Research Summary

Citrulline improves microvascular function and muscle strength in T2D

Key finding

CITS increased the LnRHI (Δ0.11 ± 0.16 vs. Δ−0.08 ± 0.24, p < 0.05)

Citrulline supplementation improved microvascular function and muscle strength in patients with type 2 diabetes compared to placebo.

Evidence strength

Moderate confidence

Study type

RCTs

Follow-up

Short-Term (≤3 mo)

Some Concerns bias

Last updated July 8, 2026

Quick read

Study at a glance

The essential study design details in one scan.

Population

Young Adult (19–39), Middle Aged (40-64), Male, Female, Asia-Pacific (APAC), with T2 Diabetes

Intervention

Citrulline supplementation, Placebo

Study type

RCTs

Follow-up

Short-Term (≤3 mo)

Primary outcome

Log-transformed reactive hyperemia index (LnRHI)

Comparator

Placebo

Plain-language summary

What this paper says

A plain-language read of the study's main message and where it applies.

Study focus

Citrulline supplementation improved microvascular function and muscle strength in patients with type 2 diabetes compared to placebo.

Clinical relevance

Improving microvascular function and muscle strength in patients with type 2 diabetes can enhance overall health and reduce complications associated with the disease. Citrulline supplementation may offer a simple, effective strategy to support these improvements, potentially leading to better management of diabetes-related issues.

Keep in mind

Limited sample size may affect generalizability. Short duration of the study may not capture long-term effects. Potential confounding factors not fully controlled.

Published in

Journal Reference

Publication details and source links for this paper.

Arturo F, Katherine ND, Danielle EL, Yejin K, Carlo MP. Citrulline Supplementation Improves Microvascular Function and Muscle Strength in Patients with Type 2 Diabetes. Nutrients. 2025;17(17):2790. doi:10.3390/nu17172790

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Main Effects

Citrulline supplementation increased the LnRHI by Δ0.11 ± 0.16 (p < 0.05).

Citrulline supplementation increased the TOI range by Δ2.6 ± 3.3% (p < 0.01).

Citrulline supplementation increased calf muscle strength by Δ1.5 ± 2.8 kg (p < 0.05).

Evidence network

How this study fits

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Evidence Context

This study contributes evidence to L-citrulline supplementation (Phase 1) and Glucose iAUC (OGTT), Log-transformed reactive hyperemia index (LnRHI), Muscular strength, and 3 more.

This study contributes evidence to

Intervention

L-citrulline supplementation (Phase 1)

Outcome

Glucose iAUC (OGTT)

Evidence topic

Glycemic Control

Primary intervention

L-citrulline supplementation (Phase 1)

Primary outcomes

Glucose iAUC (OGTT)
Log-transformed reactive hyperemia index (LnRHI)
Muscular strength

Evidence topics

Glycemic Control

Primary intervention

L-citrulline supplementation (Phase 1)

Primary outcomes

Glucose iAUC (OGTT)Log-transformed reactive hyperemia index (LnRHI)Muscular strength

Evidence relationships

Intervention and outcome relationships this study adds to the evidence network.

Evidence pairs

Relationships

Evidence topics

contributes_evidence

Editorial context

Why this study matters

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Evidence network role

This section describes how the study fits into the current evidence network. It does not determine whether an intervention works on its own.

Moderate contributionModerate confidenceNetwork score: 63

Why it is useful

Contributes to 6 evidence relationships
Includes primary outcome data
Linked to 1 direct semantic evidence topic

Topic contributions

Evidence topic

L-citrulline supplementation (Phase 1) → TOI hyperemic response

Evidence profile

StrongIncreaseClinical Outcomes

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Evidence Suggest

Citrulline raised plasma arginine levels by Δ43 μM/L (p < 0.001).
Citrulline improved TOI hyperemic response by Δ1.2% (p < 0.05).
Placebo did not significantly change any measured outcomes.

