Chapter 9.8

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Suggested citation for this chapter.

Moroz,N. (2022) Improving human nutrition, The Encyclopedia for Small Scale Farmers. Editor, M.N. Raizada, University of Guelph, Canada. http://www.farmpedia.org

Folate Deficiency

This chapter will outline how folate deficiency can be detrimental to one’s health, while also outlining various sources of folate found in many seeds and legumes grown throughout the developing world. Folate deficiency (FD) results from a reduced intake of folate – a generic term that encompasses both naturally occurring food folate as well as folic acid (NIH, 2016). FD can also occur due to heightened folate demands during pregnancy or because of impaired absorption occurring from mal-absorption disorders (Merck Manuel, 2016). Folate is a water soluble-B vitamin complex that is naturally available in foods while also frequently enriched in foods or provided as food supplements (NIH, 2016). Folic acid is the term used for the fully oxidized form of the vitamin complex used in dietary supplements and in fortified foods (NIH, 2016).

Folate deficiency is thought to contribute to the prevalence of many major diseases and severe birth defects (Basset, Quinlivan, Gregory, & Hanson, 2005). To help understand the common causes of folate deficiency, they are listed on the table 1. Inadequate intake can be the result of diseases that impacts absorption, use of various drugs, of simply inadequate dietary intake (Merck Manuel, 2016).

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Health Issues Resulting from Folate Deficiencies

Folate deficiency is associated with multiple cancers, cardiovascular disease, and Neural Tube Defects (NTDs) (Basset et al., 2005; NIH, 2016). Folate is a critical factor for the synthesis of the components of DNA, namely for the synthesis of purines and pyrimidines, as well as for the development of the fetal nervous system, red blood cells, and other cellular components (Merck Manuel, 2016). Furthermore, folate is important during phases of rapid cell growth, such as during fetal development, due to heightened cellular demands (NIH, 2016). Because this vitamin complex is an imperative cofactor for the synthesis of DNA precursors, one can see the range of adverse health effects that can occur in FD individuals. This section will briefly discuss the adverse health outcome resulting from FD starting with NTDs – a severe defect due to FD during pregnancy.

NTDs result in dangerous malformations that occur during fetal development, including various malformations of the spine (spina bifida), skull, and brain (anencephaly) in a newborn following a folate deficient pregnancy (NIH, 2016; Merck Manuel, 2016). NTDs are a failure for the neural tube to close at the upper or lower end between days 21 to 28 of post-conception pregnancy (NIH, 2016). As such, NTDs should be of concern for all pregnant women. Women lacking in folate intake are at risk of having children with NTDs, along with other complications such as low birth weight and early delivery (NIH, 2016). However, multiple clinical trails have clearly shown that a substantial proportion of NTDs can be easily addressed by taking folic acid pre-conceptionally (NIH, 2016). This evidence has led to required food fortification programs that have reduced by NTD rates by 25%-30% in the USA, and researchers believe this rate could be reduced even more if access inequalities are addressed (NIH, 2016). Risk of NTD is not always dependent solely on folate status, but rather a combination of other factors, such as obesity and low intake of other key nutrients, that may affect NTD risk (NIH, 2016).

While the relationship between FD and NTD is well established, the implications if FD in other major diseases are less certain. FD has been inversely associated with risk of multiple cancers (including colorectal, pancreatic, and more) as folate may influence the development of cancers due to its importance in DNA replication and cell division (NIH, 2016). However, further research is needed due to the high uncertainties around the role of folate in carcinogenesis, cardiovascular disease, and many health issues (NIH, 2016). What is certain is that folate is a key micronutrient for metabolism and many bodily processes (NIH, 2016).

