Somatic and germinal mosaicism in a Han Chinese family with laminopathies.

"Laminopathies" refers to a wide spectrum of myopathies caused by mutations in the LMNA gene. These myopathies include limb girdle muscular dystrophy type 1B (LGMD1B) and dilated cardiomyopathy 1 A (DCM1A), which are both autosomal dominant neurogenetic diseases. There have been few studies on mosaicism in laminopathies. Herein, a Han Chinese family with laminopathies was enrolled in our study. Genetic analysis revealed that the proband carried a novel splice site mutation, c. 1158-3 C > T, in the LMNA gene due to her mother having de novo somatic and gonadal mosaicism. Reverse-transcription polymerase chain reaction (RT-PCR) analysis revealed reduced levels of LMNA mRNA in the proband, which were probably due to nonsense-mediated mRNA decay (NMD). Western blotting revealed reduced lamin A/C protein levels in the skeletal muscle tissue of the proband. In this family, the clinical phenotypes of the proband's mother were normal, and the c. 1158-3 C > T splicing mutation was identified in the blood sample of the proband's mother. Thus, the mutation could be easily considered to be nonpathogenic. Our study emphasizes the importance of mosaicism in the identification of pathogenic variants and genetic counseling.

Alanine transaminase is predominantly increased in the active phase of anti-HMGCR myopathy.

Autoantibodies against 3­hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the signal recognition particle (SRP) are representative antibodies causing immune-mediated necrotizing myopathies (IMNM), called as anti-HMGCR and anti-SRP myopathies, respectively. Here, we analyzed the differences in routine blood test results between 56 anti-HMGCR and 77 anti-SRP myopathy patients. A higher alanine transaminase (ALT) level and a lower aspartate transaminase (AST)/ALT ratio were observed in anti-HMGCR myopathy patients [ALT, 265.7 ±â€¯213.3 U/L (mean ± standard deviation); AST/ALT ratio, 0.88 ±â€¯0.32] than in anti-SRP-myopathy patients (ALT, 179.3 ±â€¯111.2 U/L, p < 0.05; AST/ALT ratio, 1.28 ±â€¯0.40, p < 0.01). In the active phase, anti-HMGCR myopathy often showed ALT predominance, whereas anti-SRP myopathy often showed AST predominance. In addition, there were differences in erythrocyte sedimentation rate (ESR), total cholesterol (TChol) level, and high-density lipoprotein (HDL) level between anti-HMGCR and anti-SRP myopathies (ESR: HMGCR, 24.4 ±â€¯20.8 mm/1 h; SRP, 35.7 ±â€¯26.7 mm/1 h, p = 0.0334; TChol: HMGCR, 226.7 ±â€¯36.6 mg/dL; SRP, 207.6 ±â€¯40.8 mg/dL, p = 0.0163; HDL: HMGCR, 58.4 ±â€¯13.9 mg/dL; SRP, 46.2 ±â€¯17.3 mg/dL, p < 0.01). Additional studies on the differences in routine blood test results may further reveal the pathomechanisms of IMNM.

Belimumab for Immune-Mediated Necrotizing Myopathy Associated With Anti-SRP Antibodies: A Case Report and Retrospective Review of Patients Treated With Anti-B-Cell Therapy in a Single Center and Literature.

