New discoveries show that osteoarthritis may largely be caused by inflammation, not worn out joints
Researchers at Stanford University have made an explosive discovery that threatens to show how medicine got it all wrong when it comes to osteoarthritis. Doctors have long assumed that the disease is largely caused by traumatic injury or mechanical problems of 'wear and tear', like a piece of worn-out machinery. But as the Stanford research suggests, the disease and what appears to be mechanical wear may in fact be largely driven by low-grade inflammation.
In 2011, associate professor of immunology and rheumatology William Robinson and his colleagues at Stanford carried out studies showing that osteoarthritic joint tissues contain larger numbers of migratory inflammatory cells that secrete certain substances early on in the progression of the disease.
The presence of these substances triggers the 'complement cascade', a chain of molecular events that eventually escalates into an attack-mounted by the body's own defense systems, usually only deployed against invading microorganisms-against the joint itself.
Doctors have witnessed evidence of inflammation in the cells of arthritis patients (albeit not nearly as much as in rheumatoid arthritis), but the Stanford team's discovery of a heightened number of inflammatory cells in the early stages of the disease, before it causes symptoms, suggests that inflammation could be the central 'driver' of osteoarthritis as well.
This may mean that osteoarthritis, like rheumatoid arthritis, is in fact an autoimmune condition-where the body begins to attack itself. This would also explain why osteoarthritis is not simply a disease of the elderly but, in many instances, starts in a person's 40s.
Robinson and his team made use of sophisticated lab techniques to compare levels of proteins present in the joint fluid of osteoarthritis patients with protein levels in the joints of healthy, non-arthritic people. The team discovered an enhanced expression of genes that activate inflammatory proteins, a larger than normal number of proteins that accelerate the complement cascade and a fewer than normal number of proteins that act as a brake.
When the researchers examined how this process could lead to osteoarthritis in both the joints of animals and human tissue, they discovered a cluster of proteins called the 'membrane attack complex' (MAC), the nuclear weaponry of the complement system, that binds to cartilage-producing cells. Ordinarily the MAC reserves its might to punch holes in virus- or bacteria-infected cells, whereas binding to cartilage cells causes them to secrete more complement-cascade proteins, inflammatory chemicals and enzymes than usual.
This process ultimately destroys cartilage in the spaces between cells, while a breakdown product of this cartilage destruction called 'fibromodulin' keeps switching the complement system on, so creating a continuing cycle of destruction.
When the researchers examined the joints of animals that had developed arthritis, they found an association between the level of attack by the complement system and the level of functional impairment-the more active the complement system, the more abnormal the animal's gait.1
"This low-grade complement activation contributes to the development of degenerative diseases, including Alzheimer's disease and macular degeneration. Our results suggest that osteoarthritis can be added to this list," said Robinson.2
Robinson considers their discovery a paradigm shift in the way medicine views arthritis. The current medical view is that osteoarthritis is incurable and the usual recommendations are to lose weight, exercise and take numerous drugs to manage pain and supposedly inflammation too, and look forward to joint-replacement surgery. The course of treatment is a tightrope walk between reducing pain without bringing about a load of toxic effects on the heart and liver.
These new findings also have huge implications for how medicine deals with osteoarthritis. Rather than treating it as an inevitable part of growing old, the Stanford research suggests that an individual's lifestyle might be analyzed to determine what's causing the chronic inflammation and what sorts of natural compounds might help lower it to inhibit progression of the cycle.
These new findings offer the first laboratory confirmation of what many practitioners of functional medicine have found to be the case in clinical practice. Dr John Mansfield, author of Arthritis: The Allergy Connection (Chivers Press, 1991), who successfully treated several thousands of arthritis patients in the UK at his clinic in Surrey before recently retiring, believes that most forms of arthritis are "environmentally induced" by an intolerance to food or certain environmental chemicals and that some 90 per cent of patients can be improved or fully cured just by making certain lifestyle changes.
Finding out what in your lifestyle is causing inflammation in your body is a matter of doing a bit of detective work. Ideally you should carry out this investigation with a qualified and experienced nutritional practitioner, who can help you find the cause and choose from among a plethora of natural treatments that have been shown to work as well as, and sometimes even better than, drugs.
Are you overweight?
