Effects of Physical Exercise and a Nutritional Supplement on Body Composition, Metabolic Function, and Overall Health in Adults With a Metabolically Challenging Profile

NCT07504068 | Recruiting

• 1 other identifier: 2025-FIS-4275027
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Aging; Adults With Overweight and Obesity; Supplementation; Exercise

Keywords

Older adults; Adults with metabolic disorders; Nutritional supplement; Multicomponent exercise; Healthy aging; Quality of life; Non-pharmacological intervention; Randomized controlled trial

Outcome Measures

Primary Outcomes (12)

• Change in body composition via Dual-Energy X-ray Absorptiometry (DXA)

  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

  Pre and post-intervention of 12 weeks

• Change in fat distribution via Dual-Energy X-ray Absorptiometry (DXA)

  Android/gynoid fat distribution will be analyzed through Dual-Energy X-ray Absorptiometry (DXA).

  Pre and post-intervention of 12 weeks

• Change in hormonal biomarkers (glucagon-like peptide-1;GLP-1)

  glucagon-like peptide-1 (GLP-1) will be collected through a blood sample in the morning in a fasted state to assess hormonal state

  Pre and post-intervention of 12 weeks

• Change in hormonal biomarkers (acylated ghrelin)

  Acylated ghrelin levels will be collected through a blood sample in the morning in a fasted state to assess hormonal state

  Pre and post-intervention of 12 weeks

• Change in hormonal biomarkers (leptin)

  Leptin levels will be collected through a blood sample in the morning in a fasted state to assess hormonal state

  Pre and post-intervention of 12 weeks

• Change in metabolic biomarkers (glucose)

  Glucose levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state.

  Pre and post-intervention of 12 weeks

• Change in metabolic biomarkers (total cholesterol)

  Total cholesterol levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state.

  Pre and post-intervention of 12 weeks

• Change in metabolic biomarkers (HDL cholesterol)

  HDL cholesterol levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state.

  Pre and post-intervention of 12 weeks

• Change in metabolic biomarkers (LDL cholesterol)

  LDL cholesterol levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state.

  Pre and post-intervention of 12 weeks

• Change in metabolic biomarkers (triglycerides)

  Triglycerides levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state.

  Pre and post-intervention of 12 weeks

• Change in metabolic biomarkers (creatine)

  Creatinine levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state.

  Pre and post-intervention of 12 weeks

• Change in metabolic biomarkers (aspartate aminotransferase; ATS)

  AST (Aspartate aminotransferase) levels will be collected through a blood sample in the morning in a fasted state to assess metabolic state.

  Pre and post-intervention of 12 weeks

Secondary Outcomes (15)

• Change in body composition via bioelectrical impedance analysis (BIA)

  Pre and post-intervention of 12 weeks

• Changes in distance covered/aerobic capacity

  Pre and post-intervention of 12 weeks

• Changes in lower limb strength

  Pre and post-intervention of 12 weeks

• Changes in agility and dynamic balance

  Pre and post-intervention of 12 weeks

• Changes in handgrip strength

  Pre and post-intervention of 12 weeks

Other Outcomes (5)

• Adherence to supplement and exercise

  Every day for nutritional supplement and each exercise session during the 12 weeks of intervention.

• Demographic characteristics (age)

  Pre and post-intervention of 12 weeks

• Demographic characteristics (sex)

  Pre and post-intervention of 12 weeks

Study Arms (2)

Group 1: Exercise + thermogenic supplement (EX-TS)

EXPERIMENTAL

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 exercise program (3 sessions per week, 60 minutes each) for 12 weeks

Dietary Supplement: Group 1: Exercise + thermogenic supplement (EX-TS)

Group 2: Exercise + placebo supplement (EX-PL)

PLACEBO COMPARATOR

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 for 12 weeks

Dietary Supplement: Group 2: Exercise + placebo supplement (EX-PL)

Interventions

Group 1: Exercise + thermogenic supplement (EX-TS) DIETARY_SUPPLEMENT

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.

Group 1: Exercise + thermogenic supplement (EX-TS)

Group 2: Exercise + placebo supplement (EX-PL) DIETARY_SUPPLEMENT

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.

Group 2: Exercise + placebo supplement (EX-PL)

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: Between 50 and 65 years at the time of screening.
• Weight status (non-obese): Body mass index (BMI) between 25.0 and 29.9 kg/m² (overweight range, without clinical obesity).
• 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.
• 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.
• Previous treatment and lifestyle:

You may not qualify if:

• 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.
• 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.
• 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
• Specific prior supplementation: Use of capsaicin, phenylcapsaicin, or other thermogenic or appetite-modulating supplements within the previous 3 months.

Sponsors & Collaborators

• University of Valencia: lead

Study Sites (1)

Physical activity and Sport Science Faculty

Valencia, Valencia, 46010, Spain

RECRUITING

MeSH Terms

Conditions

Obesity; Motor Activity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Central Study Contacts

Juan Carlos Colado Sánchez, Chair full professor

CONTACT

(9639) 83470; juan.colado@uv.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chaired Full Professor of Physical Education

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: March 31, 2026
• Study Start: March 25, 2026
• Primary Completion: July 30, 2026
• Study Completion: July 30, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

ES (1)