Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Muscle Growth

I still lift and train now for my own personal goals and for competition, but when I compare my current training to the level of training that I did when I was in my college days, they aren’t even close. Partly it is because I participated in some collegiate athletics for a short time period, but also because a big part of it was I had a lot more focus on vanity and a lot more time. I remember I often spent 2-3 (or more) hours in the gym a day. How I had that much time then, I had no idea. I had good grades, but I now realize I could have had even better grades if I would have spent more time focusing on academics instead of aesthetics.

In my younger days, there were a lot of things that I tried and experimented with in my training. Things that have helped me learn about what my body responds to that I still use today, things that I made more efficient, and things that I would not even consider now in my training. One of the things that I tried in my younger days that I don’t currently do is not necessarily part of my training program, but more a part of my supplementation. That was the use of Ibuprofen with the idea of decreasing inflammation and soreness that came from my lifting. My thoughts were, if it is supposed to help healing when I am injured and it is supposed to help pain when I am injured, then it should help the micro-injuries that lifting causes muscle tissue and it will help with the soreness from the lifting I was doing. Makes sense right. Even now that I know more, the logic (to me) is still there. For a younger semi-educated college kid it was pretty simple and straightforward. Now that I am older and more educated, there is still some logic to the idea, but there are things that make it a little more blurry and now that I know more of the information, it for sure isn’t as cut and dry. In this article, I will discuss what the current research on non-steroidal anti-inflammatory drugs (NSAIDs) and how their consumption may positively or negatively influence a muscle growth program.

NSAIDs are widely used to alleviate pain, reduce inflammation, and manage various conditions such as arthritis. These drugs work by inhibiting enzymes involved in the production of inflammatory molecules, thus providing relief to patients suffering from pain and inflammation. However, as beneficial as these medications may be, they have been shown to disrupt the intricate balance of the body’s healing processes.

There can be a few physiological mechanisms in which NSAIDs affect the healing process. One of the primary ways in which anti-inflammatory agents affect healing is by interfering with the inflammatory response itself. Inflammation is a critical part of starting the healing process, as it helps to remove damaged tissue, fight infection, and initiate tissue repair. By dampening the body’s inflammatory response, NSAIDs may inadvertently hinder the initial stages of healing, which are vital for clearing away debris and preparing the wound for regeneration.

Furthermore, NSAIDs can impede the production of collagen, a protein essential for wound healing. Collagen forms the structural framework for tissues, providing strength and stability. Inhibition of collagen synthesis by anti-inflammatory agents can lead to weakened scar tissue formation, prolonging the healing process and increasing the risk of complications.

Other concerns for the use of NSAIDs and healing include a negative impact on bone healing and the potential to hinder the body’s natural immune response to infections, but that may be discussed in the future as that is not the focus of this current article.

So let’s look into the research so we can see what it tells us… But first, there are a couple of things that need to be considered.

A lot of the research has been done on animals. There is human research, and animal studies can be generally projected to humans, but studies with significant clinical differences with human subjects are preferred when being used to determine the best course of use.

Next, with the exception of one study that went 12 weeks long (and this study does not completely correlate as it focused on individuals with osteoarthritis in the knee), the length of the studies that I reviewed are relatively short. The next longest was 8 days and most of the studies are only less than 24-36 hours. This makes it hard to use this information when determining the positive or negative effect of NSAIDs use for an individual over the course of a 12 week to 6 month muscle growth training program.

Third, the number of participants in most of the studies was relatively low. Low numbers of subjects does not invalidate the information, but it does make it less strong. It makes is harder to generalize the information to a larger group of people, but it does help us know where we should study more and where the results of the information are pointing.

Lastly, what I found in what often determined a positive or a negative conclusion was dictated by the what was being measured (surprising…). Delayed onset muscle soreness (DOMS), creatine kinase, neutrophils, prostaglandins, satellite cell activity, other chemical markers, and pain among others were things that were used to determine the effect of nonsteroidal anti-inflammatory drugs post exercise. Arguments for all the above can be made as to their correlation to the response in a muscle and the subsequent markers for healing. What I did not find (of course may be a limitation on my part) was a study that measured more of different combinations of markers together.

