Dietary supplementation with l-lysine affects body weight and blood hematological and biochemical parameters in rats

  • Chao-Wu Xiao
  • Carla Wood
  • Jesse Bertinato
Original Article


l-Lysine (Lys) is a popular additive in foods, but the physiological effects of excess Lys supplementation are poorly understood and upper limits of safe intake have not been established. The objectives of this study were to examine the effects of dietary supplementation with increasing amounts of Lys on body weight (BW), food intake, and various blood hematological and biochemical parameters in rats. Male Sprague–Dawley rats at 10 weeks of age were assigned to ten diet groups (eight rats/group) and fed diets containing either 7% or 20% casein and supplemented with either 0% (Control), 1.5%, 3%, 6% Lys, or 6% Lys + 3% arginine for 1 week. Rats fed 7% casein with ≥ 1.5% Lys supplementation had lower serum albumin and leptin and higher LDL cholesterol (LDLC), ratios of total cholesterol (TC):HDL cholesterol (HDLC) and LDLC:HDLC than those fed 7% casein Control diet (P < 0.05). Rats fed 7% casein diet supplemented with 3% Lys diet had lower BW gain, food intake, serum alkaline phosphatase activity, and increased mean corpuscular hemoglobin concentration, blood urea nitrogen and serum pancreatic polypeptide compared to rats fed the Control diet (P < 0.05). Addition of 6% Lys in 7% casein caused significant BW loss (P < 0.001) and altered additional parameters. Addition of 6% Lys in a 20% casein diet reduced BW gain and food intake and altered numerous parameters. Arg supplementation normalized many of the endpoints changed by Lys. Collectively, these results show that Lys supplementation affects BW, food intake and a number of hematological and biochemical parameters. These effects of Lys supplementation were confined primarily in diets with lower levels of dietary protein. In the context of a low protein diet (7% casein), levels of Lys supplementation ≥ 1.5% may exert adverse health effects in rats.


l-Lysine l-Arginine Supplementation Biomarkers Biochemical parameters Rats 



Amino acid






Alkaline phosphatase


Alanine aminotransferase




Aspartate aminotransferase


Blood urea nitrogen


Body weight


High density lipoprotein cholesterol


Low density lipoprotein cholesterol




Mean corpuscular hemoglobin concentration


Nitric oxide


Pancreatic polypeptide



This research was funded by Health Canada. We thank the technicians in the Scientific Service Division (SSD), Food Directorate, Health Canada for their outstanding assistance during the animal experimentation phase. We thank Mr. Dominique Patry (SSD) for measuring the blood hematological and biochemical parameters, and Mr. Philip Griffin for his technical assistance at necropsies.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

All authors in this paper have read the final manuscript and approved for publication.

Research involving animals

The animal experimental protocol (ACC#2014-018) was approved by the Health Canada-Ottawa Animal Care Committee, and all animal handling and care followed the guidelines of the Canadian Council for Animal Care.


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Copyright information

© Her Majesty the Queen in Right of Canada, represented by the Minister of Health 2018

Authors and Affiliations

  1. 1.Nutrition Research Division, Bureau of Nutritional Sciences, Food Directorate, Health Products and Food BranchHealth CanadaOttawaCanada
  2. 2.Food and Nutrition Science Program, Department of ChemistryCarleton UniversityOttawaCanada

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