First isolated from spinach in 1941, folate derived its name from the Latin word folium, which means leafy. Folate is the generic term that comprises naturally occurring folate derivatives and includes the synthetic folic acid found in fortifi ed foods and supplements as well as in poultry and swine feeds.

This vitamin functions in DNA synthesis and many single-carbon transfer reactions and is especially vital during rapid cell growth. Folate also can take part in epigenetics and modify 1-generational phenotypic expression (Zeisel, 2009; Ingrosso and Perna, 2009). In addition, an insuffi ciency is regarded as being pivotal in the risk of developing some cancers (Ericson et al., 2007).

The remethylation of homocysteine to methionine requires folate, and elevated plasma homocysteine can signal a low folate status (Miller et al., 1994). High blood levels of homocysteine could predispose arterial walls to platelet aggregation and clot formatin, thus posing a risk for cardiovascular disease and stroke (Malinow, 1995).

Geriatric requirements

In elderly patients, high blood homocysteine is regarded as a reliable marker for dementia caused by folate/ vitamin B12 defi ciency (Nilsson et al., 2001).

In a three-year study with participants 50 years of age and older, twice the recommended daily allowance (RDA) for folate improved short-term memory, mental agility and verbal fl uency (Durga et al., 2007). In other work, mental depression (Coppen and Bolander- Gouaille, 2005) and Alzheimer’s disease (Corrada et al., 2005) were attributed to a shortage of folate.

Generally, studies can associate some age-related mental debility with folate insuffi ciency. Folate is necessary for the synthesis of neurotransmitters, which play roles in depression and dementia in elderly subjects (Brocker et al., 1986), presenting at least one route to couple folate with such disorders.

According to recent US Department of Human & Health Services data, the segment of the US population 65 years and older will increase from 37.3 million people in 2006 to 71.5 million by 2030. Folate nutrition may become more prominent in this group.

Food fortification

Folate received a lot of attention when an inadequacy was clearly related to an increased risk of neural tube defects in infants (Shaw et al., 1995). Compliance with higher dietary recommendations was woefully inadequate (Eichholzer and Zimmermann, 2006). As a result, mandatory folic acid fortifi cation of cereal products in the US and Canada was implemented in 1998 to target 100 μg of folic acid per day per person.

This program is now credited with reducing spina bifi da (De Wals et al., 2007) and possibly stroke (Yang et al., 2006). Prior to this fortifi cation programme, an estimated 26 per cent of the US population was folate defi cient (Dietrich et al., 2005).

Most European countries disregard mandatory folic acid fortifi cation due to the recognition that crystalline folic acid at high levels poses tumorigenetic risks. Although the threat of toxicity is low (Hathcock, 1997), folic acid in excess of 1 mg per day can obscure anemia caused by vitamin B12 deficiency. If permitted to continue, this anemia results in irreversible neurological damage (Dickinson, 1995).

In view of the wide range of roles this vitamin plays, coupled with concerns for the use of synthetic folic acid, additional strategies are needed to ensure adequate folate intake for all segments of society.

Dietary folate equivalents

Folate or folic acid recommendations are expressed as dietary folate equivalents (DFE), and one DFE equals 1 μg of dietary folate or 0.5-0.6 μg of folic acid supplement. DFE assumes a 50 per cent difference in bioavailability between supplemented folic acid and folate from food sources — a notion that is not without controversy.

Recommendations fall within the range of 150-600 μg per person per day, depending on age and country. For pregnancy and lactation, the RDA is 500- 600 μg per day.

Egg fortification

Synthetic crystalline folic acid added to laying hen diets is deposited in the egg as natural folate, and 95 per cent is found in the yolk (Sherwood et al., 1993). More than 80 per cent of the folate in eggs is 5-methyltetrahydrofolate (5-MTF), a form of folate that is rapidly absorbed (McKillop et al., 2003).

The active 5-MTF metabolite does not mask anemia caused by vitamin B12 defi ciency. Relative to green leafy vegetables, folates in animal products are generally stable during cooking (McKillop et al., 2002).

