Plasma, liver and kidney folate and plasma homocysteine concentrations are poor response variables at very low dietary folate intakes, in a folate depletion/repletion rat model

Folate depletion/repletion rat models are popular protocols for assessing the bioavailability of folate. Much of the early work carried out on folate bioavailability concentrated on foods naturally high in folate. However, foods low in folate often contribute significantly to folate intake because of their high consumption in the general population. Therefore, the assessment of the bioavailability of foods low in folate is essential to properly estimate folate intake. The present study investigated plasma, liver and kidney folate and plasma homocysteine concentrations as appropriate response variables for measuring folate bioavailability in the rat at very low dietary folate intakes. One hundred and one weanling male rats (Wistar strain) were fed a folate-deficient diet containing 1% succinyl sulfathiazole for 28 d. Following depletion, six rats were randomly assigned to each of 16 repletion diets containing folic acid, fortified white bread, unfortified wholemeal bread or unfortified rye bread calculated to provide 6.25, 12.5, 18.75 and 25 micrograms folate/kg of each diet. After a further 28 d, plasma, liver and kidney folate concentrations were determined by microbiological assay. Plasma homocysteine was measured by HPLC as a functional indicator of folate status. Only a weak correlation was found between the response variables measured and dietary folate intake, indicating that this folate depletion/repletion rat model is not suitable for testing the response of rats fed diets containing very low levels of folate.