Adults With Overweight and Obesity, Aging, Exercise, Supplementation
Conditions
Keywords
Older adults, Adults with metabolic disorders, Nutritional supplement, Multicomponent exercise, Healthy aging, Quality of life, Non-pharmacological intervention, Randomized controlled trial
Brief summary
Early-onset metabolic disturbances (such as mild hyperglycemia, subclinical dyslipidemia, excess body fat, and reduced functional capacity) represent one of the major public health challenges among middle-aged and older adults. Although body mass index (BMI) remains the primary clinical criterion for classifying excess weight, growing evidence indicates that BMI does not adequately discriminate cardiometabolic risk, particularly in individuals classified as overweight who present elevated body fat levels (Wu et al., 2024). Several studies have identified altered metabolic phenotypes that do not meet the criteria for obesity, including the so-called "metabolically unhealthy normal weight" (MUNW) or "metabolically unhealthy non-obese" phenotypes. These individuals are characterized by excess body fat, central adiposity, and alterations in glucose and lipid metabolism despite having a non-obese BMI (Stefan, 2020). This profile is associated with increased insulin resistance, low-grade systemic inflammation, and elevated cardiovascular risk, underscoring the need for targeted interventions in "metabolically challenged" individuals. Xiong et al. (2024) demonstrated that metabolic health status independently predicts cardiovascular risk, even when BMI is within non-obese ranges. This evidence supports the rationale of the present project: to intervene in a group of adults without clinical obesity (BMI \< 30 kg/m²) but presenting at least two indicators of mild metabolic dysfunction. Nutritional supplements with thermogenic properties that promote fat oxidation and satiety-such as phenylcapsaicin, an analog of capsaicin designed to improve bioavailability and reduce pungency, thereby enhancing tolerability in adults-may offer a promising complementary strategy. Recent studies have shown that low doses of phenylcapsaicin were sufficient to increase fat oxidation during exercise, reduce respiratory exchange ratio, and lower maximal heart rate during submaximal testing compared with placebo (Jiménez-Martínez et al., 2023a). Furthermore, additional research reported that phenylcapsaicin improved strength performance, reduced perceived exertion, and attenuated markers of muscle damage following resistance training (Jiménez-Martínez et al., 2023b). These findings suggest that thermogenic and fat-oxidation-enhancing supplementation may act as a safe and effective metabolic modulator, particularly when combined with exercise, positioning it as an innovative strategy for adults presenting mild metabolic risk. The present study would integrate: (1) a multicomponent functional exercise program designed to improve strength, balance, and aerobic capacity in older adults; (2) a thermogenic and fat-oxidation-enhancing nutritional supplement as a safe metabolic activation strategy; (3) a standardized dietary control protocol to isolate the specific effects of the supplementation; (4) dual-energy X-ray absorptiometry (DXA) for precise body composition assessment; (5) hormonal and lipid biomarkers to evaluate underlying physiological mechanisms; and (6) validated questionnaires addressing quality of life, sleep, and appetite to capture the holistic dimension of this stage of adulthood. This multidimensional approach would provide an innovative intervention for a growing yet underexplored population: non-obese but metabolically challenged adults at increasing cardiometabolic risk. References: * Jiménez-Martínez P, Sánchez-Valdepeñas J, Cornejo-Daza PJ, Cano-Castillo C, Asín-Izquierdo I, Alix-Fages C, Pareja-Blanco F, Colado JC. Effects of different phenylcapsaicin doses on neuromuscular activity and mechanical performance in trained male subjects: a randomized, triple-blinded, crossover, placebo-controlled trial. Front Physiol. 2023a Aug 2; 14: 1215644. * Jiménez-Martínez P, Cornejo-Daza PJ, Sánchez-Valdepeñas J, Asín-Izquierdo I, Cano-Castillo C, Alix-Fages C, Pareja-Blanco F, Colado JC. Effects of different phenylcapsaicin doses on resistance training performance, muscle damage, protein breakdown, metabolic response, ratings of perceived exertion, and recovery: a randomized, triple-blinded, placebo-controlled, crossover trial. J Int Soc Sports Nutr. 2023b Dec; 20 (1): 2204083. * Stefan N. Metabolically healthy and unhealthy normal weight and obesity. Endocrinol Metab (Seoul). 2020 Sep;35(3):487-493. * Xiong Q, Zang Y, Li J, An Y, and Yu S. Comparison of cardiovascular disease risk association with metabolic unhealthy obesity identified by body fat percentage and body mass index: Results from the 1999-2020 National Health and Nutrition Examination Survey. PLoS One. 2024 Aug 14; 19 (8): e0305592. * Wu Y, Li D, and Vermund SH. Advantages and limitations of the body mass index (BMI) to assess adult obesity. Int J Environ Res Public Health. 2024 Jun 10; 21 (6): 757.