So, with that being said, let’s start to breakdown the research that is available out there…

First, I will start with what some of the arguments that I can think of that could indicate the use of NSAIDs with a muscular strength and hypertrophy program.

1. Taking NSAIDs will help with DOMS. This will help with the ability to keep working out or workout again sooner.

There are a number of studies that do show improvement in DOMS with the use of NSAIDs.^{1, 2, 3} There is evidence to support no improvement in DOMS with the use of NSAIDs. ^{1, 3} And some studies showed there was no difference in DOMS.^{4, 5, 6} The one thing that is more clear is there was no evidence (that I found) where taking NSAIDs increased any muscle soreness. For me, there were two interesting things to note with the area of DOMS. First is that topical anti-inflammatory was more effective in improving pain when compared to oral anti-inflammatories.³ Second is, prophylactic use of NSAIDs with exercise is potentially more effective at reducing muscle soreness when compared to just taking NSAIDs after exercise which shows it can be less effective and delayed.^{4, 5}

2. From what I know, inflammation is bad and an anti-inflammatory will help me heal faster because it will decrease inflammation.

To tackle this idea, the first thing that we have to address is the idea that inflammation is always bad. Chronic inflammation or elevated levels of inflammation are bad, but an appropriate level of inflammation is actually a normal and needed to start the healing cascade. The goal of any training program to promote muscle growth is to create enough stress in the muscle tissue (structurally, metabolically, or neurologically) that the healing process starts and rebuilds the muscle in a bigger and stronger way. In this, the inflammation that is part of the muscle tissue repair is needed to start the muscle rebuilding cascade. Because of this, inflammation is not bad.

There may be other arguments that you can think of that would support the use of NSAIDs for muscle growth, but in the world that I work in, these are the two main arguments that I have seen and heard. Now, with that being said, here are the arguments that would go against using NSAIDs with a muscle growth program.

1. Taking NSAIDS can mask pain or injury that may cause additional injury or make a present injury get worse.

This isn’t directly related to muscle growth, but it is a valid concern. I often have people express concern when they are injured about not taking NSAIDs or other pain meds as they are worried about it masking the pain and not truly knowing what something they are doing is causing more or less pain and whether they (or I) can really know what is going on if the pain is moderated by taking pain meds. Does this relate to muscle growth? Directly no. In the ideal scenario an individual is able to train with no injury, no pain, no limitation. This can happen most of the time, but injuries can occur during training, even with all efforts to minimize them. Most of the time, the injuries are not significant in the sense of having to restrict activities, miss workouts, or take time off. A muscle pull, a “shoulder pain”, a “knee pain”, a sprained ankle.

An example of the concern of NSAIDs masking pain and  affecting recover is with an ankle sprain. There is evidence that ankle instability and decreased ROM after injury despite faster return to activity with taking NSAIDs.^{7, 8} Chemically and physiologically the mechanism that causes NSAIDs to slow the healing process is more researched, but in my clinical experience, with a well-designed rehab program, I don’t know if I have ever been able to confidently say that an individual taking NSAIDs has limited their recovery process from an observational perspective. More research needs to be done in this area.

2. Taking anti-inflammatories is bad for gastrointestinal (GI) and cardiovascular (CV) health.

This is much more well known. NSAID use is linked to GI, CV, and other organ problems such as with the kidneys.⁹ Any quick search for NSAIDs and GI or CV issues will bring up information about the connection between NSAIDs and the health risks and problems. Once again, this does not directly correlate with NSAID use and muscular growth, but one can argue that if there is no significant upside to the use of the NSAIDs with improving muscle growth, then the advice would be to not take them due to the known potential negative side effects.