Background: Immune-mediated necrotizing myopathy (IMNM) is characterized by markedly elevated creatinine kinase and histologically scattered necrotic muscle fibers and generally associated with autoantibodies against signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coA-reductase (HMGCR). Poor clinical response to conventional therapies and relapses commonly occur in severe cases. Anti-B-cell therapies have been used in refractory/relapsing cases. Methods: The characteristics of a patient with IMNM associated with anti-SRP antibodies including physical examination, laboratory tests, and disease activity assessment were evaluated. Conventional therapy, belimumab treatment schedule, and follow-up data were recorded. Medical records of IMNM patients treated in our department from September 2014 to June 2021 were reviewed to evaluate the efficacy and safety of anti-B-cell therapy for anti-SRP IMNM. A literature review of patients with anti-SRP IMNM treated with anti-B-cell therapies was performed. Results: We describe a case of a 47-year-old woman with IMNM associated with anti-SRP antibodies who relapsed twice after conventional therapy but showed good response and tolerance to belimumab at 28 weeks follow-up. In this review, three patients from our department were treated with rituximab. Two of the three patients rapidly improved after treatment. Twenty patients and five retrospective studies were included in the literature review. All patients were administered rituximab as an anti-B-cell drug. Conclusion: Despite a lack of rigorous clinical trials, considerable experience demonstrated that anti-B-cell therapy might be effective for patients with IMNM associated with anti-SRP antibodies. Belimumab in association with steroids might be an encouraging option for refractory/relapsing cases.

The role of potassium in muscle membrane dysfunction in end-stage renal disease.

OBJECTIVE: Uremic myopathy is a condition seen in end-stage renal disease (ESRD), characterized by muscle weakness and muscle fatigue, in which the pathophysiology is uncertain. The aim of this study was to assess the role of abnormal serum constituents in ESRD patients by relating them to the excitability properties of the tibialis anterior muscle, at rest and during electrically induced muscle activation, by recording muscle velocity recovery cycles (MVRC) and frequency ramp responses. METHODS: Eighteen ESRD patients undergoing hemodialysis were evaluated by blood sample, MVRC, and frequency ramp (before and near the end of dialysis treatment), quantitative electromyography, and nerve conduction studies. Patients were compared to 24 control subjects. RESULTS: In patients, muscle relative refractory period, early supernormality, late supernormality after 5 conditioning stimuli, and latency of the last of 15 and 30 frequency ramp pulses were strongly associated with potassium levels (p < 0.01), showing depolarization before and normalization in the end of hemodialysis. CONCLUSIONS: In ESRD patients, the muscle membrane is depolarized, mainly due to hyperkalemia. SIGNIFICANCE: Since normal muscle fatigue has been attributed to potassium-induced depolarization, it seems likely that this mechanism is also a major cause of the exaggerated muscle fatigue and weakness in ESRD patients.

Incidence and clinical spectrum of rhabdomyolysis in general neurology: a retrospective cohort study.

The objective of this retrospective cohort study was to evaluate demographic, clinical and laboratory characteristics of patients with rhabdomyolysis as defined by a serum creatine kinase (sCK) activity > 950 U/L. A total of 248 patients were recruited from the Department of Neurology, Medical University of Vienna, between 01/2000 and 12/2017, with a median sCK activity of 2,160 U/l (IQR 1,342-4,786). Seizures (31.9%), illicit drugs/alcohol (9.7%) and exercise (8.5%) were the most common trigger factors. Rhabdomyolysis incidence rates in specific neurological diseases as estimated by the ratio between rhabdomyolysis cases and the total number of cases with the corresponding disease were highest in myopathies (49.8/1,000 person-years, 95% CI 32.3-67.4), followed by epilepsy (16.4/1,000 person-years, 95% CI 12.8-20.0) and stroke (11.9/1,000 person-years, 95% CI 8.4-15.4). The half-life of sCK activity was 1.5 days in the total cohort. In myopathies, sCK activity was significantly higher as compared to other disease entities 7 days after the peak measurement (p = 0.0023). Acute kidney injury (AKI) developed in 18 patients (7.3%) with no AKI-related deaths during the study period. In conclusion, rhabdomyolysis occurred in a broad range of neurological entities but was associated with a favorable prognosis in most cases rarely resulting in AKI and death.

MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase.

Striated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants in MLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels. The biallelic truncating variants were predicted to result in disruption of the nuclear localizing signal of MLIP. Additionally, reduced overall RNA expression levels of the predominant MLIP isoform were observed in patients' skeletal muscle. Collectively, our data increase the understanding of the genetic landscape of rhabdomyolysis to now include MLIP as a novel disease gene in humans and solidifies MLIP's role in normal and diseased skeletal muscle homeostasis.

