Arthritis of Spine

Two forms of arthritis that may affect the spine are osteoarthritis and rheumatoid arthritis.

  • Osteoarthritis. Osteoarthritis is the most common form of arthritis and is more likely to occur in middle-aged and older people. It is a chronic, degenerative process that may involve multiple joints of the body. It wears away the surface cartilage layer of joints, and is often accompanied by overgrowth of bone, formation of bone spurs, and impaired function. If the degenerative process of osteoarthritis affects the facet joint(s) and the disk, the condition is sometimes referred to as spondylosis. This condition may be accompanied by disk degeneration, and an enlargement or overgrowth of bone that narrows the central and nerve root canals.
  • Rheumatoid Arthritis. Rheumatoid arthritis usually affects people at an earlier age than osteoarthritis does and is associated with inflammation and enlargement of the soft tissues (the synovium) of the joints. Although not a common cause of spinal stenosis, damage to ligaments, bones, and joints that begins as synovitis (inflammation of the synovial membrane which lines the inside of the joint) has a severe and disrupting effect on joint function. The portions of the vertebral column with the greatest mobility (for example, the neck area) are often the ones most affected in people with rheumatoid arthritis.

Arthritis

Arthritis is a general term for conditions that affect the joints and surrounding tissues. Joints are places in the body where bones come together, such as the knees, wrists, fingers, toes, and hips. The two most common types of arthritis are osteoarthritis and rheumatoid arthritis.

Osteoarthritis (OA) is a painful, degenerative joint disease that often involves the hips, knees, neck, lower back, or small joints of the hands. OA usually develops in joints that are injured by repeated overuse from performing a particular task or playing a favorite sport or from carrying around excess body weight. Eventually this injury or repeated impact thins or wears away the cartilage that cushions the ends of the bones in the joint. As a result, the bones rub together, causing a grating sensation. Joint flexibility is reduced, bony spurs develop, and the joint swells. Usually, the first symptom of OA is pain that worsens following exercise or immobility. Treatment usually includes analgesics, topical creams, or nonsteroidal anti-inflammatory drugs (known as NSAIDs); appropriate exercises or physical therapy; joint splinting; or joint replacement surgery for seriously damaged larger joints, such as the knee or hip. Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that usually involves various joints in the fingers, thumbs, wrists, elbows, shoulders, knees, feet, and ankles. An autoimmune disease is one in which the body releases enzymes that attack its own healthy tissues. In RA, these enzymes destroy the linings of joints. This causes pain, swelling, stiffness, malformation, and reduced movement and function. People with RA also may have systemic symptoms, such as fatigue, fever, weight loss, eye inflammation, anemia, subcutaneous nodules (bumps under the skin), or pleurisy (a lung inflammation).

Although osteoporosis and osteoarthritis are two very different medical conditions with little in common, the similarity of their names causes great confusion. These conditions develop differently, have different symptoms, are diagnosed differently, and are treated differently. Studies show that people with OA are less likely than average to develop osteoporosis. On the other hand, people with RA may be more likely to develop osteoporosis. This is especially true because some medications used to treat RA can contribute to osteoporosis.

Osteoporosis and arthritis do share many coping strategies. With either or both of these conditions, many people benefit from exercise programs that may include physical therapy and rehabilitation. In general, exercises that emphasize stretching, strengthening, posture, and range of motion are appropriate. Examples include low-impact aerobics, swimming, tai chi, and low-stress yoga. However, people with osteoporosis must take care to avoid activities that include bending forward from the waist, twisting the spine, or lifting heavy weights. People with arthritis must compensate for limited movement in affected joints. Always check with your doctor to determine whether a certain exercise or exercise program is safe for your specific medical situation.

Most people with arthritis will use pain management strategies at some time. This is not always true for people with osteoporosis. Usually, people with osteoporosis need pain relief when they are recovering from a fracture. In cases of severe osteoporosis with multiple spine fractures, pain control also may become part of daily life. Regardless of the cause, pain management strategies are similar for people with osteoporosis, OA, and RA. These strategies are included in the following chart.

