Folic acid effects two-faced depending on B12 levels, says study

"In this study of older Americans in the age of folic acid fortification, we found direct associations between high serum folate and both anaemia and cognitive impairment in subjects with low vitamin B12 status,"​ wrote lead author Martha Morris from Tufts University's Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging.

"Among subjects with normal vitamin B12 status, on the other hand, high serum folate was associated with protection from cognitive impairment."​

The results, published in the current issue of the American Journal of Clinical Nutrition​, have important implications for mandatory folic acid fortification worldwide.

Maternal consumption of folate, or its synthetic form folic acid, is strongly associated with a reduced risk of neural tube defect (NTD) in the early states of pregnancy. Fortification of certain food groups with folic acid has been mandatory in North America since 1998, and the number of pregnancies affected by NTDs is reported to have fallen by 26 per cent.

To date no European country has followed suit, although the wheels are in motion in Ireland and it now looks increasingly likely that the UK will introduce measures in 2007.

Folic acid fortification has been on the table in the UK since 2000, following a report by the Scientific Advisory Committee on Nutrition's (SACN) predecessor COMA, which concluded that universal fortification of flour with folic acid would significantly reduce the number of conceptions and births complicated by NTDs.

But after consultation with stakeholders the decision was taken not to make fortification mandatory at that time due to concern that it may mask vitamin B12 deficiency in some sectors of the population and because it would impinge on consumer choice.

"This idea is controversial, however, because observational data are few and inconclusive,"​ wrote Morris.

The results of the new study, based upon data from 1459 subjects (average age 70, 64 per cent female), appear to support these concerns. The researchers divided the subjects into two groups, depending on their vitamin B12 levels. Low B12 status was defined as having blood levels less than 148 picomoles per litre and accounted for 25 per cent of the study participants.

After adjusting their data for various factors which may have affected the results, Morris and her co-workers report that low vitamin B12 status was significantly associated with an increase in anaemia (170 per cent) and cognitive impairment (150 per cent), while the four per cent of subjects with the low B12 and high serum folate levels (greater than 59 nanomoles per litre) had even higher associations with anaemia (210 per cent) and cognitive impairment (160 per cent, compared to those with normal B12 levels.

In people with normal B12 levels, high serum folate levels were associated with a 60 per cent decrease in cognitive impairment, compared to those with normal folate levels.

"In conclusion, we undertook this investigation to shed light on long-held but evolving ideas about the effects of folic acid fortification on the elderly. We found a higher prevalence of both anemia and cognitive impairment in association with high serum folate in older Americans with a low vitamin B-12 status,"​ said the researchers.

"We encourage further study of these relations and their underlying mechanisms and hope our findings both inform the continuing debate about folic acid fortification and influence efforts to detect and treat low vitamin B-12 status in seniors,"​ they said.

In an accompanying editorial David Smith from the University of Oxford said that, assuming future studies confirm the results, "challenging questions about future research and health policies that relate to the puzzling interactions between folate and vitamin B-12 will need to be answered."​

Smith also said that the findings had immediate implications for folic acid fortification. He notes that the four per cent of the study population that fell into the low B12, high folate group would, if extrapolated to the general US population, be equivalent to about 1.8 million seniors at risk of both anaemia and enhanced cognitive impairment.

He asked the question whether it is ethical to save one child from NTDs but put more than 1000 elderly persons at risk of poorer health.

Numerous questions remain to be answered, said Dr. Smith, including:

"Should the issue of fortifying food with vitamin B-12 be reopened in those countries that have already fortified certain foods with folic acid? An expert group has already recommended vitamin B-12 fortification in the Americas​

Should countries considering folic acid fortification defer a decision until more is known about the interaction between folate and vitamin B-12 status? This question is particularly pertinent for the many countries that have a high prevalence of poor vitamin B-12 status​

Should supplements containing folic acid be combined with high doses of vitamin B-12 to ensure an optimal balance of the 2 vitamins?"​

Source: American Journal of Clinical Nutrition​ January 2007, Volume 85, Number 1, Pages 193-200 "Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification"​ Authors: M.S. Morris, P.F. Jacques, I.H. Rosenberg and J. Selhub