アミノ酸の安全性
Safety Studies of Amino Acids in Animals
Amino Acid | Animal | Method of administration | Duration (recovery period) |
Dose | Reference | |
Indispensable Amino Acids | ||||||
---|---|---|---|---|---|---|
L-histidine | Fischer rat | Mixed food | 13W | 0.31, 0.62, 1.25, 2.5, 5% (w/w) | [Japanese] Bull Natl Ins Health Sci (1994), 112:57-63 "13-week subchronic toxicity study of L-histidine monohydrochloride in F344 rats" Ikezaki S, Nishikawa A, et al. |
|
L-isoleucine | SD rat | Mixed food | 13W (5W) | 1.25, 2.5, 5% (w/w) | Int J Toxicol (2004), 23(2):119-126 “Thirteen-week oral toxicity study of branched-chain amino acids in rats” Tsubuku S, Hatayama K, et al. |
|
L-leucine | SD rat | Mixed food | 13W (5W) | 1.25, 2.5, 5% (w/w) | Int J Toxicol (2004), 23(2):119-126 “Thirteen-week oral toxicity study of branched-chain amino acids in rats” Tsubuku S, Hatayama K, et al. |
|
L-lysine/HCl | SD rat | Mixed food | 13W (5W) | 1.25, 2.5, 5% (w/w) | Int J Toxicol (2004), 23(2):113-118 “Thirteen-week oral toxicity study of L-lysine hydrochloride in rats” Tsubuku S, Mochizuki M, et al. |
|
L-methionine | Fischer rat ♂ | Mixed food | 4W | 0.1, 0.3, 0.9, 2.7% (w/w) | Int J Toxicol (2015), 34(3):233-241 "A 4-week toxicity study of methionine in male rats" Chin K, Toue S, et al. |
|
L-phenylalanine | SD rat | Mixed food | 28 days | 0.5, 1.5, 5.0% | Fund Toxicol Sci (2014), 1(2):29-38 "28-Day dietary toxicity study of L-phenylalanine in rats" Shibui Y, Miwa T, et al. |
|
L-threonine | SD rat | Mixed food | 13W (5W) | 1.25, 2.5, 5.0% | Fund Toxicol Sci (2014), 1(2):49-62 "A 13-week feeding toxicity study of L-threonine in rats with a recovery period of 5 weeks" Aoki M, Ishida S, et al. |
|
L-tryptophan | SD rat | Mixed food | 13W (5W) | 1.25, 2.5, 5.0% | J Appl Toxicol (2018), 38(4): 552-563 "Thirteen week toxicity study of dietary L‐tryptophan in rats with a recovery period of 5 weeks" Shibui Y, Matsumoto H, et al. +LOAEL(mg/kg/day) was calicurated using original research data (BW for LOAEL). |
|
L-valine | SD rat | Mixed food | 13W (5W) | 1.25, 2.5, 5% (w/w) | Int J Toxicol (2004), 23(2):119-126 “Thirteen-week oral toxicity study of branched-chain amino acids in rats” Tsubuku S, Hatayama K, et al. |
|
Dispensable Amino Acids | ||||||
L-alanine | SD rat | Gavage | 4W (2W) | 2,000mg/kg/day | Fund Toxicol Sci (2014), 1(2):63-72 “A 4-week oral toxicity study of L-alanine in rats with a recovery period of 2 weeks” Aoki M, Mochizuki M, et al. |
|
L-arginine | SD rat | Mixed food | 13W (5W) | 1.25, 2.5, 5% (w/w) | Int J Toxicol (2004), 23(2):101-105 “Thirteen-week oral toxicity study of L-arginine in rats” Tsubuku S, Hatayama K, et al. |
|
Pig | Mixed food twice a day | 13W | 1.21, 1.81, 2.42% (w/w) |
Amino Acids (2015), 47(5):925-936 “Safety of long-term dietary supplementation with L-arginine in pigs” Hu S, Li X, et al. |
||
Mixed food twice a day | 13W | 1.0, 1.5, 2.0% (w/w) |
||||
SD rat | Drinking water |
13W | 2.18, 4.35 g/kg/day |
Amino Acids (2015), 47(9):1909-1920 “Safety of long‑term dietary supplementation with L‑arginine in rats” Yang Y, Wu Z, et al. |
||
L-asparagine | Fischer rat | Mixed food | 90 days | 1.25, 2.5, 5% (w/w) | Food Chem Toxicol (2008), 46(7):2568-2572 "A 90-day toxicity study of L-asparagine, a food additive, in F344 rats" Yokohira M, Hosokawa K, et al. |
|
L-aspartic acid | Fischer rat | Mixed food | 90 days | 0.05, 1.25, 2.5, 5.0% (w/w) | Food Chem Toxicol (2008), 46(8):2789-2795 "Toxic effects of L-aspartic acid at high dose levels on kidneys and salivary glands in Fischer 344 rats detected in a 90-day feeding study" Tada Y, Yano N, et al. |