 

Rheumatoid Arthritis: new research findings and their implications to integrative therapies

Rheumatoid Arthritis (RA) is an autoimmune disorder that has defied understanding due to the complexity of the underlying factors that lead to this systemic inflammatory dysfunction. While the disease has been diagnosed at a late stage in the disorder, when episodic joint swelling and pain, usually in the hands, feet or cervical spine occur, and become debilitating, we now know that the disorder progresses slowly over many years, and affects a wide variety of tissues in the body. Early diagnosis and prevention are thus of great importance to the population most affected. The late stage diagnosis of RA occurs mainly with persons between the ages of 40 to 50, with women diagnosed 3 times more than men, but the time to start prevention and early treatment is in your 30's. For those with advanced RA, treatment of the underlying contributors to the disease, as well as treatment of the associated health factors that put you most at risk need to be addressed holistically. While a number of pharmaceutical prescriptions may decrease symptoms and address some cardiovascular risk factors, these drugs do not address the restoration of health. This is where Complementary and Integrative Medicine comes into play. This field of medicine, supported by explosive growth in research, offers improved symptom control, treatment of the problem from the ground up, and healthy prevention of associated systemic problems that could put you at high risk for stroke and heart attack, as well as a variety of common debilitating health problems that you might not be associating with the pathology of rheumatoid arthritis.

Proof of direct medical efficacy of acupuncture, herbal medicine, nutrient medicine, physiotherapies, and healthy treatment regimens such as Tai Chi, has been achieved with very limited resources devoted to standard double-blinded placebo controlled human trials (see the link to the U.S. National Institutes of Health website below). Clinical empirical evidence has been accumulated for the last 2000 years in China, though, and a wealth of current research provides proof of efficacy related to the myriad of health problems now associated with Rheumatoid Arthritis. This is not to say that there is a miracle cure for this very difficult disease, or that standard therapy should be abandoned for these other therapies. What we are sure of is that there is a lot of sound research-based evidence to help guide an integration of Complementary Medicine into standard protocol.

Research in recent years has validated a number of medical herbal and nutrient treatments to integrate into the care of Rheumatoid Arthritis. Alkaloids in the Chinese herbs Stephania Tetrandre and Trypterygium Wilfordii have been shown to significantly suppress the most important pro-inflammatory cytokines that perpetuate Rheumatoid Arthritis, such as interleukin-1 and -6, nuclear factor kappa Beta, and tumor necrosis factor-alpha. Research at Harvard Medical School has produced an advanced bio-identical collagen supplement proven to benefit restoration of the inflamed synovial joint membranes. Optimization of the herbal chemical curcumin has produced a product that can achieve therapeutic blood levels with oral medicine. These and other herbal and nutrient medicines may be prescribed by professional herbalists such as Licensed Acupuncturists, or TCM physicians. Links to research summaries can be seen below.

Vascular inflammation, or vasculitis, atherosclerosis, or stiffening of the arteries, fibrosis of the lungs, resulting in pneumonia, bronchitis, and increase in the risk of heart attack, amyloidosis, or accumulation of protein fragments in tissue, especially in the kidney and brain, but also contributing to irritable bowel syndromes, lymphatic dysfunction, and cardiovascular disease, are all highly associated with Rheumatoid Arthritis, and point to the array of underlying health problems that make the disease origin so elusive for research. A large study at Aberdeen University Medical School in Scotland, in 2009, found that in RA patients without overt arterial disease, the progression of the disease is highly associated with increased arterial stiffness independent of other cardiovascular risk factors (Journal or Rheumatology; Crilly et al, Dec.2009). While blood pressure and cholesterol medications are often prescribed in the overall treatment of Rheumatoid Arthritis, these medications do not directly treat or reverse stiffening of the arteries, or atherosclerosis. In fact, the medications prescribed may contribute to these various associated pathologies. Statin drugs prescribed for high cholesterol are well known to cause accumulations of protein fragments (as in amyloidosis), which accounts for the high incidence of tissue and joint pain with chronic use, as well as the more rare rhabdomyolysis. Steroid medications are a well known cause of lung fibrosis, as well as atherosclerosis, and increases in cholesterol and triglycerides. Chronic use of NSAIDS, such as Cox-2 inhibitors, comes with considerable risk of cardiovascular disease. Newer immunosuppressant drugs come with even more dramatic risks and negative health consequences.

