“Folates”, also known as vitamin B9, is a generic term for folic acid and its derivatives – dihydro-, tetrahydro-, methyl- and formyl compounds – which have metabolic activity. B9 is a water-soluble vitamin that occurs naturally in a variety of foods such as broccoli, cabbage, cauliflower, fruit and nuts. Like some other vitamins, folates cannot be synthesized in mammalian cells and are obtained from exogenous sources such as food. Polyglutamylated folic acid, tetrahydrofolate (THF), 5-methyl-THF and 5,10-formyl-THF are ubiquitously present in foods. Low folate status in all populations, caused by reduced intake or health conditions, is associated with a number of health problems, such as megaloblastic anemia, increased cardiovascular risk and colorectal cancer, and neurocognitive decline in the elderly.
To improve folate status in the population, especially in women of childbearing age, many countries have introduced folic acid fortification through food supplements and fortified foods. For example: to prevent neural tube defects in newborns, the WHO recommends an intake of 400 µg per day from conception to the twelfth week of pregnancy.
Folate supplements include the oxidized form, folic acid, and the reduced form, mainly methyltetrahydrofolate ((6S)-5-MTHF) as calcium, monosodium or glucosamine salt.
Folic acid, a synthetic oxidative form, is often used in food supplements because of its low price, satisfactory thermostability and bioavailability. However, folic acid has no coenzyme activity and must be reduced in the cells to the metabolically active form, tetrahydrofolate. 5-MTHF is the predominant form of folate in the diet and is considered a better alternative to folic acid as it is less likely to mask symptoms of B12 deficiency in older people, however it is less stable and particularly sensitive to oxygen and moisture. Therefore, more stable salts of 5-MTHF are being developed and used as food supplements.
HEALTH CLAIMS
European legislation has approved claims based on sound and independent scientific evidence that may be included in the labeling of food supplements.
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“Folate contributes to maternal tissue growth during pregnancy”
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“Folate contributes to normal amino acid synthesis”
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“Folate contributes to normal blood formation”
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“Folate contributes to normal homocysteine metabolism”
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“Folate contributes to normal psychological function”
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“Folate contributes to the normal function of the immune system”
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“Folate contributes to the reduction of tiredness and fatigue”
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“Folate has a role in the process of cell division”
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“Supplemental folic acid intake increases maternal folate status. Low maternal folate status is a risk factor in the development of neural tube defects in the developing fetus”
Food supplements manufacturers must ensure that all consumers can trust the health benefits claimed on the food supplements and make well-informed choices because the results from consumption of food supplements and fortified food can only be achieved if these products have confirmed quality in accordance with the declared values.
Recent studies on content determination of food supplements with folic acid showed huge differences with declared folate content which emphasize the need to implement improvements in the quality control of food supplements by the manufacturers and regulatory organs.
QUALITY CONTROL
Typically, food manufacturers include overdosage of the active ingredient (up to 50%) to overcome issues related to the poor quality and/or stability of folic acid and its derivatives, but recent expert opinion on the tolerable upper intake level for folate conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorized forms, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts), namely risk of cobalamin-dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer, raised concerns for the regular users of food supplements containing high doses of folic acid/5-methyltetrahydrofolic acid salts. Caution is also advised with high doses of maternal supplements (≥1000 μg/day), as recent research has shown that this can have a negative impact on birth outcomes and the cognitive development of children later in life.
The saturated market for food supplements needs to be more regulated and products must be tested to ensure safety and quality.
Water-soluble folic acid and folate derivatives are added to supplements and fortified food in µg and mixed with complex matrices, so analysis must be performed with a sensitive and selective analytical method to ensure reliable results. In addition, it is well known that folic acid and its derivatives are not stable under many conditions and it is recommended to follow up the content by stability studies.
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