An interventional study of Caffeine (5 mg/kg) and Placebo in Energy Metabolism, sponsored by Pontificia Universidad Catolica de Chile. Not yet recruiting. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-14.
Sponsored by Pontificia Universidad Catolica de Chile · Not applicable, Interventional, and Basic science
This randomized, double-blind, placebo-controlled crossover study will evaluate the acute effects of caffeine consumption on substrate utilization, resting energy metabolism, and mitochondrial function in peripheral blood mononuclear cells (PBMCs) in healthy young adults. Approximately 10 healthy men and women aged 18 to 35 years will participate. Each participant will complete two experimental visits, receiving caffeine in one visit and placebo in the other, in randomized order. The two visits will be separated by a 48-hour washout period. Participants will attend the laboratory after an overnight fast of approximately 14 hours and will abstain from caffeine, alcohol, and intense physical activity before each visit. Resting gas exchange will be measured before ingestion and 1 and 3 hours after caffeine or placebo administration. Blood samples will be collected at the same time points to isolate PBMCs and obtain plasma for metabolic analyses. Mitochondrial function will be assessed by high-resolution respirometry, and mitochondrial dynamics and morphology will be evaluated using protein analyses and transmission electron microscopy. The study will determine whether acute caffeine consumption alters resting substrate utilization and mitochondrial responses in PBMCs in healthy young adults.
Caffeine is one of the most widely consumed psychoactive compounds and is commonly used because of its stimulant and metabolic effects. By antagonizing adenosine receptors, caffeine may increase sympathetic activity, promote the mobilization of free fatty acids, and alter energy metabolism. Mitochondria are central regulators of cellular energy production, and mitochondrial function and dynamics may respond to changes in nutrient availability and metabolic stress. Peripheral blood mononuclear cells (PBMCs) provide a minimally invasive cellular model that may reflect systemic metabolic responses in humans. However, the acute effects of caffeine on substrate utilization and mitochondrial function and dynamics in human PBMCs remain insufficiently characterized.
This study will use a randomized, double-blind, placebo-controlled, crossover design. Approximately 10 healthy adults aged 18 to 35 years will be recruited. Eligible participants will have a body mass index between 18.5 and 27 kg/m², will not smoke, will not be chronic caffeine consumers exceeding 200 mg/day, and will not use medications or supplements known to affect energy metabolism. Individuals with chronic metabolic, cardiovascular, or inflammatory diseases; recent use of antioxidant supplements or ergogenic substances; or known caffeine hypersensitivity or previous adverse reactions to caffeine will be excluded.
Each participant will complete two experimental visits separated by a 48-hour washout period. Before each visit, participants will avoid caffeine, alcohol, and intense physical activity for 24 hours and will attend the laboratory after an overnight fast of approximately 14 hours. After 30 minutes of supine rest under thermoneutral conditions, resting gas exchange will be measured for 30 minutes using a breath-by-breath pulmonary gas-analysis system. A weight-adjusted dose of caffeine, corresponding to approximately 4 to 6 mg/kg of body weight, or placebo will then be administered with approximately 250 mL of water. Resting gas exchange and venous blood samples will be obtained before ingestion and 1 and 3 hours after ingestion.
Blood samples will be collected from the antecubital vein by qualified healthcare personnel. PBMCs will be isolated using a density-gradient method, and plasma will be obtained for analysis of glucose, lactate, lipid profile, insulin, and non-esterified fatty acids. Mitochondrial respiration in PBMCs will be assessed using high-resolution respirometry, including basal respiration, maximal respiratory capacity, and mitochondrial ATP-linked respiration. Mitochondrial biogenesis, mass, fusion, and fission will be evaluated by assessing PGC-1α, TOM20, MFN1, OPA1, DRP1, and FIS1 protein expression. Mitochondrial morphology will be examined using transmission electron microscopy.
The primary objective is to determine the acute effect of caffeine on mitochondrial function in PBMCs. Additional objectives are to evaluate its effects on resting energy metabolism, substrate utilization, plasma metabolic markers, mitochondrial dynamics, and mitochondrial morphology. Participants will receive a snack at the end of each experimental visit.
Pontificia Universidad Catolica de Chile is the lead sponsor of 222 studies on the registry; 57 are open to participants now.
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Participants assigned to this sequence will receive caffeine during the first experimental visit and placebo during the second experimental visit. The visits will be separated by a 48-hour washout period. Resting gas exchange and venous blood samples will be collected before intervention ingestion and 1 and 3 hours after ingestion during each study period.
Dietary Supplement: Caffeine (5 mg/kg) · Other: Placebo
Participants assigned to this sequence will receive placebo during the first experimental visit and caffeine during the second experimental visit. The visits will be separated by a 48-hour washout period. Resting gas exchange and venous blood samples will be collected before intervention ingestion and 1 and 3 hours after ingestion during each study period.
