Nitric Oxide

Nitric oxide supplements contain nitrates or amino acids such as L-arginine and L-citrulline that are used to synthesize nitric oxide within the body. Increasing nitric oxide is of interest to athletes due to its potential effects on improving blood flow and regulating muscle hypertrophy. This may lead to exercise performance improvements, especially endurance outcomes. L-arginine is the primary ingredient in most nitric oxide supplements; however, oral supplementation is controversial with regards to increasing nitric oxide levels. Emerging evidence suggests L-citrulline and citrulline malate supplementation may be more effective than L-arginine at improving nitric oxide levels, thereby providing potential ergogenic performance benefit. (Bloomer 2010, Jones 2016)

Nitric oxide (NO) is a vasodilator that may lead to increased blood flow, oxygen delivery, and nutrient transport to tissues including skeletal muscle (Mendel 2005). It is suggested that increasing nitric oxide production can improve tolerance to physical exercise and recovery mechanisms (Besco 2012).

L-arginine is a precursor to nitric oxide biosynthesis and is correlated with increased vasodilation (Bloomer 2010). However, L-citrulline supplementation may be more effective at increasing plasma arginine levels than actual L-arginine supplementation (Jones 2016).

Nitric oxide precursors such as L-arginine may be effective for enhancing cardiorespiratory adaptation and tolerance to endurance exercise in moderately trained or untrained subjects (Bescos 2012). Benefits of L-arginine supplementation have been demonstrated for untrained and sedentary individuals, but have shown no effect on trained athletes (Jones 2016).

Intravenous L-arginine has shown to increase blood flow, but oral supplementation is ineffective (Cholewa 2019). The way oral L-arginine is metabolized contributes to its ineffectiveness and is why L-citrulline supplementation may serve as an alternative to increase nitric oxide levels and improve performance. Cholewa (2019) stated "orally ingested l-citrulline is not subject to extensive pre-systemic degradation and therefore increases plasma arginine levels more efficiently than oral l-arginine supplementation".

Recent research evaluating aerobic exercise performance has documented improvements in time to exhaustion after L-citrulline supplementation (Cholewa 2019). In general, L-citrulline alone does not improve exercise performance, but the addition of malate may lead to increased nitric oxide metabolites (Bescos 2012).

While there is some evidence that shows improved aerobic and endurance exercise performance with increased nitric oxide concentration, there is no human evidence that shows nitric oxide precursor supplements promote muscle hypertrophy in young, healthy muscle. This is mainly because the current evidence focuses on endurance performance. L-arginine has shown to be ineffective as an oral supplement and while L-citrulline and citrulline malate show more promise for improving nitric oxide levels, the effect on athletic performance remains unclear. (Cholewa 2019)


Besco R, Sureda A, Tur JA, Pons A (2012). The effect of nitric-oxide-related supplements on human performance. Sports Medicine, 42(2), 99-117.

Bloomer RJ (2010). Nitric oxide supplements for sports. Strength and Conditioning Journal, 32(2), 14-20.

Cholewa J, Trexler E, Lima-Soares F, de Araújo Pessôa K, Sousa-Silva R, Santos AM, Zhi X, Nicastro H, Cabido CET, de Freitas MC, Rossi F, Zanchi NE (2019). Effects of dietary sports supplements on metabolite accumulation, vasodilation and cellular swelling in relation to muscle hypertrophy: A focus on "secondary" physiological determinants. Nutrition (Burbank, Los Angeles County, Calif.), 60, 241.

Jones AM (2016). Dietary Nitric Oxide Precursors and Exercise Performance. Gatorade Sports Science Institute. Retrieved March 26, 2019, from

Mendel R (2005). SPORTS SUPPLEMENTS: Supplements that regulate nitric oxide: Logical or physiological? Strength and Conditioning Journal, 27(2), 38.

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