Human serum collected after fermented whey protein supplementation stimulates myocellular growth and protein synthesis: A randomized, double-blind, active-controlled crossover trial - ScienceDirect

Highlights

• • Age-related anabolic resistance contributes to skeletal muscle loss.
• • Fermented whey protein was compared with conventional whey protein.
• • Postprandial serum from young and older males was treated with C2C12 myotubes.
• • Fermented whey protein increased protein synthesis and myotube hypertrophy.

Abstract

Background

Age-related anabolic resistance has been proposed as one contributor to skeletal muscle loss in older adults, although its magnitude varies substantially among individuals and experimental conditions. Whey protein stimulates muscle protein synthesis (MPS) through increased circulating amino acid availability and activation of mechanistic target of rapamycin complex 1 (mTORC1), whereas fermented whey protein may exert greater anabolic effects due to enhanced bioactivity. However, its effects on skeletal muscle anabolic and metabolic responses during aging remain unclear.

Methods

This randomized, double-blind, placebo-controlled, crossover study investigated the effects of fermented whey protein ingestion on serum-mediated anabolic and metabolic responses in cultured skeletal muscle cells from young and older males. Participants consumed fermented whey protein (Fermentis) and conventional non-fermented protein (control whey) on separate occasions. Differentiated C2C12 myotubes were cultured in medium containing 10% postprandial human serum to evaluate MPS, mitochondrial-related signaling, and myotube hypertrophy.

Results

Serum obtained after Fermentis ingestion increased myotube diameter compared with serum obtained after conventional whey protein, with no age × protein interaction. For MPS, we observed a significant age × protein interaction, and MPS was greater in myotubes treated with post-Fermentis serum from older donors than from young donors. In addition, serum obtained after Fermentis ingestion markedly enhanced S6K1 Thr389 phosphorylation and oxidative metabolism-related signaling molecules compared with non-fermented protein treatment.

Conclusions

The present findings may provide mechanistic insights into the development of nutritional strategies to attenuate age-associated anabolic resistance and improve skeletal muscle oxidative metabolic function.

https://journals.humankinetics.com/view/journals/ijsnem/aop/article-10.1123-ijsnem.2026-0168/article-10.1123-ijsnem.2026-0168.xml?content=fulltext

Abstract

This article provides a synopsis of the 10 Questions/10 Experts session at the 2026 American College of Sports Medicine Annual Meeting, which examined whether sports nutrition guidelines are equally applicable from recreational to elite athletes. Each speaker considered the validity of a given common “myth” statement and provided an evidence-based opinion to support, bust, or qualify propositions addressing the following questions: (a) Are sports nutrition guidelines based primarily on studies of elite athletes, and are they too serious for recreational athletes? (b) Do recreational marathon runners need the same in-race carbohydrate recommendations as elite marathon runners? (c) Must recreational athletes consume 1.6 g·kg⁻¹·day⁻¹ of protein to benefit from exercise training? (d) Does nitrate supplementation benefit elite and recreational athletes equally? (e) Do recreational athletes need a structured fluid intake plan? (f) Is sodium bicarbonate loading relevant only to elite athletes? (g) Do recreational and elite athletes require more micronutrients than suggested by the Recommended Dietary Allowances? (h) Is eating after 8:00 p.m. detrimental to performance or recovery in recreational athletes? (i) Are recreational athletes at greater risk for suboptimal vitamin D status because indoor occupations reduce sunlight exposure? and (j) Should recreational athletes train with low carbohydrate availability to amplify adaptation? This article describes the content of each presentation, including the most important evidence, practical implications, and conclusions identified by the presenters.

