Natural Compound

Gotu Kola

Centella asiatica

Evidence TierBWADA NOT PROHIBITED

tuneTypical Dose

60-120 mg TTFCA

watchEffect Window

4-8 weeks for CVI. 2-4 weeks for wound healing. Acute for anxiolytic.

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Gotu kola (Centella asiatica) contains triterpenes that influence connective tissue and microcirculation. It is used for wound healing, venous health symptoms, and calm cognitive support goals.

The best human evidence for gotu kola is still vascular rather than cognitive. Standardized triterpene extracts improve chronic venous-insufficiency symptoms and objective microcirculation markers, while the cognition and anxiety signals remain small, indirect, or confounded by co-interventions. Effects depend heavily on standardized extract use and appropriate duration.

Triterpene saponins (asiaticoside, madecassoside) stimulate collagen I/III synthesis in vessel walls and fibroblasts, improving venous integrity and wound repair. Secondary GABAergic activity provides mild anxiolysis. BDNF promotion supports neuroprotection in preclinical models.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Improves chronic venous insufficiency symptoms (edema, leg heaviness, microcirculation)
  • Promotes wound healing and scar reduction

Secondary Outcomes

  • Mild anxiolytic effect (acoustic startle reduction in pilot study)
  • Neuroprotective and cognitive support (preclinical BDNF/dendrite data)

Safety

Contraindications and Interactions

Contraindications

  • Active liver disease
  • Pregnancy (insufficient data)
  • Apiaceae allergy

Side effects

  • Mild GI upset
  • Headache
  • Skin sensitivity (topical)

Interactions

  • Sedatives (additive CNS depression)
  • Hepatotoxic drugs (additive liver risk)

Avoid if

  • History of drug-induced liver injury
  • Children under 12
  • Pre-surgical (discontinue 2 weeks prior)

Evidence

Study-level References

gotu-kola-SRC-001Multicenter, double-blind, placebo-controlled randomized trial
Sourceopen_in_new

Pointel JP, Boccalon H, Cloarec M, et al. Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs. Angiology. 1987;38(1 Pt 1):46-50. doi:10.1177/000331978703800106. PMID:3544968.

Population: Adults with venous insufficiency of the lower limbs.

Dose protocol: 60 mg or 120 mg TECA daily for 2 months

Key findings: Significant improvement in plethysmographic parameters (capillary filtration rate, venous distensibility) and reduction in subjective symptoms (leg heaviness, edema, paresthesia) compared to placebo at both doses. The 120 mg dose showed numerically larger effects.

Notes: Landmark trial. Widely cited in European phytotherapy guidelines for CVI.

Paper content

This placebo-controlled multicenter trial randomized 94 adults with venous insufficiency to 60 mg/day or 120 mg/day of gotu kola extract or placebo for 2 months. Both active doses improved lower-limb heaviness, edema, and global patient assessment, and plethysmographic venous-distensibility measures also improved. It remains one of the strongest direct human trials for gotu kola, but it is old and focused on venous outcomes rather than cognition or anxiety.

gotu-kola-SRC-002Prospective, randomized, placebo-controlled trial
Sourceopen_in_new

Cesarone MR, Belcaro G, De Sanctis MT, et al. Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension. A clinical, prospective, randomized trial using a combined microcirculatory model. Angiology. 2001;52(Suppl 2):S15-S18. PMID:11666126.

Population: Adults with venous hypertensive microangiopathy.

Dose protocol: 60 mg TTFCA twice daily for 6 weeks

Key findings: TTFCA significantly improved microcirculation parameters including skin flux (laser Doppler), PO2, and PCO2. Ankle swelling rate decreased significantly versus placebo.

Notes: Confirms and extends Pointel findings with microcirculation-specific endpoints.

Paper content

This placebo-controlled randomized trial used a combined microcirculatory model and found that gotu kola's total triterpenic fraction improved objective laser Doppler and transcutaneous oxygen/carbon-dioxide measures, along with subjective venous symptoms. It strengthens the venous-insufficiency case for gotu kola and also shows a dose response favoring 120 mg/day.

gotu-kola-SRC-003Double-blind, placebo-controlled trial
Sourceopen_in_new

Bradwejn J, Zhou Y, Koszycki D, Shlik J. A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. J Clin Psychopharmacol. 2000;20(6):680-684. doi:10.1097/00004714-200012000-00015. PMID:11106141.

