アミノ酸の安全性

アミノ酸の非臨床安全性試験

アミノ酸 動物種、系統 投与方法 投与期間
(回復期間)
投与量 参考文献
必須アミノ酸
L-ヒスチジン Fischerラット 混餌 13週間 0.31, 0.62, 1.25, 2.5, 5% (w/w) [Japanese]
Ikezaki S, Nishikawa A, et al.
"13-week subchronic toxicity study of L-histidine monohydrochloride in F344 rats"
Bull Natl Ins Health Sci (1994), 112:57-63
L-イソロイシン SDラット 混餌 13週間(5週間) 1.25, 2.5, 5% (w/w) Tsubuku S, Hatayama K, et al.
Thirteen-week oral toxicity study of branched-chain amino acids in rats
Int J Toxicol (2004), 23(2):119-126
L-ロイシン SDラット 混餌 13週間(5週間) 1.25, 2.5, 5% (w/w) Tsubuku S, Hatayama K, et al.
Thirteen-week oral toxicity study of branched-chain amino acids in rats
Int J Toxicol (2004), 23(2):119-126
L-リジン塩酸塩 SDラット 混餌 13週間(5週間) 1.25, 2.5, 5% (w/w) Tsubuku S, Mochizuki M, et al.
Thirteen-week oral toxicity study of L-lysine hydrochloride in rats
Int J Toxicol (2004), 23(2):113-118
L-メチオニン Fischerラット(雄) 混餌 4週間 0.1, 0.3, 0.9, 2.7% (w/w) Chin K, Toue S, et al.
"A 4-week toxicity study of methionine in male rats"
Int J Toxicol (2015), 34(3):233-241
L-フェニルアラニン SDラット 混餌 28日間 0.5, 1.5, 5.0% Shibui Y, Miwa T, et al.
"28-Day dietary toxicity study of L-phenylalanine in rats"
Fund Toxicol Sci (2014), 1(2):29-38
L-スレオニン SDラット 混餌 13週間(5週間) 1.25, 2.5, 5.0% Aoki M, Ishida S, et al.
"A 13-week feeding toxicity study of L-threonine in rats with a recovery period of 5 weeks"
Fund Toxicol Sci (2014), 1(2):49-62
L-トリプトファン SDラット 混餌 13週間(5週間) 1.25, 2.5, 5.0% Shibui Y, Matsumoto H, et al.
+LOAEL(mg/kg/day) was calicurated using original research data (BW for LOAEL).
"Thirteen week toxicity study of dietary L‐tryptophan in rats with a recovery period of 5 weeks"
J Appl Toxicol (2018), 38(4): 552-563
L-バリン SDラット 混餌 13週間(5週間) 1.25, 2.5, 5% (w/w) Tsubuku S, Hatayama K, et al.
Thirteen-week oral toxicity study of branched-chain amino acids in rats
Int J Toxicol (2004), 23(2):119-126
非必須アミノ酸
L-アラニン SDラット 強制経口 4週間(2週間) 2,000mg/kg/日 Aoki M, Mochizuki M, et al.
A 4-week oral toxicity study of L-alanine in rats with a recovery period of 2 weeks
Fund Toxicol Sci (2014), 1(2):63-72
L-アルギニン SDラット 混餌 13週間(5週間) 1.25, 2.5, 5% (w/w) Tsubuku S, Hatayama K, et al.
Thirteen-week oral toxicity study of L-arginine in rats
Int J Toxicol (2004), 23(2):101-105
ブタ 混餌(2回/日) 13週間 1.21, 1.81, 2.42% (w/w) Hu S, Li X, et al.
Safety of long-term dietary supplementation with L-arginine in pigs
Amino Acids (2015), 47(5):925-936
混餌(2回/日) 13週間 1.0, 1.5, 2.0% (w/w)
SDラット 飲水 13週間 2.18, 4.35 g/kg/日 Yang Y, Wu Z, et al.
Safety of long‑term dietary supplementation with L‑arginine in rats
Amino Acids (2015), 47(9):1909-1920
L-アスパラギン Fischerラット 混餌 90日間 1.25, 2.5, 5% (w/w) Yokohira M, Hosokawa K, et al.
"A 90-day toxicity study of L-asparagine, a food additive, in F344 rats"
Food Chem Toxicol (2008), 46(7):2568-2572
L-アスパラギン酸 Fischerラット 混餌 90日間 0.05, 1.25, 2.5, 5.0% (w/w) Tada Y, Yano N, et al.
"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"
Food Chem Toxicol (2008), 46(8):2789-2795
L-システイン SDラット 強制経口 4週間 500, 1000, 2000 mg/kg/日 Shibui Y, Sakai R, et al.
