Do painkillers affect muscle growth?

I'm talking about taking non-steroidal anti-inflammatory drugs - you know, those painkillers that you can find in any pharmacy in copious quantities.

There are dozens of brands and active ingredients to choose from: Aspirin, ibuprofen, diclofenac, etc. And it's not hard to get your hands on these medications. Most can be purchased without a doctor's prescription and even without a pharmacist's admonishing words.

Non-steroidal anti-inflammatory drugs have become an integral part of the daily training program of many strength athletes. In most cases, they are used to alleviate the effects of delayed onset muscle soreness, which can sometimes last for several days after an intense training session.

On the surface, taking non-steroidal anti-inflammatory drugs to reduce delayed onset muscle soreness seems to make sense - just pop a few pills and your soreness miraculously disappears. No missed training sessions, no reduction in performance. What's the problem?

Well, let's look a little deeper. Although the exact mechanisms are not yet fully understood, delayed onset muscle soreness is believed to be the product of damage to muscle tissue.

The proposed model looks something like this: Forces associated with muscular contractions-especially eccentric actions-cause the formation of small microtears in the contractile elements and surface membrane (sarcolemma) of working muscle fibers.

These microtears allow an outflow of calcium from the muscles, disrupting the intracellular balance and causing further injury to the muscle fibers.

Different proteins then interact with the free nerve endings surrounding the damaged fibers, resulting in local pain and stiffness. These symptoms can be exacerbated by swelling within the muscle fibers, which exerts pressure on sensory receptors (pain receptors), thereby increasing the pain (6).

Non-steroidal anti-inflammatory drugs are believed to reduce pain primarily by inhibiting cyclooxygenases (COX), a family of enzymes that catalyze the conversion of arachidonic acid into pro-inflammatory prostanoids (5, 22).

Prostanoids have been shown to be responsible - at least in part - for the pain associated with delayed onset muscle soreness. Studies have shown that they promote inflammation and make pain receptors more sensitive, thereby increasing pain sensitivity (16).

By inhibiting the synthesis of prostanoids, non-steroidal anti-inflammatory drugs can significantly reduce the pain experienced after exercise, allowing you to train hard and heavy day in, day out. And this should lead to better gains in muscle mass and strength, right?

Maybe not.

The acute post-workout inflammatory process appears to play a role in muscular adaptations to resistance training. Prostanoids in particular have been shown to play a role in anabolic signaling. They are involved in the stimulatory pathways responsible for the execution of protein synthesis (13, 18).

Considering that non-steroidal anti-inflammatory drugs impair the production of prostanoids, it seems logical that these drugs could also have a negative effect on muscle development. In fact, early studies have shown that this is the case.

Studies conducted in rodents have consistently shown that non-steroidal anti-inflammatory drugs impair protein metabolism (13, 18, 21) and reduce muscle development in response to muscle overload (3, 21).

Devastating effects on muscle adaptations have been observed with the use of both selective and non-selective non-steroidal anti-inflammatory drugs, resulting in a reduction in hypertrophy of up to 50% (19). In other words, muscle growth was halved after administration of non-steroidal anti-inflammatory drugs!

Confusing results in humans

The studies with rats and mice seem very convincing. But what about humans? Well, an early human study seemed to confirm these results.

In 2002, a team of researchers led by Dr. Todd Trappe found that non-selective non-steroidal anti-inflammatory drugs taken after a session of supramaximal eccentric exercise reduced protein synthesis by 50 to 75%. This appeared to be the final nail in the coffin for non-steroidal anti-inflammatory drugs. All evidence pointed to these drugs interfering with muscle development.

But something interesting happened. Follow-up studies conducted in humans were unable to reproduce the initial results in humans. Studies involving both young and older subjects taking selective and non-selective COX inhibitors showed no differences in protein synthesis (4, 11, 15).

If these results aren't confusing enough, consider some recent studies that examined the long-term effects of nonsteroidal anti-inflammatory drug use on muscle growth in humans. None of these studies were able to find any negative effects on muscle hypertrophy (8, 14, 20).

In fact, one of these studies even showed that non-steroidal anti-inflammatory drugs increased muscle hypertrophy by about 50% (20). Yes, you heard right - the group taking painkillers significantly increased their muscle gains!

What are the explanations for these contradictions?

If you look at the research, it seems that non-steroidal anti-inflammatory drugs are highly catabolic in small rodents, but not in humans. You might even suspect that regular use might have performance-enhancing effects. Considering the studies mentioned, this seems logical, right?

Not so fast. A whole range of factors need to be considered before any relevant conclusions can be drawn on the subject.

First of all, these protein synthesis studies, interesting as they may be, need to be considered in the right context. Acute studies of anabolic processes in humans do not necessarily correlate with long-term hypertrophy.

Just because protein synthesis or signaling factors are increased after exercise does not necessarily mean that this will result in greater gains in muscle mass over a period of weeks or months (1).

