Ar9.0

Arginine Research

40 peer-reviewed studies · Evidence score: 9/10

L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: A Systematic Review and Meta-Analysis

Makama M et al. • BJOG : an international journal of obstetrics and gynaecology (2025)

L-arginine may be promising for pre-eclampsia prevention and treatment, but findings should be interpreted cautiously.

In prevention trials, L-arginine was associated with a reduced risk of pre-eclampsia (relative risk [RR] 0.52; 95% confidence interval [CI], 0.35, 0.78; low-certainty evidence, four trials) and severe pre-eclampsia (RR 0.23; 95% CI, 0.09, 0.55; low-certainty evidence, three trials).
In treatment trials, L-arginine may reduce mean systolic blood pressure (MD -5.64 mmHg; 95% CI, -10.66, -0.62; very low-certainty evidence, three trials) and fetal growth restriction (RR 0.46; 95% CI, 0.26, 0.81; low-certainty evidence, two trials).
L-arginine may be promising for pre-eclampsia prevention and treatment, but findings should be interpreted cautiously.

Meta-Analysisn=2,028

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Nutraceutical interventions for erectile dysfunction: a systematic review and network meta-analysis

Barbonetti A et al. • The journal of sexual medicine (2024)

Against a background of general ineffectiveness of most nutraceutical interventions, L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED.

In patients with organic ED, the efficacy of Sildenafil and Tadalafil was significantly improved by PLC + ALC and L-Arginine, respectively.
Against a background of general ineffectiveness of most nutraceutical interventions, L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED.
Further research warranted to confirm findings

Meta-Analysisn=1,000

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Nutritional interventions for preventing and treating pressure ulcers

Langer G et al. • The Cochrane database of systematic reviews (2024)

The benefits of nutritional interventions with various compositions for pressure ulcer prevention and treatment are uncertain.

Compared to standard diet, protein supplements may result in little to no difference in pressure ulcer incidence (protein 21 per 1000, standard diet 28 per 1000; RR 0.75, 95% CI 0.49 to 1.14; 4 studies, 4264 participants; low-certainty evidence).
The evidence is very uncertain about the gastrointestinal side effects of these supplements (protein 109 per 1000, standard diet 155 per 1000; RR 0.70, 95% CI 0.06 to 7.96; 2 studies, 140 participants, very low-certainty evidence).
Compared to standard diet, energy, protein and micronutrient supplements may slightly increase the number of healed pressure ulcers (energy, protein and micronutrients 366 per 1000, standard diet 253 per 1000; RR 1.45, 95% CI 1.14 to 1.85; 3 studies, 577 participants, low-certainty evidence).

Meta-Analysisn=7,920

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Antioxidant supplementation for sickle cell disease

Bolarinwa AB et al. • The Cochrane database of systematic reviews (2024)

There was inconsistent evidence on all outcomes to draw conclusions on the beneficial and harmful effects of antioxidants.

Zinc versus placebo Zinc may not be better than placebo at reducing the frequency of crisis at six months (rate ratio 0.62, 95% CI 0.17 to 2.29; 1 study, 36 participants; low-certainty evidence).
We are uncertain whether zinc is better than placebo at improving sickle cell-related complications (complete healing of leg ulcers at six months: RR 2.00, 95% CI 0.60 to 6.72; 1 study, 34 participants; very low-certainty evidence).
Zinc may be better than placebo at increasing haemoglobin level (g/dL) (MD 1.26, 95% CI 0.44 to 1.26; 1 study, 36 participants; low-certainty evidence).

Meta-Analysisn=1,609

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Comparative Effects of Different Nutritional Supplements on Inflammation, Nutritional Status, and Clinical Outcomes in Colorectal Cancer Patients: A Systematic Review and Network Meta-Analysis

Ye J et al. • Nutrients (2023)

Future well-designed RCTs are needed to further confirm these findings.

Glutamine was superior in decreasing tumor necrosis factor-α (MD -25.2; 95% CrI [-32.62, -17.95]), whereas combined omega-3 and arginine supplementation was more effective in decreasing interleukin-6 (MD -61.41; 95% CrI [-97.85, -24.85]).
No nutritional supplements significantly maintained nutritional indicators in CRC patients.
Future well-designed RCTs are needed to further confirm these findings.

Meta-Analysisn=2,841

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Impact of Perioperative Immunonutrition on Postoperative Outcomes for Patients Undergoing Head and Neck or Gastrointestinal Cancer Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Matsui R et al. • Annals of surgery (2024)

Nutritional intervention with perioperative immunonutrition in patients with HAN and GI cancers significantly reduced total postoperative complications and infectious complications.

