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Supplement

L-Citrulline

Arginine precursor to support nitric oxide bioavailability.[3115,3853,4015, etc.]

Superscript reference numbers link to the Sources bibliography.

Strong Evidence
PerformanceHeart Healthalias: citrulline malate

Composite Rating

3.8/5

Blends evidence depth, community direction, safety friction, and completeness.

Evidence Intensity

100/100

High depth from human/RCT/meta counts

Community Direction

2

Mixed / Neutral • confidence Minimal

Safety Friction

100/100

High signal from adverse/interaction markers

Data Completeness

100%

Studies 15 • mentions 5 • links 25

Not medical advice. This product is for educational and informational purposes only. It does not diagnose, treat, cure, or prevent any disease and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions regarding a medical condition.

FDA disclaimer: These statements have not been evaluated by the Food and Drug Administration. Dietary supplements are not intended to diagnose, treat, cure, or prevent any disease. Results may vary. Not intended for use by pregnant or nursing women, individuals under 18, or those with known medical conditions without physician consultation.

If you are experiencing a medical emergency, call 911 or your local emergency number immediately.

Implementation Blueprint

Goal alignment: Performance, Heart Health.[538,686,910, etc.]

Dose guide: Human-study daily dose: 200 mg-6000 mg/day (higher-confidence extraction from PubMed abstracts)..[538,686,910, etc.]

Category: amino-acid.[538,686,910, etc.]

Category

Amino Acid

Evidence Tier

HIGH

Daily Guide

Human-study daily dose: 200 mg-6000 mg/day (higher-confidence extraction from PubMed abstracts).

Dosing Guide

Human-study daily dose: 200 mg-6000 mg/day (higher-confidence extraction from PubMed abstracts).[3115,3853,4015, etc.]

Safety and Pitfalls

  • Blood pressure can drop in sensitive users[538,686,910, etc.]
  • Potential side effect: GI upset[538,686,910, etc.]
  • Interaction check: nitrates[538,686,910, etc.]
  • Interaction check: antihypertensives[538,686,910, etc.]
  • Legacy caution group: Thiamine-deficient individuals (supplement B1 alongside)[538,686,910, etc.]
  • Legacy caution group: Hypoglycemia-prone without monitoring[538,686,910, etc.]

At-A-Glance Evidence Architecture[3115,3853,4015, etc.]

Clinical Depth

Humans: 188 • RCTs: 71 • Meta: 8

Cohort / Real-World

Cohort signals: 0

Safety Markers

Adverse signals: 56 • Interactions: 115

Evidence Tracking

Freshness, trend, and study timeline for this item

Evidence Tracking

Status

New Evidence

Trend

→ Stable evidence base

Depth

365 total studies · 5 recent

Timeline

20182025

Top Signal Metrics[3115,3853,4015, etc.]

Animal-only studies

776

Total indexed

365

In vitro / tissue

202

Human studies

188

Interaction signals

115

Randomized trials

71

Community Direction Mix[538,686,910, etc.]

Weighted direction score: 2 (Mixed / Neutral)

Benefit2 (40%)
Adverse1 (20%)
No Effect1 (20%)
Mixed1 (20%)

Evidence Quality Summary[3115,3853,4015, etc.]

High when >=2 human meta-analyses, or >=5 human RCTs with substantial human literature volume.

Animal-only studies

776

Total indexed

365

In vitro / tissue

202

Human studies

188

Interaction signals

115

Randomized trials

71

Safety adverse signals

56

Meta-analyses

8

Study Type Breakdown

Distribution of evidence by study design strength

Meta-AnalysesLevel 1a8
Randomized TrialsLevel 1b71
Human Studies (other)Level 3-4109
All IndexedAll levels365
100

Evidence Strength: High

Composite of study volume, RCTs, and meta-analyses

Top Human Studies[3115,3853,4015, etc.]

PMID 34965876 • 2021 Dec 29

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.

J Int Soc Sports Nutr

Open PubMed

PMID 39800868 • 2025 May

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

BJOG

Open PubMed

PMID 30284051 • 2018 Oct 3

Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials.

Curr Hypertens Rep

Open PubMed

PMID 41097202 • 2025 Sep 30

Effects of Citrulline or Watermelon Supplementation on Body Composition: A Systematic Review and Dose-Response Meta-Analysis.