3. Taking nonsteroidal anti-inflammatory drugs can negatively affect healing because the inflammatory process is part of the healing cycle. This will affect my ability to grow muscle.

This, for me is the meat and potatoes concern when an individual considers using NSAIDs during or as part of a muscle growth program. Is an individual going to limit their ability to improve by taking NSAIDs? As we look at what information is out there, you can see that there is arguments coming from all angles. Here is the breakdown…

First there are the studies that overall demonstrate no effect on muscle growth or the markers of muscle growth.^{10, 11, 12, 13, 14, 15} This outcome is determined by lack of significant changes in inflammation pathway markers¹⁰, heat shock proteins¹¹, creatine kinase¹², neutrophils¹³, or other markers of gene expression and protein synthesis.¹⁴ Each one of these areas is a part of the physiologic process of muscle growth, but the information needs to be expanded and further researched to provide more clarification.

Then, there are studies that do not support the use of anti-inflammatory drugs.^{16, 17, 18, 19, 20, 21, 22} These results are determined for reasons such as inhibition of connective tissue healing¹⁶, negative effects on muscle repair and regeneration^{17, 18}, attenuation of satellite cells^{19, 22}, and suppression of protein synthesis.^{20, 21} While these studies were more negative when considering the use of NSAIDs in relation to muscle growth, one study did suggest that only higher doses of NSAIDs affected protein synthesis while lower doses did not have much effect.²⁰ Each one of these physiologic processes is an important part of the muscle and tendon development and growth. A disruption in any of these can lead to the decreased potential for muscle growth. Still because of the lack of consistent and layered results, more investigation needs to be done.

Last, there are studies that support the use of NSAIDs to help promote muscle growth.^{1, 23, 24} The mechanism of this is inflammation was reduced, creatine kinase levels were lower, a decrease in acute muscle weakness, and as discussed before soreness was reduced. Creatine kinase is a substance in muscle cells that helps produce energy. Creatine kinase also gets released in the body when their damaged (in this case strenuous exercise). Higher levels of muscle damage will result in elevated creatine kinase levels in the blood. Having reduced levels of creatine kinase would demonstrate lower levels of muscle tissue damage with strenuous exercise. Decreased soreness and decreased muscle weakness would allow for sooner repeat workouts that can be more effective as well as an individual just feeling better. This could provide a significant impact over time by allowing an individual to repeat higher intensity workouts.

In summary (or something of the sort), taking NSAIDS can be beneficial because it can decrease muscle soreness and decrease muscle weakness after exercise. This combined with lower levels of creatine kinase represent lower levels of tissue damage. This potential of decreased breakdown of the muscle is offset by the negative effects on repair and growth which are demonstrated by the inhibited satellite cells, connective tissue repair, and protein synthesis. From what my understanding of the complete picture is, a simplified explanation is, when taking NSAIDs there is a decrease in muscle tissue breakdown which is a benefit, but the tissue that is broken down is disrupted in the healing and building process.

So… even though I did my best to answer those “common” questions that I hear, is there really a solid overall answer to whether you should or should not take NSAIDs when focusing on a program for muscle growth? The only solid answer I would give is, we need to do more research. There is support for any direction you choose and you could form a biased argument for any option.

Should I Take NSAIDs While Working On Muscle Growth?

If I were to give my opinion (once again, I repeat my opinion)… my answer would be, I would shy away from NSAID use when participating in a muscle growth program, but if taking NSAIDs was warranted for other reasons, I would not be concerned about short-term use. My reason for shying away from NSAID use is because of the potential negative GI and CV effects that can happen when using NSAIDs over time. I also am biased toward the muscle growth side. I want to allow the body to do its best at rebuilding stronger which is more negatively affected from the available information. Also as somebody who is working with a lot of people in a rehabilitative sense where the tissue may already be compromised and damaged, anything that would compromise the ability of tissue to regenerate or grow would be something that I would prefer to avoid.

