NSAID Impact on Muscle Hypertrophy

I came into this topic expecting to know the information already considering I have seen multiple people in the know discuss it with absolutisms, but it is with some pleasure that I can say I did not expect I would have my conclusions altered as significantly as I did reading the research for this article. I hope that we can make some sense of the data and with an open mind understand some of the possible mechanisms for the conclusions drawn from the research. In this article, we will discuss what Non-Steroid Anti-Inflammatory drugs are, if they have an impact on your muscle growth, and what possible mechanisms give us some explanation for this impact (or lack thereof) – pop some NSAIDs (kidding) and let the wild ride begin.

What is an NSAID?

NSAIDs are an abbreviation for Non-Steroidal Anti-Inflammatory Drug (NSAID) and that fancy name is simply the main descriptor of many of the drugs we purchase over the counter day to day like ibuprofen [7]. You can look on the bottle of your pain relieving drug and it should clearly state if it is an NSAID or not.

Do NSAIDs impact Muscle Hypertrophy?

Well, before we confuse one another, we should quick mention that to grow muscle, muscle protein synthesis (creation) must be more prevalent than muscle atrophy (breakdown) – this is absolutely necessary to understand for us to make any sense of NSAID impact on anything related to muscle growth.

Ok, now we can answer the question – we have no clue.

Pack your bags, we’re done here!

In all honesty, we really have a lot of conflicting data behind many well produced studies, so the answer likely lies in the conditions we apply and is highly unlikely to be an absolute answer at this point. Many rodent (aka, non-human) studies have shown us that NSAIDs have a profound impact at reducing muscle protein synthesis and are clearly not something to ingest if one wants to gain muscle [4]. There are even human studies – well laid out human studies, at that – that substantiate muscle protein synthesis is significantly decreased if a person consumes maximal doses of acetaminophen or ibuprofen (both are, predictably, NSAIDs)[6]. However, the same people who saw a decrease in muscle protein synthesis in humans also published a study showing no difference in muscle protein synthesis between groups of elderly individuals using the same dosage of the same drugs, but for a longer period of time [5]. Other human studies concur with the latter conclusion [1][2][3][4]. So, what gives?

On one side we have several rodent studies and one human study that show a definitive “YES” and on the other side we have several human studies that show a definitive “NO”. The likelihood is lower that NSAIDs impact muscle protein synthesis since more numerous, more applicable/relatable, and more comprehensive studies point toward the direction of these drugs having no impact on muscle protein synthesis; however, this still leaves the confusion of this variability in results and this we will attempt to explain in the next section.

Understanding the Physiology?

Alright, there are many different possibilities for why NSAIDs seem to not impact muscle protein synthesis, but most of them get eliminated in one way or another which leaves us with two prevailing theories and even these two theories need quite some substantiating.

Cyclooxygenase & Prostaglandin

First off, we understand that NSAIDs are thought to impact muscle recovery at the inflammation level. If you are not aware, when we exercise we create micro trauma to the musculature which then prompts a bunch of different signals (hormonal, structural, neurological, etc.) to begin the recovery and growth process (you can learn about in detail in my article Physiology of Muscle Hypertrophy). One of the main recovery processes are brought on by inflammation via a variety of enzymes and immune cells and this is where Non-Steroidal Anti-Inflammatory Drugs (NSAID) play a role – especially the last part of their title, “Anti-Inflammatory”. The idea is that if a person ingests enough NSAIDs, the inflammation process does not occur as readily and therefor, muscle protein synthesis is not as readily activated.

So, we understand now that NSAIDs impact inflammation, but the reason this is so important to understand is in how it impacts inflammation; and, this is where things get a bit more biochemical.