Carrying too much weight does increase the load on joints and seems to be one of the major factors in advancement of the disease. Common targets for osteoarthritis in overweight people include not only the weight-bearing joints of the body like the knees, but the finger joints too, suggesting that the link between obesity and osteoarthritis is due to factors other than just biomechanical loading.
Researchers at the Department of Orthopaedic Surgery at Washington University School of Medicine in St Louis, Missouri, believe that fat tissue is a major source of proinflammatory mediators like cytokines, chemokines and adipokines, metabolic factors known to have inflammation-boosting properties that help to 'orchestrate' the process of osteoarthritis.3
The obesity connection may have more to do with a patient's overall diet and lifestyle, and how they contribute to insulin resistance and metabolic imbalances-the so-called 'metabolic syndrome', which is connected with atherosclerosis, diabetes and other modern-day degenerative diseases. The major contributors are too much sugar, processed foods and fried foods, which release oxidizing free radicals into the system that, in excess, can damage the tissues around joints.
What to do about it:Get off fried foods and the white stuff-refined sugars and carbs and all processed foods. Adopt a plant-based Mediterranean diet that's low in saturated fats, and include generous amounts of inflammation-reducing foods like citrus and dark leafy greens (both as fresh as possible). Citrus fruits are high in antioxidants and the greens are rich in vitamin K, another natural anti-inflammatory.
Do you have an imbalance of fatty acids?
Today's processed diets feature too-high intakes of omega-6 fatty acids, known to lead to inflammation and, in turn, joint destruction, swelling and pain, and too-low intakes of omega-3 fatty acids.4 Patients with osteoarthritis also suffer from dysfunctional mitochondria, the power packs of our body's cells that supply the energy needed for cells to do their jobs.5
What to do about it:Balance your intake of omega-6 to omega-3 fats to the ideal ratio of 1:1 to 5:1 by supplementing with omega-3s.
Suggested daily dosage:1,400 mg of EPA and 1,000 mg of DHA.
Do you have a food intolerance?
Many nutritional specialists such as nutritional doctors and naturopaths find that osteoarthritis is often caused by food allergies or intolerances, and that a majority of arthritis patients are sensitive to nightshades. This food family includes white potatoes, eggplant (aubergine), sweet and hot peppers like cayenne and paprika (not the black and white kind sprinkled on food), tomatoes and tobacco. The entire nightshade family (the Solanaceae plant family) contains many of the natural toxic chemicals of belladonna (deadly nightshade). In a survey of 5,000 arthritis sufferers, 68 per cent reported complete or substantial relief after eliminating nightshades from their diets.6
The late San Francisco-based Dr Collin H. Dong, himself a victim of arthritis, developed a 'caveman-type' diet to deal with his own crippling arthritis. Within a few months he was free of symptoms and able to return to playing golf.
The Dong diet was devised to avoid many of the most common allergens, including artificial ones, and avoids meat, fruit (including tomatoes), dairy, vinegar and other acids, all varieties of pepper, hot spices, chocolate, dry-roasted nuts, all alcohol and particularly wine, soft drinks, and all additives, preservatives and chemicals, especially monosodium glutamate (MSG). Because it avoids meat, the diet is naturally high in fish, and fish oils are now widely recommended as good for arthritis patients.
The 15 most common allergens
Potatoes and other nightshades (tomatoes, peppers, aubergine and tobacco)
What to do about it:Suspect an allergy if you have: weight issues (either over- or underweight); swelling of the hands, eyes, ankles or abdomen; excessive sweating, even with no exertion; constant fatigue despite adequate sleep; and a too-rapid heart rate, especially after meals. Work with an experienced nutritional therapist to carry out food-allergy tests, and try an elimination diet, the intradermal provocative-neutralization (skin-prick) method or the enzyme potentiated desensitization (EPD) technique developed by Dr Len McEwen, formerly of the department of allergy at St Mary's Hospital in London. With neutralization techniques (favoured by Mansfield and subject to many more safety tests), the patient is given (by either injection or drops under the tongue) tiny amounts of various triggering agents, and any reactions (usually skin wheals) suggest that the person is intolerant of that agent. Remove those foods from your diet or get yourself desensitized to them.
Is your gut leaky?