|
L-cysteine | SD rat | Gavage | 4W | 500, 1000, 2000 mg/kg/day | J Toxicol Pathol (2017), 30(3):217-229 "Comparisons of L-cysteine and D-cysteine toxicity in 4-week repeated-dose toxicity studies of rats receiving daily oral administration" Shibui Y, Sakai R, et al. |
|
L-glutamate | - | - | - | - | Acceptable daily intake (ADI) is not specified in JECFA report. ADI can be driven from NOAEL, so that NOAEL of L-Glu/Na is not also specified.: Principles for the safety assessment of food additives and contaminants in food. World Health Organization International Program on Chemical Safety in Cooperation with the Joint FAO/WHO Expert Committee on Food Additives, Geneva, Environmental Health Criteria 70 (1987). |
|
CD-1 mouse | Mixed food | 3-genaration reproductive toxicity: F0:Gestation & lactation F1: Postweaning – Lactation F2: Postweaning – Lactation F3: Birth - Weaning |
1.0, 4.0% (w/w) | Glutamic Acid: Advances in Biochemistry and Physiology, ed. by Filer LJ, et al., Raven Press, NY (1979):231-253 “In utero and dietary administration of monosodium L-glutamate to mice: Reproductive performance and development in a multigeneration study” Anantharaman K |
||
L-glutamine | SD rat | Mixed food | 13W (5W) | 1.25, 2.5, 5% (w/w) | Int J Toxicol (2004), 23(2):107-112 “Thirteen-week oral toxicity study of L-glutamine in rats.” Tsubuku S, Hatayama K, et al. |
|
L-glycine | SD rat | Gavage | 28 days | 500, 1000, 2000 mg/kg/day | J Toxicol Pathol (2013), 26(4) 405–412, 2013 "A 4-week repeated dose toxicity study of glycine in rats by gavage administration" Shibui Y, Miwa T, et al. |
|
L-proline | Fischer rat | Mixed food | 90 days | 0.625, 1.25, 2.5, 5.0% | Regul Toxicol Pharmacol (2010), 58(1):114-120 "Toxicological evaluation of L-proline in a 90-day feeding study with Fischer 344 rats" Tada Y, Yano N, et al. |
|
L-serine | SD rat | Gavage | 13W | 500, 1500, 3000 mg/kg/day | Food Chem Toxicol (2009), 47(9):2356-2360 "A 13-week subchronic oral toxicity study of L-serine in rats" Kaneko I, Han L, et al. |
|
Fischer rat | Mixed food | 90 days | 0.06, 0.5, 1.5, 5.0% | J Toxicol Pathol (2010), 23(1):39-47 "A 90-day feeding toxicity study of L-serine in male and female Fischer 344 rats" Tada Y, Yano N, et al. |
||
L-tyrosine | SD rat | Gavage | 13W | 200, 600, 2000 mg/kg/day | Food Chem Toxicol (2016), 87:55-64 "13-week repeated dose toxicity study of l-tyrosine in rats by daily oral administration" Shibui Y, Manabe Y, et al. |
|
Non-code protein Amino Acids | ||||||
L-ornithine | SD rat | Mixed food | 13W (5W) | 1.25, 2.5, 5.0% | Regul Toxicol Pharmacol (2013), 67(3):360-71 "Genotoxicity and subchronic oral toxicity of L-ornithine monohydrochloride" Ishida S, Sarada M, et al. |
|
L-citrulline | SD rat | Gavage | 4W | 2000 mg/kg/day | Fund Toxicol Sci (2017), 4(5):219-227 "A 4-week oral gavage toxicity study of L-citrulline in rats" Morita M, Yamaguchi T, et al. |
|
L-hydroxyproline | SD rat | Gavage | 28 days (14 days) | 40, 200, 1000, 4000 mg/kg/day |
Fund Toxicol Sci (2019), 6(3):65-74 “Twenty-eight-day oral toxicity study of L-hydroxyproline in rats with 14-day post-treatment observation period” Akiduki S, Kawada Y, et al. |
Safety Studies of Amino Acids in Human
Amino Acid | [L1]: Safety Assessment Study | [L2]: Safety Review | [L3] Case Study (short term, one dose, etc) | |
Review | ||||
