Table 1.
Articles describing glycine administration in humans stratified by characteristics of physiological systems measured
| First author (year) | Population | Study type | Age (y) | Sex (%F) | Sample size (n) | Glycine duration, dose, delivery, medium | Comparator(s) | |
|---|---|---|---|---|---|---|---|---|
| Glycine Comparator(s) | ||||||||
| RCT (//) | ||||||||
| Endocrine & Metabolic system | ||||||||
| González-Ortiz (2001) [24] | Healthy first-degree relatives of T2DM patients | RCT (//) | Gly: 23.7(4.1) Comparator: 24.7(8.0) | 67 | 6 | 6 | Single bolus (short-term), 5 g (30 min before test), O, NR | Placebo (Magnesium oxide) |
| Endocrine & Metabolic + Cardiovascular systems | ||||||||
| Díaz-Flores (2013) [12] | Metabolic Syndrome | RCT (//) | Glycine*: 47.5 (8.2) Comparator*: 46.9 (7.8) | 56* | 30 | 30 | 3 m, 5 g X 3/d (15 g/d), O, glycine powder dissolved in water | Placebo (starch) dissolved in water |
| Endocrine & Metabolic + Cardiovascular + Immune systems | ||||||||
| Cruz (2008) [13] | T2DM | RCT(//) | 58.5 (10) | 54 | 38 | 36 | 3 m, 5 g X 3/d (15 g/d), O, powder dissolved in water | Placebo (starch powder dissolved in water) |
| Endocrine & Metabolic + Immune + Renal systems | ||||||||
| Daly (1988) [25] | GI malignancies | RCT (//) | Glycine: 62 (10) Comparator: 66 (8) | 20 | 14 | 16 | 7d, 43 g X 1/d (43 g/d), E, L-glycine-supplemented enteral diet (solution) | L-arginine supplemented enteral diet (solution) |
| Nervous system | ||||||||
| Aliyev (2005) [26] | Alcohol hallucinosis | RCT (//) | Glycine: 42 (6.0) Comparator: 41.0 (5.0) | 0 | 20 | 20 | 7d, 700 mg/d, S, glycine tablets | Placebo (NR) |
| Greenberg (2009) [27] | Obsessive compulsive disorder | RCT (//) | Glycine: 44.2 (14.3) Comparator: 36.1 (12.2) | 63 | 12 | 12 | 12w, 30 g X 2/d (60 g/d), O, glycine powder dissolved in water or juice | Placebo (dextrose, fructose, fine granular citric acid, orange flavouring and ProSweet™ flavour enhancer dissolved in water or juice) |
| Greenwood (2018) [28] |
Schizophrenia/ Schizoaffective disorder; |
RCT (//) |
37.8 (8.4) | 57 | 12 | 10 | 6w, start @ 0.2 g/kg/d (0.2 g/kg X 2/d after 7d; 0.2 g/kg X 3/d after 14d onwards), O, NR | Placebo (NR) |
| Potkin (1999) [29] | Schizophrenia | RCT (//) |
Glycine: 35.3 (5.26) Comparator: 34.4 (4.75) |
12.5 | 12 | 12 | 12w, 10 g X 3/d after meals (30 g/d), O, solution of glycine dissolved in 1 oz water | Placebo (similar-tasting solution) |
| Javitt (1994) [30] | Schizophrenia |
i) RCT (//) ii) Open label trial |
i) Glycine: 36 (9.7) ii) Comparator: 38.1 (7.2) |
i) 0 ii) NR |
i) 7 ii) 15 |
i) 7 ii) NA |
i) 8w, start at 2 g/d to maximum dose (0.4 g/kg bw – approx. 30 g/d) during first 2w, O, glycine powder dissolved in juice ii) 8w, 0.4 g/kg bw (approx. 30 g/d), O, glycine powder dissolved in juice |
i) Placebo (taste-matched) ii) NA |
| Serrita (2019) [31] | Schizophrenia and alcohol dependence |
RCT (//) |
Glycine: 49.2 (4.84) Comparator: 48.6 (5.01) |
0 | 10 | 10 | 12w, 0.8 g/kg, O, glycine powder mixed in solution | Placebo (powder mixed in solution) |
| Nervous + Cardiovascular systems | ||||||||
| Gusev (2000) [32] | Acute ischaemic stroke |
RCT (//) |
63.7 (10.1)* | 45* |
0.5 g/d: 53 1.0 g/d: 53 2.0 g/d: 53 |
53 | 5d, 0.5 or 1.0 or 2.0 g/d, S, tablet | Placebo tablet (similar in appearance & taste) |
