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Citrulline

L-Citrulline is an amino acid. It is turned into L-arginine in the kidneys after supplementation, which means L-citrulline supplementation is a more effective method of increasing L-arginine levels in the body than L-arginine supplementation.

Our evidence-based analysis on citrulline features 76 unique references to scientific papers.

Research analysis led by .
Reviewed by
Examine.com Team
Last Updated:

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects citrulline has on your body, and how strong these effects are.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b - Very High See all 3 studies
There do not appear to be any significant influences of supplemental citrulline on blood glucose concentrations
grade-b - High See all 4 studies
Most studies note that there is no significant change in insulin concentrations, although a lone study (not replicated) suggested that the exercise-induced increase in insulin was suppressed with citrulline. As this study also noted performance degradation, it may be a flaw
grade-c Notable Moderate See all 3 studies
The decrease in fatigue during exercise is thought to underlie most of the benefit seen with training capacity (work volume), although in men who self-report fatigue issues supplemental citrulline appears to help with that as well (independent of exercise)
grade-c Notable - See study
The lone study using citrulline acutely pre-workout noted a 40% reduction in muscle soreness the following two days after the workout.
grade-c Notable Very High See 2 studies
Nitric oxide derivatives (nitrate and urinary cGMP, since nitric oxide itself is hard to measure these biomarkers are indicative of nitric oxide production) appear to be reliably increased following oral consumption of citrulline supplementation
grade-c Notable Very High See 2 studies
Citrulline can increase plasma arginine concentrations, and due to acting as a resevoir of arginine it is actually more effective overall at increasing plasma arginine than arginine itself (acute peaks are still observed to a higher level with arginine supplementation).
grade-c Notable - See study
The increase in work capacity seen with citrulline supplementation appears to be time dependent. While there are no inherent and immediate effect, the reduction of fatigue later in a weight lifting workout causes a relative increase that has at least one doubled reps conducted (on set 8 of exhaustive exercise)
grade-c Minor - See study
An increase in blood flow is noted with citrulline supplementation in persons with impaired blood flow
grade-c Minor Moderate See all 3 studies
A decrease in blood pressure is noted secondary to increasing plasma arginine (and thus increasing nitric oxide), but this blood pressure reduction may only occur in those with hypertension or prehypertension
grade-c Minor - See study
A slight increase in creatinine has been noted with citrulline supplementation, practical relevance unknown.
grade-c Minor Very High See 2 studies
An increase in growth hormone has been noted with exercise, but not at rest. Practical significance of this information is unknown, since Arginine supplementation has unreliable effects itself
grade-c Minor - See study
Neutrophil oxidative burst post-workout appears to be enhanced when the exercise is preloaded with citrulline supplementation
grade-c Minor Moderate See 2 studies
Although acute usage does not appear to influence plasma glutamine, a week of high dose supplementation (0.18g/kg) has been noted to reduce glutamine concentrations slightly.
grade-c Minor - See study
An increase in plasma nitrate has been noted with citrulline supplementation, but not to the degree of supplemental nitrate itself
grade-c Minor - See study
An increase in urea is seen with citrulline supplementation (possibly due to increased serum ornithine sequestering ammonia)
grade-c - - See study
No significant influence on a treadmill test to exhaustion nor oxygen kinetics during this test
grade-c - - See study
No significant influence on C-reactive protein concentrations
grade-c - - See study
No significant influence of citrulline on DNA damage
grade-c - - See study
No significant influence on HDL-C concentrations
grade-c - Moderate See 2 studies
No significant influence on heart rate seems likely, although at least one study noted a random but significant reduction post-exercise
grade-c - - See study
No demonstrated effects on IGF-1 concentrations following the usage of citrulline supplementation
grade-c - - See study
No significant influence on LDL-C concentrations in serum following citrulline supplementation
grade-c - - See study
No significant influence on lactate production seen with citrulline supplementation before exercise
grade-c - - See study
No significant influence of citrulline on lipid peroxidation has been noted
grade-c - - See study
Plasma concentrations of LDH are unaffected following citrulline supplementation
grade-c - - See study
Currently no human evidence to support a practically significant increase in muscle protein synthesis at rest with citrulline supplementation
grade-c - - See study
No significant influence on total cholesterol concentrations
grade-d Minor - See study
Hardness of erections in persons with mild erectile dysfunction appears to be increased following supplementation of citrulline supplementation.
grade-d Minor - See study
Citrulline has been noted to increase physical exercise capacity in persons with heart failure.
grade-d Minor - See study
An increase in muscle ATP production via aerobic means was noted in men given 6g citrulline daily, but this appeared to be attenuated with time.
grade-d Minor - See study
In persons with heart failure with normal ejection fractions, right ventricular ejection fraction during exercise appears to be increased relative to control.

Studies Excluded from Consideration

  • Confounded with the inclusion of L-arginine[1]

Click here to see all 76 references.
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