Absorption of Folate and Folic Acid

As can be discerned in table 1, FD in isolation is not as common as its coexistence with multiple other nutrition deficiencies associated with mal-absorptive disorders, drug intake, and poor diet (NIH, 2016). Considering the causes of poor folate uptake into the human body, the following groups are considered at heightened risk of FD: 1. People with alcohol dependence, as alcohol interferes with folate absorption and accelerates its breakdown (NIH, 2016). 2. Women of childbearing age, as FD increases the risk of NTDs, and these women should obtain 400 micrograms/day of folic acid (NIH, 2016; WHO, 2012). 3. Pregnant women, as the demands for folate intake increase due to the growing fetus’s need for cellular division and DNA synthesis (NIH, 2016). These women require 600 micrograms/day. 4. People with mal-absorptive or digestive-tract disorders, as these medical conditions can lower the natural folate absorption into the body (NIH, 2016). Generally, poor absorption of folate and increased demands predispose people to the greatest risk of FD. Additionally, prolonged cooking destroys folate and can predispose people to inadequate intake (Merck Manuel, 2016). This is important information for subsistence farmers and those without access to enriched gains who may meet folate dietary needs through local raw green vegetables, legumes, and intake of seeds.

Natural Sources of Folate and Folate Fortification/Supplementation

Consumption of a diversity of foods and vegetables is key to providing adequate supply of folate, among other vitamins and minerals. Beans and dark green vegetables are some of the foods with the highest natural folate concentrations (NIH, 2016). Many of the leafy greens are also high in iron, folate, and vitamin A. Natural folate can be found in beans and dark green leafy vegetables such as spinach, turnips, and seaweed. Folate can also be found in nuts, seeds, diary/egg products and meats, (NIH, 2016). Some of these products can be seen from table 2. The benefits of legume consumption for folate are further outlined in table 4.

Many countries (U.S., Canada, South Africa, Chile) have now established folic acid fortification programs, mainly enriching breads, cereals, flours, and other grain products with folic acid (NIH, 2016). The highest amounts of folate are now found among folic acid-enriched cereals (USDA, 2017). The U.S. Food and Drug Administration’s fortification program has aimed to increased folic acid intake by 100 micrograms per day (NIH, 2016). As such, folic acid supplementation is an effective disease-prevention measure for helping to addressing folate deficiency on a large scale. It should also be noted that the National Institute of Health reports that folic acid is more bioavailable (85% availability) than folates naturally present in foods, which are said to have 50% bioavailability and requiring higher intake (NIH, 2016).

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Eat Seeds and Legumes for Higher Natural Folate and Mineral Nutrition

In general, the seeds of fruits and vegetables are very high in iron, zinc, folate and other minerals (USDA, 2017-a). The seed’s outermost layer, known as the pericarp, contains the highest concentration of minerals, helping to strengthen this protective outer layer of the seed. This means that the pericarps of fruit and vegetable seeds are generally the area of the seed highest in mineral content. Seeds are often referred to as nutrient “sinks” because seeds accumulate nutrients for long-term storage from their parent plants (Zhang et al., 2007). The amount of folate in seeds is significant, as seen in table 1.3.

Seeds can also provide the necessary protein and fat content needed to fight many micronutrient deficiencies, as fat intake is important for micronutrient absorption (Wickens, 1995; FAO/WHO, 2002). Pumpkin and squash seeds kernels can provide more than 30 grams of protein per 100 grams of seeds (USDA, 2017-b).

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As such, seed of fruits and vegetables should be considered in malnutrition interventions by relief organizations, in addition to the possible fortification of staple crops. Seeds and legumes keep for a long period of time, acting as a reliable food source throughout the year in drought-stricken regions. Considering the seeds of local fruits and vegetables as well as legume pulses (legume grains) may be an advantageous folate/nutrition source, especially give that pulses and seeds can be stored and keep over the dry season, when other crops are not available.

