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Open research questions in Nutrition and Health in Aging

100 unresolved questions extracted from the limitations and future-work sections of 661 Nutrition and Health in Aging papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Background Several triglyceride-glucose (TyG)-related indices are used to assess insulin resistance (IR), but the better indicator for patients with cancer remains undetermined.

    Association of TyG-BMI and malnutrition with reduced survival outcomes in patients with cancer: a prospective study · 2026 · DOI

  • Abstract Introduction Malnutrition affects more than 25% of hospitalized older adults, is often underrecognized, and is associated with adverse clinical outcomes.

    Improving healthcare staff awareness of malnutrition in acute geriatric care: a European multicenter quality improvement project · 2026 · DOI

  • 3%); however, it should be noted that these rankings were primarily based on indirect comparisons with a limited evidence base, and the results should be interpreted with caution.

    Effectiveness of different modes of digital health interventions for sarcopenia in older adults: a systematic review and network meta-analysis · 2026 · DOI

  • Background Sarcopenia is prevalent in heart failure (HF), but its role in incident HF and underlying metabolic mechanisms remains unclear.

    Sarcopenia and Its Associated Metabolic Profile Predict Incident Heart Failure: A Prospective Cohort Study of 267 335 Adults in the UK Biobank · 2026 · DOI

  • Finally, the medi- ating effect of depression was relatively modest, suggesting that addi- tional biological or behavioral pathways may also contribute to the association between handgrip strength decline and cardiovascular disease risk and warrant further exploration (14).

    Trajectories of grip strength decline and risk of new-onset cardiovascular disease: evidence from the HRS and ELSA cohorts · 2026 · DOI

  • Furthermore, trials combining personalized nutritional support, targeted resistance exercise, and medication optimization strategies are warranted to determine the most effective multidomain approaches for preserving function and improving quality of life in this highly vulnerable population.

    Nutrition, functional status, polypharmacy, and digestive disturbances in institutionalized patients with dementia: insights from comprehensive screening at admission · 2026 · DOI

  • While consensus definitions are essential for standard- ization, midlife women expose a remaining gap: early decline may be dominated by deteriorating muscle quality and strength and may therefore be under-recognized by BMI/WC-anchored screening in the absence of menopause-calibrated thresholds.

    Adipose–muscle crosstalk during the menopausal transition: mechanistic links to sarcopenic obesity in midlife women · 2026 · DOI

  • Abstract Aim Sarcopenia, defined as progressive loss of skeletal muscle mass and function, may influence cardiovascular outcomes, yet its prognostic role after myocardial infarction (MI) remains uncertain.

    Prognostic Impact of Sarcopenia Following Myocardial Infarction: A Systematic Review and Meta-analysis of Mortality and Recurrent MI · 2026 · DOI

  • Aim: Myostatin (MSTN) and Brain-Derived Neurotrophic Factor (BDNF) are muscle-related biomarkers involved in muscle metabolism, but their roles in detecting sarcopenia in critically ill patients remain unclear.

    Myostatin and BDNF as potential biomarkers of sarcopenia in ICU patients: A radiologic and biochemical correlation study · 2026 · DOI

  • Conclusions: Although the BCA parameters SM/B and, to a lesser extent, SAT/B appear to be promising biomarkers, external validation and investigation within well-defined patient subgroups are warranted to establish their generalizability in clinical practice.

    Automated Pretreatment Thoracic CT-Based Body Composition Analysis Predicts Progression-Free Survival in Head and Neck Cancer · 2026 · DOI

  • Abstract Introduction Telemedicine provides outcomes comparable to in-person follow-up after Metabolic Bariatric Surgery (MBS), but evidence on multicomponent online interventions in the late postoperative period remains scarce.

    Multicomponent Online Intervention Improves Sarcopenia-Related Traits Following Long-Term Metabolic Bariatric Surgery: A Randomized Clinical Trial · 2026 · DOI

  • Although the Geriatric Nutritional Risk Index (GNRI), a simple nutritional assessment tool, has been associated with prognosis in various diseases, its impact on ICU admission risk following gastrointestinal tumor surgery remains unclear.