Nutrients

Open PubMed

PMID 37111214 • 2023 Apr 21

Absence of Effects of L-Arginine and L-Citrulline on Inflammatory Biomarkers and Oxidative Stress in Response to Physical Exercise: A Systematic Review with Meta-Analysis.

Nutrients

Open PubMed

PMID 33308806 • 2020 Dec

Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: A systematic review and meta-analysis.

J Sport Health Sci

Open PubMed

PMID 34579009 • 2021 Sep 8

L-Citrulline Supplementation and Exercise in the Management of Sarcopenia.

Nutrients

Open PubMed

PMID 37242187 • 2023 May 14

The Effect of Acute Pre-Workout Supplement Ingestion on Basketball-Specific Performance of Well-Trained Athletes.

Nutrients

Open PubMed

PMID 39638148 • 2025 Feb

Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial.

Am J Clin Nutr

Open PubMed

PMID 33876875 • 2021 Jun

The impact of L-citrulline supplementation on glucose homeostasis, lipid profile, and some inflammatory factors in overweight and obese patients with type 2 diabetes: A double-blind randomized placebo-controlled trial.

Phytother Res

Open PubMed

PMID 39662304 • 2025 Mar 1

Malate or Not? Acute Effects of L-Citrulline Versus Citrulline Malate on Neuromuscular Performance in Young, Trained Adults: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial.

Int J Sport Nutr Exerc Metab

Open PubMed

PMID 40010353 • 2025 Apr 1

Effects of Combined Versus Single Supplementation of Creatine, Beta-Alanine, and L-Citrulline During Short Sprint Interval Training on Basketball Players' Performance: A Double-Blind Randomized Placebo-Controlled Trial.

Int J Sports Physiol Perform

Open PubMed

PMID 36480969 • 2022 Dec 13

Micronutrient Supplementation to Reduce Cardiovascular Risk.

J Am Coll Cardiol

Open PubMed

PMID 36771366 • 2023 Jan 28

Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature.

Nutrients

Open PubMed

PMID 36904267 • 2023 Mar 3

Dietary Arginine and Citrulline Supplements for Cardiovascular Health and Athletic Performance: A Narrative Review.

Nutrients

Open PubMed

Community Report Frequency[538,686,910, etc.]

Benefit reports: 2

Adverse reports: 1

No-effect reports: 1

Mixed reports: 1

Unclear reports: 0

Signal confidence: 0.00

Top Reported Effects[538,686,910, etc.]

Benefits

  • Universal antioxidant protection: 1
  • Blood sugar regulation: 1
  • Diabetic neuropathy improvement: 1
  • Heavy metal chelation: 1
  • Regenerates other antioxidants: 1
  • Neuroprotection: 1
  • Skin anti-aging: 1

Adverse

  • Thiamine-deficient individuals (supplement B1 alongside): 1
  • Hypoglycemia-prone without monitoring: 1

No Effect

  • no noticeable effect: 1

Popular in stimulant-free performance stacks. | Step2: Insufficient empirical signal for a directional adjustment.

Reddit evidence: 0 mentions (confidence 0.00).

Amazon signal: 0 products scanned (confidence 0.00).

GNC signal: 0 products scanned (confidence 0.00) [BLOCKED].

PerimeterX / captcha block encountered.

Search fetch failed: Failed to fetch after retries: https://old.reddit.com/search.json?raw_json=1&sort=relevance&t=year&limit=12&q=%22l-citrulline%22%20(supplement%20OR%20dosage%20OR%20stack%20OR%20side%20effects%20OR%20review)%20(subreddit%3ASupplements%20OR%20subreddit%3ANootropics%20OR%20subreddit%3ABiohackers%20OR%20subreddit%3Alongevity%20OR%20subreddit%3ANutrition%20OR%20subreddit%3AHubermanLab%20OR%20subreddit%3ASleep%20OR%20subreddit%3AFitness%20OR%20subreddit%3Aketoscience%20OR%20subreddit%3AStackAdvice)

Fallback search failed: Failed to fetch after retries: https://old.reddit.com/search.json?raw_json=1&sort=comments&t=all&limit=16&q=%22l-citrulline%22%20(supplement%20OR%20capsule%20OR%20powder%20OR%20experience%20OR%20results%20OR%20side%20effects)

Broad search failed: Failed to fetch after retries: https://old.reddit.com/search.json?raw_json=1&sort=new&t=all&limit=16&q=l-citrulline

Use adverse/interactions PubMed signal counts for screening; perform clinician review before high-dose or multi-drug stack use.

