Folic acid excretion

In humans and rats, early investigations showed that large doses of folic acid resulted in increased excretion of a substance that stimulated the growth of P. cerevisiae and that was presumed to be citrovorum factor.45 This response is now also associated with other reduced folates. 

For correlation with the serum folic acid, FIGlu determinations were carried out using two methods (L9, S6). Both proved insensitive, notably where no urinary FIGlu was excreted despite clinical proof of PGA deficiency. 

A4. Anderson, B., Belchar, E. H., Chanarin, I., and Mollin, D. L., The urinary and fecal excretion of radioactivity after oral doses of 3H-folic acid. Brit. J. Haematol. 6, 439-455 (1960). 

Excretion of thiamine appears to vary from individual to individual,23 and some other data are available regarding the other better-known B vitamins.24 The differences in the excretion of nicotinic acid-like compounds strongly suggest the existence of individual pattems.25,26 The urinary excretion of vitamin B12, folic acid, and the citrovorum factor by different individuals, even on controlled diets, was found to vary through rather wide ranges (2- to 9-fold) though the study was not concerned with individual differences and individual patterns were not established. 27... 

Folic acid appears in the plasma approximately 15 to 30 minutes after an oral dose peak levels are generally reached within 1 hour. After IV administration, the drug is rapidly cleared from the plasma. Folic acid is metabolized in the liver. Normal serum levels of total folate have been reported to be 5 to 15 ng/mL normal CSF levels are approximately 16 to 21 ng/mL. In general, folate serum levels less than 5 ng/mL indicate folate deficiency, and levels less than 2 ng/mL usually result in megaloblastic anemia. A majority of the metabolic products appeared in the urine after 6 hours excretion was generally complete within 24 hours. 

Lactation Folic acid is excreted in breast milk. 

As indicated earher, sulfonamides are effective in both gram-positive and gramnegative bacteria. Mostly prescribed for humans in the United States, in this class is sulfamethoxazole, mostly in combination with trimethoprim (SMZ-TMP) in a 5 1 ratio. Trimethoprim inhibits dihydropholic acid reductase and this, just like sulfonamides, also interferes with the synthesis of folic acid (Fig. 1.8). As a matter of fact, use of the combined SMZ-TMP has been steadily increasing recently as is displayed by the number of prescriptions (Fig. 1.7). Oral doses of sulfonamides are absorbed well and eliminated by the liver and kidney with 20-60% excreted as the parent compound (Queener and Gutierrez, 2003). 

Once a diagnosis of megaloblastic anemia is made, it must be determined whether vitamin B12 or folic acid deficiency is the cause. (Other causes of megaloblastic anemia are very rare.) This can usually be accomplished by measuring serum levels of the vitamins. The Schilling test, which measures absorption and urinary excretion of radioactively labeled vitamin B12, can be used to further define the mechanism of vitamin Bi2 malabsorption when this is found to be the cause of the megaloblastic anemia. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

Vitamins and Minerals. Milk is a rich source of vitamins and other organic substances that stimulate microbial growth. Niacin, biotin, and pantothenic acid are required for growth by lactic streptococci (Reiter and Oram 1962). Thus the presence of an ample quantity of B-complex vitamins makes milk an excellent growth medium for these and other lactic acid bacteria. Milk is also a good source of orotic acid, a metabolic precursor of the pyrimidines required for nucleic acid synthesis. Fermentation can either increase or decrease the vitamin content of milk products (Deeth and Tamime 1981 Reddy et al. 1976). The folic acid and vitamin Bi2 content of cultured milk depends on the species and strain of culture used and the incubation conditions (Rao et al. 1984). When mixed cultures are used, excretion of B-complex vita-... 

Factors which cause a decrease in bioavailability include 111 high urinary excretion (2) destruction by certain mlesiinal bacteria (2) increased urinary excretion caused by vitamin C (4) presence of sulfonamides which block intestinal synthesis and (5) a decrease in absorption mechanisms. Increase in bioavailability can be provided by stimulating intestinal bacterial synthesis in certain species. No toxicity due to folic acid has been reported in humans. 