"Comparisons of L-cysteine and D-cysteine toxicity in 4-week repeated-dose toxicity studies of rats receiving daily oral administration"
J Toxicol Pathol (2017), 30(3):217-229
L-グルタミン酸 - - - - 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マウス 混餌 3世代繁殖試験
F0:妊娠及び授乳期間
F1:離乳後~授乳期間
F2:離乳後~授乳期間
F3: 出生~離乳
1.0, 4.0% (w/w) Anantharaman K
In utero and dietary administration of monosodium L-glutamate to mice: Reproductive performance and development in a multigeneration study
Glutamic Acid: Advances in Biochemistry and Physiology, ed. by Filer LJ, et al., Raven Press, NY (1979):231-253
L-グルタミン SDラット 混餌 13週間(5週間) 1.25, 2.5, 5% (w/w) Tsubuku S, Hatayama K, et al.
Thirteen-week oral toxicity study of L-glutamine in rats.
Int J Toxicol (2004), 23(2):107-112
L-グリシン SDラット 強制経口 28日間 500, 1000, 2000 mg/kg/日 Shibui Y, Miwa T, et al.
"A 4-week repeated dose toxicity study of glycine in rats by gavage administration"
J Toxicol Pathol (2013), 26(4) 405–412, 2013
L-プロリン Fischerラット 混餌 90日間 0.625, 1.25, 2.5, 5.0% Tada Y, Yano N, et al.
"Toxicological evaluation of L-proline in a 90-day feeding study with Fischer 344 rats"
Regul Toxicol Pharmacol (2010), 58(1):114-120
L-セリン SDラット 強制経口 13週間 500, 1500, 3000 mg/kg/日 Kaneko I, Han L, et al.
"A 13-week subchronic oral toxicity study of L-serine in rats"
Food Chem Toxicol (2009), 47(9):2356-2360
Fischerラット 混餌 90日間 0.06, 0.5, 1.5, 5.0% Tada Y, Yano N, et al.
"A 90-day feeding toxicity study of L-serine in male and female Fischer 344 rats"
J Toxicol Pathol (2010), 23(1):39-47
L-チロシン SDラット 強制経口 13週間 200, 600, 2000 mg/kg/日 Shibui Y, Manabe Y, et al.
"13-week repeated dose toxicity study of l-tyrosine in rats by daily oral administration"
Food Chem Toxicol (2016), 87:55-64
たんぱく質を構成しないアミノ酸
L-オルニチン SDラット 混餌 13週間(5週間) 1.25, 2.5, 5.0% Ishida S, Sarada M, et al.
"Genotoxicity and subchronic oral toxicity of L-ornithine monohydrochloride"
Regul Toxicol Pharmacol (2013), 67(3):360-71
L-シトルリン SDラット 強制経口 4週間 2000 mg/kg/日 Morita M, Yamaguchi T, et al.
"A 4-week oral gavage toxicity study of L-citrulline in rats"
Fund Toxicol Sci (2017), 4(5):219-227
L-ヒドロキシプロリン SDラット 強制経口 28日間 (14日間) 40, 200, 1000, 4000 mg/kg/日 Akiduki S, Kawada Y, et al.
Twenty-eight-day oral toxicity study of L-hydroxyproline in rats with 14-day post-treatment observation period
Fund Toxicol Sci (2019), 6(3):65-74

人におけるアミノ酸の臨床安全性評価

アミノ酸 区分 対象者 投与方法 投与期間 投与量 参考文献
レビュー
全アミノ酸 レビュー - - - - Elango R.
Tolerable Upper Intake Level for Individual Amino Acids in Humans: A Narrative Review of Recent Clinical Studies
Advances in Nutrition (2023), 14(4): 885-894.
レビュー - - - - Blachier F, et al.
Tolerable amounts of amino acids for human supplementation: summary and lessons from published peer-reviewed studies
Amino Acids (2021) 53(9):1313-1328
必須アミノ酸
L-ヒスチジン 臨床安全性試験 健康成人男女 経口 4週間 4, 8, 12, 16g/日 Gheller ME, et al.
Tolerance to graded dosages of histidine supplementation in healthy human adults
American Journal of Clinical Nutrition (2020), 112(5): 1358-1367.
レビュー - - - - Thalacker-Mercer AE, et al.
Benefits and Adverse Effects of Histidine Supplementation
The Journal of Nutrition (2020), 150(Suppl1), 2588S-2592S.
レビュー - - - - Cynober L, et al.
