Effect of caffeine and citrulline malate on resistance exercise and jumping performance: a randomized double-blind placebo-controlled crossover study

ISRCTN	ISRCTN11694009
DOI	https://doi.org/10.1186/ISRCTN11694009

Submission date: 02/11/2022
Registration date: 10/02/2023
Last edited: 17/07/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Background and study aims
The mechanisms underlying the ergogenic (enhanced physical performance) effects of caffeine and citrulline malate (CitMal) and the potential interactions between them remain to be elucidated, but co-ingestion could potentially both attenuate and hamper the performance-enhancing effects of either supplement ingested in isolation. Therefore, this study aimed to explore the isolated and combined effects of caffeine and CitMal on jumping performance, muscular strength, endurance, and pain perception.

Who can participate?
Healthy volunteers aged between 18 and 45 years old

What does the study involve?
Performing a strength test with countermovement jump, and dynamic exercises for maximal strength. Along with this, supplements were used to see the effect on performance and pain perception.

What are the possible benefits and risks of participating?
Potential benefits are feedback on their own training technique and testing in safe environments with experienced and contribution to science. Potential risks are injuries that can occur under maximal effort strength training.

Where is the study run from?
Nord University (Norway)

When is the study starting and how long is it expected to run for?
November 2021 to June 2022

Who is funding the study?
1. Investigator initiated and funded (Norway)
2. Nord University lab (Norway)

