Citrulline is a non-essential amino acid. In hepatocytes, L-citrulline is synthesized in the urea cycle by the addition of carbon dioxide and ammonia to ornithine. L-citrulline is converted into L-arginine by the enzymes argininosuccinate synthetase and argininosuccinate lyase in the presence of L-aspartate and ATP. Subsequently, L-arginine is converted to nitric oxide by nitric oxide synthase and L-citrulline is regenerated as a by-product.

Citrulline is an amino acid. It is made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine as a by-product of the reaction catalyzed by NOS family. Its name is derived from citrullus, the Latin word for watermelon, from which it was first isolated.

From Pharmacology from NCIt & pubchem.ncbi.nlm.nih.gov

Benefits of Citrulline Supplement

A study shows that “Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness.”

The purpose of the study was to determine the effects of a single dose of citrulline malate (CM) on the performance of flat barbell bench presses as an anaerobic exercise and in terms of decreasing muscle soreness after exercise. Forty-one men performed 2 consecutive pectoral training session protocols (16 sets). The study was performed as a randomized, double-blind, 2-period crossover design. Eight grams of CM was used in 1 of the 2 training sessions, and a placebo was used in the other. The subjects’ resistance was tested using the repetitions to fatigue test, at 80% of their predetermined 1 repetition maximum (RM), in the 8 sets of flat barbell bench presses during the pectoral training session (S1-4 and S1′-4′). The p-value was 0.05. The number of repetitions showed a significant increase from placebo treatment to CM treatment from the third set evaluated (p <0.0001). This increase was positively correlated with the number of sets, achieving 52.92% more repetitions and the 100% of response in the last set (S4′). A significant decrease of 40% in muscle soreness at 24 hours and 48 hours after the pectoral training session and a higher percentage response than 90% was achieved with CM supplementation. The only side effect reported was a feeling of stomach discomfort in 14.63% of the subjects. We conclude that the use of CM might be useful to increase athletic performance in high-intensity anaerobic exercises with short rest times and to relieve postexercise muscle soreness. Thus, athletes undergoing intensive preparation involving a high level of training or in competitive events might profit from CM.

“It helps remove ammonia from the body so that tiredness doesn’t set in as quickly. Using this supplement, athletes can work longer, increase endurance capacity and recover more quickly with less soreness.”

“Oral L-citrulline supplementation (as in [pre-workout]) enhances cycling time trial performance in healthy trained men.”

References

https://www.ncbi.nlm.nih.gov/pubmed/20386132

https://health.ucsd.edu/news/features/Pages/2016-04-29-nutritional-supplements-and-exercise.aspx

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759860/

Safety Issues

“Women who are pregnant or breastfeeding should not use citrulline supplements.”

References

https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=19&contentid=Citrulline

From Wikipedia

The organic compound citrulline is an α-amino acid. Its name is derived from citrullus, the Latin word for watermelon, from which it was first isolated in 1914 by Koga & Odake. It was finally identified by Wada in 1930.[2] It has the formula H2NC(O)NH(CH2)3CH(NH2)CO2H. It is a key intermediate in the urea cycle, the pathway by which mammals excrete ammonia.

In the body, citrulline is produced as a byproduct of the enzymatic production of nitric oxide from the amino acid arginine, catalyzed by nitric oxide synthase.[3] This is an essential reaction in the body because nitric oxide is an important vasodilator required for regulating blood pressure.

Citrulline is made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine as a by-product of the reaction catalyzed by NOS family (NOS; EC 1.14.13.39).[4] It is made from arginine by the enzyme trichohyalin at the inner root sheath and medulla of hair follicles.[5] Arginine is first oxidized into N-hydroxyl-arginine, which is then further oxidized to citrulline concomitant with release of nitric oxide.

–Wikipedia

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Beta Alanine (β-Alanine) is an amino acid that occurs naturally in the human body. Not only is Beta Alanine a precursor to Carnosine, it is the rate limiting precursor. In other words, your body runs out of Beta Alanine before any other “ingredient” when creating Carnosine.

Beta Alanine is one of the most common ingredients in a majority of pre-workout supplements as a precursor to nitric oxide as a vaso-dilator (a set of enzymes that widen blood vessels increasing blood flow to muscles). More blood flow to muscles means more oxygen and nutrients when you need them most.

Benefits of Beta Alanine

β-alanine supplementation has become a common practice among competitive athletes participating in a range of different sports. Although the mechanism by which chronic β-alanine supplementation could have an ergogenic effect is widely debated, the popular view is that β-alanine supplementation augments intramuscular carnosine content, leading to an increase in muscle buffer capacity, a delay in the onset of muscular fatigue, and a facilitated recovery during repeated bouts of high-intensity exercise.

β-alanine supplementation appears to be most effective for exercise tasks that rely heavily on ATP synthesis from anaerobic glycolysis. However, research investigating its efficacy as an ergogenic aid remains equivocal, making it difficult to draw conclusions as to its effectiveness for training and competition. The aim of this review was to update, summarize, and critically evaluate the findings associated with β-alanine supplementation and exercise performance with the most recent research available to allow the development of practical recommendations for coaches and athletes. A critical review of the literature reveals that when significant ergogenic effects have been found, they have been generally shown in untrained individuals performing exercise bouts under laboratory conditions. The body of scientific data available concerning highly trained athletes performing single competition-like exercise tasks indicates that this type of population receives modest but potentially worthwhile performance benefits from β-alanine supplementation. Recent data indicate that athletes may not only be using β-alanine supplementation to enhance sports performance but also as a training aid to augment bouts of high-intensity training. β-alanine supplementation has also been shown to increase resistance training performance and training volume in team-sport athletes, which may allow for greater overload and superior adaptations compared with training alone. The ergogenic potential of β-alanine supplementation for elite athletes performing repeated high-intensity exercise bouts, either during training or during competition in sports which require repeated maximal efforts (e.g., rugby and soccer), needs scientific confirmation.

