Background And Relevant Pharmacokinetics

Folate is the generic term for a large family of chemically similar trace compounds that fall within thevitamin B group. Folate is also known as folacin and vitamin B9. Folic acid (pteroylmonoglutamic acid or PGA) is the most oxidised and stable form of folate and the one most often used in supplements and food fortification. Folate found in animal sources is present in a 'free form' and is readily absorbed; however, aside from the organ meats, animal products are notoriously poor sources. Folic acid found in plant foods exists in a conjugated form, which has to be converted in the gut prior to absorption. This deconjugation process requires a zinc-dependent intracellular enzyme (Kelly 1998), which then makes folate available for absorption in the small intestine. This is inhibited by chronic alcohol ingestion and some foods, including oranges and legumes (Gropper et al 2005).

The average bioavailability of natural folate is between 50% and 66%, although synthetic forms, such as those found in fortified foods or supplements, show almost a twofold increase in bioavailability (Carmel 2006, Kelly 1998). Small amounts of folacin are endogenously produced by bacteria in the intestines, but this appears to be predominantly lost via faeces (Gropper et al 2005). Conversion into folate's active forms is a multistep pathway beginning within the intestinal cell wall and finishing in the liver. Secretion into the bile of these tetrahydrofolate (THF) derivatives and their subsequent reabsorption through the enterohepatic circulation enables redistribution throughout the body. Distribution of folate appears to be regulated via an unknown mechanism, ensuring increased availability to those tissues demonstrating rapid cell division (Gropper et al 2005). Although many of the biochemical pathways in which folate is involved act to regenerate the nutrient, there is still a significant amount that is broken down and eliminated, chiefly in the urine.

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