Alterations in skeletal muscle repair in young adults with type 1 diabetes mellitus.

Though preclinical models of type 1 diabetes (T1D) exhibit impaired muscle regeneration, this has yet to be investigated in humans with T1D. Here, we investigated the impact of damaging exercise (eccentric quadriceps contractions) in 18 physically active young adults with and without T1D. Pre- and postexercise (48 h and 96 h), the participants provided blood samples, vastus lateralis biopsies, and performed maximal voluntary quadriceps contractions (MVCs). Skeletal muscle sarcolemmal integrity, extracellular matrix (ECM) content, and satellite cell (SC) content/proliferation were assessed by immunofluorescence. Transmission electron microscopy was used to quantify ultrastructural damage. MVC was comparable between T1D and controls before exercise. Postexercise, MVC was decreased in both groups, but subjects with T1D exhibited moderately lower strength recovery at both 48 h and 96 h. Serum creatine kinase, an indicator of muscle damage, was moderately higher in participants with T1D at rest and exhibited a small elevation 96 h postexercise. Participants with T1D showed lower SC content at all timepoints and demonstrated a moderate delay in SC proliferation after exercise. A greater number of myofibers exhibited sarcolemmal damage (disrupted dystrophin) and increased ECM (laminin) content in participants with T1D despite no differences between groups in ultrastructural damage as assessed by electron microscopy. Finally, transcriptomic analyses revealed dysregulated gene networks involving RNA translation and mitochondrial respiration, providing potential explanations for previous observations of mitochondrial dysfunction in similar cohorts with T1D. Our findings indicate that skeletal muscle in young adults with moderately controlled T1D is altered after damaging exercise, suggesting that longer recovery times following intense exercise may be necessary.

Circulating skeletal muscle related microRNAs profile in Piedmontese cattle during different age.

Piedmontese cattle is known for double-muscle phenotype. MicroRNAs (miRNAs) play important role as regulators in skeletal muscle physiological processes, and we hypothesize that plasma miRNAs expression profiles could be affected by skeletal muscle growth status related to age. Plasma samples of cattle were collected during four different ages from first week of life until the time of commercial end of the fattening period before slaughter. Small-RNA sequencing data analysis revealed the presence of 40% of muscle-related miRNAs among the top 25 highly expressed miRNAs and, 19 miRNAs showed differential expression too. Using qRT-PCR, we validated in a larger bovine population, miRNAs involved in skeletal muscle physiology pathways. Comparing new-born with the other age groups, miR-10b, miR-126-5p, miR-143 and miR-146b were significantly up-regulated, whereas miR-21-5p, miR-221, miR-223 and miR-30b-5p were significantly down-regulated. High expression levels of miR-23a in all the groups were found. Myostatin, a negative regulator of skeletal muscle hypertrophy, was predicted as the target gene for miR-23a and miR-126-5p and we demonstrated their direct binding. Correlation analysis revealed association between miRNAs expression profiles and animals' weights along the age. Circulating miRNAs could be promising for future studies on their biomarker potentialities to beef cattle selection.

Statin-associated anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy: Imaging findings on thigh-muscle magnetic resonance imaging (MRI) in six patients.

