Objective and subjective effects of a nutraceutical fixed combination in patients with symptoms suggestive of early chronic venous disease: a prospective observational pilot study

Early chronic venous disease may significantly impair quality of life even in the absence of overt varicose disease, and effective conservative strategies are needed to relieve symptoms and possibly slow disease progression. This prospective observational pilot study evaluated the effectiveness and tolerability of a nutraceutical fixed combination with venotropic, anti-inflammatory and draining activity in adults with symptoms suggestive of early-stage chronic venous disease (CEAP C0s-C1s). Sixty patients aged 35-70 years were enrolled, and 40 completed the 90-day follow-up; the 33.3% drop-out/non-completer rate is explicitly reported as a major real-world limitation. Participants received one tablet daily containing micronized flavonoids (μsMIN® Plus; 570 mg, including diosmin 450 mg), Boswellia serrata (Bospure®), bromelain (Bromeyal®), hesperidin, Melilotus officinalis, pineapple extract, and vitamin C. The primary endpoint was the change in ankle circumference from baseline to day 90. Secondary endpoints included patient-reported symptoms assessed by visual analogue scales for pain, heaviness/warmth, itching, nocturnal cramps, self-perceived edema/swelling, visible varicosity, and self-perceived quality of life. Of the 60 enrolled patients, 40 completed the study, corresponding to a 33.3% drop-out/non-completer rate (20/60). Eight patients were lost to follow-up and 12 did not consistently take the tested product (adherence <70%). This high drop-out rate substantially limits the statistical analysis and the value of the final outcomes. In the completer population, mean ankle circumference significantly decreased from 23.1±1.8 cm at baseline to 21.4±1.4 cm at Day 90, corresponding to a mean reduction of 1.7±0.5 cm (p=0.023). Significant improvements were also observed in all subjective parameters except visible varicosity, with benefits already detectable at Day 45 and maintained or enhanced at Day 90. No adverse events leading to treatment discontinuation were reported. In this real-world cohort of patients with symptoms suggestive of early chronic venous disease, the tested nutraceutical combination was associated with significant improvements in both objective and subjective outcomes and was well tolerated. However, given the uncontrolled observational design and the 33.3% drop-out/non-completer rate, these findings should be considered preliminary and not definitive evidence of a causal treatment effect.