Five adverse events were recorded among four participants, all classified as grade 1: three cases of fatigue and two cases of muscular pain in the extremities. None prevented continued participation, and no serious adverse event occurred. The trial was too small and recruitment fell below target, so its clinical results remain exploratory and do not show whether exercise improved fitness, quality of life, fatigue, complications or hospital stay.

The study, known as the PReOperaTive Exercise Therapy for patients with cancer, or PROTECT, study, recruited adults scheduled for surgery at least two weeks away and medically cleared for exercise. Patients with metastatic disease, absolute contraindications to exercise testing or an adverse event during initial testing that made participation unsafe were excluded. The two-arm trial was registered prospectively and used a computer-generated allocation sequence in a 1:1 ratio, with participants stratified by primary cancer diagnosis.

Although an effectiveness objective and a non-inferiority sample-size calculation formed part of the original registration, the researchers shifted the report’s emphasis to feasibility and safety after the planned recruitment target was not reached. That revision was based on the recruitment shortfall, not on the direction or magnitude of the clinical results. Participants and intervention staff could not be blinded, while outcome assessors and data analysts were also unblinded.

The reported findings therefore concern whether a limited programme could be delivered safely and consistently, rather than whether it is effective. Prehabilitation uses the interval between diagnosis and surgery to prepare patients for the physiological stress of an operation. The PROTECT intervention consisted of one-on-one, on-site aerobic training delivered by an Accredited Exercise Physiologist two or three times per week until 48 to 72 hours before surgery.

Each session lasted 45 to 60 minutes, including a warm-up and cool-down, with at least 30 minutes of continuous cycling on an electronically braked cycle ergometer. Training began at 40% of heart-rate reserve, calculated from resting and maximum heart rate measured during a baseline cardiopulmonary exercise test. When patients adapted and no longer reached the lower intensity anchors confirmed by heart rate and perceived exertion, the target could be increased by 10 percentage points of heart-rate reserve every three sessions.

Intensity remained between 40% and 70% of heart-rate reserve, corresponding to ratings of perceived exertion from 11 to 16. Individual delivery was initially used because few patients were enrolled concurrently and was retained because of COVID-19 restrictions. Recruitment proved to be a major limitation of the single-centre study.

During the recruitment period, 312 patients with breast, colorectal or prostate cancer underwent surgery with curative intent at the study centre, but only 47 were identified as potentially eligible and approached for formal screening. Of those, 23 enrolled and were randomised: 14 to prehabilitation and nine to usual care, a recruitment rate of 1.92 participants per month. Twelve people did not meet the inclusion criteria, 11 declined, and one could not participate because of COVID-19-related issues.

Three participants were lost between the baseline and pre-surgery assessments because of public-health restrictions, leaving 11 in the intervention group and nine in usual care for those assessments. Recruitment began in October 2019, paused in March 2020, resumed in March 2021 and ended in September 2021. The original target was 50 patients, but only 23 were enrolled, below the minimum of 38 estimated for the registered non-inferiority analysis.

That calculation used a 2.0 ml·kg⁻¹·min⁻¹ margin, an assumed standard deviation of 1.8 ml·kg⁻¹·min⁻¹, 90% power and a one-sided significance level of 2.5%. Those who began the programme completed a median of five sessions, with a range of three to 11. The median interval from baseline assessment to surgery was 18.5 days, while enrolment to surgery took a median of 26.5 days, so the number of sessions was broadly consistent with the intended schedule of one every two to three days.

Total supervised exercise exposure was 63 hours. Five grade 1 adverse events occurred, equivalent to one event per 12.6 exercise hours. The researchers noted that this frequency was higher than expected and that comparisons with other studies are limited by differing definitions, surveillance practices and denominators.

Nevertheless, every event was mild: fatigue accounted for three reports and extremity pain for two. There were no grade 2 or more severe events, no serious adverse events, and no interruptions to exercise caused by adverse symptoms. The sample was too small to provide a precise estimate of uncommon harms, but within the participants studied, the supervised programme was tolerated without a serious safety signal.

Cardiorespiratory fitness, health-related quality of life and fatigue were assessed at baseline, immediately before surgery and 30 days after surgery. Fitness was measured with a symptom-limited cardiopulmonary exercise test on a cycle ergometer. The researchers determined peak oxygen uptake from the average of the highest consecutive 20-second values and identified the ventilatory threshold using a modified V-slope method confirmed through the ventilatory-equivalents approach.

Quality of life was measured with the Functional Assessment of Cancer Therapy–General questionnaire, covering physical, social and family, emotional and functional well-being, while the 13-item Functional Assessment of Chronic Illness Therapy–Fatigue scale quantified fatigue and its effects on daily activity. Mixed-effects models examined group-by-time changes, and Hedges’ g effect sizes with 95% confidence intervals were calculated for exercise-test outcomes. No significant group-by-time interaction was found for cardiorespiratory fitness, health-related quality of life or fatigue.

Given the small, heterogeneous sample and short intervention, these imprecise estimates neither demonstrate benefit nor establish that the programme has no effect. Post-operative results were likewise reported descriptively because the study was not powered to compare them. Within 30 days of surgery, six intervention participants and four usual-care participants experienced at least one complication.

Most were Clavien–Dindo grade I, meaning no treatment was required, although one grade III complication occurred. The median hospital stay was four days in both groups, and one 30-day readmission was recorded. The groups differed in several baseline characteristics, including habitual physical activity, body mass and the proportion receiving neoadjuvant chemotherapy, adding uncertainty to any between-group comparison.

Both groups also maintained physical well-being, fatigue and overall health-related quality of life from baseline to the pre-surgery assessment. The researchers could not separate an effect of exercise from other influences, including reassurance and support from repeated contact with an exercise professional, the burden of travelling to appointments, and possible disruption to daily routines. Standard quality-of-life measures may also incompletely capture concerns described by patients preparing for surgery, including preparedness, control and agency in recovery.

The recruitment data show that reaching patients in time was difficult at this regional centre. Although about half of the 47 people formally approached consented, only 47 of the 312 patients who underwent surgery with curative intent during the recruitment period were identified as potentially eligible and approached for screening. Patients cited travel burden, limited availability and short notice between enrolment and surgery as reasons for declining.

In a regional service, travel can require additional money, accommodation, time away from work or support from relatives and carers. Centre-based delivery enabled direct supervision and individual adjustment, but it also required dedicated staff, facilities and repeated journeys. The authors therefore propose that future studies examine broader referral pathways and remote or hybrid supervision, while preserving exercise monitoring and fidelity.

Cost-effectiveness and resource use were not evaluated, however, so the pilot cannot establish which delivery model is preferable or scalable. It also did not prespecify formal feasibility thresholds against which the programme could be judged to pass or fail, limiting objective interpretation of the recruitment and adherence results. The absence of a clear clinical signal should not be mistaken for evidence that prehabilitation is ineffective.

The exposure was brief: the median number of sessions was five before surgery, leaving limited time for exercise progression or physiological adaptation. The PROTECT sample also mixed breast, prostate and colorectal cancers, whose surgical pathways, perioperative care and expected complications differ, and was drawn from one centre. A single-centre design further limits transfer to services with different populations, staffing and referral systems.

Future work should therefore test specific cancer groups in adequately powered trials, examine strategies that produce a meaningful physiological stimulus within short surgical pathways, and evaluate remote or hybrid delivery as a possible response to geographic and time barriers.

Subject of Research: Safety and feasibility of supervised aerobic prehabilitation before cancer surgery

Article Title: Feasibility and safety of an exercise-based prehabilitation intervention before cancer surgery: a pilot randomised controlled trial

Article References: Hennessy, D. T., Shee, A. W., Rawstorn, J. C., Evans, L., Brown, S., & Wallen, M. P. (2026). Feasibility and safety of an exercise-based prehabilitation intervention before cancer surgery: a pilot randomised controlled trial. Supportive Care in Cancer, 34(11), Article 1132. https://doi.org/10.1007/s00520-026-11356-9

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11356-9

Keywords: prehabilitation, cancer surgery, supervised exercise, aerobic training, treatment safety, pilot randomised trial, cardiorespiratory fitness, postoperative outcomes, regional healthcare, exercise oncology, Feasibility, safety

Idiopathic generalized epilepsies are epileptic syndromes characterized by seizures involving widespread networks without a localized seizure onset on neuroimaging and a presumed genetic etiology. They account for approximately 20% of all epilepsies, according to the study’s background, but remain underrepresented in research. Unlike focal epilepsy, which is associated with discrete seizure foci, idiopathic generalized epilepsies are linked to dysfunction in thalamocortical networks. The thalamus and anterior cingulate cortex, or ACC, are central components of this circuitry and participate in functions including cognitive control, attention and error detection, making them important regions for investigating physiological features of idiopathic generalized epilepsies.

