Clinical Research Directory

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

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.

Administration of Fiber as a Dietary Supplement to Improve the Management of Alcohol Withdrawal

The goal of this clinical trial is to demonstrate that a fiber-enriched diet (with a high proportion of inulin and pectin) combined with standard care can reduce intestinal permeability in patients with alcohol use disorder (AUD) aged between 19 and 65. The hypothesis of our study is that a diet rich in different dietary fibers (mainly inulin and pectin), by modifying the gut microbiota and its metabolites, will induce a decrease in intestinal permeability, restore the composition of the gut microbiota and its metabolites, and further improve abstinence, levels of craving and anxiety, inflammation, steatosis, and hepatic fibrosis in patients with alcohol use disorder. The study consists of two parallel groups (a group eating fiber-rich snacks every day for 28 days (in addition to their usual care) versus a group not eating any snacks). Participants will be required to provide stool, blood, and saliva samples, and complete questionnaires.

Effects of Chronic Creatine and Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Oxidative Stress, Inflammation, Muscle Strength, and Body Composition in Individuals With Down Syndrome

Purpose: This study will test whether 8 weeks of creatine and HMB supplementation can improve muscle strength, body composition, balance, and overall health in people with Down syndrome. Participants will also receive nutrition tips during the study. Who can participate: People with Down syndrome who can perform basic physical tasks. Must provide consent from the participant and legal guardian. What participants will do: Take creatine (3 g/day) and HMB (3 g/day) or placebo for 8 weeks. Complete tests for muscle strength, balance, and cognitive function. Undergo body composition scans and give blood samples for health markers. Timing: All tests and blood samples are taken before and after each 8-week period. Importance: Results will help determine if creatine and HMB can safely improve strength, balance, and overall health in people with Down syndrome.

Effect of a Short-term Multi-strain Probiotic Supplementation in Endurance Athletes

The aim of this project is to evaluate and identify the effect of a short-term 2-week multi-strain probiotic (MPRO) supplementation on the exercise-associated gastrointestinal (GI) symptoms and perturbations in high level female athletes of the Polish national team during strictly controlled conditions of a training camp, based on recommendations for best practices for probiotic (PRO) research in athletes and assessment of EX-associated GI perturbations.

Effects of β-alanine and Sodium Bicarbonate Supplementation on Physical Capacity and Biochemical Markers Concentrations

This randomized, double-blind, placebo-controlled, parallel-group study aims to evaluate the potential synergistic effect of beta-alanine (BA) and sodium bicarbonate (SB) supplementation, compared to their separate administration or placebo (PL), on physical performance and selected blood biochemical markers in highly trained female basketball players.

Evaluation of the Effects of Two Dietary Supplement Formulations on the Lipid Profile in Mild Hypercholesterolemia

A single-center, randomized, parallel-group, double-blind, placebo-controlled clinical study followed by an open-label phase to evaluate the effects of a new formulation of a supplement on lipid profile in subjects with mild hypercholesterolemia who are non-responsive to the Mediterranean diet. The study population consists of 99 subjects with mild hypercholesterolemia who are non-responsive to the Mediterranean diet. The participants will be divided into three groups: Group A: Test Product A (study product) Group B: Test Product B (comparative product) Placebo group: placebo The following visits are scheduled during the study: T-2 (day -35) - Screening visit, 5 weeks before T0 T-1 (day -28) - Enrollment visit, 4 weeks before T0 T0 (day 0) - Randomization visit, baseline T1 (day 56) - Interim visit, 8 weeks after T0 T2 (day 112) - Final visit, 16 weeks after T0 After the first 8 weeks of the study (double-blind), all three groups will continue with only Product A for an additional 8 weeks. This experimental design aims to highlight whether any differences between Test Product A and Test Product B observed during the first 8 weeks can be minimized when both arms receive the same treatment. Additionally, the effect of Product A will be observed at 8 and 16 weeks, thus providing efficacy data over a longer treatment period. This may also provide insights into the potential achievement of a plateau. Regarding the placebo group, it will be possible to distinguish the effect of the diet alone from the combined effect of the diet and supplementation with Test Product A.

