Evidence Based Recovery Part 4 : Medications And Supplements
Physical activity, weight training, and sports are associated with a wide variety of post-exercise sequelae including muscle fatigue, delayed onset muscle soreness, discomfort, pain, and soreness. In our previous 3 posts, we have reviewed the following as recovery modalities:
In part 4, we will review medications and supplements that can help or have been investigated to help with recovery.
NSAIDS. Non‐steroidal anti‐inflammatory drugs (NSAIDs) are the most widely used class of drugs in the world. Generally, they are used to treat pain, fever and/or inflammation. In athletes, they are used frequently to treat pain. One in 7 high school athletes and 29% of college athletes use NSAIDs as a preventative measure on gameday [6].
The mechanism of action of NSAIDS involves inhibition of cyclooxygenase (COX)‐1 and cyclooxygenase (COX)‐2. These inhibit the downstream production of prostaglandins, prostacyclins and thromboxanes which are responsible for a variety of physiologic processes. This class of drugs can be further subdivided divided into non-selective NSAIDS and selective COX-1 inhibitors. Non-selective NSAIDS have been shown to impair healing in animal models (Warden, 2005). There is less evidence to support the notion that selective COX-1 inhibitors inhibit healing in animal models (Reuben, 2007). Furthermore, there is emerging evidence that the action of cyclooxygenase (COX) enzymes, and COX-2 in particular, are important and even necessary to achieve maximal skeletal muscle hypertrophy in response to functional overload [7].
NSAIDS may help with DOMS. In rabbit models, NSAIDS demonstrated reduced histologic evidence of contraction-induced skeletal muscle damage [9]. In a study of 33 athletes performing eccentric elbow contractions, celecoxib alleviated muscle soreness but did not detectably affect recovery of muscle function or markers of inflammation (Paulsen, 2010). O’Grady et al found that diclofenac given before exercise lowered post exercise muscle damage [8]. In a 2017 meta-analysis, Morelli et al found that overall NSAID reduces strength loss, soreness, and blood CK levels after an acute muscle injury [4]. Trappe et al found that ibuprofen suppressed skeletal muscle protein breakdown (measured by phenylalanine levels), and had no serum CK or sensation of DOMS compared to placebo [10].
Based on current evidence, there is little reason to believe that the occasional use of NSAIDs will negatively affect muscle growth, although the efficacy for their use in alleviating inflammatory symptoms remains questionable. Evidence on the hypertrophic effects of the chronic use of NSAIDs is less clear. In those who are untrained, it does not appear that regular NSAID use will impede growth in the short term, and at least one study indicates that it may in fact have a positive impact. Given their reported impairment of satellite cell activity, however, longer-term NSAID use may well be detrimental, particularly in those who possess greater growth potential [7]. One study found NSAID use may inhibit muscle growth. In young adults taking ibuprofen daily, muscle strength and hypertrophy were inhibited compared to controls [5].
In summary, the overall evidence is lacking to support or refute NSAID use as a recovery aid. In general, it is likely to help with the symptoms of pain and DOMS following exercise. In that context, it is likely helpful when used sparingly and as needed. However, when taken daily for recovery purposes, there is some evidence to suggest that it does not provide any benefit and may be harmful. Thus, NSAID use can only be recommended on as needed basis for symptom relief following exercise.
Acetaminophen. Acetaminophen, also known as paracetamol or commonly referred to by it’s trade name of tylenol, is a medication used to treat fever and pain. Unlike NSAIDS, acetaminophen is not thought to have the same anti-inflammatory effects. The mechanism of acetaminophen is not well understood, but is thought to affect the central nervous system.
Overall, the role of acetaminophen in recovery from exercise is less well studied than NSAIDS. Peterson et al found that acetaminophen did not affect concentrations of macrophages or neutrophils when taken 24 hours after eccentric exercises [11]. Trappe et al found that acetaminophen suppressed skeletal muscle protein breakdown (measured by phenylalanine levels), and had no serum CK or sensation of DOMS compared to placebo [12].
It’s worth noting acetaminophen taken before athletes did allow them to cycle harder [13] and longer [14]. However, there was no effect mean power output, blood lactate accumulation, pain perception, or total work done [16] This effect was thought to be due to attenuation of pain perception. In marathon runners, acetaminophen taken after the race reduced the sensation of DOMS [15].
In summary, there is limited evidence to make any firm recommendations about the use of acetaminophen in recovering athletes. Like NSAIDS, it probably helps with post exercise pain and DOMS. Other than that, there is no evidence to support or refute its use. The best recommendation that can be made with confidence is to use it when needed for pain relief, but not as a daily recovery medication.