The study was conducted at the University of Alabama at Birmingham using baseline data from two related projects: a blinded randomized controlled trial of combined endurance and resistance exercise training in patients with idiopathic generalized epilepsies and an endurance-training pilot study in healthy controls. The analysis did not test whether exercise changed brain measures. Adults with a clinician-confirmed diagnosis of idiopathic generalized epilepsy and healthy controls underwent the same general procedures, including a physical examination, maximal graded exercise test and magnetic resonance imaging on the same 3T scanner. Most patients were taking one or more antiseizure medications, with leviracetam, lamotrigine and sodium valproate among the most frequently prescribed drugs. This medication heterogeneity was not controlled statistically and could influence exercise capacity, cerebral perfusion or metabolite measurements.

During the cycling test, work began at 25 watts and increased by 25 watts every two minutes while investigators monitored respiratory exchange, blood pressure, heart rate and perceived exertion. Peak oxygen uptake, calculated from the final two 30-second measurements, served as the primary measure of cardiorespiratory fitness. Two participants did not complete the test, leaving 44 people in the fitness analysis: 14 healthy controls, 16 seizure-free patients and 14 patients with active seizures. After adjustment for age and sex, estimated mean peak oxygen uptake was 20.41 millilitres per kilogram per minute in the idiopathic generalized epilepsy group and 22.85 millilitres per kilogram per minute in controls. The difference was not statistically significant, with a p-value of 0.203 and a partial eta-squared of 0.04. Seizure-control status also produced no significant overall difference in fitness, although the estimated mean was lowest among participants with active seizures, at 18.72 millilitres per kilogram per minute, compared with 21.85 among seizure-free patients and 22.88 in controls.

That null result should be interpreted in light of how the comparison group was selected. Both patients and healthy controls had low leisure-time physical activity, with the study requiring activity below the American Heart Association recommendation of 150 minutes per week of moderate-intensity endurance exercise. Their self-reported activity did not significantly differ: estimated marginal means were 2.31 in controls and 2.18 in the idiopathic generalized epilepsy group, with a p-value of 0.696. No objective activity tracker was used. The authors said this similarity may have reduced variation in fitness, potentially masking differences associated with the disorder, although the cross-sectional design cannot establish that explanation. Antiseizure medications may also have influenced exercise capacity. The result therefore indicates no detectable difference in this selected sample, not that cardiorespiratory fitness is unaffected in all people with idiopathic generalized epilepsy.

For cerebral blood flow, researchers used a five-delay pseudo-continuous arterial spin-labeling sequence with post-labeling delays of 500, 1,000, 1,500, 2,000 and 2,500 milliseconds. A multi-delay kinetic model estimated blood flow and arterial transit time, while calibration produced absolute perfusion values in millilitres per 100 grams of tissue per minute. Investigators extracted atlas-based regional values from the ACC and thalamus. Eight participants were excluded because of ghosting artifacts or perfusion variance above the predefined threshold, leaving 38 people for the comparison. After adjustment for age and sex, the idiopathic generalized epilepsy group had significantly higher ACC blood flow than controls: estimated means were 59.61 and 52.72 millilitres per 100 grams per minute, respectively. The difference was 6.89 millilitres per 100 grams per minute, with a p-value of 0.039 and a partial eta-squared of 0.12. Thalamic blood flow did not differ significantly between groups, and seizure-control status was not associated with a significant perfusion difference in either region.

The researchers also used proton magnetic resonance spectroscopy to measure concentrations of N-acetylaspartate, or NAA, and the combined glutamate-glutamine signal, Glx, relative to total creatine in the ACC and thalamus. NAA is considered a marker of neuronal integrity, while Glx reflects aspects of excitatory neurotransmission and cognitive processing. Point-resolved spectroscopy used separate voxels over the bilateral ACC and thalamus, and the resulting spectra were corrected for tissue composition. Seven participants were excluded under predefined spectral-quality criteria, leaving 39 participants in the metabolite analysis. In the thalamus, NAA relative to total creatine was lower in patients with idiopathic generalized epilepsies than in controls, with estimated means of 1.35 and 1.49, respectively. The difference was 0.14, with a p-value of 0.012 and a partial eta-squared of 0.16. Neither ACC metabolite ratio nor the overall thalamic Glx ratio differed significantly between the main study groups.

Seizure-control status was associated with specific thalamic differences. Patients with active seizures had a lower thalamic NAA-to-total-creatine ratio than healthy controls, with an estimated mean of 1.29 compared with 1.49 in controls and a post-hoc p-value of 0.017. Patients who had been seizure-free for the preceding six months did not differ significantly from controls in post-hoc comparisons. The active-seizure group also had a lower thalamic Glx-to-total-creatine ratio than the seizure-free group, with estimated means of 0.57 and 0.81 and a difference of 0.24. The post-hoc p-value was 0.004, while the overall seizure-status effect had a p-value of 0.005 and a partial eta-squared of 0.26. The authors described this pattern as consistent with altered thalamocortical network physiology, but the measurement is not a direct readout of extracellular glutamate or acute seizure activity. Single-voxel spectroscopy has limited spatial and temporal resolution, cannot separate glutamate from glutamine, and could not detect GABA peaks. Medication effects are also plausible because the participants’ drug regimens varied substantially, including both monotherapy and polytherapy.

Several limitations constrain how far the results can be generalized. The sample was relatively small, particularly for the spectroscopy subgroup comparisons, and the investigators used atlas-based regions that averaged across distinct thalamic nuclei and ACC subregions. Such averaging may obscure localized perfusion effects and could contribute to the absence of a significant thalamic blood-flow difference. Seizure control was reduced to a binary classification based on whether any seizures had occurred during six months, without incorporating seizure frequency, severity or type, and the investigators noted that definitions of seizure freedom vary across epilepsy research. Medication effects were not analyzed directly, physical activity was not measured objectively, and the deliberately inactive healthy controls could not establish whether more active people would show different results. The findings are observational associations from a selected cohort, not evidence that altered blood flow or metabolite ratios cause seizures, that exercise can correct them, or that these measurements can predict clinical outcomes. Nevertheless, the combined measurements show that idiopathic generalized epilepsies are associated in this sample with region-specific differences in thalamocortical perfusion and metabolism, while the role of cardiorespiratory fitness remains unresolved.

Subject of Research: Cardiorespiratory fitness, cerebral perfusion and thalamic metabolism in adults with idiopathic generalized epilepsies

Article Title: Investigating cardiorespiratory fitness, cerebral blood flow, and brain metabolism in epilepsy

Article References: Lien, Y., Mitchell, B. S., Szaflarski, J. P., Ver Hoef, L., Buford, T. W., Goodman, A. M., Willoughby, W. R., Morgan, C. J., Moyana, A., Pilkington, J., August, A. R., Bennett, J. T., & Allendorfer, J. B. (2026). Investigating cardiorespiratory fitness, cerebral blood flow, and brain metabolism in epilepsy. Frontiers in Network Physiology, 6, Article 1894335. https://doi.org/10.3389/fnetp.2026.1894335

Image Credits: AI Generated

DOI: 10.3389/fnetp.2026.1894335

Keywords: idiopathic generalized epilepsies, cerebral blood flow, brain metabolism, cardiorespiratory fitness, thalamocortical network, magnetic resonance spectroscopy, arterial spin labeling, seizure control, anterior cingulate cortex, thalamic metabolism, Investigating, cardiorespiratory

The research team searched PubMed, Web of Science, and the Cochrane Library from their inception to 6 February 2026, with additional searches of Scopus and Embase conducted on 17 August 2026. After screening more than 1,300 records, they identified 22 study reports representing 17 unique trials — 15 randomised and 2 non-randomised controlled trials — encompassing 588 unique participants. The clinical populations spanned hypertension, prediabetes, type 1 and type 2 diabetes, breast cancer, prostate cancer, and broader metabolic risk profiles. Participants ranged in age from roughly 14 to 67 years, and interventions ran from 8 weeks to 12 months, typically delivered two to three times per week at moderate-to-vigorous intensity, with net playing time between 7 and 45 minutes per session.

Methodologically, the analysis was more sophisticated than most in this field. Because some trials contributed multiple effect estimates — through multiple intervention arms, linked reports from the same cohort, or repeated measures of the same outcome — the authors used three-level random-effects meta-analyses that treated effect sizes as nested within trials. They then applied cluster-robust (CR2) variance estimation, clustering on the independent trial, to every outcome as a robustness check, and drew conclusions only where the two inferential procedures agreed. Certainty of evidence was rated with the GRADE framework, and prediction intervals were reported to show how variable the true effects might be across different settings.

