µsmin Plus improves leg discomfort and quality of life at low dosage according to a new RCT

Published: 17-May-2021

The results further strengthen µsmin Plus’ superiority in the diosmin marketplace showing dramatic improvements in leg circumference, quality of life (QOL), leg pain and common symptoms associated to Chronic Venous Disease (CVD)

Giellepi is pleased to announce the publication of a new clinical study on µsmin Plus (Microsmin Plus), a diosmin preparation with enhanced bioavailability, titled “Efficacy of a Low-Dose Diosmin Therapy on Improving Symptoms and Quality of Life in Patients with Chronic Venous Disease: Randomized, Double-Blind, Placebo- Controlled Trial”. The results published in Nutrients further strengthen µsmin Plus’ superiority in the diosmin marketplace showing dramatic improvements in leg circumference, quality of life (QOL), leg pain and common symptoms associated to CVD.

Healthy leg veins are essential for the normal return of blood from the legs to the heart. If leg veins fail to act in a normal manner and become compromised, there is a blockage of normal blood flow and blood can pool in the legs. This can lead to leg pain, swelling, itchiness, restless leg syndrome, a burning sensation, and heaviness and can significantly affect quality of life.1

As vein health becomes further compromised, symptoms progress from milder clinical signs such as spider veins and varicose veins to more advanced symptoms associated with Chronic Venous Insufficiency (CVI), an advanced form of CVD.2 With the population living longer and rising of obesity (two risk factors for CVI), the worldwide prevalence is expected to dramatically increase.3 With annual disease progression rates estimated at 4%, early diagnosis and treatment and care strategies that can prevent disease progression are critical to reduce costs associated with varicose veins and CVD.

The use of nutraceuticals is one strategy to help reduce symptoms and avoid complications and disease progression. One of the most widely studied and recommended nutraceuticals is diosmin.4 Diosmin (3’,5,7-trihydroxy-4’-methoxyflavone-7- rhamnoglucoside) is a naturally occurring flavonoid present in citrus fruits and typically extracted from hesperidin. Like many flavonoids, diosmin is poorly bioavailable in humans. The development of a micronized diosmin improved bioavailability to a certain extent and has been recommended for the treatment of CVD at the common dose of 500 mg twice daily.5 Despite the success of the micronized diosmin technology to improve bioavailability, further increases in oral bioavailability are required to achieve optimal therapeutic efficacy.

Developed by Giellepi Health Science (Lissone, Italy), µsmin Plus is an innovative diosmin formulation (>80% diosmin and 90% total flavonoids) with enhanced absorption and bioavailability compared to standard micronized diosmin. In a double-blind, crossover study, µsmin Plus showed greater plasma concentration and 9.4 times greater bioavailability compared to standard micronized diosmin.6 Based on these exciting results, a double-blind, placebo-controlled clinical trial was completed in individuals with mild to moderate CVD and published this year.7 In the eight-week study, subjects were randomized to receive either one tablet of µsmin Plus (equal to 450 mg of diosmin) or a matched placebo tablet. Key outcomes included changes in mid-calf circumference and QOL measured by the Global Index Score (GIS). Also assessed was changes in pain, overall symptom severity as well as patient and investigator assessment of effectiveness.

Figure 1

Figure 1

Compared to the placebo group, the µsmin Plus had a statistically significant reduction in leg circumference at both 4 and 8 weeks. At 8 weeks, QOL was significantly improved in the µsmin Plus group compared to placebo (see Figure 1). Overall pain relief was greater in the µsmin Plus group with 42% reduction reported at 8 weeks (see Figure 2). Overall symptom relief was also more greatly reduced during the study.

Figure 2

Figure 2

Notable is the fact that investigators and subjects gave very favourable ratings to the reduction of symptoms in the µsmin Plus group. The study found that 68% of the subjects in the µsmin Plus group experienced a reduction in symptoms at two weeks compared to only 11% in the placebo group. When asked about overall satisfaction with the treatment, investigators responded that they considered µsmin Plus to be good to excellent in 97% of subjects. In subjects, 100% responded that they were satisfied or very satisfied and 95% decided to continue using µsmin Plus after the study finished. “We are delighted with the results of this study which revealed the ability of µsmin Plus in quickly delivering leg vein health benefits at almost less than half dosage recommended with conventional micronized diosmin”, says Dr Rosario Russo Scientific Officer at Giellepi. “The highly bioavailable formulation of µsmin Plus along with these new findings will help our customers further differentiate and standout in a marketplace dominated by micronized diosmin ingredients.” Here the full text: https://bit.ly/3boapRv

μsmin Plus, already distributed in US by Maypro S.A. (https://bit.ly/3tEvhdP), is the only diosmin on the market providing up to 9X better absorption than standard micronized diosmin and proven efficacy at low-dose regimen.


  1. Daview AH. The seriousness of chronic venous disease: A review of real-world evidence. Adv Ther 2019; 36(Suppl 1):5-12.
  2. Labropoulos N. How does chronic venous disease progress from the first symptoms to the advanced stages? A review. Adv Ther 2019;36(Suppl 1):13-19.
  3. Nicolaides NA, Labropulous N. Burden and suffering in chronic venous disease. Adv Ther 2019;36(Suppl 1):1-4.
  4. Monograph. Diosmin. Altern Med Rev 2004. 9(3):308-11.
  5. Ulloa JH. Micronized purified flavonoid fraction (MPFF) for patients suffering from chronic venous disease: A review of new evidence. Adv Ther 2019;36:S20-S25.
  6. Russo R, Chandradhara D, De Tommasi N. Comparative bioavailability of two diosmin formulations after oral administration to healthy volunteers. Molecules 2018;23:2174. doi:10.3390/molecules23092174.
  7. Serra R, Ielapi N, Bitoni A, et al. Efficacy of a low-dose therapy on improving symptoms and quality of life in patients with chronic venous disease: Randomized, double-blind, placebo- controlled trial. Nutrients 2021;13:999. https://doi.org10.3390/nu.13030999.

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