Type of Papers: Reports completed by expert consultations and published by the World Health Organization jointly with the Food and Agriculture Organization of the United Nations (FAO).
Note: Two WHO reports were summarized together as they contain much of the same information. See references below.
- Folate (vitamin B9) is involved in cell multiplication and tissue growth (through methylation of nucleotides).
- It functions closely with vitamin B12 in protein synthesis and metabolism.
Prevalence of Deficiency:
- There is very little data on the prevalence worldwide.
- Folate deficiency is more prevalent in populations who consume large amounts of refined cereals (which are low in folate) and small amounts of leafy greens and fruit (which are high in folate). Examples include:
- In Germany, lacto-ovo vegetarians (vegetarians who also consume eggs and dairy) had higher levels of red blood cell folate than non-vegetarians. This finding was likely due to a high consumption of folate-rich vegetables by the vegetarians.
- Low plasma folate is rare in countries where diets high in fruits and vegetables are common, such as Guatemala, Mexico, and Thailand. However, despite diets high in fruits and vegetables and little folate deficiency in adults, 10% of children under 4 years of age were found to have low blood folate in Mexico.
Risk Factors for Deficiency:
- Dietary factors:
- Low intakes of leafy greens and fruits
- High intakes of refined cereals
- Malabsorption and infection with intestinal parasites (e.g., Giardia lamblia)
- There is some evidence that folate status may be associated with birth weight. Therefore, infants born with low birth weight may be at an increased risk for folate deficiency.
- Genetic disorders of folate metabolism
- Bacterial overgrowth
- Folate indicators:
- Red cell folate is the best index of long-term folate status and tissue stores of folate.
- Plasma folate has greater fluctuations and is closely related to recent dietary intake of folate.
- Other indicators:
- Hematologic indicators are also important in assessing folate status (e.g., elevated mean corpuscular volume, hypersegmentation of neutrophils, anemia) as folate can cause megaloblastic anemia.
- Plasma homocysteine is also a possible indicator of folate status. Homocysteine is elevated with low folate status. Homocysteine may be elevated even when red blood cell folate is within normal limits. However, homocysteine may also be elevated due to low vitamin B2, B6, or B12 status, and these causes must be eliminated before diagnosing low folate status.
Dietary Sources and Bioavailability:
- Best Dietary Sources: Green leafy vegetables (at least 3 servings are recommended per day), breakfast cereals and flours that are fortified (i.e., have folic acid added). Fruits, yeast, and liver are also good sources.
- Poor Sources: Folate in animal products is lost during cooking. Food staples (e.g., white rice, corn) that are not fortified are poor sources.
- Bioavailability: Folate is the natural form of the vitamin that is found in food, and folic acid is the synthetic form that is used to fortify foods and is in supplements. The synthetic form, folic acid, has greater bioavailability than the natural form, folate.
- The bioavailability (the amount absorbed in the diet) of folate is approximately 50%. Folate is also quite unstable, losing much of its biochemical activity (as much as 50-75%) during harvesting, storage processing, and preparation.
- The bioavailability of folic acid is approximately 85%. Folic acid is quite stable for months to years.
Recommended Nutrient Intakes (µg/day): The following are the Recommended Nutrient Intakes (RNI) as defined by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization. .
- There is no evidence that too much natural folate is toxic.
- However, too much folic acid (in fortified foods or supplements) may mask a vitamin B12 deficiency and pernicious anemia. The high levels of folic acid will correct the anemia caused by inadequate vitamin B12 causing the vitamin B12 deficiency to be undiagnosed. In such cases, the vitamin B12 deficiency will go untreated and other symptoms of the vitamin B12 deficiency, such as neuropathy, will develop.
- One solution may be to fortify foods with both folic acid and vitamin B12.
- However, the level of folic acid that has been used to fortify grain products in the U.S. is low enough to not reach the tolerable upper limit for any age range.
- There may also be other less well-defined effects of folic acid toxicity.
- The tolerable upper limit (UL) for folic acid in fortified foods or supplements for children 1-3 years is 300 µg/day.
- Fortification of foods such as cereals and flours has been widely used and has been effective in increasing plasma folate concentrations and decreasing plasma homocysteine.
Health Consequences of Deficiency and Benefits of Intervention:
- Although not specific to children, clinical manifestations of a folate deficiency include:
- Megaloblastic anemia (low hemoglobin with large immature red blood cells)
- Increased susceptibility to infection, decreased blood clotting, intestinal malabsorption
- Risk for cardiovascular disease (associated with increased homocysteine levels)
- Neural tube defects in infants exposed prenatally (soon after conception) to inadequate folate
- Birth defects in infants exposed prenatally (e.g., oro-facial clefts)
- Cognitive impairment
Folate and folic acid. Vitamin and mineral requirements in human nutrition. Report of a joint FAO/WHO expert consultation on human vitamin and mineral requirements, Bangkok, Thailand, 21–30 September 1998. 2nd ed. Geneva: World Health Organization, 2004:289-302.