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Citrulline Malate

Writer: James ShmagranoffJames Shmagranoff

Updated: May 5, 2021

Overview

· A nonessential amino acid (Figueroa et al., 2017)

· Endogenous precursor of L-arginine, a substrate for NO synthase (Figueroa et al., 2017)

· Converted to arginine in urea cycle (Figueroa et al., 2017)

· Not catabolized by arginase enzymes (Figueroa et al., 2017)

Effective inhibitor or arginase enzyme (Figueroa et al., 2017)

· Bypasses liver uptake and degradation (Figueroa et al., 2017).

· Typically bonded to malate salts (Papadia et al., 2017)

Malate functions in the krebs cycle as an intermediary (Papadia et al., 2017)

Increases cellular energy production (Papadia et al., 2017)

Function

· Nitric oxide (NO) is a modulator of blood flow in the body (Suzuki et al., 2016) and is a vasorelaxant (Gropper & Smith, 2013)

· NO is produced within the endothelium of arterioles (Powers & Howley, 2015)

· NO promotes smooth muscle relaxation, causing vasodilation and thus increased blood flow

Occurs via nitric oxide-cyclic guanosine triphosphate pathway (Figueroa et al., 2017).

Smooth muscle relaxation is caused by decreases in Ca2+ levels (Figueroa et al., 2017).

· NO is a requirement for optimal muscle blood flow regulation during exercise

· NO is also a modulator of muscle energy metabolism and mitochondrial respiration during bouts of exercise (Suzuki et al., 2016)


NO binds to cytochrome c oxidase within mitochondria to restrict oxygen consumption(Figueroa et al., 2017)

L-citrulline consumption may have a positive effect on improving the match between metabolic demands and muscle oxygenation (Figueroa et al., 2017).


· Consumption of foods high in citrulline or synthetic citrulline supplementation can increase l-arginine bioavailability and increase synthesis rates of NO (Figueroa et al., 2017)

Supplementation with L-arginine does not seem to produce the same effect since supplementation is catabolized by arginase enzyme causing this not to be a suitable route of supplementation (Figueroa et al., 2017)


Sources

· Citrulline present in fruit (most notably watermelon which is the richest source)

· Found in vegetables such garlic and onion

· Legumes such as chick peas

· Salmon and red meat

· Almonds, walnut and peanuts

· Dark chocolates

· Supplemental sources: Citrulline Malate, di-citrulline malate, and various ratios of citrulline to malic acid blends (ie: 1:1, 2:1)


Citrulline effects on health

· 8 weeks of citrulline supplementation was found to have a favorable effect on artery flow mediated dilation in patients suffering from vasospastic angina (Figueroa et al., 2017)

· Previous research demonstrated and increased endothelium-dependent vasorelaxation with citrulline supplementation which caused reductions in arterial stiffness (Bailey et al., 2015)

· Reduces endothelial damage (Papadia et al., 2017)

· 6g/day reduced brachial and aortic systolic and diastolic blood pressure by (~7/3mmHg) and (~9/3mmHg) respectively among prehypertensive patients, hypertensive obese postmenopausal women and even patients with heart failure (Figueroa et al., 2017)

· Citrulline supplementation can reduce blood pressure in otherwise healthy populations and those with healthy normotensive adults (Bailey et al., 2015)

· Citrulline supplementation effects the immune system by reducing total number of leukocytes and neutrophils in circulation (Papadia et al., 2017)


Citrulline effects on exercise

· Significant effect on increasing plasma arginine levels

Enhances nitric oxide (NO) levels in the body, improving sports performance

· Positive subjective effects on muscle fatigue and concentration

· Clinical research demonstrating reduced time to perform cycle ergometer trials

· Citrulline supplementation increased VO2 kinetics due to enhanced O2 muscle availability during exercise bouts and increased muscle oxidative ATP production

· Shown to enhance endurance exercise performance and exercise tolerance

· Demonstrated to increase muscle force production, reduce declined force production with endotoxemia, and improve contractile efficiency

· Lower rate of phosphocreatine degredation, and reduced post exercise blood ammonia and lactate concentrations

· Studies using 8g of citrulline pre workout demonstrated a 40% decrease in muscle soreness following trainng at both the 24 and 48 hour mark

· 57% increase in nitrogen balance associated with citrulline supplementation demonstrating an anabolic effect from citrulline


Effective Doses and considerations for supplementation

o Doses utilized in most studies ranged from 2.4g/day, 6g/day, 8g day

o Considered safe for oral consumption witch no long term identified toxicity, even in oral doses of up to 15g (Papadia et al., 2017)


Disclaimer

All programs and articles provided are intellectual property of James Shmagranoff. No copies or redistribution of these is allowed without express permission from James Shmagranoff. James Shmagranoff is not a doctor and nothing contained within this article is to be taken as medical advice. Always follow the directions of your medical practitioner.



References

Bailey, S.J., Blackwell, J.R., Lord, T., Vanhatalo, A., Winyard, P.G., & Jones, A.M. (2015). L-citrulline supplementation improves 02 uptake kinetics and high intensity exercise performance in humans. J Appl Physiol, 119, 385-395. Retrieved from https://pdfs.semanticscholar.org/94e2/eb7ca741f2232c7bb404233ae6edd3c74033.pdf


Figueroa, A., Wong, A., Jaime, S.,J., & Gonzales, J.U. (2017). Influence of l-citrulline and watermelon supplementation on vascular function and exercise performance. Curr Opin Clin Nutr Metab Care, 20(1), 92-98. doi:10.1097/MCO.0000000000000340


Gropper, S.S., & Smith, J.L. (2013). Advanced Nutrition and Human Metabolism (6th ed)(pp419). Belmont, CA: Wadsworth, Cengage Learning


Papadia, C., Osowska, S., Cynober, L., & Forbes, A. (2017). Citrulline in health and disease. Review on human studies. Clinical nutrition. doi: 10.1016/j.clnu.2017.10.009


Powers, S.K., & Howley, E.T. (2015). Exercise Physiology: Theory and application to fitness and performance(9th ed.) (pp. 207). New York, NY: McGraw Hill Education.


Suzuki, T., Morita, M., Kobayashi, Y., & Kamimura, A. (2016). Oral l- citrulline supplementation enhances cycling time trial performance in healthy trained men: double blind randomized placebo controlled 2 way crossover study. Journal of the International Society of Sports Nutrition, 13(6). Retrieved from https://jissn.biomedcentral.com/articles/10.1186/s12970-016-0117-z

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