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Research · Supplements

Diosmin and hesperidin

In seven placebo-controlled trials (1,692 patients), MPFF reduced leg pain, heaviness, feeling of swelling and ankle circumference in chronic venous disease. Three hemorrhoid reviews found less bleeding. One lymphedema trial after breast cancer found no difference in arm volume. Across all phlebotonics, adverse events were slightly more common than on placebo, mostly digestive.

Add to Bio HackChecked 2026-11-13
Status
Dietary supplement in the US. Not FDA-approved for any condition.
Also called
diosmin, hesperidin, micronized purified flavonoid fraction, MPFF, Daflon, Detralex, citrus flavonoids, micronized diosmin
Taken for
chronic venous insufficiency, varicose veins, leg swelling, swelling, edema, heavy legs, hemorrhoids, lymphedema, venous leg ulcers

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help2

Reported risks1

What people take it for, and what was found

Shown to help2

Strong

Leg symptoms and swelling in chronic venous disease

Shown to reduce leg pain, heaviness, swelling and cramps in adults with chronic venous disease, with ankle circumference about 6 mm smaller after two months.

The numbers and sources
Effect
In 7 placebo-controlled trials (1,692 patients), MPFF reduced leg pain (RR 0.53), heaviness (RR 0.35), feeling of swelling (RR 0.39) and cramps (RR 0.51). Ankle circumference fell (SMD -0.59, 95% CI -1.15 to -0.02) and quality of life improved (SMD -0.21, 95% CI -0.37 to -0.04) [1]. In 8 studies of 1,000 mg a day (1,635 patients), ankle circumference fell by 6.0 mm (95% CI 3.6 to 8.4) after two months and 7.0 mm (95% CI 0.9 to 13.1) after six months or more. Calf circumference fell by 5.7 mm at two months [2]. Across all phlebotonics, including 11 trials of diosmin or hidrosmine, a Cochrane review found less lower leg edema (RR 0.70, 95% CI 0.63 to 0.78, 13 studies, 1,245 people) and smaller ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93, 15 studies, 2,010 people), with moderate certainty [3].
Population
Adults with chronic venous disease, mostly women, mean age 47 [2]. 7,690 participants with a mean age of 50 in the Cochrane review [3].
Sources
[1], [2], [3]
Caveats
The 2024 analysis combined RCTs with non-comparative studies and measured change from baseline, with I² of 93.5% for ankle circumference [2]. The Cochrane figures pool all phlebotonics, not diosmin alone, and found little or no difference in quality of life (SMD -0.06) [3]. The first two reviews share an author [1][2].
Limited

Swelling after knee replacement

One trial found less leg swelling and less pain during movement after knee replacement, with no change in pain at rest, knee scores or range of motion.

The numbers and sources
Effect
In 330 patients after total knee replacement, diosmin 0.9 g twice a day for 14 days was linked to less calf, thigh and upper kneecap swelling at every time point and lower pain during movement. Pain at rest, knee scores, range of motion, inflammatory markers and complications did not differ [7].
Population
330 patients at 13 university-affiliated hospitals [7].
Sources
[7]
Caveats
The control group received no placebo, so patients knew their treatment. One trial.

Mixed results2

Moderate

Hemorrhoid bleeding

Mixed results: two reviews found less bleeding, itching and discharge from hemorrhoids, and a third found a bleeding difference but no effect on other outcomes.

The numbers and sources
Effect
Across 20 trials of phlebotonics (2,344 participants), bleeding (OR 0.12, 95% CI 0.04 to 0.37), itching (OR 0.23), discharge (OR 0.12) and bleeding after hemorrhoid surgery (OR 0.18) were less common than in controls, and overall symptoms improved (OR 15.99) [4]. In 4 pooled MPFF studies, bleeding (OR 0.082, 95% CI 0.027 to 0.250) and discharge (OR 0.12) fell, and overall improvement rose by patient rating (OR 5.25) [5]. A third review of 10 MPFF trials (1,164 participants) found a difference in bleeding (RR 1.46, 95% CI 1.10 to 1.93) and no significant effect on any other outcome [6].
Population
Adults with hemorrhoidal disease or after hemorrhoid surgery [4][5][6].
Sources
[4], [5], [6]
Caveats
The third review rated the bleeding evidence low quality, with few and inconsistent studies [6]. Most trials did not describe randomization well [6].
Limited

Venous leg ulcers

Limited evidence: pooled trials found more ulcers healed, but the one low-bias trial and a wider phlebotonic review found no difference from placebo.

