Maryland U.S.A. and the National Institutes of Arthritis and Musculoskeletal and Skin Diseases of the U.S. NIH, found that this standardized herbal extract from Trypterygium wilfordii and Celastrus aculeatus inhibited TH17 producing cytokines and chemokines, and exerted T-regulatory modulation to successfully treat joint inflammation in Rheumatoid Arthritis: http://www.ncbi.nlm.nih.gov/pubmed/25660987
  42. A 2007 study at Sun Yat-sen University, in Guangzhou, China, found that a key chemical in the Chinese herb Artemesia qinghao, artesunate, effectively inhibits TNF-alpha, IL-1beta, Il-6 and IL-8 to attenuate Rheumatoid Arthritis. Qing hao is an herb now famous as an anti-malarial, but has applications in clearing parasitic microbials and : http://www.ncbi.nlm.nih.gov/pubmed/17049776
  43. A 2007 study at Hong Kong Baptist University found that a standard Chinese herbal formula (here called QFGJS) used to treat Rheumatoid Arthritis, significantly reduced blood levels of pro-inflammatory mediators TNF-alpha, IL-1beta, and IL-6 in animal studies, showing that this formula was a great candidate for human clinical trials to treat Rheumatoid arthritis: http://www.ncbi.nlm.nih.gov/pubmed/17049776
  44. A 2003 study at Seoul National University College of Medicine, published in the Oxford Journals Rheumatology, found that a Chinese herbal formula, here called PG201, was effective in treating Rheumatoid Arthritis via a number of effects, including downregulation of the expression of key pro-inflammatory cytokines TNF-alpha, IL-1beta, and upregulation of beneficial inhibitors of metalloproteinase such TIMP-3, exerting modulatory effects on the metalloproteinase pathway. Regulation of the upstream immune cytokines IL-4 and IL-10 also contributed to control of the cartilage autoimmune destruction in RA. The formula PG201, here in alcohol extract, is composed of Chaenomelis Fructus (Quince), Achyranthis Radix (Niu xi), Carthami Flos (Hong hua), Cnidii Rhizoma (She chuang zi), Cinnamomum Cortex (Rou gui), Angelica Radix (Du huo), Gastrodiae Rhizoma (Tian ma), Ledebourieallae Radix (Fang feng), Gentiana Macrophylla Radix (Qin jiao), Acathopanacis Cortex (Wu jia pi), Phlomidis Radix, and Clematidis Radix (Wei ling xian), is typical of Chinese Herbal Formulas to treat arthritis: http://rheumatology.oxfordjournals.org/content/42/5/665.full
  45. A 2014 study at Peking Union Medical College and Binzhou Medical University, in China, found that an herbal salicylate, bphMSL, from the herb Gaultheria yunnanensis (Franch.), a type of wintergreen (Bai zhu shu), traditionally used to treat RA in China, effectively inhibited TNF-alpha, IL-1, IL-6, and suppressed the accumulation of nitric oxide, preventing the progression of Rheumatoid Arthritis in animal studies, without producing irritation to the stomach mucosa: http://www.ncbi.nlm.nih.gov/pubmed/24712652
  46. A 2014 study at the National Institute of Pharmaceutical Education and Research, in Punjab, India, found that the alcohol extract of herb Cajanus cajan leaf (pigeon pea) effectively inhibits TNF-alpha and IL-1beta, the targets of biologics such as Enbrel and Humira, the main drugs used to treat Rheumatoid Arthritis: http://www.ncbi.nlm.nih.gov/pubmed/24680612
  47. A 2004 study published in the Oxford Journals found that IP6, or inositol hexaphosphate, significantly reduced 2 of the key growth factors found in excess in rheumatoid arthritis, VEGF and pFGF: http://carcin.oxfordjournals.org/content/25/11/2115.full
  48. A 2000 study at Humbolt University in Germany found that during inflammation and hemostasis VEGF, a growth factor of angiogenesis correlated with the degeneration in RA, is stimulated not by hypoxia, but by increased blood heat and acidosis affecting platelets, and white blood cells: http://ajpheart.physiology.org/cgi/content/abstract/279/2/H817