Human-study daily dose signal: 200 mg-6000 mg/day (confidence HIGH).

Extracted from 10 dosing mentions across 3 PubMed studies (mg/day).

Imported legacy community score: 7.0/10 (heuristic mapping confidence 1.00).

Imported legacy monthly cost signal: ~$18.00.

Legacy community note: Well-respected for blood sugar and neuropathy. R-ALA form gaining preference over racemic ALA. ALCAR + ALA "mito stack" is popular in anti-aging community. Some users report skin improvements.

Community Evidence Examples[538,686,910, etc.]

aggregate • benefit

Aggregate community signal: 5 directional mentions (benefit 2, adverse 1, no-effect 1, mixed 1).

Open mention

Retail Signal Examples

amazon

Amazon search for L-Citrulline

Rating: n/a | Reviews: n/a

Open product

Primary Source Links

Evidence Sources

  • https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22l-citrulline%22)%20AND%20(supplement*%5BTitle%2FAbstract%5D%20OR%20supplementation%5BTitle%2FAbstract%5D%20OR%20intake%5BTitle%2FAbstract%5D%20OR%20dietary%20supplements%5BMeSH%20Terms%5D)
  • https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22l-citrulline%22)%20AND%20humans%5BMeSH%20Terms%5D%20AND%20(supplement*%5BTitle%2FAbstract%5D%20OR%20supplementation%5BTitle%2FAbstract%5D%20OR%20intake%5BTitle%2FAbstract%5D%20OR%20dietary%20supplements%5BMeSH%20Terms%5D)
  • https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22l-citrulline%22)%20AND%20animals%5BMeSH%20Terms%5D%20NOT%20humans%5BMeSH%20Terms%5D
  • https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22l-citrulline%22)%20AND%20humans%5BMeSH%20Terms%5D%20AND%20(supplement*%5BTitle%2FAbstract%5D%20OR%20supplementation%5BTitle%2FAbstract%5D%20OR%20intake%5BTitle%2FAbstract%5D%20OR%20dietary%20supplements%5BMeSH%20Terms%5D)%20AND%20randomized%20controlled%20trial%5BPublication%20Type%5D
  • https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22l-citrulline%22)%20AND%20humans%5BMeSH%20Terms%5D%20AND%20(supplement*%5BTitle%2FAbstract%5D%20OR%20supplementation%5BTitle%2FAbstract%5D%20OR%20intake%5BTitle%2FAbstract%5D%20OR%20dietary%20supplements%5BMeSH%20Terms%5D)%20AND%20meta-analysis%5BPublication%20Type%5D
  • https://pubmed.ncbi.nlm.nih.gov/34965876/
  • https://pubmed.ncbi.nlm.nih.gov/39800868/
  • https://pubmed.ncbi.nlm.nih.gov/30284051/
  • https://pubmed.ncbi.nlm.nih.gov/41097202/
  • https://pubmed.ncbi.nlm.nih.gov/37111214/
  • https://pubmed.ncbi.nlm.nih.gov/33308806/
  • https://pubmed.ncbi.nlm.nih.gov/34579009/
  • https://pubmed.ncbi.nlm.nih.gov/37242187/
  • https://pubmed.ncbi.nlm.nih.gov/39638148/
  • https://pubmed.ncbi.nlm.nih.gov/33876875/
  • https://pubmed.ncbi.nlm.nih.gov/39662304/
  • https://pubmed.ncbi.nlm.nih.gov/40010353/
  • https://pubmed.ncbi.nlm.nih.gov/36480969/
  • https://pubmed.ncbi.nlm.nih.gov/36771366/
  • https://pubmed.ncbi.nlm.nih.gov/36904267/

