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Supplement × Supplement·Evidence index

L-Arginine and L-Citrulline: what the research found

PubMed indexes 8 records that name L-Arginine and L-Citrulline together, either in the title or in an interaction, co-administration, or pharmacokinetic context. The key findings come first, in the authors’ own words, followed by every study with its design and PubMed link.

A summary of published research, not medical advice. A pharmacist can check any combination against your full list of medicines and supplements.

Key findings

What the studies concluded.

Reviews and human studies first. Each quote is the authors’ own conclusion about their study, not a NutriStack assessment, and a single study is not a consensus.

“L-arginine may be promising for pre-eclampsia prevention and treatment, but findings should be interpreted cautiously. More trials are needed to determine the optimal dose and time to commence supplementation and support clinical decision-making.”

Makama et al. · 2025 · Review or meta-analysis · details

“Foods rich in polyphenols and nitrate provide trivial benefits for endurance exercise performance, although these effects may be food dependent. Highly trained endurance athletes do not appear to benefit from consuming nitrate-rich foods but may benefit from polyphenol consumption. Further research into food sources, dosage and supplementation duration to optimise the ergogenic response to polyphenol consumption…”

d'Unienville et al. · 2021 · Review or meta-analysis · details

“Plasma arginine and citrulline were significantly elevated in type 2 diabetic patients with DR compared to diabetic controls. None of the tested metabolites significantly differed between NPDR and PDR patients in the adjusted analysis.”

The research

8 studies naming L-Arginine and L-Citrulline.

Strongest relevance first: papers naming both substances in the title, then human trials and systematic reviews.

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

BJOG : an international journal of obstetrics and gynaecology · 2025 · PMID 39800868

Systematic ReviewMeta-AnalysisHuman subjects

“L-arginine may be promising for pre-eclampsia prevention and treatment, but findings should be interpreted cautiously. More trials are needed to determine the optimal dose and time to commence supplementation and support clinical decision-making.”

Makama et al. · Authors' conclusion

Names both L-Arginine and L-Citrulline in its title.

Effect of food sources of nitrate, polyphenols, L-arginine and L-citrulline on endurance exercise performance: a systematic review and meta-analysis of randomised controlled trials.

Journal of the International Society of Sports Nutrition · 2021 · PMID 34965876

Meta-AnalysisSystematic ReviewHuman subjects

“Foods rich in polyphenols and nitrate provide trivial benefits for endurance exercise performance, although these effects may be food dependent. Highly trained endurance athletes do not appear to benefit from consuming nitrate-rich foods but may benefit from polyphenol consumption. Further research into food sources, dosage and supplementation duration to optimise the ergogenic response to polyphenol consumption is warranted.”

d'Unienville et al. · Authors' conclusion

Names both L-Arginine and L-Citrulline in its title.

Arginine deprivation/citrulline augmentation with ADI-PEG20 as novel therapy for complications in type 2 diabetes.

Molecular metabolism · 2024 · PMID 39214514

Animal study

“ADI-PEG20 treatment limited signs of DR and DPN and enhanced wound healing in db/db mice. Studies using BMDM suggest that the anti-inflammatory effects of ADI-PEG20 involve blockade of the JAK2-STAT1 signaling pathway via l-arginine depletion and l-citrulline production.”

Abdelrahman et al. · Authors' conclusion

Names both L-Arginine and L-Citrulline in its title.

Plasma Arginine and Citrulline are Elevated in Diabetic Retinopathy.

American journal of ophthalmology · 2022 · PMID 34587493

Research Support, N.I.H., ExtramuralHuman subjects

“Plasma arginine and citrulline were significantly elevated in type 2 diabetic patients with DR compared to diabetic controls. None of the tested metabolites significantly differed between NPDR and PDR patients in the adjusted analysis.”

Peters et al. · Authors' conclusion

Names both L-Arginine and L-Citrulline in its title.

The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure.

Nutrients · 2019 · PMID 31336573

ReviewHuman subjects

“Thus, elevated plasma Arg concentrations would not be expected to increase endogenous NO production significantly, but have nonetheless been observed in other studies. This phenomenon is known as the "l-arginine paradox".”

Khalaf et al. · From the abstract

Names both L-Arginine and L-Citrulline in its title.

Arginine and citrulline and the immune response in sepsis.

Nutrients · 2015 · PMID 25699985

ReviewHuman subjects

“The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target.”

Wijnands et al. · From the abstract

Names both L-Arginine and L-Citrulline in its title.

Mitochondria: role of citrulline and arginine supplementation in MELAS syndrome.

The international journal of biochemistry & cell biology · 2014 · PMID 24412347

ReviewHuman subjects

“Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS syndrome are needed.”

El-Hattab et al. · From the abstract

Names both L-Arginine and L-Citrulline in its title.

Limitations

What this evidence cannot tell you.

Search-based evidence indexes have real limits, and it is worth being explicit about them:

How to read this page

A literature summary, not guidance.

NutriStack

Track what you actually take.

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