can we please analyze this part of the article in reference to taking some aspirin before excercise and the use of anti-oxidants. thank you, PK[/quote]
More from the review (note the observation on individual responses to eccentric exercise in the last paragraph):
[quote]Pharmacological Treatment of DOMS Using NSAIDs
One of the many treatment modalities advocated to facilitate recovery of muscle function and alleviate the symptoms of DOMS is NSAIDs. The value of NSAID therapy in the treatment of DOMS is equivocal, with the majority of studies showing no effect despite a strong theoretical basis for efficacy. The following sections will address the inflammatory response of the tissue to mechanical damage, the effects of NSAIDs on this response, and the potential mechanism for alleviating DOMS.
Nonsteroidal anti-inflammatory drugs work after strenuous exercise by inhibiting the COX enzyme and thus PGE2 synthesis. Nonsteroidal anti-inflammatory drugs can be classified as single- or dual-action drugs. Nonsteroidal anti-inflammatory drugs such as aspirin, naproxen, flurbiprofen, and ibuprofen are COX inhibitors only and are single-action drugs. Other NSAIDs such as diclofenc and ketoprofen are dual-action NSAIDs blocking both the COX and LIPOX pathways of arachidonic acid metabolism. The latter NSAIDs may therefore have a more powerful anti-inflammatory effect than the single-action NSAIDs.
Dual-action NSAIDs may be more similar to steroid hormones in their effects on inflammation. Corticosteroids, such as glucocorticoids, inhibit phospholipase A2 and thus block the initial cleavage of arachidonic acid from the cell membranes, resulting in a more complete anti-inflammatory effect than most commonly used over-the-counter single-action NSAIDs. However, glucocorticoids have numerous side effects including facilitation of bone and muscle loss, edema, and hypertension (51); thus, their role as an anti-inflammatory agent should be limited. The NSAIDs also have negative side effects such as gastrointestinal distress and renal and hypertensive effects (6); however, these side effects are less frequent and of less severity than those of the glucocorticoids.
At lower doses NSAIDs tend to exert an analgesic effect, whereas at higher doses an anti-inflammatory effect is achieved (32). One possible explanation for this is that NSAIDs at higher doses disrupt the activity of certain white blood cells such as neutrophils and macrophages (2). Thus, NSAIDs may have a direct inhibitory effect on inflammation, independent of the pain-reducing effects of PGE2 inhibition.
The Efficacy of NSAIDs on DOMS
This review is limited to a discussion of human studies examining NSAIDs and their effects on DOMS and other pertinent indirect measurements of muscle damage. All studies used some form of eccentric exercise that standardized the injury protocol. However, the modes of eccentric exercise differed between studies and included isokinetic dynamometry (24, 30, 44), cycle ergometry (42), drop jumping (75), high-force eccentric exercise (18, 29, 33, 34, 67, 74), box stepping (66), and downhill running (16, 17). The NSAID therapy in these studies was either prophylactic, beginning before the eccentric exercise (as a prevention to exercise damage), or therapeutic, beginning after eccentric exercise (as a treatment to exercise damage).
A summary of the results of studies demonstrating either no efficacy or some efficacy of NSAIDs on DOMS is shown in Tables 2 and 3, respectively. For organizational purposes, we first discuss studies showing no efficacy of NSAIDs on DOMS and then present those showing an effect on DOMS.
Studies Demonstrating No Efficacy of NSAIDs on DOMS
Most of the NSAID studies showing no effect on DOMS involved the use of ibuprofen or flurbiprofen. Both medications are from the same carboxylic acid classification and the same propionic acid subclassification (16, 29, 33, 34, 42, 67, 75). One study used aspirin (4). The reader should note that direct comparison among study findings is not always straightforward because of variations in study design, most noticeably medication dosage and damage protocol.
Kuipers et al. (42) were the first to address the question of whether anti-inflammatory medications showed efficacy in the treatment of DOMS. This study used 6 subjects in a crossover design. Subjects were treated prophylactically with either 150 mg of flurbiprofen or a placebo 24 hours before eccentric cycling and then for 72 hours after exercise. Although the researchers reported no effect of flurbiprofen on DOMS, creatine kinase (CK), or muscle histology, there was significantly lower muscle soreness after the second eccentric exercise bout, which was administered 3 weeks after the first bout. This phenomenon has been described widely as the repeated bout effect (RBE) and has been shown by multiple investigators (52, 60, 63, 65). In light of the RBE, the exact effect of the flurbiprofen remains unclear.
