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COX-2 or Not COX-2

by Dr. Marcus Laux

Published 03/05/09

The rise and crashing fall of synthetic COX-2 inhibitor drugs has been one of the biggest news stories of the decade. It has seemed like a nightmare to many patients, but it may mark the end of the hype for the super aspirin being a better and safer drug for pain and inflammation. COX-2 inhibitors are no better at pain relief than other available drugs, and their safety was never definitively demonstrated. 

The change may be bad for the pharmaceutical pushers, but it's very good for you. There are plenty of viable alternatives that offer relief, with few adverse effects and none of the health threats of the highly COX-2-selective drugs.

Whence the Problem?

COX-2 inhibitors cause trouble because they work too well. The synthetic chemicals used in the drug versions are masterfully crafted, and work very efficiently and speedily, but they throw the relationship between COX-1 and COX-2 out of balance-which increases the likelihood of adverse effects. The damaging bleeding effects of the COX-1-inhibitory NSAIDs led to the research into COX-2 inhibitors. Now it looks like we're at the end of this road.

What are COX-1 and COX-2 anyway? They are enzyme systems designed to help you take care of your body's housekeeping needs. COX-1 enzymes are found all over, and help protect and repair your GI tract lining, platelet functioning, and kidney/blood vessel control. COX-2 enzymes are required for inflammation-a healthy and necessary part of healing. However, if out of balance and over-activated, persistent inflammation is damaging and painful.

Here's the rub with all the drug choices. The classical NSAIDs cause gastric inflammation at least partly by shunting arachidonic acid into the lipoxygenase pathway-causing an overproduction of damaging and pro-inflammatory leukotrienes. Not good.  

OK, then let's try door #2-the highly selective COX-2 enzyme inhibitors. These drugs push arachidonic acid the other way, increasing the production of thromboxane A2 over prostaglandin I2. This imbalance can lead to thrombosis and cardiac concerns. Also not good. Either choice works at relieving pain, but both carry serious adverse effects and have caused countless tragic deaths. 

The highly selective, over-efficient functioning of the COX-2 synthetic drugs means they are damned, doomed, and done. Because of the potential promise of this class of drugs, however, people have been searching for a safer and more natural COX-2 inhibitor. 

This may be the wrong solution, or at most a part of the solution. Any compound that is highly selective for COX-2, whether synthetic or taken right from nature, will cause the same problems. A new type of thinking is needed to provide better, safer, more dependable pain relievers. Fortunately, better products are available, and have been for quite a long time. 

What Makes Nature Safer?

There is talk of "natural COX-2 alternatives." Are they different? Are they safe? From what we know now, yes, on both counts, but there is more to the story. 

What is being called a natural COX-2 inhibitor does indeed inhibit COX-2 binding, but there are some significant differences to note. The most important difference is that these natural products are not highly selective, meaning that they affect both COX-1 and COX-2 pathways. As a result, they will not throw your body out of balance the way drugs do. It may mean that they take a bit longer to reach full effect, or that you may need to add something else to intensify the effect, but the result is that you run a much lower risk of adverse events.

Another difference is that natural alternatives have nowhere near the activity level the synthetic drugs have. The analogy I'd use is the difference between the real female hormone estradiol and the plant phytoestrogens or isoflavones. They affect the same receptor, but have a very different degree of strength. Or, the use of statins, where the original ones were weaker than the newer ones with all the major problems and adverse effects. They work the same, but the high-powered efficient ones shut down a pathway with dire consequences, while the weaker ones interfere to a lesser degree to achieve a new balance.

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