The Centers for Disease Control (CDC) of the United States reports that and estimated 1.5 million adults were diagnosed with Rheumatoid Arthritis in 2007. Since the diagnosis of RA is difficult in the early stages it is believed that a large number of cases that are developing serious and classic symptoms are undiagnosed or diagnosed as another form of arthritis. More than one in five adults in the United States are diagnosed with arthritis, and the CDC estimates that by 2030, an estimated 67 million Americans ages 18 or older are projected to have a doctor-diagnosed arthritis. In 2007, an estimated 294,000 children under the age of 18 had some form of arthritis or rheumatic condition. These alarming figures show that there is a great need in the United States to initiate early treatment and prevention with Complementary and Integrative Medicine. Presently, 7.6% of the U.S. population between the ages of 18-44 report a doctor-diagnosed arthritis, and nearly 30% of persons between the ages of 45 to 64 report a doctor-diagnosed arthritis. A higher prevalence of arthritis diagnosis occurs with overweight and obese patients, women, and patients with depression. A large number of persons with arthritis go undiagnosed, or misdiagnosed, especially in early stages of the disease mechanisms. Presently, about 5% of women over the age of 55 are diagnosed with RA.

Because the general public sees Rheumatoid Arthritis as a disease of the hands only, many patients with common symptoms attribute their health problems to other diseases. The American Academy of Orthopaedic Surgeons states that about 90% of people with RA eventually develop symptoms related to the foot or ankle, usually first manifesting as inflammatory swelling and pain in the toes and forefeet, which often is mistaken for gout. These orthopedic experts state that athritic symptoms in the feet are sometimes the first manifestation of the systemic disease. Milder stages of the disease may simply cause foot deformities, such as claw or hammer toe, and flat feet. This often leads to low back or knee pain over time. Other symptoms of RA that the association state are common include episodic mild feverishness or flush, easy fatique, and loss of appetite. Television advertisements for pharmaceuticals that treat gout may contribute to the hasty misdiagnosis as the public seeks out these drugs that are advertised rather than waiting until a sound diagnosis is achieved. Diagnosis of RA in early stages may take months, as repeat tests and exams monitor the progression of the disease.

The American College of Rheumatology emphasizes that there are 3 categories of disease duration. Early disease often lasts less than 6 months, while stages of intermediate duration last 6-24 months, and stages of long duration last longer than 24 months. Remission of the disease is often seen. The intelligent pro-active patient will do everything sensible to insure that the disease is limited to the early stage and goes into remission, and then will follow a course of preventative maintenance to insure that remission is prolonged. This is where Complementary and Integrative Medicine plays its biggest role. Prevention of the onset of RA is also a smart choice, and utilizing acupuncture, herbal medicine, physiotherapy, and nutritional medicine is the only medical treatment that is presently offered to potentially prevent the onset or worsening of the disease with aging.

For patients diagnosed with Rheumatoid Arthritis at intermediate and late stages, Complementary and Integrative Medicine offers much therapy to help reverse autoimmune mechanims, help control inflammatory dysfunction, help nourish degenerative joint tissues, treat associated disorders, such as cardiovascular disease, osteoporosis, fibrosis of the lung, interstitial pneumonias and bronchitis, anemia, leukopenia, and other tissue inflammations. In addition, the problems of depression and anxiety that often come with RA, and the many side effects of the standard pharmacological treatments may also be treated with Complementary and Integrative Medicine. A knowledgeable Licensed Acupuncturist may offer much in the overall treatment protocol.

Diagnosis and Early Detection: Difficult Problems

A true diagnosis of Rheumatoid Arthritis is often difficult and time consuming. If the General Practitioner diagnoses RA, the patient should insist on a visit to a rheumatologist. Rheumatoid Arthritis is diagnosed with a combination of laboratory tests and assessment of symptoms and signs of the disease. The clinical history is by far the most important diagnostic tool, and laboratory tests should be used to support the diagnosis, as the laboratory and radiological findings may often be unclear or nonspecific. A skilled physical examination should confirm swelling and inflammation of the joint synovium, and follow-up exams to objectively recognize the appropriate pattern of changes with exam, assessment and repeat testing is important to an accurate diagnosis. The patient may be denied the most effective treatment if the diagnosis is incorrect.

