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Grape seeds are rich sources of non-extractable polyphenols, mainly high-molecular-weight proanthocyanidins. Their use as functional supplements or ingredients has aroused worldwide interest. In fact, oral grape seed products are typically available in pharmacies or grocery stores around the world. Wide-ranging evidence of their biological effects has been available since the popularity of the so-called French paradox. The aim of this chapter is to summarise the use of non-extractable polyphenols from grape, mostly as grape seed proanthocyanidins, to treat human diseases, focusing mainly on information from clinical trials. There is much verified information that relates consumption of grape seed proanthocyanidins with a reduction in blood pressure and some blood lipid parameters, such as total cholesterol. Most of the beneficial effects reported are explained by the antioxidant properties of the polyphenolic fraction, despite its relatively low bioavailability, and seem to be more pronounced in healthy subjects than in subjects with specific diseases or conditions. Therefore, grape seed products could be better used to prevent diseases, but without ruling out their use as adjuvant treatments. Additionally, emerging uses of grape seed proanthocyanidins against conditions related to dentistry, the menopause and skin disorders are showing promising results. However, clinical evidence of their biological effects is limited.

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