Does NSAID Kill Your Gains? Potential Negative Effects on Strength and Hypertrophy

Most serious athletes have at some time or another had training sessions or longer periods of training plagued by pains and aches. Some have even accepted the pain as a constant training partner. These pains can be the result of chronic inflammation, acute injury or the remains of past injuries, often the result of training through an injury instead of working around it.

Regardless of the cause of these pains, a cure in the form a pill is often used to be able to train pain-free or at least with reduced symptoms. This article is all about these pills, these pain relief medications. They range from anti-inflammatory drugs based on ibuprofen or diclofenac like Advil and Voltaren to medicines with paracetamol as the active ingredient, like Tylenol and Panadol, which offer pain relief but without the same anti-inflammatory effect.

The anti-inflammatory medicines are called nonsteroidal anti-inflammatory drugs or NSAID for short. The fact that recent research has demonstrated the potential harmful effects of pain relief medications and NSAIDs on both health and training adaptations, a scientific overview of the effects and side effects of these drugs is needed in order for physicians and athletes to be able to make informed decisions based on facts rather than on myths or old habits.

Recently, a meta-analysis summarized the scientific evidence for and against the use of pain relief medication and NSAIDs in sport, and the purpose of this article is to discuss these findings.¹

Table of Contents

The Use of NSAIDs by Athletes

Non-steroidal anti-inflammatory drugs are some of the most commonly prescribed pain medications. Data from 2013 show that over 30 million individuals use some type of NSAID on a daily basis, and nothing indicates that this number has gone down since then.² Several types of NSAIDs are available over the counter, without the need of a prescription, and they are both easy and cheap to obtain.

The use of NSAIDs in athletes is commonplace. Often they are used not only to treat serious inflammations where the use of anti-inflammatory medications are actually indicated, but also to treat banal disorders like moderate pain, to improve recovery and healing, and to decrease the time missed from training due to relatively minor pains and medical issues. The use NSAIDs by high-level athletes is more widespread than the use among the general population.³

Sometime NSAIDs are used preventively ahead of a training session or a competition, even when the athlete is uninjured.

Unfortunately, this prevalent use of NSAIDs hides the symptoms rather than cures the cause of the pain. This makes it possible to continue training, even though the injury is still present. Avoiding the pain through pharmaceutical means can turn an acute injury into a chronic one over time. It is also likely that many athletes abuse these drugs by using them in unintended ways, to relieve minor pains related to normal training adaptation.

How NSAIDs Can Influence Training Adaptations

Cyclooxygenase (COX) is an enzyme responsible for the formation of prostaglandins, hormone-like compounds that, among other things, control inflammation. The anti-inflammatory effects of drugs like diclofenac are mediated through the inhibition of cyclooxygenase. Classical COX-inhibitors inhibit all types of cyclooxygenase, but newer NSAIDs selectively target the COX-2 enzyme. Selectively targeting this enzyme makes it possible to reduce inflammation and pain with less risk of the gastric irritation prevalent with non-selective COX-inhibitors.

Pain relief medication using paracetamol as the active ingredient do not belong to the COX-inhibiting classes of drugs, although recent research demonstrate that paracetamol do inhibit the synthesis of prostaglandins. The mechanisms of paracetamol are similar to those of selective COX-2 inhibitors, although the effects are less powerful.⁴

Post-exercise, there is an acute inflammatory response, and these inflammations are likely not counterproductive or harmful processes to be avoided or suppressed. Exercise also initiates a number of processes producing and controlling growth factors that coincide with the acute inflammatory response. Scientific evidence indicates that this inflammatory response is an important part of building muscle. Thus, suppressing or eliminating the post-exercise inflammatory response would also suppress the desired training adaptations.

Exercise Performance Benefits from NSAID… At Least in the Short Term

The effects pain relief medication exert on training results are not all negative. These drugs can enhance performance during endurance training, sometimes dramatically.

One study demonstrated that cyclists were able to generate a higher rate of force development and reach higher heart rate and levels of lactate after ingestion of 1,500 mg of paracetamol compared to placebo, without any increase in perceived exertion.⁵

Another study showed that 20 mg of paracetamol per kilogram of fat free mass before training allowed for a 4-minute increase in time to exhaustion during cycling in heat, which is a very large improvement.⁶

High intensive interval training performance can also benefit from pre-exercise pain relief medication. Track sprint cyclists experienced lower levels of perceived pain after ingesting 1,500 mg of paracetamol prior to a race, allowing them to perform closer to their maximum compared to a placebo group.⁷

In a resistance training study, 1,000 mg of paracetamol maintained muscle activation during maximal leg extension contractions for a longer time, increasing the time to exhaustion, compared to placebo.⁸

The evidence shows that pain relief medication can have significant performance-enhancing effects when used in conjunction with exercise, both endurance exercise, sprint training, and resistance training. These studies have mostly used physically active individuals, but not high-level athletes. It is unknown if advanced athletes, who are used to intensive and often painful training, and also are more accepting of physical pain during training, would experience the same level of ergogenic benefits.