    Preoperative low Geriatric Nutritional Risk Index increases intensive care unit admission risk in patients undergoing gastrointestinal tumor surgery · 2026 · DOI

  • Author contributions Strengths of this umbrella review include a strict exercise-based retention rule, six-database search, independent screening and extrac- tion, AMSTAR-2 appraisal, CCA calculation and conservative inter- pretation of review-level estimates. The approach clarified which conclusions were truly exercise-based and prevented nutrition-only or other non-exercise interventions from driving the primary narrative. Several limitations should be acknowledged. First, the strict main pool was deliberately narrow, which improved interpretabil- ity but excluded adjacent reviews that examined broader non- pharmacological or mixed exercise-nutrition management, including Yu et al. (41). Second, our unit of analysis was the pub- lished review-level estimate; we did not reconstruct all primary- study datasets or conduct a new primary-study meta-analysis. Third, effect measures, SO definitions and intervention protocols varied across reviews, preventing valid statistical re-pooling. Fourth, AMSTAR-2 appraised review quality rather than out- come-level certainty, and a formal de novo GRADE assessment, JBI evidence grading, or CINeMA assessment for the network component was not performed because these approaches would require reconstruction and reappraisal of every primary trial across overlapping reviews, including trial-level risk-of-bias and evidence-domain judgments. Instead, we applied conservative umbrella-level low/very-low certainty qualifiers, which should not be interpreted as formal GRADE, JBI or CINeMA ratings. Fifth, safety, adherence and dropout reporting was inconsistent across source reviews and could not be synthesized robustly. Sixth, the high overlap means that agreement across reviews should be read as consistency of published synthesis rather than independent confirmation.

    Exercise-based interventions for sarcopenic obesity in middle-aged and older adults: an umbrella review of systematic reviews with pairwise meta-analyses and network meta-analyses · 2026 · DOI

  • Strengths include a nationally representative NHANES sample with National Death Index linkage and a median follow-up exceeding a decade; survey-weighted analysis with multiple imputation; and restricted cubic-spline modeling of non-linear dose–response relationships. The within-cohort comparison of three index categories provides directly comparable evidence, and sensitivity analyses (landmark, complete-case, and dietary- adjusted) converged on the same conclusions. This study has limitations. First, the cohort is heterogeneous (congestive heart failure, coronary heart disease, angina, myocardial infarction, stroke), and NHANES lacks cardiac- specific characterization such as left ventricular ejection fraction or natriuretic peptides; the 20 findings should not be extrapolated to phenotype-specific decisions without validation in cohorts with detailed cardiac phenotyping. Second, the comparison between the nutritional indices and the SII is conceptually asymmetric: the former integrate a chronic exposure and the latter reflects an acute snapshot. Third, all indices were measured at a single visit, precluding evaluation of longitudinal trajectories. Finally, despite multivariable adjustment, multiple imputation, and sensitivity analyses, residual confounding cannot be excluded.

    Comparative prognostic performance of nutritional, immune-inflammatory, and anthropometric indices for cardiovascular and all-cause mortality in older adults with cardiovascular disease (NHANES 2009–2018) · 2026 · DOI

  • This review has few limitations. The inclusion of studies published between 2018 and 2025 may have excluded earlier evidence relevant to longterm in adolescent nutrition. The heterogeneity of study designs, populations, and outcome measures limited direct comparability and precluded quantitative synthesis. A large included studies were crossproportion of sectional, inference. Additionally, reliance on self-reported dietary data may reporting bias.

    ADOLESCENT NUTRITION AND HEALTH IN LOW- AND MIDDLE-INCOME COUNTRIES: A SCOPING REVIEW OF THE DOUBLE BURDEN, DIETARY TRANSITIONS, AND INTERVENTION GAPS · 2026 · DOI

  • Several significant limitations must be acknowledged when interpreting our study findings. Firstly, we cannot exclude the possibility of confounding in this observational study, which may have influenced our conclusions even after adjusting for available clinical factors. For example, a competing risk of death may be incurred by participants who died during follow-up before the repeated measurements. It is possible that these participants were more likely to have sarcopenia. It is difficult to estimate how excluding these participants affected the results, although excluding more sarcopenia individuals may have attenuated the observed effects. Nevertheless, our findings provide novel supporting evidence of early cardio-sarcopenia occurring over time in a communitybased adult population. Second, our multilevel mixedeffects models did not include detailed longitudinal data on physical activity or specific pharmacological treatments. Direct measures of functional capacity, such as VO2peak, were unavailable. Since regular exercise influences remodeling differently from sedentary behavior, this absence of data limits our ability to adjust for physical activity as a confounding factor. Additionally, we could not account for specific medications that influence cardiac function, particularly beta-blockers and reninangiotensin system inhibitors. To address these limitations, we adjusted our models for hemodynamic loading conditions, specifically mean arterial pressure and pulse pressure. These adjustments reflect key pathways through which antihypertensive agents influence left ventricular mass. While some residual confounding from non-hemodynamic drug effects or physical activity may still exist, we believe that the observed parallel decline likely reflects a fundamental aging process in this community-dwelling cohort. Several design features were implemented to minimize potential bias from unmeasured factors. For example, participants with structural heart disease, such as reduced ejection fraction or significant valvular disease, were excluded. This approach reduces the inclusion of individuals requiring high doses of guideline-directed medical therapies, which could significantly distort natural cardiac remodeling. Regarding potential mechanisms, we proposed that shared factors, such as inflammaging and cellular senescence, are plausible drivers of the observed parallel declines; however, our analysis did not include concurrent inflammatory Wong et al. BMC Medicine (2026) 24:317 Page 11 of 14 biomarkers, which limits our understanding of these connections.

