Purpose. This systematic review and meta-analysis was performed to determine the effectiveness of Omega-3 polyunsaturated fatty acid ( PUFA) supplement on muscle soreness after eccentric exercise. Methods. PubMed, EMBASE, CENTRAL, and ISI Web of Science were searched to identify randomized controlled trials (RCTs) that assessed the efficacy of PUFA on muscle soreness after eccentric exercise. Mean difference (MD) and the associated 95% confidence interval (95% CI) were calculated by RevMan 5.3 to indicate delayed onset muscle soreness (DOMS) that measured two days after eccentric trainings. Subgroup analyses according to duration and daily dosage of PUFA supplements before eccentric exercises were performed to determine whether these factors will influence the overall effect size. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. The protocol of this systematic review and meta-analysis was registered at PROSPERO (CRD42018085869). Results. 12 RCTs containing 145 subjects and 156 controls were included in this study. Meta-analysis revealed a significantly decreased DOMS (MD -0.93; 95% CI -1.44, -0.42; ) in PUFA supplement groups, while no significant differences in isometric muscle strength and range of motion (ROM) were detected. However, the pooled effect size for DOMS was lower than the minimal clinically important difference (MCID) of 1.4 on the 10-unit VAS, suggesting that the effect size of less muscle soreness with PUFA supplements did not appear to be clinically relevant. Conclusion. There is low-quality evidence that PUFA supplementation does not result in a clinically important reduction of muscle soreness after eccentric exercise. Isometric muscle soreness and range of motion were not improved by PUFA supplementation either (low-quality evidence). To further elucidate the overall role of PUFA on muscle damage in this area, large-scale RCTs are still needed.
Omega-3 polyunsaturated fatty acids ( PUFAs) are essential fatty acids rich in fish oils. The predominant components of PUFA including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), which can reduce the production and release of arachidonic acid and proinflammatory prostaglandins (PGs), are believed to have potent anti-inflammatory effects. Nutritional intervention with PUFA is widely believed to have the potential to alter the trajectory of a wide range of diseases including autoimmune diseases such as rheumatoid arthritis , inflammatory bowel diseases [2–5], and lupus nephritis , as well as cancer [7–10], cardiovascular diseases [11–14], metabolic disorders , and even neuropsychiatric decrements [16–18]. As for healthy individuals, current literatures focus on its implicit roles in metabolism  as well as skeletal muscle functions [20, 21], among which a number of researches have also revealed its temporal effects in skeletal muscle, and even implied that it may play a role in delayed onset muscle soreness (DOMS) after eccentric exercise.
DOMS is recognized as a kind of common muscle discomfort occurring after unfamiliar exercises especially when a person is repeatedly exposed to high eccentric muscle contractions or unaccustomed exercise . It increases within the first 24 h postexercise, and rises to peak between 24 to 48 hours [23–26] or 48 to 72 hours [23, 27] according to different studies, then subsides and eventually disappears in 5 to 7 days [23, 28]. Similar to acute muscle soreness, it presents with muscle stiffness, aching pain, and/or muscular tenderness [28–30]. Though the exact physiological mechanism of DOMS remains equivocal, researches have revealed its relations with damage of sarcomeres, ensuing swelling of damaged muscle fibers, and subsequent initiation of an inflammatory response [31–34]. So far, physical therapies, including postexercise massage [35, 36], cryotherapy , low-level phototherapy , and vibration therapy [39, 40], as well as the application of pharmacologic nonsteroidal anti-inflammatory drugs (NSAIDs) [41–46], are the predominant means employed to alleviate DOMS. Actually, since DOMS is widely accepted as a common self-treated condition, current studies have been turning to dietary interference, such as caffeine , ginger [48, 49], and taurine [50, 51], and some studies also revealed PUFA as a potential therapeutic agent to blunt DOMS. Despite the fact that majority of these studies are randomized controlled trials (RCTs), their sample sizes are relatively small, which though seems to be a common fault of trials in sports medicine, could not afford adequate statistical power. Therefore, to further elucidate the gainful benefit of PUFA in this field, we conducted a systematic review and meta-analysis based on the variable outcomes from current evidences.
This systematic review and meta-analysis was performed and reported following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline . The protocol for this study was registered with PROSPERO (CRD42018085869).
2.1. Literature Search Strategy
A thorough literature search was conducted by searching PubMed, EMBASE, CENTRAL, and ISI Web of Science to identify potentially eligible articles about PUFA supplementation and muscle soreness after eccentric exercises. Four electronic databases were searched from their inception date to the latest issue (June, 2018) without language restriction. A combination of medical subject headings (MeSHs) and free terms were used based on the specifications of each database. An example of literature search strategy for PubMed was as follows: (“Fatty Acids, Omega-3”[MeSH] or omega-3 or polyunsaturated fatty acid or PUFA or “Eicosapentaenoic Acid”[MeSH] or Eicosapentaenoic Acid or EPA or “alpha-Linolenic Acid”[MeSH] or alpha-Linolenic Acid or Linolenic acid or “Docosahexaenoic Acids”[MeSH] or Docosahexaenoic Acids or DHA or “Fish Oils”[MeSH] or fish oil or fish oils) and (randomized controlled trial or random or randomly or placebo or controlled trial) and (eccentric contraction or eccentric training or eccentric exercise). The bibliographies of related systematic reviews were also searched. In addition, the reference section for each included study was also manually searched for inclusion of further eligible studies.
