TABLE 3.
Summary of studies in humans for determining tolerable upper intake level of amino acids
| Reference | Amino acid | Study design | Participants | Amino acid doses | Length of exposure | Primary outcomes | Other measures |
|---|---|---|---|---|---|---|---|
| Elango et al., 2012 [12] | Leucine | Acute, repeated measures study | n = 5 male; 27.2 ± 2.1 y; 23.7 ± 1.2 kg/m2 | 3.5, 10.5, 17.5, 35, 52.5, 70, and 87.5 g/d | 8 h | Oxidation of 1-13C-Leucine, as a marker of metabolic excess | Blood ammonia, complete blood, and urine biochemistry |
| Hirasutka et al., 2013 [13] | Tryptophan | Subacute, randomly assigned, double-blind, placebo-controlled, crossover intervention study | n = 17 female; 20.2 ± 0.6 y; 20.1 ± 0.3 kg/m2 | 0, 1, 2, 3, 4, and 5 g/d | 21 d | Surrogate biomarkers of tryptophan metabolites, including 3-hydroxykynurenine (3-HK) in blood and urine | Food intake, body weight, and general blood and urine biochemistry |
| Rasmussen et al., 2016 [14] | Leucine | Acute, repeated measures study | n = 6 male; 72.2 ± 3.5 y; 26.6 ± 5.0 kg/m2 | 10.5, 17.5, 24, 5, 31.5, 38.5, 45.5, and 52.5 g/d | 8 h | Oxidation of 1-13C-Leucine, as a marker of metabolic excess | Blood ammonia, complete blood, and urine biochemistry, including amino acids |
| Deutz et al., 2017 [15] | Methionine | Subchronic, repeated measures study | n = 15 (9 male:6 female); 58.9 ± 6.1 y; 28.6 ± 0.9 kg/m2 | 0.6, 1.6, 3.2, and 6.4 g/d | 4 wk | Plasma homocysteine concentrations | Health questionnaires, neurocognitive tests, complete blood and urine biochemistry, and bone mineral density |
| McNeal et al., 2018 [16] | Arginine | Subchronic, cross-sectional study | n = 74 (36 male:38 female); 22–57 y; ∼36 kg/m2 | 0, 15, and 30 g/d | 90 d | Cardiovascular function (systolic and diastolic blood pressures) | Complete blood and urine biochemistry to test renal, metabolic function, and arginine metabolites |
| Hayamizu et al., 2019 [17] | Lysine | Systematic review | Included studies had n = 3–211 and age range, 1.6–76.7 y | 0.2–17.5 g/d | 1–1095 d | Report adverse events, including gastrointestinal tract symptoms such as nausea, stomachache, and diarrhea | — |
| Gheller et al., 2020 [18] | Histidine | Subchronic, repeated measures and cross-sectional study | n = 40 (n = 20 male, n = 20 female); ∼33 y; ∼24 kg/m2 | 4, 8, 12, and 16 g/d | 4 wk | Complete blood biochemistry, including ferritin concentrations and liver enzyme values | Anthropometry, body composition, blood histamine concentrations, and sleep quality |
| Miura et al., 2021 [19] | Phenylalanine | Subchronic, repeated measures study | n = 23 male; ∼38 y; ∼23.5 kg/m2 | 3, 6, 9, and 12 g/d | 4 wk | Complete blood biochemistry | Adverse event reporting, sleep quality, and body weight changes |
| Miura et al., 2021 [19] | Serine | Subchronic, repeated measures study | n = 30 male; ∼38 y; ∼23.5 kg/m2 | 3, 6, 9, and 12 g/d | 4 wk | Complete blood biochemistry | Adverse event reporting, sleep quality, and body weight changes |
| Miura et al., 2022 [20] | Ornithine | Subchronic, repeated measures study | n = 23 male; ∼41 y, ∼23.8 kg/m2 | 3.2, 6, 9.2, and 12 g/d | 4 wk | Complete blood biochemistry | Sleep quality, mental fatigue, and dietary intake surveys |
| Miura et al., 2022 [20] | Citrulline | Subchronic, repeated measures study | n = 23 male; ∼42 y, ∼23.6 kg/m2 | 6, 12, 18, and 24 g/d | 4 wk | Complete blood biochemistry | Sleep quality, mental fatigue, and dietary intake surveys |