Folate type affects bioavailability, says study

Supplements of a folic acid derivative result in higher blood folate levels than straight folic acid, and could be an alternative for the prevention of neural tube defects, says a study from Germany.

In 1998 the US-FDA required the addition of folic acid to enriched breads, flours, cereals, and other grain products to increase folic acid intake in the whole population. Birth defects have declined by 26 percent since 1998.

Calls have been getting louder in Britain with some analysts now saying it is a question of 'when' and not 'if' the UK government introduces compulsory fortification of some flour products with folic acid.

Previous studies have shown that folic acid is more easily absorbed from fortified foods (85 per cent) and supplements (100 per cent) than the folate found naturally in foods (50 per cent).

New research from the University of Bonn in Germany goes even further by suggesting that the folic acid derivative, [6S]-5-methyltetrahydrofolate ([6S-5-MTHF), is even more bioavailable when given as supplements than folic acid, and could be an alternative for the primary prevention of neural tube defects.

This conclusion is based on the results of a double-blind, randomized, placebo-controlled intervention trial with 144 healthy women aged between 19 and 33. The women were divided into four groups and assigned to receive daily supplements containing 400 micrograms of folic acid, the equimolar amount of [6S]-5-MTHF (416 micrograms), 208 micrograms [6S]-5-MTHF, or placebo 24 weeks.

The supplements were manufactured by German-based PCI Services and provided as hard gelatin capsules. The [6S]-5-MTHF was in the form of the calcium salt (MetaFolin, Merck Eprova).

The researchers, led by Dr. Yvonne Lamers, measured red blood cell and plasma folate concentrations at the start of the study and then every four weeks.

The results, published in the July issue of the American Journal of Clinical Nutrition (Vol. 84, pp. 156-161), show that the group receiving daily supplements of 416 micrograms [6S]-5-MTHF had significantly higher red blood cell folate levels (ca. 1400 nanomoles per litre) than the other groups (ca. 1250 nmol/L for folic acid, ca. 1100 nmol/L for 208 micrograms [6S]-5-MTHF, and ca. 700 nmol/L for placebo).

No stabilisation of the red blood cell folate levels was observed in the three supplementation groups, but the plasma folate levels levelled off after 12 weeks.

"We showed that administration of [6S]-5-MTHF is more effective than is folic acid supplementation at improving folate status," said the researchers.

Moreover, based on the times needed for the stabilisation of folate levels in red blood cells, Dr. Lamers and her colleagues said that current recommendations that women of childbearing age start taking folic acid supplements four weeks before conception should be revised. The Bonn researchers called for the period to be extended to greater than 12 weeks for maximal prevention of NTDs based on folate concentrations.

According to the new report from American voluntary health agency March of Dimes, eight million babies are born with defects every year, equivalent to about six per cent of all births worldwide.

One of the most common birth problems identified was neural tube defects such as spina bifida and anencephaly. However, both conditions occur in the very early stages of pregnancy, often before women are aware that they are expecting.