Benefits
Leg vein comfort: heaviness, feeling of swelling and cramps
In 7 placebo-controlled trials pooled together (1,692 adults with leg vein problems), MPFF, a micronized vein medicine prescribed in France that is 90% diosmin, eased leg heaviness, feeling of swelling, cramps and pain more than placebo. On rating scales the gain was large for heaviness and feeling of swelling but small for pain and quality of life. These results are for MPFF, not plain diosmin.
Ankle and lower-leg swelling (edema)
Across vein-tone products as a class, including rutosides and diosmin, a review of placebo-controlled trials in adults with leg vein problems found moderate-certainty evidence of slightly less lower-leg swelling and about 4 mm less ankle circumference, with little or no change in quality of life. In the 7 MPFF trials, ankle circumference was also smaller than with placebo.
Leg swelling and comfort with a diosmin supplement (not MPFF)
In 72 adults with leg vein problems, a micronized diosmin supplement (450 mg once daily, with little hesperidin) reduced calf circumference more than placebo at weeks 4 and 8 and improved pain, quality-of-life and severity scores by week 8. The maker, Giellepi, funded the trial; a research company ran it.
Leg swelling after knee replacement surgery
In 330 adults after knee replacement, diosmin 0.9 g twice daily for 14 days led to less calf, thigh and knee swelling and less pain during movement than no treatment. Pain at rest, knee function, range of motion and inflammation markers did not differ. The comparison group took no placebo.
Rectal comfort in flavonoid and MPFF studies
In people with hemorrhoids, a pooled analysis of 14 flavonoid trials found less bleeding and fewer persisting symptoms, but its authors say quality limits and possible publication bias raise doubts. A Servier-funded review pooled two MPFF trials for bleeding and found less of it. In a 100-person placebo trial, MPFF improved exam findings at day 4 but not symptoms, and nothing differed at day 14.
Mechanism of action
Vein tone and capillary leakiness (MPFF)
A Servier-funded review states that in people with leg vein problems MPFF has been shown to improve vein tone and reduce capillary leakiness, activation of the blood-vessel lining and inflammation. The review cites earlier studies for this and presents no new data on these effects.
Micronized diosmin is absorbed better
In a double-blind crossover study in 12 healthy men given a single 500 mg tablet with traced diosmin, about 58% of the dose was absorbed from micronized MPFF versus about 33% from non-micronized diosmin, judged by urinary radioactivity. Supplements are not necessarily micronized.
Effects on drug-handling proteins
In two small studies in healthy men, diosmin 500 mg a day for 10 days raised blood levels of carbamazepine, which the authors attribute to CYP3A4 inhibition, and of fexofenadine, which they attribute to P-glycoprotein inhibition. This is why diosmin may change levels of some medicines.
Clinical trials
Cochrane systematic review (2020 update) of 69 randomized, double-blind, placebo-controlled trials of oral phlebotonics; 56 trials (7,690 participants) gave usable data, 11 of them on hidrosmine and diosmine. The abstract does not report results for diosmin alone. Three authors had run an included trial of another vein drug supported by its maker; no ties to diosmin makers are declared. (Martinez-Zapata et al. 2020, Cochrane Database Syst Rev)
Adults with chronic venous insufficiency at any stage (mean age 50 years).
Phlebotonics probably reduce lower-leg swelling slightly (RR 0.70; 13 studies) and ankle circumference (MD -4.27 mm; 15 studies) and probably make little or no difference to quality of life (moderate certainty). Ulcer healing did not differ (low certainty). Adverse events were slightly more common than with placebo (RR 1.14; 37 studies, 5,789 participants), mostly digestive, and only short-term safety data were available.
Meta-analysis of 14 randomized trials (1,514 patients) comparing any type of flavonoid with placebo or no therapy in symptomatic hemorrhoids; not specific to diosmin. (Alonso-Coello et al. 2006, Br J Surg)
1,514 patients with symptomatic hemorrhoids across 14 trials.