Nutritional organisations consider hen eggs a poor source of folate. However, folic acid fortifi cation of hen diets can increase folate in eggs by almost threefold and elevate eggs to an “excellent” source of folate. Furthermore, while the Institutes of Health places an upper limit on synthetic folic acid in fortifi ed foods, it considers “no health risk” for natural sources of folate.

Manitoba research

University of Manitoba studies found that laying hens fed 4 μg of folic acid per kilogram of feed can produce eggs with about 40 μg of folate per egg on the basis of 5-MTF in the yolk (House et al., 2002; Dickson et al., 2005). This compares to 17 μg per egg with no added dietary folic acid.

Higher egg folate levels were achieved, but the effi ciency of deposition declined signifi cantly as supplementation rates increased.

The Manitoba work tested two Hy-Line layer strains: the W36 and W98 (Hebert et al., 2005). Increased folic acid signifi cantly decreased plasma homocysteine in W98 birds but not in W36 birds.

Furthermore, Hy-Line W98 hens laid more eggs as folic acid supplementation increased to 64 mg/kg, implying a higher folic acid requirement for early-maturing birds. Elevated dietary folic acid was also associated with increased feed intake (House et al., 2002).

Of particular interest, the researchers found egg yolk folate bioavailability to be 100 per cent compared to folic acid. Egg folate more effectively lowered plasma homocysteine than crystalline folic acid in bio-assay evaluations (House et al., 2002).

Enriched eggs stored for four weeks at 36°F (4°C) experienced no change in folate levels (House et al., 2002). These conditions correspond with typical storage of commercial eggs and indicate that storage losses are of little concern. Of the folate derivatives, 5-MTF is the most stable.

Hence, two folate-fortifi ed eggs provide about 20 per cent of the US RDA of 400 μg per day or 40 per cent of the Canadian RDA of 200 μg per day.

UK study

A recent study investigated folate fortifi cation of eggs with a slight twist (Hoey et al., 2008): Total folate was assayed in whole eggs as opposed to only analysing egg yolks for 5-MTF.

Across several levels of dietary crystalline folic acid in hen diets, the maximum folate content was about 90 μg of folate per 60 g egg from hens fed 16 mg of folic acid per kilogram of feed (Hoey et al., 2008). This is about 1.5 times higher than reported by the Manitoba research, albeit with four times more folic acid. Hens fed 4 mg of folic acid per kilogram of diet attained a level of 60 μg of folate per egg.

Regardless of the supplementation level of folic acid, the unmetabolized folic acid remained about 10 per cent of total egg folate — too low to be of any worry to populations concerned with synthetic folic acid (Hoey et al., 2008).

The fi ndings from the UK confirm that folate-fortifi ed eggs could be a crucial source of folate. Two eggs can supply about 180 μg folic acid, which is equivalent to 45 per cent of the US RDA.

What about toxicity?

Folic acid is generally regarded as nontoxic by the National Research Council’s Subcommittee on Vitamin Tolerance (NRC, 1987). No deleterious effects occurred in hens fed 128 mg of folic acid per kilogram of feed over a three-week period (Hebert et al., 2005), and that was a level 8-32 times more than needed for meaningful egg fortifi cation.

Economics favorable

Enrichment of eggs plateaus within three weeks of supplementation (Hoey et al., 2008). Hence, it is a quick return on investment. At typical industry supplementation rates, which haven’t changed much over the years for laying hens (Ward, 1993), folic acid accounts for 1 per cent of vitamin costs, or about 2 cents per ton of feed at current prices.

To obtain two eggs that provide 45 per cent of the US RDA, the additional folic acid will cost about 30 cents per ton of feed. This equates to less than 0.05 cents/doz. eggs on the basis of typical egg production and feed conversion. Two eggs to provide about 20 per cent of the US RDA entail about one-quarter of the cost (House et al., 2002).

Summary

Coupled with the high bioavailability of yolk folate, the common table egg can be crafted into an extraordinary source of natural folate. The investment to produce folate-enriched eggs is miniscule and permits considerable opportunity for egg producers to exploit a novel market.

References

The full list of references is available online at www.feedstuffs.com or by e-mailing [email protected].

March 2010