Immunonutrition reduced the total postoperative complications (relative risk ratio: 0.78; 95% CI, 0.66-0.93; certainty of evidence: high) and infectious complications (relative risk ratio: 0.71; 95% CI, 0.61-0.82; certainty of evidence: high) compared with standard nutritional therapy.
Further research warranted to confirm findings

Meta-Analysisn=4,825

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Effects of L-arginine supplementation on blood pressure: A systematic review and meta-analysis of randomized clinical trials

Bahadoran Z et al. • Clinical Nutrition (2021)

L-arginine supplementation significantly reduced systolic and diastolic blood pressure in pooled analysis of RCTs.

Significant reduction in systolic blood pressure (mean -5.39 mmHg)
Significant reduction in diastolic blood pressure (mean -2.66 mmHg)
Effects mediated through nitric oxide pathway enhancement

Meta-Analysisn=1,198

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An updated systematic review and meta-analysis of the effect of statins on asymmetric dimethylarginine

Zinellu A et al. • Nitric oxide : biology and chemistry (2022)

Statin treatment significantly lowers ADMA concentrations.

In 23 studies, reporting 25 treatment arms in 845 participants (mean age 53 years, 57% males, treatment duration 4-48 weeks), statins significantly reduced ADMA concentrations (SMD = -0.39, 95% CI -0.62 to -0.16, p = 0.001; moderate certainty of evidence).
In sensitivity analysis, the corresponding SMD values were not substantially modified when individual studies were sequentially removed.
Significant associations were observed, in meta-regression, between the SMD and publication year (t = -3.25, p = 0.003), but not baseline cholesterol concentrations.

Meta-Analysisn=845

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L-arginine impact on inflammatory and cardiac markers in patients undergoing coronary artery bypass graft: a systematic review and meta-analysis of randomized controlled trials

Mohammadi Z et al. • BMC cardiovascular disorders (2024)

Our findings suggest that L-arginine may benefit patients undergoing CABG, as it helps reduce inflammatory reactions and limits myocardial ischemia.

In a meta-analysis of three trials that reported troponin T levels, we found a significant impact of L-arginine on reducing troponin T levels (WMD = -0.61 ng/ml; 95% CI: -1.07, -0.15).
Our analysis also showed that L-arginine had a noticeable impact on decreasing interleukin-6 (IL-6) levels (WMD = -7.72 pg/ml; 95% CI: -15.05, -0.39).
Our findings suggest that L-arginine may benefit patients undergoing CABG, as it helps reduce inflammatory reactions and limits myocardial ischemia.

Meta-Analysisn=393

DOI

Effects of L-arginine on blood pressure: A systematic review and meta-analysis

Dong JY et al. • American Heart Journal (2011)

L-arginine supplementation significantly lowered systolic and diastolic blood pressure.

Modest blood pressure reduction
Effects seen within 4 weeks
Greater effects in those with hypertension

Meta-Analysisn=1,166

DOI

Nutritional interventions for treating foot ulcers in people with diabetes

Moore ZE et al. • The Cochrane database of systematic reviews (2020)

Evidence for the impact of nutritional interventions on the healing of foot ulcers in people with diabetes compared with no nutritional supplementation, or compared with a different dose of nutritional supplementation, remains uncertain, with eight studies showing no clear benefit or harm.

It is also uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement increases the proportion of ulcers healed at 16 weeks compared with placebo (RR 1.09, 95% CI 0.85 to 1.40).
It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, reduces the number of deaths (RR 0.96, 95% CI 0.06 to 14.60) or amputations (RR 4.82, 95% CI 0.24 to 95.88) more than placebo.
It is uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement increases health-related quality of life at 16 weeks more than placebo (MD -0.03, 95% CI -0.09 to 0.03).

Meta-Analysisn=629

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Effects of different dietary supplements on athletic performance in soccer players: a systematic review and network meta-analysis

Luo H et al. • Journal of the International Society of Sports Nutrition (2025)

This study suggests that a range of dietary supplements, including caffeine, creatine, creatine + sodium bicarbonate, magnesium creatine chelate, carbohydrate + electrolyte, carbohydrate + protein, arginine, beta-alanine, bovine colostrum, Kaempferia parviflora, melatonin, and sodium pyruvate, can improve athletic performance in soccer players.

Kaempferia parviflora (SMD: 0.46, small) was associated with a significant effect on enhancing muscular strength.
Beta-alanine (SMD: 0.83, moderate), melatonin (SMD: 0.75, moderate), caffeine (SMD: 0.37, small), and creatine (SMD: 0.33, small) were associated with a significant effect on enhancing jump height.
Magnesium creatine chelate (SMD: -3.0, very large), melatonin (SMD: -1.9, large), creatine + sodium bicarbonate (SMD: -1.4, large), and arginine (SMD: -1.2, moderate) were associated with a significant effect on decreasing sprint time.

