L-Citrulline: Benefits, Dosage, Contraindications
Other name(s)
Citrulline
Scientific name(s)
2-amino-5-(carbamoylamino)pentanoic acid
Family or group:
Amino acids
Indications
Rating methodology
EFSA approval.
Sports Performance ✪✪✪✪✪
Clinical evidence suggests that L-citrulline intake seems to improve certain measures of athletic performance, particularly related to anaerobic performance. L-citrulline has been used in amounts from 2.4 grams to 5 g per day for 7 days. A single dose of 8 g of L-citrulline malate was also used just before exercise. It is suggested that increased nitric oxide production from L-citrulline supplementation could boost exercise capacity. Nitric oxide dilates arterial and venous blood vessels and increases glucose uptake and insulin secretion. Moreover, L-citrulline also seems to enhance amino acid use during exercise, which could reduce muscle soreness and fatigue.
Posologie
Oral
2.4 - 5 g
7 - days
Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study.
Citrulline: A Valuable Ally in Therapeutic Management?
Citrulline malate improves anaerobic athletic performance and relieves muscle soreness.
Eight weeks of resistance training combined with glutathione and L-citrulline supplementation increase lean mass and have no adverse effect on clinical blood safety markers in trained resistance men.
Consumption of watermelon juice enriched with L-citrulline and pomegranate ellagitannins improved metabolism during physical exercise.
Congestive Heart Failure ✪✪✪✪✪
Some clinical research suggests L-citrulline malate could provide additional benefits to heart failure patients already receiving standard medications. Taking 3 grams of L-citrulline malate daily for 2 to 4 months reduced systolic pulmonary arterial pressure and improved right and left ventricular ejection fraction after an exercise test in heart failure patients with preserved ejection fraction.
Posologie
Oral
3 g
4 - months
L-citrulline malate
Citrulline: A Valuable Ally in Therapeutic Management?
Effect of oral L-arginine or L-citrulline supplementation on blood pressure and right ventricular function in patients with heart failure with preserved ejection fraction.
Healthy Aging ✪✪✪✪✪
Aging is accompanied by profound pathophysiological changes. Age is responsible for structural and metabolic alterations, the accumulation of which promotes the development of chronic diseases. One of the major characteristics of aging is the change in body composition. Indeed, older individuals lose muscle mass (the ultimate form being sarcopenia) which makes them more frail. Furthermore, this sarcopenia is challenging to manage as it is accompanied by a resistance to refeeding. Significant interest has been directed towards the use of specific amino acids to restore nitrogen homeostasis. Among the proposed strategies, citrulline appears to be the most promising due to its direct action on muscular function. A clinical study examined the impact of citrulline supplementation (10 g/day for 3 weeks) during refeeding in hospitalized undernourished elderly patients. This study demonstrated that citrulline administration resulted in an increase in lean mass. Another study investigated the effect of citrulline supplementation (10 g/day for 12 weeks) combined with intermittent physical exercise in elderly obese subjects. The results showed that citrulline enhanced muscular and functional parameters, with a slight increase in lean mass and a decrease in fat mass. Additionally, in the brain of older individuals, the quantity of enzymes involved in nitric oxide (NO) production is decreased, potentially contributing to cognitive decline. Indeed, NO is involved in synaptic plasticity, learning, and memory. Moreover, a study showed that Alzheimer's disease involves neuronal changes partly linked to an alteration in NO production. Citrulline can generate NO in the CNS and thus mitigate the detrimental effects of aging.
Posologie
Oral route
10 g
3 - weeks
Sickle Cell Disease ✪✪✪✪✪
Preliminary clinical research suggests that taking L-citrulline at a dosage of 0.09–0.13 grams/kg per day in two divided doses for up to 9 months may reduce neutrophilia and symptoms in patients with sickle cell disease.
Posologie
Oral route
90 - 130 mg/kg
9 - months
Erectile Dysfunction ✪✪✪✪✪
Preliminary clinical research shows that taking L-citrulline at a dosage of 1.5 g per day for one month improves erection, shifting from "mild erectile dysfunction" to "normal erectile function", in 50% of patients suffering from erectile dysfunction.
Posologie
Oral route
1.5 g
1 - month
Properties
Metabolic
Citrulline is created in the body by one of two pathways: it is either recycled from arginine (with the conversion of arginine into nitric oxide leaving citrulline as a byproduct), or produced from nitrogen (and part of the carbon) contained in L-glutamine. In hepatic mitochondria, L-citrulline is an intermediate in the urea cycle, which converts ammonia into urea. Ammonia and bicarbonate are combined with L-ornithine by the enzyme ornithine transcarbamylase to produce L-citrulline. It is converted by argininosuccinate synthetase into argininosuccinate, then into L-arginine by argininosuccinate lyase. Urea is formed when L-arginine is reconverted into L-ornithine, thus completing the cycle. In certain enzymatic disorders of the urea cycle preventing the conversion of L-ornithine into L-citrulline, there is a reduced production of L-arginine for protein synthesis. This issue could be corrected by using L-citrulline supplements. In cases of defects in L-ornithine transport leading to hyperammonemia, L-citrulline supplementation might restore normal ammonia processing by increasing L-ornithine production via the urea cycle in the liver, bypassing the transport defect. Additionally, an increase in hepatic sequestration and metabolism of amino acids might contribute to a poor response to a high-protein diet, sometimes observed in elderly people suffering from malnutrition. L-citrulline, bypassing the liver, could enhance nitrogen delivery to peripheral tissues for protein synthesis.