Another potential problem with the current state of studies is that all studies to date have been conducted with untrained subjects. You don't have to be a rocket scientist to realize that adaptations differ between people with no training experience and people who regularly train with weights. Would the results have been different in a group of serious strength athletes? Quite possibly.

In addition, two of the three studies that examined hypertrophy were conducted with older subjects. In fact, the age of the subjects in the study that observed significant hypertrophy benefits with the use of non-steroidal anti-inflammatory drugs was between 60 and 85 years.

The problem here is that older people - and especially older people who do not exercise regularly - are susceptible to subthreshold inflammation. In contrast to acute post-workout inflammatory processes, chronic inflammation has devastating effects on muscle development, impairing anabolism and accelerating muscle protein breakdown (17).

It is therefore quite possible - if not likely - that non-steroidal anti-inflammatory drugs may have helped to reduce underlying inflammation in these subjects, thereby promoting the positive effects on muscle growth. This is irrelevant for healthy, young exercisers, as subliminal inflammation is not an issue for these people.

The satellite connection

If you're serious about strength training, the biggest dilemma with using non-steroidal anti-inflammatory drugs is their potential negative impact on satellite cells.

Simply put, satellite cells are muscle stem cells located next to the muscle fibers. These non-specialized cells remain dormant until they are needed for muscle repair or regeneration, as is the case after resistance training.

One of the most important roles of satellite cells is their ability to increase the number of nuclei in the muscle, which are responsible for the production of proteins needed for muscle growth.

During normal daily activities, the number of nuclei in the muscles is sufficient to remodel the muscle tissue. This is no longer the case when you perform intensive training with weights.

Heavy training substantially increases the need for protein synthesis. This is where satellite cells come into play. Muscle contractions activate satellite cells, which then divide, form (become more specialized) and fuse with the working muscle fibers, donating their nuclei so that the muscle can produce more protein to support continued growth.

The current theory is that without a consistent available supply of satellite cells, muscle hypertrophy will eventually stall (1).

But what does all this have to do with non-steroidal anti-inflammatory drugs?

Well, recall that non-steroidal anti-inflammatory drugs exert their effects by blocking the synthesis of various prostanoids. However, prostanoids are known to stimulate the division, formation and fusion of satellite cells (2).

And (drum roll please) studies conducted with both animals and humans have repeatedly observed a significant reduction in satellite cell activity when non-steroidal anti-inflammatory drugs were administered in response to muscle damage (2, 3, 9, 10).

This raises the possibility that non-steroidal anti-inflammatory drugs, although they may not affect hypertrophy in the short term, could have devastating effects on long-term muscle growth.

Conclusion on the use of non-steroidal anti-inflammatory drugs

Based on the research currently available, it seems clear that the occasional use of non-steroidal anti-inflammatory drugs will not derail your training efforts. However, it is too early to draw any firm conclusions about chronic use of these drugs.

Studies are limited and more research is needed - especially with well-trained strength athletes - to understand how these drugs affect muscle hypertrophy in the long term. Further information can be found in a recent review published in the Journal Sports Medicine(https://www.ncbi.nlm.nih.gov/pubmed/23013520).

In the meantime, it seems wise to avoid regular use of non-steroidal anti-inflammatory drugs for the treatment of muscle pain and/or performance enhancement. Apart from one isolated study that showed positive effects in older people, the effects of non-steroidal anti-inflammatory drugs on muscle adaptations to exercise will be neutral at best.

Furthermore, the data regarding satellite cells suggest that non-steroidal anti-inflammatory drugs may have a negative effect on long-term muscle gains. This is a particular concern for those with extensive training experience, as an inability to increase the number of nuclei in the muscles could be a limiting factor in maximizing muscle development.

And then there are the side effects. Continuous use of non-steroidal anti-inflammatory drugs has been associated with stomach problems in a large proportion of the population. Other potentially more dangerous consequences that are less common include bleeding stomach ulcers, cardiovascular complications and even liver and kidney failure. Not a good risk/benefit ratio, to say the least.

Interestingly, curcumin may be a safer alternative to non-steroidal anti-inflammatory drugs. Curcumin, which usually turns out to be free of side effects, has similar mechanisms of action to relieve pain. If you need a boost to exercise through a sore muscle, then this would be a better way to go.

As a final note, it is worth mentioning that it is questionable whether non-steroidal anti-inflammatory drugs really help to reduce perceived pain and promote recovery of muscle function. The majority of studies seem to indicate that their use has no better therapeutic effect than a placebo (7).

It may well be that the primary pain-relieving benefits of these drugs are largely psychological. If this is indeed the case, the question arises as to whether non-steroidal anti-inflammatory drugs are worth the risk at all in light of all their potential negative effects.

