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 .
NSAIDS may help with DOMS. In rabbit models, NSAIDS demonstrated reduced histologic evidence of contraction-induced skeletal muscle damage . 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 . 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 . 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 .
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 . One study found NSAID use may inhibit muscle growth. In young adults taking ibuprofen daily, muscle strength and hypertrophy were inhibited compared to controls .
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.
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 . 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 .
It’s worth noting acetaminophen taken before athletes did allow them to cycle harder  and longer . However, there was no effect mean power output, blood lactate accumulation, pain perception, or total work done  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 .
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 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 . Vitamin D deficiency has catabolic effects on muscle tissue, causes muscle weakness, and impairs cross-bridge formation, all of which could impair athletic performance . In patients recovering from ACL surgery, low vitamin D was linked impaired strength recovery .
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 . 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 . 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 .
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 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 . 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 . Vitamin C supplementation also did not aid in rates of perceived exertion .
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 . 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.
Hoffman et al found that pre-and post-exercise protein supplements improved 80% 1RM squat reps at 24 and 48 hours compared to placebo . 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 . At 3 and 7 days following exercise, whey protein consumption was superior to carbohydrates for recovery of isometric and isokinetic muscle forces .
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” . Dahlstrom et al found no effect on muscle soreness or CK .
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 does appear to help with exercise recovery. Hurley et al showed that caffeine supplementation aids in reducing DOMS . In a separate study, caffeine supplementation attenuated DOMS and force loss following eccentric exercises . 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 . A similar follow up study was not able to reproduce these results . In another interesting physiology study, athletes consuming caffeine had elevated oxygen consumption and free fatty acid (FFA) levels compared to placebo .
Not all studies show benefit. One study showed that showed that caffeine impaired autonomic recovery due to increased sympathetic activity . 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 .
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.
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