Condition
Chronic Venous Insufficiency
Chronic venous insufficiency happens when damaged valves in the leg veins let blood pool instead of flowing back to the heart, leading to heaviness, aching, swelling and sometimes skin changes. Among supplements, gotu kola, horse chestnut and diosmin have the strongest evidence, and studies found signs of the condition improved with the first two, while a large review found diosmin-type products reduced leg swelling compared with placebo. Many of the individual trials were fairly small, and the size of the benefit was moderate at best.
Sources: PMID 6896366; PMID 7936334
- Supplements studied
- 7
- Graded outcomes
- 12
- Trials
- 12
- People studied
- 1,612
Evidence by supplement
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Leg Edema Reduction Cochrane meta-analysis (56 RCTs, n=7690, 2020): Phlebotonics including diosmin/MPFF reduced lower leg edema (RR 0.70, 95% CI 0.63-0.78) and ankle circumference (MD -4.27mm, 95% CI -5.61 to -2.93) vs placebo. Moderate-certainty evidence. | Improves (the measure goes up) | Moderate effect | ||||
| Chronic Venous Insufficiency Symptoms Systematic review and meta-analysis: MPFF (Daflon) highly effective in improving leg symptoms including pain, heaviness, fatigue, paresthesia. MPFF is the only venoactive drug with Grade 1B recommendation in international CVD guidelines. | Improves (the measure goes down) | Moderate effect | ||||
| Quality of Life in CVD RCT for low-dose diosmin: Improved symptoms and quality of life in CVD patients. However, Cochrane meta-analysis found phlebotonics probably make little or no difference in QoL compared with placebo (moderate-certainty evidence). | Improves (the measure goes up) | Small effect | ||||
| Safety Profile Cochrane meta-analysis: Phlebotonics probably increase adverse events slightly vs placebo (RR 1.14, 95% CI 1.02-1.27). GI disorders most common. Generally well-tolerated for short-term use. Long-term safety data limited. | Improves (the measure goes up) | Moderate effect |
Horse Chestnut
- Chronic Venous Insufficiency Signs: improves
- High-density lipoprotein (HDL)
- Leg Edema: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Chronic Venous Insufficiency Signs Moderate Improvement | Improves (the measure goes up) | Moderate effect | 297 people | |||
| High-density lipoprotein (HDL) No effect | NoneNo effect | 40 people | ||||
| Leg Edema | Improves (the measure goes down) | 3 studies | 297 people | |||
| Low-density lipoprotein (LDL) | Improves (the measure goes down) | 40 people | ||||
| Pain | Improves (the measure goes down) | 543 people | ||||
Pycnogenol
- Chronic Venous Insufficiency Signs: improves
- High-density lipoprotein (HDL): improves
- Leg Edema: changes; see studies
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Chronic Venous Insufficiency Signs Moderate Improvement | Improves (the measure goes up) | Moderate effect | 1 study | 126 people | ||
Studies that measured chronic venous insufficiency signs | ||||||
| High-density lipoprotein (HDL) | Improves (the measure goes up) | 1 study | 40 people | |||
Studies that measured high-density lipoprotein (hdl) | ||||||
| Leg Edema | Changes; see studies | 1 study | 423 people | |||
| Low-density lipoprotein (LDL) | Changes; see studies | 1 study | 40 people | |||
Studies that measured low-density lipoprotein (ldl) | ||||||
| Total cholesterol | Changes; see studies | 40 people | ||||
Butcher's Broom
- Chronic Venous Insufficiency Signs: improves
- Leg Edema: improves
- Subjective Well-Being: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Chronic Venous Insufficiency Signs Small Improvement | Improves (the measure goes up) | Small effect | 1 study | 110 people | ||
Studies that measured chronic venous insufficiency signs | ||||||
| Leg Edema Improvement | Improves (the measure goes down) | 110 people | ||||
| Subjective Well-Being | Improves (the measure goes up) | 110 people | ||||
Rutin
- Leg Symptoms: improves
- Edema: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Leg Symptoms Small-moderate improvements in leg heaviness, cramps, swelling (systematic review) | Improves (the measure goes down) | Small effect | 600 people | |||
| Edema Modest reduction in ankle swelling | Improves (the measure goes down) | Small effect | 450 people |
Calendula Officinalis
- Wound Healing: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Wound Healing | Improves (the measure goes up) | 2 studies | 57 people | |||
Key findings
- Chronic Venous Insufficiency SignsImproves (the measure goes up)
- Leg Edema ReductionImproves (the measure goes up)
- Chronic Venous Insufficiency SymptomsImproves (the measure goes down)
Safety notes in the studies
- Cochrane meta-analysis: Phlebotonics probably increase adverse events slightly vs placebo (RR 1.14, 95% CI 1.02-1.27).
