Folic Acid Supplements

It is recommended that women of childbearing age take 400 pg/d synthetic folic acid as a supplement in order to reduce the risk of neural tube defects of the embryo when they later become pregnant (periconcep-tional folic acid supplementation) [2]. When supplementing folic acid, it should be considered that this vitamin can mask the simultaneous presence of vitamin B12 deficiency. The typical symptom of vitamin B12 deficiency, megaloblastic (= macrocytic) anemia, will be reduced by high doses of folic acid, yet the nervous system will - in the long run - be irreversibly damaged (= funicular myelitis) when vitamin B12 is not provided as well. 

Give supplemental folic acid, 1-4 mg daily, to all women of child-bearing potential Use monotherapy whenever possible Use the lowest doses that control seizures Continue pharmacotherapy that best controls seizures prior to pregnancy... 

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... 

D. Clinical Use and Toxicity Folic acid deficiency is most often caused by dietary insufficiency or by malabsorption. Anemia due to folic acid deficiency is readily treated by oral folic acid supplementation. Folic acid supplements will also correct the anemia but not the neurologic deficits of vitamin B, deficiency. Therefore, vitamin B 2 deficiency must be ruled out before one selects folic acid as the sole therapeutic agent in the treatment of a patient with megaloblastic anemia. Folic acid has no recognized toxicity. 

Supplement folic acid deficiency states, impaired absorption, increased requirements (pregnancy, increased stimulation with exogenic estrogens) treatment with folic acid antagonists... 

The results of the RCTs are in contrast to a number of observational cohort studies that report either a reduced risk for those participants ingesting high amounts of food folate or supplemental folic acid, or those having the highest... 

However, the protective effect of supplemental preconceptional folic acid for the prevention of neural tube defects in women of childbearing age is proven. This seems to be the only proven protective effect of supplemental folic acid intake. 

Whitrow MJ, Moore VM, Rumbold AR, Davies MJ. Effect of supplemental folic acid in pregnancy on childhood asthma a prospective birth cohort study. Am J Epidemiol 2009 170(12) 1486-93. 

Claradiastase and trypsin in phosphate buffer have been used for hydrolysis of sample matrix for the determination of supplemental folic acid (27). Jacoby and Henry (26) further modified the method of Hoppner and Lampi (41) for folic acid by HPLC, in which the folic acid added to infant formulas and liquid medical nutritionals is quantitatively extracted with the aid of bacterial protease and papain. One disadvantage of the enzymatic extraction method was the large number of UV-absorbing compounds that are formed during enzymatic hydrolysis. These can interfere in the quantitation of the folate peaks. Thus, addition of a-amylase and protease to enhance extraction has not been common practice for methods involving HPLC. However, Pfeiffer et al. (13) suceessfiilly used triple-enzyme treatment prior to HPLC analysis with a purification method based on affinity chromatography. 

Folate is important for cells and tissues that divide rapidly therefore, high-dose methothrexate is often used to treat cancer because this compound interferes with folate metabolism. Methothrexate, however, has undesirable side effects, including inflammation in the digestive tract. It is not known whether folic acid supplementation can help control these side effects without decreasing the effectiveness of methro-threxate. Low-dose methothrexate is used to treat a variety of diseases, such as rheumatoid arthritis, lupus, psoriasis, asthma, and inflammatory bowel disease. Low-dose treatment can deplete folate stores and cause side effects similar to folate deficiency. In this case, supplemental folic acid may help reduce the undesirable effects of low-dose methothrexate without decreasing treatment effectiveness. 

