Het acute effect van beta-guanidinopropionzuur en creatine

Rationale: Beta-guanidinopropionic acid (GPA), a creatine

analogue, can be obtained without prescription on the internet,

and is used by sportsmen to increase muscle mass and

endurance capacity. In contrast, creatine is used to improve

short-duration/high-intensity exercise.

Although previous studies assessed the effect on muscle

performance of creatine in humans, and of GPA in animals,

none of these studies reported the effect on peripheral

hemodynamic parameters, or the effect on ADP-dependent

platelet aggregation. Our new data from animal studies

indicate an anti-hypertensive effect of GPA. However, to our

knowledge, there are no published human data on the effects

and side effects of GPA.


Objective: In this study we will assess in human volunteers,

the tolerability of GPA 100 mg during 1 week, as a primary

outcome, compared to placebo and creatine 5 g.


Study design: Randomized, double-blind, placebo-controlled,

double-dummy intervention study.


Study population: 24 healthy male volunteers, 18-50 years old

recruited in the Netherlands.


Intervention: One week of daily oral administration of GPA 100

mg, creatine 5 g, or placebo.


Main study parameters/endpoints: Tolerability for GPA

assessed with a questionnaire; hemodynamic parameters,

including blood pressure, heart rate, cardiac output and total

peripheral resistance; biochemical parameters, including

serum CK, GPA, creatine, glucose, insuline, creatinine after

acute oral administration of GPA and one week of intervention

with GPA or creatine; ADP-induced platelet aggregation.

Nature and extent of the burden and risks associated with

participation, benefit and group relatedness: In this study,

we will assess the effects of GPA, a freely available creatine

analogue, and creatine in healthy subjects. This will not

directly benefit the participants. The risks associated with

participation can be considered negligible and the burden can

be considered minimal.

Beta-guanidinopropionic acid (GPA), a creatine analogue, can be obtained without prescription on the internet, and is used by sportsmen to increase muscle mass and endurance capacity. In contrast, creatine is used to improve short-duration/high-intensity exercise. Although previous studies assessed the effect on muscle performance of creatine in humans, and of GPA in animals, none of these studies reported the effect on peripheral hemodynamic parameters. Our new data indicate a potential blood pressure lowering effect of GPA in hypertensive animals. However, to our knowledge, there are no published human data on the effects and side effects of GPA.

Therefore, in this RCT we will assess in human volunteers, the tolerability of GPA as a primary outcome, and the haemodynamic effects in comparison with creatine as a secondary outcome.

T=0 Baseline measurements (before intake of trial supplements or placebo)


Primary outcome: General history taking


Secondary Outcome:

Hemodynamic parameters (Resting blood pressure; heart rate, cardiac output and total peripheral resistance, measured non-invasively) and ADP-induced platelet aggregation.

T=2 days (After 1 day of use of trial supplements or placebo)

Primary Outcome: The probability of adverse drug reactions will be estimated with the validated Naranjo adverse drug reaction probability scale.

Secondary Outcome:
Hemodynamic parameters (Resting blood pressure; heart rate, cardiac output and total peripheral resistance, measured non-invasively)



T=7 days (after 7 days of use of trial supplements or placebo)

Primary Outcome: The probability of the adverse drug reactions will be estimated with the validated Naranjo adverse drug reaction probability scale.

Secondary Outcome:
Hemodynamic parameters (Resting blood pressure; heart rate, cardiac output and total peripheral resistance, measured non-invasively) and ADP-induced platelet aggregation.



T=21 days, 2 weeks after stopping the use of trial supplements or placebo

Primary Outcome: The probability of adverse drug reactions will be estimated with the validated Naranjo adverse drug reaction probability scale.

The participants will be asked to come to the hospital an overnight fasts.

At visit 1 (day 0), after baseline measurements, they will receive a 24 h blood pressure measurement device and a container to collect 24h urine.

At visit 2, the next day (day 1 of the trial supplements), they will take first capsules with GPA 100 mg, creatine 5 g, or placebo in the hospital (Figure 4B) after receiving a 24 h blood pressure measurement device and a container to collect 24h urine.

At visit 3 (day 2 of the trial supplements), haemodynamic and blood tests will be performed, trial supplements will be taken, and participants will receive trial supplements to take at home at day 3, 4,5, and 6 after an overnight fast.

The participants return to the hospital for visit 4 at day 7 of the trial supplements, to take the final trial supplements after receiving a 24 h blood pressure measurement device and a container to collect 24h urine.

They will return for visit 5 on day 8 for haemodynamic measurements and blood tests.

The 6th and last visit is at day 21, for the final assessment of tolerability.