Legumes also contain an outer layer “coating” structure that is high in minerals and folate. For example, the red layer surrounding kidney beans is good source of minerals, including folate. The high folate content of various legumes can be seen in table 4. From table 4, analysis of the species name of Kidney, Pinto and Black beans shows that many frequently consumed beans are in fact the same species, Phaseolus vulgaris, also known as “the common bean.” Phaseolus vulgaris exists in various varieties. Table 4 shows that although the legume species is the same, nutritional concentrations can differ between varieties, even if their pulses look similar.

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Despite the natural sources of folate, many products may not be the staple crops of a particular region. Furthermore, the strong enrichment programs that exist in some nations may not exist in others. Therefore, when addressing FD in regions endemic with FD, it is important to increase folate intake by promoting food choices or enriched staple crops that are accessible for each particular region.

Critical Analysis of Folate Deficiencies and Supplementation Guidelines

Folic acid supplementation can address anemia but not the potentially permanent neurological damage that can result from vitamin B12 deficiency (NIH, 2016). As such, it is important to beware the affects of masking affect that folate supplementation can have in covering up vitamin B12 deficiency (NIH, 2016). Folate should not be consumed over the recommended upper limits due to possible health risks (NIH, 2016).

As part of a micronutrient deficiency supplementation program, the WHO recommends iron and folic acid supplementation in menstruating women in areas of high anemia prevalence. It is recommended that the supplemental dose of folate be seven times the 400 micrograms daily recommended dose to improve red call folate concentrations and reduce the risk of NTDs in menstruating women (WHO, 2011). Also note that as the neural tube closes by the 28th day of pregnancy, folic acid supplementation after this day will not prevent NTDs (WHO, 2012).

More Resources Moving Forward

National Institute of Health Office of Dietary Supplements: https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

Merck Manuel Professional Version Folate Information: http://www.merckmanuals.com/en-ca/professional/nutritional-disorders/vitamin-deficiency,-dependency,-and-toxicity/folate

Scientific Book on the health benefits of eating seeds and nuts: Preedy V. R., Watson R. W., Patel V.B. (2011). Nuts and Seeds in Health and Disease Prevention. Academic Press. London, UK.

References

1. Basset, G. J., Quinlivan, E. P., Gregory, J. F., & Hanson, A. D. (2005). Folate synthesis and metabolism in plants and prospects for biofortification. Crop Science, 45(2), 449-453.

2. FAO/WHO, Joint (2002). Human vitamin and mineral requirements. Chapter 7. Rome, Food and Agriculture Organization of the United Nations and World Health Organization.

3. Merck Manuel, Professional Version. (2016). Folate (Folic Acid), Nutritional Disorders. Merck & Co., Inc. Retrieved from: http://www.merckmanuals.com/en-ca/professional/nutritional-disorders/vitamin-deficiency,-dependency,-and-toxicity/folate

4. NIH, National Institute of Health. (2016 – last update). Folate. NIH, Office of Dietary Supplements. Retrieved from: https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

5. USDA (United States Department of Agriculture)-a, 2017. USDA Food Composition Databases. Retrieved from: https://ndb.nal.usda.gov/ndb/search/list

6. USDA (United States Department of Agriculture)-b, 2017. USDA Food Composition Databases. Retrieved from: https://ndb.nal.usda.gov/ndb/nutrients/report/nutrientsfrm?max=25&offset=0&totCount=0&nutrient1=417&nutrient2=&nutrient3=&subset=0&sort=c&measureby=g

7. WHO. (2011). Guideline: Intermittent iron and folic acid supplementation in menstruating women. Geneva, World Health Organization.

8. WHO. (2012). Guideline: Daily iron and folic acid supplementation in pregnant women. Geneva, World Health Organization.

9. Wickens, G.E. (1995). Edible Nuts. Rome, Food and Agriculture Organization of the United Nations

10. Zhang, W. H., Zhou, Y., Dibley, K. E., Tyerman, S. D., Furbank, R. T., & Patrick, J. W. (2007). Nutrient loading of developing seeds. Functional Plant Biology, 34(4), 314-331