In terms of amino acids bacterial protein is similar to fish protein. The yeast s protein is almost identical to soya protein fungal protein is lower than yeast protein. In addition, SCP is deficient in amino acids with a sulphur bridge, such as cystine, cysteine and methionine. SCP as a food may require supplements of cysteine and methionine whereas they have high levels of lysine vitamins and other amino acids. The vitamins of microorganisms are primarily of the B type. Vitamin B12 occurs mostly hi bacteria, whereas algae are usually rich in vitamin A. The most common vitamins in SCP are thiamine, riboflavin, niacin, pyridoxine, pantothenic acid, choline, folic acid, inositol, biotin, B12 and P-aminobenzoic acid. Table 14.4 shows the essential amino acid analysis of SCP compared with several sources of protein. 

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. 

Methyl-tetrahydro folic acid is furthermore, together with vitamin B12 and B6, required to regenerate homocysteine (see Vitamin B12, Fig. 1). Homocysteine results when methionine is used as a substrate for methyl group transfer. During the last few years, homocysteine has been acknowledged as an independent risk factor in atherosclerosis etiology. Folic acid supplementation can help reduce elevated homocysteine plasma levels and is therefore supposed to reduce the risk of atherosclerosis as well [2]. 

Overall, supplementation with folic acid is considered safe as the vitamin has low acute and chronic toxicity. 

Folic Acid Supplements Reduce the Risk of Neural Tube Defects Hyperhomocysteinemia... 

Elevated homocysteine concentrations have been associated with an increased risk for cardiovascular disease in both epidemiologic and clinical studies.43 Several studies have evaluated the benefit of lowering homocysteine levels with folic acid supplementation. One study reported a reduction in major cardiac events with the combination of folic acid, vitamin B12, and vitamin B6 following PCI.44 However, a more recent study found an increased risk of instent restenosis and the need for target-vessel revascularization with folate supplementation following coronary stent placement.45 The role of folate in the management of IHD is currently unclear. 

No specific dietary restrictions are recommended for patients with IBD, but avoidance of high-residue foods in patients with strictures may help to prevent obstruction. Nutritional strategies in patients with long-standing IBD may include use of vitamin and mineral supplementation. Administration of vitamin B12, folic acid, fat-soluble vitamins, and iron may be needed to prevent or treat deficiencies. In severe cases, enteral or parenteral nutrition maybe needed to achieve adequate caloric intake. 

Water-soluble vitamins removed by hemodialysis (HD) contribute to malnutrition and vitamin deficiency syndromes. Patients receiving HD often require replacement of water-soluble vitamins to prevent adverse effects. The vitamins that may require replacement are ascorbic acid, thiamine, biotin, folic acid, riboflavin, and pyridoxine. Patients receiving HD should receive a multivitamin B complex with vitamin C supplement, but should not take supplements that include fat-soluble vitamins, such as vitamins A, E, or K, which can accumulate in patients with renal failure. 

Folic acid supplementation with 1 mg daily generally is recommended in adult SCD patients, women considering pregnancy, and any SCD patient with chronic hemolysis.6 Because of accelerated erythropoiesis, these patients have an increased need for folic acid. There are conflicting studies in the SCD population, especially among infants and children, but if the child has chronic hemolysis, supplementation is recommended.21... 

Administer prophylactic folic acid supplementation to SCD patients receiving hydroxyurea because folate deficiency may be masked by the use of hydroxyurea. 

Prognosis is more favorable in the pyridoxine-respon-sive patients. Patients who respond to large doses of vitamin B6 (250-500 mg/day for several weeks) have the best prognosis. Efficacy of treatment usually is reflected in a reduction of blood homocystine and methionine to normal or near-normal levels. Since supplementation with pyridoxine can cause a deficiency of folic acid, the latter should be given (2-5 mg daily) at the same time. Any patient receiving pyridoxine should be monitored carefully for any signs of hepatotoxicity and for a peripheral neuropathy (see Ch. 36). 

Folic acid supplementation, 1 mg twice daily, should be given. 

Patients receiving sulfasalazine should receive oral folic acid supplementation since sulfasalazine inhibits folic acid absorption. 

All women with epilepsy should take a folic acid supplement, 0.4 to 5 mg daily. 

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