Folate Levels Decline Slightly, But No Cause for Concern Yet

ATLANTA, Sept. 7 -- Folate levels in the American diet have declined slightly in the last few years, but not enough to cause alarm, said CDC investigators.

A review of blood folate and vitamin B-12 levels over the past two decades showed about a 10% recent decline in folate levels. This followed a significant spike in levels of both nutrients in response to a food-fortification program instituted in the 1990s, reported Christine M. Pfeiffer, Ph.D., of the CDC's National Center for Environmental Health, and colleagues.

The decrease warrants further surveillance, but is "unlikely to be functionally important," the authors wrote in the September issue of the American Journal of Clinical Nutrition.

"The rise and fall in blood folate concentrations in the United States and the potential for these changes to have health-related consequences provide the incentive for further investigations to identify and monitor changes in the specific sources of folic acid intake," wrote Lynn B. Bailey, Ph.D., of the University of Florida, in an accompanying editorial.

Folate deficiency in pregnancy has been associated in several studies with an increased risk of children with neural-tube defects, the investigators noted.

"Monitoring the folate status of the U.S. population over time has been a priority since the results for serum and red blood cell folate concentrations from the second National Health and Nutrition Examination Survey (NHANES II; 1976-1980) suggested that the folate status of some population groups may be a public health concern and since data from the third NHANES (NHANES III, 1988-1994) confirmed these findings," they wrote.

In 1998, the U.S. government mandated fortification with folic acid of enriched cereal and grain products, and the following year the NHANES program began continuous surveillance of folate and B-12 levels to see whether the mandate met its target goals.

The authors looked at measurements of blood indicators of the two nutrients (serum and red blood cell levels of folate and serum levels of B-12) among about 23,000 NHANES III participants, and among about 8,000 participants in NHANES surveys conducted in the post-foritification period (1999 to 2004).

They found that for each age group in the immediate post-fortification period, serum folate levels increased by119% to 161% over pre-fortification levels, and red-blood-cell folate concentrations rose by 44% to 54% over baseline.

But between the first and third post-fortification surveys, serum folate levels in most age groups dropped slightly, ranging from a 5% to a 13% decline, and folate concentrations in red blood cells dropped by 6% to 9%. There were no significant changes in serum vitamin B-12 concentrations over the same period, however.

One of the major goals of the fortification mandate was to reduce the incidence of neural-tube defects by decreasing the prevalence of low folate levels among women of childbearing age, and the data strongly suggest that this goal was achieved, the authors noted.

Prevalence estimates of low serum concentrations in this population went from 21% before fortification to less than 1% after, and the prevalence of low RBC concentrations of folate showed a similar drop, from 38% pre- to 5% post-fortification, and remained unchanged thereafter.

There were also before-and-after changes in prevalence estimates of high serum folate concentrations in children (from 5% to 42%) and in older adults (from 7% to 38%) but the estimates for both of these groups decreased slightly in the second and third post-fortification surveys.

The reasons for the mild declines in folate concentrations are unclear, but may be related to the low-carbohydrate diet enthusiasm that swept the country for a few years, the authors suggested.

Another possible cause, but one that will be difficult to detect, suggested Dr. Bailey in her editorial, is a reduction in the amount of folic acid added to enriched-grain cereal products.

In an analysis of a number of enriched foods during the early post-fortification period (1998-1999), the total folate content of many of the analyzed foods far exceeded the amount required by federal regulations, she wrote. "Although there has been no systemic examination of changes in folate content of enriched cereal-grain products, two research groups have reported data supporting the conclusion that the amount of folic acid added to the food supply has been reduced."

As to the public health implications of their findings, Dr. Pfeiffer and colleagues noted that when they applied a different assay with different cutoff points to some of the samples, they found that for each of the three post-fortification survey periods, there were fewer than four participants out of 8,000 with low serum folate and, fewer than 40 with low RBC folate.

"Thus, from the perspective of nutritional adequacy relative to generally accepted nutritional status criteria, the slight downward trend after fortification seems unlikely to be functionally important," they wrote.