References

1. Adams, G, and Bamman, MM. Characterization and regulation of mechanical loading-induced compensatory muscle hypertrophy. Comprehensive Physiology 2829, 2012.
2. Bondesen, BA, Mills, ST, Kegley, KM, and Pavlath, GK. The COX-2 pathway is essential during early stages of skeletal muscle regeneration. Am. J. Physiol. Cell Physiol. 287: 475-483, 2004.
3. Bondesen, BA, Mills, ST, and Pavlath, GK. The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms. Am. J. Physiol., Cell Physiol. 290: 1651-1659, 2006.
4. Burd, NA, Dickinson, JM, Lemoine, JK, Carroll, CC, Sullivan, BE, Haus, JM, Jemiolo, B, Trappe, SW, Hughes, GM, Sanders, CE,Jr, and Trappe, TA. Effect of a cyclooxygenase-2 inhibitor on postexercise muscle protein synthesis in humans. Am. J. Physiol. Endocrinol. Metab. 298: E354-61, 2010.
5. Burian, M, and Geisslinger, G. COX-dependent mechanisms involved in the antinociceptive action of NSAIDs at central and peripheral sites. Pharmacol. Ther. 107: 139-154, 2005.
6. Clarkson, PM, and Hubal, MJ. Exercise-induced muscle damage in humans. Am. J. Phys. Med. Rehabil. 81: 52-69, 2002.
7. Connolly, DA, Sayers, SP, and McHugh, MP. Treatment and prevention of delayed onset muscle soreness. J. Strength Cond Res. 17: 197-208, 2003.
8. Krentz, JR, Quest, B, Farthing, JP, Quest, DW, and Chilibeck, PD. The effects of ibuprofen on muscle hypertrophy, strength, and soreness during resistance training. Appl. Physiol. Nutr. Metab. 33: 470-475, 2008.
9. Mackey, AL, Kjaer, M, Dandanell, S, Mikkelsen, KH, Holm, L, Dossing, S, Kadi, F, Koskinen, SO, Jensen, CH, Schroder, HD, and Langberg, H. The influence of anti-inflammatory medication on exercise-induced myogenic precursor cell responses in humans. J. Appl. Physiol. 103: 425-431, 2007.
10. Mikkelsen, UR, Langberg, H, Helmark, IC, Skovgaard, D, Andersen, LL, Kjaer, M, and Mackey, AL. Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise. J. Appl. Physiol. 107: 1600-1611, 2009.
11. Mikkelsen, UR, Schjerling, P, Helmark, IC, Reitelseder, S, Holm, L, Skovgaard, D, Langberg, H, Kjaer, M, and Heinemeier, KM. Local NSAID infusion does not affect protein synthesis and gene expression in human muscle after eccentric exercise. Scand. J. Med. Sci. Sports 21: 630-644, 2011.
12. Novak, ML, Billich, W, Smith, SM, Sukhija, KB, McLoughlin, TJ, Hornberger, TA, and Koh, TJ. COX-2 inhibitor reduces skeletal muscle hypertrophy in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296: R1132-9, 2009.
13. Palmer, RM. Prostaglandins and the control of muscle protein synthesis and degradation. Prostaglandins Leukot. Essent. Fatty Acids 39: 95-104, 1990.
14. Petersen, SG, Beyer, N, Hansen, M, Holm, L, Aagaard, P, Mackey, AL, and Kjaer, M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients. Arch. Phys. Med. Rehabil. 92: 1185-1193, 2011.
15. Petersen, SG, Miller, BF, Hansen, M, Kjaer, M, and Holm, L. Exercise and NSAIDs: effect on muscle protein synthesis in patients with knee osteoarthritis. Med. Sci. Sports Exerc. 43: 425-431, 2011.
16. Prisk, V, and Huard, J. Muscle injuries and repair: the role of prostaglandins and inflammation. Histol. Histopathol. 18: 1243-1256, 2003.
17. Rieu, I, Magne, H, Savary-Auzeloux, I, Averous, J, Bos, C, Peyron, MA, Combaret, L, and Dardevet, D. Reduction of low grade inflammation restores blunting of postprandial muscle anabolism and limits sarcopenia in old rats. J. Physiol. 587: 5483-5492, 2009.
18. Rodemann, HP, and Goldberg, AL. Arachidonic acid, prostaglandin E2 and F2 alpha influence rates of protein turnover in skeletal and cardiac muscle. J. Biol. Chem. 257: 1632-1638, 1982.
19. Soltow, QA, Betters, JL, Sellman, JE, Lira, VA, Long, JH, and Criswell, DS. Ibuprofen inhibits skeletal muscle hypertrophy in rats. Med. Sci. Sports Exerc. 38: 840-846, 2006.
20. Trappe, TA, Carroll, CC, Dickinson, JM, LeMoine, JK, Haus, JM, Sullivan, BE, Lee, JD, Jemiolo, B, Weinheimer, EM, and Hollon, CJ. Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300: R655-62, 2011.
21. Vandenburgh, HH, Hatfaludy, S, Sohar, I, and Shansky, J. Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle. Am. J. Physiol. 259: C232-40, 1990.
22. Vane, JR, and Botting, RM. Anti-inflammatory drugs and their mechanism of action. Inflamm. Res. 47 Suppl 2: S78-87, 1998.

By Brad Schoenfeld, PhD | 11/13/12

Source: https://www.t-nation.com/training/do-pain-pills-impair-muscle-growth