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PURPOSE: Curcumin is a natural polyphenolic compound with antioxidant and anti-inflammatory properties. In vitro and in vivo animal studies have demonstrated that exposure to curcumin leads to dysregulation of the ubiquitin-proteasome system (UPS). However, to date, no study has investigated curcumin's ability to influence UPS activity in a human model. Therefore, the purpose of this study was to investigate the effects of curcumin supplementation on markers of UPS activity in the presence of elevations in UPS activity due to exercise-induced muscle damage. METHODS: Twenty-three recreationally active male and female participants between the ages of 18-30 were randomized into a curcumin (CUR; n=11) or placebo (PLA; n=12) group. Both groups were instructed to consume 2 g of their respective supplement and 20 mg of piperine for 11 consecutive days. Following 8 consecutive days of supplementation, participants performed a 45 minute eccentrically-biased muscle damaging treadmill protocol at 60% VO2max. Muscle biopsies and delayed onset muscle soreness (DOMS) analyses were performed 30 minutes prior and 3, 24, 48, and 72 hours following exercise-induced muscle damage. Skeletal muscle ubiquitin, MAFbx/Atrogin-1, ubiquitin specific peptidase 19 (USP19), and chymotrypsinlike protease concentrations were measured using ELISA. A 3-way repeated measures ANOVA with pairwise comparisons was conducted with significance set at p≤0.05. RESULTS: Both groups had a significant time effect for DOMS (p < .001). Pairwise comparisons indicated DOMS was significantly greater from baseline at all time points except 72 hours following muscle damage. No significant differences were found for USP19 between groups. Regardless of time, a significant main effect for condition was observed for ubiquitin (p=.016) and MAFbx/Atrogin-1 (p=.006) where CUR was significantly lower than PLA. Additionally, a significant main effect for gender was observed for MAFbx/Atrogin-1 (p=.013) where females were greater than males. A significant group x gender interaction was found for chymotrypsin-like protease (p = .049) where males had lower values with curcumin supplementation while females had slightly higher. CONCLUSION: Curcumin supplementation in humans does appear to dysregulate UPS activity in the presence of exercise-induced muscle damage. Specifically, curcumin's ability to suppress protein ubiquination provides preliminary evidence of curcumin supplementation's potential therapeutic role in decreasing protein degradation associated with skeletal muscle damage and perhaps other atrophic scenarios.

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Blood flow restriction (BFR) training and betaine supplementation are emerging training tools with growing evidence, potentially providing a synergistic stimulus to augment skeletal muscle adaptation. Betaine may facilitate stretch-mediated anabolism secondary to BFR-induced extracellularto-intracellular fluid influx, whereby their combination may promote a new, low-barrier avenue for athletes and clinical practitioners to elicit hypertrophy and strength. This review aims to (a) demonstrate existing evidence on BFR-and betaine-mediated skeletal muscle growth, (b) provide rationale for their combination as a superior anabolic stimulus, and (c) advocate for athletes and the elderly as prime demographics for a potentially valuable BFR-betaine synergistic therapy.

Machek, SB, Hwang, PS, Cardaci, TD, Wilburn, DT, Bagley, JR, Blake, DT, Galpin, AJ, and Willoughby, DS. Myosin heavy chain composition, creatine analogues, and the relationship of muscle creatine content and fast-twitch proportion to Wilks coefficient in powerlifters. J Strength Cond Res 34(11): 3022–3030, 2020—Little data exist on powerlifting-specific skeletal muscle adaptations, and none elucidate sex differences in powerlifters. Powerlifters tend to display higher fast-twitch fiber content and phosphagen system dependence. Nevertheless, it is unknown whether fast-twitch fiber or muscle creatine content are predictive of competitive powerlifting performance (via Wilks coefficient). Twelve actively competing powerlifters (PL; n = 6M/6F; age = 21.3 ± 1.0; 3.0 ± 1.8 year competing; 7.3 ± 6.6 meets attended) and 10 sedentary controls (CON; n = 5M/5F; age = 19.4 ± 2.0 year) underwent vastus lateralis muscle biopsies and venipuncture to compare the myosin heavy chain (MHC) fiber type and creatine analogue profiles between groups of both sexes, and determine whether MHC IIa and muscle total creatine (MTC) composition predict powerlifting performance. Samples were analyzed for specific MHC isoform (I, IIa, and IIx) content via mixed homogenate SDS-PAGE, and creatine analogues (MTC, muscle creatine transporter [SLC6A8], serum total creatine [STC], and serum creatinine [CRT]). Furthermore, MHC IIa and MTC content were compared with Wilks coefficient using Pearson correlation coefficients. Male PL MHC content was 50 ± 6% I, 45 ± 6% IIa, and 5 ± 11% IIx, versus 46 ± 6% I, 53 ± 6 IIa, and 0% IIx in female PL. Conversely, male CON MHC content was 33 ± 5% I, 38 ± 7% IIa, and 30 ± 8% IIx, vs. 35 ± 9% I, 44 ± 8% IIa, and 21 ± 17% IIx in female CON. Muscle total creatine, SLC6A8, STC, and CRT did not significantly differ between groups nor sexes. Finally, neither MHC IIa content (r = −0.288; p = 0.364) nor MTC (r = 0.488; p = 0.108) significantly predicted Wilks coefficient, suggesting these characteristics alone do not determine powerlifting skill variation.