Friday, July 15, 2011

NSAIDs - Risks and Alternatives

Now with New and Improved Side Effects!
Doctors used to say “Take two aspirin and call me in the morning.” These days it sounds more like “take two NSAIDs and call me in the morning.” Aspirin was the first pharmaceutical to take advantage of the natural healing qualities found in Willow Bark. Aspirin has the ability to decrease inflammation, pain and fever. Aspirin has many valuable qualities but also a large number of side effects and dangers, gastro-intestinal bleeding being the most recognized example.

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) are the single most commonly used class of drugs in the developed world. Almost everyone from professional athletes to elderly patients in nursing homes use them, many on a daily basis, to reduce swelling (inflammation) or pain. They come in many shapes, sizes, colors, and brand names -- Aspirin, Ibuprofen, Ketoprofen, Aleve (Sodium Naproxen), and many more. NSAIDs are considered by many to be a great treatment for inflammation or pain, and indeed they work well for this purpose, but there is more to the story.

Pharmaceutical companies have tried over the years to develop new drugs that could improve on Aspirins anti-inflammatory qualities and hopefully decrease some of the risks that Aspirin carries. Non-Steroidal Anti-Inflammatory drugs (NSAIDs) are the result of this research. Unfortunately, most of these drugs are as risky to use as Aspirin and many can be even more dangerous.

The problem is that the pathways and mechanisms that lead to inflammation are also essential in other systems in the body. Inflammation, it turns out, is not always a bad thing. In fact, inflammation is essential to normal body healing and repair. Inflammation is part of a complex system which recognizes when an area has sustained some damage (even minor damage in a few cells) and the inflammatory response is one of our bodies ways of healing us. Inflammation only becomes a problem when it goes beyond its original purpose and can’t stop doing it’s job, at this point it can start to lead to pain or even physical damage.

An obvious question arises, why do we ever want to interfere with the bodies efforts to heal us? Therein lies one of the key issues I want to address in this post. Why do we think it’s a good idea to simply pop Aleve, Ibuprofen, Aspirin, or any other anti-inflammatory medication at the first sign of a problem? Shouldn't we give our bodies an opportunity to take care of the problem without chemical interference? And if we do want to interfere, could there be products available that actually help the body safely repair itself, while reducing symptoms like pain and inflammation? In other words, wouldn’t we want to find an anti-inflammatory medication that not only has very few side effects, but also one that is actually valuable and necessary for the body to use in it’s healing?

My answer to these questions is simple, there are anti-inflammatory substances that do exactly this. So why are they not recognized, prescribed, or advertised to physicians and the public as such? Unfortunately, as is often the case, the story focuses around money.


There are many natural anti-inflammatory agents available that work on the same mechanisms as NSAIDs but which also have beneficial effects on the body apart from their anti-inflammatory activities. Most of these substances have been used for hundreds or even thousands of years and our ancestors turned to these substances (or had them as part of their diets) for many reasons. Solid and convincing research has surfaced over the last few decades which demonstrate their safety and efficacy in reducing inflammation. And, as I mentioned, they often also have the benefit of having “side effects” that are actually health promoting!

One of the most effective, widespread, and safe alternatives to NSAIDs is fish oil.

Fish oil is a natural and healthy source of anti-inflammatory substances known as Omega-3 fatty acids. Omega-3 (and Omega-6) fatty acids have a rather amazing combination of health benefits and very few known bad side-effects or contraindications. For example, Omega-3 fatty acids can inhibit the production of pro-inflammatory eicosanoids (chemical messengers in the central nervous system) and serve as precursors for resolvins (protective lipids that help reduce inflammation). In addition, fish oils help prevent cardiovascular disease (one of the very things NSAIDs effect negatively) and have positive effects on many inflammatory disorders, such as arthritis, asthma, and ulcerative colitis.
While the benefits of fish oil are many, there are still some risks associated with taking them.

It is important that the fish oil come from the fish’s body and not the liver. Cod liver (and other fish liver) oil contains the active form of Vitamin A. At high levels, Vitamin A can be extremely dangerous and can cause Hypervitaminosis A.

Fish oil may also contain toxic chemicals (mercury, PCBs, dioxins, etc.) and should be purified by the manufacturer. As with any other product, it is important to find a quality manufacturer that takes the extra effort to ensure a supplement that is safe and effective.

Persons with bleeding disorders or patients undergoing surgery should check with their doctor before taking fish oil, as fish oils have some effects on blood clotting.

Other effective and safe Anti-inflammatory agents include Green tea extracts, Turmeric, White Willow bark, Ginger, Boswellia (look for a later posts where we will discuss these and other alternatives in greater detail).


There are a number of problems and side effects associated with taking NSAIDs. Our bodies are very sophisticated and use many systems redundantly as a way of backup in case one or more systems fail. So, why create a new system and group of chemicals when your body can use the ones it already has. The problem is that targeting one problem like inflammation often leads to many other changes that you may not have wanted to have happen at all.

Therefore, interfering with one system, like inflammation, affects many other systems that also use or need those chemicals for their function. In the case of anti-inflammatory drugs, the list of other effected areas can be extensive -- especially your gut, heart, lungs, and kidneys. So things can, and do, go very wrong in these systems when you start using NSAID’s or Aspirin for any significant length of time. But, how bad could it really be?

