About this trial
This study will be a randomized, double-blind, placebo-controlled trial. It will be conducted over a 8-week intervention investigating the effects of creatine (5g Creatine monohydrate); placebo control (5g resistant dextrin), and a combination group containing both creatine and tyrosol (5g creatine monohydrate + 150mg tyrosol/day). Endurance, strength, cognition, and fatigue resistance will be examined through repeated strength and endurance testing (described below).
Participants who pass initial screening will be invited on-site for day one (Visit 1) of testing where the participants will proceed with a series of tests which will include the following: (1) body composition; (2) mood and cognitive testing; (3) full-body strength testing; (4) 5RM (repetition maximum) bench press, leading to multiple sets of bench press (based on the previous weight) completed to failure; (5) finally, a time to exhaustion endurance test will be conducted followed by (6) repeat cognitive testing.
After the 8-week supplementation period (\~56-60 days), all original measures will be repeated as before in the same order (Visit 2). Approximately 24 hours later (Visit 3) participants will complete a questionnaire for muscle soreness remotely, and again at 48 hours post-Visit 2 (visit 4).
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Healthy males aged 20-55
Currently active (engaged in moderate to vigorous activity at least 2-days per week as defined by the American College of Sports Medicine Guidelines)
Estimated VO2 max greater than the 40th percentile of the population norm for age (assessed via ACSM guidelines, 2014). The VO2 max estimation at screening will be obtained by following a non-exercise regression model validated and described by Bradshaw et al. (2005).
Able to read and write in English
Disqualifiers
Known diagnosis of any cardiovascular, metabolic, endocrine, or renal disease
Uncontrolled stage II hypertension or higher
Recent musculoskeletal injury (<3-months)
Recent orthopaedic surgery (<12-months)
Trial design
Factorial
Treatments tested in this trial
Tyrosol
Dietary supplementphenolic compound found in olive oil
Creatine Monohydrate
Dietary supplementchemical produced naturally by the body used to rapidly regenerate ATP
Resistant Dextrin
Dietary supplementA type of soluble dietary fiber that is resistant to digestion in the small intestine. It is a byproduct of the starch hydrolysis process, where starch is broken down into smaller chains of glucose molecules
Treatment groups
Trial outcomes
Primary outcomes
Mid Thigh Pull
Utilizing a pronated clean grip, subjects will be instructed to assume a body position similar to the second pull of the snatch and clean. Once body positioning is stabilized, the subject will be given a countdown. Minimal pre-tension will be allowed to eliminate slack prior to initiation of the IMTP. Each subject will perform two warm-up reps, one at 50% and one at 75% of perceived maximum effort. Thereafter, subjects will complete two maximal IMTPs separated by approximately two minutes of rest. Force kinematics from the IMTP will be collected and recorded using a linear position transducer.
Bench Press 5 Repetition Max (RM)
Subjects will be asked to perform a 5 repetition maximum (RM) lift in order to calculate their 1RM for determination of weight needed for the protocol. The participants will start with a warm-up consisting of the following: 1 set of 8-10 reps of a light weight of their choosing followed by 1-2 sets of 3-5 reps of progressively heavier weights (\~50-70% of self-estimated 1RM). Following a 2-minute rest, subjects will select a weight they feel confident they can do for 5-7 reps but not more than 7 reps (based on warm-up weights). Weight will be increased until the subject is only able to complete 5 reps with good form. This will be their 5RM. For safety, a spotter will always be present for lifts and a set of safety bars will be used as well. Subject's 1RM will be calculated from this 5RM using the Brzycki formula (Macarilla CT, et.al. 2022) 1RM = W / (1.0278 - 0.0278 × R), where W represents the weight lifted in pounds, and R represents the number of repetitions.
Bench Press Repetitions to Failure
After calculating the estimated 1RM from the 5RM, subjects will then perform 4 sets of bench press at 50% of the calculated 1RM to failure with a two-minute rest between all sets. Total repetitions for each of these sets will be recorded and will be used to determine fatigue and compared to follow-up Visit 2 performance for fatigue resistance. For safety, a spotter will always be present for lifts and a set of safety bars will be used as well.
Muscle/aerobic endurance (Graded Cycling time to exhaustion)
Participants will complete a graded cycling test on a calibrated cycle ergometer to assess aerobic performance. The total duration in minutes participants are able to sustain the incremental cycling workload until volitional fatigue is recorded. This measures endurance capacity during the graded test. Proper cycle ergometer setup, including seat height and handlebar position, will be standardized for all participants. Testing will be conducted by trained technicians for consistency.
Secondary outcomes
Stroop
Subjects will complete the Stroop task electronically using the Milliseconds platform for cognitive assessment. Stroop is designed to measure executive function, cognitive flexibility, and response inhibition. It includes three conditions: simple reaction to color words, matching color and word, and identifying mismatched color-word combinations. Key metrics include simple and complex reaction times and commission errors. Faster reaction times and fewer errors reflect stronger executive control, while delayed times or errors may indicate cognitive slowing, impulsivity, or difficulty inhibiting automatic responses.
Abbreviated Profile of Mood States Questionnaire
Subjects will complete The Abbreviated Profile of Mood States (POMS) as an electronic 40-item self-report instrument used to assess an individual's transient emotional state across seven distinct dimensions: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue-Inertia, Confusion-Bewilderment, Vigor-Activity (Energy), and Esteem-Related Affect. Each item is rated on a 5-point Likert scale ranging from 0 ("Not at all") to 4 ("Extremely"). Domain scores are calculated by summing item responses within each subscale. A Total Mood Disturbance (TMD) score is computed as the sum of negative mood domains (Tension, Depression, Anger, Fatigue, and Confusion) minus the sum of positive mood domains (Vigor and Esteem-Related Affect). A constant of 100 is added to the TMD score to eliminate negative values, resulting in a total score range of 0 to 200. Higher TMD scores indicate greater overall mood disturbance, whereas lower scores indicate a more favorable mood state.
Body Composition (DXA)
Total and regional body composition will be determined by a whole-body scan on a dual-energy x-ray absorptiometry device (DXA) (Horizon A DXA System, Hologic Inc, Marlborough, MA). Each subject will be scanned by a certified technician, and the digital segmentation will be determined via computer algorithm. Fat-free mass, fat mass, and body fat percentage will be determined for each scan. Calibration will be performed against a phantom prior to testing. The abdominal region will be delineated by an upper horizontal border located at half of the distance between the acromion processes and external end of iliac crests, a lower border determined by the external end of iliac crests and the lateral borders extending to the edge of the abdominal soft tissue. All trunk tissue within this standardized height region will be selected for analysis.
Upper Body Muscle Soreness
A 7-point likert scale will be used for upper body muscle soreness, after performing 5 bodyweight pushups (modified for women, standard for men). The likert scale is a validated instrument designed to assess self reported muscle soreness, measured across a 7-point scale. The scale ranges from 0 (no soreness), to 6 (unbearable soreness), and has good validity and reliability (Impellizzeri, F., et al., 2007).
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