  49. A 2000 study at Humbolt University in Germany found that during inflammation and hemostasis VEGF, a growth factor of angiogenesis correlated with the degeneration in RA, is stimulated not by hypoxia, but by increased blood heat and acidosis affeting platelets, and white blood cells: http://ajpheart.physiology.org/cgi/content/abstract/279/2/H817
  50. A 2005 study at the Rheumatism Research Center of the Catholic University of Korea found that IL-18 (interleukin 18) was the key cytokine that stimulated excess angiogenesis via VEGF, which is highly associated with synovial degeneration in RA, and that IL-18 is inhibited by Curcumin, an herbal component of various Chinese herbs: http://www.sciencedirect.com/science
  51. A joint American and Italian study has found that AGE accumulation and excess AGE receptors may play a key role in the amplification of inflammatory responses that cause such diseases as Rheumatoid arthritis, atherosclerosis and other chronic inflammatory disorders: http://circ.ahajournals.org/cgi/content/abstract/105/7/816
  52. A 2009 study at the Southern Medical University in Guangzhou, China, found that AGEs (advanced glycation endproducts) and lipopolysaccharides (bacterial membrane products) cooperatively induce proinflammatory cytokine production in inflammatory disease: http://www.ncbi.nlm.nih.gov/pubmed/19645720
  53. Insulin resistance and increased duration of circulating insulin has been found to be a potent modulator of chronic vascular tone, activating protein kinase C in vascular tissues and inhibiting an important enzyme mediator PI-3 kinase, affecting endothelial nitric oxide synthase expression adversely. Chronic enhancement of nitric oxid production may be linked to atherosclerosis, hypertension and myocardial dysfunction. http://www.circ.ahajournals.org/cgi/content/abstract/101/6/676
  54. The goal of standard medical management of Rheumatoid Arthritis is to achieve disease remission, but this is rarely achieved. As this website of general practice M.D. training reveals, a more realistic goal of standard therapy is to control the inflammatory synovitis and slow or reduce joint damage. This treatment uses steroids, NSAIDS, and a group of drugs called disease modifying antirheumatic drugs (DMARDS). DMARDS help control the disease, but do not cure it, and come with considerable side effects. : http://www.gp-training.net/rheum/ra.htm
  55. Studies in 2004 at the Friedrich-Schiller University Institute for Diagnostic and Interventional Radiology revealed that bone mineral density loss in the small bones was progressive in Rheumatoid Arthritis, and newer digital technology revealed this osteoporotic progression while standard bone mineral density tests did not. In addition, the study shows that osteoporosis in RA is often attributed to chronic steroid medication use: http://www.ncbi.nlm.nih.gov/pubmed/15605213
  56. Studies at Columbia University College of Physicians in 1995 showed that vascular cell adhesion molecule-1 (VCAM-1) was highly associated with the development of atherosclerosis, and that AGEs (advanced glycation endproducts) induced expression of this growth factor in human cells: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC185762/
  57. Studies at the New York University Langone Medical Center, in 2013, found that receptors for advanced glycation endproducts (RAGEs) were primary mediators of oxidative stress in a number of chronic diseases, including Rheumatoid Arthritis, Pulmonary fibrosis, atherosclerosis, and neurodegeneration. Treatment to help the body clear excess AGEs, thus reducing excess RAGEs, may be integral to an effective integrative Complementary Medicine approach to treatment of RA and associated health problems: http://www.ncbi.nlm.nih.gov/pubmed/24084731
  58. Studies have cast doubt on the ability of aminoguanidine to inhibit AGE formation: http://www.ncbi.nlm.nih.gov/pubmed/10221660