Laboratory tests include ethrocyte sedimentation rate (ESR), antinuclear antibody (ANA), rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP), and C-reactive protein (CRP), as well as x-ray, ultrasonography, and MRI. All of these tests could be negative or unclear in early stages of the disease, and a true diagnosis is only clear when positive test results are confirmed with a physical assessment. Only about 40% of RA patients with a clear diagnosis test positive for ANA, and false-positives are noted in RA as well, as 5% of the healthy population will test positive. About 20% of patients with Rheumatoid Arthritis will have a negative RF, as well. Rheumatoid factor is an IgG antibody associated with an autoimmune reaction against normal joint tissue. ESR is a non-specific test for the rate of red blood cells that precipitate in a period of one hour, and indicates a higher than normal rate of inflammatory reaction. ESR is affected by the amount of fibrinogen in the body, which is a pro-sedimentation factor, and this could be affected by the amount of advanced glycation endproducts in the body, which is an important subject that you may read about further along in this article. Anti-CCP (ACCP), a test for autoantibodies to protein fragments that may be associated with RA has a sensitivity rating similar to RF, and CRP positives may indicate a wide variety of inflammatory disorders. A sound diagnosis depends upon more than just one of these tests being positive or negative.

A more recent laboratory development is the anti-citrullinated antibody (ACPA) test. ACPA are autoantibodies that are formed as the body creates an inflammatory reaction to normal proteins, specifically protein fragments or altered proteins of the amino acid arginine. Citrulinated vimentin is one of these autoantigens noted in RA, and is secreted by immune cytokines such as tumor-necrosis factor (TNFalpha). Newer ELISA tests utilize ACPA with a genetically modified citrullinated vimentin (MCV) to optimize the performance of the test. These tests have been shown to diagnose patients with RA when the anti-CCP test is negative, and the ACPA tests are considered more specific than RF. These types of newer tests also give the patient and physician a better idea of the specific underlying causes of the RA, which could significantly benefit a research-oriented Complementary Medicine physician.

The American Academy of Rheumatology criteria for the diagnosis of Rheumatoid Arthritis requires the 4 of 7 key criteria be present. These 7 important criteria include:

1. morning stiffness in an around joints lasting more than 1 hour, and relieved by range of motion or simple activity 2. simultaneous signs of arthritis in 3 or more joint areas, typically the middle joints of the index and middle finger, as well as the wrist, but also seen in various small joints in the body, especially the elbows, shoulders, knees, ankles, and feet. The upper cervical spine is often affected in later stages of the disease, and swelling and pain in the distal finger joints is generally not seen. 3. arthritis noted in at least one area in a wrist, metacarpal or proximal interphalangeal joint of the hand or finger, which is the most typical areas of advanced symptoms 4. symetrical arthritis involving the same joint areas on both sides of the body 5. rheumatoid nodules: firm, non-tender, subcutaneous nodules commonly found at the elbow, back of the forearm, or metacarpophalangeal joint at the base of the finger; seen in about 25% of RA cases 6. positive rheumatoid factor (RF) in blood tests 7. radiological changes typical of RA on hand and wrist x-rays

The intelligent patient will take a pro-active approach when a diagnosis of RA is pursued. Instead of assuming that the diagnosis is correct with minimal testing and no actual diagnosis by a rheumatologist, the intelligent patient will insist on the correct testing and assessment, and also seek objective information on these tests and what they may reveal as to the underlying mechanisms of the disease. Standard medicine still has little to offer for treatment of Rheumatoid Arthritis, and there is a tendency to not fully explore diagnostic testing, which is often difficult and time consuming, and instead just prescribe the standard therapy, which is a sort of one-size-fits-all approach. Newer tests will differentiate underlying mechansisms and may present the Complementary Medicine physician with diagnostic data that can be applied to recent research and specific herbal chemicals, nutritional medicine, and even acupuncture research and approach. Newer anti-rheumatic drugs come with significant side effects and many patients are unable to tolerate current drug therapies, while others do not respond to these drugs, or have an initial response that diminishes over time. Complementary Medicine may help treat these side effects and potentially aid these therapies as well.

