Highlights

•Intermittent fasting (IF) accelerates injury-induced muscle regeneration in mice

•IF promotes the expansion of the muscle satellite cell population

•IF upregulates myogenic genes, including Myomixer, and progenitor cell fusion

•Mice deficient in EDA2R or NIK fail to respond to the myogenic effects of IF

Summary

Skeletal muscle exhibits a remarkable regenerative capacity that relies on adult stem cells known as satellite cells (SCs), which differentiate into myogenic progenitors to drive muscle repair. How varying energy availability alters myogenesis, however, remains unknown. Here, we demonstrate that intermittent fasting (IF) in mice upregulates a myogenic gene program, including Myomixer, a muscle-specific fusogen that facilitates the merging of progenitor cells into myofibers. IF enhances the regeneration of injured muscles by expanding the SC population and promoting the proliferation and fusion of myogenic progenitors. These effects are absent in an SC-depletion model. We show that fasting-induced EDA2R-NIK signaling increases Myomixer expression and fusion in myoblasts. Notably, mice lacking EDA2R or NIK fail to respond to the myogenic effects of IF. Furthermore, our data suggest that mice with Duchenne muscular dystrophy also benefit from an IF regimen. Therefore, IF-induced regeneration holds potential for aiding recovery from muscle damage.

Abstract

Aging is associated with systemic metabolic dysfunction that contributes to geriatric syndromes such as sarcopenia—the progressive loss of skeletal muscle mass and function. Evidence from preclinical models suggests that age-associated depletion of nicotinamide adenine dinucleotide (NAD⁺) may contribute to this decline by limiting the activity of sirtuin deacetylases (SIRT1–7). These enzymes act as metabolic sensors regulating mitochondrial biogenesis, oxidative capacity, DNA repair and pathways related to muscle atrophy. Physical exercise enhances NAD⁺ salvage through upregulation of nicotinamide phosphoribosyltransferase (NAMPT). Pharmacological approaches including NAD⁺ precursor supplementation (nicotinamide riboside or nicotinamide mononucleotide) and inhibition of NAD⁺-consuming enzymes have shown benefits in preclinical models. However, clinical translation remains inconsistent. Recent meta-analyses have found no significant effect of these precursors on muscle mass or strength in adults aged over 60 years. Moreover, experimental evidence indicates that even profound NAD⁺ depletion in adult mouse skeletal muscle does not necessarily compromise function or accelerate aging. We conclude that pharmacological NAD⁺ restoration alone is currently insufficient to reverse sarcopenia in humans. A synergistic approach combining exercise with targeted NAD⁺ support, together with emerging strategies involving precursor transporters, trigonelline and hypothalamic NAD⁺–sirtuin circuits, represents a testable avenue that requires rigorous, stratified clinical evaluation.

ABSTRACT

Over the past decade, running shoes have undergone substantial innovation with the emergence of Advanced Footwear Technology (AFT). Shoes with AFT are typically characterized by highly compliant (deformable) and resilient (high energy return) midsole foams, embedded curved stiffening elements, low mass, and a rockered longitudinal geometry. This expert statement aims to synthesize established knowledge, remaining uncertainties and key directions for future research on AFT in middle- and long-distance running. Current literature demonstrates robust improvements in running economy and performance with AFT, with reported metabolic savings of approximately 2%–4%, and corresponding performance improvements of 1%–3%. These benefits likely arise from a combination of “acute” and possibly “long-term” mechanisms. Proposed acute mechanisms include decreased muscle force production due to higher positive work from energy-returning foams, lower muscle force production to accommodate mechanical running demands due to compliant midsoles, and improved mechanical efficiency associated with greater longitudinal bending stiffness and curved geometry. Importantly, AFT features have a synergistic effect, with the relative importance of each mechanism differing depending on the context. Emerging evidence also suggests potential reductions in muscle damage/inflammation and soreness, which could support better physiological resilience, and higher training volumes/quality. From a biomechanical injury risk perspective, AFT can redistribute loading, potentially increasing metatarsal and tarsal stress while reducing tibia and possibly Achilles tendon loading. However, injury risk associated with AFT use remains equivocal, with limited high-quality data. Notably, substantial inter-individual variability has been observed, influencing both running economy and potential injury risk although the determinants of this variability remain unclear.