Maternal Adherence to MMS in Nepal

Although clinical studies highlight the value of MMS for pregnant and lactating women, implementation research studies are necessary to understand adherence and acceptability to the product and to uncover potential obstacles to implementation in specific contexts. For Nepal, it is crucial to establish whether adherence to MMS supplementation is non-inferior to the existing IFA supplementation for 180 tablets, which has a high (65%) adherence rate. It is also important to investigate how whether providing MMS in bottles (containing a substantial quantity, such as 90 count bottles twice during pregnancy) might impact ANC utilization, particularly in terms of ensuring that pregnant women attend at least eight ANC visits. Furthermore, assessment of MMS acceptability, including pill taste, smell, size, swallowability, side effects, benefits as well as aspects such as product labeling and packaging, among end users in Nepal, is needed to understand acceptability of MMS vs. IFA. Finally, implementation issues within the health system, including the need of trainings for healthcare workers' and, female community health volunteers (FCHVs)' training needs; and government stakeholders' interest and barriers;; community s Social and behavioral change communication needs, and issues around supply chain issues should be well-understood and documented to inform prior to scale-up to support a smooth transition of MMS. Thus, Helen Keller International, in collaboration with Nepal's Ministry of Health and Population (MoHP) and the Eleanor Crook Foundation (ECF), will conduct a set of four mixed-methods studies to generate evidence and insights that inform the development of an MMS supplementation strategy. This trial in one province of Nepal is the first study that will be complemented by one additional quantitative study and two qualitative studies to generate evidence on the topics mentioned.

Caffeine Kinetics and CrossFit®-Specific Performance

The study aims at assessing the relation between caffeine (CAF) and paraxanthine (PAX) kinetics after acute ingestion of caffeine (3 mg/kg body mass) in the form or mono- or multi-ingredient preparations and CrossFit®-specific performance or selected indicators of psychophysiological state. Blood indicators of muscle damage/recovery, acid-base balance and electrolytes levels will be evaluated. The impact of genetic variations in the polymorphisms rs5751876 in ADORA2A gene and rs762551 in CYP1A2 on CAF/PAX kinetics will be considered.

Acute Sodium Bicarbonate Supplementation in Athletes

The purpose of this study is to verify the effect of acute sodium bicarbonate (SB) and placebo (PLA) supplementation on buffering potential kinetics, physical capacity, discipline-specific performance as well as concentration of diagnostically significant blood biochemical indices in athletes, in a randomised, double-blind, placebo-controlled crossover trial.

Creatine Supplementation and Resistance Training in Patients With Breast Cancer

Background: Creatine supplementation is an effective ergogenic nutrient for athletes, as well as people for people starting a health or fitness program. Resistance training previously been identified as an important method of increasing muscle mass and strength among people, specially in people with cancer to avoid sarcopenia. The potential of creatine supplementation for adaptations produced by strength training in cancer patients are still unknown. Objective: the primary aim of this study is to evaluate the effectiveness of a 16-week supervised resistance training program intervention with and without creatine supplementation in patients with breast cancer. Methods: A multicentre, randomized, double-blind, placebo-controlled study designed to evaluate the effects of creatine supplementation in addition to resistance training in breast cancer patients. Patients will be randomly assigned to 3 groups: a control group (CG) and two experimental groups. The first resistance training group (RG) will perform resistance training, while the second resistance-creatine experimental group (RCG) will perform the same resistance training as the RG and will also receive a 5 g/day supplementation of creatine for the duration of the exercise the 16-week intervention. RG participants will follow the same daily dosing protocol, but in their case, with dextrose/maltodextrin. Resistance training will be a 16-week supervised workout that will consist of a series of resistance exercises (leg press, knee extension, knee bends, chest press, sit-ups, back extensions, pull-ups, and shoulder press) that involved the largest muscle groups of the body and will be performed three times a week on non-consecutive days. Both the RG and the RCG will receive a supplement of soluble protein powder (20-30 g) daily. Discussion: The results of this intervention will help to better understand the potential of non-pharmacological treatment for improving strength and wellbeing values in breast cancer patients with and without creatine supplementation.

HMB and Exercise-induced Muscle Damage

The study aims at assessing the influence of β-hydroxy-β-methylbutyrate (HMB) supplementation (4.0 g/day) supplemented for 7 days in a group of speed-strength trained individuals on lower-body strength performance, selected muscle histological, molecular and blood markers of muscle recovery in response to resistance exercise-induced muscle damage.