Citrulline is a nonessential alpha-amino acid that is organically produced in the rind and flesh of watermelon. Citrulline is not coded for by human DNA but is still present in certain proteins and the urea cycle (as a by-product of arginine oxidation or from reaction of carbamoyl phosphate and ornithine). L-Citrulline appears to have a variety of synergistic effects with other popular peri-workout supplements, such as arginine and branched-chain amino acids (BCAAs) and is gaining reputation as a potent “pump”/blood flow enhancer.
Physiological role of citrulline
Citrulline is primarily relegated to bolstering nitric oxide-dependent signaling, but also plays a myriad of physiological roles. Citrulline is an important component of the urea cycle and manufactured by a variety of other amino acids in the liver; the urea cycle facilitates the elimination of ammonia and other nitrogenous toxins from the blood (most of which takes place in the liver of mammals). Nitrogen metabolites accrue from digestion, absorption, and metabolism of proteins. Given that bodybuilders/health enthusiasts generally consume large amounts of protein, proper nitrogen metabolism is crucial.
Oral citrulline supplementation has been demonstrated to elevate plasma arginine concentration and thus augments production of arginine-derived metabolites (i.e. nitrite, creatinine, ornithine, etc). 
As previously discussed, this is imperative as synthesis and elimination of urea is necessary for removing nitrogenous toxins from the body. Citrulline works along with citric acid, aspartic acid, and magnesium to improve nitrogen metabolite excretion.
In exceptionally rare instances, a disorder may occur in humans called citrullinemia; this condition occurs when there is a deficiency of the enzyme necessary to catalyze the [citrullinearginine]
reaction of the urea cycle. Research suggests that supplementing with the mineral zinc can improve the conversion of citrulline to arginine in the liver and lower blood ammonia levels. 
Moreover, since pyridoxine (vitamin B-6) activates transaminases (i.e. enzymes that convert an amino acid to a different amino acid) in the urea cycle, it may be useful to supplement with if there is a suspected malfunction in the liver. That being said, such clinical abnormalities should always be addressed by a qualified health professional/personal care physician.
Primary benefits of citrulline (malate) supplementation
Citrulline supplementation, generally in malic acid salt form (aka citrulline malate), has a strong body of scientific and empirical evidence supporting its benefits in the realm of physical performance enhancemen. Aside from being a necessary biomolecule in the urea cycle, citrulline may enhance health and performance by:
- Elevating nitric oxide (NO2) production which is a positive regulator of vasodilation and blood flow
Possible side effects of citrulline supplementation
Unlike some other nitric oxide enhancing supplements, citrulline is a generally well-tolerated compound and the side effects are benign. Most commonly the side effect people supplementing with citrulline may encounter is gastrointestinal distress, but this can be avoided by taking citrulline on an empty stomach.
Who can benefit from citrulline supplementation:
- Physique competitors
- Athletes looking to increase their performance capability
- Those looking for increased blood flow and more intense “pumps” during training
Who should avoid citrulline supplementation:
- Those with citrullinemia as this would worsen the condition
When to take citrulline:
- Optimally, citrulline should be ingested about 15-30 minutes before training.
- May also take citrulline during and/or after training if desired
- Start with a once-daily dose of 6-8g (Altius pre-workout contains 8g of citrulline malate per serving)
- If desired, dose may be increased to 15-20g split into multiple doses throughout the day
The Altius Difference
Many consumers may notice that Altius contains a much higher amount of citrulline malate than most pre-workouts on the market. Reason being is that many companies simply include a minimal dose of citrulline in their products just to make them seem better when all they really are is under-dosed garbage. Altius contains a scientifically-proven amount of citrulline malate in each serving, none of these trivial doses you see from cheap brands just trying to make a quick buck.
Citrulline Malate FAQs:
Q: I’ve heard citrulline should be taken on an empty stomach, is this true?
A: This is likely due to the rare occurrence of GI distress that may occur after ingesting citrulline; it is fine to take citrulline with or without a meal depending on how you tolerate it.
Q: How long does it usually take for me to notice the effects of citrulline?
A: This will vary for most individuals, but acute effects such as endotoxin removal will happen after the first dose; more progressive benefits such as strength increases and decreased delayed-onset muscle soreness may take a few weeks to notice.
Q: Is it true citrulline may enhance libido and treat impotence?
A: This is actually another nice “benefit” of citrulline supplementation as the increase in nitric oxide will relax blood vessels and increase blood flow (which can help improve erections, among other things).
Q: Can I just eat watermelon rather than supplementing with citrulline?
A: Unfortunately is not very practical to obtain the doses of citrulline suggested herein through diet, and most of the citrulline found in watermelon is actually in the rind of the fruit, not the flesh (the part that is most edible)
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