  59. A study in 2000, at the Institute of Food Research, in Norfolk, United Kingdom, found that omega-3 essential fatty acids modulate the expression of antigen presenting cells from the Major Histocompatibility Complex (MHC) and Human Leukocyte Antigen (HLA), and inhibit expression, but only on activated monocytes, revealing the potential mechanism of benefit of supplements such as krill oil in control of symptoms of Rheumatoid Arthritis: http://www.ncbi.nlm.nih.gov/pubmed/10617997
  60. Effects on nitric oxide inhibition by chemicals in Huang qin, studied at Taipei Medical University: http://www.ncbi.nlm.nih.gov/pubmed/11331078
  61. Effects on nitric oxide inhibition by chemicals in Hu zhang, Polygonum cuspidatum, studied at Sungkyunkwan University in South Korea, Department of Biological Science: http://www.ncbi.nlm.nih.gov/pubmed/17553752
  62. Effects on nitric oxide inhibition by Fang feng, studied at Taipei Medical University: http://cat.inist.fr/?aModele=afficheN&cpsidt=1968748
  63. Effects on nitric oxide inhibition by a number of chemicals found in Chinese herbs, studied at Taipei Medical University: http://cat.inist.fr/?aModele=afficheN&cpsidt=821477
  64. Effects on inducible nitric oxide synthase that are beneficial point to a problem with drug protocols that block all iNOS to counter excess AGE harmful effects: http://www.ncbi.nlm.nih.gov/pubmed/10861252
  65. Effects on inhibition of AGE formation, as well as significant antioxidant activity was found in the herb Huang qi, Astragalus: http://www.ncbi.nlm.nih.gov/pubmed/19681610
  66. The systemic effects of AGE excess on receptors (RAGE), and the overexpression of RAGE and subsequent interaction with the various chemicals that may overstimulate the receptors, is found to be an important factor contributing to a host of important chronic disorders, including Alzheimer's: http://circres.ahajournals.org/cgi/content/abstract/84/5/489
  67. A 2010 study at Tohoku University in Japan found that AGEs may play a role in the development of various diabetic complications, including neuropathy and retinopathy, and confirm that P5P and benfotiamine both inhibit AGE formation and are found to inhibit the development of these diabetic health problems: http://www.ncbi.nlm.nih.gov/pubmed/20957396
  68. The biochemical reasons that benfotiamine acts to reduce AGEs, and how AGEs are implicated in a number of chronic inflammatory diseases: http://www.ncbi.nlm.nih.gov/pubmed/20188835
  69. A 2013 study at Kyung Hee University, in Seoul, South Korea, found that the nutrient medicine phosphatidylserine exerted anti-inflammatory effects as well as benefiting membrane functions, and affected a number of key inflammatory cytokines that are associated with Rheumatoid Arthritis. It was recommended by these experts that phosphatidylserine be utilized as an adjunct treatment for RA: http://www.ncbi.nlm.nih.gov/pubmed/23507231
  70. A number of inflammatory mediators, or cytokines, are central to the tissue destruction seen in Rheumatoid arthritis: http://www.ncbi.nlm.nih.gov/pubmed/8717520
  71. Hyperprolactinemia, a hormonal imbalance, has been shown to be prevalent in Rheumatoid Arthritis and Lupus patients and is correlated with the disease mechanism: http://www.ncbi.nlm.nih.gov/pubmed/7920527
  72. A review of virtually all medications used to treat Rheumatoid Arthritis and the negative implications for fertility, conception, pregnancy and breastfeeding was published in 2000 in the Journal of the American Medical Association (JAMA) Internal Medicine: http://archinte.jamanetwork.com/article.aspx?articleid=1729684
  73. A review of the many adverse health effects seen with the use of immunosuppressive drugs is provided by Brown University: http://biomed.brown.edu/Courses/BI108/BI108_2004_Groups/Group04/Side_Effects.htm
  74. A 5-year multicenter study in Japan, of the high rate of cervical spine instabilities in Rheumatoid Arthritis, found that corticosteroid therapy was a substantial risk factor in the development of cervical spine degeneration and compressive neuropathy involving both the nerve roots and spinal cord: http://www.ncbi.nlm.nih.gov/pubmed/24558457
