Another recent report, by Troen et al (16), studied an index of
immune function—natural killer (NK) cell cytotoxicity—in
postmenopausal women and also showed both “good” and “notso-good”
sides of folic acid. NK cells are an important part of the
nonspecific immune response and can kill tumor cells and virally
infected cells. Inthis studythe authors found aninverse U-shaped
relation between total folate intake and NK cytotoxicity. Women
in the bottom tertile of dietary folate intake (233 g/d) who
took daily supplements containing 400 g folic acid displayed
better immune function than did those who took no supplementary
folic acid; however, women with a dietary folate intake
233 g/d who took supplements providing 400 g folate/d
had impaired NK cytotoxicity. Although a relation between total
plasma folates and NK cytotoxicity was evident, a highly significant
inverse linear association between the amount of folic acid
in plasma and NK cytotoxicity was observed, particularly in
women aged 60 y. The only important sources of folic acid are
from fortified foods and dietary supplements. These findings
raise the hypothesis that excess folic acid from supplements or
from fortified food can suppress NK function, which is vital for
normal immune function. This hypothesis could, and therefore
should, be tested. It would also be of interest to know whether an
association between vitamin B-12 status and NK cytotoxicity
exists. Is it possible that poor vitamin B-12 status influences the
metabolism of folic acid or the function of NK cells after high
intakes of folic acid?
A notable feature of the 3 recent studies that described an
adverse effect of high folate status is that many participants
(33– 67%) in each of the studies reported the use of folatecontaining
supplements (9, 10, 16). Folic acid is used to fortify
food and is contained in almost all folate-containing supplements.
Hence, these subjects were being exposed to folic acid
from supplements as well as from fortified food—a matter that
has already raised concern (17). It is perhaps not surprising that
Troen et al (16) detected unmetabolized folic acid in fasting
plasma samples from 78% of the subjects in their study.