The latest meta-analysis has revealed: citrus flavonoids are effective in improving lower limb edema in chronic venous disease

Guide

Recently, a systematic review and meta-analysis focusing on citrus flavonoids (purified micronized flavonoids, MPFF) to improve lower limb edema in chronic venous disease (CVD) was published at Int Angiol.:

• The effectiveness of citrus flavonoids in the treatment of CVD edema has been previously confirmed by several different types of studies and recognized by international CVD-related guidelines.
• This systematic review and meta-analysis is the first study to integrate various types of prospective studies to comprehensively and accurately assess the effectiveness of citrus flavonoids in the treatment of CVD edema.
• The results confirmed that citrus flavonoid therapy was effective in reducing edema and swelling in patients with C0s-C5 CVD, and this benefit was validated from the first month of treatment and lasted until 1 year, which provided strong support for the early and lasting improvement of CVD edema with citrus flavonoids.

Review of study design

A total of eight prospective studies, including one placebo-controlled RCT, four active controlled RCTs, and three non-comparative prospective studies, were included in this review and meta-analysis, involving 1635 patients, 89% of whom were female, with a mean age of 47 years. To comprehensively evaluate the effect of oral citrus flavonoids (1000mg/day) on ankle and/or calf circumference in patients with CVD.

The results of the study are interpreted in depth

• Treatment for 2 months

Ankle circumference: Of the eight included studies, three of them had a baseline value of 2 months, and the analysis found an average reduction in ankle circumference of 6.8 mm (95%CI: 4.9-8.8, P<0.001), with significant heterogeneity (I2=89.7%; τ2=5.93; P<0.01)。 Consistent benefits were also observed in several other meta-analyses conducted in this review (Table 1).

Table 1. In other meta-analyses, the magnitude of ankle circumference reduction after 2 months of citrus flavonoid treatment

In addition, other meta-analyses have confirmed the effectiveness of citrus flavonoids in improving ankle circumference: a meta-analysis conducted by Allaert et al. investigating the effects of different intravenous active drugs (citrus flavonoids, rutin, pseudophylla extract, diosmin) on the reduction of ankle circumference showed that citrus flavonoids were significantly superior to placebo, rutin, aculium extract, and diosmin, with an average reduction in ankle circumference of 8.0 mm (95% CI: 7.5-8.5 mm)2.

Calf circumference: three studies evaluating changes in calf circumference from baseline to two months of citrus flavonoid therapy showed an average reduction in calf circumference of 5.7 mm (95% CI: 2.8 to 8.6; P<0.001), there was significant heterogeneity (I2=81.1%; τ2=5.00; P<0.01)。

Swelling: Three studies reported the effect of swelling and showed a significant reduction of 2.2 (95% CI: 0.2-4.2; P=0.028), and there was significant statistical heterogeneity (I2=98.51%; τ2=2.95; P<0.01)。

Previous published studies also support the significant benefit of citrus flavonoids in reducing swelling in patients with CVD: a meta-analysis by Kakkos et al. showed that citrus flavonoids reduced swelling, heaviness, and pain in CVD patients, while also improving functional discomfort and overall quality of life3.

Summary: The effectiveness of citrus flavonoids in the treatment of CVD edema has been verified in a number of studies, and this study found that after 2 months of treatment, citrus flavonoids can reduce the ankle circumference by 6.8 mm, the calf circumference by 5.7 mm, and reduce the swelling of CVD patients.

• Short-, medium- and long-term treatment

From the results of the study, it can be seen that citrus flavonoid treatment can effectively reduce ankle circumference, calf circumference and swelling in patients with CVD, whether it is a short-term, medium-term, or long-term course of treatment (Table 2).

Table 2. Changes in ankle circumference, calf circumference, and swelling during short, medium, and long-term treatments

• Changes in ankle circumference over time after citrus flavonoid treatment

  

Figure 1. Changes in ankle circumference over time after citrus flavonoid treatment

summary

The effectiveness of citrus flavonoids in reducing CVD edema has been confirmed by several different types of studies and international CVD-related guidelines, and this meta-analysis showed that the improvement of edema (reduction in ankle and calf circumference) and the reduction of swelling were observed after 1 month of treatment with citrus flavonoids, and lasted up to 1 year, suggesting that citrus flavonoids have considerable efficacy in early and ongoing treatment. It is expected that with more studies and experiments, the efficacy of citrus flavonoids in edema can be further explored, so that more patients with CVD can benefit from it, so as to help improve the long-term prognostic outcomes and quality of life of CVD patients.

bibliography

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1.Rabe E,Blanc-Guillemaud V,Onselaer MB,et al. Epub ahead of print.

2.Allaert FA. Int Angiol 2012; 31:310–5.

3.Kakkos SK, Nicolaides AN. Int Angiol 2018; 37:143–54.

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