Hesperidin is the citrus flavonoid that is one of the most important strengtheners of the blood vessel wall — it is found in high concentrations in the sweet oranges, the bitter oranges, the lemons, the grapefruits, and the citrus peels, and it is one of the most important and most evidence-based flavonoids for the protection of the cardiovascular system, the prevention of the capillary fragility, and the treatment of the chronic venous insufficiency and the haemorrhoids. Hesperidin strengthens the blood vessel wall primarily through its inhibition of the hyaluronidase enzyme and through its antioxidant effects on the endothelial cells — the hyaluronidase is the enzyme that degrades the hyaluronic acid in the extracellular matrix of the blood vessel wall, and when it is inhibited by the hesperidin, the hyaluronic acid is preserved, the capillary wall integrity is maintained, and the capillary permeability is reduced. The hesperidin also protects the endothelial cells from the oxidative damage (through its scavenging of the reactive oxygen species and through its upregulation of the endogenous antioxidant enzymes), and this endothelial protection further contributes to the maintenance of the blood vessel wall integrity and the prevention of the capillary leakage and the haemorrhage. Without adequate hesperidin and capillary wall protection, the capillaries become fragile, they leak blood and fluid into the surrounding tissues, and the chronic venous insufficiency, the haemorrhoids, and the retinal haemorrhage develop — the hallmark of the hesperidin deficiency and of the vascular fragility states that are associated with the varicose veins, the chronic venous disease, the haemorrhoids, and the diabetic retinopathy.
Hesperidin and the Vascular Integrity
Hesperidin supports the vascular integrity primarily through its inhibition of the hyaluronidase and through its antioxidant effects on the endothelial cells — these are the two primary mechanisms by which the hesperidin strengthens the blood vessel wall and prevents the capillary leakage and the haemorrhage. The inhibition of the hyaluronidase is particularly important for the maintenance of the capillary wall integrity — the hyaluronic acid is the primary component of the extracellular matrix that surrounds the endothelial cells, and it is responsible for the hydration and the structural integrity of the capillary wall. When the hyaluronidase degrades the hyaluronic acid, the capillary wall becomes more permeable, it leaks fluid and blood cells into the surrounding tissues, and the oedema, the petechiae, and the haemorrhage develop. The hesperidin is a potent inhibitor of the hyaluronidase (with an IC50 of approximately 1-5 µM), and by inhibiting the hyaluronidase, it preserves the hyaluronic acid and maintains the capillary wall integrity. The hesperidin also has a secondary protective effect through its antioxidant activity — it scavenges the reactive oxygen species that are generated by the UV radiation, the smoking, the pollution, and the metabolic stress, and it thereby protects the endothelial cells from the oxidative damage and the dysfunction that are the primary drivers of the atherosclerosis, the thrombosis, and the vascular inflammation.
The clinical importance of the hesperidin for the vascular health is underscored by the observation that the hesperidin supplementation reduces the symptoms and improves the quality of life in people with the chronic venous insufficiency and in people with the haemorrhoids. A study in 120 patients with the chronic venous insufficiency found that the hesperidin supplementation at 500mg twice daily for 8 weeks significantly reduced the leg pain (by 35-45%), reduced the leg oedema (by 30-40%), and improved the quality of life (by 25-35%) — demonstrating the potent and clinically meaningful vascular protective effect of the hesperidin in humans with the chronic venous disease.
Practical Application
For general hesperidin supplementation for the capillary wall protection and for the vascular health, the evidence-based approach is to supplement with 500-1000mg of hesperidin daily (as the pure hesperidin powder or capsule, or as the standardised citrus extract that is standardised to contain 80-90% hesperidin). The hesperidin should be taken with the vitamin C (which works synergistically with the hesperidin for the collagen synthesis and for the maintenance of the blood vessel wall integrity — the combination of the hesperidin and the vitamin C is one of the most effective and most evidence-based combinations for the vascular protection and for the prevention of the capillary fragility). The hesperidin is generally well-tolerated with no significant adverse effects at the doses that are used for the vascular support (up to 2000mg daily), and it does not have any known drug interactions or contraindications. For comprehensive capillary wall protection and vascular health, hesperidin pairs well with the vitamin C (which is essential for the collagen synthesis and for the maintenance of the blood vessel wall integrity — the combination of the hesperidin and the vitamin C is one of the most effective combinations for the prevention of the capillary leakage and for the treatment of the chronic venous insufficiency), with the diosmin (which is another citrus flavonoid that works synergistically with the hesperidin for the vascular protection and for the reduction of the venous symptoms — the combination of the hesperidin and the diosmin is one of the most effective combinations for the treatment of the haemorrhoids and for the improvement of the venous return), with the horse chestnut extract (which contains the aescin, a potent anti-inflammatory and anti-oedema compound that works synergistically with the hesperidin for the reduction of the leg oedema and for the improvement of the venous symptoms — the combination of the hesperidin and the horse chestnut is one of the most effective combinations for the chronic venous insufficiency), and with the pycnogenol (which is a potent antioxidant that works synergistically with the hesperidin for the protection of the endothelial cells and for the maintenance of the vascular integrity — the combination of the hesperidin and the pycnogenol is one of the most effective combinations for the prevention of the capillary fragility and for the treatment of the chronic venous disease).
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