The Effect of Anti-inflammatory Drugs on Muscle Protein Synthesis

Athletes whose main goal is muscle hypertrophy are probably more interested in how these drugs affect the mechanisms controlling the growth of skeletal muscle, muscle protein synthesis more specifically. Unfortunately, the evidence from available studies are equivocal, making it hard to draw any definite conclusions.

In an early study from 2002, 24 young men ingested 1,200 mg of ibuprofen, 4,000 mg of paracetamol, or a placebo following 10–14 high intensive sets of leg extension.⁹

A robust stimulation of muscle protein synthesis was measured in the control group, but the elevation of muscle protein synthesis usually expected following resistance training was absent in the ibuprofen and paracetamol groups. Post-exercise prostaglandin levels increased in the placebo group, but not in either of the groups given pain relief medication.

This indicates that both high dose NSAID and paracetamol-based pain relief drugs are powerful inhibitors of the stimulation of muscle protein synthesis that resistance training normally initiates, likely through the same mechanisms that inhibit the formation of inflammatory prostaglandins. These effects have also been demonstrated in animal studies.

It should be noted that the doses used in the 2002 study were high, although not above the maximum recommended daily dose for over-the-counter dosing of the same medications.

Nine years later researchers conducted another study using leg extension as the training method. In this study, indometacine, a nonsteroidal anti-inflammatory drug usually prescribed for pain, fever, and inflammation, was injected into the working muscle of one of the legs.¹⁰

This procedure resulted in a similar stimulation of muscle protein synthesis in both legs, even though one had been administered intramuscular NSAID.

It is possible that the discrepancy between the results of the two studies means that the 7.5-hour long injection did not produce as significant an effect as a substantial oral dose, or that collagen protein synthesis simultaneously measured could have masked the actual muscle protein synthesis.

Signaling Mechanisms and Satellite Cells

Resistance training activates signaling by the mammalian target of rapamycin (mTOR), which initiates post-exercise muscle protein synthesis and the induction of hypertrophy. Two studies have demonstrated that both ibuprofen and paracetamol partially or completely shut these signals down.¹¹¹² Since the synthesis of protein is dependent on these processes for initiation and maintenance, long-term pharmaceutical inhibition of muscle protein synthesis likely also means a reduced hypertrophic effect following resistance training.

Satellite cells are cells that lie dormant in the musculature but activate and proliferate when exposed to stimulation like resistance training and play a key role in repairing and remodeling muscle fibers following exercise. Not only can nonsteroidal anti-inflammatory drugs inhibit post-exercise muscle protein synthesis, but also the satellite cell proliferation following a training session. This effect is apparent following both strength and endurance types of exercise.

Inhibition of one type of cyclooxygenase seems to disturb satellite cell proliferation, while the same effect has not been observed after inhibition of another type of cyclooxygenase. While much research remains, available evidence indicates that NSAIDs have the capacity to disturb the normal and advantageous effects exercise has on satellite cells.

Real-life Effects on Training Adaptation

While inhibition of muscle protein synthesis and disturbed signaling pathways are theoretically interesting, these mechanisms mean little to the athlete unless they also translate into diminished results for the efforts expended in the gym. In a real-life setting, not many athletes are interested in what occurs at a cellular level, as long as the training sessions result in muscular hypertrophy and strength increases.

A number of animal studies have demonstrated diminished hypertrophic effects resulting from muscular if the animal is administered anti-inflammatory medication. Relevant human studies are very limited, with only a few published in the last decade.

In one of these studies, the participants received 800–1,200 mg of ibuprofen per week on training days.¹³ There were no significant differences in muscle growth, strength or muscle damage compared to control. However, the doses were low and distributed over only a few days per week over a relatively short period of weeks, which makes it difficult to hypothesize the results of higher, long-term doses, which are common amongst athletes.

The second relevant study had the participants ingest 1,200 mg of ibuprofen each day for eight weeks, while they performed resistance training in the form of leg extensions.¹⁴ A control group received a much smaller dose of NSAID in the form of 75 mg of acetylsalicylic acid (Aspirin), while following the same resistance training protocol.

The group receiving the small dose of Aspirin increased their muscle size twice as much as the ibuprofen group. Strength gains were also larger in the Aspirin group.

Since paracetamol exhibit NSAID-like mechanisms, similar inhibitory effects would not be surprising. However, an absence of research prevents any evidence-based conclusions.

Unfortunately, there are no studies featuring elite athletes. This is a particularly unfortunate omission since elite athletes use pain relief medication and NSAIDs to a higher extent than the general population.

