Folic acid daily requirements

In acute and chronic urinary tract infection, the combination of trimethoprim and sulfamethoxazole (Bactrim, Septra) exerts a truly synergistic effect on bacteria. The sulfonamide inhibits the utilization of p-amino-benzoic acid in the synthesis of folic acid, whereas trimethoprim, by inhibiting dihydrofolic acid reductase, blocks the conversion of dihydrofolic acid to tetrahydrofolic acid, which is essential to bacteria in the de novo synthesis of purines, pyrimidines, and certain amino acids. Because mammalian organisms do not synthesize folic acid, but require it as a vitamin in their daily diets, trimethoprim-sulfamethoxazole does not interfere with the metabolism of mammalian cells. 

Folic deficiency was thought to be rare in humans, but more and more cases of deficiency were reported as the methods for diagnosis improved. It is now sometimes assumed to be one of the most common vitamin deficiencies. In humans, megaloblastic anemia develops after five months of administration of a folic acid-deficient diet, suggesting that it takes that long to deplete the body of its folic acid reserves or sources. The exact human requirements for folic acid are unknown, but it is estimated that 50-250 pg of folic acid is required daily in adults and 5-20 pg in infants. These figures are based on the hematological response observed in patients with folic acid deficiency. 

Spinach, salad, cereal germ, and bran as well as pulses are good sources of folic acid. Liver and yeast contain high amounts of this vitamin, too, but are not consumed frequently enough to be relevant for the coverage of daily requirements [1,2]. 

When treating folic acid deficiency, an initial daily dose of 1 mg/day by mouth typically is effective. Absorption of folic acid generally is rapid and complete. However, patients with malabsorption syndromes may require larger doses (up to 5 mg/day). Similar to vitamin B12 deficiency, resolution of symptoms and reticulocytosis is prompt, occurring within days of commencing therapy. Hgb will start to rise after 2 weeks of therapy and may take from 2 to 4 months to resolve the deficiency completely. Afterwards, if the underlying deficiency is corrected, folic acid replacement can be discontinued. However, in cases where folic acid is consumed rapidly or absorbed poorly, chronic replacement may be required. 

Addisonian pernicious anemia - Parenteral therapy is required for life oral therapy is not dependable. Administer 100 meg daily for 6 or 7 days by IM or deep subcutaneous injection. If there is clinical improvement and a reticulocyte response, give the same amount on alternate days for 7 doses, then every 3 to 4 days for another 2 to 3 weeks. By this time, hematologic values should have become normal. Follow this regimen with 100 meg monthly for life. Administer folic acid concomitantly if needed. 

About 10-25%, i.e. 50-200 pg, of the daily dietary intake of folic acid in yeasts, liver, and green vegetables is absorbed via active and passive transport in the proximal jejunum. As humans do not have dihydropteroate synthetase, which synthesizes folic acid in bacteria, we require folic acid in the diet. Only small amounts of folate can be stored in the body and dietary deficiency for only a few days can result in symptomatic folate deficiency. 

Parenteral administration of folic acid is rarely necessary, since oral folic acid is well absorbed even in patients with malabsorption syndromes. A dose of 1 mg folic acid orally daily is sufficient to reverse megaloblastic anemia, restore normal serum folate levels, and replenish body stores of folates in almost all patients. Therapy should be continued until the underlying cause of the deficiency is removed or corrected. Therapy may be required indefinitely for patients with malabsorption or dietary inadequacy. Folic acid supplementation to prevent folic acid deficiency should be considered in high-risk patients, including pregnant women, patients with alcohol dependence, hemolytic anemia, liver disease, or certain skin diseases, and patients on renal dialysis. 

Recommended daily requirement [RDA) or adequate intake CAQ for men and nonpregnant women over 20 years old. Recommended values for certain vitamins Ce.g., folic acid) may be higher in women who are pregnant. Values for children are typically lower, and are adjusted according to the child s age. 

