Folate derived from the diet requires a complicated conversion to a variety of THF derivatives. In contrast, the synthetic form of folate, known as folic acid or PGA, is used in food fortification and supplements because it is more stable and offers better © 2007 Elsevier Australia
bioavailability. A pharmaceutical form known as folinic acid (5-formyl-THF) acts as an immediate precursor to the primary metabolite (Kelly 1998).
Clinical note — Is synthetic folate the superior form?
Given its profound instability in processing, poor bioavailability, and complex conversion to active forms, adequate folate appears more difficult to achieve with the natural form than with synthetic forms, because the latter are comparatively stable and some act as an immediate precursor to the primary metabolite (Kelly 1998). Importantly, when synthetic folate is taken with food, it offers a higher bioavailability than dietary forms, 85-100% compared with 50-66% respectively. As such, both supplementation and fortification of grains and cereals may actually be a more reliable manner of increasing tissue levels. Accurate assessment of an individual's folate status may therefore require an adjustment made for increased bioavailability of synthetic forms using the equation:
1 dietary folate = 1 fjg of dietary folate equivalent r ,
= 0.6 ¡jq of folic acid from a fortified source or supplement taken with food
= 0.5 fjg of folic acid from a supplement taken on an empty stomach (NHMRC 2005).
One residual concern regarding high dose exposure to folic acid is due to the passive diffusion of unmodified PGA across the epithelium and into the bloodstream. This monoglutamate form is not naturally seen in human blood and the discovery of high levels in supplemented patients has raised questions regarding its biological effects (Lucock 2004). Until further research is conducted in this area, the implications are unclear.
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