Usages associés
Cardiovascular
Citrulline supplementation (CIT) appears to be a promising substitute to increase arginine bioavailability necessary for maintaining vascular integrity. Indeed, in healthy and obese older subjects, CIT intake reduces arterial stiffness. Cardiovascularly, CIT improves ventricular function. A study in heart failure patients shows CIT increases ventricular ejection fraction by improving maximal arterial amplitude. Moreover, acute CIT ingestion boosts de novo arginine and NO synthesis, increasing their availability, favoring vascular tone maintenance. Additionally, CIT seems to protect from vascular endothelial alterations due to its antihypertensive effects. Furthermore, CIT supplementation reduces cholesterol levels and inflammatory status, thus diminishing atheroma plaque expansion and preventing cardiovascular alterations. Moreover, in sickle cell disease, inflammatory endothelial lesions are partly mediated by increased levels of activated neutrophils releasing proteolytic enzymes and superoxide anions, decomposing nitric oxide. L-citrulline, as a precursor to L-arginine and nitric oxide, could thus be useful in sickle cell disease. NO-induced vasodilation might also favor the circulation of deformed red blood cells. Preliminary animal data suggest L-citrulline can improve endothelium-dependent vasorelaxation and relax arterial smooth muscle.
Usages associés
Musculoskeletal Effects
In vivo (malnourished rats) and vitro (cultured myotubes) approaches have highlighted that citrulline (CIT) has a direct and targeted action in the muscle. It increases the expression of primary components of myofibrils (contractile units of muscle fibers), along with the amount of proteins involved in muscle contraction. These experimental findings are supported by clinical studies showing that CIT administration in healthy volunteers improved nitrogen balance by 57%.
Usages associés
Neurological
Given CIT's role in the vascular system, coupled with it being a precursor to nitric oxide (NO) and its ability to cross the blood-brain barrier, it might modulate central nervous system (CNS) mechanisms. A study in healthy older rats showed CIT supplementation enhanced motor activity and increased striatal levels of a key enzyme involved in dopamine production. Although the mechanism of this system remains to be clarified, CIT seems to act on the dopaminergic pathway, involved in initiating voluntary movements. CIT can then generate NO directly in the CNS. Furthermore, in the brain of elderly individuals, enzyme levels involved in NO production are decreased, which might contribute to cognitive function decline. Indeed, NO is implicated in synaptic plasticity, learning, and memory. Moreover, a study indicated Alzheimer's disease involved neuronal changes partly related to an alteration in NO production. CIT can generate NO in the CNS, thereby mitigating deleterious effects of aging.
Usages associés
Safety dosage
Adult from 18 year(s): 1.5 g - 15 g
L-citrulline is well absorbed and well tolerated. No side effects have ever been reported with its consumption. In clinical trials, L-citrulline has been safely used for up to 9 months at doses of 1.5 to 9 grams per day. Doses up to 15 grams have also been used as single doses or over a 24-hour period.
Child from 1 up to 18 year(s): 5.7 g
L-citrulline administration appears safe when used orally and appropriately. L-citrulline has been apparently safely used in infants at a dose of 0.17 grams/kg/day and in a 2-year-old child at a dose of 5.7 grams/day for about 20 months.
Interactions
Médicaments
Nitrates: strong interaction
L-citrulline is converted into L-arginine, which can cause vasodilation. Theoretically, concomitant use may enhance vasodilation and increase the risk of hypotension. Taking L-citrulline with other medications that increase blood flow to the heart could increase the risk of dizziness and vertigo.
Antihypertensive: moderate interaction
L-citrulline may lower blood pressure. Taking L-citrulline with high blood pressure medications could cause an excessive drop in blood pressure (hypotension). These antihypertensives include: captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), and many others.
PDE5 Inhibitor: strong interaction
L-citrulline may lower blood pressure. Some medications for male sexual dysfunction may also lower blood pressure. Taking L-citrulline with medications for male sexual dysfunction could cause an excessive drop in blood pressure. These medications for male sexual dysfunction include: sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra).
Plantes ou autres actifs
L-Citrulline: strong interaction
Watermelons contain high levels of L-citrulline. Excessive watermelon consumption can cause hypercitrullinemia. Avoid concurrent use of L-citrulline supplements and large quantities of watermelon.
Precautions
Pregnant woman: avoid
Avoid use due to a lack of reliable and sufficient information.
Breast-feeding woman: avoid
Avoid use due to a lack of reliable and sufficient information.