Pooled results suggested a 58% lower risk of persisting or unimproved symptoms (RR 0.42) and an apparent reduction in bleeding (RR 0.33), persistent pain (RR 0.35), itching (RR 0.65) and recurrence (RR 0.53). Trials were of moderate quality with variable results and possible publication bias, which the authors say raise questions about the apparent benefit. The trials covered flavonoids generally, not diosmin specifically.
Systematic review and meta-analysis of 7 randomized, double-blind, placebo-controlled trials of MPFF (Daflon, a vein medicine frequently prescribed in France), mostly at low risk of bias; funding and conflicts of interest are not stated in the abstract, and the publisher page could not be read. (Kakkos et al. 2018, Int Angiol)
1,692 patients with chronic venous disease across 7 trials.
Versus placebo, MPFF reduced leg pain (RR 0.53), heaviness (RR 0.35), feeling of swelling (RR 0.39), cramps, paresthesia and functional discomfort and reduced ankle circumference. On continuous scales the effect was small for pain (SMD -0.25) and quality of life (SMD -0.21) and larger for heaviness (SMD -0.80). The tested product was MPFF, not diosmin alone.
Randomized, double-blind, placebo-controlled multicenter trial of a micronized diosmin supplement (μsmin Plus: 80% micronized diosmin, 90% total flavonoids, little hesperidin), 450 mg diosmin once daily for 8 weeks. Funded by the maker, Giellepi; a contract research organization managed the study, and the authors state the company did not analyze the results. (Serra et al. 2021, Nutrients)
Adults with chronic venous disease (CEAP C2 to C4); all 72 randomized completed (37 diosmin, 35 placebo).
Calf circumference fell more than with placebo at week 4 (p = 0.033) and week 8 (p = 0.016), by an average of 4.67% versus 0.32% at week 8. Pain scores (p = 0.014), a quality-of-life index and a venous severity score (both p < 0.001) improved more than with placebo by week 8. No treatment-related side effects were recorded.
Randomized, controlled trial at 13 hospitals; diosmin 0.9 g twice daily for 14 days starting the day after surgery versus no diosmin and no placebo. Funded by a West China Hospital research project. (Wang et al. 2024, J Bone Joint Surg Am)
330 adults having total knee arthroplasty.
Calf, thigh and upper-knee swelling was lower with diosmin at every time point through day 14, and pain during movement was lower. Pain at rest, knee function scores, range of motion, C-reactive protein, interleukin-6 and complication rates did not differ.
Double-blind, placebo-controlled trial; Daflon (Servier) or placebo added to a bulk laxative; 12 tablets in three divided doses during the first 4 days, then two tablets twice daily for another 10 days. Funding is not stated in the abstract. (Thanapongsathorn et al. 1992, Dis Colon Rectum)
100 patients with acute first- or second-degree internal hemorrhoids, 50 per group.
On day 4 the MPFF group showed more objective improvement (P < 0.01) but no difference in symptoms. On day 14 neither objective nor subjective improvement differed from placebo. Two placebo patients left the trial on day 4 because they worsened. No side effects of MPFF were detected.
Systematic review of 11 randomized trials (13 articles) of MPFF versus placebo or no treatment; 4 studies entered the meta-analysis, with 2 or 3 pooled per outcome, and 7 of the 11 studies had unclear or high risk of bias in at least two areas. Funded by Servier, the maker of MPFF, which supported the search, statistics and writing and reviewed the manuscript; all three authors received speaker fees from Servier. (Sheikh et al. 2020, Adv Ther)
Patients with acute hemorrhoids, or with symptoms after medical or surgical hemorrhoid treatment.
Pooling two trials each, MPFF lowered the odds of bleeding (OR 0.082) and of discharge or leakage (OR 0.12) at day 7, and pooled trials favored MPFF on overall ratings by patients and investigators. Pain showed only a non-significant trend with high heterogeneity (OR 0.11, P = 0.06). Reported side effects were mild, such as stomach pain and diarrhea.