The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure
Abstract
:1. Introduction
2. Nitric Oxide in Blood Pressure Regulation
2.1. Nitric Oxide-Mediated Vasodilation
2.2. Mechanisms Mediated by Oral Administration of l-Arginine and l-Citrulline on the Vasculature
3. l-Citrulline and l-Arginine as Antihypertensive Compounds
3.1. Pharmacokinetics of l-Citrulline and l-Arginine
3.2. Results of Clinical Trials
4. Discussion
5. Conclusions and Outlook
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | Dose (mg) × Number of Daily Administrations | Plasma [arginine] AUC (μmol·h·L−1) ± SEM |
---|---|---|
l-citrulline | 750 × 2 | 271 ± 38 |
lL-citrulline | 1500 × 2 | 421 ± 65 |
lL-citrulline | 3000 × 2 | 898 ± 67 |
lL-arginine slow release | 1600 × 2 | 289 ± 50 |
lL-arginine immediate release | 1000 × 3 | 283 ± 51 |
Title and trial identifier | Objective | Design | Status and results |
---|---|---|---|
l-arginine treatment in mild hypertension (LAHN) NCT02894723 | To evaluate the efficacy of Arg treatment on blood pressure control patients with stage 1 hypertension | Dietary Supplement: Arg Dietary Supplement: syrup Patients will receive Arg 30 mL twice a day for eight weeks. Phase 4 | Not yet recruiting |
l-arginine effects on chronic hypertension in pregnancy NCT00974714 | To evaluate the effects of oral Arg administration on pregnant women at second trimester of gestation with chronic hypertension, with respect with placebo. | Oral Arg 2 g twice a day, for 14 weeks Placebo-controlled Phase 3 | Completed (2010) |
l-Arginine metabolism in essential hypertension NCT00137124 | This study determines whether metabolism and transport of Arg are altered in patients with essential hyper-tension and whether these potential alterations can be targeted therapeutically. | Interventional, randomized trial with 120 participants, oral administration of Arg for 4 weeks Phase 2 | Completed (2009) |
Effects of oral l-arginine on chronic hypertension in pregnancy NCT00571766 | To evaluate the effects of oral Arg in pregnant women with chronic hypertension. | Interventional (Clinical Trial), randomized with 80 participants, oral Arg 2 g twice a day for 14 weeks Phase 3 | Completed (2008) |
Effect of l-arginine and pycnogenol on light to moderate hypertension and endothelial function NCT02392767 | To evaluate the effect of a combination product (Verum) with Arg, Pycnogenol, vitamin K2, R-(+)-alpha-lipoic acid, and vitamins B6, B12, and folic acid | A randomized, double-blind, placebo-controlled cross-over study Two tablets twice a day for four weeks. Verum/Placebo | Completed (2015) Systolic blood pressure decreased significantly under the Arg-based multi-ingredient product (AbMIP) [50] |
Impact of citrulline and arginine supplementation on the post-exercise hypotension (PEH) NCT03378596 | To increase the knowledge regarding non-pharmacological models aimed at the prevention and treatment of hypertension in normotensive and hypertensive patients. Cit (6 g) Arg (8 g) | Interventional (clinical trial), randomized, 20 participants, ambulatorial blood pressure monitoring | Recruiting |
Effects of inhibition of NO synthesis on renal hemodynamics and sodium excretion in patients with essential hypertension and healthy controls NCT00345150 | To test the hypothesis that systemic and renal nitric oxide synthesis is changed in essential hypertension by investigating the effects of a non-selective nitric oxide inhibitor on renal hemodynamics and sodium excretion in patients with essential hypertension. NG-monomethyl- l-arginine | Interventional (clinical trial), randomized, 30 participants Phase 1 | Completed (2006) |
l-arginine, vascular response and mechanisms NCT01482247 | To employ the supplement Arg to test the hypothesis that the activation of blood flow to the brain during cognitive tasks is regulated by nitric oxide in older subjects with diabetes mellitus and/or hypertension. Arg as supplement | Interventional (Clinical Trial), randomized, 25 participants. Phase 2 | Completed (2014) |
Author and Publication Year | Supplement | Total Number of Trials and Participants | Reduction in SBP | Reduction in DBP | Dose and Duration |
---|---|---|---|---|---|
Dong et al. 2011 [46] | l-arginine | 11 trials 387 participants | 5.39 mmHg (95% CI: 2.25–8.54, p = 0.001) | 2.66 mmHg (95% CI:1.54–3.77, p < 0.001) | 2–24 weeks 4–24 g/day |
Mahboobi et al. 2019 [49] | l-citrulline or watermelon extract | 15 trials 424 participants | 7.54 mmHg (95% CI: 5.63-9.44, p = 0.0001) | 3.77 mmHg for DBP (95% CI: 1.86–5.67, p = 0.0001) | 1–16 weeks 2.7–8.4 g/day |
Barkhidarian et al. 2019 [48] | l-citrulline | 8 trials 190 participants | 4.10 mmHg (95% CI: 0.26–7.94. p = 0.037) | 2.08 mmHg (95% CI: −0.16–4.32. p = 0.069) | 1–17 weeks 3–9 g/day |
Mirenayat et al. 2018 [47] | l-citrulline | 5 trials 114 participants | Brachial: 0.28 mmHg (95% CI: −2.87 to 2.31) Aortic: 0.22 mmHg (95% CI: −4.81 to 4.38) | Brachial: −1.56 mmHg (95% CI: −4.30 to 1.20) Aortic: 0.26 mmHg (95% CI: −2.27 to 2.80) | 1–8 weeks 3–6 g/day |
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Khalaf, D.; Krüger, M.; Wehland, M.; Infanger, M.; Grimm, D. The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure. Nutrients 2019, 11, 1679. https://doi.org/10.3390/nu11071679
Khalaf D, Krüger M, Wehland M, Infanger M, Grimm D. The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure. Nutrients. 2019; 11(7):1679. https://doi.org/10.3390/nu11071679
Chicago/Turabian StyleKhalaf, David, Marcus Krüger, Markus Wehland, Manfred Infanger, and Daniela Grimm. 2019. "The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure" Nutrients 11, no. 7: 1679. https://doi.org/10.3390/nu11071679