Since diagnosis may be unclear, considerations of differential diagnosis, or other possible diagnoses, is important. Since RA is part of a category of multijoint inflammatory diseases, it may be mistaken for other arthritic diseases in this classification, especially Lupus, Polymyositis-Dermatomyositis, Psoriatic arthritis, Sjogren's syndrome, Scleroderma, and Reactive arthritis, especially if the disease is in early stages. Viral joint disease is also a possibility, such as hepatitis C small-joint polyarthritis, which is very similar to RA. Gout, pseudogout, Lyme disease, sarcoidosis, amyloidosis, Whipple's disease, gonococcal arthritis, ankylosing spondylitis spreading to small joints, and hemochromatosis are all considerations in differential diagnosis, as is fibromyalgia. Many cases of early stage osteoarthritis are also mistakenly diagnosed as Rheumatoid Arthritis, and acute rheumatic fever with joint pain and swelling may be mistaken for RA as well. The patient should make sure that the diagnosis is correct. The key to this process is making sure that a respected rheumatoid disease specialist makes an exam, assessment, orders the proper tests, and follows up over time if this is needed.

Finally, early signs and symptoms are an important consideration for patients seeking to prevent the disease, or stop it before it proceeds to a stage of long duration. Symptoms that often precede the classic morning stiffness and joint swelling include fatique, malaise, depression, and low-grade fever. Fatique often occurs about 4-6 hours after waking. Early treatment and reversal of the disease is the key to a successful outcome. Slowing the complex mechanisms of RA in early stages may result in a short course of classic symptoms, and give the patient the time to improve systemic health and correct the underlying causes of the disease. Waiting until the joint swelling and deformity becomes severe and degenerates the cartilage is not sensible. Early treatment, preventative measures, and treatment that addresses complex underlying mechanisms is the realm of Integrative and Complementary Medicine.

Understanding the disease mechanisms of Rheumatoid Arthritis so that all systemic health problems are addressed in therapy

Research is uncovering the pieces of the puzzle to understand the underlying mechanisms of disease that lead to Rheumatoid Arthritis. While the patient may be focused on the specific joints that flare with symptoms of swelling and pain, there is no doubt that RA is a systemic disease, and many of the mechanisms of this disease either go unnoticed, or are diagnosed as other health problems that the patient does not connect to the RA. As stated, there is a strong correlation between stiffening of arterial walls and RA, and a common underlying health problem shared between these disorders is the accumulation of advanced glycation endproducts (AGEs) and subsequent excess formation of receptors for AGEs, called RAGEs. This subject is explained in detail below. There is also a growing concern with hormonal imbalances, especially as we see a predominance of the disease in women in the years of premenopausal to postmenopausal states, and excess prolactin in a high percentage of patients, indicating an endocrine disorder. A growing science of the relationship between hormonal balance, inflammatory dysfunction, and even neurotransmitter imbalance seen in standard medicine and research is also revealing of the systemic problems associated with RA (e.g. psychoimmunoneurology and mind-body medicine).

The activity of key inflammatory mediators, or cytokines, is the subject of much research related to the pathophysiology of RA, especially concerning tumor necrosis factor alpha (TNF-alpha). For the last 20 years, we have known that TNF-alpha, Interleukin-1 and 6 (IL-1, IL-6), GM-CSF (a white blood cell growth factor) and IL-8 are proinflammatory cytokines found in excess in RA patients. The cytokines that are meant to temper these inflammatory signaling chemicals are often deficient, including IL-10, TGF-beta, IL-1ra, and TNF-R. This signifies that an immune imbalance underlies the autoimmune mechanisms of RA. Deficiency or excess of growth factors also indicates that there may be a hormonal imbalance, and hyperprolactinemia has been highly associated with Rheumatoid Arthritis and other related autoimmune disorders, such as Lupus. Hyperprolactinemia is associated with hypothalamic dysfunction and hypothryoidism. Bringing the immune system, as well as the endocrine system, back into homeostatic balance is thus very important. Complementary Medicine has always had the goal of restoring homeostatic balance through natural therapeutic means. The amount of research that now is underway revealing how herbal and nutrient medicine achieves this goal, and how acupuncture may play a key role in homeostatic modulation, as well as deep tissue physiotherapy, is very impressive. The modern physician that specializes in these areas may utilize this research data to improve the therapeutic results.