Vitamin D. Vitamin D, a fat soluble micronutrient is wildly popular as both a supplement and subject of research. The active form most commonly available is 25-hydroxyvitamin D. Low vitamin D is associated with a variety of disease states including cardiovascular disease, diabetes and multiple sclerosis. It is most commonly supplement for bone health as it plays a critical role in calcium and bone homeostasis. Among athletes, it has started to gain traction as a recovery supplement.
Vitamin D is linked to skeletal muscle by unclear physiological mechanisms however there is significant research from other areas of musculoskeletal medicine which set a strong basis for aid in recovery. Previous research has linked higher vitamin D to faster recovery of skeletal muscle strength after injury [18]. Vitamin D deficiency has catabolic effects on muscle tissue, causes muscle weakness, and impairs cross-bridge formation, all of which could impair athletic performance [20]. In patients recovering from ACL surgery, low vitamin D was linked impaired strength recovery [22].
There is decent evidence to support vitamin D as a recovery supplement. In athletes supplementing vitamin D for 28 days, eccentric leg exercises were performed and the authors then measured recovery parameters for the following 7 days. They found vitamin D enhanced the recovery in peak isometric force, circulating biomarkers representative of muscle damage (ALT or AST), but had no effect on DOMS [19]. A 2015 narrative review of the literature concluded that vitamin D levels above the normal reference range (up to 100 nmol/L) might increase skeletal muscle function, decrease recovery time from training, increase both force and power production, and increase testosterone production, each of which could potentiate athletic performance [20]. Owens et al found supplemental vitamin D3 at 4000 IU/day has a positive effect on the recovery of force following a bout of damaging eccentric exercise [23].
In summary, vitamin D has both a strong physiologic basis and research basis to recommend it as a supplement for recovering athletes. Several different studies have found it helped with decreased recovery time and force recovery. The available evidence suggests it does not help with DOMS. At this time, given other potential benefits and the relative safety profile of vitamin D, it can be recommended with confidence as a recovery supplement. Better studies are needed to draw firmer conclusions
Vitamin C. Vitamin C is another popular supplement. It plays a role in immune function, collagen synthesis, cortisol production and removes free radicals. Exercise at moderate to severe intensity increases reactive oxygen species. Thus supplementing with vitamin C provides a theoretically basis for how it may aid in recovery from sport. There are few studies evaluating Vitamin C and exercise, especially in regards to exercise recovery.
Vitamin C supplementation before activity may aid in recovery. Bryer et al found that 3 g/d of vitamin for two weeks prior and four days after eccentric elbow extensions reduced muscle soreness and CK increase at 48 hours. They also found vitamin C attenuated the oxidation of glutathione [25]. Other studies have found no benefit. In a 2003 study, 200 mg of post-exercise vitamin C did not aid in recovery from muscle soreness, muscle function, CK or myoglobin [24]. Vitamin C supplementation also did not aid in rates of perceived exertion [29].
In a review of the available studies in 2012, Braakhuis found that doses exceeding 1 g/day impaired sports performance in four studies, while four other studies found non-statistically significant impairments. Other studies have also demonstrated the attenuation of benefits of physical exercise with vitamin C supplementation [27]. It should be noted that one study found no impairment at 1 g/day over 4 weeks of training.
In summary, there are few studies evaluating vitamin C as a recovery supplement. Ultimately, there is only one favorable study. Several studies showed no benefit. More concerning is that at higher doses, namely 1 g/day or more, vitamin C supplementation may impair the benefits of physical exercise. At this time, vitamin C can not be recommended as a recovery supplement and you may consider avoiding it depending on other goals.
Protein. Protein and the amino acids from which they are constructed are the constituent building blocks for myofibrillar protein synthesis. Resistance exercise stimulates protein synthesis leading to muscle hypertrophy. For this reason, protein supplements are likely the most consumed recovery supplement. Athletes consistently cite expectations for “increased muscle mass, improved exercise recovery and improved performance as reasons for protein supplement use” [31]. “Consumers also believe protein supplementation will promote lean muscle mass accretion by enhancing rates of protein synthesis and decreasing rates of protein degradation, and optimize recovery of muscle function and physical performance following exercise by attenuating muscle damage and muscle soreness” [30]. In exercising athletes, a net negative protein balance can occur in the absence of adequate nutrition leading to relative rates of muscle degradation exceeding synthesis. Protein intake does stimulate anabolic activity, muscle strength and size after resistance exercise [32, 33].