Advil can kill you at anytime
Image Credit from Rob! at Flickr
Perhaps the most serious complication of chronic NSAID use is Gastro-Intestinal (GI) bleeding. NSAID related GI bleeding is the #15 leading cause of all deaths in the US (Lanier, 2004). Regular use of NSAIDs can disrupt the regrowth of the cells lining your stomach and intestine causing stomach acid to break through and cause ulcers and serious (even life threatening) bleeding. This is why many physicians prescribing NSAIDs will now also prescribe a drug (e.g a proton pump inhibitor) to protect the patient’s stomach during treatment. Isn’t it odd that to take the “helpful” NSAID you need to take a second drug to protect you from this dangerous side effect?

Kidney failure is also a serious risk with long term use of NSAID drugs. In fact, the #1 cause of all kidney failure in the US is NSAID related. Over time, use of NSAIDs will reduce the flow of blood to the kidneys (Nessel, 2010). Dehydration makes kidney damage even more likely. Since NSAIDs are used often during or after people exercise or perform strenuous activities, related dehydration may also increase the likelihood of NSAIDs doing damage (Lanier, 2004). For someone who likes to exercise, the consequences of having to undergo regular dialysis and change their lifestyle so dramatically because of kidney failure can be severe.

Asthma can also be worsened or triggered by use of NSAIDs. The chemicals that NSAIDs act upon (prostoglandins) are important for relaxing the bronchial muscles, and this can cause asthma attacks, even with light physical activity (Lanier, 2004).

And then there is the small matter of heart attacks and strokes. Significant congestive heart failure is a serious concern for people who have a history of heart problems. A recent study in the American Journal of Medicine (July 2011) showed regular use of NSAIDs doubled the number of deaths in elderly patients with hypertension or coronary artery disease. In addition, NSAIDs are known to interact with heart medications such as diuretics and ACE inhibitors. Even more surprising, if a patient takes Aspirin for its heart protecting properties, the effects can be completely negated by taking another NSAID at the same time.

With so many risks involved, why do doctors prescribe these drugs so readily and why are they allowed to be sold over the counter at pharmacies without even requiring a prescription? The real question that needs to be asked is, are there are any safer and effective alternatives to NSAIDs for inflammation? If so, why are they not being prescribed instead of these more dangerous drugs? With all of these problems, why are NSAIDs allowed to even be marketed?


Some of the drug companies who developed and sold these drugs were recently caught withholding information about their safety. This information caused a huge media storm when congressional hearings exposed that the Merck, the manufacturer of Vioxx, a widely prescribed “miracle drug”, deliberately buried evidence of the drug’s terrible side effects. Even Merck’s own studies showed an increased risk of heart attacks and strokes associated with using Vioxx.

The VIGOR (Vioxx GI Outcomes Research) study, conducted by Bombardier, et al., was conducted to determine how safe and effective Vioxx and Naproxen (Aleve) were for patients. Merck scientists found that Vioxx showed a 4x increased risk of heart attack versus Naproxen (0.4% vs 0.1% increase over placebo). Instead of reporting that Vioxx significantly increases the risk of heart attack in at risk patients, they instead claimed that Naproxen has a "protective effect" against heart attacks. Many scientists roundly rejected this absurd claim and eventually, the FDA sent a letter to Merck’s CEO warning them to stop their misleading marketing by essentially lying to the public.
"Your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator non-steroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen)."
In other words, it’s not that Naproxen has a protective effect, it’s that Naproxen causes heart attacks and strokes less often than Vioxx, but they both caused more than placebo.

So Merck got into trouble because of their false marketing and burying of evidence, but the truth is, almost all NSAIDs generally work using similar mechanisms to Vioxx. Since Vioxx was removed from the drug market due to these very serious safety issues, why have other NSAIDs remained  available for anyone to buy over the counter?


Given that the risks of fish oil are so dramatically lower than any NSAID drug, while also having increased health benefits, we can’t understand why more doctors are not suggesting that patients take fish oil supplements as a first line therapy for inflammation. As always, ask your health care provider about whether fish oil would be a good choice for you. If so, make sure that you check with your practitioner which products they recommend as safe and toxin free, as well as what dosage would be appropriate  in your particular case.  Fish oil and/or other natural anti-inflammatory agents may allow you to transition away from long term NSAID use or perhaps, to never start taking these risky drugs in the first place.


For more information:

Adverse Events Associated with NSAIDs
Chronic NSAID Use Doubles CV Deaths in Elderly
NSAIDs and Musculoskeletal Treatment What Is the Clinical Evidence?
The Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in Treating Delayed Onset Muscle Soreness (DOMS)

On Fish Oil and other Natural Anti-Inflammatory Agents:
Is there research on whether fish oil supplements help ease joint pain?
Omega 3 Fatty Acids Overview: The University of Maryland Medical Center
Natural Antiinflammatory Agents for Pain Relief in Athletes: Overview of Natural Antiinflammatory Agents
Anti-inflammatory actions of marine-derived omega-3 fatty acids; From the University of Connecticut
Fish oil and rheumatoid arthritis: past, present and future.

Researched and written by Dr. Rebecca Malamed, M.D. with assistance from Mr. Malcolm Potter.

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