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Head-to-head evidence comparison — which supplement is right for you?
PEA wins 3 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Mostly mechanism / observational
Verdict
Likely helps
6 of 6 studies with measurable effects showed benefit.
Top outcomes
300mg standardized extract twice daily (providing ~50mg aescin per dose; ~100mg aescin/day)
with-meals
Aescin-standardized, enteric-coated seed extract
600-1200mg
With meals, Split into 2-3 doses
Micronized or ultra-micronized PEA
2-12 weeks
2-8 weeks
Days
2-8 weeks
4-8 weeks
Ongoing
Horse chestnut seed extract for chronic venous insufficiency.
The Cochrane database of systematic reviews (2012) · Meta analysis
Significantly reduced leg pain, edema, and itching vs placebo
Horse chestnut seed extract for chronic venous insufficiency.
The Cochrane database of systematic reviews (2006) · Meta analysis
Reduced leg volume and ankle/calf circumference
Horse-chestnut seed extract for chronic venous insufficiency. A criteria-based systematic review.
Archives of dermatology (1998) · Systematic review
Most RCTs favored HCSE over placebo
Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis
Nutrients (2024) · Meta analysis · n=742
These two obtained scores corresponded to a 35.1% pain intensity reduction within the first month, followed by a further 35.4% during the second month.
Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials
Nutrients (2023) · Meta analysis · n=774
PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001).
Navigating agitation in neurodevelopmental disorders: A comparative study of pharmacotherapies via network meta-analysis in children and adults with autism spectrum disorder or intellectual disabilities
Journal of psychopharmacology (Oxford, England) (2025) · Meta analysis · n=2503
Importantly, these treatments were generally well-tolerated, with no significant increase in all-cause dropouts compared to placebo, highlighting their suitability for clinical use in managing agitation in individuals with ASD or ID.
Based on multiple meta-analyses showing ~35% pain reduction. Studies primarily used micronized formulations which may have better bioavailability than standard forms. Most benefits observed within 4-6 weeks of treatment.
AI-estimated from published studies. Interpret as directional guidance.
PEA has a higher evidence score (7.5/10 vs 7/10) and wins in 3 of 3 categories.
For reduce inflammation, PEA has a higher relevance score (85 vs 45).
No known interactions between Horse Chestnut and PEA have been documented in our database. However, always consult a healthcare provider before combining supplements.