The headline findings are striking for a group of patients often excluded from vigorous team sport. Recreational football was associated with significant improvements in cardiorespiratory fitness, with a standardised mean difference (SMD) of 0.70 for peak oxygen uptake (VO₂peak) and an even larger 1.43 for Yo-Yo Intermittent Endurance Test performance. Cardiovascular outcomes also improved: diastolic blood pressure fell (SMD −0.53), mean arterial pressure dropped (SMD −0.89), and resting heart rate showed the largest effect in the entire synthesis (SMD −1.01). In clinically interpretable units, the pooled mean differences amounted to roughly a 5 mmHg reduction in mean arterial pressure and a 5.7 beats-per-minute reduction in resting heart rate.

Body composition and blood lipids moved in the right direction too. Body fat percentage declined significantly (SMD −0.36), muscle mass increased modestly (SMD 0.22), and both triglycerides (SMD −0.56) and total cholesterol (SMD −0.69) fell. Notably, body weight, BMI, and waist circumference did not change significantly — a pattern the authors attribute to the insensitivity of scale-based measures to compositional change when fat is lost and lean tissue is gained, particularly in patients taking medications with weight-active effects. One prostate cancer trial, for example, reported a between-group lean body mass difference of about 0.7 kilograms after 12 weeks of football training in men undergoing androgen deprivation therapy.

The bone-health results tell a subtler story. Plasma osteocalcin, a marker of bone formation, rose significantly (SMD 1.07), and P1NP, another formation marker, increased under the primary analysis (SMD 1.28). Yet DXA-derived bone mineral density and content showed no significant changes, and the P1NP effect did not survive cluster-robust inference. The authors interpret this as evidence of early anabolic signalling in response to the mechanical loading of football — the jumps, turns, accelerations, and decelerations that small-sided games demand — without enough training exposure to produce measurable structural remodelling in older, clinically vulnerable cohorts. Bone turnover markers can respond within weeks, whereas density changes typically require longer and are most visible at mechanically loaded lower-limb sites.

Several seemingly positive findings proved fragile under scrutiny. Borderline effects on fat mass, systolic blood pressure, and LDL cholesterol were not retained under cluster-robust inference, and effects on body fat percentage, fat mass, muscle mass, systolic pressure, and LDL were sensitive to the assumed pre–post correlation used to derive change-score statistics. No significant pooled effects emerged for HbA1c, fasting glucose, fasting insulin, HDL cholesterol, or C-reactive protein. Across 27 outcomes, the statistical interpretation was unchanged for 22 under the robust procedure — but certainty of evidence was rated low to very low for most outcomes, and prediction intervals for several significant findings crossed zero, meaning the average benefit was not reproduced consistently across diagnoses and programmes.

On feasibility, the picture is encouraging but not uniform. Mean attendance across 13 independent trials was 82.7 percent, and mean attrition across 14 trials was 15.6 percent — respectable figures for exercise interventions in clinical populations, and consistent with the idea that the social structure, team affiliation, and sheer enjoyment of football help sustain engagement where solitary treadmill work often fails. Adverse events were summarised narratively because quantitative pooling was impossible: most reported events were musculoskeletal, including muscle soreness, strains, joint pain, and lower-limb injuries, with occasional serious injuries such as fibular fractures and Achilles tendon ruptures. Several trials noted that injuries clustered in the early phase of training, underscoring the importance of progressive exposure, warm-up, and qualified supervision.

The authors are explicit that these results should not be read as evidence that football can replace established exercise prescriptions or as a disease-specific therapy. The included populations differ enormously in pathophysiology, treatment burden, medication status, and baseline fitness, and the number of studies within any single diagnostic category was too small for firm conclusions. In hypertension, blood-pressure effects were inconsistent, particularly among patients already on antihypertensive medication, where residual headroom for further lowering may be limited. In diabetes, glycaemic outcomes were largely unchanged at the pooled level, plausibly because fasting indices and HbA1c are relatively insensitive to modest exercise effects in pharmacologically controlled patients. Cancer-related evidence came from small, highly selected samples with variable attendance.

Nevertheless, the synthesis marks a milestone for the ‘Football is Medicine’ platform, which has argued for years that small-sided games deliver a uniquely multimodal stimulus — cardiovascular, neuromuscular, and osteogenic load within a single session — that continuous aerobic training and isolated resistance exercise cannot match. The physiological profile is coherent: heart rates of 80 to 90 percent of maximum, repeated high-intensity efforts, and weight-bearing impacts together explain the concurrent gains in fitness, heart rate, body fat, and bone formation markers. For appropriately screened patients who prefer group-based, game-based activity and can participate safely under supervision, the authors conclude that recreational football may be considered a supervised adjunctive exercise option — particularly where cardiorespiratory fitness is the target. Adequately powered, diagnosis-specific trials with standardised reporting of training dose, adherence, and adverse events are the next step before football earns a formal place in the clinical exercise toolkit.

Subject of Research: Effects and feasibility of recreational football exercise in patients with chronic diseases

Article Title: Recreational football as medicine? A meta-analysis of its effects and feasibility in patients with chronic diseases

Article References: Wei, K., Chen, G., Wang, T., & Wang, B. (2026). Recreational football as medicine? A meta-analysis of its effects and feasibility in patients with chronic diseases. Frontiers in Public Health, 14, Article 1869982. https://doi.org/10.3389/fpubh.2026.1869982

Image Credits: AI Generated

DOI: 10.3389/fpubh.2026.1869982

Keywords: recreational football, meta-analysis, chronic disease, cardiorespiratory fitness, blood pressure, hypertension, type 2 diabetes, cancer survivors, bone health, exercise as medicine, body composition, feasibility

The research team, led by Sai Long and Yao Li of the School of Physical Education at Jiangxi Normal University Science and Technology College in China, conducted the review in accordance with the PRISMA 2020 reporting standard and prospectively registered the protocol in PROSPERO. They searched six major databases—PubMed, Embase, Cochrane CENTRAL, Scopus, Web of Science, and SPORTDiscus—from inception through June 2026, screening 4,694 records and ultimately including 25 trials published between 2003 and 2026. The trials spanned Asia, Europe, North America, Australia, and the Middle East, and the exercise programs they tested were remarkably diverse: aerobic training, resistance training, high-intensity interval training, combined regimens, Pilates, yoga, and walking-based programs, lasting anywhere from six weeks to twelve months.

The headline numbers are striking. Across 15 trials involving 504 participants, exercise reduced alanine aminotransferase, or ALT, by a mean of 7.33 units per liter compared with control conditions, with a 95 percent confidence interval of −10.71 to −3.95. Aspartate aminotransferase, or AST, fell by 5.52 units per liter across 13 trials with 439 participants. Body mass index dropped by a pooled 1.54 kilograms per square meter across 17 trials, and peak or maximal oxygen uptake—VO2peak or VO2max, the gold standard measure of cardiorespiratory fitness—rose by 4.08 milliliters per kilogram per minute across seven trials. These are not trivial changes. ALT and AST are the workhorse blood markers of hepatocellular injury, and reductions of this magnitude are comparable to those seen with some pharmacological interventions studied in fatty liver disease.

But the analysis also delivered a sobering counterpoint: the pooled effects on liver fat itself, insulin resistance measured by HOMA-IR, and longer-term glycemic control measured by HbA1c did not reach statistical significance. Seven trials with 233 participants contributed liver fat or steatosis data, yielding a standardized mean difference of −0.36 with a confidence interval spanning −0.93 to 0.20—suggestive of a benefit but far from conclusive. HOMA-IR, pooled from six trials, showed a non-significant reduction of 0.49, and HbA1c, also from six trials, showed a non-significant drop of 0.18 percentage points. The authors are careful to note that improvements in BMI, glycemic markers, or fitness are clinically relevant in the broader cardiometabolic context of MASLD but should not be read as direct evidence that the liver disease itself has resolved.

The methodological machinery behind these conclusions is worth unpacking, because it reveals both the strength and the fragility of the evidence. The researchers used the Cochrane RoB 2 tool to assess risk of bias and found that no trial was judged at high overall risk; roughly half were rated low risk and the remainder had some concerns, most often involving incomplete reporting of randomization procedures or missing outcome data. They then applied the GRADE framework to rate certainty of evidence, and the results were uneven: moderate certainty for the ALT and BMI findings, low certainty for cardiorespiratory fitness, and very low certainty for AST, liver fat, HOMA-IR, and HbA1c. That gradation matters enormously for how clinicians and patients should weigh each result.

Heterogeneity was a persistent theme. Statistical heterogeneity, quantified by the I² statistic, reached 71.3 percent for ALT, 93.8 percent for AST, and 72.3 percent for VO2peak—meaning that the trials varied substantially in the size of the effects they reported. The authors addressed this in several ways. They ran leave-one-out sensitivity analyses, which generally preserved the direction of the pooled estimates. They conducted duration subgroup analyses, splitting trials into those lasting twelve weeks or less versus longer programs. Intriguingly, shorter interventions showed a larger ALT reduction—10.09 units per liter versus 2.46 units per liter for longer programs, a statistically significant difference. But the authors caution against interpreting this as evidence that shorter programs are physiologically superior; the comparison is observational, and duration may simply proxy for differences in baseline enzyme levels, exercise intensity, supervision, and adherence across trials.