2.2. Inclusion and Exclusion Criteria
2.2.1. Types of Participants
Subjects enrolled in our systematic review were required to be adults that undertook eccentric exercise to induce muscle soreness. No restrictions on race, gender, and specific type of eccentric exercise were imposed. Volunteers were excluded if they consumed any kind of PUFA supplementation within the last 6 months. Participants were also excluded if they had engaged in specific upper limb or lower limb eccentric training or other kinds of resistance training in the previous 6 months.
2.2.2. Types of Intervention
Participants were required to take PUFA supplements before and/or after a bout of eccentric exercise. The main components of supplements consumed should be PUFA (i.e., EPA, DHA, or linolenic acid), and a combination of EPA, DHA, and linolenic acid was deemed eligible for inclusion in our study.
2.2.3. Types of Control
Participants in control groups were required to take placebo capsules that did not containPUFA. The main component of placebo capsules could be sunflower oil, corn oil, rice powder, and so forth. Both PUFA capsules and placebo capsules ought to be identical in appearance.
2.2.4. Types of Outcome
The primary outcome of our study was DOMS after eccentric exercises, measured using the VAS; secondary outcomes included joint range of motion (ROM), isometric muscle strength, MVC, upper arm/thigh circumferences, skin temperature, jump performance, and M-wave latency as well as blood markers such as serum CK, CRP, IL-6, TNF-alpha, IL-1ra, cortisol, iron, and LDH measured after eccentric trainings. Considering DOMS and inflammatory reaction in response to muscle damage training peak within 1 to 2 days or 2 to 3 days postexercise, according to different studies, we combined the data measured two days after the exercises.
2.2.5. Types of Studies
Only RCTs that assessed the efficacy of PUFA on muscle soreness after eccentric exercises were included. Non-RCTs such as case reports, case series, book chapters, and editorials were excluded.
2.3. Risk of Bias Assessment
In order to assess the risk of bias among our included studies, the Cochrane Collaboration’s tool is utilized, which is based on seven items: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other sources of bias. Two reviewers (ZL and JZ) judged the risk of bias among studies independently, and the results were compared afterwards. In case of disagreements regarding the risk of bias judgment, discussion was conducted until a consensus was reached. Only data from studies with low or unclear risk of bias can be included in the analysis.
2.4. Data Extraction
Two investigators (ZL and JZ) screened each article independently and were blinded to the findings of the other reviewer. Following the prespecified inclusion criteria, two reviewers performed a rigorous screening to identify eligible articles. Data were collected from these selected articles using a predetermined standardized data collection sheet, which included first author, year of the publication, country, sample size, demographic characteristics of participants in different groups, details of PUFA supplementation and control, detailed protocol of eccentric exercise, and main outcomes.
Discrepancies between two reviewers were resolved through discussion until a general consensus could be reached. The third review author (WZ) was sought for opinions if a consensus could not be reached.
2.5. Data Synthesis
For DOMS and other continuous variables measured two days after eccentric trainings, mean difference (MD) and the associated 95% confidence interval (95% CI) were calculated using the Rev Man 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Standard mean difference (SMD) and the associated 95% CI were calculated for continuous variables using the same methodology if the outcomes were measured using different ways. The chi-squared test and the Higgins test were used to assess the heterogeneity among studies ( and indicate acceptable heterogeneity) prior to the combination of data from an individual study . Regardless of the between-study heterogeneity detected, the random-effect model was selected for statistical analysis because of the variety of types of eccentric exercises and dosage of PUFA supplements among the included studies; the random-effect model is preferable in the presence or anticipation of interstudy variances .
Power analysis of our meta-analysis was performed using the Power and Sample Size Calculation (PS) program (https://biostat.mc.vanderbilt.edu/wiki/Main/PowerSampleSize) to evaluate whether our current study could offer adequate power to detect the beneficial effect of PUFA on DOMS at a level of significance of 0.05. Subgroup analyses according to duration and daily dosage of PUFA supplements before eccentric exercises were performed to determine whether these factors will influence the overall effect size. The leave-one-out sensitivity analysis was conducted by removing each included study in turn and reevaluating the resulting effect on pooled results to test the robustness of the summary estimate. Begg’s rank correlation test and Egger’s linear regression test as well as funnel plots using Stata version 12.0 (StataCorp LP, USA) were used to assess the publication bias .
2.6. GRADE Approach
The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence for each outcome measurement . In this approach, evidence from RCTs was initially regarded as “high quality” but could be downgraded to “moderate quality,” “low quality,” or “very low quality” depending on the presence and seriousness of five categories of limitations: limitations in the study design and implementation (risk of bias), indirectness of evidence, high and unexplained heterogeneity of results, imprecision of results, and high probability of publication bias. Two independent reviewers (ZL and JZ) finished the evaluation independently. Any discrepancy was resolved through discussion until a common consensus was reached. Otherwise, the third reviewer (WZ) was consulted for help. A table for the summary of findings was generated to explain the final results.
3.1. Literature Search
An initial search yielded 58 potential citations, among which 16 were from PubMed, 5 were from EMBASE, 24 were from ISI Web of Science, and 13 were from CENTRAL. 27 citations were deleted because they were duplicates. After screening the titles and abstracts of the remaining 31 citations, 15 studies were selected and retrieved for full-text assessment based on the predetermined inclusion criteria, among which 3 were excluded with reasons, 2 were unrelated, and 1 contained duplicate data. Finally, a total of 12 RCTs [57–68] were considered eligible for inclusion and went into qualitative and quantitative syntheses. The literature screening process is presented in Figure 1.