Merck's Metafolin receives EU approval

The EU has given the green light for the use of Merck Eprova's Metafolin, a patented form of folate with superior bioavailability, in dietary supplements and dietetic foods in the EU, thereby giving formulators the means to differentiate their products from those containing folic acid.

The EU Standing Committee on the Food Chain and Animal Health voted to include Calcium L-Methylfolate (Metafolin) in the positive list of vitamins covered in the EU Directives 2002/46/EC (food supplements) and 2001/15/EC (foods for particular nutritional uses).

Metafolin is the predominant folate found in foods such as orange juice, green leafy vegetables, salads and yeast, and is a form that can be directly used by the body.

Until now, however, supplement-makers have only been able to use synthetically produced folic acid, the most oxidised form of folate which has to be reduced in four metabolic steps for the body to use it.

In fact, although it is the best-known folate form, folic acid does not occur naturally in foods but is produced synthetically.

Merck Eprova has developed a proprietary process for the production of a stable synthetic crystalline L-methylfolate; in the past, stability issues have prevented its use in foods and supplements.

"Metafolin is a proprietary folate with excellent bioavailability. We believe Metafolin is an interesting tool for a differentiation strategy in a highly competitive market," explained product manager Roger Weibel.

A 2003 study involving 24 healthy female volunteers concluded that Metafoline is more than 50 percent more bioavailble than folic acid over an eight hour period - 99.83 AUC (h x nmol/l) compared to 63.94 (Prinz-Langenohl R. et al. J. Inherit. Metab. Dis. 26 (1), 124 2003).

Weibel told NutraIngredients.com that if the metabolic pathway works as it should, folic acid is normally converted to L-methylfolate. But one cannot be one hundred percent sure that all the folic acid will be converted, which may mean that some unmetabolised folic acid remains in the body.

The long-term effects of any such unmetabolised folate acid are unknown - a factor that has led to some criticism of folic acid fortification programmes in countries including the US.

Metafolin is already used in supplements and medical foods in the US, since it was approved by the FDA in 2001. It is not yet approved for use in mainstream foods on either side of the Atlantic, and although this may be a possibility for the future, Weibel said that the company is taking one step at a time.

Since there is awareness about folic acid amongst consumers, Weibel expects that it will be some time before Metafolin becomes equally well-known. However scientific journals and newspapers are increasingly preferring to use the blanket term 'folate'.

Weibel was not able to comment on the company's marketing plan for the EU, save that, since Metafolin is not a commodity but a proprietary substance, this creates the opportunity for product differentiation by leading supplement-makers.

The ingredient has already received several rubber-stamps on the road to EU approval: in October 2004 it was positive evaluation by the European Food Safety Authority (EFSA), and a further positive evaluate from JECFA (Joint FAO/WHO Expert Committee on Food Additives) followed in July 2005.

Merch Eprova general manager Martin Ulmann, General Manager of Merck said that the favourable outcome of the vote enables the company to "provide EU consumers with a naturally occurring folate, at a time when there is growing awareness of the health benefits of folate supplementation."

"Food is the major source for folates. However, in a large part of the population folate intake with food is insufficient. An adequate intake of folates is essential for the prevention of many disorders including anaemia, neural tube defects, various forms of cardiovascular diseases, Alzheimer's disease, colon cancer and depression," added Dr Rudolf Moser, scientific director.