One trial in particular shaped the AST picture. A 2025 study by Kim and colleagues reported an unusually large AST reduction, and when the authors excluded it in a dedicated sensitivity analysis, the pooled effect shrank from 5.52 to 3.25 units per liter while heterogeneity collapsed from 93.8 percent to 33.5 percent. The direction of the benefit held, but the magnitude proved sensitive to a single influential study. For BMI, funnel-plot asymmetry detected by Egger regression—significant at p=0.018—raised the possibility of small-study effects, though the authors stopped short of calling it definitive publication bias, noting that asymmetry can arise from multiple sources and that the BMI dataset included small, imprecise trials. No such asymmetry was detected for ALT or AST.

Perhaps the most conceptually important contribution of the review is its insistence on separating domains of response. ALT and AST are markers of hepatocellular injury, not direct measures of hepatic function, so their reduction signals biochemical improvement rather than histological resolution. Liver fat was measured with non-equivalent methods across trials—some used MRI-derived proton density fat fraction or proton magnetic resonance spectroscopy, which directly quantify intrahepatic lipid, while others used the controlled attenuation parameter from transient elastography, an indirect marker. Pooling these on a standardized scale cannot erase that measurement mismatch. Meanwhile, gains in aerobic capacity are biologically consistent with improved skeletal-muscle oxidative capacity, glucose disposal, fatty-acid utilization, and whole-body metabolic flexibility—adaptations that may reduce metabolic substrate delivery to the liver, but which the non-significant HOMA-IR and HbA1c results show were not uniform across metabolic domains.

The findings arrive amid a rapidly evolving evidence landscape. A 2024 network meta-analysis by Huang and colleagues ranked exercise modalities across metabolic and liver-function outcomes; a 2025 synthesis examined Mediterranean diet combined with exercise; and a 2026 meta-analysis by Wang and colleagues focused specifically on high-intensity interval training versus moderate-intensity continuous training, including dose-response analyses. The new review distinguishes itself by treating structured exercise as a single common exposure and applying one consistent post-intervention analytical framework across seven prespecified outcome domains. It also reports prediction intervals—ranges describing the expected effect in a future, comparable setting—which for ALT, BMI, and VO2peak all crossed the null, a statistical way of saying that the average benefit does not guarantee a uniform response in every clinical context.

For the millions of people living with MASLD, the practical message is cautiously encouraging. Structured exercise emerges as a physiologically relevant component of management, particularly when the goals include lowering elevated liver enzymes, reducing body mass, and building cardiorespiratory fitness. But the authors are explicit that the optimal prescription—the right combination of mode, intensity, and duration to produce reproducible hepatic adaptations independent of weight loss—remains unknown. They call for future trials that report exercise dose and adherence in sufficient detail, use standardized and sensitive measures of intrahepatic fat, and prespecify metabolic and cardiorespiratory outcomes. Until then, the liver enzyme improvements documented here stand as the most consistent signal that exercise does something real for the fatty liver, even as the deeper question of whether it reshapes the diseased organ itself awaits stronger evidence.

Subject of Research: Effects of exercise training on hepatic, metabolic, and cardiorespiratory outcomes in adults with metabolic dysfunction-associated steatotic liver disease

Article Title: Exercise training improves hepatic enzymes, body mass index, and cardiorespiratory fitness in adults with metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis

Article References: Long, S., & Li, Y. (2026). Exercise training improves hepatic enzymes, body mass index, and cardiorespiratory fitness in adults with metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis. Frontiers in Physiology, 17, Article 1976073. https://doi.org/10.3389/fphys.2026.1976073

Image Credits: AI Generated

DOI: 10.3389/fphys.2026.1976073

Keywords: MASLD, NAFLD, exercise training, liver enzymes, ALT, AST, body mass index, cardiorespiratory fitness, meta-analysis, liver fat, insulin resistance, HOMA-IR

The investigation was conducted between August 2021 and April 2022 and drew participants from five Chinese cities spanning considerable geographic and cultural diversity: Shanghai and Suzhou in the east, Kunming in the southwest, Urumqi in the far northwest, and Changsha in central China. In total, 10,327 adolescents aged 12 to 17 years took part. This age range captures the middle school and early high school years, a developmental window in which depressive symptoms often first emerge and in which academic pressure, social change, and biological maturation all converge. The study received ethics approval from the East China Normal University Committee on Human Research Protection, and written informed consent was obtained from both the participants and their parents, with participant names coded to protect privacy.

What sets this study apart from much of the existing literature is its focus on health-related physical fitness as a whole, rather than on a single dimension such as cardiorespiratory endurance. Previous research has suggested that higher cardiorespiratory fitness may ameliorate depressive symptoms in adolescents, but the relationship between depression and the broader fitness profile has remained unclear. To capture that broader profile, the researchers administered a battery of physical tests: measurements of height and weight to calculate body mass index, a standing long jump to assess lower-body explosive strength, a thirty-second sit-up test to gauge muscular endurance, the twenty-meter shuttle run test to estimate cardiorespiratory fitness, and a sit-and-reach test to evaluate flexibility. Together, these measurements were combined into a composite score known as the health-related physical fitness Z-score, or HPF-Z, which summarizes each participant’s overall fitness relative to the group.

Depressive symptoms, meanwhile, were evaluated using the Center for Epidemiological Studies Depression Scale, a widely used and well-validated screening instrument known as the CES-D. Rather than diagnosing clinical depression, the scale captures the frequency of symptoms such as low mood, loss of interest, and feelings of hopelessness over the preceding week, providing a snapshot of psychological distress in the general population. The researchers then employed a series of statistical techniques, including the Kruskal-Wallis H test, t-tests, chi-square tests, and binary logistic regression, to examine how fitness levels related to the likelihood of reporting depressive symptoms after accounting for other variables.

The headline finding is stark. The overall prevalence of depressive symptoms among the adolescents studied was 28.6 percent, but that figure concealed a pronounced gender gap: 24.2 percent of boys reported depressive symptoms compared with 33.1 percent of girls, meaning roughly one in three girls in the sample showed signs of psychological distress. This gender disparity echoes patterns documented in adolescent mental health research worldwide and underscores that girls in this age group may be a particularly vulnerable population.

After adjusting for covariates, the association between fitness and depression emerged clearly. Adolescents in the lowest grade group of the overall HPF-Z score had a prevalence of depressive symptoms 1.41 times higher than those in the highest grade group, with an odds ratio ranging from 1.244 to 1.602 and a p-value below 0.001. In other words, the least fit teenagers were roughly forty percent more likely to report depressive symptoms than the fittest, even after statistical adjustment for other factors. The pattern held when each fitness component was examined individually. Those in the lowest group for the standing long jump showed depressive symptom prevalence 1.35 times higher than the top group; for thirty-second sit-ups, the figure was 1.25 times; for the twenty-meter shuttle run test, also 1.25 times; and for the sit-and-reach test of flexibility, 1.18 times. Each of these differences was statistically significant, with p-values ranging from below 0.001 to 0.015.

Body composition told a complementary story. Adolescents in the normal weight group had a prevalence of depressive symptoms 0.85 times that of the obesity group, meaning they were about fifteen percent less likely to report symptoms. The researchers also detected significant dose-response trends: the prevalence of depressive symptoms decreased as body mass index decreased, with a trend p-value of 0.009, and decreased as performance improved on the standing long jump, thirty-second sit-ups, twenty-meter shuttle run, and sit-and-reach tests, with trend p-values of less than 0.001, 0.001, 0.001, and 0.007 respectively. Taken together, the results indicated that body mass index had a positive predictive effect on depressive symptoms, meaning higher BMI predicted more symptoms, whereas the overall fitness Z-score and each individual fitness item negatively predicted depressive symptoms, meaning better fitness predicted fewer symptoms.

From a technical standpoint, the strength of this study lies in its scale and its multi-component assessment. With more than ten thousand participants drawn from five cities, the statistical power to detect associations is considerable, and the use of objective physical tests rather than self-reported fitness removes a common source of bias in this literature. The shuttle run test, in particular, is a well-established field protocol for estimating cardiorespiratory fitness in youth, while the standing long jump and sit-up tests capture neuromuscular strength and endurance that are often overlooked in studies focused solely on aerobic capacity. The inclusion of flexibility, measured by the sit-and-reach test, is unusual in mental health research, and the finding that even this component showed a significant association suggests that the fitness-depression link may not be confined to any single physiological pathway.