Dietary Supplement: Caffeine (5 mg/kg) · Other: Placebo
Drug page: Caffeine
Caffeine will be administered orally as a single weight-adjusted dose of 5 mg/kg body weight in an opaque capsule with approximately 250 mL of water. It will be administered immediately after baseline measurements during one experimental visit. Participants will receive caffeine in one of the two study periods according to the randomized crossover sequence. Resting gas exchange and venous blood samples will be collected before ingestion and 1 and 3 hours after ingestion.
The placebo will consist of an inert substance administered orally in an opaque capsule matched in appearance to the caffeine capsule, with approximately 250 mL of water. It will be administered immediately after baseline measurements during one experimental visit. Participants will receive placebo in one of the two study periods according to the randomized crossover sequence.
Basal mitochondrial respiration in PBMCs
Basal mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) will be assessed as part of a complete high-resolution mitochondrial respirometry protocol using the Oroboros O2k system. Basal oxygen consumption will be measured before addition of respiratory modulators and expressed as oxygen consumption rate in pmol O2/cells
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Maximal mitochondrial respiratory capacity in PBMCs
Maximal mitochondrial respiratory capacity will be determined as part of the complete high-resolution mitochondrial respirometry protocol in PBMCs using the Oroboros O2k system. It will be expressed as maximal oxygen consumption rate in pmol O2/cells
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Resting energy expenditure and substrate utilization
Resting energy expenditure will be estimated from oxygen consumption and carbon dioxide production measured during 30 minutes of resting gas exchange. The outcome will be expressed in kcal/day.
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Fat oxidation rate during resting gas exchange
Fat oxidation rate will be estimated from oxygen consumption and carbon dioxide production measured during resting gas exchange. The outcome will be expressed in g/min.
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Carbohydrate oxidation rate during resting gas exchange
Carbohydrate oxidation rate will be estimated from oxygen consumption and carbon dioxide production measured during resting gas exchange. The outcome will be expressed in g/min.
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Plasma glucose concentration
Plasma glucose concentration will be measured from venous blood samples using a clinical laboratory assay. The outcome will be expressed in mg/dL.
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Plasma lactate concentration
Plasma lactate concentration will be measured from venous blood samples using a clinical laboratory assay. The outcome will be expressed in mM
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Plasma insulin concentration
Plasma insulin concentration will be measured from venous blood samples using a clinical laboratory assay. The outcome will be expressed in µU/mL
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Plasma non-esterified fatty acid concentration
Plasma non-esterified fatty acid concentration will be measured from venous blood samples using a quantitative laboratory assay. The outcome will be expressed in mM
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Mitochondrial dynamics-related protein expression in PBMCs
The expression of a prespecified panel of mitochondrial-related proteins in peripheral blood mononuclear cells (PBMCs) will be assessed by Western blot. The panel will include PGC-1α, TOM20, MFN1, OPA1, DRP1, and FIS1. Each protein will be quantified as normalized band intensity relative to the prespecified loading control and expressed in arbitrary units. Results will be reported separately for each protein.
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
Mitochondrial morphology in PBMCs
Mitochondrial morphology in peripheral blood mononuclear cells (PBMCs) will be evaluated using transmission electron microscopy. A prespecified morphological assessment will be performed using a standardized image-analysis procedure. Mitochondrial morphological features will be quantified and reported separately according to the parameters defined in the statistical analysis plan. Results will be compared between caffeine and placebo conditions across the assessment time points.
Time frame: Baseline, 1 hour, and 3 hours after caffeine or placebo ingestion during each study period
No study locations are listed for this record.
Plan to share: Yes — De-identified individual participant data underlying the results reported in the primary publication will be shared. The dataset may include participant-level data on resting energy expenditure, substrate utilization, gas exchange variables, plasma metabolic markers, and peripheral blood mononuclear cell mitochondrial respiration, mitochondrial protein expression, and mitochondrial morphology outcomes. Direct identifiers, indirect identifiers that could reasonably permit re-identification, dates of study visits, and the re-identification key will not be shared. No identifiable biological samples will be shared.
Supporting information: Study protocol, Statistical analysis plan, Analytic code
Time frame: Beginning 6 months after publication of the primary study results and continuing for 5 years after publication.
Access criteria: Access will be available to researchers who provide a methodologically sound proposal for analyses consistent with the informed consent, ethical approval, and original study objectives. Requests must be submitted to the Principal Investigator. Following review and approval by the study team and, when required, the institutional ethics committee, de-identified data and selected supporting information will be shared through a secure data-transfer method under a data use agreement. Access will be limited to the approved research purpose and will not permit attempts to re-identify participants.
No publications or documents are linked to this record.
Start is estimated for Sep 2026; primary completion for Dec 2026, 3 months later.
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Studies of the drug tested here: Caffeine
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