Proposals for Upper Limits of Safe Intake for Methionine, Histidine, and Lysine in Healthy Humans
The Journal of Nutrition (2020)150(Suppl1):2606S-2608S,
L-イソロイシン
L-ロイシン 臨床安全性試験 健康成人男性 経口 1日 50, 150, 250, 500, 750, 1000, 1250 mg/kg/日 Elango R, et al.
Determination of the tolerable upper intake level of leucine in acute dietary studies in young men
American Journal of Clinical Nutrition (2012), 96(4):759-767.
レビュー - - - - Cynober L, et al.
Proposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly
The Journal of Nutrition (2016), 146(12):2652S-2654S.
レビュー - - - - Pencharz PB, et al.
Determination of the tolerable upper intake level of leucine in adult men
The Journal of Nutrition (2012), 142(12):2220S-2224S.
L-リジン塩酸塩 レビュー - - - - Hayamizu K, et al.
Safety assessment of L-lysine oral intake: a systematic review
Amino Acids (2019), 51(4):647-659.
レビュー - - - - Cynober L, et al.
Proposals for Upper Limits of Safe Intake for Methionine, Histidine, and Lysine in Healthy Humans
The Journal of Nutrition (2020)150(Suppl1):2606S-2608S,
L-メチオニン 臨床安全性試験 健康な高齢者 経口 4週間 9.2, 22.5, 46.3, 91 mg/kg/日 Deutz NE, et al.
Tolerance to increased supplemented dietary intakes of methionine in healthy older adults
American Journal of Clinical Nutrition (2017) 106(2):675-683.
レビュー - - - - Ligthart-Melis GC. et al.
Metabolic Consequences of Supplemented Methionine in a Clinical Context
The Journal of Nutrition (2020)150(Suppl1):2538S-2547S,
レビュー - - - - Cynober L, et al.
Proposals for Upper Limits of Safe Intake for Methionine, Histidine, and Lysine in Healthy Humans
The Journal of Nutrition (2020)150(Suppl1):2606S-2608S,
症例報告 冠動脈または末梢動脈疾患患者 経口 1回 100 mg/kg Krupkova-Meixnerova L, et al.
Methionine-loading test: evaluation of adverse effects and safety in an epidemiological study
Nutrition(2002), 21(2):151-156.
症例報告 健康成人及び血栓性疾患患者 経口 1回 100 mg/kg Majluf-Cruz A, et al.
Safety of the oral methionine load test: effects on the clinical performance and laboratory tests
Revista de Investigacion Clinica (2013), 65(4):323-330.
L-フェニルアラニン 臨床安全性試験 健康成人男性 経口 4週間 3, 6, 9, 12 g/日 Miura N. et al.
Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults
Nutrients (2021) 13(6): 1976
レビュー - - - - Blachier F, et al.
Tolerable amounts of amino acids for human supplementation: summary and lessons from published peer-reviewed studies
Amino Acids (2021) 53(9):1313-1328
症例報告 健康な活動的な男性 経口 1回 3g Ueda K. et al.
The effects of phenylalanine on exercise-induced fat oxidation: a preliminary, double-blind, placebo-controlled, crossover trial
Journal of the International Society of Sports Nutrition (2017), 14:34.
L-スレオニン 症例報告 家族性痙性対麻痺患者 経口 2週間 4.5, 6 g/日 Growdon J.H. et al.
L-Threonine in the Treatment of Spasticity
Clinical neuropharmacology (1991), 14(5):403-412.
症例報告 脊椎痙縮患者 経口 - 6 g/日 Lee A. and Patterson V.
A double-blind study of L-threonine in patients with spinal spasticity
Acta Neurologica Scandinavica (1993), 88(5):334-338.
症例報告 筋萎縮性側索硬化症患者 経口 6か月 4 g/日 Tandan R. et al.
A controlled trial of amino acid therapy in amyotrophic lateral sclerosis
Neurology (1996), 47(5):1220-1226.
L-トリプトファン 臨床安全性試験 健康な日本人女性 経口 21日間 1, 2, 3, 4, 5 g/日 Hiratsuka C, et al.
Supplementing healthy women with up to 5.0 g/d of L-tryptophan has no adverse effects
The Journal of Nutrition (2013), 143(6):859-866
レビュー - - - - Cynober L, et al.
Proposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly
The Journal of Nutrition (2016), 146(12): 2652S-2654S.
L-valine
非必須アミノ酸
L-アラニン 症例報告 治療的に飢餓状態にある肥満患者 経口 1日 50 g Genuth SM.
Effects of oral alanine administration in fasting obese subjects
Metabolism. 22(7), 1973, 927-937.
L-アルギニン レビュー - - - - Cynober L, et al.
Proposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly
The Journal of Nutrition (2016), 146(12): 2652S-2654S.
