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Excerpt:
Citrus Bioflavonoids (Hesperidin, Diosmin) for Ocular HemodynamicsThe eye’s tiny blood vessels must work well to keep vision sharp. In glaucoma, reduced blood flow to the optic nerve may worsen damage. Citrus bioflavonoids like hesperidin and diosmin are plant compounds found in orange peels and other citrus fruits. These flavonoids are known to strengthen capillaries, reduce swelling, and improve circulation (). In this article we review how these compounds affect endothelial nitric oxide, venous tone, and microcirculation in the eye and body, and what clinical data suggest about blood flow and vision. We also look at their broader vascular benefits, dosing, standardization, and safety.Effects on Endothelial Nitric OxideBlood vessels relax when their lining cells (endothelium) make the gas nitric oxide (NO). Hesperidin itself is a sugar-linked molecule that is broken down in the gut to hesperetin, its active form. Hesperetin strongly activates enzymes (AMPK, Akt) that turn on endothelial NO synthase (eNOS), boosting NO production (). In lab cells, hesperetin caused a rapid rise in eNOS phosphorylation and NO levels. In people with risk factors for heart disease (metabolic syndrome), a trial of 500 mg hesperidin daily for 3 weeks significantly improved flow-mediated dilation of the brachial artery (a measure of endothelial NO function) () (). In that study, brachial FMD increased ~2.5% and blood markers of cholesterol (ApoB) and inflammation (hs-CRP) fell (). These findings suggest citrus flavonoids can improve vessel dilation in humans, likely via enhanced NO.Diosmin, which comes from the herb Scrophularia initially and is also made from hesperidin, similarly has vascular effects. It scavenges free radicals and reduces inflammation, which may indirectly preserve NO signaling. In animal models where nitric oxide was blocked (using L-NAME), diosmin still lowered blood pressure and protected vessels (). This points to antioxidant actions of diosmin (removing superoxides) that help overall endothelial function ().Venous Tone and MicrocirculationBeyond NO, hesperidin and diosmin are known as venoactive agents – meaning they make veins pump more effectively. Clinical and experimental evidence shows they increase venous tone, improve microcirculation, and reduce capillary leakage () (). For example, diosmin has been shown to improve damaged microvessels, inhibit inflammatory adhesion molecules (ICAM-1, VCAM-1), and protect capillary tight junctions () (). These actions help push blood out of swollen veins and strengthen the microvascular bed.Used as a medicine (often combined), diosmin and hesperidin improve symptoms of chronic venous insufficiency (CVI) – such as leg swelling and varicose veins. The standard drug MPFF (Micronized Purified Flavonoid Fraction) contains about 90% diosmin and 10% hesperidin, with particles micronized for better absorption (). Meta-analyses indicate that ~1000 mg/day of MPFF (equivalent to ~900 mg diosmin + 100 mg hesperidin) significantly reduces leg heaviness, swelling, and pain over weeks (). In fact, one review found 600 mg/day of pure diosmin (without micronization) was almost as effective as 1000 mg/day MPFF for venous symptoms ().In eye terms, stronger venous tone could help fluid outflow and reduce congestion. Diosmin’s capillary-stabilizing and anti-edema effects were seen in a rat study of retinal ischemia/reperfusion: rats given diosmin had less retinal swelling, preserved tight-junction proteins, and lower vascular permeability (). T
