Recommended folate

Folate antagonists (eg, methotrexate and certain antiepileptics) are used ia treatment for various diseases, but their adininistration can lead to a functional folate deficiency. Folate utilization can be impaired by a depletion of ziac (see Zinc compounds). In humans, the intestinal bmsh border folate conjugase is a ziac metaHoenzyme (72). One study iadicates that the substantial consumption of alcohol, when combiaed with an iaadequate iatake of folate and methionine, may iacrease the risk of colon cancer (73). Based on this study, it is recommended to avoid excess alcohol consumption and iacrease folate iatake to lower the risk of colon cancer. 

The amount of foHc acid required for daily iatake is estimated based oa the minimum amouat required to maintain a certaia level of semm folate. The recommeaded dietary allowance (RDA) for foHc acid accounts for daily losses and makes allowances for variation ia iadividual aeeds and bioavailabiUty from food sources (85). The U.S. recommended daily allowance for adults is 400 p.g and for pregnant women is 800 ]1 (Table 4). 

The folate antagonists, pyrimethamine and sulfadiazine, inhibit the parasite s DHFR/TS synthase enzyme complex and the DHPS, respectively (Fig. 4) (see antimalarial drugs). To avoid deficiency of folic acid in patients treated with antifolate antagonists, folinic acid supplementation is recommended to reduce bone-marrow suppression. 

Milk is an excellent source of calcium, phosphorus, riboflavin (vitamin B2), thiamine (vitamin Bl) and vitamin B12, and a valuable source of folate, niacin, magnesium and zinc (Food Standards Agency, 2002). In particular, dairy products are an important source of calcium, which is vital for maintaining optimal bone health in humans (Prentice, 2004). The vitamins and minerals it provides are all bioavailable (i.e. available for absorption and use by the body) and thus milk consumption in humans increases the chances of achieving nutritional recommendations for daily vitamins and mineral intake (Bellew et al., 2000). 

Folate deficiency The recommended dietary intake of folate has been increased (also protects against neural tube defects in the fetus), and additional folate is now added to flour (bread, pasta, and other products made liom flour)... 

Anti-epileptic drugs, such as phenytoin, carbamazepine and valproate, may lead to neural tube defects if administered during pregnancy. Concurrent administration of folate supplements, such as folic acid, is recommended. 

Except during pregnancy and lactation, do not give folic acid in therapeutic doses greater than 0.4 mg/day until pernicious anemia has been ruled out. Do not include daily doses exceeding the Recommended Dietary Allowance in multivitamin preparations if therapeutic amounts are necessary, give folic acid separately. Elderly It may be prudent to consider the status of folate in people older than 65 years of age. 

Folate deficiency Folate deficiency states may increase methotrexate toxicity. Benzyl alcohol Methotrexate sodium for injection contains the preservative benzyl alcohol and is not recommended for use in neonates. 

Folate play an important role in the biosynthesis of DNA bases and in amino acid metabolism. An adeguate intake of folate reduces the risk of abnormalities in early embryonic brain development, specifically the risk of malformations of the embryonic brain/spinal cord. Therefore a proper intake is strictly recommended for pregnant women. Megaloblastic anemia is the ultimate consequence of an inadequate folate intake. No adverse effects have been associated with the consumption of excess folate from foods [417]. 

An important indication for folic acid has become the prevention of neural tube defects when given to women three months before conception and during the first trimester. The Recommended Dietary Allowance (RDA) for folate equivalents for pregnant women is 600-800 pg, twice the normal RDA of 400 pg for women who are not pregnant. 

Prescribing perspective necessitates an awareness of this diagnostic possibility and its reliable separation from simple folate or vitamin B12 deficiency. Here cytogenetic studies may be crucial. Once the diagnosis has been made a number of individuals are seen not to be suitable for aggressive intervention. In this situation the use of stimulatory peptides is of value but are expensive and should therefore be used only on the recommendation of an experienced clinical haematologist. 

Several drugs closely related to the sulfonamides have been used effectively in the long-term treatment of leprosy. The most widely used is dapsone (diaminodiphenylsulfone). Like the sulfonamides, it inhibits folate synthesis. Resistance can emerge in large populations of M leprae, eg, in lepromatous leprosy, if very low doses are given. Therefore, the combination of dapsone, rifampin, and clofazimine is recommended for initial therapy. Dapsone may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS patients. 

Sulfasalazine has a high incidence of adverse effects, most of which are attributable to systemic effects of the sulfapyridine molecule. Slow acetylators of sulfapyridine have more frequent and more severe adverse effects than fast acetylators. Up to 40% of patients cannot tolerate therapeutic doses of sulfasalazine. The most common problems are dose-related and include nausea, gastrointestinal upset, headaches, arthralgias, myalgias, bone marrow suppression, and malaise. Hypersensitivity to sulfapyridine (or, rarely, 5-ASA) can result in fever, exfoliative dermatitis, pancreatitis, pneumonitis, hemolytic anemia, pericarditis, or hepatitis. Sulfasalazine has also been associated with oligospermia, which reverses upon discontinuation of the drug. Sulfasalazine impairs folate absorption and processing hence, dietary supplementation with 1 mg/d folic acid is recommended. 

LB Bailey. Folate intake recommendations from a nutritional science perspective. Cereal Foods World 40 63-66, 1995. 

Herbert V (1987a) Recommended dietary intakes (RDI) of folate in humans. American Journal of Clinical Nutrition 45, 661-70. 

Folate is a water-soluble vitamin. The recommended daily allowances (RDAs) of folate for the adult man and woman are 20fJ and 101) pg, respectively. The RDA is defined in the Preface. Folate is critically important for growth, and for this reason it is required in increased amounts during pregnancy (400 pg. The need for dietary folate remains elevated after pregnancy and during lactation because of the Irans-... 

Molioy, A. M., Daly S Mills, ]. L., Kirke, J Whitehead, A., Ramsbottom, D., Conley, M., W eir, D. C-, and Scott,). M. (1997). Thermolabile variant of 5,10-methyleneletrahydro-folate reductase associated with low reti-oell folates Implications for folate intake recommendations. Littcft 349, 1591-1593. 

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