The exact immune pathway in Rheumatoid Arthritis is the subject of much debate and research. Studies have revealed that an abundance of B-cells rather than T-cells, and an abundance of macrophages, exist in the synovial tissue of RA patients. Macrophages are also the predominant cells involved in creating atherosclerotic plaque lesions in atherosclerosis, which is highly correlated with RA. Macrophages play an important role in tissue regeneration, but appear to release different chemicals at different stages of tissue degradation and repair, due to the complexity of the complement immune system. While antirheumatic drugs have been created to inhibit TNF-alpha, more recent research indicates that other cytokines may be more important in the pathology of RA, and the creation of such immune specific drugs may be problematic in finding a cure or treatment for the disease. IL-18 has been implicated in RA pathology as a stimulator of excess VEGF and angiogenesis that is as effective as IL-1beta. IL-18 is a cytokine produced by macrophages and other cells that belong to the IL-1 superfamily. Studies (cited below) show that Curcumin, a chemical found in various Chinese herbs, inhibits the effects of IL-18 on VEGF. The advantage of utilizing Chinese herbal formulas in the treatment of Rheumatoid Arthritis is that the array of chemicals in the herbs affect a variety of mechanisms that are responsible for the disease pathology, and the array of chemicals in herbs are usually found to be modulatory because of complex evolution of these chemicals in plants.

Another theory of the underlying cause of RA and related autoimmune and collagen diseases is that a low grade infection related to amoebas, or protozoa, are responsible as the trigger for the autoimmune response. This is supported by the fact that drugs called pyrimidines, with anti-protozoal activity, are effective in the treatment of RA and other rheumatoid diseases. This also connects antibody responses and celiac disease to RA. Restoring health to the gastrointestinal system is often helpful, as this removes excess physiological stress on the immune system and clears low grade protozoal infections of a chronic nature. Deep low grade infections often penetrate to blood cells, and then to tissues with poor blood circulation, where natural immune defenses are more difficult, and these small microbes grow in quantity. When these infections affect blood cells, this may translate to altered immune cytokines produced by these cells, and when the infection penetrates tissues such as the joint synovium, which normally has poor vascular circulation, but even in early stages of RA develops increased vascularity in response to immune needs, an autoimmune response may result. This may be the reason why antimalarials are also effective in the treatment of RA.

While the complex pathophysiology of Rheumatoid Arthritis is still too difficult to understand completely, research has shown us the progression of disease manifestation, and this points to key areas of emphasis in treatment and prevention. RA dramatically affects the jont synovium, or tissue that covers the entire joint complex, to which muscle tendons are attached. Normally, this synovial tissue is thin and poorly vascularized, and joint motion is responsible for much of the flow of blood nutrients to the tissues. In advanced stages of RA, the joint synovium goes from a very thin states, usually 1-3 cells thick, to a thickened state called hypertrophy, usually 8-10 cells thick. The density of the cell population in this synovium of advanced RA is also dramatically increased, and the primary cells are now macrophages and fibroblasts, with a high population of B-cells. B-cells are immune white blood cells, or lymphocytes, that are manufactured in bone marrow, retain an immune memory, and manufacture antibodies to foreign microbes, toxins, etc. These immune changes in the synovium stimulate much increase in the creation of small blood vessels (angiogenesis). While the early stages, or onset, of RA may be attributable to T-cells, which are white blood cells originating the thymus, and are key cells in the learned immune responses, there is an abscence of T-cells in more advanced synovial tissues in RA. The bridge between the B-cell, or innate immune response, and T-cell, or adaptive immune response, is the NK cell, called the Natural killer T cell. NK cells recognize antigens on the glycolipid membranes of cells. This has pointed scientists to heavily research altered glycolipids in the body, and hence advanced glycation endproducts (AGEs) are a subject of considerable interest in the research.