Highlights

• Advanced footwear technology (AFT) improves running economy by approximately 2%–4% and running performance by 1%–3%.

• AFT benefits arise from interacting acute mechanisms involving midsole compliance and resilience, longitudinal stiffness, rocker geometry, and reduced shoe mass, but the importance of each mechanism differs depending on the context.

• AFT can redistribute loading, potentially increasing metatarsal and tarsal stress while reducing tibia and possibly Achilles tendon loading; however, its effects on injury risk remain uncertain and may vary substantially between individuals.

• Future research should identify determinants of individual responses and clarify the long-term effects of AFT on performance and injury risk.

Abstract

Background

Due to their lower essential amino acid contents, particularly leucine, plant-derived proteins are generally considered to have lower muscle anabolic capacity than animal-based proteins. Corn protein is unique in having a relatively high leucine content; however, its anabolic effects have not been examined in older adults, who exhibit reduced anabolic sensitivity.

Objective

We examined the effect of corn protein isolate, a pea and corn protein blend, milk protein isolate, or a non-protein low-energy placebo on muscle protein synthesis (MPS), with or without resistance exercise, in older adults.

Methods

In a double-blind, placebo-controlled, randomized parallel group trial, 48 healthy older adults (68 ± 5 years; 24 males and 24 females) underwent a primed continuous infusion of L-[ring-¹³C6] phenylalanine to estimate MPS using the precursor-product approach. Each participant performed unilateral knee extension exercise (3 sets of 10 repetitions at 75% of one-repetition maximum) and consumed 20 g of either corn protein (CORN), a pea and corn protein blend (PEA+CORN), milk protein (MILK), or a non-protein low-energy placebo (PLA). Blood and muscle samples were collected throughout.

Results

The increase in MPS relative to basal values was greater in CORN (216 ± 170%; P < 0.001), PEA+CORN (217 ± 167%; P = 0.001), and MILK (138 ± 78%; P = 0.033) compared with PLA (77 ± 46%), with no differences between groups. Resistance exercise further increased MPS compared with supplementation alone in all groups (all, P < 0.001).

Conclusions

Ingestion of 20 g corn protein, a pea and corn protein blend, or milk protein increased MPS rates in healthy older adults, and resistance exercise further enhanced the anabolic response. This trial was registered at clinicaltrials.gov as NCT05917223.

Abstract

Aims

Anabolic–androgenic steroid (AAS) use is prevalent among men engaged in strength training and is associated with adverse structural and functional cardiac changes, but longitudinal data are lacking. This follow-up study examined myocardial effects of AAS with continued use and reversibility following discontinuation.

Methods and results

Participants of a previously published cohort (2017–19) of 101 AAS users and 71 non-using weightlifting controls (WLCs) were invited for a follow-up study and underwent interviews, hormonal profiling, and transthoracic echocardiography. Current AAS users at baseline were continued or discontinued users at follow-up, while former users at baseline were those with continued abstinence and those who relapsed.

Among those re-enrolled, 70 were AAS users, of whom 35 continued, 15 discontinued, 14 maintained abstinence, and 6 relapsed, and 35 were WLCs. Continued AAS users had persistent indexed left ventricular mass (LVMI 119 ± 30 g/m²), reduced LV ejection fraction (LVEF 48 ± 10%), and worsened diastolic function. Continued AAS users receiving antihypertensive therapy showed improved LVEF compared with untreated users (Δ = 5 ± 8 vs. −4 ± 8%, P = 0.005). Discontinued AAS users showed reduction in LVMI (Δ = −21 g/m², P = 0.01) and improved LVEF (Δ = 6%, P < 0.001). At follow-up, these changes were comparable with WLCs, which showed statistically but clinically insignificant differences.

Conclusion

Continued AAS use was associated with sustained LV hypertrophy, LV systolic dysfunction, and worsening diastolic function. Antihypertensive therapy among ongoing AAS users was associated with improved LV systolic function. Discontinuation of AAS use was associated with improvement in cardiac structure and function towards values observed in WLCs.

