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Catabolism and safety of supplemental l-arginine in animals

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Abstract

l-arginine (Arg) is utilized via multiple pathways to synthesize protein and low-molecular-weight bioactive substances (e.g., nitric oxide, creatine, and polyamines) with enormous physiological importance. Furthermore, Arg regulates cell signaling pathways and gene expression to improve cardiovascular function, augment insulin sensitivity, enhance lean tissue mass, and reduce obesity in humans. Despite its versatile roles, the use of Arg as a dietary supplement is limited due to the lack of data to address concerns over its safety in humans. Data from animal studies are reviewed to assess arginine catabolism and the safety of long-term Arg supplementation. The arginase pathway was responsible for catabolism of 76–85 and 81–96 % Arg in extraintestinal tissues of pigs and rats, respectively. Dietary supplementation with Arg–HCl or the Arg base [315- and 630-mg Arg/(kg BW d) for 91 d] had no adverse effects on male or female pigs. Similarly, no safety issues were observed for male or female rats receiving supplementation with 1.8- and 3.6-g Arg/(kg BW d) for at least 91 d. Intravenous administration of Arg–HCl to gestating sheep at 81 and 180 mg Arg/(kg BW d) is safe for at least 82 and 40 d, respectively. Animals fed conventional diets can well tolerate large amounts of supplemental Arg [up to 630-mg Arg/(kg BW d) in pigs or 3.6-g Arg/(kg BW d) in rats] for 91 d, which are equivalent to 573-mg Arg/(kg BW d) for humans. Collectively, these results can help guide studies to determine the safety of long-term oral administration of Arg in humans.

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Abbreviations

AA:

Amino acid(s)

Arg:

l-arginine

AUC:

Area-under-the curve

BW:

Body weight

CAT:

Cationic amino acid transporter

d:

Day(s)

hArg:

Homoarginine

MRSD:

Maximum recommended starting dose

NO:

Nitric oxide

NOS:

Nitric oxide synthase

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Acknowledgments

This work was supported by grants from International Council of Amino Acid Science (Brussels, Belgium), Texas A&M AgriLife Research (H-8200), National Basic Research Program of China (2012CB126305), National Natural Science Foundation of China (31172217 and 31272450), Natural Science Foundation of Hubei Province (2013CFA097 and 2013CFB325), and Hubei Hundred Talent program. We thank Drs. Robert Burghardt, Zhaolai Dai, Gregory Johnson, Xilong Li, Sidney Morris, and Stephen Smith for research collaboration.

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Authors and Affiliations

  1. State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China

    Zhenlong Wu & Guoyao Wu

  2. Hubei Key Laboratory of Animal Nutrition and Feed Science, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University, Wuhan, 430023, China

    Yongqing Hou & Guoyao Wu

  3. Department of Animal Science, Texas A&M University, College Station, Texas, TX, 77843, USA

    Shengdi Hu, Fuller W. Bazer & Guoyao Wu

  4. Department of Medical Physiology, Texas A&M Health Science Center, Temple, TX, 76504, USA

    Cynthia J. Meininger & Guoyao Wu

  5. Department of Internal Medicine, Baylor Scott and White Health, Temple, TX, 76508, USA

    Catherine J. McNeal

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  1. Zhenlong Wu
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The use of animals for our research described in this review article was approved by the Institutional Animal Care and Use Committee of Texas A&M University.

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Wu, Z., Hou, Y., Hu, S. et al. Catabolism and safety of supplemental l-arginine in animals. Amino Acids 48, 1541–1552 (2016). https://doi.org/10.1007/s00726-016-2245-9

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