When micro trauma occurs, an enzyme by the name of cyclooxygenase activates, by taking lipid (fat), and creates an autacoid (similar to a hormone) by the name of prostaglandin which, locally, creates inflammation to the traumatized, damaged cells affected by the exercise bout [8][9]. NSAIDs, however, inhibit all three forms of cyclooxygenase (COX) from COX-1, COX-2, and COX-3, but the two most telling isoforms (types) are COX-1 and COX-2 when speaking about muscle protein synthesis and inflammation [8][9]. We do have a few specific NSAIDs that inhibit only COX-2 which is telling, because studies performed inhibiting COX-2 alone saw no decrease in muscle protein synthesis, either [10]!

Here is the mechanism by which COX and NSAID interact. You can see here that there are several types of prostsglandins that effect various tissues throughout the body.

So, if COX-2 is not the main mediator of inflammation in muscle micro trauma, then it might be assumed COX-1 is this said mediator, but there is considerable debate on if the sole responsibility can be laid at the COX-1 enzyme’s feet (figuratively speaking, of course!). It seems more likely that these two enzymes auto regulate themselves by sensing inhibition of one or the other and take on load or that these general COX inhibitors (most NSAIDs) may inhibit one or the other more, or even that this inhibition is dependent on circumstance (for example, a person with arthritis will always have inflammation so their COX enzyme production may already be high). As we can see, there is quite some speculation here and we cannot give a definitive answer at this time, but we do know how NSAIDs work, we know prostaglandins are essential for inflammation, we know inflammation is a key driver of repair and growth, but we are unsure as to the mechanisms that allow muscle protein synthesis to continue unmolested in the face of cyclooxygenase inhibitors.

Satellite Cells

On the other hand, another extremely important mechanism by which muscles are able to grow and muscle protein synthesis is used is through the activation of satellite cells (again, I encourage you to read my article Physiology of Muscle Hypertrophy for details). Basically, when micro trauma occurs to the muscle, miniature cells (even on a cellular level they are tiny) quite literally crawl across the muscle cell and donate their nuclei to the cell to increase the myonuclear domain (aka, the amount of the cell each nucleus is responsible for). In doing so, it allows the cell to grow as it has more nuclei to, simply put, help maintain function of the other parts of the muscle cell – the more nuclei, the more potential for growth; this is a bit like having a manager at every store if the nuclei are managers.

It seems that NSAIDs do have an impact on the ability for the body to activate these satellite cells and decrease their proliferation (aka, increase in number)[4][11]. This means that people who consume normal doses of NSAIDs tend to see a decrease in their satellite cell activation to split into further satellite cells and likely a decrease in the integration of those satellite cells into the muscle fibers.

Satellite cells are found on the muscle cell and tend to proliferate (multiply) if the muscle cell tears, but this mechanism is inhibited if NSAID are ingested.

So, here we are and we have identified two mechanisms by which muscle protein synthesis is influenced, but again, how do we reconcile the fact that the most applicable evidence (human trials) imply NSAIDs do not have a negative impact on muscle protein synthesis? Well, we did come up with a few explanations in the first subsection for cyclooxygenase, but that does not explain the evident impact on satellite cell proliferation. Again, this is considerable speculation, but with the elimination of many theories, it seems some are pointing to the idea that while satellite cell is crucial, if the myonuclear domain is not maximized, then an increase in muscle protein synthesis with a lack of satellite cell proliferation could still offer an increase in muscle hypertrophy up to a point in which the myonuclear domain is maximized.