Population: Healthy adult volunteers.

Dose protocol: Single dose of 12 g crude Centella asiatica extract

Key findings: Centella significantly attenuated peak acoustic startle response amplitude at 30 and 60 minutes post-dose versus placebo, suggesting acute anxiolytic activity without notable sedation.

Notes: Pilot study. Single-dose design with crude extract. Dose not easily translatable to standardized TTFCA protocols. No follow-up GAD trial published.

Paper content

This acute placebo-controlled human study found that a single 12 g dose of gotu kola attenuated acoustic startle response amplitude at 30 and 60 minutes without materially changing self-rated mood or cardiovascular measures. It provides a mechanistic human anxiolytic signal, but the dose was very large, the endpoint was surrogate rather than clinical, and the design does not justify broad everyday anxiety claims.

gotu-kola-SRC-004Randomized clinical trial
Sourceopen_in_new

PMID:36420467.

Population: Older adults with mild cognitive impairment (n=60)

Dose protocol: 500 mg gotu kola extract twice daily for 12 weeks, with exercise comparator

Key findings: Cognitive outcomes improved across arms, but additive effect attributable to gotu kola versus exercise alone was limited.

Notes: Helpful for real-world adjunct framing, but co-intervention confounds ingredient-specific attribution.

Paper content

Cognitive outcomes improved across arms, but additive effect attributable to gotu kola versus exercise alone was limited.

gotu-kola-SRC-005Systematic review and meta-analysis
Sourceopen_in_new

PMID:28878245.

Population: 11 randomized controlled trials (centella-containing interventions)

Dose protocol: Heterogeneous formulations and durations

Key findings: No significant effects in most pooled cognitive domains versus placebo, with smaller mood/alertness signals in selected analyses.

Notes: Important counterweight to overbroad cognition claims due to heterogeneity and variable extract quality.

Paper content

No significant effects in most pooled cognitive domains versus placebo, with smaller mood/alertness signals in selected analyses.

gotu-kola-SRC-006Phase 1 randomized, double-blind, crossover clinical trial
Sourceopen_in_new

Wright KM, Bollen M, David J, Speers AB, Brandes MS, Gray NE, Alcazar Magana A, McClure C, Stevens JF, Maier CS, Quinn JF, Soumyanath A. Pharmacokinetics and Pharmacodynamics of Key Components of a Standardized Centella asiatica Product in Cognitively Impaired Older Adults: A Phase 1, Double-Blind, Randomized Clinical Trial. Antioxidants (Basel). 2022;11(2):215. doi:10.3390/antiox11020215. PMID:35204098.

Population: Older adults with mild cognitive impairment or mild dementia who were taking cholinesterase inhibitors.

Dose protocol: Single-dose crossover study using 2 g and 4 g standardized Centella aqueous extract with 10-hour PK monitoring

Key findings: Demonstrated oral exposure of key triterpene aglycones, NRF2-linked target engagement, and short-term tolerability.

Notes: Phase 1 feasibility study in only four cognitively impaired older adults. Useful for extract plausibility, not efficacy.

Paper content

This phase 1 crossover study tested single 2 g and 4 g doses of a standardized Centella asiatica aqueous extract in four cognitively impaired older adults. The trial was not designed to show symptom improvement. Instead, it confirmed that key triterpene aglycones and caffeoylquinic-acid metabolites are orally bioavailable, that the extract engages an NRF2-related pharmacodynamic signal, and that acute dosing was well tolerated. That makes it useful as a feasibility and target-engagement anchor for standardized gotu-kola extracts, not as proof of cognitive efficacy.

gotu-kola-SRC-007Quasi-experimental comparative study
Sourceopen_in_new

PMID:27340413.

Population: Post-stroke cognitive impairment

Dose protocol: 750-1000 mg/day for 6 weeks

Key findings: Reported memory and total-score improvements in all treatment arms. Between-arm differences were uncertain.

Notes: Adds directional context but has substantial internal-validity limitations.

Paper content

Reported memory and total-score improvements in all treatment arms; between-arm differences were uncertain.

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