A similar methodological concern was also observed in a crossover design study by Donnelly et al. (16) using ibuprofen. Sixteen subjects were treated prophylactically with 2,400 mg of ibuprofen or a placebo 24 hours before and for 72 hours after a 45-minute downhill running protocol. Repeated bouts of this exercise were only 10 weeks apart, and although they report no efficacy of ibuprofen on DOMS, muscle strength, or endurance time, CK activity was actually higher in the ibuprofen group compared with the placebo after both eccentric exercise protocols. These results suggest that ibuprofen could contribute to greater levels of damage in the treated muscle. However, a study by Pizza et al. (67) showed that treatment with 2,400 mg of ibuprofen for 5 days before and 10 days after high-force eccentric exercise of the elbow flexors reduced CK activity in 10 men.
It is unclear why inconsistencies were observed when using the same NSAID; however, differences in the mode and intensity of exercise or the length of the treatment period may have contributed to the observed differences.
Two studies, however, have reported impaired recovery of muscle function with NSAID treatment after eccentric contractions (33, 57). Howell et al. (33) treated 15 subjects prophylactically with either 300 mg of flurbiprofen or a placebo 24 hours before and for 14 days after eccentric exercise of the elbow flexors. They reported no efficacy of flurbiprofen on DOMS, swelling, or stiffness; however, maximal force was significantly lower 14 days later in the flurbiprofen group. Mishra et al. (57) similarly reported impaired recovery of muscle function 28 days after a 6-day flurbiprofen treatment in the animal model.
Because most human studies have not evaluated recovery after 14 days, it is not known whether NSAIDs may contribute to long-term negative effects on muscle function reported in the Mishra et al. (57) study.
Other studies have also demonstrated a lack of efficacy of NSAID treatment after eccentric exercise (4, 29, 34, 75). Although the flurbiprofen and ibuprofen studies used dosages ranging from analgesic (34, 75) to anti-inflammatory dosages (33, 34), no efficacy was demonstrated consistently.
Furthermore, the flurbiprofen and ibuprofen studies showed a lack of efficacy over both short (16, 75) and long dosing periods (33, 67). Thus, it appears that lack of efficacy of these 2 NSAIDs is neither dose dependent nor time dependent. Also, all flurbiprofen and ibuprofen studies that showed no efficacy (16, 29, 33, 34, 42, 67, 75) used prophylactic doses. The expectation might be that prophylactic NSAID treatment would maximize the anti-inflammatory effect by inhibiting the immediate response to the mechanical injury. However, this was not observed in any of the studies.
Studies Demonstrating Efficacy of NSAIDs on DOMS
In contrast to the aforementioned studies, work by Hasson et al. (30) found that 400 or 1,200 mg of ibuprofen ingested 4 hours before or in the 24 hours after eccentric exercise, respectively, significantly enhanced recovery of muscle force and further reduced DOMS 48 hours after exercise in the quadriceps. The reader should note, however, that there were only 5 subjects in this treatment group. In contrast, both Donnelly et al. (17) and O’Grady et al. (66) used larger sample sizes when examining the effect of the NSAID diclofenac on DOMS after eccentric exercise. Donnelly et al. (17) treated 20 subjects with a prophylactic dose of diclofenac (150 mg) from 1.5 to 72 hours after exercise using a crossover design where 2 bouts of downhill running were separated by a 10-week interval.
Despite the similar design concerns previously identified (42), significant reductions in measures of DOMS at certain sites were reported after the first bout in the diclofenac group compared with the placebo group. O’Grady et al. (66) treated 27 subjects with a prophylactic dose of diclofenac (150 mg) from 14 days before to 13 days after eccentric box-stepping exercise. Not only was DOMS reduced but CK activity also was lower and histological assessment of biopsied muscle suggested less damage. In humans, therefore, both short-term and long-term diclofenac administration appears to have some positive effects on DOMS and muscle damage. One possible explanation is diclofenac’s role as a dual-action NSAID inhibiting both the COX and LIPOX pathways of arachidonic acid metabolism (6), thus providing a potentially greater anti-inflammatory effect.
Another NSAID that has shown potential in the treatment of DOMS is naproxen. Both Dudley et al. (18) and Lecomte et al. (44) demonstrated enhanced recovery of force and reduction of DOMS in the quadriceps with naproxen. Dudley et al. (18) reported that daily administration of 660 mg of naproxen up to 10 days after eccentric exercise enhanced force recovery and reduced thigh soreness 4 days after exercise when compared with a placebo. Lecomte et al. (44) reported that daily administrations of 1,000 mg of naproxen for 7 days resulted in reduced soreness 3 days after exercise and a greater recovery of quadriceps torque at 60??s?1 compared with a placebo. Interestingly, naproxen is structurally similar to ibuprofen and flurbiprofen with all 3 NSAIDs being carboxylic acids and propionic acid derivatives (32).