Hoffman et al found that pre-and post-exercise protein supplements improved 80% 1RM squat reps at 24 and 48 hours compared to placebo [34]. In a randomized, blinded parallel trial, researchers found that whey protein isolate, when compared to placebo, improved recovery of peak isometric torque with no difference in muscle soreness [35]. At 3 and 7 days following exercise, whey protein consumption was superior to carbohydrates for recovery of isometric and isokinetic muscle forces [36].
Despite this, the one major meta analysis of protein as a recovery supplement was underwhelming. A 2018 systematic review of the effects of protein supplements on muscle damage, soreness and recovery of muscle function concluded “when protein supplements are provided, acute changes in post-exercise protein synthesis and anabolic intracellular signaling have not resulted in measurable reductions in muscle damage and enhanced recovery of muscle function” [30]. Dahlstrom et al found no effect on muscle soreness or CK [39].
In summary, the literature on protein supplementation as a recovery aid for muscle soreness, DOMS or biomarkers of injury such as CK are mixed to negative. However, there are plenty of other benefits to protein supplementation including promoting anabolic activity, muscle strength and size following resistance training. For these reasons, protein is easily recommended with confidence as part of any recovery program. The optimal time to consume protein supplements is an area of continued research.
Caffeine. Caffeine is the most commonly supplement in the world. 89% of Americans consume caffeine in some form [39]. This is especially true of athletes. Caffeine been shown to be an ergogenic aid, with supplementation helping both aerobic and anaerobic exercise [40]. This is likely due to some combination of antifatigue effects, increase in free fatty acids, adrenaline, and increasing power output. What is less clear are the effects of caffeine on recovery parameters following exercise.
Caffeine does appear to help with exercise recovery. Hurley et al showed that caffeine supplementation aids in reducing DOMS [42]. In a separate study, caffeine supplementation attenuated DOMS and force loss following eccentric exercises [44]. In a very interesting study, authors gave athlete either carbohydrates or carbohydrates and caffeine and found that caffeine had an additive effect on rates of postexercise muscle glycogen accumulation [45]. A similar follow up study was not able to reproduce these results [47]. In another interesting physiology study, athletes consuming caffeine had elevated oxygen consumption and free fatty acid (FFA) levels compared to placebo [46].
Not all studies show benefit. One study showed that showed that caffeine impaired autonomic recovery due to increased sympathetic activity [41]. The significance of this on the recovering athlete is not clear. Caffeine does not appear to attenuate or decrease markers of muscle damage. Machado et al found that supplementation did not reduce CK or leukocyte levels compared to placebo [43].
In summary, caffeine can likely be recommended as a recovery supplement. It appears to help with reducing DOMS, force loss and may increase glycogen synthesis and free fatty acid production. In addition, caffeine has other exercise-related benefits including helps with power output, aerobic exercise capacity, rate of perceived exertion, and decreased in fatigue in addition to non-exercise related benefits. Caffeine has little downside in healthy individuals and can thus be recommended with confidence as a recovery supplement.
Conclusion. NSAIDS and acetaminophen are not well studied as recovery aids. They likely help with DOMS and ca be used as needed, but are not currently recommended as a daily recovery medication. Some studies suggest Vitamin D helps with force recovery and recovery time and given other benefits, should be considered as a recovery supplement. Vitamin C does not appear to show benefit and at higher doses may impair some of the benefits of exercise, so supplement should be avoided. Interestingly, the studies evaluating protein as a recovery supplement are not favorable, however given other benefits in exercising individuals, supplementation is recommended. Caffeine appears to help with DOMS and has some other physiologic benefits and can be recommended with confidence given other ergogenic and health benefits.
References
1. Paulsen, G., et al. “A COX‐2 inhibitor reduces muscle soreness, but does not influence recovery and adaptation after eccentric exercise.” Scandinavian journal of medicine & science in sports 20.1 (2010): e195-e207.
2. Warden, Stuart J. “Cyclo-oxygenase-2 inhibitors.” Sports Medicine 35.4 (2005): 271-283.
3. Reuben, Scott S., and Evan F. Ekman. “The Effect of Initiating a Preventive Multimodal Analgesic Regimen on Long-term Patient Outcomes for Outpatient Anterior Cruciate Ligament Reconstruction Surgery: Retracted.” Anesthesia & Analgesia105.1 (2007): 228-232.
4. 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 Jan;46(1):224-233. doi: 10.1177/0363546517697957.
5. Mats Lilja, Mirko Mandić, William Apró, Michael Melin, Karl Olsson, Staffan Rosenborg, Thomas Gustafsson, Tommy R Lundberg. High-doses of anti-inflammatory drugs compromise muscle strength and hypertrophic adaptations to resistance training in young adults. Acta Physiologica, 2017; DOI: 10.1111/apha.12948
6. Tricker, Ray. “Painkilling drugs in collegiate athletics: knowledge, attitudes, and use of student athletes.” Journal of drug education 30.3 (2000): 313-324.