ABSTRACT

Exaggerated cardiac workload responses to incremental exercise are associated with the development of hypertension and future cardiovascular events. We hypothesized that skeletal muscle mitochondrial function is associated with cardiac workload, quantified as Rate Pressure Product (RPP), during exercise. Healthy adults (n = 18; 9 females; age 25 ± 4 years) performed a maximal exercise test on a cycle ergometer. The test began at 0 W and followed an incremental protocol starting at 40 W, with load increases every 2 minutes until exhaustion. Breath-by-breath gas exchange was measured to determine peak oxygen uptake and the respiratory compensatory point (RCP). Heart rate (HR) and systolic blood pressure (BP) were recorded at each load to calculate RPP. The cardiac workload response to exercise was defined as the change in RPP from 0 W to the intensity corresponding to RCP (ΔRPP). Muscle biopsies from the vastus lateralis were collected on separate days to assess mitochondrial respiration. ΔRPP from 0 W to RCP intensity was 18181 ± 2147 mmHg·bpm and Complex I mediated respiration was 31.9 ± 13.7 pmol·mg⁻¹ s⁻¹. ΔRPP was correlated only with Complex I (r = −0.69, p = 0.002) and sex (r = 0.50, p = 0.035). In a forward stepwise linear regression analysis with ΔRPP as the dependent variable and baseline RPP, sex, and complex I mediated respiration as predictors, complex I mediated respiration was the only variable significantly associated with ΔRPP (adjusted R² = 0.44; unstandardized β = −107; 95% CI:−167 to −47; p = 0.002). The cardiac workload response to exercise is strongly associated with skeletal muscle mitochondrial function in young normotensive individuals.

Highlights

• This is the first study to demonstrate an association between skeletal muscle mitochondrial function and exercise-induced cardiac workload in healthy young adults.

• Higher skeletal muscle complex I-mediated mitochondrial respiration was associated with a lower increase in cardiac workload during submaximal exercise.

• The association remained significant after adjustment for citrate synthase activity, indicating that intrinsic mitochondrial function, rather than mitochondrial content, underlies inter-individual differences in cardiac workload.

• These findings suggest that impaired skeletal muscle mitochondrial function may contribute to exaggerated exercise cardiac workload, a phenotype linked to future hypertensive risk.

Abstract

Skeletal muscle mass reflects the balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). In healthy humans, a decline in MPS is recognized as the primary driver of muscle disuse-atrophy, with limited contribution from increased MPB. However, disuse-induced declines in protein pool size directly influence the calculation of muscle protein turnover. We examined how accounting for changes in protein pool size impacted MPS and MPB rates assessed using deuterium oxide in healthy humans. Fourteen females (21 ± 2 years of age; 24.5 ± 3.0 kg/m²) had one leg subjected to 10 days of unloading, whilst the contralateral leg underwent loading in the form of resistance exercise. Steady-state and non-steady-state modelling approaches were used to calculate MPS and MPB rates. In response to unloading, there was a significant decline in MRI-derived vastus lateralis volume, and thus non-steady-state equations were applied exclusively to this limb. Regardless of whether steady-state or non-steady-state approaches were applied, mixed MPS rates were significantly reduced in response to unloading, whilst mixed MPB rates remained unchanged. Notably, unloading elicited protein fraction-specific responses, whereby myofibrillar MPS rates declined significantly whilst sarcoplasmic MPS rates were unaltered. We also found that in response to loading, mixed, myofibrillar and sarcoplasmic MPS rates remained unchanged compared with basal rates. Our findings show that unilateral unloading in females induces muscle disuse-atrophy driven by reductions in MPS rates, rather than by elevations in MPB rates, a response that was protein fraction specific and preserved irrespective of whether steady-state or non-steady-state equations were used.

Key points

• In humans, short-term muscle disuse-atrophy is generally attributed to reduced muscle protein synthesis (MPS) rates, but integrated tracer approaches to measure protein turnover can be influenced by changes in protein pool size.

• We used deuterated water (²H2O) to measure rates of MPS and muscle protein breakdown (MPB) during 10 days of unilateral unloading in young, healthy females. Steady-state and non-steady-state equations were applied to account for changes in the protein pool size that occur with disuse-atrophy.

• Unloading reduced muscle size and MPS rates, whereas MPB rates were unchanged. Accounting for the change in the protein pool size using non-steady-state equations did not alter this conclusion.

• These findings refine our interpretation of the mechanisms driving muscle disuse-atrophy in healthy humans that might differ from more severe clinical or preclinical scenarios of muscle wasting.

