[6S]-5-Methyltetrahydrofolate enhances folate status in rats fed growing-up milk

To investigate the efficiency of [6S]-5-methyltetrahydrofolate or Metafolin(A (R)) ([6S]-5-CH3-H(4)folate) on the recovery of folate status, we conducted a depletion-repletion rat model study using a growing-up milk as the folate carrier. The effect of [6S]-5-CH3-H(4)folate was compared to that of folic acid (PGA or Pte-Glu), by feeding two groups of folate-depleted rats a diet of fortified growing-up milk containing either 1,000 mu g/l (2.2655 mu mol/l) of Pte-Glu or 1,041.91 mu g/l (2.2655 mu mol/l) of [6S]-5-CH3-H(4)folate over a 4-week period. At the end of the study, the folate concentration in plasma, erythrocytes and liver was measured to establish the folate status of the animals. The folate content was determined in the plasma and erythrocytes by a time-resolved fluoroimmunoassay method and in the liver by a HPLC method. Plasma, erythrocyte and liver folate concentrations were significantly (P < 0.001) lower after a depletion period in rats fed the folate-deficient diet compared to rats fed a control diet. The folate form used significantly influenced the folate concentration in erythrocytes and liver, but not in plasma, after the rats' body folate reserves were replenished by consuming the fortified growing-up milk. Thus, rats fed [6S]-5-CH3-H(4)folate-fortified growing-up milk showed significantly higher folate content in erythrocytes and liver (1,100.37 ng/ml and 4.22 mu g/g, respectively), than did those fed Pte-Glu-fortified growing-up milk (827.71 ng/ml and 3.04 mu g/g, respectively, in erythrocytes and liver). We conclude that the natural diastereomer [6S]-5-CH3-H(4)folate may adequately serve as an alternative to folic acid for the folate fortification of infant foods.