7. Schoenfeld BJ. The use of nonsteroidal anti-inflammatory drugs for exercise-induced muscle damage: implications for skeletal muscle development. Sports Med. 2012 Dec 1;42(12):1017-28.
8. O’Grady M, Hackney AC, Schneider K, Bossen E, Steinberg K, Douglas JM, Murray WJ. Diclofenac sodium (Voltaren) reduced exercise – induced injury in human skeletal muscle. Medicine Science in Sports Exercise, 32(7), 1191-6
9. MISHRA, D. K., J. FRIDEN, M. C. SCHMITZ, and L. LIEBER. Antiinflammatory medication after muscle injury: a treatment resulting in short-term improvement but subsequent loss of muscle function. J. Bone Joint Surg. 77:1510–1519, 1995.
10. Trappe, Todd A., et al. “Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis.” American Journal of Physiology-Endocrinology and Metabolism 282.3 (2002): E551-E556.
11. Peterson, Jennifer M., et al. “Ibuprofen and acetaminophen: effect on muscle inflammation after eccentric exercise.” Medicine and science in sports and exercise 35.6 (2003): 892-896.
12. Trappe, Todd A., et al. “Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis.” American Journal of Physiology-Endocrinology and Metabolism 282.3 (2002): E551-E556.
13. Foster, Josh, et al. “The influence of acetaminophen on repeated sprint cycling performance.” European journal of applied physiology 114.1 (2014): 41-48.
14. Mauger, Alexis R., et al. “Acute acetaminophen (paracetamol) ingestion improves time to exhaustion during exercise in the heat.” Experimental physiology 99.1 (2014): 164-171.
15. Prior, Mary Jane, B. Joseph Lavins, and Kimberly Cooper. “A randomized, placebo-controlled trial of acetaminophen extended release for treatment of post-marathon muscle soreness.” The Clinical journal of pain 28.3 (2012): 204-210.
16. Delextrat, Anne, et al. “Acetaminophen ingestion improves repeated sprint cycling performance in females: A randomized crossover trial.” Kinesiology: International journal of fundamental and applied kinesiology 47.2 (2015): 145-150.
17. Barker, Tyler, et al. “Supplemental vitamin D enhances the recovery in peak isometric force shortly after intense exercise.” Nutrition & metabolism 10.1 (2013): 69.
18. Barker T, Henriksen VT, Martins TB, Hill HR, Kjeldsberg CR, Schneider ED, Dixon BM, Weaver LK: Higher serum 25-hydroxyvitamin D concentrations associate with a faster recovery of skeletal muscle strength after muscular injury. Nutrients. 2013, 5: 1253-1275. 10.3390/nu5041253.
19. Stratos I, Li Z, Herlyn P, Rotter R, Behrendt AK, Mittlmeier T, Vollmar B: Vitamin D increases cellular turnover and functionally restores the skeletal muscle after crush injury in rats. Am J Pathol. 2012, 182: 895-904.
20. Dahlquist, Dylan T., Brad P. Dieter, and Michael S. Koehle. “Plausible ergogenic effects of vitamin D on athletic performance and recovery.” Journal of the International Society of Sports Nutrition 12.1 (2015): 33.
21. Barker, Tyler, et al. “Low vitamin D impairs strength recovery after anterior cruciate ligament surgery.” Journal of Evidence-Based Complementary & Alternative Medicine 16.3 (2011): 201-209.
22. Barker, Tyler, et al. “Low vitamin D impairs strength recovery after anterior cruciate ligament surgery.” Journal of Evidence-Based Complementary & Alternative Medicine 16.3 (2011): 201-209.
23.Owens DJ, Sharples AP, Polydorou I, Alwan N, Donovan T, Tang J, Fraser WD, Cooper RG, Morton JP, Stewart C, Close GL. A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy. Am J Physiol Endocrinol Metab. 2015 Dec 15;309(12):E1019-31.
24. Thompson D, Williams C, Garcia-Roves P, McGregor SJ, McArdle F, Jackson MJ. Post-exercise vitamin C supplementation and recovery from demanding exercise. Eur J Appl Physiol. 2003 May;89(3-4):393-400. Epub 2003 Apr 1.
25. Bryer SC, Goldfarb AH. Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative stress to eccentric exercise. Int J Sport Nutr Exerc Metab. 2006 Jun;16(3):270-80.