Community Sources

  • https://old.reddit.com/search.json?raw_json=1&sort=relevance&t=year&limit=12&q=%22l-citrulline%22%20(supplement%20OR%20dosage%20OR%20stack%20OR%20side%20effects%20OR%20review)%20(subreddit%3ASupplements%20OR%20subreddit%3ANootropics%20OR%20subreddit%3ABiohackers%20OR%20subreddit%3Alongevity%20OR%20subreddit%3ANutrition%20OR%20subreddit%3AHubermanLab%20OR%20subreddit%3ASleep%20OR%20subreddit%3AFitness%20OR%20subreddit%3Aketoscience%20OR%20subreddit%3AStackAdvice)
  • https://old.reddit.com/search.json?raw_json=1&sort=comments&t=all&limit=16&q=%22l-citrulline%22%20(supplement%20OR%20capsule%20OR%20powder%20OR%20experience%20OR%20results%20OR%20side%20effects)
  • https://old.reddit.com/search.json?raw_json=1&sort=new&t=all&limit=16&q=l-citrulline
  • https://www.reddit.com/search/?q=L-Citrulline

Scientific Evidence Notes[3115,3853,4015, etc.]

1. Citrulline and high-intensity exercise

RCT • 2022 • Adults

Recreationally trained adults.

Outcome: May improve reps-to-failure and perceived exertion.[3115,3853,4015, etc.]

2. PubMed evidence summary: L-citrulline

PUBMED • Humans + preclinical triage

Counts aggregated from automated literature sweep and tiering rules.

Outcome: Tier HIGH; humans 188, RCTs 71, meta-analyses 8.[3115,3853,4015, etc.]

Open source
3. 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.

PUBMED • 2021 • Human evidence curation set

PMID 34965876 from J Int Soc Sports Nutr.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

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

PUBMED • 2025 • Human evidence curation set

PMID 39800868 from BJOG.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
5. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials.

PUBMED • 2018 • Human evidence curation set

PMID 30284051 from Curr Hypertens Rep.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
6. Effects of Citrulline or Watermelon Supplementation on Body Composition: A Systematic Review and Dose-Response Meta-Analysis.

PUBMED • 2025 • Human evidence curation set

PMID 41097202 from Nutrients.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
7. Absence of Effects of L-Arginine and L-Citrulline on Inflammatory Biomarkers and Oxidative Stress in Response to Physical Exercise: A Systematic Review with Meta-Analysis.

PUBMED • 2023 • Human evidence curation set

PMID 37111214 from Nutrients.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
8. Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: A systematic review and meta-analysis.

PUBMED • 2020 • Human evidence curation set

PMID 33308806 from J Sport Health Sci.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
9. L-Citrulline Supplementation and Exercise in the Management of Sarcopenia.

PUBMED • 2021 • Human evidence curation set

PMID 34579009 from Nutrients.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
10. The Effect of Acute Pre-Workout Supplement Ingestion on Basketball-Specific Performance of Well-Trained Athletes.

PUBMED • 2023 • Human evidence curation set

PMID 37242187 from Nutrients.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
11. Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial.

PUBMED • 2025 • Human evidence curation set

PMID 39638148 from Am J Clin Nutr.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
12. The impact of L-citrulline supplementation on glucose homeostasis, lipid profile, and some inflammatory factors in overweight and obese patients with type 2 diabetes: A double-blind randomized placebo-controlled trial.

PUBMED • 2021 • Human evidence curation set

PMID 33876875 from Phytother Res.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
13. Malate or Not? Acute Effects of L-Citrulline Versus Citrulline Malate on Neuromuscular Performance in Young, Trained Adults: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial.

PUBMED • 2025 • Human evidence curation set

PMID 39662304 from Int J Sport Nutr Exerc Metab.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
14. Effects of Combined Versus Single Supplementation of Creatine, Beta-Alanine, and L-Citrulline During Short Sprint Interval Training on Basketball Players' Performance: A Double-Blind Randomized Placebo-Controlled Trial.

PUBMED • 2025 • Human evidence curation set

PMID 40010353 from Int J Sports Physiol Perform.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
15. Micronutrient Supplementation to Reduce Cardiovascular Risk.

PUBMED • 2022 • Human evidence curation set

PMID 36480969 from J Am Coll Cardiol.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
16. Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature.

PUBMED • 2023 • Human evidence curation set

PMID 36771366 from Nutrients.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source
17. Dietary Arginine and Citrulline Supplements for Cardiovascular Health and Athletic Performance: A Narrative Review.

PUBMED • 2023 • Human evidence curation set

PMID 36904267 from Nutrients.

Outcome: See linked PubMed abstract for methods and outcomes.[3115,3853,4015, etc.]

Open source