A review.Nutrition is a major tool in human health and disease prevention.Edible berries are rich in natural anthocyanin antioxidants.The pharmacol. and therapeutic properties of berry anthocyanins have been demonstrated to exert significant chemopreventive, anti-angiogenic and anti-cancer properties.A significant number of studies have also shown that berry anthocyanins are novel cardioprotectants, beneficial in reducing age-associated oxidative stress, improving neuronal and cognitive brain function and ocular health, and protecting genomic DNA (DNA) integrity.Angiogenesis, a natural process of blood vessel growth, is a double-edged sword that can either be protective or destructive.Although therapeutic angiogenesis takes place for wound healing and for restoring blood flow in ischemic tissues/organs, unwanted growth of blood vessels may lead to the formation of varicose vein, tumor or cancer metastases-and therapeutic intervention requires an anti-angiogenic process.A healthy body controls angiogenesis through angiogenesis-stimulating growth factors or angiogenesis inhibitors.The diverse health benefits of edible berry anthocyanins have been reviewed.A synergistic formula, OptiBerry, was developed by combining wild blueberry, bilberry, cranberry, elderberry, raspberry seeds, and strawberry.This formula exhibited high antioxidant efficacy [oxygen radical absorbance capacity (ORAC) value] and cellular uptake, minimal cytotoxicity and novel anti-angiogenic properties.OptiBerry significantly inhibited both hydrogen peroxide (H2O2)- as well as tumor necrosis factor alpha (TNFα)-induced vascular endothelial growth factor (VEGF) expression, a key regulator of tumor angiogenesis, by human keratinocytes.A Matrigel assay using human microvascular endothelial cells (EC) showed that OptiBerry impaired angiogenesis.In an in vitro model of angiogenesis, OptiBerry significantly inhibited basal monocyte chemoattractant protein-1 (MCP-1) and inducible nuclear transcription factor-kappa beta (NF-κβ) transcriptions.Endothelioma (EOMA) cells pretreated with OptiBerry showed a diminished ability to form hemangioma and markedly decreased tumor growth by more than 50% in 129 P3 mice.Results demonstrated the novel antioxidant, anti-angiogenic and anti-carcinogenic potential of OptiBerry.A review of a large number of studies exhibited the health benefits of berry anthocyanins in cardiovascular dysfunction, cerebral ischemic stroke, diabetes, and healthy vision-and therapeutic angiogenesis causes intervention.Overall, berry anthocyanins favorably regulate angiogenesis in promoting human health and disease prevention.