L-Citrulline: benefits, dosage, contraindications
Other name(s)
Citrulline
Scientific name(s)
2-amino-5-(carbamoylamino)pentanoic acid
Family or group:
Amino acids
Indications
Scoring methodology
EFSA approval.
Sports performance ✪✪✪✪✪
Clinical evidence shows that taking L-citrulline appears to improve certain measures of athletic performance, particularly those related to anaerobic performance. L-citrulline has been used at doses of 2.4 grams to 5 g per day for 7 days. A single dose of 8 g of L-citrulline malate has also been used just before exercise. It has been suggested that increased nitric oxide production from L-citrulline supplementation could increase exercise capacity. Nitric oxide dilates arterial and venous blood vessels and increases glucose uptake and insulin secretion. In addition, L-citrulline also appears to enhance the use of amino acids 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 effects on clinical blood safety markers in resistance-trained men.
Consumption of watermelon juice enriched with L-citrulline and pomegranate ellagitannins improved metabolism during exercise.
Congestive heart failure ✪✪✪✪✪
Some clinical research indicates that L-citrulline malate may provide additional benefits to patients with heart failure who are already receiving standard medications. Taking 3 grams of L-citrulline malate per day for 2 to 4 months reduced systolic pulmonary arterial pressure and improved right and left ventricular ejection fraction after an exercise test in patients with heart failure with preserved ejection fraction. nn
Posologie
Orally
3 g
4 - months
L-citrulline malate
Citrulline: a valuable ally in therapeuticnnmanagement?nn
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 favors the development of chronic diseases. One of the major characteristics of aging is the change in body composition. Indeed, older adults lose muscle mass (whose ultimate form is sarcopenia), which makes them more frail. Furthermore, this sarcopenia is difficult to manage because it is accompanied by resistance to nutritional rehabilitation. nnA major interest has focused on the use of specific amino acids to restore nitrogen homeostasis. Among the strategies proposed, citrulline appears the most promising because it has a direct capacity to act on muscle function.nnA clinical study investigated the impact of citrulline supplementation (10 g/day for 3 weeks) during nutritional rehabilitation in malnourished hospitalized older adults. This work demonstrated that citrulline administration allowed an increase in lean mass.nnA second study examined the effect of citrulline supplementation (10 g/day for 12 weeks) combined with intermittent physical exercise in older obese individuals. The results show that citrulline enhances muscular and functional parameters, with a slight increase in lean mass and a decrease in fat mass.nnMoreover, in the brains of older adults, the amount of enzymes involved in the production of nitric oxide (NO) is decreased, which can contribute to deterioration of cognitive functions. Indeed, NO is involved in synaptic plasticity, learning, and memory. In addition, one study showed that Alzheimeru2019s disease involved neuronal changes partly related to altered NO production. Citrulline can generate NO in the CNS and thus reduce the deleterious effects of aging.nn
Posologie
Oral
10 g
3 - weeks
Sickle cell disease ✪✪✪✪✪
Preliminary clinical research shows that taking L-citrulline at 0.09-0.13 grams/kg per day in two divided doses for a period of up to 9 months may reduce neutrophilia and symptoms in patients with sickle cell disease.
Posologie
Oral
90 - 130 mg/kg
9 - months
Erectile dysfunction ✪✪✪✪✪
Preliminary clinical research shows that taking L-citrulline at 1.5 g per day for one month improves erections, moving from a "mild erectile dysfunction" to a "normal erectile function" in 50% of patients with erectile dysfunction.
Posologie
Oral
1.5 g
1 - month
Properties
Metabolic
Citrulline is produced in the body by one of two pathways: it is either recycled from arginine (conversion of arginine to nitric oxide leaves citrulline as a byproduct), or produced from the 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. This is converted by argininosuccinate synthase into argininosuccinate, then into L-arginine by argininosuccinate lyase. Urea is formed when L-arginine is reconverted into L-ornithine, thereby completing the cycle. In certain enzymatic disorders of the urea cycle that prevent the conversion of L-ornithine into L-citrulline, there is a reduced production of L-arginine for protein synthesis. This problem could be corrected by using L-citrulline supplements. In the case of a defect in L-ornithine transport leading to hyperammonemia, supplementation with L-citrulline could restore normal ammonia handling by increasing the production of L-ornithine via the hepatic urea cycle and bypassing the transport defect. Additionally, increased hepatic sequestration and amino acid metabolism are thought to contribute to the poor response to a high-protein diet sometimes observed in elderly individuals suffering from malnutrition. L-citrulline, which bypasses the liver, could increase the delivery of nitrogen to peripheral tissues for protein synthesis.