| Cardiovascular system | ||||||||
| Khan (2006) [33] | Obstructive CAD | RCT (//) | 61.1 | 21 | 111 | 112 | 6 m, 297.9 g X 2/d (595.8 g/d), O, glycine dissolved in water | Starch powder dissolved in water |
| Immune + Integumentary systems | ||||||||
| Peng (2006) [34] | Severe burn | RCT (//) |
Patients: 36.5 (11.4); 18 – 60 |
40 | 23 | 25 | 14d, 0.5 g/kg/d, oral or tube feeding, granules | Glutamine granules (oral or tube feeding) |
| Immune + Renal systems | ||||||||
| D’Angelo (2016) [35] | Early preeclampsia |
RCT (//) |
Glycine*: 32.7 (4.8) Comparator: 31.1 (4.3) |
100 | 20 | 20 | Up to 7d, daily bolus of 60 ml injectable water containing 1% glycine, NR, solution | Antithrombin dissolved in 60 ml injectable water |
| Immune + Digestive systems | ||||||||
| Den Hond (1999) [36] | Crohn’s disease | RCT (//) |
Glycine: 38.2 (13.4) Comparator: 25.0 (7.9) |
All: 71 Glycine: 57 Comparator: 86 |
7 | 7 |
4w, 7 g X 3/d (21 g/d), O, glycine powder dissolved in water |
Glutamine powder dissolved in water |
| Leite (2013) [37] | HIV/AIDS | RCT (//) |
All: 37.3 (3.0) Glycine: 40.1 (1.9) Comparator: 34.2 (1.7) |
22 | 24 | 22 | 10d, 25 g/d, O, 50 ml solution of orange juice enriched with glycine | Alanyl-glutamine in 50 ml solution of orange juice |
| Immune system | ||||||||
| Shabert (1999) [38] | HIV/AIDS |
RCT (//) |
Glycine*: 42; 33 – 53 Comparator*: 40; 30–50 |
All*: 10 Glycine*: 11 Compar-ator*: 8 |
9* | 12* | 12w, 40 g/d in 4 divided doses, NR, NR | L-glutamine + antioxidants (ascorbic acid, α-tocopherol, β-carotene, selenium, N-acetyl cysteine) |
| Digestive + Muscular systems | ||||||||
| Buchman (1999) [39] | Marathon runners | RCT (//) | 25 – 49 |
All: 39 Gly: 20 Arg: 38 |
17 | 17 | 14d, 10 g X 3/d (30 g/d), O, glycine dissolved in water or orange juice | L-arginine dissolved in water or orange juice |
| Digestive system | ||||||||
| Manir (2014) [40] | Nonmetastatic pelvic malignancy | RCT (//) |
Glycine*: 56.2 (9.6) Comparator*: 57.2 (8.1) |
66 | 43* | 42* | NR, NR (given 1 h prior radiation), O, NR | Glutamine granules dissolved in 100 ml fruit juice |
| Bushen (2004) [41] | HIV/AIDS | RCT (//) |
All: 36 (6); Median: 36; 23 – 52 |
29 | 9 |
Glutamine: 11 Lo Ala-Gln: 11 Hi Ala-Gln: 10 |
7d, 46 g/d (spectrum), O, NR |
i) Gln (30 g Gln + 15 g glycine/d) or, ii) Lo Ala-Gln (4 g Ala-Gln + 42 g glycine/d) or, iii) Hi Ala-Gln (44 g Ala-Gln/d) |
| Integumentary system | ||||||||
| Peng (2005) [42] | Severe burn | RCT (//) |
36.5 (11.4); 18 – 60 |
40 | 23 | 25 | 14d, 0.5 g/kg/d, oral or tube feeding, granules | Glutamine granules (oral or tube feeding) |
| RCT (X) | ||||||||
| Endocrine & Metabolic system | ||||||||
| Gannon (2002) [43] | Healthy | RCT (X) | 21 – 52 | 44 | 9 | 9 |
Single bolus (short-term) over 120 min, 1 mmol/kg lean bm, O |
i) Water, or ii) 25 g glucose, or, iii) 1 mmol glycine/kg lean bm + 25 g glucose |
| Endocrine & Metabolic + Immune + Digestive systems | ||||||||
| Genton (2021b) [44] | Chronic haemodialysis with PEW | RCT (X) |
Total*: 61.2 (13.7) |
36* | 37 | 37 | 4 m, 7 g X 2/d (14 g/d), O, granules | BCAA granules |
| Endocrine & Metabolic + Immune + Digestive + Muscular + Renal + Skeletal systems | ||||||||
| Genton (2021a) [45] | Chronic haemodialysis with PEW | RCT (X) |
Total*: 61.2 (13.7) BCAA-Glycine*: 63.3 (13.4) Glycine-BCAA*: 58.6 (14.2) |