The Chronic Venous Insufficiency (CVI) protocol
2 primary supplements · 4 supporting supplements
- Horse Chestnut Seed Extract300 mg twice daily (standardized to 50 mg aescin per dose)
- Gotu Kola (Centella asiatica)60–180 mg triterpenes daily (standardized extract)
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The supplements graded A or B for Chronic Venous Insufficiency. Each opens third-party tested products for that supplement.
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- Grade A
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Studies cited
60 studies from PubMed
- Is There a Difference in the Clinical Efficacy of Diosmin and Micronized Purified Flavonoid Fraction for the Treatment of Chronic Venous Disorders? Review of Available Evidence
- Phlebotonics for venous insufficiency
- Micronized Purified Flavonoid Fraction in Hemorrhoid Disease: A Systematic Review and Meta-Analysis
- Efficacy of micronized purified flavonoid fraction (Daflon) on improving individual symptoms, signs and quality of life in patients with chronic venous disease: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials
- Recommendations for the medical management of chronic venous disease: The role of Micronized Purified Flavanoid Fraction (MPFF)
- Therapeutic potential of micronized purified flavonoid fraction (MPFF) of diosmin and hesperidin in treatment chronic venous disorder
- Flavonoids for treating venous leg ulcers
- Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids
- From symptoms to leg edema: efficacy of Daflon 500 mg
- Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency
- Efficacy and safety of a Butcher's broom preparation (Ruscus aculeatus L. extract) compared to placebo in patients suffering from chronic venous insufficiency
- The effect of versus metronidazole on bacterial vaginosis in women: A double-blind randomized controlled trial.
- Therapeutic effectiveness of a Calendula officinalis extract in venous leg ulcer healing.
- Evaluation of Calendula officinalis as an anti-plaque and anti-gingivitis agent.
- Comparing the effects of Calendula officinalis and clotrimazole on vaginal Candidiasis: A randomized controlled trial.
- Treatment of acute wounds in hand with L.: A randomized trial.
- Antioxidant capacity of calendula officinalis flowers extract and prevention of radiation induced oropharyngeal mucositis in patients with head and neck cancers: a randomized controlled clinical study.
- No differences between Calendula cream and aqueous cream in the prevention of acute radiation skin reactions--results from a randomised blinded trial.
- Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer.
- Use of calendula ointment after episiotomy: a randomized clinical trial.
- Low-level laser therapy and Calendula officinalis in repairing diabetic foot ulcers.
- Calendula extract: effects on mechanical parameters of human skin.
- Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs
- Flight microangiopathy in medium- to long-distance flights: prevention of edema and microcirculation alterations with total triterpenic fraction of Centella asiatica
- Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcPO2-CO2, and leg volumetry
- Centella asiatica extract in venous disorders of the lower limbs. Comparative clinico-instrumental studies with a placebo
- Centella asiatica extract in venous pathology of the lower limbs and its evaluation as compared with tribenoside
- The microcirculatory activity of Centella asiatica in venous insufficiency. A double-blind study
- Improvement of capillary permeability in patients with venous hypertension after treatment with TTFCA
- Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica
- A clinical study on the management of generalized anxiety disorder with Centella asiatica
- Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined microcirculatory model
- Effects of the total triterpenic fraction of Centella asiatica in venous hypertensive microangiopathy: a prospective, placebo-controlled, randomized trial
- Treatment of edema and increased capillary filtration in venous hypertension with total triterpenic fraction of Centella asiatica: a clinical, prospective, placebo-controlled, randomized, dose-ranging trial
- Treatment of diabetic microangiopathy and edema with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled randomized study
- Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model
- The efficacy and side effects of oral Centella asiatica extract for wound healing promotion in diabetic wound patients
- A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects
- Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency
- Horse chestnut seed extract for chronic venous insufficiency
- Double blind study of reparil in proctology
- Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency
- Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women
- Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation
- French maritime pine bark extract Pycnogenol dose-dependently lowers glucose in type 2 diabetic patients
- Pycnogenol((R)) in the Management of Asthma
- Pycnogenol® improvements in asthma management
- Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans
- Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile
- Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials.
- Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies
- Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study
- Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects
- Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study
- Efficacy of Functional Foods, Beverages, and Supplements Claiming to Alleviate Air Travel Symptoms: Systematic Review and Meta-Analysis.
- Pycnogenol® supplementation improves cognitive function, attention and mental performance in students
- Treatment of erectile dysfunction with pycnogenol and L-arginine
- Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients
- Supplementation with Pycnogenol® improves signs and symptoms of menopausal transition
- Pycnogenol® supplementation improves the control of irritable bowel syndrome symptoms