Usages associés
Cardiovascular
A supplementation with citrulline (CIT) appears to be a promising substitute to increase arginine bioavailability for producing the nitric oxide (NO) necessary to maintain vascular integrity. Indeed, in healthy and obese older subjects, CIT intake reduces arterial stiffness. At the cardiac level, CIT improves ventricular function. A study in heart failure patients shows that CIT increases left ventricular ejection fraction by improving maximal arterial amplitude. In addition, acute ingestion of CIT increases de novo synthesis of arginine and NO, and thus their bioavailability, thereby promoting the maintenance of vascular tone. Furthermore, CIT appears to protect against alterations of the vascular endothelium through its antihypertensive effects. Moreover, CIT supplementation lowers cholesterol levels and improves inflammatory status, thereby reducing the expansion of atherosclerotic plaques and preventing cardiovascular damage. Also, in sickle cell disease, inflammatory endothelial lesions are partly mediated by increased levels of activated neutrophils, which release proteolytic enzymes and superoxide anions and degrade nitric oxide. L-citrulline, as a precursor of L-arginine and nitric oxide, could therefore be useful in sickle cell disease. Nitric oxide–induced vasodilation could also help the circulation of deformed red blood cells. Preliminary animal data suggest that L-citrulline can improve endothelium-dependent vasorelaxation and relax arterial smooth muscle.
Usages associés
Musculoskeletal effects
An in vivo (malnourished rats) and in vitro (cultured myotubes) approach highlighted that citrulline (CIT) has a direct and targeted action in muscle. Indeed, it increases the expression of the main components of myofibrils (the contractile units of muscle fibers), as well as the amount of proteins involved in the muscle contraction process. These experimental data were confirmed by the results of clinical studies showing that administration of CIT to healthy volunteers improved nitrogen balance by 57%.
Usages associés
Neurological
Given the role of citrulline (CIT) in the vascular system, coupled with the fact that it is a precursor of nitric oxide (NO) and that it crosses the blood–brain barrier, it could modulate mechanisms of the central nervous system (CNS). A study conducted in healthy aged rats showed that CIT supplementation improved the animals' locomotor activity and increased striatal levels of a key enzyme involved in dopamine production. Although the mechanism of action of this system remains to be clarified, it appears that CIT acts on the dopaminergic pathway, which is involved in the initiation of voluntary movements. CIT can therefore generate NO directly in the CNS. On the other hand, in the brains of elderly people, the levels of enzymes involved in NO production are decreased, which may contribute to a deterioration of cognitive functions. Indeed, NO is involved in synaptic plasticity, learning, and memory. Moreover, a study showed that Alzheimer's disease involved neuronal changes partly related to impaired NO production. CIT can generate NO in the CNS and thus reduce the deleterious effects of aging.
Usages associés
Safe dosage
Adults aged 18 years and older: 1.5 g - 15 g
L-citrulline is well absorbed and well tolerated. No side effects related to its consumption have ever been reported. In clinical trials, L-citrulline has been used safely 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.
Children aged 1 to 18 years: 5.7 g
Administration of L-citrulline appears to be safe when used orally and appropriately. L-citrulline has been used with apparent safety 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 increase vasodilation and raise the risk of hypotension. Taking L-citrulline with other medications that increase blood flow to the heart could increase the risk of lightheadedness and dizziness.
Antihypertensives: moderate interaction
L-citrulline may lower blood pressure. Taking L-citrulline with medications for high blood pressure could cause an excessive drop in blood pressure (hypotension).nnThese antihypertensives include: captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), and many others.
PDE5 inhibitors: strong interaction
L-citrulline may lower blood pressure. Some medications for male sexual dysfunction can also lower blood pressure. Taking L-citrulline with medications for male sexual dysfunction could cause an excessive drop in blood pressure.nnThese 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 consumption of watermelon may cause hypercitrullinemia. Avoid using L-citrulline supplements at the same time as consuming large amounts of watermelon.
Precautions
Pregnant women: avoid
Avoid use due to lack of reliable and sufficient information. nn
Breastfeeding women: avoid
Avoid use due to lack of reliable and sufficient information. nn
