The vicious cycle of NSAID use

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world for the treatment of osteoarthritis (OA) symptoms, and are taken by 20-30% of elderly population in developed countries. Because of the potential for significant side effects of these medications on the liver, stomach, gastrointestinal tract and heart, including death, treatment guidelines advise against their long term use to treat OA. One of the best documented but lesser known long-term side effects of NSAIDs is their negative and degenerative impact on articular cartilage.

In the normal joint, there is a balance between the continuous process of cartilage matrix degradation and repair. In OA, there is disruption of this balance thus leading to the breakdown of chondrocytes. It is clear from the scientific literature that NSAIDs from in vitro and in vivo studies in both animals and humans have a significantly negative effect on cartilage matrix which causes an accelerated deterioration of articular cartilage in osteoarthritic joints. The evidence shows that NSAIDs have no beneficial effect on articular cartilage in OA and accelerate the very disease for which they are most often used and prescribed. Some of the effects of NSAIDs on the articular cartilage in OA include inhibition of chondrocyte proliferation, synthesis of cellular matrix components, glycosaminoglycan synthesis, collagen synthesis and proteoglycan synthesis. The net effect of all or some of the above is an acceleration of articular cartilage breakdown.

Lets go into more details on the affects of NSAIDs:

1. Promotion of bone necrosis and cartilage destruction: many of the drugs interfere with chondrocyte function and cartilage formation and thus promote the destruction of joints. In addition, NSAIDs reduce glycosaminoglycan synthesis (provide lubrication and act as a shock absorber). NSAID also inhibit COX-2 which impairs anabolic bone activity that is neccessary for the preservation of bone strength.

2. Gastric ulceration and gastrointestinal bleeding: Almost all NSAIDs cause gastric ulceration and gastrointestinal bleeding. Those patients who regularly use NSAIDs will develop intestinal inflammation and develop gastroduodenal ulceration. All the NSAIDs differ greatly in their ability too damage the gastrointestinal mucosa but aspirin appears to be the most problematic. NSAIDs also promote and exacerbate colitis and inflammation of the large intestine.

3. Increased intestinal permeability: NSAIDs damage the mucosa of the small intestine and promote macromolecular absorption and paracellular permeability i.e. "leaky gut". Increased permeability contributes to the exacerbation of many rheumatic and musculoskeletal disorders by inducing inflammation via immune activation that are deposited into synovial tissues for the induction of a local inflammatory response inside the joint.

4. Promotion of hepatic and renal injury and failure: chronic use of NSAIDs is an important risk factor for the development of renal failure. Hepatic injury is less common than renal failure but can be achieved with high drug doses and alcohol consumption. 


Natural Alternatives to NSAIDs

1 Avoiding pro-inflammatory foods: Arachidonic acid (high in cows milk, beef, liver, pork and lamb) is the direct percursor to pro-inflammtory prostaglandins and leukotrienes and pain-promoting isoprostances. Saturated fat promotes inflammation. high-glycemic foods cause oxidative stress and inflammation via activation of NFkB as well suppress the immune system. 

2. Fish oil: prerequisite to reducing the pro-inflammatory effects of omega 6 fatty acids

3. Ginger: Ginger has a long history for its anti-inflammatory effects as well as anti-nausea and gastro-protective properties. Ginger has been shown to reduce production of the leukotriene LTB4 by inhibiting 5-lipoxygenase and to reduce production of the prostagladin PGE2 by inhibiting cycloxygenase. With its dual reduction in prostagladin and leukotrienes, ginger has been shown to safely reduce non-specific musculoskeletal pain and to provide relief from OA of the knees and migraine. 



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Krina Panchal