Now, even though I would lean toward not using NSAIDs when focusing on muscle growth unless anti-inflammatory use was warranted, if I were to use NSAIDs, here would be my guidelines for use.

• Talk to a medical professional who understands the mechanism of NSAIDs, their potential effects on the body, and your goals
• Do not use if you already have any GI, CV, or other organ dysfunction
• Do not use if you are recovering from, suffer from, or have a history of developing connective tissue injuries, broken bones, or any other injury
• Use lower doses of NSAIDs
• Separate the dosing and take some before and just after the workout
• Use for short time periods (7-10 days) followed by a NSAID use break
• Use only for higher intensity and strenuous exercise cycles of a training program and not during lower intensity levels of training

Where Do We Go From Here?

Now what from here? The biggest thing that I feel needs to be done going forward is to do more research to be able to provide a clearer picture. For me, in the future, some of the questions that would help clarify whether or not NSAID use is beneficial or detrimental to muscle growth would be…

• Over time, is there more muscle growth from the positive effects of taking NSAIDs (decreased muscle weakness, decreased soreness, decreased creatine kinase levels)? Or is there more of a negative effect on muscle growth from the inhibiting effects of NSAIDs (satellite cells, attenuated connective tissue repair, suppressed protein synthesis)? Or does this even itself out and show no overall effect?
• I would like to see these studies formed for longer periods of time. This does not mean 12 weeks straight of anti-inflammatory use, but it may mean that there is a periodic cycle of NSAID use on and off (for example 10 days on followed by 10 days off). This may be hard to do as any research should not knowingly harm anyone and the concerns over more long-term NSAID use for other side effects would cause worry.
• What dosages are more clinically significant? There is some insight into large versus small doses, but what would be the smallest meaningful dosage?
• How do ages of individuals affect the results? There is some suggestion that older individuals may respond better and may have more potential for muscle growth improvements when compared to younger individuals.^{19, 26, 28} This needs to get investigated further.
• Untrained individuals show that NSAID is less likely to affect muscle growth.¹⁵ Is there a more significant negative effect on trained individuals? Trained individuals are more accustomed to the training and thus less likely to experience the tissue damage and stress that may come with exercise. Does this mean that the negative effects of taking NSAIDs will negatively effect muscle growth?
• Studies to research the effects of NSAIDs on muscle growth are mostly focused on the cellular and protein levels. Having detailed information is good and it is needed for further understanding, but sometimes it can be nice to have a step back and see the overall effect from a broader perspective. If we just study whether individuals get stronger or build muscle while taking NSAIDs through other measurement tools such as body fat percentage, muscle biopsies for size, scans for tissue size, or strength measurements what would this show?

The human body is an amazing thing. The body’s ability to heal, adapt to changing environments and stresses, and do it all without much help from outside sources is pretty awesome. However, research has shed light on the potential consequences of interfering with these processes, particularly through the use of NSAIDs. While these medications serve a vital role in managing pain and reducing inflammation, they also may come with the unintended consequence of slowing down the body’s natural healing mechanisms. It’s important to note that while the evidence can suggest a potential negative impact of anti-inflammatory agents on healing, the overall evidence in relation to muscle growth and strength adaptations is underwhelming (for both for a positive and negative outcome) and the extent of the NSAIDs effect can vary depending on the specific drug, dosage, timing, and individual patient characteristics. Short-term use of these medications is generally considered safe, especially when the benefits outweigh the potential drawbacks. The use of anti-inflammatory agents offers benefits in terms of pain management and reducing inflammation. However, it’s essential to recognize the potential consequences of interfering with the body’s natural healing mechanisms. As medical research continues to uncover the intricacies of the body’s healing processes, not only do healthcare practitioners need to find a balance between providing relief and supporting the body’s innate ability to heal itself, athletes, trainers, and coaches also will need to expand their understanding of how using potential resources such as NSAIDs may affect their goal of improving performance.