レビュー - - - - Shao A, et al.
Risk assessment for the amino acids taurine, L-glutamine and L-arginine
Regulatory Toxicology and Pharmacology (2008), 50(3):376-399,
臨床安全性試験 成人男女 経口 90日間 0、15、30g/日 McNeal CJ, et al.
Safety of dietary supplementation with arginine in adult humans.
Amino Acids (2018), 50(9):1215-1229.
L-アスパラギン
L-アスパラギン酸 症例報告 - 経口 - 5、10g Harold EC. et al.
Stimulation of pituitary hormone secretion by neurotransmitter amino acids in humans.
Metabolism. 38(12), 1989, 1179-1182.
L-システイン 症例報告 - 経口 - 5、10g Harold EC. et al.
Stimulation of pituitary hormone secretion by neurotransmitter amino acids in humans.
Metabolism. 38(12), 1989, 1179-1182.
L-グルタミン酸 レビュー - - - - 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
レビュー - - - - International Program on Chemical Safety in Cooperation with the Joint FAO/WHO Expert Committee on Food Additives, Geneva, Environmental Health Criteria 70 (1987).
L-グルタミン 臨床安全性試験 健康成人男性、AIDS 関連の体重減少のある HIV 患者、消耗性の癌患者 経口 - 14 g Rathmacher JA. et al.
Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters
Journal of Parenteral and enteral nutrition (2004) 28(2):65-75.
レビュー - - - - Shao A, et al.
Risk assessment for the amino acids taurine, L-glutamine and L-arginine
Regulatory Toxicology and Pharmacology (2008), 50(3):376-399,
症例報告 健康成人男性 経口 1日 0.3, 0.6, 0.9 g/除脂肪体重kg Ogden HB, et al.
Gastrointestinal Tolerance of Low, Medium and High Dose Acute Oral l-Glutamine Supplementation in Healthy Adults: A Pilot Study
Nutrients (2020) 12(10):2953.
グリシン 臨床安全性試験 健康成人男女 経口 7日間 9 g/日 Inagawa K, et al.
Assessment of Acute Adverse Events of Glycine Ingestion at a High Dose in Human Volunteers
Journal of Urban Living and Health Association (2006), 50(1):27-32.
L-プロリン
L-セリン 臨床安全性試験 健康成人男性 経口 4週間 3, 6, 9, 12 g/日 Miura N. et al.
Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults
Nutrients (2021) 13(6): 1976
レビュー - - - - Blachier F, et al.
Tolerable amounts of amino acids for human supplementation: summary and lessons from published peer-reviewed studies
Amino Acids (2021) 53(9):1313-1328
L-チロシン 症例報告 本態性高血圧症患者 経口 2週間 7.5 g/日 Sole MJ. Et al.
Chronic dietary tyrosine supplements do not affect mild essential hypertension
Hypertension (1985), 7(4):593-596.
症例報告 ナルコレプシーとカタプレキシーのある被験者 経口 4週間 9 g/日 Elwes RDC. et al.
Treatment of narcolepsy with L-tyrosine: double-blind placebo-controlled trial
The Lancet (1989), 334(8671):1067-1069.
症例報告 - 経口 1日 150 mg/日 Neri DF. et al.
The effects of tyrosine on cognitive performance during extended wakefulness
Aviation, Space and Environmental Medicine (1995), 66(4):313-319.
症例報告 ネマリンミオパチー患者 経口 - 250 to 3000 mg/日 Monique MR. et al.
Dietary L-tyrosine supplementation in nemaline myopathy
Journal of Child Neurology (2008),23(6):609-13.
たんぱく質を構成しないアミノ酸
L-オルニチン塩酸塩 臨床安全性試験 健康成人男性 経口 4週間 3.2, 6, 9.2, 12 g/日 Miura N. et al.
Subchronic tolerance trials of graded oral supplementation with ornithine hydrochloride or citrulline in healthy adults
Amino Acid (2022); 1-13.
症例報告 健康成人男女 経口 - 2000 mg/日 7 日間および 6000 mg/日 1 日 Sugino T. et al.
L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism
Nutrition Research (2008), 28(11):738-743.
L-シトルリン 臨床安全性試験 健康成人男性 経口 4週間 6, 12, 18, 24 g/日 Miura N. et al.
Subchronic tolerance trials of graded oral supplementation with ornithine hydrochloride or citrulline in healthy adults
Amino Acid (2022); 1-13.
症例報告 健康成人男性 経口 1日 2, 5, 10, 15 g Moinard C. et al.
Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study
British Journal of Nutrition (2008), 99(4):855-862.
L-ヒドロキシプロリン