Detailed description
The present project is designed as a longitudinal, randomized, controlled, parallel-group, triple-blind clinical trial, with a 12-week active intervention and pre- and post-intervention assessments. The study will be conducted at a single center (single-center trial) and will include two parallel groups: * Experimental group: multicomponent functional exercise + thermogenic and appetite-modulating nutritional supplement. * Control group: multicomponent functional exercise + placebo supplement (identical in appearance, without active ingredient). Randomization will be performed using balanced block allocation, stratified by sex and baseline body fat percentage, with a 1:1 allocation ratio. The study will be triple-blind: * Participants, * The intervention and assessment team, * And the statistician responsible for data analysis will remain unaware of group allocation (experimental or control). The design corresponds to a comparative efficacy trial aimed at evaluating the additional effect of the nutritional supplement compared to placebo, while maintaining identical exercise programming and dietary control in both groups. This approach allows isolation of the specific impact of the supplement on body composition, metabolic function, functional capacity, and perceived health in adults with a metabolically challenged profile but without clinical obesity. As is standard practice, participants will be informed that their allocation may correspond to either the placebo or experimental group, without disclosure of their actual assignment. As appropriate in experimental studies, standardized collection of biological samples and psychometric and perceived health data will be conducted at pre- and post-intervention time points to quantify changes in these metrics and analyze them as dependent variables of the applied protocol.
Interventions
DIETARY_SUPPLEMENTGroup 1: Exercise + thermogenic supplement (EX-TS)
Participants in this group will receive an oral daily dose of the nutritional supplement with thermogenic and appetite-modulating effects in combination with a supervised multicomponent functional program (3 sessions per week, 60 minutes each) for 12 weeks, composed by three exercise blocks: 1) joint mobility and postural control exercises block, 2) functional strength block with three sets of two strength exercises using elastic bands at 70%-85 of 1RM (RPE 6-7 at the beginning and 9 at the end of the set) and, 3) coordination and agility exercises block. Participants will undergo a standardized dietary control plan based on Individualized energy deficit equivalent to 0.7% of body weight per week, adjusted using the Harris-Benedict equation, and macronutrient distribution: protein: 2 g/kg; fat: 0.8 g/kg; remaining energy intake allocated to carbohydrates.
DIETARY_SUPPLEMENTGroup 2: Exercise + placebo supplement (EX-PL)
Participants in this group will receive a placebo supplement identical in appearance, color and taste to the active supplement, together with the same multicomponent functional exercise program and dietary control for 12 weeks.
Sponsors
University of Valencia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Individuals will be eligible to participate in the study if they meet all of the following criteria: 1. Age: Between 50 and 65 years at the time of screening. 2. Weight status (non-obese): Body mass index (BMI) between 25.0 and 29.9 kg/m² (overweight range, without clinical obesity). 3. Metabolically challenged profile (non-obese): Presence of at least two of the following criteria, in addition to the specified BMI range: A) Altered body composition (primary criterion): Body fat percentage ≥ 30% in women or ≥ 25% in men, assessed by DXA. B) Borderline metabolic markers (one or more): * Fasting glucose: 100-125 mg/dL * Triglycerides: ≥ 150 mg/dL * HDL cholesterol: \< 50 mg/dL in women or \< 40 mg/dL in men * LDL cholesterol: ≥ 130 mg/dL C) Sedentary lifestyle: Low or very low physical activity level, defined as ≤ 600 MET·min/week according to the IPAQ questionnaire. 4. Clinical and functional status: * Clinically stable condition, without acute disease or recent decompensation. * Ability to perform moderate-intensity exercise three times per week, according to medical assessment. 5. Previous treatment and lifestyle: * No participation in structured exercise programs (≥ 2 days/week) during the previous 6 months. * No intensive hypocaloric diets or medical weight-loss treatments during the previous 3 months. 6. Administrative and ethical aspects: * Ability to understand study explanations and follow instructions. * Signed informed consent prior to initiation of any study procedures.