That said, the study’s design imposes important limits on interpretation. Because the data are cross-sectional, collected at a single point in time, the findings demonstrate association rather than causation. It is possible that low fitness contributes to depressive symptoms, but it is equally plausible that depression leads to reduced physical activity and declining fitness, or that shared underlying factors, such as socioeconomic circumstances, sleep, or academic stress, influence both. The binary logistic regression adjusted for covariates, but no observational study can rule out residual confounding entirely. Longitudinal follow-up and intervention studies would be needed to establish whether improving fitness actually reduces depressive symptoms, and the authors’ own framing of BMI and fitness as predictors should be read in this associative sense rather than as proof of causal direction.

Nevertheless, the public health implications are significant. Nearly three in ten adolescents in the sample reported depressive symptoms, a burden that carries consequences for academic performance, social development, and long-term mental health. If physical fitness is indeed one modifiable lever, school-based physical education, active commuting, and community sports programs become potential channels for prevention, particularly for girls, whose symptom prevalence in this study was markedly higher. The composite HPF-Z approach also offers a practical message: no single test determines the outcome, and improvements across any component, from endurance to strength to flexibility, were each associated with lower symptom prevalence. As youth mental health services worldwide remain stretched far beyond capacity, evidence that the gymnasium and the playing field may play a role alongside the clinic is a finding worth taking seriously, even as researchers work to confirm whether the relationship is causal and to identify the biological and psychological mechanisms that might connect a fitter body to a healthier mind.

Subject of Research: The association between health-related physical fitness and depressive symptoms in Chinese adolescents

Article Title: Depressive symptoms in Chinese adolescents: the role of health-related physical fitness

Article References: Zhang, T., Guo, Y., Li, M., Liu, Y., Sun, P., Yin, X., & Zhang, F. (2026). Depressive symptoms in Chinese adolescents: the role of health-related physical fitness. BMC Public Health. https://doi.org/10.1186/s12889-026-29840-6

Image Credits: AI Generated

DOI: 10.1186/s12889-026-29840-6

Keywords: adolescent health, depression, physical fitness, cardiorespiratory fitness, body mass index, mental health, CES-D, China, public health, obesity, exercise, BMC Public Health

The investigation was led by Daniel Arriscado-Alsina of the Universidad de La Laguna and Raúl Jiménez-Boraita of the Universidad Internacional de La Rioja. Their team recruited 949 students aged 9 to 15 years from 60 schools across the islands of Tenerife and Gran Canaria. The breadth of the sampling frame matters: by drawing participants from dozens of schools rather than a handful of classrooms, the researchers reduced the risk that their findings reflect the quirks of one particular educational environment. The study protocol was approved by the Research Ethics and Animal Welfare Committee of the University of La Laguna, and written informed consent was obtained from the parents or legal guardians of every participating student.

Sleep problems were measured with the Sleep Self-Report questionnaire, a validated instrument completed by the children themselves rather than their parents. This design choice is technically significant. Self-reported sleep captures the child’s own experience of difficulties such as trouble falling asleep, waking during the night, or feeling unrefreshed in the morning, which may diverge from parental observation. Each participant’s score placed them somewhere along a continuum of sleep difficulties, and the researchers divided the sample into tertiles, or three groups of roughly equal size ranging from the fewest to the most reported problems, to test whether outcomes shifted systematically across those groups.

The measurement battery extended far beyond sleep. Moderate-to-vigorous physical activity and sedentary time were assessed through questionnaires, as were health-related quality of life and the children’s own perception of their academic performance. Body composition was evaluated using anthropometric techniques, including the body mass index-for-age z-score, a standard pediatric metric that expresses a child’s BMI relative to population norms for their age and sex, and waist circumference, a direct marker of central adiposity. Physical fitness was tested in the field using handgrip strength measured with a dynamometer, the standing long jump as an index of lower-body explosive power, and a cardiorespiratory fitness test. Academic functioning was captured both through official grades and through the students’ self-assessment of how well they were doing at school.

Because students clustered within schools, the analysts used statistical methods that account for such grouping, examining differences across the sleep-problem tertiles with cluster-adjusted analyses. They then built separate generalized estimating equation models for each indicator, a technique well suited to repeated or correlated observations within groups. Each model was adjusted for sex, age treated as a continuous variable, family affluence, and area of residence, with school included as the clustering variable. The handgrip strength model received an additional layer of statistical control for body weight and height, since stronger children tend to be larger, and raw grip strength can therefore confound comparisons across body sizes.

The pattern of results was strikingly coherent. Higher sleep-problem scores were inversely associated with moderate-to-vigorous physical activity, health-related quality of life, standing long jump performance, cardiorespiratory fitness, academic grades, and perceived academic performance. In other words, as reported sleep difficulties rose, every one of these indicators fell. The inverse associations extended across domains that are usually studied in isolation: a child’s nighttime struggles showed up in the gymnasium, in the classroom, and in their own sense of wellbeing. Conversely, sleep problems were positively associated with sedentary time, the BMI-for-age z-score, and waist circumference, meaning children with more sleep difficulties tended to sit more and carry more central body fat.

One result broke from the pattern. Handgrip strength, a measure of isometric upper-body strength, showed no significant association with sleep problems once the model was adjusted for body weight and height. This null finding is informative rather than disappointing. It suggests that the apparent relationship between sleep difficulties and grip strength may be largely explained by differences in body size, whereas the associations with explosive lower-body power and cardiovascular endurance appear to persist independently of the adjustments applied. The distinction hints that different components of physical fitness may relate to sleep through different physiological pathways, a question the authors flag for future work.

The researchers also applied a false-discovery-rate correction, a statistical safeguard used when many associations are tested at once. Because a large battery of indicators multiplies the chances that at least some associations will appear significant by chance alone, this correction recalibrates the threshold for significance across the entire set of tests. The fact that all significant associations survived this stricter procedure strengthens confidence that the reported links are not statistical artifacts, even though the study’s cross-sectional design still limits the strength of the conclusions that can be drawn.

Indeed, the authors are explicit about the limits of their evidence. Because the data were collected at a single point in time, the indicator-specific models do not establish independence, temporal ordering, or causality. The relationships could run in either direction, or both. A child who sleeps poorly may feel too fatigued to exercise, and reduced physical activity is itself known to disrupt sleep, creating a potential feedback loop. Similarly, poor sleep can impair attention and memory, dragging down grades, while academic stress and screen-heavy evenings can in turn delay bedtime. Rising adiposity and poor sleep are also thought to reinforce one another through metabolic and hormonal pathways, including alterations in appetite regulation and circadian rhythm. Disentangling these reciprocal dynamics requires longitudinal designs that follow the same children over months and years, and the study’s authors call for exactly that.

Even with those caveats, the findings carry practical weight for schools, families, and public health planners. Sleep problems in childhood and early adolescence are common, modifiable, and increasingly recognized as relevant to school health, yet lifestyle, fitness, wellbeing, body composition, and academic functioning are not always assessed together in school-based research. By measuring all of these domains in one coordinated effort, the Canary Islands study demonstrates that sleep sits at the intersection of nearly every indicator educators and clinicians care about. If future longitudinal work confirms that sleep difficulties drive downstream harm, or that improving sleep lifts activity, fitness, and learning, then sleep could become one of the most efficient levers available for improving children’s health on multiple fronts at once. For now, the message is a sobering correlation: the children struggling most with sleep are, on average, the same children struggling most with movement, weight, wellbeing, and school.

Subject of Research: Associations between sleep problems and lifestyle, body composition, fitness, wellbeing, and academic outcomes in schoolchildren

Article Title: Associations of sleep problems with lifestyle, health-related quality of life, body composition, physical fitness, and academic performance in schoolchildren

Article References: Arriscado-Alsina, D., & Jiménez-Boraita, R. (2026). Associations of sleep problems with lifestyle, health-related quality of life, body composition, physical fitness, and academic performance in schoolchildren. Journal of Activity, Sedentary and Sleep Behaviors. https://doi.org/10.1186/s44167-026-00116-z

Image Credits: AI Generated

DOI: 10.1186/s44167-026-00116-z

Keywords: sleep problems, schoolchildren, physical activity, sedentary behavior, physical fitness, health-related quality of life, body composition, obesity, academic performance, cardiorespiratory fitness, cross-sectional study, adolescent health

The endothelium, the delicate single layer of cells lining the interior of every blood vessel, is far more than passive plumbing. It actively regulates vascular tone by releasing vasodilating and vasoconstricting compounds, controls oxidative processes, modulates cell adhesion, and influences arterial stiffness. When the endothelium falters, vessels stiffen, their dilatory responses weaken, and the earliest silent stages of cardiovascular disease take hold. Flow-mediated dilation of the brachial artery, measured with high-resolution ultrasound after a temporary ischemic stimulus, captures this dysfunction early and tracks closely with coronary artery function, which is why the research team led by Simon Iskra and Armin Paravlić of the University of Ljubljana centered their analysis on it.