1. Ticchi SJ. The effect of nonsteroidal anti-inflammatory drugs on muscle recover and strength after injury. 2009. (positive and negative but better results with prophylactic use – the studies discussed found that NSAID use pre-, during, or post-exercise was beneficial to the injured muscle in one or more ways: inflammation was lessened, serum creatine kinase elevations were blunted, DOMS reduced, and strength was either gained or decreased less compared to placebo)
2. Warden S J. Prophylactic use of NSAIDs by athletes: a risk/benefit assessment. The Physician and Sports Medicine. 2020;1(38). (some positive change in pain especially with prophylactic use)
3. Nahon RL, Lopes JSS, de Magalhes AM, de Soucha Machado A, Cameron LC. Anti-inflammatories for delayed onset muscle soreness: systematic review and meta-analysis. Rev Bras Med Esporte. 2021;27(6):646-658. (positive and negative for changes in DOMs with topical being most effective)
4. Bourgeois J, MacDougall D, MacDonald J, Tarnopolsky M. Naproxen does not alter indices of muscle damage in resistance exercise trained men. Med Sci Sports Exerc. 1999;31(1):4-9. (no change in pain)
5. Vella L et al. Ibuprofen ingestion does not affect markers of post-exercise muscle inflammation. Frontiers in Physiology. 2016;7(86): doi: 10.3389/fphys.2016.00086. (no change in pain)
6. Arendt-Nielsen L, Weidner M, Bartholin D, Rosetzsky A. A double-blind randomized placebo controlled parallel group study evaluating the effects of ibuprofen and glucosamine sulfate on exercise induced muscle soreness. J Musculoskeletal Pain. 2010;15(1):21-28. (no change in DOMS)
7. O’Leary H, McCreesh K. Non-steroidal anti-inflammatory drugs (NSAIDs) and musculoskeletal conditions: considerations for physiotherapy practice. Physiotherapy Ireland. 2011;32(2). (ankle sprains return faster but have a higher rate of instability – inhibit tendon cell activity and limit protein synthesis)
8. Tscholl Ph M, Gard S, Schindler M. A sensible approach to the use of NSAIDs in sports medicine. Swiss Sports & Exercise Medicine. 2016;65(2):15-20. (decreased ankle stability and ROM along with negative effect on muscular and tendinous adaptations)
9. Warden S J. Prophylactic use of NSAIDs by athletes: a risk/benefit assessment. The Physician and Sports Medicine. 2020;1(38).
10. Vella L, Markworth JF, Peake JM, Snow RJ, Cameron-Smith D, Russell AP. Ibuprofen supplementation and its effects on NF-kB activation in skeletal muscle following resistance exercise. Physiol Rep. 2014;2(10): doi: 10.14814/phy2.12172. (no change in transcription pathway with use of ibuprofen vs placebo)
11. Mikkelsen UR et al. The heat shock protein response following eccentric exercise in human skeletal muscle is unaffected by local NSAID infusion. Eur J Appl Physiol. 2013;113:1883-1893. (No changes in heat shock response proteins)
12. Bourgeois J, MacDougall D, MacDonald J, Tarnopolsky M. Naproxen does not alter indices of muscle damage in resistance exercise trained men. Med Sci Sports Exerc. 1999;31(1):4-9. (no changes in creatine kinase, muscle strength, or soreness with use of NSAIDs)
13. Vella L et al. Ibuprofen ingestion does not affect markers of post-exercise muscle inflammation. Frontiers in Physiology. 2016;7(86): doi: 10.3389/fphys.2016.00086. (no changes in neutrophils, markers of muscle damage, or muscle soreness)
14. Mikkelsen U R et al. Local NSAID infusion does not affect protein synthesis and gene expression in human muscle after eccentric exercise. Scandanavian J of Medicine & Science in Sports. 2010;21(5):630-644. (inhibited satellite cells, but limited changes in gene expression and protein synthesis)
15. Schoenfeld B. The use of NSAID’s for exercise-induced muscle damage: implications for skeletal muscle development. (no effect of short-term use on muscle growth)
