The Concept of Folic Acid in Health and Disease

Abstract

Folates have a pterine core structure and high metabolic activity due to their ability to accept electrons and react with O-, S-, N-, C-bounds. Folates play a role as cofactors in essential one-carbon pathways donating methyl-groups to choline phospholipids, creatine, epinephrine, DNA. Compounds similar to folates are ubiquitous and have been found in different animals, plants, and microorganisms. Folates enter the body from the diet and are also synthesized by intestinal bacteria with consequent adsorption from the colon. Three types of folate and antifolate cellular transporters have been found, differing in tissue localization, substrate affinity, type of transferring, and optimal pH for function. Laboratory criteria of folate deficiency are accepted by WHO. Severe folate deficiencies, manifesting in early life, are seen in hereditary folate malabsorption and cerebral folate deficiency. Acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure. Given the observational data that folates have a protective effect against neural tube defects, ischemic events, and cancer, food folic acid fortification was introduced in many countries. However, high physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells.

Metagenome-Scale Metabolic Network Suggests Folate Produced by Bifidobacterium longum Might Contribute to High-Fiber-Diet-Induced Weight Loss in a Prader–Willi Syndrome Child

“…The effects of folate production by Bifidobacteria on human health indicate its potential as a probiotic [58] and different strains are known to produce different amounts of folate [59]. Folate was reported to be important for reducing obesity; acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure [60]. Though we could not provide experiment verification due to inapplicability, this evidence supports our findings that high-fiber-induced folate secretion by Bifidobacterium longum strains is important this kind of nutrition therapy that is used for treating obesity.…”

Changes in the Folate Content and Fatty Acid Profile in Fermented Milk Produced with Different Starter Cultures during Storage

“…Folates cannot be synthesized by humans and must be obtained exogenously. The richest sources are animal liver, yeast, wheat germ, and green leafy vegetables, such as spinach, broccoli and asparagus, and pulses [ 4 ]. Folates belong to the water-soluble B vitamins group and are essential components of the human diet for the synthesis reaction of nucleotides and vitamins.…”

“…Despite such an important role, acquired folate deficiency is common and affects billions of people worldwide, both in developing and developed countries and in different age groups. This micronutrient deficiency is associated with poor diet, malabsorption, alcohol consumption, obesity, and kidney failure [ 1 , 4 ]. An increased risk of folate deficiency especially concerns the elderly (because of lower food intake), children (who are likely to consume a limited variety of food), and pregnant women (because of the critical role of folates in fetus neural tube development).…”

“…An increased risk of folate deficiency especially concerns the elderly (because of lower food intake), children (who are likely to consume a limited variety of food), and pregnant women (because of the critical role of folates in fetus neural tube development). Low folate intake increases the risk of birth defects (spina bifida, anencephaly, encephalocele) [ 4 ]. Prolonged insufficient folate consumption is also linked to macrocytic anemia, cardiovascular diseases, neurodegenerative diseases (Alzheimer’s, Parkinson’s), certain forms of cancers (colorectal, breast, cervical, lung, pancreatic cancer), and even an increased risk of depressive mental disorders [ 6 , 7 ].…”

“…Moreover, higher levels of synthetic folic acid in the diet can cause adverse effects, such as masking a vitamin B12 deficiency, which may result in the progression of neuropathy to an irreversible point [ 11 ]. Moreover, high physiological folate concentrations and folate overload, as a result of excessive supplementation with folic acid, may increase the risk of impaired brain development in embryogenesis and even possess a growth advantage for pre-cancerous altered cells [ 4 , 5 ]. Therefore, due to the potential risk of using synthetic folic acid, but also limited availability of folate-rich foods (depending on the season and geographic and economic factors), food fortification by natural folate is a necessary alternative [ 9 ].…”