Who this applies to

Adults diagnosed with type 2 diabetes.
Patients experiencing muscle weakness or vascular issues.

Keep in Mind

Results may not apply to other types of diabetes.
Further research needed to confirm long-term benefits.
Study findings are based on a specific population sample.

Between the Lines

Limited sample size may affect generalizability.
Short duration of the study may not capture long-term effects.
Potential confounding factors not fully controlled.

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Connected Evidence

Explore related studies, evidence collections, and research questions.

This study contributes to evidence on L-citrulline supplementation (Phase 1) and Log-transformed reactive hyperemia index (LnRHI), L-citrulline supplementation (Phase 1) and Muscular Strength.

Related evidence relationships

Explore in Evidence Archive

This study contributes to the evidence on the following intervention-outcome relationships.

L-citrulline supplementation (Phase 1)Log-transformed reactive hyperemia index (LnRHI)

Supplements

1 studies

Detailed evidence

L-citrulline supplementation (Phase 1)Muscular Strength

Supplements

Latest published studies

recency_collection

Published within the last 2 years.

Does L-citrulline supplementation (Phase 1) improve muscular strength?

Emerging Evidence

L-citrulline supplementation (Phase 1) appears to improve Muscular strength.

ConsensusScore™: Results are consistent across studies.

Ranked evidence signals

1
Muscular strength
EvidenceScore™ Emerging | EvidenceScore™ 50.5 | strong positive | ConsensusScore™ Consistent | 1 study

Why this answer: This answer is based on a single supporting study.

Limitations

Only one supporting study is available.
Population details are unavailable.

View Full Evidence

Does L-citrulline supplementation (Phase 1) improve log-transformed reactive hyperemia index (lnrhi)?

Emerging Evidence

L-citrulline supplementation (Phase 1) appears to improve Log-transformed reactive hyperemia index (LnRHI).

ConsensusScore™: Consistency cannot yet be determined from the available evidence.

Ranked evidence signals

1
Log-transformed reactive hyperemia index (LnRHI)
EvidenceScore™ Emerging | EvidenceScore™ 50.5 | strong positive | ConsensusScore™ Unclear | 1 study

Why this answer: This answer is based on a single supporting study.

Limitations

Only one supporting study is available.
Consistency cannot yet be determined.
Population details are unavailable.

View Full Evidence

Does L-citrulline supplementation (Phase 1) improve plasma arginine levels?

Emerging Evidence

L-citrulline supplementation (Phase 1) appears to improve Plasma arginine levels.

ConsensusScore™: Consistency cannot yet be determined from the available evidence.

Ranked evidence signals

1
Plasma arginine levels
EvidenceScore™ Emerging | EvidenceScore™ 50.5 | strong positive | ConsensusScore™ Unclear | 1 study

Why this answer: This answer is based on a single supporting study.

Limitations

Only one supporting study is available.
Consistency cannot yet be determined.
Population details are unavailable.

View Full Evidence

Does L-citrulline supplementation (Phase 1) improve toi hyperemic response?

Emerging Evidence

L-citrulline supplementation (Phase 1) appears to improve TOI hyperemic response.

ConsensusScore™: Consistency cannot yet be determined from the available evidence.

Ranked evidence signals

1
TOI hyperemic response
EvidenceScore™ Emerging | EvidenceScore™ 50.5 | strong positive | ConsensusScore™ Unclear | 1 study

Why this answer: This answer is based on a single supporting study.

Limitations

Only one supporting study is available.
Consistency cannot yet be determined.
Population details are unavailable.

View Full Evidence

How connections are generated

Next steps

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Evidence topics

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Glycemic Control Evidence Hub

Explore in archive

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All studies on L-citrulline supplementation (Phase 1) and Log-transformed reactive hyperemia index (LnRHI)All studies on L-citrulline supplementation (Phase 1) and Muscular strength All studies on L-citrulline supplementation (Phase 1) and Plasma arginine levels All studies on L-citrulline supplementation (Phase 1) and TOI hyperemic response

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