Tumor necrosis factor (TNF-alpha) is an immune cytokine that is one of the many cytokines in the complement system that may promote the excess inflammatory responses and systemic health problems in RA, such as endocrine dysfunction, appetite suppression, low grade fever, increased C-reactive protein, and insulin resistance. TNF is mainly produced by macrophages, but also by other lymphoid cells, mast cells, endothelial cells, fatty tissues, fibroblasts, and nerve tissues. Excess amounts of TNF are released in response to lipopolysaccharides, bacterial products, and the cytokine IL-1. Lipopolysaccharides are similar to advanced glycation endproducts, and cell receptors for advanced glycation endproducts (RAGES) may respond to lipopolysaccharides. It is theorized that AGEs may stimulate increased TNF responses as well, or at least act cooperatively with lipopolysaccharides to induce proinflammatory cytokine production (see study link below). Lipopolysaccharides compose the outer shell of bacteria, and when these bacteria are broken down by T-cells and cytokines, an excessive TNF response may result. Ultimately, the patient, in advanced stages of RA is prescribed TNF inhibitors. The problem is, since the TNF response is so integral to our normal healthy immune responses, which keep us alive, systemic inhibition of TNF with synthetic drugs is problematic. The problems presented by the therapy are dramatic. This leads many patients, and a growing number of MDs, to consider other approaches. Research has led us to the holistic approaches of Complementary and Integrative Medicine. While this approach is more complicated than simply taking one pill, a TNF inhibitor, the safety and overall benefits are dramatic, and worth the effort.

It is well known that chronic Rheumatoid Arthritis is often exacerbated by emotional and psychological stress. In recent years, the subject of an interrelationship between the immune, endocrine and nervous systems has been finally explored in more depth, usually referred to as Psychoimmunoneurology. This is a field now of standard medicine that admits to a holistic emphasis on scientific understanding of chronic disease mechanisms. For decades, research has unveiled the important relationship between hormones, inflammatory cytokines, and neurotransmitters, which often all stimulate the same cell receptors. Neurotransmitters may play an important role at times as hormonal triggers, hormones may stimulate nervous responses, and cytokines may modulate these effects dramatically. For this reason, holistic medicine is now becoming an important consideration for diseases such as RA. The complexity of these mechanisms requires a more holistic and comprehensive treatment strategy that must utilize Integrative and Complementary Medicine to fulfill the goals of better outcomes.

Systemic manifestations and related diseases

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.

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.

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.

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 cancerour 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.

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 pothological processes reveals both the need for holistic Complementary integrative Medicine, and provides the Complementary physician access to new specifics to aid therapy.

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.

Information Resources

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 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://gretchen till The American Academy of Orthopaedic Surgeons states that Rheumatoid Arthritis manifests with foot symtpoms 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 fatique, and loss of appetite: http://orthoinfo.aaos.org/topic.cfm?topic=A00163 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 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 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 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 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 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 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 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 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 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 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 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 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 Studies in 2010 at the University of Maryland School of Medicine found that methanol tincture of the Chinese and Indian herb Celastrus aculeatus, and the product Celastrol, both effectively attenuated inflammatory responses to significantly improve rheumatoid arthritis:http://www.jbc.org/content/286/17/15138.abstract 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 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 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 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 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 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 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 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 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 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 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 induced expression of this growth factor in human cells:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC185762/ Studies have cast doubt on the ability of aminoguanidine to inhibit AGE formation:http://www.ncbi.nlm.nih.gov/pubmed/10221660 Effects on nitric oxide inhibition by chemicals in Huang qin, studied at Taipei Medical University: http://www.ncbi.nlm.nih.gov/pubmed/11331078 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 Effects on nitric oxide inhibition by Fang feng, studied at Taipei Medical University:http://cat.inist.fr/?aModele=afficheN&cpsidt=1968748 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 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 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 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 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 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 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 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