To assemble the evidence, the researchers searched six major databases from inception through multiple updated searches in 2023, 2025 and 2026, screening nearly 1,900 records against strict PICOS criteria. Only randomized controlled trials in adults that reported brachial artery flow-mediated dilation alongside at least one secondary outcome made the cut. The final pool spanned healthy volunteers and patients with cardiovascular disease, metabolic syndrome, diabetes, kidney disease, cancer, and even mental and neurological disorders. Participants ranged from about 20 to 78 years old, 43 percent were women, and interventions lasted from four to 26 weeks, with roughly two-thirds of study arms using continuous training and one-third using interval formats.

The headline result survived every robustness check the team threw at it. A random-effects model yielded a mean difference of 2.35 percent in flow-mediated dilation, a fixed-effects model produced 1.90 percent, and a trim-and-fill adjustment for publication bias still left a significant adjusted estimate of 1.74 percent. Sensitivity analysis removing the single largest study did not change the conclusion. Heterogeneity was high, as expected when pooling trials across such diverse populations and protocols, but the direction and clinical relevance of the effect were consistent. By the classification scheme the authors applied, the pooled gain qualifies as small but clinically meaningful, sitting above the 1 percent threshold considered the minimal clinically important difference.

The most novel contribution, however, lies in the meta-regression, which asked which physiological changes actually drive the vascular improvements. Four clusters emerged as significant moderators. Greater reductions in body weight and body fat were associated with larger gains in endothelial function, with regression coefficients of -4.021 and -1.721 respectively. Drops in systolic and diastolic blood pressure also tracked with better flow-mediated dilation, at coefficients of -0.525 and -0.484. On the positive side, improvements in maximal oxygen uptake, the classic index of cardiorespiratory fitness, showed a strong association with endothelial gains at a coefficient of 0.656, and changes in insulin levels moderated the effect as well. Notably, blood lipids, fasting glucose, HbA1c, and insulin resistance measured by HOMA-IR did not significantly moderate the vascular response, suggesting lipid and glucose improvements run on partly independent tracks.

Beneath these statistical associations lies a coherent mechanistic story. During aerobic exercise, blood flow to working muscles surges, subjecting the vessel walls to elevated shear stress. This mechanical signal activates endothelial nitric oxide synthase, boosting production of nitric oxide, the principal vasodilator of healthy arteries. The meta-analysis confirmed this biochemistry in blood: nitric oxide and its metabolites rose substantially, with standardized mean differences of 1.23 for both, while endothelin-1, the vessels’ chief constricting agent, fell moderately. Enhanced nitric oxide bioavailability combined with reduced endothelin-1 shifts vascular tone toward dilation, plausibly explaining much of the measured improvement in flow-mediated dilation, even though the biomarkers themselves did not reach statistical significance as moderators, likely because relatively few studies measured them.

The hemodynamic findings add another layer. Aerobic training produced small but significant reductions in systolic pressure, diastolic pressure, and mean arterial pressure, and the meta-regression tied these blood pressure drops directly to endothelial gains. The authors interpret this as evidence of a feedback loop: healthier endothelia dilate more readily, lowering vascular resistance and pressure, which in turn protects the vessel wall. Arterial stiffness told a subtler tale. Peripheral stiffness, measured at the brachial-ankle segment, decreased significantly, but central stiffness, measured at the carotid-femoral segment, and the augmentation index did not change. The researchers attribute this to the time course of vascular remodeling, since peripheral arteries adapt faster than the stiffer central vessels, and to the small number of trials that measured central outcomes alongside flow-mediated dilation.

Cardiorespiratory fitness emerged as perhaps the most intriguing partner in the adaptation. Maximal oxygen uptake rose moderately across trials, and the stronger the fitness gains, the stronger the endothelial improvements. The relationship is likely bidirectional. Repeated shear stress from training enhances nitric oxide signaling and vascular homeostasis, while preserved endothelial function optimizes skeletal muscle perfusion and oxygen delivery, supporting further fitness gains. The authors caution that because the meta-regression works at the study level, causality cannot be established; the pattern reflects interconnected adaptations rather than a simple cause-and-effect chain. Still, the convergence of fitness, body composition, blood pressure, and insulin changes as moderators paints exercise as a multi-front intervention rather than a single-target drug.

Body composition results carried their own surprise. Even though the analysis excluded trials that combined exercise with dieting, aerobic training alone significantly reduced body weight, body mass index, and body fat percentage, with no change in skeletal muscle mass. The regression confirmed that fat loss amplified the vascular benefit, and the authors suggest that shrinking adipose tissue dampens chronic low-grade inflammation, a process tightly linked to endothelial health. Inflammation markers moved in the expected direction, with a small significant fall in C-reactive protein and a moderate, near-significant decrease in TNF-alpha. Lipid changes were real but modest, with small rises in HDL cholesterol and small falls in LDL and triglycerides, while glucose metabolism improved through fasting glucose, HbA1c, and insulin resistance, even without significant changes in insulin itself.

The authors are candid about limitations. The restriction to trials reporting brachial artery flow-mediated dilation means conclusions may not generalize to other endothelial assessments. Flow-mediated dilation tends to normalize over longer interventions as structural remodeling proceeds, so pooled changes may understate peak functional adaptation. Pooling healthy and clinical populations yields general tendencies rather than disease-specific prescriptions, and the use of standardized mean differences for secondary outcomes, while necessary given heterogeneous measurement methods, obscures absolute changes. Publication bias was detected for the primary outcome and several secondary markers, though corrections preserved the core finding. Even so, the message is hard to dismiss: aerobic exercise acts simultaneously on fat mass, fitness, blood pressure, insulin regulation, nitric oxide signaling, and inflammation, and these converging pathways collectively rebuild endothelial function. For clinicians and the public alike, the analysis reinforces aerobic training as one of the most powerful non-pharmacological tools available for protecting the vascular system, with benefits that compound across nearly every measurable dimension of cardiovascular health.

Subject of Research: Effects of aerobic exercise on endothelial function and cardiovascular disease markers

Article Title: Impact of Aerobic Exercise on Endothelial Function and Other Cardiovascular Disease Markers in Health and Disease: A Systematic Review and Meta-analysis with Meta-regression of Randomized Controlled Trials

Article References: Iskra, S., Turnšek, G., Drole, K., & Paravlić, A. (2026). Impact of Aerobic Exercise on Endothelial Function and Other Cardiovascular Disease Markers in Health and Disease: A Systematic Review and Meta-analysis with Meta-regression of Randomized Controlled Trials. Sports Medicine – Open, 12(1), Article 150. https://doi.org/10.1186/s40798-026-01110-0

Image Credits: AI Generated

DOI: 10.1186/s40798-026-01110-0

Keywords: aerobic exercise, endothelial function, flow-mediated dilation, cardiovascular disease, meta-analysis, nitric oxide, blood pressure, cardiorespiratory fitness, body composition, insulin, arterial stiffness, vascular health

Cardiorespiratory fitness is usually expressed as peak oxygen uptake, or VO2peak, the maximum rate at which the body can consume oxygen during incremental exercise. It is not merely a number for athletes. Across pediatric and adult populations, VO2peak is one of the strongest predictors of long-term cardiovascular health and all-cause mortality, and low fitness in adulthood tracks back to low fitness in childhood. For childhood cancer survivors, the stakes are even higher. Treatments that save lives, including anthracycline chemotherapy agents such as doxorubicin, chest-directed radiation, and certain targeted therapies, can impair cardiac contractility, reduce lung capacity, blunt the autonomic regulation of heart rate, and accelerate vascular aging. A landmark study by Lipshultz and colleagues in the New England Journal of Medicine as far back as 1991 documented late cardiac effects of doxorubicin in children treated for acute lymphoblastic leukemia, and subsequent work has repeatedly linked treatment exposure to measurable declines in exercise capacity.

The scale of the problem was quantified in a 2026 systematic review and meta-analysis by Weinkauf and colleagues in the European Journal of Preventive Cardiology, which pooled fitness data from childhood cancer survivors across multiple studies and found substantially reduced cardiorespiratory fitness compared with healthy peers. Earlier work by Caru and colleagues reached a similar and striking conclusion: survivors of childhood acute lymphoblastic leukemia had significantly lower fitness levels than healthy Canadians even when their self-reported physical activity levels were clinically equivalent. That dissociation is critical. It suggests that the fitness deficit is not simply a matter of survivors exercising less, but reflects underlying physiological impairment, whether cardiac, pulmonary, skeletal muscle mitochondrial, or autonomic, that only objective testing can reveal.

