Citrulline / L-Citrulline for Hypertension

Verdict: A small, real but unreliable blood-pressure dip

L-citrulline appears to lower blood pressure modestly, on the order of about 4 mmHg systolic, but the effect is small, the trials are short and tiny, and it is no substitute for proven first-line treatment. It earns a Weak Evidence (C) grade.

C 🟠 C Weak Evidence Published with Warning

🔬Why this grade7-layer evidence engine

Three meta-analyses point the same direction, which is why this isn't dismissed outright. A 2025 pooled analysis of 415 adults (PMID 40789388) found systolic pressure fell about 4.0 mmHg and diastolic about 2.5 mmHg, with a much larger drop (~10 mmHg systolic) when citrulline was combined with arginine. Two 2019 meta-analyses agree: PMID 31889969 reported brachial systolic -4.5 mmHg, and PMID 30788274 found systolic -4.1 mmHg, though diastolic only reached significance at doses of 6 g/day or more.

The grade stays at C rather than higher because the foundation is shaky. The supporting randomized trials are very small and low quality: a postmenopausal-women study (PMID 36297080, n=25) was underpowered to roughly nine per group, and an acute post-exercise study (PMID 39385595, n=20) tested only a single dose. The pooled trials mixed citrulline, watermelon extract, and citrulline malate, most ran only 4-8 weeks, funding was undisclosed, and one earlier meta-analysis was retracted and excluded.

Authorities are unconvinced. The EU's EFSA has issued no approved health claims and unfavorable opinions; the US FDA treats citrulline only as a dietary-supplement ingredient with no endorsement; NHS and WHO do not address it. The Mayo Clinic (via arginine) says it 'might' help but warns it can stack dangerously with blood-pressure drugs. The ~4 mmHg effect is far below diet, exercise, or medication, so it cannot be claimed to treat hypertension.

⚖️

Scoring transparency

All scores computed by a 7-layer evidence engine — fully auditable
Raw score 0.61
D
C
B
A
S
← counter-evidence / ineffectiveeffective / strong evidence →
Final grade
C · Published with Warning
Confidence
66%
Broadly consistent
Evidence level
E2
Multiple high-quality MAs (≥2 independent, consistent)

How strongly each layer supports this effect

lower = less supportive
L1 ExamineGlobal benchmark
0.50
L5 Clinical bodiesAuthoritative stance
0.50
L11 AI re-checkIndependent read
0.50
L3 MechanismPlausibility
0.65
L2 PubMedPrimary literature
0.75
Against Mixed Supports
View the full decision path (audit trail)
  1. compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.613
  2. tier_from_score — 依分數區間映射至 tier letter
  3. apply_hec_rules — 高品質 SR/MA 顯示 positive (2 篇 > 0 negative)
  4. tier_strict_requirement_check — | B→C 因 scope.conflation_risk=true 且 L11 獨評較低 (B7-2 tier cap)
  5. detect_disputes — 偵測到 0 個 hard + 0 個 soft dispute
  6. decide_status — 依 tier + dispute 結果決定 status

📄PubMed studies (5)L2 · primary research & systematic reviews

Does l-citrulline supplementation and watermelon intake reduce blood pressure in middle-aged and older adults?
PMID: 40789388 2025 統合分析 n = 415
Finding: Significant SBP reduction -4.02 mmHg (95% CI -6.54 to -1.50, p=0.002) and DBP -2.54 mmHg (95% CI -4.27 to -0.81, p=0.004); citrulline+arginine combo yielded SBP -10.44 mmHg (p<0.01).
Effect size: MD SBP -4.02 mmHg; MD DBP -2.54 mmHg
View on PubMed
Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials
PMID: 31889969 2019 統合分析
Finding: Brachial SBP -4.49 mmHg (95% CI -7.33 to -1.65, p=0.002); brachial DBP -3.63 mmHg (95% CI -5.83 to -1.43, p=0.001); aortic SBP -6.76 mmHg (95% CI -10.99 to -2.53, p=0.002).
Effect size: MD brachial SBP -4.49 mmHg; MD brachial DBP -3.63 mmHg
View on PubMed
Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis
PMID: 30788274 2019 統合分析
Finding: SBP reduced -4.10 mmHg (95% CI -7.94 to -0.26, p=0.037); DBP non-significant overall (-2.08 mmHg, p=0.069); doses >=6 g/day yielded significant DBP reduction -2.75 mmHg (p=0.04).
Effect size: MD SBP -4.10 mmHg; MD DBP -2.08 mmHg (NS overall)
View on PubMed
Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women
PMID: 36297080 2022 RCT (double-blind) n = 25
Finding: Aortic DBP decreased (delta -2 vs +2 mmHg, p=0.01); mean arterial pressure decreased (delta -2 vs +2 mmHg, p=0.04); FMD improved (p=0.03); very small n.
🟠 Limited quality Effect size: MD aortic DBP approx -4 mmHg vs placebo
View on PubMed
Acute Effects of Citrulline Malate Supplementation on Nocturnal Blood Pressure Dipping After Exercise in Hypertensive Patients
PMID: 39385595 2024 RCT (double-blind) n = 20
Finding: DBP reduction favoring citrulline malate at 24h (delta -14 vs -6 mmHg, p=0.047) and wakefulness (-12 vs -4 mmHg, p=0.024); no significant difference in nocturnal dipping or SBP.
🟠 Limited quality Effect size: MD 24h DBP delta approx -8 mmHg vs placebo
View on PubMed

🏛️Regulatory & authoritative positionsL4/L5 · FDA / EMA / NIH ODS / Cochrane / Mayo …

L4a US FDA
Neutral
L4b EU EFSA
Against
L4d TW TFDA / 衛福部
Neutral
相關作用機轉仍在科學研究階段(the related mechanism of action remains in the scientific research stage);目前西瓜的壯陽效果尚不確定(watermelon's purported enhancement effects remain unconfirmed)。台灣食品法規好像沒有把這個成分列為可添加用途。 source↗
L5a NIH Office of Dietary Supplements
Cautious
L5b Mayo Clinic
Cautious
L-arginine might be effective at lowering blood pressure... some research has shown that oral L-arginine can lower blood pressure in healthy people, people with mild blood pressure elevation and diabetes... If you take a blood pressure drug, talk to your doctor before using L-arginine. source↗
L5c Cleveland Clinic
Neutral
L5d Harvard Health
Neutral
L5e Specialty Society (condition-mapped)
Not addressed
PMID 100% verifiedevery citation checked via NCBI Entrez
🔬5 PubMed studiesindependently re-checked by multiple sub-agents
engine_version: v1.0 claim_id: CLM-COND-hypertension-INT-citrulline-001 繁體中文版 →