Exclusion criteria
Individuals presenting any of the following conditions will be excluded from the study: 1. Clinical obesity or anthropometric extremes: * BMI ≥ 30.0 kg/m² (obesity). * Any weight-related or clinical condition that, in the judgment of the principal investigator, contraindicates participation. 2. Relevant or uncontrolled chronic diseases: * Previous diagnosis of type 1 or type 2 diabetes mellitus. * Moderate or severe cardiovascular disease (e.g., ischemic heart disease, heart failure, uncontrolled clinically significant arrhythmias). * Moderate or severe renal, hepatic, or respiratory disease. * Neurological or musculoskeletal disorders limiting or contraindicating the prescribed exercise program. 3. Pharmacological treatments interfering with energy metabolism or body weight: Current use (or use within the previous 3 months) of: * Weight-loss medications or GLP-1 receptor agonists * Systemic corticosteroids at moderate or high doses * Thyroid hormones at non-replacement doses * Anabolic agents or other drugs significantly affecting body composition 4. Specific prior supplementation: Use of capsaicin, phenylcapsaicin, or other thermogenic or appetite-modulating supplements within the previous 3 months. 5. Functional or cognitive limitations: * Cognitive, psychiatric, or mental health disorders that may impair study comprehension or protocol adherence. * Physical limitations preventing safe participation in exercise. 6. Substance use: * Alcohol consumption at levels considered high risk (\> 20 g/day). * Heavy smoking (\> 10 cigarettes/day), unless deemed clinically stable by the investigator. 7. Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in body composition via Dual-Energy X-ray Absorptiometry (DXA) | Pre and post-intervention of 12 weeks | Whole body and segmental composition will be assessed through Dual-Energy X-ray Absorptiometry (DXA). Parameters analyzed will be: total and regional fat mass and lean mass |
| Change in fat distribution via Dual-Energy X-ray Absorptiometry (DXA) | Pre and post-intervention of 12 weeks | Android/gynoid fat distribution will be analyzed through Dual-Energy X-ray Absorptiometry (DXA). |
| Change in hormonal biomarkers (glucagon-like peptide-1;GLP-1) | Pre and post-intervention of 12 weeks | glucagon-like peptide-1 (GLP-1) will be collected through a blood sample in the morning in a fasted state to assess hormonal state |
| Change in hormonal biomarkers (acylated ghrelin) | Pre and post-intervention of 12 weeks | Acylated ghrelin levels will be collected through a blood sample in the morning in a fasted state to assess hormonal state |
| Change in hormonal biomarkers (leptin) | Pre and post-intervention of 12 weeks | Leptin levels will be collected through a blood sample in the morning in a fasted state to assess hormonal state |
| Change in metabolic biomarkers (glucose) | Pre and post-intervention of 12 weeks | Glucose levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state. |
| Change in metabolic biomarkers (total cholesterol) | Pre and post-intervention of 12 weeks | Total cholesterol levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state. |
| Change in metabolic biomarkers (HDL cholesterol) | Pre and post-intervention of 12 weeks | HDL cholesterol levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state. |
| Change in metabolic biomarkers (LDL cholesterol) | Pre and post-intervention of 12 weeks | LDL cholesterol levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state. |
| Change in metabolic biomarkers (triglycerides) | Pre and post-intervention of 12 weeks | Triglycerides levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state. |
| Change in metabolic biomarkers (creatine) | Pre and post-intervention of 12 weeks | Creatinine levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state. |
| Change in metabolic biomarkers (aspartate aminotransferase; ATS) | Pre and post-intervention of 12 weeks | AST (Aspartate aminotransferase) levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in body composition via bioelectrical impedance analysis (BIA) | Pre and post-intervention of 12 weeks | Whole body fat-free mass will be assessed through bioelectrical impedance analysis (BIA) |
| Changes in distance covered/aerobic capacity | Pre and post-intervention of 12 weeks | Distance covered/aerobic capacity will be assessed through the 6- Minute walking test |
| Changes in lower limb strength | Pre and post-intervention of 12 weeks | Lower limb strength will be assessed through the 30-second Chair Stand Test |
| Changes in agility and dynamic balance | Pre and post-intervention of 12 weeks | Agility and dynamic balance will be assessed through the Timed Up and Go Test |
| Changes in handgrip strength | Pre and post-intervention of 12 weeks | Handgrip strength will be assessed through the Handgrip dynamometry (Jamar Hand Dynamometer). |
| Changes in quality of life specific for older adults | Pre and post-intervention of 12 weeks | Quality of life will be assessed through the World Health Organization Quality of Life-OLD (WHOQOL-OLD) questionnaire |
| Changes in general quality of life | Pre and post-intervention of 12 weeks | Quality of life will be assessed through the Short Form-36 Health Survey (SF-36) questionnaire |
| Changes in general health perception | Pre and post-intervention of 12 weeks | General health perception will be assessed through the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) questionnaire |
| Change in sleep quality | Pre and post-intervention of 12 weeks | Sleep quality will be assessed through Pittsburgh Sleep Quality Index |
| Change in perceived insomnia | Pre and post-intervention of 12 weeks | Perceived insomnia will be assessed through the Insomnia Severity Index |
| Change in eating behavior | Pre and post-intervention of 12 weeks | Eating behavior will be assessed through the Emotional Eater Questionnaire |
| Change in appetite behavior | Pre and post-intervention of 12 weeks | Appetite behavior will be assessed through the Simplified Nutritional Appetite Questionnaire |
| Anthropometric changes (waist and hip circumferences) | Pre and post-intervention of 12 weeks | Waist circumference and hip circumference will be measured |
| Anthropometric changes (waist -hip index) | Pre and post-intervention of 12 weeks | waist -hip index will be measured |
| Anthropometric changes (waist to height index) | Pre and post-intervention of 12 weeks | waist to height index will be measured |
Countries
Spain
Contacts
CONTACTJuan Carlos Colado Sánchez, Chair full professor
Outcome results
None listed