Ability of endogenous folate from soy protein isolate to maintain plasma homocysteine and hepatic DNA methylation during methyl group depletion in rats.

We investigated different means of achieving methyl depletion by feeding weanling rats modified AIN diets depleted of folate (FD), folate + choline (FCD), and folate + choline + methionine (FCMD), and examined the consequent effects on folate status, homocysteine levels, and methylation status. Control rats were fed a 12% protein diet consisting of either casein or soy protein isolate (SPI) and containing 2 mg/kg folate, 0.2% choline, and 0.4% methionine. After the rats had been on the diets for 4 and 8 weeks, whole blood folate concentration was measured and found to be significantly depleted in the folate deficient treatments compared with controls at 4 weeks (p < 0.001), this reduction being significantly greater (p < 0.03) in casein-fed rats (60%) than in SPI-fed rats (32%). The omission of choline and methionine from the diet had no further influence on whole blood folate. A significant inverse correlation was observed in the casein-fed rats after 8 weeks between mean plasma homocysteine concentration and decreasing methyl content of the diet (r2 = 0.978, p < 0.002), an effect not seen in the corresponding SPI-fed rats. Hypomethylation of hepatic DNA evidenced by a reduction in 5-methylcytosine content was present in the casein rats fed FCD and FCMD relative to control (p < 0.05). No hepatic DNA methylation changes were observed in the SPI-fed rats. The results obtained in the present work demonstrate that a soy-based diet can compensate against methyl group depletion by maintaining plasma homocysteine levels and an adequate level of DNA methylation, a result we attribute to endogenous folate content.