This is where cardiopulmonary exercise testing, commonly abbreviated as CPET, enters the picture. Unlike a simple treadmill time or a six-minute walk distance, CPET directly measures the exchange of oxygen and carbon dioxide at the mouth while the patient exercises on a cycle ergometer or treadmill with progressively increasing intensity. Breath-by-breath gas analysis, combined with continuous electrocardiography, blood pressure monitoring, and often pulse oximetry, allows clinicians to distinguish among the multiple organ systems that can limit exercise performance. A cardiac limitation, a ventilatory limitation, a peripheral muscular limitation, or simply poor effort each leaves a characteristic fingerprint in the CPET data. In a population where multiple organ systems may be quietly compromised by treatment, that diagnostic specificity is invaluable.

The technical foundations of modern CPET were established decades ago. The 1983 study by Buchfuhrer and colleagues in the Journal of Applied Physiology demonstrated how to optimize incremental exercise protocols so that the test lasts long enough to capture true maximal oxygen uptake but short enough to avoid fatigue-driven underestimation. Consensus statements from the American Thoracic Society and the American College of Chest Physicians in 2003, and from the European Association for Cardiovascular Prevention and Rehabilitation and the American Heart Association in 2012, codified how CPET data should be collected and interpreted in specific patient populations. Applied to children, the test is safe, well tolerated, and feasible even in patients treated for leukemia, as demonstrated in feasibility studies of post-chemotherapy leukemia patients published in Annals of Rehabilitation Medicine.

The evidence that CPET detects real, subclinical dysfunction in survivors is compelling. A 2020 study by Long and colleagues in Medicine and Science in Sports and Exercise showed that cardiovascular exercise testing uncovered underlying dysfunction in childhood leukemia survivors that standard resting assessments missed. Caru’s own work has shown that doxorubicin exposure induces significant changes in the cardiac autonomic nervous system of long-term survivors, alterations that manifest during the dynamic stress of exercise long before they would appear at rest. Because exercise places simultaneous demand on the heart, lungs, blood vessels, and muscles, it functions as a physiological stress test for the entire integrated system, exposing vulnerabilities that a resting echocardiogram or a routine checkup would never reveal.

The clinical significance of these measurements extends beyond diagnosis. Exercise intolerance in adult survivors of childhood cancer has been linked to mortality and organ system impairment in a major study by Ness and colleagues published in the Journal of Clinical Oncology, making fitness a genuine prognostic marker rather than a soft measure of wellbeing. If low VO2peak identifies survivors at elevated risk, it also creates a target for intervention. A 2026 meta-analysis by Van Ermengem and colleagues in the same journal, Supportive Care in Cancer, examined the impact of exercise interventions on cardiorespiratory fitness in childhood cancer survivors and found that structured training programs can improve fitness, echoing earlier meta-analyses of exercise interventions and cardiovascular health in childhood cancer. Randomized trials, including a dose-graded aerobic exercise regimen studied by Elnaggar and colleagues and a home-based program tested by Manchola-González and colleagues, have shown that carefully prescribed aerobic training improves cardiopulmonary fitness and physical functioning in pediatric survivors of acute lymphoblastic leukemia.

Translating those findings into practice requires qualified professionals. The authors emphasize the role of the exercise physiologist, a health professional with formal training in exercise science, exercise physiology, or kinesiology, often certified by recognized bodies such as the American College of Sports Medicine, who is qualified to conduct exercise testing, assess cardiovascular and metabolic responses, and prescribe individualized, evidence-based exercise programs. In a survivorship clinic, such a specialist can administer a CPET safely, interpret the ventilation and gas-exchange curves in the context of the patient’s specific treatment exposures, and convert the results into a training prescription with appropriate intensity, progression, and safety margins. Fitness gains in this population also ripple outward: research by Dubnov-Raz and colleagues has linked improvements in fitness to improvements in body composition and bone health in children after cancer, both of which are common sites of treatment-related harm.

Despite this accumulating evidence, CPET remains underused in routine pediatric oncology follow-up, where surveillance typically focuses on imaging, blood counts, and endocrine function. The authors’ argument is essentially a call to close the gap between what the literature shows and what clinics do. Objective measurement of cardiorespiratory fitness would allow clinicians to identify the most impaired survivors early, track their response to rehabilitation, and intervene before deficits compound into adult cardiovascular disease. It would also standardize outcome measures across trials of exercise interventions, making it easier to compare programs and establish dose-response relationships between training and health outcomes.

For a generation of survivors who will live decades beyond their diagnosis, the message is clear: the heart, lungs, and muscles that carried them through treatment need to be measured, monitored, and trained, not assumed healthy. Cardiopulmonary exercise testing offers a precise, safe, and scientifically validated window into the long-term physiological cost of curing childhood cancer, and, paired with structured exercise prescription, a practical pathway to repairing it. As the survivor population continues to grow, integrating this technology into standard survivorship care may prove to be one of the most consequential steps yet in ensuring that children who beat cancer do not simply survive, but thrive.

Subject of Research: Cardiopulmonary exercise testing to assess cardiorespiratory fitness in childhood cancer survivors

Article Title: Cardiopulmonary exercise testing to measure cardiorespiratory fitness in childhood cancer survivors

Article References: Caru, M., Wilson, R. L., Sholler, C., & Dieli-Conwright, C. M. (2026). Cardiopulmonary exercise testing to measure cardiorespiratory fitness in childhood cancer survivors. Supportive Care in Cancer, 34(10), Article 1068. https://doi.org/10.1007/s00520-026-11285-7

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11285-7

Keywords: cardiopulmonary exercise testing, cardiorespiratory fitness, childhood cancer survivors, VO2peak, pediatric oncology, anthracycline cardiotoxicity, exercise physiology, survivorship care, acute lymphoblastic leukemia, exercise interventions, cardiovascular health, Supportive Care in Cancer

The research, led by Ferdinand Anokwuru and Scott R. Bauer with colleagues at the Charles R. Drew University of Medicine and Science, the San Francisco Coordinating Center, the University of Pittsburgh, Wake Forest University, and other institutions, drew on baseline data from the Study of Muscle, Mobility and Aging, known as SOMMA. This cohort was designed to uncover the cellular biology behind age-related loss of mobility, and it gave the team an unusual opportunity. Rather than relying on questionnaires alone, the investigators measured the actual physiology of energy production and energy expenditure in 629 community-dwelling adults aged seventy and older, then asked whether those measurements tracked with the severity of lower urinary tract symptoms.

The technical core of the study rests on three quantities. The first is VO2peak, the maximum rate of oxygen consumption a person can achieve during a symptom-limited treadmill cardiopulmonary exercise test using a modified Balke protocol. This is the classic measure of cardiorespiratory fitness, the ceiling of the body’s aerobic engine. The second is the energetic cost of walking, abbreviated ECw, defined here as the average oxygen consumption while walking slowly at a fixed treadmill speed of 0.67 meters per second for five minutes. This captures how metabolically expensive it is for an individual to perform one of the most fundamental tasks of daily life. The third quantity is the cost-capacity ratio, or CCR, calculated as one hundred times the energetic cost of walking divided by VO2peak. In plain terms, the CCR expresses what fraction of a person’s total aerobic capacity is consumed simply by walking at a slow pace.

The logic behind the cost-capacity ratio is what makes this study conceptually striking. Two older adults can have identical walking costs but very different fitness levels, and two can have identical fitness levels but very different walking costs. Only the ratio captures the lived experience of effort. When the energy required to move approaches the energy available to move, every step feels harder, and the margin left over for everything else, including the physiological work of maintaining continence and bladder control, shrinks. The researchers hypothesized that this energetic squeeze might be visible in urinary symptoms, which previous work has repeatedly linked to mobility limitation, frailty, and functional decline.

To measure symptoms, the team used the 10-item LURN Symptom Index, a validated instrument that scores lower urinary tract symptoms over the past week on a scale from zero to thirty-eight, with higher scores indicating worse symptoms. They then fitted linear and logistic regression models relating VO2peak, ECw, and CCR to symptom scores and to the presence of urinary incontinence. Crucially, the models were adjusted for a demanding set of potential confounders: demographics, anthropometrics such as body size, smoking status, multimorbidity, and obstetric factors in women. The investigators also tested for interactions by sex, recognizing that the anatomy and physiology of the lower urinary tract differ substantially between men and women.

The results were nuanced but suggestive. In minimally adjusted models, both a higher energetic cost of walking and a higher cost-capacity ratio were associated with worse total scores on the LURN Symptom Index. For the cost-capacity ratio, each one standard deviation increase corresponded to a beta of 0.36 points on the symptom scale, with a ninety-five percent confidence interval of 0.05 to 0.67. When the models were fully adjusted for the complete set of confounders, however, the confidence intervals widened to include zero, meaning these overall associations could no longer be distinguished from chance. The authors are appropriately careful on this point: the evidence points toward a modest association rather than a dramatic one.