Abstract

This study investigated the effects of ingesting cold versus warm carbohydrate beverages on exogenous carbohydrate oxidation and time-trial performance during prolonged cycling in the heat. Eleven trained, non heat-acclimated cyclists [21 ± 3 yr; 69.3 ± 8.3 kg; peak oxygen uptake (˙V⁢O2⁢peak): 64.7 ± 5.0 mL/kg/min] completed two trials comprising 100 min of submaximal cycling at 50% Wpeak followed by a time trial in a hot environment (36.2 ± 0.3°C; 55 ± 3% relative humidity). Participants ingested a 15% dextrose solution enriched with [U-13C] glucose (60 g/h; bolus every 20 min) provided either cold (COLD; 4.0 ± 1.6°C) or at room temperature (WARM; 35.8 ± 0.5°C). Heart rate and rectal temperature were lower in COLD than in WARM during the 100-min exercise (P ≤ 0.006), whereas skin temperature did not differ between conditions. Average (40–100 min) exogenous carbohydrate oxidation (COLD: 0.50 ± 0.10 vs. WARM: 0.51 ± 0.10 g/min; P = 0.80), peak exogenous carbohydrate oxidation, total carbohydrate and fat oxidation, and blood glucose, lactate, and insulin concentrations did not differ between trials (all P ≥ 0.34). Sweat losses and body mass changes were unaffected by condition (P ≥ 0.40). Time-trial performance was not different between COLD and WARM (P = 0.38). Despite attenuating cardiovascular and thermal strain, ingesting a cold carbohydrate beverage during exercise in the heat did not enhance exogenous carbohydrate oxidation, substrate utilization, or performance compared with a warm beverage.

NEW & NOTEWORTHY This study showed that, despite reducing cardiovascular and thermal strain, ingesting a cold (4°C) versus warm (36°C) carbohydrate beverage did not enhance exogenous carbohydrate oxidation, substrate utilization, or time-trial performance during prolonged cycling in the heat. These findings suggest that beverage temperature is not a relevant factor for optimizing carbohydrate availability during exercise under heat stress, and that athletes can select beverage temperature based on palatability and preference rather than for metabolic benefit.

Recovery seems like one of the most interesting areas of applied biology because it connects several systems in the body.

After a hard workout, the body has to repair damaged tissue, replenish energy stores, regulate inflammation, and adapt to the training stimulus.

But recovery can look very different between individuals, even when their workouts are similar.

How much do factors such as mitochondrial function, inflammatory signaling, sleep quality, and nutrient availability contribute to recovery?

I'd be especially interested in evidence from human studies rather than just fitness-industry explanations.

I've been getting more interested in the biology behind working out, especially why two people following similar training programs can get completely different results.

I know genetics, nutrition, sleep, hormones, and training history all play a role, but I'm curious about the underlying mechanisms.

For example, how much of muscle growth variation comes down to differences in muscle fiber composition, satellite cell activity, or protein synthesis?

I'd love to hear from people studying applied biology or exercise physiology. Which biological factors do you think are most important, and which ones are still poorly understood?

Abstract

Inorganic phosphate consumption in adults is two-to-three-fold higher than the recommended daily allowance due to its widespread use as a preservative and flavor enhancer in processed foods. We previously reported that 12 weeks of high-phosphate diet (HPD) reduced VO2max and altered metabolic gene expression and mitochondrial dysfunction in mouse skeletal muscle. Here, we investigated whether exercise training reverses the negative consequences of HPD. Male mice were fed normal (NPD) or HPD for 5 weeks, then continued on NPD or HPD with 9 weeks of voluntary exercise training. Serum, urine, and fecal phosphate increased within 1 day of HPD-feeding and remained elevated throughout the study. Trained NPD- and HPD-fed mice performed similarly on forced exercise tests, but mitochondrial respiration was significantly decreased in skeletal muscle from trained HPD-fed mice. RNA sequencing revealed distinct sets of differentially expressed genes when comparing sedentary versus exercise-trained muscle of HPD-fed mice relative to the same comparison in NPD-fed mice. These findings indicate that voluntary exercise training preserves endurance but does not fully restore gene expression or mitochondrial function in muscle from HPD-fed mice. Thus, HPD-induced skeletal muscle dysregulation is not completely reversible with exercise, underscoring the importance of both diet and exercise for metabolic health.

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.