Abstract

Kassiano, W, Manske, I, Miguel, A, Dias, RNdS, Siqueira, JP, Dantas, L, Prado, A, Costa, B, and Cyrino, ES. Progressive overload and muscle hypertrophy: Its relation to muscle use in training session. J Strength Cond Res XX(X): 000–000, 2026—To investigate the effects of progressive overload on skeletal muscle hypertrophy and its relationship with muscle use during training. The study comprised 2 components: a training intervention (part 1) and 2 acute resistance exercise bouts (part 2). Forty-one untrained young women had each arm randomized to progressive overload (n = 29), no-progressive overload (N-PO, n = 23), or a time-matched nonexercise control (Ctrl, n = 30). In part 1, subjects performed unilateral elbow flexion (3 sets of 8–12 repetitions, 3 d·wk⁻¹) for 8 weeks. Progressive overload (PO) increased load when the upper repetition limit was reached, whereas N-PO maintained constant load and repetitions. Elbow flexor muscle thickness was measured pre- and post-training at 60 and 70% of arm length and summed (∑EF). In part 2, subjects performed an acute exercise bout at pre- and post-testing. Muscle thickness was measured before and immediately after exercise as a proxy for muscle use. Both training conditions increased muscle thickness vs. Ctrl, with greater increases in PO than N-PO. Acute thickness increases were similar between conditions at pretesting, but at post-testing were greater in the Ctrl and N-PO than PO, with no differences between Ctrl and N-PO. Progressive overload augments muscle hypertrophy, likely by maintaining higher muscle use during exercise.

Highlights

•Multi-omics profiling across 22 tissues characterizes exercise adaptation

•Single-nucleus methylome reveals cell-type-specific exercise-induced remodeling

•Exercise responses vary by tissue, sex, and circadian phase

•A conserved molecular signature predicts exercise across species

Summary

Exercise reduces all-cause mortality, yet its molecular effects across organs, sexes, and circadian phases remain incompletely understood. We subjected mice to 8 weeks of voluntary wheel running and collected 22 tissues and plasma during active and inactive phases for bulk RNA sequencing, metabolomics, proteomics, and single-nucleus RNA and methylation sequencing. Exercise induced canonical fiber-type switching and widespread, tissue-specific remodeling, with the largest transcriptomic changes in skeletal muscle. Except for the hypothalamus, kidney, and lung, most tissues changed more during the active phase. Females showed broader transcriptional responses, with distinct downregulation. Pairing single-nucleus methylomes with transcriptomes resolved the cell types driving exercise-induced epigenetic remodeling—changes undetectable by bulk studies. These included coordinated gene-body demethylation and transcription that tracked with fiber-type switching in specific myonuclei. Cell-type-resolved methylation, including partially methylated domains characterized in muscle, revealed a strong, sex-biased epigenetic response to training. Machine learning identified conserved exercise signatures across mammalian species.

Abstract

Skeletal muscle disuse during injury decreases muscle mass and function. Previous studies have determined differential gene expression associated with atrophy, but changes in alternative splicing (AS) in response to unloading is poorly defined. This study aimed to identify global changes in differential alternative splicing (DAS) in skeletal muscle following unloading. Twenty-one healthy males (26.0 ± 5.7 years; 81.2 ± 11.6 kg) underwent 14 days unilateral knee-brace immobilization. Participants underwent strength and muscle mass assessment before and after the immobilization and vastus lateralis muscle biopsies were taken pre-immobilization, and on days 3 and 14. RNA-sequencing was performed, and DAS events were identified using the rMATS package. Leg strength decreased − 21.5 kg (P < 0.0001) while mid-thigh circumference was reduced ~ 2% (P = 0.016). A total of 157,464 and 159,395 splicing events affecting 15,219 and 15,374 genes identified on day 3 and 14, respectively. Most DAS events occurred in coding sequence regions and were primarily due to exon skipping. A higher number of DAS events were observed by day 14 than day 3, indicating time-dependent regulation. Gene Ontology analysis of DAS at day 14 revealed 37 enriched GO biological processes related to MAPK signalling, mitochondrial function, and organelle organization. Unloading-induced atrophy was associated with widespread changes in AS, particularly in genes linked to muscle maintenance and protein synthesis. AS appears to promote down-regulation of target genes and subsequent differentially enriched biological pathways associated with the functional outcomes of decreased muscle mass and strength. These findings indicate changes in alternative splicing is a regulatory mechanism in muscle wasting during immobilization.

