Heavy weightlifting, like most any sport, can cause pain and soreness. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen are what most people turn to first and for many these drugs are part of a daily routine. When it comes to NSAIDs and bodybuilding/weight lifting the debate over whether they hurt muscle and strength gains is ongoing and often filled with misinformation and bro-science. So do NSAIDs negatively affect protein metabolism?
NSAIDs are taken regularly by approximately 33 million Americans and over 30 billion doses of NSAIDs are consumed annually in the United States making them the most used medications on the market. The major side effects of NSAIDs are related to their effects on the stomach and bowels and this is where much of the misinformation stems from.
How do NSAIDs work?
Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. This inhibition is competitively reversible, as opposed to the mechanism of aspirin, which is irreversible inhibition. COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid. Prostaglandins act as messenger molecules in the process of inflammation, where NSAIDs get their claim to fame. COX-1 has a “house-keeping” role in regulating many normal physiological processes. One of these is in the stomach lining, where prostaglandins serve a protective role, preventing the stomach mucosa from being eroded by its own acid. COX-2 is an enzyme facultatively expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.
When nonselective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, ulcers of the stomach or duodenum internal bleeding can result. The discovery of COX-2 led to research to development of selective COX-2 inhibiting drugs that do not cause gastric problems characteristic of older NSAIDs.
Tylenol (acetaminophen) is not considered an NSAID because it has little anti-inflammatory activity. It treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body.
The Effect of NSAIDs on Muscle Gains
It has been posited by many a bro-science practitioner that NSAIDs have negative effects on muscle recovery. Arguments range from the largely unscientific; muscle have to feel pain to grow. To more scientific associations; NSAIDs keep your stomach from repairing itself by blocking COX-1 so blocking COX-1 in muscle must therefor prevent muscle repair. Not a terrible argument, but what’s the science say?
In the 1960s and 70s studies demonstrated that prostaglandins were present in skeletal muscle and that their concentrations increased during and after exercise (Karim et al. 1967, Herbaczynska-Cedro and Staszewska-Barczak 1974, Herbaczynska-Cedro et al. 1976). Later studies demonstrated that prostaglandin supplementation led to increased protein synthesis in an in vitro study involving rat skeletal muscle (Rodeman & Goldberg 1982). This effect was decreased with the use of a COX inhibitor. NSAIDs are useful in that they block prostaglandin production decreasing pain and inflammation, but if prostaglandins are also involved in skeletal muscle protein synthesis, what would the effect be on muscle growth if NSAIDs are used chronically?
Acetaminophen (4g/day) and ibuprofen (1.2g/day) have been shown to significantly negate resistance training-induced increases in prostaglandin production and protein synthesis 24 hours after a single strenuous resistance training session (Trappe et al. 2002). This same effect on protein synthesis has also been shown to occur when taking an NSAID as early as 16 hours prior to an exercise session (Boushel et al. 2002).
So there is some evidence of decrease protein synthesis in single dose/workout scenarios, what is the effect in the case of chronic NSAID? Interestingly, training studies with younger subjects seem to have no negative repercussions, and even have been shown to elicit some enhancements in older subjects. Young individuals, who were divided into a control group and a study group, underwent a biceps training program. The study group was given a low dose of ibuprofen. The study lasted six weeks and at the end of those six weeks, the researchers found that there was no difference between the group given ibuprofen and the control group in terms of muscle growth (Krentz et al 2008).
In older individuals there may actually be an enhancement of muscle growth and strength. In a 12-week study, healthy men and women (ages 60-78) where given either acetaminophen (4 grams/day) or ibuprofen (1.2 grams/day), and they were trained three days per week. The group using NSAIDs increased muscle mass and strength by 25 to 50 percent more compared to the control group (Trappe et al.).
Following exercise prostaglandin PGE2 is up-regulated which itself stimulates production of Interlukin-6 (IL-6) and Murf-1. IL-6 can inhibit protein synthesis and negatively influence muscle growth. Murf-1 is proteolytic, so it may also do bad things to muscle. Down-regulation of PGE2, with NSAID use, along with a training-induced increase in intramuscular COX-1 and apparently muscle-friendly prostaglandin PGF2α, may be beneficial to muscles. It is unclear if this effect is specific to older individuals, there is certainly evidence of an exaggerated inflammatory response with aging.
In an acute sense, NSAIDs appear to negatively influence protein synthesis. However, in the long run there may be a net increase in protein synthesis due to the ability of the NSAIDs to block production of IL-6 and MURF-1, which both facilitate muscle deterioration. This later effect has only been demonstrated in older individuals, so it is unwise to jump to the conclusion that chronic NSAID use would have a positive effect in younger individuals muscle mass. That said, the evidence is lacking to say whether or not NSAIDs have a positive or negative influence on muscle growth. So, use wisely. Don’t fear NSAIDs for occasional aches and pains, they won’t negate your gains.
- Boushel R, Langberg H, Gemmer C, Olesen J, Crameri R, Scheede C, Sander M, and Kjaer M. Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise. J Physiol 543: 691-698, 2002.
- Herbaczynska-Cedro K, and Staszewska-Barczak J. Proceedings: Muscular 562 work and prostaglandin release. Brit J Pharm 52: 454P-455P, 1974.
- Herbaczynska-Cedro K, Staszewska-Barczak J, and Janczewska H. Muscular work and the release of prostaglandin-like substances. Cardiovasc Res 10: 413-565 420, 1976.
- Karim SM, Sandler M, and Williams ED. Distribution of prostaglandins in humans 593 tissues. Br J Pharmacol Chemother 31: 340-344, 1967.
- 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.
- Rodemann HP, and Goldberg AL. Arachidonic acid, prostaglandin E2 and F2α influence rates of protein turnover in skeletal and cardiac muscle. J Biol Chem 257:720 1632-1638, 1982.
- Trappe TA, White F, Lambert CP, Cesar D, Hellerstein M, and Evans WJ. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am J826 Physiol Endocrinol Metab 282: E551-556., 2002.
- 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: R655-662, 2011.
- Trappe, T. A., & Liu, S. Z. (March 28, 2013). Effects of Prostaglandins and COX Inhibiting Drugs on Skeletal Muscle Adaptations to Exercise. Journal of Applied Physiology.