Response of red blood cell folate to intervention: implications for folaterecommendations for the prevention of neural tube defects

Committees worldwide have set almost identical folate recommendations for t he prevention of the first occurrence of neural tube defects (NTDs). We eva luate these recommendations by reviewing the results of intervention studie s that examined the response of red blood cell folate to altered folate int ake. Three options are suggested to achieve the extra 400 mu g folic acid/d being recommended by the official committees: increased intake of folate-r ich foods, dietary folic acid supplementation, and folic acid fortification of food. A significant increase in foods naturally rich in folates was sho wn to be a relatively ineffective means of increasing red blood cell folate status in women compared with equivalent intakes of folic acid-fortified f ood, presumably because the synthetic form of the vitamin is more stable an d more bioavailable. Although folic acid supplements are highly effective i n optimizing folate status, supplementation is not an effective strategy fo r the primary prevention of NTDs because of poor compliance. Thus, food for tification is seen by many as the only option likely to succeed. Mandatory folic acid fortification of grain products was introduced recently in the U nited States at a level projected to provide an additional mean intake of 1 00 mu g folic acid/d, but some feel that this policy does not go far enough . A recent clinical trial predicted that the additional intake of folic aci d in the United States will reduce NTDs by >20%, whereas 200 mu g/d would b e highly protective and is the dose also shown to be optimal in lowering pl asma homocysteine, with possible benefits in preventing cardiovascular dise ase. Thus, an amount lower than the current target of an extra 400 mu g/d m ay be sufficient to increase red blood cell folate to concentrations associ ated with the lowest risk of NTDs, but further investigation is warranted t o establish the optimal amount.