The Influence of NSAIDs on Physiologic Processes and Exercise

Introduction

As physical therapists, it is important to understand the effects of Non-Sterodial Anti-Inflammatory Drugs (NSAIDs) on the human body because many of our patients will be taking NSAIDs to allieviate their pain. Some patients may take NSAIDs prior to a physical therapy session to avoid pain that may arise from certian interventions that require movement of previously immobilized joints or muscles. Thus, understanding the effects of NSAIDs on the body will improve physical therapists' abilities to appropriately prescribe exercise and assess exercise responses of patients taking NSAIDs. 

Non-Sterodial Anti-Inflammatory Drugs (NSAIDs), including acetaminophen (Asprin) and Ibuprophen, simply put, reduce inflammation and pain. NSAIDs are widely and commonly used, which is why researchers are countinuously studying the risks and benefits of their effects on the human body. 

NSAIDs work by inhibiting the activity of an enzyme called cycoloxygenase (COX), which is crucial in the formation of prostaglandins. Prostaglandins play a role in the generation of pain and in the inflammatory response; however, they also have roles in many other bodily functions. When NSAID's inhibit prostaglandin synthesis they can reduce pain and inflammation, but they can also hamper gastrointestinal functions and post-exercise protein synthesis, as well as cause a number of other positive and negative side effects. These effects on physiological processes and exercise are further discussed for the following body systems: muscular, cardiovascular, metabolic, pulmonary, neuromotor and gastrointestinal. 

Muscular

Based on the literature, the effects of NSAIDs on the muscular system differs for young individuals vs. old individuals, acute vs. chronic use, and for timing of use (pre vs. post exercise) . 

NSAIDs are often used to help people who are sore after exercise. This review looked at the literature and said that NSAID “use for brief periods of time is beneficial to short term recovery of muscle function.”  NSAIDs do this by helping to manage inflammation. A short term use of NSAIDs seems to work well, but long term use of NSAIDs can lead to gastrointestinal complications, renal failure, liver failure, and heart failure. NSAIDs are best used for short term relief of soreness for muscles.

Young vs. Old

Recent studies have revealed that older adults who consume NSAIDs have greater muscle strength gain and hypertrophy from resistance training compared to older adults who do not consume NSAIDs. These findings were contrary to the researchers initial beliefs on the effects of NSAIDs on the muscular system adaptations to resistance training, and so they went on to research the mechanisms possibly responsible for their findings. The mechanisms that the researches concluded were at least partially responsible for their initial findinwer were, 1) NSAIDs reduced muscle loss by reducing the amount of IL-6 and MuRF-1, which promote muscle loss, 2) NSAIDs induced PGF2a receptor upregulation, which increased skeletal muscle sensitivity to PGF2a, and thus, stimulation of protein synthesis. On the contrary, NSAIDs also supressed PGF2a, which would reduce protein synthesis stimulation. Although overall, these mechanims inhibited protein breakdown more than they inhibited protein synthesis, which resulted in an increased net muscle protein balance. These studies involved participants between the ages of 60 and 85, which shows that the effects of NSAIDs may be age-dependent. Even though NSAIDs may have a beneficial effect on the muscular system in older adults, consumers of NSAIDs need to address the effects of NSAIDs on other body systems. The previously discussed studies did not address other body systems and only assessed the effects of NSAIDs on the muscular system after a 12-week resistance training program with particpants consuming 4 g/day and 1.2 g/day of acetaminophen and ibuprophen, respectfully. Further reseach should address the effects of NSAIDs on older adults after an even more long-term time period. 

Acute vs. Chronic Use

Because NSAIDS are available over-the-counter, they are taken for multiple different reasons and for different lengths of time. The Food and Drug Administration recommends that regular use of NSAIDS exceeding ten consecutive days should be accompanied by a consultation with a health care provider . 

Timing of Use (Pre vs. Post Exercise)

Many athletes take NSAIDs before physical activity in order to prevent the inflammation and/or pain that may occur. Some clinical evidence involving surgical trials supports these claims, finding that using NSAIDS prior to an inflammatory event could reduce inflammatory response, pain, and recovery time. In exercise induced muscle damage, rather than surgically induced, studies have shown that pre-exercise administration of NSAIDs could reduce the amounts of creatine kinase circulating after exercise as compared to a placebo group. This difference in creatine kinase levels may illustrate that less muscle damage occurred in the treatment group.

In another study researchers investigated the impact of a specific NSAID, ibuprofen, on time until fatigue in runners with muscle damage induced by exercise. The authors found that ibuprofen did not reduce the impact of muscle damage and pain on aerobic performance. Similar studies have also shown that NSAIDs as a preventative measure have little to no effect. In addition to these unclear results, frequent and preemptive NSAID use could allow the pain of an underlying condition to go unnoticed and become further damaged as the athlete continues to put stress on the injury. The overall negative effects of frequent use of NSAIDs as discussed below could outweigh the possible benefits of pre-exercise use. More studies are needed to determine the efficacy of taking NSAIDs before exercise.

Skeletal

Recent studies have looked at the effect of NSAIDs on bone density, with attention to exercise adaptations. This study was the first to run trials on humans. Previous studies have been performed on animals. The randomized, double blinded, placebo controlled study included 95 healthy premenopausal women ages 21 to 40. They participated in an exercising program lasting 9 months. The three groups consisted of a group that took a placebo before and after exercise, a group that took a ibuprofen before and after exercise, and a group that took a placebo before and an ibuprofen after exercise.

The reasoning behind the study was that prostaglandin E2 goes up in bone after exercise. One of the enzymes involved in the production of prostaglandin E2 is cyclooxygenase, which is inhibited by NSAIDs. This inhibits bone formation after any type of mechanical loading. The authors found that “taking 400 mg of ibuprofen immediately after exercise augmented the beneficial adaptions of BMD” compared to the other groups in the study. This group showed the largest increase in BMD, or bone mineral density. This information has important ramifications, but this is the first human study. Further studies need to be done to confirm this information, and understand the mechanism behind this information.

Cardiovascular

The use of NSAIDs can have negative effects on the cardiovascular system. The article: Bavry, A., Kaliq, A., Gong, Y., Handberg, E., Cooper-Dehoff, R., Pepine, C. 2011. Harmful effects of NSAIDs among patients with hypertension and coronary artery disease. American Journal of Medicine. 124(7). p. 614-619, states that chronic use of NSAIDs by individuals with hypertension and coronary artery disease can have negative side effects. Some of the side effects that are mentioned in the article are stroke and myocardial infarction. These are some significant considerations that need to be kept in mind when working with older individuals who may have some of these cardiac issues. It is important to ask these patients what medications they are taking because some of these patients may be taking NSAIDs without a prescription, therefore these medications may not be listed on their chart.

Gastrointestinal

Daily long-term use of NSAIDs, even of low dosage, can have a negative effect on the gastrointestional tract. Cryer and Feldman explored the effect of 10mg, 81mg, and 325mg asprin/day on serum TXB2 and gastrointestinal prostaglandin (PG) levels in the stomach, duodenum, and rectum. Results from their study indicated all three daily doses of asprin significantly decreased serum TXB2 levels after 1.5 months of use. The average stomach PG level was reduced to 34-44% of baseline, with the 10mg dosage reducing levels as much as the 81 and 32mg doses. It was found the 10mg dosage had no significant effect on duodenal PG levels, while the 81 and 325mg doses similarly reduced the levels to 45% of baseline. Lastly, only the 325mg dose affected the rectum by significantly reducing PG levels to 60% of baseline.