One finding did survive full statistical adjustment, and it is the most intriguing result in the paper. A higher energetic cost of walking was associated with significantly greater odds of urinary incontinence in men, with an odds ratio of 1.67 and a confidence interval of 1.10 to 2.54, but the same association was not observed in women. This sex-specific pattern raises questions the study was not designed to answer. In men, incontinence and other lower urinary tract symptoms often arise in the context of prostate enlargement and bladder outlet changes, and it is possible that a metabolically expensive gait pattern reflects underlying vascular or muscular deterioration that also compromises the systems supporting urinary control. In women, obstetric history and pelvic floor mechanics may dominate the symptom picture in ways that swamp any energetic signal.

Notably, VO2peak by itself was not associated with lower urinary tract symptoms in any of the adjusted models. This null result is informative. It suggests that raw aerobic capacity, the sheer size of the engine, matters less than the relationship between that capacity and the cost of using it. A person with a modest VO2peak who walks efficiently may fare as well symptomatically as someone with a larger engine and a costlier gait. This reframing matters for intervention design, because it implies that reducing the energetic cost of walking, through gait retraining, weight management, or improved muscle mitochondrial function, could be as meaningful as raising fitness itself.

The study builds on a growing body of SOMMA research connecting energetics to aging outcomes. Earlier work from the same cohort has shown that lower muscle mitochondrial energetics are associated with greater phenotypic frailty and with multimorbidity burden, and that walking energetics and perceived fatigability interact with gait speed. Prior epidemiological studies have also linked physical activity to urinary health, finding that higher activity levels are associated with lower risk of urinary incontinence in women and reduced lower urinary tract symptom risk in men, while obesity increases risk. The new analysis adds a mechanistic dimension to this literature by proposing a specific physiological pathway, the cost-capacity relationship, through which overall physical condition and urinary symptoms could be connected.

The authors are candid about the limitations. The data are cross-sectional, so the direction of the relationship cannot be established. It is entirely possible that severe urinary symptoms, particularly nocturia that fragments sleep or incontinence that discourages leaving home, lead to reduced physical activity, deconditioning, and a rising cost-capacity ratio rather than the reverse. The associations, where they existed, were modest, and the fully adjusted models attenuated several of them. Still, the paper’s central proposal is compelling: energetic capacity, the balance between what movement costs and what the body can supply, may represent a novel intervention target for the large population of older adults in whom lower urinary tract symptoms and mobility limitations occur together. If future longitudinal and experimental studies confirm the pathway, the humble treadmill walk test could become an unexpected window into urinary health in aging.

Subject of Research: Associations between walking energetics, cardiorespiratory fitness, and lower urinary tract symptoms in older adults

Article Title: Energetic pathway to lower urinary tract symptoms in older adults: associations with cardiorespiratory fitness and walking energetics in the study of muscle, mobility and aging

Article References: Anokwuru, F., Mansfield, T. A., Chen, B. H., Glynn, N. W., Mau, T., Kritchevsky, S. B., McVary, K., Gill, H. K., Barnes, H. N., Goodpaster, B. H., Cummings, S. R., Cawthon, P. M., & Bauer, S. R. (2026). Energetic pathway to lower urinary tract symptoms in older adults: associations with cardiorespiratory fitness and walking energetics in the study of muscle, mobility and aging. GeroScience. https://doi.org/10.1007/s11357-026-02524-0

Image Credits: AI Generated

DOI: 10.1007/s11357-026-02524-0

Keywords: lower urinary tract symptoms, urinary incontinence, aging, cardiorespiratory fitness, VO2peak, walking energetics, cost-capacity ratio, GeroScience, SOMMA, geriatrics, mobility, energy metabolism

The study, published in the Journal of Autism and Developmental Disorders, was conducted by Fatih Mirze and Cihat Demirel of Muş Alparslan University in Turkey. The researchers set out to answer a deceptively simple question: how does flexibility relate to the other components of physical fitness in adults with intellectual disabilities, and do those relationships shift depending on sex, age, or the severity of the disability?

To find out, the team recruited 106 adults between the ages of 18 and 40 and assessed them with the SAMU DIS-FIT battery, a test suite specifically designed and validated for people with intellectual disabilities. The battery covers four domains: body composition, motor performance, musculoskeletal fitness, and cardiorespiratory fitness. Flexibility itself was captured with two distinct measures, the classic Sit-and-Reach Test, which probes the hamstrings and lower back, and the Functional Shoulder Rotation Test, which evaluates the mobility of the shoulder girdle through a rotational movement pattern.

The choice of two flexibility tests matters. Trunk and hip flexibility, as measured by the sit-and-reach, and upper-body joint mobility, as measured by shoulder rotation, reflect different anatomical regions and different functional demands. By including both, the researchers could test whether flexibility behaves as a single unified trait or as a multidimensional component whose various expressions connect to fitness in different ways. The answer, according to the data, leans strongly toward the multidimensional view.

The results revealed a familiar pattern of sex differences in some domains but not in others. Men outperformed women on the Timed Up and Go Test, a measure of mobility and dynamic balance, as well as on the Handgrip Test, the Timed Stand Test, the 30-second Sit-Up Test, and the 6-minute Walk Test. Yet when it came to body composition and to both flexibility measures, the sexes were statistically indistinguishable. That absence of a flexibility gap is notable, because in the general population sex differences in hamstring extensibility are often reported, with men typically showing lower sit-and-reach scores, a difference that has been attributed largely to variations in stretch tolerance rather than tissue properties.

Age and disability severity told a clearer story. Participants aged 19 to 29 posted more favorable values than their older counterparts across most parameters, and participants with mild intellectual disability consistently outperformed those with moderate intellectual disability on most measures. These gradients matter for practice: they suggest that fitness declines and disparities are already detectable in early adulthood within this population, and that the degree of disability shapes physical capacity in ways that assessment protocols and intervention programs must account for.

The core of the study lies in the associations between the two flexibility measures and the rest of the fitness profile. Both the Sit-and-Reach Test and the Functional Shoulder Rotation Test were negatively associated with the Timed Up and Go Test, meaning that more flexible participants completed the mobility task faster. Better flexibility was also linked to stronger muscular performance and to greater walking endurance on the 6-minute Walk Test. The Functional Shoulder Rotation Test carried an additional association, correlating negatively with body composition, so participants with more favorable body composition tended to show greater shoulder mobility.

These findings carry weight because they intersect with an ongoing debate in exercise science. In 2020, a prominent paper in Sports Medicine argued that flexibility should be retired as a major component of physical fitness, contending that its health relevance was overstated and its evidence base thin. That argument was largely built on data from the general population. The new results from adults with intellectual disabilities complicate the picture. In this group, flexibility does not appear to be a decorative extra; it travels with balance, strength, and aerobic capacity, the very qualities that predict independence and quality of life.

The stakes are high for this population. Previous research has repeatedly documented that adults with intellectual disabilities show lower physical fitness than their peers without disabilities, spend more time in sedentary behavior, and face elevated risks of chronic disease. Physical fitness in this group has even been shown to predict five-year survival in older adults, and gait quality is closely tied to fitness levels. If flexibility is woven into that web of associations, then stretching and mobility work may deserve a more deliberate place in exercise programs designed for people with intellectual disabilities, rather than being treated as an optional warm-up ritual.

The authors conclude that flexibility should be addressed alongside other fitness components through a holistic approach to assessment and intervention. Because the study is cross-sectional, it cannot establish whether improving flexibility would directly improve balance, strength, or endurance; the associations could reflect an underlying general physical activity effect, shared biomechanical factors, or causal pathways in either direction. The datasets are not publicly available due to privacy and ethical restrictions, though anonymized data can be requested from the corresponding author with ethics approval. Still, the message for practitioners is concrete: when evaluating or training adults with intellectual disabilities, measuring flexibility at both the trunk and the shoulder, and designing interventions that develop it in concert with strength and aerobic work, may capture a dimension of fitness that standard batteries have too often left out.

Subject of Research: Associations between flexibility and physical fitness parameters in adults with intellectual disabilities

Article Title: Associations Between Flexibility and SAMU DIS-FIT Physical Fitness Parameters in Adults With Intellectual Disabilities: A Cross-Sectional Study

Article References: Mirze, F., & Demirel, C. (2026). Associations Between Flexibility and SAMU DIS-FIT Physical Fitness Parameters in Adults With Intellectual Disabilities: A Cross-Sectional Study. Journal of Autism and Developmental Disorders. https://doi.org/10.1007/s10803-026-07521-y

Image Credits: AI Generated

DOI: 10.1007/s10803-026-07521-y

Keywords: flexibility, intellectual disabilities, physical fitness, SAMU DIS-FIT, Sit-and-Reach Test, shoulder rotation, balance, muscular strength, cardiorespiratory fitness, cross-sectional study, exercise intervention, developmental disabilities