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L-Arginine and L-Citrulline Benefits: Fitness, Vascular Health, and More

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What Is L-Arginine?

L-arginine is an amino acid that plays a vital role in wound healing, detoxification reactions, and immune functions, and it promotes the secretion of several hormones, including glucagon, insulin, and growth hormone. 

L-arginine also plays a key role in blood vessels in the formation of nitric oxide, a key chemical used by the body to determine the tone of blood vessels. Specifically, nitric oxide exerts a relaxing effect on blood vessels, thereby improving blood flow.[1]

L-arginine supplementation is often used as a sports nutrition supplement to support heart and vascular health. However, results from human clinical studies have yet to consistently show that L-arginine supplementation, even at dosages above 3 g daily, provides many benefits. 

L-Arginine Food Sources

L-arginine is naturally found in many nuts and seeds and is also found in meat, seafood, and soy. Even when dietary intake is insufficient, normally, the body makes enough L-arginine to meet demand. However, in some instances, the body may need additional support through supplementation to meet its needs. 

What Is L-Citrulline?

L-citrulline has shown very positive results as a precursor to L-arginine. L-citrulline is a unique amino acid naturally found primarily in watermelon. In the body, L-citrulline is converted to L-arginine.[2-5]

L-citrulline supplementation has been shown to be more efficient than L-arginine for raising L-arginine levels in the body. As a result, L-citrulline is much more effective in supporting and producing positive clinical results. L-citrulline has surpassed L-arginine in popularity as a sports supplement and is also included in many combination products.[2-5]

Fitness Benefits

In experimental studies, L-arginine supplementation has been shown to influence growth hormone production, blood flow, mitochondrial function, and energy metabolism. All these effects may benefit athletes and others. However, results from human clinical trials show little benefit with L-arginine supplementation in improving physical performance. In contrast, L-citrulline has shown positive results in many double-blind human studies.[1-5] 

Most of these studies show that L-citrulline supplementation at a typical dosage of 2.4 to 6 grams daily may enhance strength, power, and endurance during high-intensity resistance exercise.[2-5] Endurance in strength training exercises is defined as repetitions required to reach failure to produce one more repetition. In strength training, exercising to be unable to do one more rep is regarded as the most potent way to stimulate muscle growth. So, the ability of L-citrulline supplementation to increase the number of reps before failure is viewed as a very beneficial effect.

While not all studies with L-citrulline supplementation in sports medicine have shown benefits, several reviews of all current data have concluded that L-citrulline supplementation significantly benefits high-intensity strength and power performance.[2-5] L-citrulline supplementation has also shown some effects in reducing muscle soreness after weight training.[6] It does not, however, improve aerobic exercise endurance.[7]

Effects on Growth Hormone Secretion

One of the more popular uses of L-arginine has been to promote the secretion of growth hormone by the pituitary gland. Growth hormone is responsible for stimulating muscle and skeletal growth. 

Bodybuilders often utilize L-arginine supplementation to try to boost the natural output of growth hormone. There appears to be some basis for this use with some caveats. The effect of L-arginine on increasing growth hormone output is well accepted. In fact, measuring growth hormone levels in the blood after L-arginine is administered intravenously is used to gauge whether a child or adult is secreting enough growth hormone. L-arginine supplementation (10 g per day) slightly boosted growth hormone secretion in younger adult males.[8] However, L-arginine supplementation does not appear to enhance growth hormone release in older subjects. Even at 15 g per day, L-citrulline did not raise growth hormone levels in healthy males.[9]

Cardiovascular Support

L-arginine supplementation has been shown to be beneficial in supporting the health of the heart and blood vessels. By increasing nitric oxide levels, L-arginine supplementation improves blood flow, reduces blood clot formation, and improves blood fluidity (the blood becomes less dense and flows through blood vessels more quickly). 

Again, L-citrulline has produced better results in human clinical trials. This has been clearly demonstrated in human trials, showing that L-citrulline or watermelon extracts exert better effects than L-arginine on supporting blood pressure control. In addition, L-citrulline appears to have better results in restoring blood vessel wall flexibility.[5]

Supporting Erectile Function

Nitric oxide is a necessary physiologic signal critical in producing an erect penis. Based upon the results of a recent study, it turns out that many men who have erectile dysfunction have low blood levels of L-arginine and L-citrulline compared to men who more easily achieve penile erection. Low levels of these amino acids are also associated with lower blood flow through erectile tissue. The reduced ability to achieve an erection and the more insufficient penile blood flow are thought to be the result of reduced formation of nitric oxide due to the low L-arginine and L-citrulline levels.[10]

L-citrulline supplementation (1.5 g per day for one month) was shown to improve the erection hardness score in one human clinical trial. Only 8.3% of the men taking the placebo achieved an average erection hardness score, while 50% of the men taking L-citrulline achieved this level. The average number of times of sexual intercourse per month increased from 1.37 at baseline to 2.3 after the L-citrulline supplementation.[11]

There have also been several clinical trials that have utilized either L-arginine combined with pine bark extract or L-citrulline combined with resveratrol, which have also shown positive results.[12,13]

References:

  1. Gupta MN, Uversky VN. Biological importance of arginine: A comprehensive review of the roles in structure, disorder, and functionality of peptides and proteins. Int J Biol Macromol. 2023 Dec 5:128646.
  2. Rashid J, Kumar SS, Job KM, et al. Therapeutic Potential of Citrulline as an Arginine Supplement: A Clinical Pharmacology Review. Paediatr Drugs. 2020 Jun;22(3):279-293.
  3. Park HY, Kim SW, Seo J, et al. Dietary Arginine and Citrulline Supplements for Cardiovascular Health and Athletic Performance: A Narrative Review. Nutrients. 2023 Mar 3;15(5):1268. D
  4. Gonzalez AM, Townsend JR, Pinzone AG, Hoffman JR. Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature. Nutrients. 2023 Jan 28;15(3):660.
  5. Trexler ET, Persky AM, Ryan ED,. Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis. Sports Med. 2019 May;49(5):707-718. 
  6. Rhim H.C., Kim S.J., Park J., Jang K.-M. Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: A systematic review and meta-analysis. J. Sport Health Sci. 2020;9:553–561.
  7. Viribay A, Fernández-Landa J, Castañeda-Babarro A, et al. Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis. Nutrients. 2022 Aug 24;14(17):3479.
  8. Apolzan JW, Stein JA, Rood JC, et al. Effects of acute arginine supplementation on neuroendocrine, metabolic, cardiovascular, and mood outcomes in younger men: A double-blind, placebo-controlled trial. Nutrition. 2022 Sep;101:111658.
  9. Moinard C, Nicolis I, Neveux N, et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008 Apr;99(4):855-62.
  10. Barassi A, Corsi Romanelli MM, Pezzilli R, et al. Levels of l-arginine and l-citrulline in patients with erectile dysfunction of different etiology. Andrology. 2017 Mar;5(2):256-261.
  11. Cormio L, De Siati M, Lorusso F, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011 Jan;77(1):119-22.
  12. Shirai M, Hiramatsu I, Aoki Y, Shimoyama H, et al. Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. Sex Med. 2018 Dec;6(4):291-296. 
  13. Tian Y, Zhou Q, Li W, Liu M, Li Q, Chen Q. Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023 Oct 4;14:1211720.

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