Supplementation with the antioxidant vitamins ascorbic acid (250 mg) and mixed natural tocopherols (50 IU on alternate days) may be beneficial. Higher doses may vitiate the impact of lipid lowering therapy. Other naturally occurring antioxidants such as resveratrol, 3-catechin, selenium, and various carotenoids found in a variety of fruits and vegetables may provide additional antioxidant defense. Homocysteine, which initiates proatherogenic changes in endothelium, can be reduced in many patients by restriction of total protein intake to the amount required for amino acid replacement. Daily supplementation with up to 2 mg of folic acid plus other B vitamins is also recommended. 

It is estimated that the minimum daily requirement of folate is 5 micrograms/kg. Liver stores are about 160 micrograms in premature children, and 220 micrograms in full-term infants. Infants who require parenteral nutrition will rapidly become folate deficient unless fohc acid is included in the regimen. Since many multivitamin supplements do not contain folic acid, its inclusion should be ensured by the addition of folic or folinic acid. 

Based on folate concentrations in liver biopsy samples, and assuming that the liver contains about half of ail body stores, total body stores of folate are estimated to be between 12 and 28 Kinetic studies that show both fast-turnover and very-slow-turnover folate pools indicate that about 0.5% to 1% of body stores are catabolized or excreted daily,suggesting a minimum daily requirement of between 60 and 280)Llg to replace losses. In calculating nutritional requirement, the concept of dietary folate equivalents (DFE) has been used to adjust for the nearly 50% lower bioavailabihty of food folate compared with supplemental folic acid, such that 1 p.g DFE = 0.6 Llg of folic acid from fortified food = 1 j,g of food folate 0.5 p.g foUc acid supplement taken on an empty stomach. Before the fortification program of cereal grains with folic acid conducted between 1988 and 1994, the median intake of folate from food in the United States was approximately 250p.g/day this figure is expected to increase by about 100 Llg/day after fortification. Recommendations... 

Folic acid deficiency is one of the most common vitamin deficiencies in the United States, largely due to its association with excessive alcohol intake and pregnancy. Requirements for folate in pregnancy are about five times higher than normal daily requirements. 

Supplementation with folic acid [400 meg daily starting 1 week before first dose continued days after last dose] and vitamin B 2 [1000 meg IM during week prior to first dose and even cycles thereafter] is required during administration to reduce toxicity. 

Little information is available concerning alterations in vitamin requirements in ARF. Reduced plasma concentrations of vitamin A, ascorbate, vitamin D, and vitamin E have been reported in patients with ARF, whereas vitamin K concentrations are relatively increased. Losses of vitamins via dialysis also must be considered. Traditional HD clears several water-soluble vitamins such as folic acid, vitamins C and B12, and pyridoxine, but not the highly protein-bound vitamins A and D. The clinical significance of these findings in ARF is unknown. Currently, it seems prudent to administer vitamins at least daily in doses recommended by the Nutrition Advisory Group of the American Medical Association for patients receiving PN (see Chap. 137)." Administration of ascorbic acid should be restricted to under 200 mg/day to avoid secondary oxalosis which may worsen renal function." If the enteral route is used for nutritional support, vitamin administration should at least meet the recommended daily allowances (RDAs). 

Considerable uncertainty and controversy exists concerning the folate requirement for humans. Hie review of data concerning the human folate requirement by the Food and Nutrition Board (1989) suggests that the daily maintenance requirement is 100-200 fig of avaUable folic acid equivalents. The 1989 RDAs were reduced to 200 and 180 fig for adult men and women, respectively, from the previous RDA of 400 on the basis of such evidence (Food and Nutrition Board, 1989). Similarly, the Canadian RDA for folate was set at 3 /ig/kg body wt or 210 fig for a 70-kg individual. These lower RDAs may be inadequate for certain population groups, however (Sauberlich, 1990 Bailey, 1992 McPartlin etai, 1 3). It is currently difficult or impossible to predict the quantitative effect on folate nutritional status of factors such as (a) changes in folate intake, (b) differences in folate bioavailability, (c) effects of pregnancy and lactation on folate requirements, and (d) pharmaceuticals with antifolate properties. In addition, the development of mathematical models would improve our ability to evaluate methods of nutritional status assessment for this vitamin. 

Specific treatment schedules are devised for patients with one of the various forms of congenital metabolic disturbance of cobalamin metabolism. In general these conditions require daily injections, sometimes in combination with folic acid, carnitine, betaine, or choline (50). 

---