36* | 37 | 37 | 4 m, 7 g X 2/d (14 g/d), O, granules | BCAA granules |
| Endocrine & Metabolic + Nervous systems | ||||||||
| Munts (2009) [46] | CRPS with dystonia | RCT (X) | 41{34 – 51} | 95 | 19 | 19 | 4w, 21 mg/ml, IT, solution | Placebo (0.9% sodium chloride IT solution) |
| Nervous system | ||||||||
| Bannai (2012) [47] | Healthy | RCT (X) |
41.4; 30 – 61 |
0 | 10 | 10 | 3 consecutive nights, 3 g/d (30 min before bedtime), O, flavoured glycine | Flavoured placebo (reduced form of malt sugar) |
| O’Neill (2011) [48] | Healthy | RCT (X) |
23 (4.1); 18 – 45 |
0 | 16 | 16 | Single bolus (short-term), 0.8 g/kg, O, glycine mixed with 200 ml orange juice | Placebo (flour powder mixed with 200 ml orange juice to mimic texture of glycine treatment) |
| Palmer (2008) [49] | Healthy | RCT (X) | 23.15 (4.26); 19 – 36 | 0 | 13 | 13 | Single bolus (short-term), 0.8 g/kg, O, glycine powder dissolved in 200 ml orange juice | Placebo (flour powder mixed with 200 ml orange juice) |
| Leung (2007) [50] | Healthy | RCT (X) |
23 (4.1); 19 – 36 |
0 | 16 | 16 | Single bolus (short-term), 0.8 g/kg bw, O, mixed with 200 ml orange juice | Flour mixed with 200 ml orange juice |
| O’Neill (2007) [27] | Healthy | RCT (X) |
23 (4.1); 19 – 36 |
0 | 16 | 16 | Single bolus (short-term) over 90 min, 0.8 g/kg bw, O, glycine powder mixed with 200 ml orange juice | Placebo (flour powder mixed with 200 ml orange juice) |
| Yamadera (2007) [51] | Healthy | RCT (X) |
40.5 (10.1); 30 – 57 |
73 | 11 | 11 | 2 consecutive nights, 3 g/d (1 h before bedtime), O, flavoured glycine | Flavoured placebo (reduced form of malt sugar) |
| Neumeister (2006) [52] | Healthy | RCT (X) | 28.5 (10.5) | 33* | 13 | 13 | Single bolus (short-term), 200 mg/kg bw over 45 min, IV infusion | Placebo (saline solution) |
| Inagawa (2006) [53] | Dissatisfaction with sleep | RCT (X) |
31.1; 24 – 53 |
100 | 19 | 0 | 4d, 3 g/d (1 h before bedtime), O, flavoured glycine (medium NR) | Placebo (flavoured) |
| Heresco-Levy (2004b) [54] | Schizophrenia | RCT (X) | 44.7 (10.8) | 24 | 17 | 17 | 6w, initiated at 4 g/d (↑ 4 g/d until 0.8 g/kg bw/d after 10d – 17d) in 3 divided doses, O, glycine powder dissolved in water (20% solution) | Placebo (glucose solution) |
| Heresco-Levy (2004a) [55] | Schizophrenia | RCT (X) | 42.4 | 41 | 17 | 17 | 6w, start at 4 g/d (↑ 4 g/d until 0.8 g/kg bw/d) in 3 divided doses, O, glycine powder dissolved in water | Placebo (glucose solution) |
| Javitt (2001) [56] | Schizophrenia | RCT (X) | 39.6 (5.5) | 33 | 12 | 12 | 6w, 0.8 g/kg/d, O, glycine powder dissolved in orange juice | Placebo (glucose) dissolved in orange juice |
| Heresco-Levy (1999) [57] | Schizophrenia | RCT (X) | 38.8 (11.0) | 45 | 22 | 22 | 6w, initiated at 4 g/d (↑ 4 g/d until 0.8 g/kg bw/d after 9d – 19d) in 3 divided doses, O, glycine powder dissolved in water (20% solution) | Placebo (glucose solution) |
| Heresco-Levy (1996) [58] | Schizophrenia | RCT (X) |
41.4* 22 – 60* |
55* | 12 | 12 | 6w, start at 4 g/d (↑ 4 g/d until 0.8 g/kg bw/d) in 3 divided doses, O, glycine powder dissolved in water | Placebo (glucose solution) |
| Digestive system | ||||||||
| Amin (2018) [59] |
i) Healthy ii) Healthy |
i) RCT (X) ii) RCT (X) |
i) 39.4 (11.4) ii) 36.0 (10.8) |
i) 86 ii) 89 |
i) 7 ii) 9 |
i) 7 ii) 9 |