INTRODUCTION/AIMS: Anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy is a rare but serious complication of statin use. The aim of this study was to describe the imaging features of statin-associated anti-HMGCR myopathy on thigh muscle magnetic resonance imaging (MRI). METHODS: Thigh muscle MRI images of six patients with statin-associated anti-HMGCR myopathy were reviewed for muscle edema, fatty replacement, and fascial edema in four compartments of each thigh: gluteal, anterior, medial, and posterior. Signal intensity ratio (SIR) was calculated in 17 muscles in both thighs on T2-weighted fat-suppressed images. Intracompartmental comparison of T2 SIRs of different muscles were performed. RESULTS: All patients demonstrated bilateral symmetrical pan-compartmental muscle edema. Three patients had fatty infiltration, involving gluteal and/or posterior compartments. In the anterior compartment, rectus femoris and vastus lateralis most frequently demonstrated the highest T2 SIR. In the posterior compartment, semimembranosus most frequently demonstrated the highest T2 SIR. The long head of the biceps femoris always had a higher T2 SIR than the short head. DISCUSSION: Statin-associated anti-HMGCR myopathy commonly demonstrates bilateral symmetrical pan-compartmental edema on thigh muscle MRI, with anterolateral predilection in the anterior compartment, and greater involvement of the semimembranosus with relative sparing of the short head of the biceps femoris in the posterior compartment. These observations can contribute to the diagnosis of statin-associated anti-HMGCR myopathy.

Circulating Carboxylated Osteocalcin Correlates With Skeletal Muscle Mass and Risk of Fall in Postmenopausal Osteoporotic Women.

Background: Bone and skeletal muscle represent a single functional unit. We cross-sectionally investigated body composition, risk of fall and circulating osteocalcin (OC) isoforms in osteoporotic postmenopausal women to test the hypothesis of an involvement of OC in the bone-muscle crosstalk. Materials and Methods: Twenty-nine non-diabetic, non-obese, postmenopausal osteoporotic women (age 72.4 ± 6.8 years; BMI 23.0 ± 3.3 kg/m2) underwent to: 1) fasting blood sampling for biochemical and hormone assays, including carboxylated (cOC) and uncarboxylated (uOC) osteocalcin; 2) whole-body dual energy X-ray absorptiometry (DXA) to assess total and regional body composition; 3) magnetic resonance imaging to determine cross-sectional muscle area (CSA) and intermuscular adipose tissue (IMAT) of thigh muscles; 4) risk of fall assessment through the OAK system. Results: Appendicular skeletal muscle index (ASMMI) was low in 45% of patients. Forty percent got a low OAK score, consistent with moderate-severe risk of fall, which was predicted by low legs lean mass and increased total fat mass. Circulating cOC levels showed significantly correlated with ßCTx-I, lean mass parameters including IMAT, and OAK score. Fractured and unfractured women did not differ for any of the analyzed parameters, though cOC and uOC positively correlated with legs lean mass, OAK score and bone markers only in fractured women. Conclusions: Data supported the relationship between OC and skeletal muscle mass and function in postmenopausal osteoporotic women. Serum cOC, but not uOC, emerges as mediator in the bone-muscle crosstalk. Circulating cOC and uOC levels may be differentially regulated in fractured and unfractured osteoporotic women, suggesting underlying differences in bone metabolism.

Severe acute myopathy following SARS-CoV-2 infection: a case report and review of recent literature.

BACKGROUND: SARS-CoV2 virus could be potentially myopathic. Serum creatinine phosphokinase (CPK) is frequently found elevated in severe SARS-CoV2 infection, which indicates skeletal muscle damage precipitating limb weakness or even ventilatory failure. CASE PRESENTATION: We addressed such a patient in his forties presented with features of severe SARS-CoV2 pneumonia and high serum CPK. He developed severe sepsis and acute respiratory distress syndrome (ARDS) and received intravenous high dose corticosteroid and tocilizumab to counter SARS-CoV2 associated cytokine surge. After 10 days of mechanical ventilation (MV), weaning was unsuccessful albeit apparently clear lung fields, having additionally severe and symmetric limb muscle weakness. Ancillary investigations in addition with serum CPK, including electromyogram, muscle biopsy, and muscle magnetic resonance imaging (MRI) suggested acute myopathy possibly due to skeletal myositis. CONCLUSION: We wish to stress that myopathogenic medication in SARS-CoV2 pneumonia should be used with caution. Additionally, serum CPK could be a potential marker to predict respiratory failure in SARS-CoV2 pneumonia as skeletal myopathy affecting chest muscles may contribute ventilatory failure on top of oxygenation failure due to SARS-CoV2 pneumonia.

Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study.

OBJECTIVE: The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW). METHODS: An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients. RESULTS: 111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes. CONCLUSIONS: CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness. SIGNIFICANCE: COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM.

Patients with low IGF-I after curative surgery for Cushing's syndrome have an adverse long-term outcome of hypercortisolism-induced myopathy.

BACKGROUND: Glucocorticoid excess leads to muscle atrophy and weakness in patients with endogenous Cushing's syndrome. Insulin-like growth factor I (IGF-I) is known to have protective effects on muscle loss. We hypothesized that individual serum IGF-I concentrations might be predictive for long-term myopathy outcome in Cushing's syndrome. PATIENTS AND METHODS: In a prospective longitudinal study of 31 patients with florid Cushing's syndrome, we analyzed IGF-I and IGF binding protein 3 (IGFBP 3) concentrations at the time of diagnosis and following surgical remission over a period of up to 3 years. We assessed muscle strength by grip strength measurements using a hand grip dynamometer and muscle mass by bio-impedance measurements. FINDINGS: Individual serum IGF-I concentrations in the postoperative phase were strongly predictive of long-term grip strength outcome (rs = 0.696, P ≤ 0.001). Also, lower IGF-I concentrations were associated with a lower muscle mass after 3 years (rs = 0.404, P = 0.033). While patients with high IGF-I s.d. scores (SDS; >1.4) showed an improvement in grip strength within the follow-up period (P = 0.009), patients with lower IGF-I SDS (≤-0.4) had a worse outcome with persisting muscle dysfunction. In contrast, preoperative IGF-I concentrations during the florid phase of Cushing's syndrome did not predict long-term muscle function outcome (rs = 0.285, P = 0.127). CONCLUSION: Lower individual IGF-I concentrations 6 months after curative surgery for Cushing's syndrome are associated with adverse long-term myopathy outcome and IGF-I might be essential for muscle regeneration in the early phase after correction of hypercortisolism.

SRP-positive necrotising myopathy: takes more than just the muscles.

Necrotising myopathy is an autoimmune disease that commonly affects muscles. Here we examine a case of a middle-aged women presenting with a chief report of shortness of breath, who subsequently developed muscle weakness. Her clinical course was complicated by respiratory failure and pulmonary hypertension likely due to the underlying pathology of signal recognition particle-positive necrotising myopathy. After further evaluation, her shortness of breath was thought to be secondary to muscle pathology rather than cardiopulmonary pathology. She was transferred to our institution for workup by rheumatology. At the time of admission, 6 months after initial presentation, her weakness progressed, so that she was unable to lift her arms and legs against gravity. Furthermore, neurological examination revealed mild facial and nuchal weakness, severe proximal weakness, more moderate distal weakness and global areflexia.

Gene spectrum and clinical traits of 10 patients with primary carnitine deficiency.

BACKGROUND: Rare studies focused on the tandem mass spectrometry (MS/MS) findings for the primary carnitine deficiency (PCD) in the neonates in China mainland. In this study, we aim to analyze the gene mutation spectrum of PCD in Fujian Province in China mainland. METHODS: Primary carnitine deficiency (PCD) samples used in this study were selected from 95,453 cases underwent neonatal screening between May 2015 and February 2020. SLC22A5 gene sequencing was performed on the neonates and their parents with C0 level of less than 8.8 µmol/L. RESULTS: Ten patients (male: 7; female: 3) were finally included in this study. Among these patients, nine were neonates, and one was maternal decline of C0 of less than 8.8 µmol/L. The maternal case showed two types of mutations of SLC22A5 including c.760C>T(p.R254*) and c.1400C>G(p.S467C). The other nine neonates showed compound mutations involving nine types in 18 sites, among which two mutations [i.e., c.37G>T(p.E13*) and c.694A>G(p.T232A)] were novel that had never been reported before. Bioinformatic analysis indicated that c.37G>T(p.E13*) was a pathogenic mutation, while the c.694A>G (p.T232A) was considered to be likely pathogenic. CONCLUSION: MS/MS screening on PCD contributed to the early diagnosis and screening. In addition, SLC22A5 gene mutation analysis contributed to the PCD screening.