Increased intestinal permeability (so-called leaky gut) leads to the absorption of incompletely digested proteins through the gut wall, which has been linked to many diseases, including arthritis and joint problems.7 If you've been taking non-steroidal anti-inflammatory drugs (NSAIDs) over the long term, then you almost certainly have a leaky gut as these drugs are known to adversely affect intestinal permeability. Just a single dose of, for example, aspirin or indomethacin can increase permeability in the gut wall by blocking synthesis of the protective lipid compound prostaglandin.8
Long-term NSAID use as occurs with osteoarthritis leaves the gut very inflamed and highly permeable and so perpetuates the problem.
What to do about it:Take the lactulose/mannitol challenge test for gut permeability (available from the Biolab Medical Unit in London or Genova Diagnostics in North Carolina in the US), then follow our '7 Steps to a Good Gut' (in the October 2013 issue of WDDTY). Be sure to take probiotics, shown to improve gut permeability, and pick a brand that includes lactobacilli, bifidobacteria, Saccharomyces boulardii and non-disease-causing strains of Escherichia coli and streptococci.
Are you sensitive to a chemical?
Besides food, Dr Mansfield finds that numerous environmental chemicals such as tobacco smoke, pesticides, perfume and even hair spray can bring on arthritis, as can house dust, dust mites and moulds. The late Dr Theron Randolph of Chicago, Illinois, who first developed the theory of chemical sensitivity, found that household gas, formaldehyde and the pesticides found in food supplies also contributed to many cases of arthritis. Indeed, many of Dr Mansfield's patients proved to be allergic to household gas, and immediately improved or entirely resolved their symptoms when they switched from gas to electricity for cooking.
What to do about it:Besides cooking gas and petrol fumes, suspect the chemicals in personal toiletries and home-cleaning products. Breast implants and other silicone prostheses may also cause arthritis-like symptoms like joint swelling and promote antibodies to collagen, which then collect in susceptible tissues.9 Some women have seen their arthritic symptoms disappear after having their implants removed. Intradermal neutralization treatment can also be used for chemical or inhaled allergies or intolerance (available at the Burghwood Clinic in Banstead, Surrey; tel: 01737 352 245; www.burghwoodclinic.co.uk).
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NANS: the non-anti-inflammatories
If you're less than happy with the drugs you take for osteoarthritis, Dr Peter Gotzsche, head of the Scandinavian arm of the Cochrane Collaboration and one of its founders, believes he knows why.
He has made the extraordinary charge that non-steroidal anti-inflammatory drugs (NSAIDs) don't reduce inflammation.
"The idea of an anti-inflammatory effect of NSAIDs is a hoax, like so many other myths about drugs that the drug companies have invented and marketed," he states uncategorically in his latest book, Deadly Medicines and Organised Crime: How Big Pharma has Corrupted Healthcare (Radcliffe Publishing, 2013; see News Focus, page 18).
Gotzsche has conducted extensive studies into non-steroidal anti-inflammatories, beginning from the time he was medical director at Astra-Syntex in 1977. Astra had produced naproxen, an early NSAID and, when Gotzsche investigated the actions of various NSAIDs, he discovered that drug companies were manipulating information about this entire class of drugs and giving doctors the impression, through inference and with no supporting data, that NSAIDs were better than paracetamol (acetaminophen) because they didn't just reduce pain, but also reduced inflammation.
When Gotzsche and a group of orthopaedic surgeons carried out their own independent study of naproxen, they found that the drug had no effect on reducing inflammation in patients with twisted ankles; patients recovered faster simply by moving the affected limb.
After studying some 244 NSAID trials, Gotzsche uncovered an overwhelming amount of bias favouring any given sponsoring company's drug over the control drug.1 Then, in his own studies, the drugs failed to work as anti-inflammatories; when compared with placebos, they had no effect on swollen finger joints in patients with rheumatoid arthritis.
But the most scandalous aspect of the NSAID trials, he says, was that dangers of the drugs, many of which cause gastrointestinal bleeding and heart attacks, were minimized.
