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Unlikely amino acid may have star qualities

According to research, L-Citrulline Supplementation: Impact on Cardiometabolic Health, appearing in the July 2018 issue of the online journal Nutrients, this unique, neutral, non-essential amino acid is an important component of the urea cycle in the liver and kidneys.

The urea cycle, as referenced in Basic Neurochemistry: Molecular, Cellular, and Medical Aspects, 6th edition, “mediates the removal of ammonia as urea in the amount of 10 to 20 grams per day in the healthy adult. The absence of a fully functional urea cycle may result in hyper-ammonemic encephalopathy (increased ammonia in the brain), and irreversible brain injury in severe cases.”

L-citrulline is rarely found in food sources, except for watermelon, where it can range from 1.6 to 3.5 grams per kilogram.

Researchers from the Pennington Biomedical Research Center in Baton Rouge, Louisiana, LSU Departments of Comparative Biomedical Sciences, School of Veterinary Medicine, and Kinesiology, and Penn State University’s Department of Kinesiology, chose to review the research on the health applications of L-citrulline – which, “are largely predicated on the capacity for L-citrulline to increase L-arginine (amino acid) availability for NO (nitric oxide) production.”

NO production affects numerous biological functions that, “contribute to the development of multiple age-and lifestyle-related risk factors and diseases, including hypertension, atherosclerosis, insulin resistance, type 2 diabetes (T2D), and cardiovascular disease,” as noted by the reviewers.

Within endothelial cells that line the inside surface of blood and lymphatic vessels, NO is created from the L-arginine and L-citrulline. The researchers comment that, “augmenting L-arginine levels in the circulation may represent a potential therapeutic mechanism to increase NO synthesis and bioavailability.”

Here’s what the Nutrient researchers say about some of L-citrulline’s health applications: As to endothelial function, “L-citrulline may protect against the liver damage and endothelial dysfunction induced by chronic exposure to a high fat/high cholesterol diet.”

From an inflammatory perspective, “L-citrulline possess qualities, as an amino acid, which make it a functional antioxidant under certain physiological conditions” – due to its ability to reduce ROS (reactive oxygen species) – an unstable molecule that contains oxygen that easily reacts with other molecules in a cell that may cause damage – resulting in cell death.

From an anti-hypertensive (high blood pressure) perspective, “pre-clinical studies suggest that L-citrulline increases renal (kidney) NO levels, contributing to the prevention of hypertension,” due to, “adaptations to physiological and environmental stressors to reduce vessel wall stiffness and allow for improved blood flow responses.”

As to how L-citrulline might interact or benefit those individuals currently using blood pressure medication, Tim Allerton, Ph.D., an Exercise Physiologist at the Pennington Biomedical Research Center, and lead researcher on this L-citrulline review, said, “the combination of citrulline and blood pressure medications has not been extensively studied to my knowledge.”

Additionally, Allerton referenced that, “there is a nice amount of data on the benefits of citrulline or watermelon juice/extract (rich source of citrulline) improving blood pressure alone in pre-hypertensive and hypertensive men and women. The addition of citrulline to an existing pharmacological regimen warrants further research.”

For heart disease patients, Allerton commented that, “citrulline has the potential to improve the health of the vascular endothelium and some preclinical trials show it is able to improve blood lipids. However, there aren’t any long-term trials in these populations. Long-term studies using arginine supplementation have shown either no improvement or some harm in patients with heart disease. Therefore, it would always be wise to ask your cardiologist prior to starting any supplement.”

As to benefitting athletic performance, “citrulline-malate is more frequently studied in the context of athletic or exercise performance. The studies regarding the benefits of citrulline (alone) or citrulline-malate are equivocal. When beneficial effects are observed in studies, it is difficult to determine if citrulline or malate or the combination of the two-caused improvement. In some cases, citrulline malate has been shown to decrease performance,” notes the Baton Rouge researcher.

Pass the watermelon.

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