16. Dideriksen K. Muscle and tendon connective tissue adaptation to unloading, exercise and NSAID. Connective Tissue Research. 2014;55(2):61-70. (non-steroidal anti-inflammatory drugs seem to inhibit the healing process of connective tissue and the stimulating effect of exercise on connective tissue protein synthesis, these drugs are often consumed in relation to connective tissue injury and soreness)
17. Bryant AE et al. Effects of delayed NSAID administration after experimental eccentric contraction injury – a cellular and proteomics study. PlosS One. 2017;12(2):e0172486. (new molecular evidence supporting the notion that NSAIDs have a direct negative influence on muscle repair after acute strain injury in mice)
18. Bondesen BA, Mills ST, Kegley KM, Pavlath GK. The COX-2 pathway is essential during early stages of skeletal muscle regeneration. Am J Physiol Cell Physiol. 2004;287(2):C475-83. (COX-2-dependent PG synthesis is required during early stages of muscle regeneration and thus raise caution about the use of COX-2-selective inhibitors in patients with muscle injury or disease)
19. Mackey A L et al. The influence of anti-inflammatory medication on exercise-induced myogenic precursor cell responses in humans. J Appl Physiol. doi:10.1152/japplphysiol.00157.2007. (Ingestion of anti-inflammatory drugs attenuates the exercise-induced increase in satellite cell number, supporting the role of the cyclooxygenase pathway in satellite cell activity.)
20. Bateman et al. Effects of ibuprofen on muscle hypertrophy and inflammation: a review of literature. Current Physical Medicine and Rehabilitation Reports. 2023;11:43-50. (that large doses of NSAIDs used after high-intensity interval training can reduce muscle protein synthesis and hypertrophy while lower doses have little to no effect on these factors)
21. Trappe T A, White F, Lambert C P, Cesar D, Hellerstein M, Evans W J. Effect of ibuprofen and acetaminophen on post-exercise muscle protein synthesis. AJP-Endo Articles. DOI 10.1152/ajpendo.00352.2001. (results suggest that over-the-counter doses of both ibuprofen and acetaminophen suppress the protein synthesis response in skeletal muscle after eccentric resistance exercise)
22. Makey AL. Does an NSAID a day keep satellite cells at bay? J Appl Physiol. 2013: doi:10.1152/japplphysiol.00044.2013. (more evidence pointing towards a negative, at least in young healthy individuals, warning against use, but more work needs to be done)
23. Morelli KM, Brown LB, Warren GL. Effect of NSAIDs on recovery from acute skeletal muscle injury: a systematic review and meta-analysis. AM J Sports Med. 2018;46(1):224-233. (analysis supports NSAID use for reducing strength loss, soreness, and blood creatine kinase level after an acute muscle injury, at least for humans and in the short term)
24. Lanier AB. Use of nonsteroidal anti-inflammatory drugs following exercise-induced muscle injury. Sports Med. 2003;33(3):177-185. (NSAID use for brief periods of time is beneficial for short-term recovery of muscle function)
25. Urso M L. Anti-inflammatory interventions and skeletal muscle injury: benefit of detriment? J Appl Physiol. 2013: doi:10.1152/japplphysiol.00036.2013. (no clear message with regards to the effect and mode of action of anti-inflammatory interventions and how they can best promote muscle healing and functional recovery)
26. Jozo G. No pain, no gain? Examining the influence of ibuprofen consumption on muscle hypertrophy. Strength and Conditioning Journal. 2023;45(4):481-485.
27. Ziltener J L, Leal S, Fournier P E. Non-steroidal anti-inflammatory drugs for athletes: an update. Annals of Physical and Rehabilitation Medicine. 2010;53:278-288.
28. Alturki M, Beyer I, Mets T, Bautmans I. Impact of drugs with anti-inflammatory effects on skeletal muscle and inflammation: a systemic literature review. Experimental Gerontology. 2018;114:33-49.