TABLE 2.
Characteristics of included studies investigating the effects of l-arginine supplementation on blood pressure in adults1
| Sample size | Trial duration, | Intervention | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study | Sample size | Age, y | BMI, kg/m2 | Intervention | Control | Adverse | ||||||||
| Study (ref) | Country | design | Participants | and sex | IG | CG | d | IG | CG | IG | CG | dose, g/d | group | effect |
| Chin-Dusting et al., 1996 (15) | China | Parallel, R, PC, DB | Healthy adults | M (16) | 8 | 8 | 28 | 21.9 ± 0.6 | 20.9 ± 1.0 | NR | NR | 20 | Placebo (deionized water (600 mL) and compound hydroxybenzoate solution (5 mL) made up to 900 mL with either aromatic or orange syrup | No adverse effect |
| Clarkson et al., 1996 (41) | England | Cross over, R, PC, DB | Hypercholesterolemic adults (>162 mg/dL, with cholesterol mean: 238 ± 43; who were not hypertensive or diabetic) | M/F (F: 9, M: 18) | 15 | 15 | 28 | 29 ± 5 | 29 ± 5 | NR | NR | 21 | Placebo (identical powder formulations, which when mixed with water made a palatable drink) | Stool frequency and abdominal bloating |
| Piatti et al., 2001 (42) | Italy | Parallel, R, PC, DB | Adults with T2D | M/F (F: 4, M: 8) | 6 | 6 | 28 | 58 ± 7.34 | 58 ± 7.34 | 25.3 ± 2.20 | 25.3 ± 2.20 | 9 | Placebo (identical powder formulations, which were mixed with water and 200 mg aspartame) | No statement |
| Sydow et al., 2002 (43) | Germany | Parallel, R, PC, DB | Adults with peripheral arterial occlusive disease | M/F (F: 3, M: 15) | 9 | 9 | 56 | 64 ± 12.3 | 68.8 ± 8.4 | 25.44 | 27.02 | 24 | Placebo | No statement |
| Rytlewski et al., 2005 (12) | Poland | Prospective, R, PC | Adults with pre-eclampsia | F (61) | 30 | 31 | 21 | 29.3 ± 6.7 | 29.2 ± 5.9 | NR | NR | 3 | Placebo | No adverse effect |
| West et al., 2005 (44) | France | Cross over, R, PC, DB | Hypercholesterolemic adults | M (16) | 8 | 8 | 21 | 45 ± 5.37 | 45 ± 5.37 | 28 ± 3.11 | 28 ± 3.11 | 12 | Placebos (supplied by Jarrow Formulas) | No statement |
| Hladunewich et al., 2006 (45) | USA | Parallel, R, PC, DB | Pregnant women with pre-eclampsia | F (45) | 19 | 20 | 7 | 29 ± 6 | 28 ± 7 | NR | NR | 14 | Placebo | No adverse effect |
| Lucotti et al., 2006 (47) | Italy | Parallel, R, PC, DB | Adults with T2D | M/F (F: 25, M: 8) | 16 | 17 | 21 | 56.4 ± 8.04 | 56.4 ± 8.04 | 39.1 ± 2.87 | 39.1 ± 2.87 | 8.3 + hypocaloric diet and exercise training program | Placebo + hypocaloric diet and exercise training program | No adverse effect |
| Facchinetti et al., 2007 (48) | Italy | Parallel, R, PC, DB | Adults with pre-eclampsia | F (74) | 39 | 35 | 28 | 32.8 ± 5.4 | 32.6 ± 4.9 | 29.0 ± 7.7 | 27.4 ± 5.3 | 4 + (20 g/500 mL) intravenously daily, for 5 d followed by 4 g/d orally for 14 d | Saline infusion, 500 mL intravenously over 4 h given daily for 5 d, then oral placebo for 14 d | Diarrhea in three patients |
| Fontanive et al., 2009 (49) | Italy | Parallel, R, PC, DB | Adults with mild-to-moderate systolic HF and LV ejection fraction ≤45% | M/F (F: 23, M: 45) | 37 | 31 | 21 | 64 ± 11 | 64 ± 8 | NR | NR | 6 | Placebo | Three patients in the l-arginine group consisting of; asthenia, skin rash, eosinophilia |
| Lucotti et al., 2009 (46) | Italy | Parallel, R, PC, DB | Adults with coronary artery disease | M/F (F: 2, M: 28) | 16 | 14 | 180 | 65 ± 10 | 64 ± 11 | NR | NR | 6.4 | Placebo | No adverse effect |
| Ast et al., 2010(a) (11) | Poland | Parallel, R, PC, DB | Healthy adults | M/F (F: 24, M: 30) | 7 | 3 | 28 | 38.3 ± 11.2 | 35.5 ± 5.7 | 23.9 ± 3.3 | 22.9 ± 3.7 | 6 | Placebo | No adverse effect |
| Ast et al., 2010(b) (11) | Poland | Parallel, R, PC, DB | Healthy adults | M/F (F: 24, M: 30) | 6 | 3 | 28 | 39.2 ± 7.9 | 35.5 ± 5.7 | 27.2 ± 2.2 | 22.9 ± 3.7 | 12 | Placebo | — |
| Ast et al., 2010(c) (11) | Poland | Parallel, R, PC, DB | Healthy adults | M/F (F: 24, M: 30) | 12 | 5 | 28 | 36.4 ± 6.7 | 39.1 ± 10.4 | 28.4 ± 3.7 | 25.4 ± 2.9 | 12 | Placebo | — |