Pyrimethamine acts synergistically with suifadoxine (as Fansidar) to inhibit folic acid metabolism (see antifols, above) suifadoxine is excreted in the urine. The combination is chiefly used with quinine to treat acute attacks of malaria caused by susceptible strains of Plasmodium falciparum a single dose of pyrimethamine 75 mg plus suifadoxine 1.5 g (3 tablets) usually suffices. 

Vitamin M Vitamin M is also called pteroylglutaminic add or folic acid. It was isolated from yeast extract by Wills in 1930. Its structure was described by Anger in 1946. Folic add is made up of pteridine + p-aminobenzoic add + glutamic add. There are several known derivatives, called folates, which are capable of mutual restructuring. The coenzyme tetrahydrofolic acid, which plays a role in many biochemical reactions, is formed with the help of Bi2. Around 50% of total body folate are stored in the liver. A folate-binding protein (FBP) is available for transport. Folate undergoes enterohepatic circulation. The release of folate from the liver cells is stimulated by alcohol, which increases urine excretion. Folate deficiency (e.g. in the case of alcohol abuse) is accompanied by the development of macrocytosis. 

Rabinowitz, j. C, and Tabor, fl- (1958). The urinary excretion of formic acid and fonmimi-nogtutamic acid in folic acid deficiency /. Biol. Chem. 233, 252-253,... 

The sulfonamides are a group of organic compounds with chemotherapeutic activity they are antimicrobial agents and not antibiotics. They have a common chemical nucleus that is closely related to PABA, an essential component in the folic acid pathway of nucleic acid synthesis. The sulfonamides are synergistic with the diaminopyrim-idines, which inhibit an essential step further along the folate pathway. The combination of a sulfonamide and a diaminopyrimidine is advantageous because it is relatively non-toxic to mammalian cells (less sulfonamide is administered) and is less likely to select for resistant bacteria. Only these so-called potentiated sulfonamides are used in equine medicine. These drugs are formulated in a ratio of one part diaminopyrimidine to five parts sulfonamide, but the optimal antimicrobial ratio at the tissue level is 1 20, which is achieved because the diaminopyrimidines are excreted more rapidly than the sulfonamides. 

Peak serum levels occur within 30-60 mm. Folic acid is converted in the liver to tetrahydrofolic acid in the presence of ascorbic acid by dihydrofolate reductase. Tetrahydrofolic acid and its derivatives are distributed into all body tissues with approximately half of it in the liver. It is excreted renally almost entirely as metabolite. Excessive amounts of folic acid (beyond the daily needs) are excreted unchanged in the urine. 

Water-soluble vitamins are absorbed in water in the small intestine and excreted in urine, except for folic acid. They are not stored in the body therefore, the body requires a continuous supply of water-soluble vitamins. 

Vitamin C is used to metabolize carbohydrates, for tissue repair and capillary endothelium, and for synthesis of protein, lipids, and collagen. Vitamin C is also needed for absorption of iron and folic acid metabolism. Vitamin C is found in citrus fruits, tomatoes, leafy green vegetables, and potatoes. Excess serum levels of vitamin C are excreted without any negative effects. Vitamin C is commercially available as Ascorbicap, Cecon, Cevalin, and SoluCap C. 

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... 

Krumdieck CL, Fukushima K, Fukushima T, Shiota T, Butterworth CE, Jr. A long-term study of the excretion of folate and pterins in a human subject after ingestion of 14C folic acid, with observations on the effect of diphenyUiydantoin administration. Am J Clin Nutr 1978 31 88-93. 

Shuster et al. (Sll) measured B12 levels in the sera of 20 patients with psoriasis and found normal levels in all but one. Folic acid levels were decreased below normal in 21 out of 28 patients, urinary FIGLU excretion was elevated in 19 of 30, and in 5 of 9 patients sternal marrow puncture revealed megaloblastic erythropoiesis, thereby implying a true folate deficiency. Neither serum iron deficiency nor lack of absorption of folate could be implicated as a cause of the folate deficiency, and presumably it is related to the skin lesions. 

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