Who is the main contact?
Markus Haugen, haugen.research@gmail.com

Contact information

Mr Markus Haugen
Scientific

Johannes Bruns gate 7
Bergen
5008
Norway

ORCID ID	0000-0003-0797-664X
Phone	+ 47 46823821
Email	haugen.research@gmail.com

Study information

Study design	Randomized double-blind placebo-controlled crossover trial
Primary study design	Interventional
Secondary study design	Randomised cross over trial
Study setting(s)	Community
Study type	Other
Participant information sheet	Not available in web format, please use the contact details to request a participant information sheet
Scientific title	Effect of isolated and combined ingestion of caffeine and citrulline malate on resistance exercise and jumping performance: a randomized double-blind placebo-controlled crossover study
Study hypothesis	We hypothesized that both caffeine and citrulline malate (CitMal) would be ergogenic and that their combined ingestion would produce additive effects on exercise performance
Ethics approval(s)	Approved 03/12/2021, Ethics Committee for the Norwegian Center for Research Data (Harald Hårfagres gate 29, N-5007, Bergen, Norway; +47 53 21 15 00; postmottak@sikt.no), ref: 445723
Condition	Sports-related outcomes
Intervention	Study design A randomized, double-blind, placebo-controlled, crossover trial is being used to investigate the isolated and combined effects of caffeine and CitMal on countermovement jump (CMJ) performance, maximal strength, muscular endurance, and pain perception. In the first session, the participants are being familiarized with the testing protocol, which will then be repeated for all the experimental sessions. The experimental sessions involve four testing trials where the participants will receive either placebo (zero-calorie drink), 5 mg/kg caffeine, 12 g of CitMal, or the respective dosages of caffeine and CitMal combined, mixed in 500 mL non-caloric cordial. In all four conditions, supplementation is provided 60 minutes before the start of the testing protocol. All testing trials are separated by a minimum of 72 hours and a maximum of seven days to ensure treatment washout and sufficient recovery. The participants are instructed to refrain from caffeine, alcohol, and training 24 hours prior to every testing session. All participants are recording a 24-hour diet log the day prior to testing and a weekly caffeine log. The participants are instructed to replicate the food log before every trial to reduce variation in energy intake and hydration level. The order of the trials is counterbalanced and randomized using Microsoft Excel (Version 2205, 64-bit). Participants A total of 40 healthy resistance-trained males (n=20) and females (n=20) with no known medical condition, injuries, or any other health limitation are being recruited. The study is being performed in accordance with the Helsinki Declaration and approved by the Norwegian Center for Research Data (NSD) (project nr: 445723) and by the local ethics committee at the University of Agder (Kristiansand, Norway). All participants are signing a written consent. Supplementation All supplement conditions will have a similar color and taste as they are mixed in 500 mL of Fun Light zero-calorie sweetened water (200 ml water and 300 ml non-caloric Fun light sweetener; Fun Light©, Stabburet, Nordre Follo, Norway), and consist of: 1. 5 mg/kg of caffeine as an anhydrous powder (Caffeine, ReagentPlus, Sigma-Aldrich) 2. 12 g of CitMal powder with a ratio between L-citrulline and malate of 2:1 (Citrulline Malate, Trade Ingredients) 3. The same dosages of caffeine (5 mg/kg) and CitMal (12 g) combined 4. Placebo (water and Fun Light sweetener) Participants are provided with the drink in bottles 60 minutes prior to testing and are required to complete the whole drink within one minute to ensure that they reached peak or close to peak plasma levels of caffeine and CitMal when the tests are initiated. Bottles with supplements are shaken between every sip. An independent researcher who will not participate in other measurements or analyses will randomize the treatment order, mix, and administer the treatments. This researcher will unblind the conditions only after the data collection for all participants is completed. After every testing session, participants will be asked which supplement they thought they have received. A standard question is given to all participants at the end of the testing sessions: “Which supplement do you think you received?” Answers included: placebo; only caffeine; both caffeine and CitMal; only CitMal. Measurements Countermovement jump Each testing session starts with the CMJ test on a force plate (Muscle lab, Ergotest Technology AS, Porsgrunn, Norway), which is used to evaluate jump height (cm), maximal power (W), rate of force development (kN/s), and peak force (N/kg). The CMJ is performed with feet shoulder-width apart and hands on the hips during the whole jump. From a standing position, participants are required to squat to a self-selected depth and then perform a maximal vertical jump. The feet have to be straight during the flight time. Jump height is calculated with impulse (Muscle lab, Ergotest Technology AS, Porsgrunn, Norway). As a warm-up, the participants perform three submaximal CMJ trials with approximately 50%, 75%, and 90% intensity (45 seconds of rest between attempts). Following the warm-up, three CMJ attempts are performed, and the participants rest 15 seconds between each attempt. Highest values for each of the analyzed variables are used for statistical analysis. 1RM squat and bench press Participants are completing a 1RM test for both the squat and the bench press. In both exercises, a five sets warm-up protocol is utilized. In the first set, the participants complete several repetitions only with the barbell. Then, they complete 8, 6, 3, and 2 repetitions with loads amounting to 40%, 60%, 70%, and 80% of their estimated 1RM, respectively. 1RM attempts start following the completion of the warm-up sets. After every successful 1RM attempt, the weight is increased by 0.25 kg to 5 kg (subjectively evaluated) until a final 1RM is reached. Four minutes of rest are provided between 1RM attempts. Equipment used for the testing includes: a half rack (half rack easy 2.0, Group AS, Asker, Norway), a calibrated (± 10 g) 20 kg barbell (Powerbar stainless steel 29mm, Group AS, Asker, Norway), and calibrated (± 10 g) plates from 0.25 kg to 50 kg (Powerlifting Steel Plate, Group AS, Asker, Norway). For the squat, the participants are required to reach the depth requirement set by the International Powerlifting Federation, which requires that the top surface at the hip joint should be below the knees. A test leader visually inspects the depth together with a rubber band that the participants can use as external feedback. Safety pins and two experienced spotters are used in the 1RM attempts to ensure safety. In the bench press, the elbows have to be fully extended at the completion of the lift for a 1RM to be approved. A pause on the chest at the bottom of the lift is not mandatory (self-selected by the participants and standardized for all testing sessions). However, the shoes have to be in touch with the floor and the gluteal region and upper back in touch with the bench throughout the lift. Stance width in the squat and grip width in the bench press is recorded in the familiarization session, and the same width is used in all experimental sessions. Equipment such as lifting belts, shoes, wrist wraps, knee sleeves and chalk are allowed, but participants have to use the self-selected equipment at all trials to ensure standardization. Repetitions to failure and pain perception Muscular endurance is being evaluated by having the participants complete one set of repetitions to muscular failure in the squat and bench press using 60% of 1RM (from 1RM measured at each trial). During the set, the number of completed repetitions is counted out loud by the test leader. No breaks are allowed between repetitions. Technical requirements are the same as in the 1RM tests. Muscular failure is defined as not being able to complete a full repetition without assistance or failing to keep up the standardized tempo set by the test leader on two consecutive repetitions. Specifically, if a participant includes too long of a pause (>1 sec) between muscle actions, a warning from the test leader is provided; if the same occurs in the next repetition, this is deemed as muscular failure, thus denoting the end of the test. Within 15 seconds of completion of the test, the participants are required to rate their perceived pain on an 11-point numerical rating scale, with the instruction that 0 points are equivalent to “no pain” and 10 points are their “worst imaginable pain”.
Intervention type	Supplement
Primary outcome measure	1. Jump height (cm) measured using a force plate at every trial before the strength test and after warmup 2. Maximal power (W) measured using a force plate at every trial before the strength test and after warmup 3. Rate of force development (kN/s) measured using a force plate at every trial before the strength test and after warmup 4. Peak force (N/kg) measured using a force plate at every trial before the strength test and after warmup 5. Maximal strength measured using a barbell and plates for loading at every trial after the jump test 6. Number of repetitions to failure with barbell and plates for loading on every trial after the jump test
Secondary outcome measures	Pain perception measured using a numerical rating scale straight after the number of repetitions to failure test for both bench press and back squat
Overall study start date	30/11/2021
Overall study end date	01/06/2022