For both studies: Single bolus (short-term), 17.1 mmol, O, hypromellose capsules |
For both studies: i) L-arginine hydrocholoride in hypromellose capsules or, ii) empty hypromellose capsules (vehicle) |
| Luiking (1998) [60] | Healthy | RCT (X) | 24.2 (4.1) | 0 | 10 | 10 | 8d, 13 g/d over 4 doses, O, solution | Placebo (glucose + chloride) solution |
| Muscular system | ||||||||
| Antonio (2002) [61] | Resistance-trained | RCT (X) | 21.5 (0.3) | NR | 6 | 6 | Single bolus (short-term), 0.3 g/kg, O, glycine mixed with 250 ml calorie-free fruit juice |
i) Glutamine mixed with calorie-free fruit juice, or ii) Placebo (calorie-free fruit juice only) |
| Non-randomised trials | ||||||||
| Endocrine & Metabolic systems | ||||||||
| Kasai (1980) [62] | Non-obese normal | Open-label trial (//) | 18 – 46 | 48 | 25 | NA | Single bolus (short-term) over 150 min, 4 g or 8 g, IV; single bolus (short-term) over 180 min, 12 g, IV | NA |
| Kasai (1978) [63] |
i) Non-obese normal; gastroduodenal anastomosis (partially gastrectomied) ii) Non-obese normal; non-obese diabetics |
i) Open-label trial ii) Open-label trial |
i) 20 – 70 ii) 20 – 70 |
i) 39 ii) 47 |
i) 31 ii) 15 |
i) NA ii) NA |
i) Single bolus (short-term) over 180 min, 250 ml 0.3 M, O ii) Single bolus (short-term) over 180 min, 250 ml 0.3 M, ID |
i) NA ii) NA |
| Nervous + Cardiovascular + Renal + Reproductive systems | ||||||||
| Sugaya (2021) [64] | Overactive bladder | Pilot (//) | 67 (16) | 20 | 20 | 20 | 4w, 3 g X 2/d (6 g/d), O, NR | Placebo (glucose) |
| Nervous system | ||||||||
| Truong (1988) [65] | Myoclonus | Open-label trial; crossov-er trial |
38; 18 – 58 |
NR | 7 | NA | Up to 9w, start @ 200 mg X 3/d (600 mg/d) then ↑ daily by 300 mg until therapeutic effect achieved or up to max dose 6 g/d in 3 divided doses over 6w, O, capsule | NA |
| Strzelecki (2011) [66] | Schizophrenia | Open-label trial |
32.3 (8.8)*; Median: 29.5; 20 – 50* |
45* | 32 | NA | 6w, 0.8 g/kg bm/24 h/3 doses, O, glycine crystillizate dissolution in approx. ½ glass of water or orange juice | NA |
| Javitt (1994) [30] | Schizophrenia |
i) RCT (//) ii) Open label trial |
i) Glycine: 36 (9.7) ii) Comparator: 38.1 (7.2) |
i) 0 ii) NR |
i) 7 ii) 15 |
i) 7 ii) NA |
i) 8w, start at 2 g/d to maximum dose (0.4 g/kg bw – approx. 30 g/d) during first 2w, O, glycine powder dissolved in juice ii) 8w, 0.4 g/kg bw (approx. 30 g/d), O, glycine powder dissolved in juice |
i) Placebo (taste-matched) ii) NA |
| Rosse (1989) [67] | Chronic psychotic disorder | Open-label trial |
38; 30 – 68 |
0 | 6 | NA | 4d – 8w, 10.8 g in 3 divided doses daily, O, glycine capsule | NA |
Age data are presented as: mean (SD); or median {IQR}
(X) crossover trial, (//) parallel trial, (*) value(s) given only for participants who completed trial and/or included in analysis, AIDS acquired immune deficiency syndrome, Arg arginine, BCAA branched-chain amino acid, bm body mass, bw body weight, d day, CAD coronary artery disease, DCS D-cycloserine, E enteral, F female, g gram, GI gastrointestinal, Gly glycine, Hi high dose, HIV human immunodeficiency virus, I inhalation, ID intraduodenal, IT intrathecal, IV intravenous, Lo Low dose, O oral ingestion, PEW protein energy wasting, NA not applicable, NR not reported, m month, RCT randomised controlled trial, T2DM type 2 diabetes mellitus, w week, y years