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Dietary betaine is readily absorbed into the circulation and then distributed throughout the organism in a tissue-specific manner. Betaine accumulates efficiently within the liver's hepatocytes where it acts as a methyl donor. Due to its physicochemical properties, betaine acts as an organic osmolyte regulating water balance in various tissues. Notably, betaine counteracts the inhibitory effects of urea and NaCl in kidney medullary cells. The physiological roles of betaine in various tissues are not yet fully understood but its role may be particularly important under challenging physiological conditions such as dehydration or metabolic stress caused by an excess of nutrients.The aim of this chapter is to review the mechanistic data on the ability of betaine to maintain tissue homeostasis under different stress conditions. The bioavailability of betaine molecules to various tissues is essential when evaluating the role of betaine in stress. The bioavailability of betaine involves its digestion, absorption, distribution, and metabolism as well as the elimination of the molecule.

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