  75. A 2014 study of adverse effects with chronic use of anti-TNF therapy for Rheumatoid arthritis and other autoimmune diseases at the Jordan University of Science and Technology, Ibrid, Jordan, found that with an average duration of use of these drugs (etanercept/Enbrel, infliximab, adalimumab) of 16.2 months, that serious infections were seen in about 20 percent of patients, with respiratory tract infections the most prevalent, followed by urinary tract infections, skin infections and tuberculosis: http://www.ncbi.nlm.nih.gov/pubmed/24790412
  76. A 2006 meta-review of all published scientific studies of the risk of serious infections and cancer malignancies with the chronic use of Anti-TNF antibody therapy for Rheumatoid Arthritis patients, but the Mayo Clinic, in Rochester, Minnesota, U.S.A. found that a significant risk for cancer malignancy and serious infection was evident. The pooled odds ratio in all studies showed that the chance of cancer malignancy was 3.3 times that of a control group for cancer malignancy, and 2.0 times that of a control group for serious infections requiring hospitalization: http://www.ncbi.nlm.nih.gov/pubmed/16705109
  77. Studies in 2012, at the National Defense Medical Center and Graduate Institute of Medical Science, in Taipei, Taiwan, found that the supplement Pycnogenol, derived and standardized from maritime pine bark and combined with mixed tocopherols, was effective in treating arthritis induced by crystals such as urate or calcium, in gout or calcified capsulitis: http://www.ncbi.nlm.nih.gov/pubmed/22198264
  78. A metareview of all published studies of the treatment of gouty arthritis, in 2014, at the Third Military Medical Univesity, in Chongqing, China, found that herbal therapies had equivalent efficacy as pharmaceutical drugs, with no adverse side effects: http://www.ncbi.nlm.nih.gov/pubmed/24465466
  79. A 2014 meta-review of studies of herbal medicine to treat gout show that numerous chemicals in herbal treatments have shown potential to treat gout, with a variety of effects: http://www.ncbi.nlm.nih.gov/pubmed/24791587
  80. A 2004 study at the Nanjing University Institute of Functional Biomedicine in China found that the herbal formula Er Miao San (Huang bai and Cang zhu fried and powdered mixed with ginger juice), as well as just the herb Huang bai (Phellodendron root), exerted xanthine oxidase inhibition and anti-inflammatory effects that reduced uric acid levels and gouty inflammation in animal studies. The effects were weaker than allopurinol, the standard treatment to reduce uric acid in gout, but the broad effects of such herbal extracts and formulas provides other beneficial effects: http://www.ncbi.nlm.nih.gov/pubmed/15234772
  81. A meta-review of all published scientific studies found that a number of Chinese herbal flavonoid chemicals exert a significant xanthine oxidase inhibition like the standard pharmaceuticals that treat gout and pseudogout, Allopurinol and Feboxostate. This study, on the European PubMed, shows that baicalein was the strongest chemical, followed by wogonin and baicalin, but that d-catechin, d-epicatechin, peurarin, quercetin, and hespiridin all exerted significant effects in this regard. Baicalein, baicalin and wogonin are found in Huang qin (Scutellaria), and the catechin and epicatechin in Pycnogenol: http://europepmc.org/abstract/med/8297130
  82. A meta-review of all published scientific studies with acupuncture in the treatment of gouty arthritis, in 2013, published in the Oxford Journals, showed that significant evidence supports the use of acupuncture for this condition: http://www.ncbi.nlm.nih.gov/pubmed/23424263
  83. A 2007 study at Jiangnan University, in Hunan, China, found that a simple application of electroacupuncture at just 2 points, SP6 and ST40, was able to reduce uric acid in the blood and enhance kidney excretion of uric acid to improve the condition of chronic gout: http://www.ncbi.nlm.nih.gov/pubmed/18271232