Role of beta-alanine supplementation on muscle carnosine and exercise performance

In this narrative review, we present and discuss the current knowledge available on carnosine and beta-alanine metabolism as well as the effects of beta-alanine supplementation on exercise performance. Intramuscular acidosis has been attributed to be one of the main causes of fatigue during intense exercise. Carnosine has been shown to play a significant role in muscle pH regulation. Carnosine is synthesized in skeletal muscle from the amino acids l-histidine and beta-alanine. The rate-limiting factor of carnosine synthesis is beta-alanine availability. Supplementation with beta-alanine has been shown to increase muscle carnosine content and therefore total muscle buffer capacity, with the potential to elicit improvements in physical performance during high-intensity exercise. Studies on beta-alanine supplementation and exercise performance have demonstrated improvements in performance during multiple bouts of high-intensity exercise and in single bouts of exercise lasting more than 60 s. Similarly, beta-alanine supplementation has been shown to delay the onset of neuromuscular fatigue. Although beta-alanine does not improve maximal strength or VO2max, some aspects of endurance performance, such as anaerobic threshold and time to exhaustion, can be enhanced. Symptoms of paresthesia may be observed if a single dose higher than 800 mg is ingested. The symptoms, however, are transient and related to the increase in plasma concentration. They can be prevented by using controlled release capsules and smaller dosing strategies. No important side effect was related to the use of this amino acid so far. In conclusion, beta-alanine supplementation seems to be a safe nutritional strategy capable of improving high-intensity anaerobic performance.

References

https://www.ncbi.nlm.nih.gov/pubmed/24276304

https://www.ncbi.nlm.nih.gov/pubmed/20479615

Beta Alanine Dosage

Stellingwerff (in press) recently published findings which demonstrate that as the dose of β-alanine supplemented increases, the duration of supplementation required to elicit changes in the muscle carnosine content is reduced. There is currently no known threshold to the storage of carnosine in muscle and therefore it would seem logical that the more β-alanine that is supplemented, be that at a lower dose over a longer duration or at a higher dose over a shorter duration, the more carnosine can be synthesised and stored in the muscle. This could lead to a greater muscle buffering capacity during high-intensity exercise and therefore an improvement in exercise outcomes. Indeed, this theory is partially supported by the data of Hill et al. (2007) in which total work done during a cycling capacity test increased by 13% after 4 weeks and a further 3.2% after 10 weeks of β-alanine supplementation, with no changes shown in the control group. Hill et al. (2007) demonstrated a continuing improvement in exercise outcome with increased amounts of β-alanine ingested, although the relationship was not linear.

The median overall effect of β-alanine supplementation is a 2.85% (−0.37 to 10.49%) improvement in the outcome of an exercise measure, when 179 g of β-alanine is supplemented; although this value is likely to change dependent upon a variety of factors. In the only test to be repeated following 4 weeks of β-alanine supplementation across two different studies, increases in exercise capacity were indeed outside this range at 11.8% (Hill et al. 2007) and 12.1% (Sale et al. 2011). From the data available to date, it can be concluded that β-alanine supplementation elicits a significant ergogenic effect on high-intensity exercise, particularly in exercise capacity tests and measures, and where the exercise lasts between 1 and 4 min. Areas which warrant further investigation due to the borderline efficacy of β-alanine, i.e., exercise lasting over 240 s, have also been highlighted. This meta-analysis has shown that exercise performance tests and measures, and exercise of less than 60 s duration are not improved by β-alanine supplementation. Given the types, intensities and durations of exercise positively influenced by β-alanine supplementation, we maintain that the most likely mechanism supporting a benefit is through an increase in intracellular pH buffering as the result of increased muscle carnosine levels.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374095/

Side Effects

“β-alanine causes paraesthesia in some individuals (Harris et al. 2006)”

“The washout period for β-alanine has been shown to be 15 weeks or longer (Baguet et al.2009; Stellingwerff (in press).”

From Wikipedia

β-Alanine (or beta-alanine) is a naturally occurring beta amino acid, which is an amino acid in which the amino group is at the β-position from the carboxylate group (i.e., two atoms away). The IUPAC name for β-alanine is 3-aminopropanoic acid. Unlike its counterpart α-alanine, β-alanine has no stereocenter.

β-Alanine is not used in the biosynthesis of any major proteins or enzymes. It is formed in vivo by the degradation of dihydrouracil and carnosine. It is a component of the naturally occurring peptides carnosine and anserine and also of pantothenic acid (vitamin B5), which itself is a component of coenzyme A. Under normal conditions, β-alanine is metabolized into acetic acid.

β-Alanine is the rate-limiting precursor of carnosine, which is to say carnosine levels are limited by the amount of available β-alanine, not histidine. Supplementation with β-alanine has been shown to increase the concentration of carnosine in muscles, decrease fatigue in athletes and increase total muscular work done. Simply supplementing with carnosine is not as effective as supplementing with β-alanine alone since carnosine, when taken orally, is broken down during digestion to its components, histidine and β-alanine. Hence, by weight, only about 40% of the dose is available as β-alanine.

–Wikipedia

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