However, ibuprofen and flurbiprofen have not demonstrated efficacy in treating DOMS. Design concerns in both Dudley et al. (18) and Lecomte et al. (44) may again limit the applicability of their findings. Dudley et al. (18) used a small sample size (n = 8), whereas Lecomte et al. (44) used an eccentric exercise that induced only 5 and 10% reductions in torque in the naproxen and control groups, respectively. It is possible that with so little damage to the muscle (and potential inflammation), differences in force recovery were due to factors other than naproxen. Moreover, a study by Bourgeoise et al. (5) using both concentric and eccentric exercise showed no effect of 48 hours of naproxen treatment on DOMS.
In contrast to the work of Barlas et al. (4) that showed no effect of aspirin on DOMS, a study by Francis and Hoobler (24) reported that treatment with aspirin after eccentric exercise resulted in a significant reduction in soreness and improved the range of motion when compared with a placebo. Conflicting findings may be explained by the fact that Barlas et al. (4) used 900 mg, whereas Francis and Hoobler (24) administered much higher dosages (2,600 mg for 48 hours).
In addition, no placebo group was used in the Francis and Hoobler (24) study; thus, these results should be interpreted with caution. A recent study by Sayers et al. (74) reported enhanced recovery of force and decreased soreness in 36 subjects after eccentric exercise of the elbow flexors using ketoprofen. Whereas most of the aforementioned studies examined a particular NSAID and its effect on recovery of muscle function over several days, Sayers et al. (74) examined the acute effects of NSAIDs during the hours of peak muscle soreness, approximately 36?44 hours after exercise.
This study design excluded those subjects who did not report at least moderate soreness (using a 50-mm cutoff criterion on a 100-mm visual analog scale [VAS]) 36 hours after eccentric exercise. It was reported that both 25 and 100 mg of ketoprofen administered at 36 hours resulted in a significant reduction in soreness over the following 8 hours when compared with a placebo. Furthermore, the 100-mg dose resulted in a significant recovery of force over the same 8-hour treatment period. These results could be due to the fact that ketoprofen, like diclofenac, which also showed efficacy, is a dual-action NSAID and may potentially exert a greater anti-inflammatory effect.
Why Discrepancies Exist Among Studies?
The reader will note the obvious contrast in the efficacy of various NSAIDs among the studies. One factor that must be considered is the mode of eccentric exercise used. Differences among studies may result in more or less soreness and damage (and perhaps more or less inflammation). Several researchers have suggested that eccentric exercise may not initiate a full inflammatory response in humans (33, 64). In addition, different eccentric exercise studies have demonstrated temporal discrepancies in the appearance of inflammatory mediators (9, 23, 38, 71).
Perhaps different modes of eccentric exercise resulted in different magnitudes of the inflammatory responses that were either able or unable to be alleviated with a particular NSAID dosage. Other differences among the studies that may contribute to the disparate finding could be the type of NSAID used and its strength, the duration of the treatment, and the dosage administered. In addition, it appears that an arm-damage model results in better control of damage than the leg-damage model.
A second explanation may be the fact that not everyone undergoing eccentric exercise demonstrates muscular soreness. Observations from our laboratories indicate that 30?35% of subjects do not demonstrate at least moderate soreness (at least 50 mm on a 100 mm VAS) during the hours of peak soreness after eccentric exercise (74). This could have important consequences in prophylactic NSAID studies because subjects with reduced muscular soreness after NSAID administration may not demonstrate the effects of the drug treatment but instead may simply not demonstrate a soreness response to eccentric exercise.
In addition, if nonresponders are placed in a placebo group, efficacy of a particular NSAID may be masked by this aberrant response. Only Howell et al. (33, 34) have reported cutoff criteria in their studies, disqualifying subjects who do not demonstrate at least a 25% force loss after eccentric exercise. However, a poor relationship has been reported between muscular force and muscle soreness after eccentric exercise (69); thus, a cutoff criterion based on force loss may not be sufficient to detect nonresponders to muscle soreness.[/quote]
Personally, I would NEVER recommend someone use NSAIDs to alleviate or prevent DOMS; the negative side effects far outweigh the benefits. More to come…