Adding L-citrulline increases plasma L-arginine in men

Relation

Suzuki T, Morita M, Hayashi T, Kamimura A. The effects of combined oral L-citrulline and L-arginine supplementation in healthy men on plasma L-arginine levels.Biosci Biotechnol Biochem. 2017;81(2):372-375.

Draft

Double-blind, randomized, placebo-controlled study

Participant

42 healthy, non-obese Japanese men aged 20-49; Smokers and men taking medications or dietary supplements were excluded. The men were randomized into 1 of 4 groups:

1. Placebo (Maisstärke) (n = 11)
2. L-Citrullin allein 2,0 g/Tag (n = 11)
3. L-Arginin allein 2,0 g/Tag (n = 10)
4. L-Citrullin mit L-Arginin, jeweils 1,0 g/Tag (n = 10)

Primary outcome measure

Plasma levels of L-arginine after supplementation

Key insights

One hour after supplementation, all groups had an increase in L-arginine plasma levels compared to placebo; however, values ​​were significantly higher in the L-citrulline, L-arginine combination group (placebo 5.4 ± 16.3; combination 121.9 ± 46.7; citrulline alone 66.3 ± 33.6; arginine alone 72.3 ± 31.5). Levels in the combination group were approximately 40% higher than in the L-arginine alone group. None of the participants experienced side effects from any of the treatments during the study.

Practice implications

While previous animal studies have shown that combining L-arginine with L-citrulline increases L-arginine plasma levels, to my knowledge this is the first human clinical study to show this effect.^1.2This is clinically significant given the research showing the diverse and important health benefits of L-arginine supplementation in men. Human clinical studies have shown that L-arginine supplementation can help improve erectile dysfunction (ED).³insulin resistance,⁴and sporting performance.⁵

Specific to ED, research shows that men with ED have low serum levels of L-citrulline and L-arginine.⁶Reduced nitric oxide levels are associated with an increased risk of erectile dysfunction. Arginine is a nitric oxide precursor, so it makes sense that low concentrations of nitric oxide synthase substrates such as L-arginine and L-citrulline could positively impact ED.

This is clinically significant given the research showing the diverse and important health benefits of L-arginine supplementation in men.

There is also evidence that supplemental L-arginine may help prevent and treat cardiovascular disease, likely due to its influence on endothelial nitric oxide production.^7.8A review by Alyavi et al. from 2016 demonstrated the clinical benefit of L-arginine supplementation specifically in ischemic heart disease and again cited synthesis of nitric oxide production as a key mechanism of action.⁹

Based on previous in vitro and in vivo research showing that L-citrulline suppresses arginase activity,¹⁰The researchers of this present study speculate that this could be a possible mechanism that explains the significant increase with the combination of the 2 amino acids. Previous research has shown that oral L-arginine has reduced bioavailability as it is broken down by arginase in the gastrointestinal tract (40%) and liver (15%) on the first pass.^11,12In the past, fairly large doses of L-arginine alone were required to produce a therapeutic effect in humans. By inhibiting arginase activity through the addition of L-citrulline, it is likely that more L-arginine can pass through the intestines and liver into the bloodstream. As shown in this study and previous studies, L-citrulline is a precursor to L-arginine and alone can increase L-arginine levels.¹³

Since we know that L-arginine can positively impact a man's health, it makes sense from a clinical perspective to investigate this combination as it appears to improve the bioavailability of an oral L-arginine supplement. Since this was a small study, further research is needed to further confirm this effect.