    Skeletal and cardiac muscle longitudinal associations in the Baltimore Longitudinal Study of Aging (BLSA) · 2026 · DOI

  • Based on the high prevalence of sarcopenia identified in this study, regular screening for muscle loss using easily accessible markers such as BMI, serum phosphorus, and eGFR should be integrated into routine clinical assess- ment of transfusion-dependent β-thalassemia (TDT) patients. Early intervention through nutritional opti- mization, correction of hyperphosphatemia, and close monitoring of renal function is essential to mitigate the risk of progressive muscle wasting. Additionally, indi- vidualized exercise and rehabilitation programs should be encouraged to enhance muscle mass and functional performance. Optimizing transfusion regimens and ensuring adherence to chelation therapy may further help reduce the impact of chronic anemia and iron overload on muscle health. A multidisciplinary approach involving hematologists, nephrologists, nutrition specialists, and physiotherapists is recommended to address the mul- tifactorial nature of sarcopenia in TDT. Finally, further longitudinal studies with larger cohorts are warranted to validate these findings and assess the effectiveness of targeted interventions in improving musculoskeletal outcomes and overall quality of life in this growing adult population.

    Skeletal muscles index in Egyptian adults with transfusion dependent Beta thalassemia · 2026 · DOI

  • The relatively small sample size (n = 100) and single- center, high cost of laboratory investigations and CT, cross-sectional design may limit the generalizability and causal interpretation of the findings. Results may have been influenced by variations in chelation therapy, nutri- tion, and transfusion frequency, and residual confound- ing from unmeasured factors such as inflammation or hormonal imbalance cannot be excluded. In addition, the diagnostic cutoffs derived from this cohort may overesti- mate accuracy and require external validation.

    Skeletal muscles index in Egyptian adults with transfusion dependent Beta thalassemia · 2026 · DOI

  • Future research should focus on identifying optimal treatment strategies that improve both clinical and economic outcomes. The absence of validated algorithms for cachexia identification in Japanese claims data represents an important limitation; our reliance on ICD-10 codes C80 and R64 likely captures only cases in which clinicians explicitly documented cachexia, missing patients who met clinical criteria but were not formally diagnosed. Finally, we could not assess QOL, nutritional status, or clinical severity metrics, which would provide deeper mechanistic insights.

    Economic Burden of Cachexia in Japanese Lung Cancer Patients: A Retrospective Claims Database Analysis · 2026 · DOI

  • First, a methodological limitation of this study is the potential for parameter estimation bias arising from the non-normal distribution of the latent trait in our sample. Furthermore, due to the cross-sectional observational nature of this study and the lack of longitudinal fol- low-up, the predictive validity of the ICF-based model could not be assessed.

    Nutrition-associated health levels in cancer patients based on the ICF: an expanded study of 300 cases · 2026 · DOI

  • Third, the present study did not perform stratified analyses by age and gender, and the optimal ZJU index cut-off values for sarcopenia prediction in different age and gender subgroups remain to be elucidated.

    Correlation between ZJU index and sarcopenia in elderly inpatients and its predictive value · 2026 · DOI

  • The feasibility of using CT-derived body composition assessments for risk stratification and intra-patient monitoring to inform treatment plan adjustments warrants further research.

    Characterization of body composition dynamics throughout treatment in patients with early-stage breast cancer · 2026 · DOI

  • The incidence of successful aging in this study was only 2.76%, a rare outcome. Although core conclusions were verified by Firth correction, the small number of positive events in some subgroups and trajectory groups limited statistical power.

    Grip strength indicators and successful aging among middle-aged and older adults: evidence from the CHARLS cohort · 2026 · DOI

  • The GBTM approach used to map muscle loss could similarly be applied to other dynamic organ functions in intensive care, such as renal recovery trajectories or cognitive decline patterns.

    Sarcopenia Index trajectories predict long-term mortality in super-elderly patients with sepsis: a retrospective cohort study · 2026 · DOI

  • Future research should aim to integrate SI trajectories with inflammatory panels (e.g., IL-6) and comprehensive geriatric assessments to create a multidimensional prognostic model that better captures the heterogeneity of the super-elderly.

    Sarcopenia Index trajectories predict long-term mortality in super-elderly patients with sepsis: a retrospective cohort study · 2026 · DOI

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100 open questions have been extracted from the limitations and future-work passages of 661 Nutrition and Health in Aging papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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