---|---|---|---|---|
Advances in Nutrition (2023), 14(4): 885-894, Elango R. | ||||
Indispensable Amino Acids | ||||
L-histidine | American Journal of Clinical Nutrition (2020), 112(5): 1358-1367, Gheller ME, et al. | The Journal of Nutrition (2020), 150(Suppl1), 2588S-2592S, Thalacker-Mercer AE, et al. The Journal of Nutrition (2020) 150(Suppl1):2606S-2608S, Cynober L, et al. |
||
L-isoleucine | ||||
L-leucine | American Journal of Clinical Nutrition (2012), 96(8):759-767, Elango R, et al. | The Journal of Nutrition (2016), 146(12):2652S-2654S, Cynober L, et al. The Journal of Nutrition (2012), 142(12):2220S-2224S, Pencharz PB, et al. |
||
L-lysine/HCl | Amino Acids (2019), 51(4):647-659, Hayamizu K, et al. The Journal of Nutrition (2020) 150(Suppl) 1):2606S-2608S, Cynober L, et al. |
|||
L-methionine | American Journal of Clinical Nutrition (2017) 106(2):675-683, Deutz NEP, et al. | The Journal of Nutrition (2020) 150(Suppl 1):2606S-2608S, Cynober L, et al. | Nutrition(2002), 21(2):151-156, Krupkova-Meixnerova L, et al. Revista de Investigacion Clinica (2013), 65(4):323-330, Majluf-Cruz A, et al. |
|
L-phenylalanine | Nutrients (2021) 13(6): 1976, Miura, et al. | Amino Acids (2021) 53(9):1313-1328, Blachier F, et al. | Journal of the International Society of Sports Nutrition (2017), 14:34, Ueda K, et al. | |
L-threonine | Clinical neuropharmacology (1991), 14(5):403-412 | |||
Acta Neurologica Scandinavica (1993), 88(5):334-338 | ||||
Neurology (1996), 47(5):1220-1226 | ||||
L-tryptophan | The Journal of Nutrition (2013), 143(6):859-866, Hiratsuka C, et al. | The Journal of Nutrition (2016), 146(12): 2652S-2654S, Cynober L, et al. | ||
L-valine | ||||
Dispensable Amino Acids | ||||
L-alanine | ||||
L-arginine | Amino Acids (2018), 50(1):1215-1229, McNeal CJ, et al | The Journal of Nutrition (2016), 146(12): 2652S-2654S, Cynober L, et al. Regulatory Toxicology and Pharmacology (2008), 50(3):376-399, Shao A, et al. |
||
L-asparagine | ||||
L-aspartic acid | Metabolism (1989), 38(2):1179-l 182 | |||
L-cysteine | Metabolism (1989), 28(12):1179-1182 | |||
L-glutamate | Acceptable daily intake (ADI) is not specified in JECFA report. ADI can be driven from NOAEL, so that NOAEL of L-Glu/Na is not also specified. : Principles for the safety assessment of food additives and contaminants in food. World Health Organization International Program on Chemical Safety in Cooperation with the Joint FAO/WHO Expert Committee on Food Additives, Geneva, Environmental Health Criteria 70 (1987). |
|||
L-glutamine | Journal of Parenteral and enteral nutrition (2004) 28(2):65-75, Rathmacher JA, et al. | Regulatory Toxicology and Pharmacology (2008), 50(3):376-399, Shao A, et al. | Nutrients (2020) 12(10):E2953, Ogden HB, et al. | |
Glycine | Journal of Urban Living and Health Association (2006), 50(1):27-32, Inagawa K, et al. | |||
L-proline | ||||
L-serine | Nutrients (2021) 13(6): 1976, Miura, et al. | Amino Acids (2021) 53(9):1313-1328, Blachier F, et al. | ||
L-tyrosine | Hypertension (1985), 7(4):593-596 | |||
The Lancet (1989), 334(8671):1067-1069 | ||||
Aviation, Space and Environmental Medicine (1995), 66(4):313-319 | ||||
Journal of Child Neurology (2008),23(6):609-13 | ||||
Non-code protein Amino Acids | ||||
L-ornithine/HCl | Amino Acid (2022); 1-13, Miura et al. | Nutrition Research (2008), 28(11):738-743 | ||
L-citruline | Amino Acid (2022); 1-13, Miura et al. | British Journal of Nutrition (2008), 99(4):855-862 | ||
L-hydroxyproline |