Table 3.
Selected clinical trials on L-citrulline/watermelon supplementation, dose, intervention period, experimental design and main outcomes.
| L-Citrulline Content/Vehicle | Subjects/Age | Intervention Period | Experimental Design | Main Outcomes | Study |
|---|---|---|---|---|---|
| watermelon rind (5 g) watermelon flesh (5 g) watermelon rind (0.1 g) |
6 overweight/obese subjects (32.2 ± 7.6 y) |
1 week | Randomized Placebo-controlled Crossover |
FMD—no effect | Fan et al. [125] |
| 4 g/30 g of micro-encapsulated watermelon | 11 healthy adults | 3 occasions with a 1 week interval | Randomized Single-blind Crossover Placebo-controlled |
↑ FMD ↑ plasma L-citrulline and L-arginine |
Volino-Souza et al. [126] |
| 500 mL watermelon juice | 17 healthy young adults (21–25 y) (6 males/11 females) |
2 weeks | Randomized Placebo-controlled Double-blind Crossover |
↑ FMD ↑ plasma L-arginine |
Vincellette et al. [127] |
| 1.63 g/Two servings of 360 mL of 100% watermelon juice |
21 healthy postmenopausal women (55–70 y) | 4 weeks | Randomized Double-blind Placebo-controlled Crossover |
FMD, PWV, MAP—no effects SBP and DBP—no effects |
Ellis et al. [128] |
| watermelon (6 g/d L-citrulline/L-arginine) | 12 postmenopausal women (57 ± 1 y) | 6 weeks | Randomized Placebo-controlled Crossover |
↓ baPWV ↓ SBP and DBP ↓ aortic SBP2 radial SBP2—no effect aortic and radial—no effects |
Figueroa et al. [129] |
| 2.7 g/in watermelon | 9 pre-hypertensives subjects (4 male/5 female) (54 ± 3 y) |
6 weeks | Randomized Placebo-controlled |
↓ AIx cfPWV—no effect |
Figueroa et al. [130] |
| watermelon (containing L-citrulline 1.3 g plus L-arginine 2.7 g) | 14 adults (11 female/3 male) (58 ± 1 y) prehypertensive or stage 1 hypertension |
6 weeks | Randomized Placebo-controlled Two-period Crossover |
↓ cAIx ↓ SBP, DBP, MAP HR and ABI—no effects |
Figueroa et al. [119] |
| 10 g/L-citrulline capsules | 7 older HF adults (>60 y) and 7 healthy young subjects (21–40 y) | 2 days | Kinetic study Placebo-controlled |
↑ plasma L-arginine (in older adults) ↑ NO synthesis rate (in older adults) ↑ NO synthesis rate (in older adults) RH-FBF—unaffected |
Kim et al. [131] |
| 6 g/citrulline capsules | 25 sedentary hypertensive postmenopausal women (50–4 y) |
4 weeks | Double-blind, Randomized Placebo-controlled |
↑ plasma L-arginine ↑ FMD ↑ aortic DBP and MAP cfPWV—no effects brachial BP—no effects |
Maharaj et al. [132] |
| 5.6 g/L-citrulline capsules | 15 healthy subjects (58.3 ± 4.4 y) | 1 week | Double-blind Randomized Placebo-controlled Parallel-group |
↓ baPWV DBP and SBP—no effects ↑ NO ↑ NOx ↑ plasma L-citrulline ↑ plasma L-arginine ↑ plasma ratio of arginine/ADMA ↑ endogenous inhibitor of NO synthase |
Ochiai et al. [133] |
| 100 mg/kg body weight in capsules | 30 CAD and FMD/NMD (<1) subjects | 2 weeks | Randomized Crossover placebo-controlled |
↑ FMD/NMD ↑ FMD |
Safi et al. [134] |
| 6 g/citrulline drink | 24 healthy subjects (12 males/12 females) (64 ± 2 y) | 4 weeks | Double-blind Randomized |
↓ SBP and DBP PWV—no effect NO—no effect |
Roux-Mallouf et al. [135] |
| 800 mg/L-citrulline capsules | 22 diagnosed vasospastic angina patients (41–46 y) | 8 weeks | Open label | ↑ plasma NOx ↓ ADMA ↑ FMD ↑ plasma L-arginine/ADMA ratio |
Morita et al. [136] |
↑increase; ↓decrease; aAIx, aortic augmentation index; ABI, ankle–brachial index; AIx, augmentation index; baPWV, brachial–ankle pulse wave velocity; CAD, coronary artery disease; cAIx, carotid augmentation index; DBP, diastolic blood pressure; FMD, mediated flow dilatation; HF, heart failure; HR, heart rate; MAP, mean arterial pressure; NO, nitric oxide; NOx, nitrate plus nitrite concentrations; PWV, pulse wave velocity; RH-FBF, reactive hyperemic forearm blood flow; SBP, systolic blood pressure; y, years.