In summary, the research is not all that clear on the topic, although many would have you believe that it is. Some research indicates NSAIDs have significant impact on muscle protein synthesis and others show no effect; however, looking at the body of research, it seems more likely that NSAIDs do not have an effect when relating it to muscle protein synthesis. While there are many ideas out there for an explanation of the mechanisms, it seems many of them fall short in one way or another, but two mechanisms we know have an impact on muscle protein synthesis seem to be influenced by NSAIDs – cyclooxygenase and satellite cells. Cyclooxygenase, while down regulated, seems to have no impact on muscle protein synthesis, but looking at the different isoforms we may eventually understand why – likely, there is a compensatory mechanism in which one isoform up regulates while the other is down regulated or, more likely, certain populations simply have higher cyclooxygenase levels due to chronic inflammation. In terms of satellite cells, it does seem rather conclusive that NSAIDs decrease satellite cell activity and the reason we see little effect on muscle protein synthesis may be because the myonuclear domain is not maximized for most populations so protein synthesis may not be bothered until the myonuclear domain maximum is met. So, in conclusion, NSAIDs may have an impact on high level trainees, no negative impact on elderly population, likely little to no impact on the casual gym-goer, and the topic will continue to be mechanistically speculative until we can get further research or discover a COX-1 inhibiting NSAID. Either way, if you need to use NSAIDs for a few days, you will likely see no impact whatsoever, so feel guilt free.

Writer: Nicolas Verhoeven
This is educational material only and not meant to be prescripton, consult your physician before making any changes.

[1] Krentz, J. R., Quest, B., Farthing, J. P., Quest, D. W., & Chilibeck, P. D. (2008). The effects of ibuprofen on muscle hypertrophy, strength, and soreness during resistance training.Applied Physiology, Nutrition, and Metabolism, 33(3), 470-475. doi:10.1139/h08-019

[2] Mikkelsen, U. R., Schjerling, P., Helmark, I. C., Reitelseder, S., Holm, L., Skovgaard, D., … Heinemeier, K. M. (2010). Local NSAID infusion does not affect protein synthesis and gene expression in human muscle after eccentric exercise. Scandinavian Journal of Medicine & Science in Sports, 21(5), 630-644. doi:10.1111/j.1600-0838.2010.01170.x

[3] PETERSEN, S. G., MILLER, B. F., HANSEN, M., KJAER, M., & HOLM, L. (2011). Exercise and NSAIDs: effect on muscle protein synthesis in patients with knee osteoarthritis.Medicine & Science in Sports & Exercise, 43(3), 425-431. doi:10.1249/mss.0b013e3181f27375

[4] Schoenfeld, B. J. (2012). The Use of Nonsteroidal Anti-Inflammatory Drugs for Exercise-Induced Muscle Damage. Sports Med, 42(12), 1017-1028. doi:10.1007/bf03262309

[5] Trappe, T. A., Carroll, C. C., Dickinson, J. M., LeMoine, J. K., Haus, J. M., Sullivan, B. E., … Hollon, C. J. (2010). Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults. AJP: Regulatory, Integrative and Comparative Physiology, 300(3), R655-R662. doi:10.1152/ajpregu.00611.2010

[6] Trappe, T. A., White, F., Lambert, C. P., Cesar, D., Hellerstein, M., & Evans, W. J. (2001). Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis.American Journal of Physiology - Endocrinology And Metabolism, 282(3), E551-E556. doi:10.1152/ajpendo.00352.2001

[7] Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). (2007). Retrieved from Food and Drug Administration website: http://www.fda.gov/downloads/drugs/drugsafety/ucm089162.pdf

[8] Ricciotti, E. (2011). Prostaglandins and Inflammation. Arteriosclerosis Thrombus Vascular Biology, 31(5), 986-1000. doi:10.1161/ATVBAHA.110.207449

[9] Cyclooxygenase and NSAIDs [PowerPoint]. (n.d.). Retrieved from http://www.albany.edu/faculty/cs812/bio366/Cyclooxygenase_ppt.pdf

[10] Burd, N. A., Dickinson, J. M., LeMoine, J. K., Carroll, C. C., Sullivan, B. E., Haus, J. M., … Trappe, T. A. (2009). Effect of a cyclooxygenase-2 inhibitor on postexercise muscle protein synthesis in humans. AJP: Endocrinology and Metabolism, 298(2), E354-E361. doi:10.1152/ajpendo.00423.2009

[11] Mackey, A. L. (2013). Does an NSAID a day keep satellite cells at bay? Journal of Applied Physiology, 115(6), 900-908. doi:10.1152/japplphysiol.00044.2013


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