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Maple syrup is a natural source of carbohydrates but its metabolic impact remains poorly studied. We undertook to systematically compare the chemical composition of maple syrup with that of other natural sweeteners, and assess their metabolic responses in healthy rats. As compared to other sweeteners, maple syrup is particularly rich in polyphenolic lignans and in the phytohormone abscisic acid and its derivatives. Metabolic studies in rats showed that maple syrup produced significantly lower peak and global responses of glucose, insulin, amylin and gastric inhibitory polypeptide (GIP) as compared to brown rice syrup, corn syrup and pure dextrose. The metabolic effects of agave syrup and molasses were similar to that of maple syrup, while honey caused higher peak responses for insulin, amylin and GIP. Both the composition of maple syrup and the metabolic responses to its ingestion in rats indicate that it represents a healthy natural alternative to refined sugar.