26. Braakhuis, Andrea J. “Effect of vitamin C supplements on physical performance.” Current sports medicine reports 11.4 (2012): 180-184.
27. Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci USA. 2009 May 26;106(21):8665-70. Doi: 10.1073/pnas.0903485106. Epub 2009 May 11.
28. Roberts LA, Beattie K, Close GL, Morton JP. Vitamin C consumption does not impair training-induced improvements in exercise performance. Int J Sports Physiol Perform. 2011 Mar;6(1):58-69.
29. Huck CJ, Johnston CS, Beezhold BL, Swan PD. Vitamin C status and perception of effort during exercise in obese adults adhering to a calorie-reduced diet. Nutrition. 2013 Jan;29(1):42-5.
30. Pasiakos, Stefan M., Harris R. Lieberman, and Tom M. McLellan. “Effects of protein supplements on muscle damage, soreness and recovery of muscle function and physical performance: a systematic review.” Sports Medicine 44.5 (2014): 655-670.
31. Lieberman HR, Stavinoha TB, Mcgraw SM, et al. Use of dietary supplements among active-duty U.S. Army soldiers. Am J Clin Nutr. 2010;92:985–95.
32. Lunn WR, Pasiakos SM, Colletto MR, et al. Chocolate milk and endurance exercise recovery: protein balance, glycogen, and performance. Med Sci Sports Exerc. 2012;44:682–91.
33. Morton RW, Murphy KT, McKellar SR, et al A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults Br J Sports Med 2018;52:376-384.
34. Hoffman, Jay R., et al. “Effect of a proprietary protein supplement on recovery indices following resistance exercise in strength/power athletes.” Amino acids 38.3 (2010): 771-778.
35. Buckley JD, Thomson RL, Coates AM, Howe PR, DeNichilo MO, Rowney MK. Supplementation with a whey protein hydrolysate enhances recovery of muscle force-generating capacity following eccentric exercise. J Sci Med Sport. 2010 Jan;13(1):178-81.
36. Cooke MB, Rybalka E, Stathis CG, Cribb PJ, Hayes A. Whey protein isolate attenuates strength decline after eccentrically-induced muscle damage in healthy individuals. J Int Soc Sports Nutr. 2010 Sep 22;7:30. Doi: 10.1186/1550-2783-7-30.
37. Burnley, Elizabeth C. Dahlstrom, et al. “Impact of protein supplements on muscle recovery after exercise-induced muscle soreness.” Journal of Exercise Science & Fitness 8.2 (2010): 89-96.
38. Grgic J, Mikulic P, Schoenfeld BJ, et al. The Influence of Caffeine Supplementation on Resistance Exercise: A Review. Sports Med. 2019 Jan;49(1):17-30. Doi: 10.1007/s40279-018-0997-y. Review. PubMed PMID: 30298476.
39. Fulgoni VL 3rd, Keast DR, Lieberman HR. Trends in intake and sources of caffeine in the diets of US adults: 2001–2010. Am J Clin Nutr. 2015;101(5):1081–7.
40. Ganio MS, Klau JF, Casa DJ, et al. Effect of caffeine on sport-specific endurance performance: a systematic review. J Strength Cond Res. 2009;23(1):315–24.
41. Bunsawat K, White DW, Kappus RM, Baynard T. Caffeine delays autonomic recovery following acute exercise. Eur J Prev Cardiol. 2015 Nov;22(11):1473-9.
42. Hurley CF, Hatfield DL, Riebe DA. The effect of caffeine ingestion on delayed onset muscle soreness. J Strength Cond Res. 2013 Nov;27(11):3101-9.
43. Machado M, Koch AJ, Willardson JM, dos Santos FC, Curty VM, Pereira LN. Caffeine does not augment markers of muscle damage or leukocytosis following resistance exercise. Int J Sports Physiol Perform. 2010 Mar;5(1):18-26.
44. Maridakis, Victor, et al. “Caffeine attenuates delayed-onset muscle pain and force loss following eccentric exercise.” The Journal of Pain 8.3 (2007): 237-243.
45. Pedersen, David J., et al. “High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine.” Journal of Applied Physiology 105.1 (2008): 7-13.
46. Chad, Karen, and Brian Quigley. “The effects of substrate utilization, manipulated by caffeine, on post-exercise oxygen consumption in untrained female subjects.” European journal of applied physiology and occupational physiology 59.1-2 (1989): 48-54.
47. Beelen M, Kranenburg Jv, Senden JM, Kuipers H, Loon LJ. Impact of caffeine and protein on postexercise muscle glycogen synthesis. Med Sci Sports Exerc. 2012 Apr;44(4):692-700.
