Project

Folate is a B-vitamin, and refers to a group of compounds that are required in the transfer of one-carbon units in a variety of metabolic reactions, including the synthesis of purine and pyrimidines. Folic acid (FA) is a synthetic oxidized form of folate that because of its stability and high bioavailability is the form of folate used in supplements and in food fortification. Mandatory FA fortification of enriched grains was introduced in Canada in ~1998 to reduce neural tube defects (NTDs). It was also hoped that fortification might have other beneficial effects to the population such as lowering cardiovascular disease. While this policy has successfully reduced NTDs and possibly stroke in Canada there are concerns that FA may be having adverse effects on the population. These include ‘masking’ of the neurological signs of vitamin B12 deficiency and possibly increased colon cancer risk. Since folate is required for the synthesis of DNA and for methyl metabolism, it has been postulated that an increase in cancer incidence with FA fortification may be mediated through an epigenetic mechanism, such as changes in DNA methylation. A reduced form of folate, L-5-methyltetrahydrofolate (L-MTHF), has recently become available, which unlike FA, does not mask vitamin B12 deficiency, and could prove to be a potentially safer form of folate fortificant. However, a major limitation in the use of L-MTHF as a fortificant is its poor stability.

This multidisciplinary project employs the disciplines of Food Chemistry and Material Science, Biochemistry, Nutrigenomics and Human Nutrition to focus on developing a stable L-MTHF folate that can provide all the benefits of FA fortification without the health risks potentially associated with excessive FA intakes.

1) We seek to provide a novel folate (e.g. L-MTHF) fortification ingredient with improved stability, and thus efficacy and safety.

2) Since L-MTHF, as with most naturally occurring folate derivatives, degrades when exposed to oxygen, light, heat and a shift in pH,9, 10 we will develop microencapsulation technologies that will preserve the folate fortificant for delivery of optimal concentrations and stabilities often challenged by different post harvest activities (e.g. processing or storage).

3) We seek to study and compare the absorption efficiency of free and microencapsulated L-MTHF in Caco-2 cells (in vitro) and in the intestine in “knock-out” mice (in vitro), important information for knowing the efficacy potential of different L-MTHF stabilized formulas and microencapsulation formats.

4) We seek to To learn more about the metabolism of free and microencapsulated L-MTHF in vitro (e.g. in Caco-2 cells) and in vivo (mice intestine in-situ), using methods not appropriate for human clinical trials.

5) We will conduct nutrigenomic studies that will determine the effect of FA versus L-MTHF on global DNA methylation and gene-specific methylation and expression in mice and humans.

6) We will also compare the effect (bioavailability) of bread fortified with L-MTHF and FA, on blood levels of folate, homocysteine in populations with sub-optimal folate status (international nutrition).