| Ast et al., 2010(d) (11) | Poland | Parallel, R, PC, DB | Adults with mild hypertension | M/F (F: 24, M: 30) | 13 | 5 | 28 | 36.4 ± 6.7 | 41.1 ± 12.0 | 27.2 ± 3.6 | 25.4 ± 2.9 | 6 | Placebo | — |
| Neri et al., 2010 (14) | Italy | Parallel, R, PC, DB | Adults with mild chronic hypertension | F (79) | 39 | 40 | 84 | 34.4 + 4.1 | 33.7 + 3.8 | 31.3 + 6.6 | 31.7 + 7.1 | 4 | Placebo | No adverse effect |
| Battaglia et al., 2010 (50) | Italy | Prospective, R, PC, DB | Female adults with polycystic ovary syndrome | F (28) | 13 | 15 | 180 | 24.3 + 3.5 | 25.2 + 5.1 | 23.5 + 4.2 | 24.4 + 4.4 | 8 + Yasmin: drospirenone + ethinylestradiol (Bayer-Schering Italia) | Placebo ++Yasmin: drospirenone + ethinylestradiol | No adverse effect |
| Willoughby et al., 2011 (51) | USA | Parallel, R, PC, DB | Male healthy adults, physically active men, resistance-trained | M (24) | 12 | 12 | 7 | 22.58 ± 3.31 | 21.75 ± 2.17 | NR | NR | 12 | Placebo (apple pectin, General Nutrition Corp.) | No adverse effect |
| Ast et al., 2012(a) (52) | Poland | Parallel, R, PC, DB | Healthy adults | M/F (F: 9, M: 10) | 6 | 3 | 28 | 37.7 ± 10.3 | 35.3 ± 5.43 | 23.9 ± 2.99 | 23.3 ± 3.48 | 6 | Placebo | No adverse effect |
| Ast et al., 2012(b) (52) | Poland | Parallel, R, PC, DB | Healthy adults | M/F (F: 9, M: 10) | 7 | 3 | 28 | 40.7 ± 7.58 | 35.3 ± 5.43 | 26.7 ± 3.4 | 23.3 ± 3.48 | 12 | Placebo | — |
| de Lima et al., 2012 (39) | Portugal | Parallel, R, PC, DB | Hypertensive adults | F (20) | 10 | 10 | 30 | 50.0 ± 1.8 | 51.5 ± 1.6 | 26.8 ± 1.0 | 27.6 ± 1.0 | 6 | Placebo | No statement |
| Malfatti et al., 2014(a) (53) | Brazil | Parallel, PC | Hypertensive adults | M (8) | 2 | 2 | 4 | 50.8 ± 9.4 | 50.8 ± 9.4 | NR | NR | 2 | Placebo | No statement |
| Malfatti et al., 2014(b) (53) | Brazil | Parallel, PC | Hypertensive adults | M (8) | 2 | 2 | 4 | 50.8 ± 9.4 | 50.8 ± 9.4 | NR | NR | 4 | Placebo | — |
| Pahlavani et al., 2014 (54) | Iran | Parallel, R, PC, DB | Healthy adults | M (54) | 25 | 27 | 60 | 21.32 ± 4.59 | 20.40 ± 4.04 | 23.34 ± 4.02 | 24.01 ± 4.53 | 2 | Placebo (maltodextrin) | No adverse effect |
| Camarena Pulido et al., 2016 (55) | Mexico | Parallel, R, PC, DB | Pregnant women who had high-risk factors for developing pre-eclampsia | F (96) | 49 | 47 | 140 | 20 ± 5.4 | 20 ± 4.7 | 28 ± 4.8 | 26.7 ± 2.9 | 3 | Placebo | Dyspepsia, in placebo group (n = 5) compared with the l-arginine group (n = 14). 3 patients, abdominal pain (placebo group, n = 1; l-arginine group, n = 2); 1 patient in each of the groups had diarrhea |
| McNeal et al., 2018(a) (56) | Austria | Parallel, R, PC, DB | Healthy overweight or obese women [BMI (kg/m2) ≥25] | F (26) | 7 | 7 | 90 | 40 ± 3.2 | 40 ± 2.6 | 34.3 ± 1.9 | 36.6 ± 1.8 | 15 | Placebo | No adverse effect |
| McNeal et al., 2018(b) (56) | Austria | Parallel, R, PC, DB | Healthy overweight or obese women (BMI ≥25) | F (25) | 6 | 6 | 90 | 34 ± 2.6 | 40 ± 2.6 | 35.4 ± 1.6 | 36.6 ± 1.8 | 30 | Placebo | — |
| McNeal et al., 2018(c) (56) | Austria | Parallel, R, PC, DB | Healthy overweight or obese women (BMI ≥25) | M (25) | 7 | 7 | 90 | 33 ± 2.6 | 35 ± 2.5 | 32.9 ± 1.7 | 36.1 ± 2.5 | 15 | Placebo | — |
| McNeal et al., 2018(d) (56) | Austria | Parallel, R, PC, DB | Healthy overweight or obese women (BMI ≥25) | M (24) | 7 | 6 | 90 | 33 ± 1.5 | 35 ± 2.5 | 32.9 ± 0.8 | 36.1 ± 2.5 | 30 | Placebo | — |
| Salmani et al., 2021 (40) | Iran | Parallel, R, PC, DB | Adults with ischemic heart failure | M/F (F: 13, M: 31) | 12 | 11 | 70 | 56.6 ± 3.3 | 55.8 ± 7.9 | 29.1 ± 4.2 | 28 ± 4 | 3 | Placebo (maltodextrin) | No adverse effect |
1
CG, control group; CO, controlled; DB, double-blinded; HF, heart failure; IG, intervention group; LV, left ventricular; NR, not reported; PC, placebo-controlled; R, randomized; ref, reference; SB, single-blinded; T2D, type 2 diabetes.