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	60
Total final enrolment	40
Participant inclusion criteria	1. Aged between 18 and 45 years old 2. A minimum of 12 months of resistance training experience 3. Currently performing resistance training at least two times per week 4. Able to perform the barbell back squat and bench press with 120% and 100% of body mass for males and 100% and 70% of body mass for females
Participant exclusion criteria	1. Smoking 2. Pregnancy or lactating
Recruitment start date	01/09/2021
Recruitment end date	01/12/2021

Locations

Countries of recruitment

Norway

Study participating centre

Nord university

Høgskolevegen 27
Levanger
7600
Norway

Sponsor information

Nord University
University/education

Høgskolevegen 27
Levanger
7600
Norway

Phone	75517000
Email	postmottak@nord.no
Website	http://www.nord.no/
"ROR"	https://ror.org/030mwrt98

Funders

Funder type

Other

Investigator initiated and funded

No information available

Nord universitet
Government organisation / Universities (academic only)

Alternative name(s): Nord University, Noerhte universitete, Nuortta universitiehtta
Location: Norway

Results and Publications

Intention to publish date	01/01/2023
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	We plan to publish this paper along with 3 other papers from the same data collection Sex differences between males and females with ingestion of caffeine The effect of Citrulline Malate on strength and power outcomes Trained versus well trained and the effect of caffeine The paper in this registration is on hold in the European journal of sports nutrition due to this registration.
IPD sharing plan	The dataset analysed during the current study will be available upon request from Markus Haugen (haugen.research@gmail.com; +4746823821). Anonymous data will be shared from every test as well as dietary intake and supplement history. Consent from participants was required and obtained. All data are anonymized according to Norwegian ethics committee standards.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		14/07/2023	17/07/2023	Yes	No

Editorial Notes

17/07/2023: Publication reference added.
25/01/2023: Trial's existence confirmed by the Ethics Committee for the Norwegian Center for Research Data, Norway.