Abstract

Physical activity improves metabolic health, but the molecular responses that mediate its benefits are not fully characterized. Here we present a high-resolution, time-resolved proteomics atlas across plasma, saliva and urine from 25 healthy men in response to acute exercise. We find that exercise regulates more than 3,000 proteins through distinct, fluid-specific temporal dynamics. Network analysis uncovers coordinated remodelling of protein secretion, extracellular matrix and immune activation across body fluids. Replication in an independent cohort shows that many exercise-responsive plasma proteins exhibit consistent responses across age, sex and exercise modalities. Integration with human genome-wide association study data links secreted, exercise-responsive proteins to cardiometabolic diseases. Functional validation of genetically prioritized muscle-specific secreted proteins in Drosophila confirms their role in endurance, behaviour and metabolism. Overall, this open-access atlas (https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/) provides a multifluid resource that complements existing exercise-omics efforts for defining molecular adaptations to exercise and for prioritizing candidate exerkines.

I (18M) used to be an athlete (swimming) and transitioned to working out in the gym, and while I've done research into working out and I've been in the gym for maybe 5 months now, a lot of fitness advice online isn't what I'm looking for.

My vague goal is to be able to perform any common physical task at a medium-high level by the age of 25. I don't need to bench the weight of a small car, but I do want to hold my own against legitimate athletes or carry a couch/chair up the stairs. My more specific goals are to bench rep 250, be able to dunk a basketball, run over 6 miles, and still be able to touch my hands behind my back. Of course I also want to be very healthy.

How does one train in the gym to be able to function in real life? From all I've heard compound movements are quite helpful, and that for strength 1-6 reps is ideal. But that seems way to simple of an answer. Carrying a couch up the stairs isn't an exercise, and while a deadlift may help with that scenario it's not automatically applied. I want to carry a couch!

One example is of a gym bro friend of mine. He trains his body in a standard manner and is considerably more advanced than me. Benches a lot more, squats more, etc. But when it comes to actually pushing against each other in a football sled esc movement, I match him without any of the same training.

Is functional strength a thing or not? Can the gym bring what I'm looking for? Do I need to just go off to Alaska and train like rocky to be functional ? And why does gym bro look so big yet can't hold a candle to a legitimate athlete? Confused.

Abstract

Background

Athletes commonly implement post-exercise cold-water immersion (CWI), with several meta-analyses having assessed its effectiveness.

Objectives

To thoroughly review, appraise, and summarise existing systematic reviews with meta-analyses (SRMA) examining the effects of post-exercise CWI on the recovery of exercise performance and adaptation.

Methods

An umbrella review was conducted in accordance with the Joanna Briggs Institute guidelines. Methodological quality was assessed using AMSTAR 2, and certainty of evidence using GRADE. PROSPERO registration: (CRD420251103267). Eight databases were searched, including Web of Science, Scopus, SPORTDiscus, CINAHL, Cochrane Library, Embase, MEDLINE, and PubMed. Systematic reviews with meta-analyses of peer-reviewed randomised controlled trials examining post-exercise CWI vs passive rest or other recovery modalities on performance, training adaptation, or physiological, biochemical, and perceptual outcomes in healthy humans were included, with restriction to the English language.

Results

Fifteen SRMAs published between 2011 and 2025, comprising 161 unique studies, were included. Overall methodological quality was low to critically low, and certainty of evidence was low to very low, mainly due to inconsistency and imprecision. Protocols of 10–15 min at 10–15 or 5–10 °C appear to be most effective for improving performance and recovery. Post-exercise CWI resulted in significant improvements in muscular power at 24 h post-high-intensity exercise and at 24–48 h post-eccentric exercise, and in jump performance at 24–48 h, despite impaired jump performance in the initial hours after post-exercise CWI. Endurance performance improved immediately after CWI, but CWI produced no later benefits or positive effects on adaptations. CWI did not improve muscular strength performance, and impaired strength and hypertrophic gains. CWI improved heart rate variability immediately after exercise, reduced muscle soreness up to 96 h, and lowered creatine kinase (CK) concentrations between 24 and 72 h, with no significant effects on C-reactive protein or interleukin-6 up to 72 h. No immediate impact on blood lactate or lactate dehydrogenase was found, although some reductions appear 24–72 h post-exercise.