Meta-Analysis

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The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis

Rhim HC et al. • The journal of sexual medicine (2019)

The results of our systematic review and meta-analysis provide evidence on the effectiveness of arginine supplements for mild to moderate ED.

The analysis demonstrated that arginine supplements with dosage ranging from 1,500 to 5,000 mg significantly improved ED compared with placebo or no treatment (odds ratios, 3.37 [1.29, 8.77], P = .01, I2 = 44).
Arginine supplements also caused significant improvements in the IIEF subdomain scores of overall satisfaction, intercourse satisfaction, orgasmic function, and erectile function, whereas the IIEF sexual desire score remain unchanged.
The adverse effect rate in the arginine-treated group was 8.3%, and that in the placebo group was 2.3%, none of which were severe.

Meta-Analysisn=540

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Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis

Tian Y et al. • Frontiers in endocrinology (2023)

These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED.

These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED.
This study will provide clinicians with more options for treating patients with ED.
More randomized controlled trials are needed in the future to further demonstrate the effect of combination therapy on sexual function in patients with ED.

Meta-Analysisn=184

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The use of oral and enteral tube-fed arginine supplementation in pressure injury care: A systematic review and meta-analysis

Cheshmeh S et al. • Nursing open (2022)

Our findings suggest that the administration of Arginine supplement in patients with PIs can accelerate the healing of this type of ulcer.

PIs were significantly improved with Arginine supplementation (SMD: -0.6; CI 95%: -0.9 to -0.3, I2 : 72.5%, p = .001).
Subgroup analysis showed that administering Arginine supplement more than 15 g/day had more beneficial effects on the healing of PIs (SMD: -2.8; CI 95%: -4.08 to -1.52, I2 : 54.7%, p = .138).
Our findings suggest that the administration of Arginine supplement in patients with PIs can accelerate the healing of this type of ulcer.

Meta-Analysisn=196

DOI

Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials

Xu Z et al. • Andrologia (2021)

Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED.

Erectile functions were significantly improved in three therapy groups compared with baseline.
Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs.
Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001).

Meta-Analysisn=373

DOI

L-arginine supplementation and exercise performance: A systematic review and meta-analysis

Viribay A et al. • Nutrients (2020)

L-arginine supplementation improved aerobic and anaerobic exercise performance parameters in trained and untrained individuals.

Improved VO2 max and time to exhaustion in aerobic exercise
Enhanced anaerobic exercise capacity and power output
Optimal dosing range of 1.5-6 g/day for performance benefits

Meta-Analysisn=578

DOI

Dietary Supplements for Erectile Dysfunction: Analysis of Marketed Products, Systematic Review, Meta-Analysis and Rational Use

Petre GC et al. • Nutrients (2023)

DSs marketed in Italy are usually blends of many substances that are frequently employed at a negligible dose or without any evidence.

Based on the scoring system, 2 (8%) supplements matched with the cluster of higher expected efficacy, 3 (12%) with the lower efficacy cluster and 20 (80%) matched with the criterion of no expected efficacy.
A systematic review of the literature was performed to evaluate the effect of DS and to detect the active ingredients able to improve erectile function-called effective ingredients (EIs)-and their minimal effective daily dose (mED).
A metanalysis identified some nutraceuticals, such as Panax ginseng, Tribulus terrestris and L-arginine, that are able to improve male sexual function.

Meta-Analysis

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A systematic review and meta-analysis of nitric oxide-associated arginine metabolites in schizophrenia

Zinellu A et al. • Translational psychiatry (2024)

This meta-analysis examined the effects of Arginine.

In subgroup analysis, the pooled SMD for ornithine was significantly different in studies of untreated, but not treated, patients.
Our study suggests that DDAH1 and arginase are dysregulated in schizophrenia.
Further studies are warranted to investigate the expression/activity of these enzymes in the brain of patients with schizophrenia and the effects of targeted treatments.

Meta-Analysis

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A systematic review and meta-analysis of GFAP gene variants in Alexander disease

Grossi A et al. • Scientific reports (2024)

This meta-analysis examined the effects of Arginine.

To identify possible associations, statistical analyses and meta-analyses were applied, thus revealing a higher than expected percentage of adult patients with ALXDRD.
Furthermore, substitution of Arginine, the most frequently altered residue among the 550 predominantly missense causative GFAP variants collected, were mostly de novo and more prevalent in early-onset forms of ALXDRD.
The effect of defective splicing in modifying the impact of GFAP variants on the age of onset of ALXDRD was also postulated after evaluating the distribution of the corresponding deleterious predictive values.

Meta-Analysis

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