Immunotherapy reversed myopathy but not cardiomyopathy in a necrotizing autoimmune myopathy patient with positive anti-SRP and MDA-5 autoantibodies.

BACKGROUND: Necrotizing autoimmune myopathy (NAM) is pathologically characterized by myofiber necrosis and regeneration with paucity or absence of inflammatory cells in muscle biopsy. Two autoantibodies, namely anti-signal recognition particle (SRP)-antibodies and anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)-antibodies, are typically specific with NAM. Anti-SRP-positive NAM can be associated with cardiomyopathy which responds well to immunotherapy. Here we reported an anti-SRP-antibody and anti-MDA5-antibody NAM patient who developed severe cardiomyopathy after gaining significant improvement of myopathy and subsequently accepted heart transplantation. CASE PRESENTATION: A NAM case with both positive anti-SRP and MDA-5 antibodies who gained significant improvement of the skeletal muscle weakness with immunotherapy, but 3 years later he developed severe dilated cardiomyopathy and at last received heart transplantation. Myocardial biopsy showed disarranged and atrophic myofibers, remarkable interstitial fibrosis without inflammatory infiltrates. Immunohistochemistry analysis revealed increased polyubiquitin-binding protein p62/SQSTM1 protein expression and the positive staining of cleaved-caspase 3 in a few cardiomyocytes. After the transplantation, the patient was symptom-free on oral prednisone (10 mg/day) and tacrolimus (2 mg/day). CONCLUSIONS: We described the first case of anti-SRP and anti-MAD5 positive NAM who had received heart transplantation because of cardiopathy. Though the myopathy had been clinically improved after immunotherapy, the cardiomyopathy remained progressive and lethal. The processes of dysfunctional autophagy and augmented apoptosis were putatively pathophysiological mechanisms underlying cardiac damage in anti-SRP and anti-MAD5 positive NAM.

The effect of Omega-3 polyunsaturated fatty acid supplementation on exercise-induced muscle damage.

BACKGROUND: Exercise-induced muscle damage (EIMD) results in transient muscle inflammation, strength loss, muscle soreness and may cause subsequent exercise avoidance. Omega-3 (n-3) supplementation may minimise EIMD via its anti-inflammatory properties, however, its efficacy remains unclear. METHODS: Healthy males (n = 14, 25.07 ± 4.05 years) were randomised to 3 g/day n-3 supplementation (N-3, n = 7) or placebo (PLA, n = 7). Following 4 weeks supplementation, a downhill running protocol (60 min, 65% V̇O2max, - 10% gradient) was performed. Creatine kinase (CK), interleukin (IL)-6 and tumour necrosis factor (TNF)-α, perceived muscle soreness, maximal voluntary isometric contraction (MVIC) and peak power were quantified pre, post, and 24, 48 and 72 h post-EIMD. RESULTS: Muscle soreness was significantly lower in N-3 vs PLA group at 24 h post-EIMD (p = 0.034). IL-6 was increased in PLA (p = 0.009) but not in N-3 (p = 0.434) following EIMD, however, no significant differences were noted between groups. Peak power was significantly suppressed in PLA relative to pre-EIMD but not in N-3 group at 24 h post-EIMD. However, no significant difference in peak power output was observed between groups. MVIC, CK and TNF-α were altered by EIMD but did not differ between groups. CONCLUSION: N-3 supplementation for 4 weeks may successfully attenuate minor aspects of EIMD. Whilst not improving performance, these findings may have relevance to soreness-associated exercise avoidance.