Conclusions

Post-exercise CWI confers outcome-specific recovery benefits but may impair resistance training adaptations with chronic use. These findings support a periodised, context-driven approach to CWI implementation rather than routine application after all exercise sessions.

Key Points

1. 1. Decision makers should individualise and periodise CWI use based on training phase, performance goals, and individual response
2. 2. Post-exercise CWI improves performance in a time-specific manner, enhancing endurance within ~1 h and power and jump performance at 24–72 h, but may impair acute explosive performance
3. 3. Post-exercise CWI consistently reduces muscle soreness and CK and accelerates vagal reactivation.
4. 4. Repeated CWI after resistance training may attenuate strength and hypertrophy adaptations, while endurance adaptations appear unaffected. Effects on strength may be protocol-dependent, with exercise-limb immersion associated with reduced gains, whereas whole-body immersion shows no clear detrimental effect

https://www.ovid.com/jnls/acsm-msse/abstract/10.1249/mss.0000000000004180~carbohydrate-intake-of-100-vs-60-gh-during-prolonged-cycling

Abstract

Purpose:

To investigate the effects of ingesting 60 versus 100 g CHO·h⁻¹ during prolonged cycling on durability, substrate oxidation, and muscle glycogen utilization in endurance athletes.

Methods:

Fifteen trained male cyclists and triathletes completed a 15-min time trial (15-min TT) in a fresh state and following two prolonged intermittent cycling (PIC) protocols. After consuming a CHO-enriched diet for 24 hours, participants cycled for 240 min at 60 % of their fresh 15-min TT mean power output (MPO₁₅min), interspersed with high-intensity intervals. In a randomized, double-blind, crossover design, participants consumed either 60 g CHO·h⁻¹ (CHO60) or 100 g CHO·h⁻¹ (CHO100) through beverages and gels in a 1:0.8 glucose:fructose ratio. Muscle biopsies were obtained from m. vastus lateralis before and after the PIC protocols to assess glycogen content.

Results:

15-min TT performance was impaired after the PIC protocol in both conditions but with a greater reduction in CHO60 compared with CHO100 (-9.3 ± -2.0% vs -6.4 ± -1.7%, P= 0.025). Accordingly, MPO₁₅ was 9 W higher in CHO100 than CHO60 (P = 0.028). Muscle glycogen content decreased substantially during exercise, with similar glycogen availability after the PIC protocols between conditions (CHO60: 192 ± 99 mmol · kg ^-1 DW; CHO100: 209 ± 111 mmol · kg ^-1 DW, P = 0.56). Whole-body CHO oxidation was better preserved during the PIC protocol in CHO100 (CHO60: 2.6 ± 0.6 g·min ^-1 to 1.9 ± 0.4 g·min ^-1, CHO100: 2.6 ± 0.4 g·min ^-1 to 2.3 ± 0.5 g·min ^-1, condition x time; P = 0.047), whereas blood glucose concentrations remained stable in both conditions (CHO60: 5.6 ± 1.0 mmol·L ^-1 to 5.7 ± 0.9 mmol·L ^-1, CHO100: 6.0 ± 0.9 mmol·L ^-1 to 6.1 ± 0.9 mmol·L ^-1, effect of time; P = 0.43).

Conclusions:

Consuming 100 versus 60 g CHO·h⁻¹ during prolonged intermittent cycling improved durability without altering muscle glycogen utilization.