The numbers and sources
Effect
In 5 MPFF trials (723 participants), more ulcers healed on MPFF than control (RR 1.36, 95% CI 1.07 to 1.74). The one trial at low risk of bias, which was unpublished, found no benefit (RR 0.94, 95% CI 0.73 to 1.22) [8]. Across all phlebotonics, ulcer healing did not differ from placebo (RR 0.94, 95% CI 0.79 to 1.13, 6 studies, 461 people, low certainty) [3].
Population
Adults with venous leg ulcers [8][3].
Sources
[8], [3]
Caveats
Four of the five MPFF trials were poorly reported, and the review authors raise publication bias [8].

Not shown to help1

LimitedStudied in women

Lymphedema

One trial found no change in arm volume in women with lymphedema after breast cancer. Lymph flow improved only in a subgroup of 24 with severe lymphedema.

The numbers and sources
Effect
In 104 women with arm lymphedema after breast cancer treatment (94 completing), two tablets a day for six months did not change arm volume or lymph scan measures against placebo. In a subgroup of 24 women with more severe lymphedema, lymph flow speed improved more on MPFF (0.84 against 0.14 cm per minute, p 0.005) [9]. A Cochrane review found this trial gave too little information to reach a conclusion [10].
Population
104 women with lymphedema after breast cancer therapy at one center [9].
Sources
[9], [10]
Caveats
One trial. The positive finding came from a subgroup of 24 and was a lymph flow measure, not limb volume [9].

Doses studied

The 2024 venous edema analysis covered MPFF 1,000 mg a day [2]. The knee replacement trial used diosmin 0.9 g twice a day for 14 days [7]. The lymphedema trial used two Daflon 500 mg tablets a day for six months [9].

Risks

Reported risks1

Moderate

Adverse events in trials

Shown to raise adverse events slightly over placebo, mostly digestive complaints, across 37 trials of phlebotonics as a group.

The numbers and sources
Effect
Across 37 studies of phlebotonics (5,789 participants), adverse events were slightly more common than on placebo (RR 1.14, 95% CI 1.02 to 1.27, moderate certainty). Digestive complaints were the most common [3]. Complication rates after knee replacement did not differ from no treatment [7].
Population
Adults with chronic venous insufficiency in RCTs [3]. Knee replacement patients [7].
Sources
[3], [7]
Caveats
The Cochrane figure pools all phlebotonics. Trials gave only short-term safety data [3].

Claims tested and not found

  1. That MPFF reduces arm volume in lymphedema after breast cancer. Arm volume did not differ from placebo over six months in 94 women [9].
  2. That phlebotonics reduce hemorrhoid pain. Pain did not differ significantly from control (OR 0.11, 95% CI 0.01 to 1.11) [4].

Sources

  1. Kakkos SK, Nicolaides AN. 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. International Angiology. 2018. https://doi.org/10.23736/S0392-9590.18.03975-5
  2. Rabe E, Blanc-Guillemaud V, Onselaer MB, et al. Reduction of lower-limb edema in patients with chronic venous disease by micronized purified flavonoid fraction: a systematic literature review and meta-analysis. International Angiology. 2024. https://doi.org/10.23736/S0392-9590.23.05084-8
  3. Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, et al. Phlebotonics for venous insufficiency. Cochrane Database of Systematic Reviews. 2020. https://doi.org/10.1002/14651858.CD003229.pub4
  4. Perera N, Liolitsa D, Iype S, et al. Phlebotonics for haemorrhoids. Cochrane Database of Systematic Reviews. 2012. https://doi.org/10.1002/14651858.CD004322.pub3
  5. Sheikh P, Lohsiriwat V, Shelygin Y. Micronized Purified Flavonoid Fraction in Hemorrhoid Disease: A Systematic Review and Meta-Analysis. Advances in Therapy. 2020. https://doi.org/10.1007/s12325-020-01353-7
  6. Aziz Z, Huin WK, Badrul Hisham MD, et al. Efficacy and tolerability of micronized purified flavonoid fractions (MPFF) for haemorrhoids: A systematic review and meta-analysis. Complementary Therapies in Medicine. 2018. https://doi.org/10.1016/j.ctim.2018.05.011
  7. Wang Q, Jin Q, Cai L, et al. Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial. Journal of Bone and Joint Surgery. 2024. https://doi.org/10.2106/JBJS.23.00854
  8. Scallon C, Bell-Syer SE, Aziz Z. Flavonoids for treating venous leg ulcers. Cochrane Database of Systematic Reviews. 2013. https://doi.org/10.1002/14651858.CD006477.pub2
  9. Pecking AP, Février B, Wargon C, Pillion G. Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to conventional therapy of breast cancer). Angiology. 1997. https://doi.org/10.1177/000331979704800115
  10. Badger C, Preston N, Seers K, Mortimer P. Benzo-pyrones for reducing and controlling lymphoedema of the limbs. Cochrane Database of Systematic Reviews. 2004. https://doi.org/10.1002/14651858.CD003140.pub2

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