Furthermore, Gotzsche discovered that doubling the dose, as patients have often been encouraged to do with all NSAIDs, produced negligible benefits, yet twice the amount of harm, including an increased risk of bleeding ulcers and death.2
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The top alternative arthritis disease-fighters
Given the persistent problems with conventional treatments, it's little wonder that many arthritis sufferers have looked to alternative medicine for help. One recent study found that 83 per cent of a sampling of patients used alternative treatments for their arthritis, and nearly half hadn't felt pain since they started doing so.10 Here are the most well-researched ones shown to have good effects in terms of lowering inflammation and improving joint function. Doctors like John Mansfield also recommend that patients supplement with a good multivitamin/mineral complex, B complex with at least 25 mg of B5 (pantothenic acid) and B3 (niacinamide), zinc (50 mg), vitamin C (up to 3,000 mg), vitamin E (400 IUs), selenium (200 mcg), and vitamin D (2,000-3,000 IU) if you are deficient
Glucosamine and chondroitin
Glucosamine is the major building block of proteoglycans, large molecules in cartilage that give it elasticity and maintain joint lubrication and flexibility by trapping water in the cartilage matrix. Chondroitin, an even larger cartilage molecule, helps to maintain joint fluidity, while slowing cartilage destruction and helping with its repair.11
Although the medical community has disparaged these supplements after several studies showed glucosamine to have no effects, those trials have since been criticized as having serious flaws and poor study design, while many other studies have shown that these supplements can be highly effective. Taken orally, these two agents take only four hours to be taken up by the joints and, in laboratory tests, they've increased the protective effects of cartilage and can even spur cartilage growth. One theory is that they work by improving the quality of the synovial fluid surrounding the joints. In addition, clinical trials (in people) show that glucosamine appears to be a natural anti-inflammatory able to inhibit progression of the disease, while chondroitin helps reduce cartilage loss and arthritis of the knee and fingers, helping to reduce cartilage loss in as little as six months after starting supplements.12
Suggested daily dosage: Glucosamine sulphate: up to 3,200 mg; chondroitin:
up to 3,600 mg
This naturally occurring compound, present in virtually every tissue and fluid in the body, is known to be a powerful anti-inflammatory; besides reducing pain, it can improve joint function and ease stiffness.13 SAMe appears to stimulate the production of cartilage and, although researchers don't know exactly why, it may even reduce inflammatory mediators, influence cartilage synthesis and survival, and boost the production of antioxidants.14
Suggested daily dosage: Up to 1,200 mg in divided dosages
A source of bioavailable sulphur found in the tissues and fluids of all plants, animals and humans, MSM can reduce pain and swelling, and stop the destruction of joints by scavenging the free radicals that cause inflammation. It's been shown to reduce pain and improve function when taken orally for at least 12 weeks.15
Suggested daily dosage: Up to 1,200 mg in divided dosages
Undenatured type-II collagen
Supplements of this nutrient appear to switch off the autoimmune response that results in inflammatory attacks on joints, at least in studies of arthritic horses.16
Suggested daily dosage: 10 mg
This form of fluid carbohydrate is one of the building blocks of cartilage, and supplements appear to decrease the production of enzymes that damage healthy cartilage tissue and also interfere with pain signals. When injected directly into the knee joint, it can help improve function.17 It can also be taken orally and, based on animal studies, this appears to work best when taken in a preparation that includes phospholipids.18 People with osteoarthritis of the knee had less pain and overall improvement in function with oral daily supplements taken for eight weeks.19
Suggested daily dosage: 40 mg
An extract of French maritime pine bark, Pycnogenol(R), reduced the pain and stiffness of mild osteoarthritis in one study-effects that kicked in after eight weeks. Those taking Pycnogenol(R) were able to reduce their use of painkillers and carry out more of their everyday activities.20
Suggested daily dosage: As directed on product packaging or by a practitioner
This protein-splitting enzyme derived from pineapples (Ananas comosus) may work better than the NSAID diclofenac in reducing pain and improving function.21
Suggested daily dosage: 90 mg three times a day
This yellow pigment, a natural plant phenolic compound derived from the turmeric plant (Curcuma longa), has long been used to treat joint inflammation in Ayurvedic medicine, the traditional system of medicine in India. It can halt cartilage destruction and reduce inflammation.22
Suggested daily dosage: 400-800 mg
Soybean/avocado unsaponifiable (ASU) oils
These special oil mixtures can promote cartilage repair and reduce circulating levels of proinflammatory cytokines, so improving function and reducing pain as well as the need to take NSAIDs.23