Abstract

The genus Homo is characterized by several anatomical and physiological traits that reflect millions of years of selection for sustained physical activity in hot environments. These adaptations include high capacity for sweating, metabolic substrate flexibility during low-intensity activity, and several morphological features of the lower limb and pelvis that facilitate energy-efficient locomotion. The present narrative review examines sports nutrition through an evolutionary lens by identifying the specific physiological strengths and vulnerabilities of Homo sapiens and assessing targeted nutritional interventions designed to address constraints on performance. Constraints discussed include submaximal resting phosphocreatine concentrations, modest proton buffering capacity, limited rates of intestinal energy and carbohydrate absorption, high water flux due to eccrine sweating, and an endurance-biased skeletal muscle phenotype that is not optimized for the accretion of large quantities of muscle tissue. Nutritional strategies reviewed include creatine monohydrate supplementation, supplements that increase muscle carnosine content, supplements that increase blood bicarbonate levels, exogenous carbohydrate delivery, fluid and electrolyte replacement protocols, and high-protein dietary strategies to support hypertrophic adaptations to resistance training. Examining sports nutrition through an evolutionary lens facilitates assessment of the physiological systems that frequently constrain exercise performance and the most viable nutritional strategies to mitigate these constraints.

Abstract

Skeletal muscle plays a central role in whole-body energy homeostasis, metabolic flexibility, and insulin sensitivity, acting as a key integrator of nutritional, mechanical, and pharmacological signals. Although diet, exercise, and pharmacotherapy are often investigated as separate interventions, they converge on shared regulatory pathways in skeletal muscle, including nutrient sensing, mechanotransduction, mitochondrial quality control, inflammatory remodeling, and anabolic–catabolic balance. Through core signaling networks such as AMPK–mTOR, SIRT1/PGC-1α, and insulin/AKT pathways, these interventions may interact in additive, complementary, synergistic, or antagonistic manners depending on physiological status, disease context, baseline metabolic condition, and intervention timing. This Review critically integrates current evidence on how diet, exercise, and pharmacotherapy regulate skeletal muscle metabolism across aging, metabolic disease, and adaptive physiological states. We propose a muscle-centered integrative framework organized around five major regulatory domains: substrate utilization and metabolic flexibility, mitochondrial remodeling, protein turnover, inflammatory control, and regenerative capacity. Within this framework, we highlight how intervention responses are shaped by key biological and clinical modulators, including age, disease state, muscle fiber composition, training status, nutritional background, and baseline metabolic health. Importantly, we distinguish findings supported by human studies from those derived primarily from preclinical or mechanistic models, thereby emphasizing differences in translational reliability. Finally, we discuss current limitations in interpreting combined interventions and outline future directions for precision-oriented strategies that integrate nutrition, exercise, and pharmacotherapy to optimize skeletal muscle function and systemic metabolic health.

Abstract

Physiological stress of environmental exposure and energy deficit impairs the absorption, transport, and utilization of exogenous carbohydrate for fuel during exercise. Blunted exogenous carbohydrate oxidation may require alternative fueling strategies to optimize carbohydrate metabolism to support physical performance. This review will overview the impact of physiological stress on exogenous carbohydrate oxidation and potential interventions to support physical performance.

Summary: Physiological stress exposure limits the effectiveness of carbohydrate supplementation to spare endogenous substrate oxidation by impeding exogenous carbohydrate oxidation.

In a small randomized crossover trial, women consumed smoothies containing 200 grams of blueberries per serving, along with banana and apple juice, before and after muscle-damaging eccentric exercise.

Peak isometric strength recovered faster in the blueberry condition over the 60-hour follow-up, although the smoothies did not prevent the initial strength loss or improve muscle soreness.

A systematic review found no significant exercise-performance benefit across the included Vaccinium berry studies and recovery benefits in only one, so this remains an early signal rather than a proven recovery protocol.

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Dr. Rhonda Patrick discusses this trial and newer research on post-exercise inflammatory signaling in her new solo episode. Here's a link to the timestamp. Also linked in the main post, but it's 46:44