L-ornithine is a non-proteinogenic amino acid which also naturally exists as a free amino acid. L-ornithine is one of the constituents of the urea cycle that converts harmful ammonia into urea in vivo. L-ornithine (mg/100g) is found in foods such as freshwater clam (shijimi) (159.9), rice (26), mustard tuna (1.9-7.2), green tea (2-15), and wheat flour bread (0.4) (Uchisawa et al., Biotech. Biochem. 68 (2004), Cagampang et al., Cereal Chemists. 48 (1971), Antoine et al., Food Chem. & Toxico. 66 (2001), Ohtsuki et al., Agric. Biol. Chem., 51 (1987), Prieto et al., J. Chromato. Sci. 28 (1990)). In recent years, L- ornithine has been used as a supplement for physiological activity that it has been reported liver function (Müting et al., Amino Acids 3 (1992)), sleep quality (Horiuchi et al., Nutr Res 3 (2013), Miyake et al., Nutr J, 3 (2014)) and so on.
The following reports on the safety of L-ornithine are available. In a non-clinical study, rats were exposed to repeated doses of L-ornithine at concentrations of 1.25, 2.5, and 5.0% diet for 13 weeks. From the results of this study, the NOAEL for L-ornithine was reported to be 5.0% diet (male: 3,444 mg/kg/ days, female: 3,985 mg/kg/ days) ((Ishida et al., Reg. Toxico. Pharm. 67 (2013)). A human safety study was conducted in which 10 g of L-ornithine-α-ketoglutarate (equivalent to 6. 4g as L-ornithine and 8g as L-ornithine hydrochloride) was ingested for 2 months. The results of this study indicate no observed adverse effects associated with the administration of 10 g/day of L-ornithine-α-ketoglutarate. There were dropouts due to gastrointestinal symptoms, but a causal association with L-ornithine ingestion has not been reported (Brocker et al., Age and ageing 23 (1994)).