General Side Effects of Pain Relief Drugs and NSAIDs

The negative effects of extensive use of nonsteroidal anti-inflammatory drugs are not limited to factors related to performance and training adaptations. While NSAIDs inhibit muscle protein synthesis, they can also inhibit the synthesis of bone, cartilage, connective tissue, and tendons.¹⁵ This means that NSAIDs are contraindicated for many types of injury, where growth of these types of tissue is paramount to healing. It could also mean that long-term use of NSAIDs increase the risk of sports related injury in general.

NSAID use has also been associated with sudden death, cardiac arrest, and myocarditis.¹⁶¹⁷ This association is especially noticeable in the case of diclofenac, even in young, otherwise healthy, athletes.

Other common side effects include bleeding gastric or duodenal ulcers from NSAIDs, and hepatotoxicity from paracetamol. One of the major causes of hepatic insufficiency is paracetamol overdose.

Differences between Young and Elderly

The studies where NSAID ingestion demonstrates a negative effect on training, as mentioned earlier in the article, have all been performed on young individuals. In the elderly, NSAID usage might not result in the same effects. Rising age often brings more frequent and more extensive systemic inflammations, and adding an acute inflammatory response from a training session to this chronic inflammatory condition might be overwhelming.

Studies using elderly subjects participating in resistance training in combination with NSAID usage have resulted in greater muscle growth and strength increases than training without anti-inflammatory medication.¹⁸ These observations support age-related differences in the young end elderly following NSAID ingestion.

“Elderly” is likely somewhere between 60 and 80 in this case, and probably closer to the higher number. When these age-related differences in how NSAID can influence training results appear is unknown, but it likely varies on an individual basis. Some 75-years olds have genetics and a lifestyle that allow their inflammatory status to be more beneficial than that of a 30-year old who lives a sedentary lifestyle based on stress, processed food and smoking.

Even if elderly strength training individuals seemingly can benefit from the anti-inflammatory effects of NSAIDs to enhance training adaptations, this practice could potentially lead to other detrimental side effects in the end. As previously mentioned, a chronic or high intake or pain relief drugs and NSAIDs are both associated with a number of less than desirable side effects.

Conclusions and Recommendations

Can the use of pain relief medication and nonsteroidal anti-inflammatory drugs diminish training adaptations? The mounting scientific evidence indicates that this is the case. Long-term and high intakes of common over the counter NSAIDs can inhibit strength gains and muscle growth in young, healthy individuals engaging in weight training.

Can painkillers and NSAIDs help the athlete in pain? Absolutely. These drugs are very effective at relieving pain and inflammation. They definitely have a place in the treatment of athletic injuries and inflammatory problems, provided that they are only prescribed to treat actual injury and injury-related inflammation, not to treat the acute inflammatory response initiated by the training itself, a response that likely is a necessary process for hypertrophic adaptations.

On the one hand, NSAIDs can be valuable parts of the athlete’s arsenal of tools to treat acute pain and inflammation, when used in the proper context. On the other hand, many athletes use them too frequently or for the wrong reasons. It is easy to develop a habit of using these drugs to reduce symptoms of normal muscular aches resulting from hard training or to reduce long-term symptoms of injury or overuse instead of dealing with the cause of these symptoms. This practice can turn an acute injury into a chronic one, leading to a need for more advanced rehabilitation and long-term negative effects on training and performance.

Since pain relief medication can have an acute ergogenic effect, it might be tempting to use these drugs before or during training and competition, even when there is no actual pain or inflammation to treat. However, such a practice could lead to long-term negative consequences, both training-related and health-related.

When considering the use of pain relief medication and nonsteroidal anti-inflammatory drugs, both the risks of and the reasons for taking them should be considered carefully.

The right reasons include taking them to treat an acute injury or inflammation, to make the return to training and competition faster and the pharmaceutical intervention shorter.

The wrong reasons include hiding the symptoms of an injury to be able to train as usual, preemptively trying to reduce post-exercise aches and pains, efforts to enhance performance, and reducing normal symptoms that are a part of training adaptations, like delayed onset muscle soreness.

Self-medication for these reasons might very well lead to diminished training results in the end, as well as health issues, and turn an acute injury into a chronic condition.

A number of chronic conditions and diseases require treatment with NSAID. In these cases, the training needs to be adapted to these conditions, and the possible diminished training adaptations might be unavoidable to manage the disease. Any exercise is better than no exercise, and the treatment and management of most medical conditions benefit from adding exercise to the list of medications. Under such conditions, resistance training might reduce the potential catabolic or anti-anabolic side effects of the pharmaceutical interventions.

Take-home Message

Nonsteroidal anti-inflammatory drugs are powerful tools to facilitate the injured athlete’s return to training and competition, but also a potential crutch that might hinder long-term training progress and performance.

When used responsibly and correctly, they can be a part of a pain-free training career. When used improperly, they have the potential to destroy it.