Folic bioavailability

With investigations of phytochemicals and functional foods, the outcome measure is generally going to be a biomarker of disease, such as serum cholesterol level as a marker of heart disease risk, or indicators of bone turnover as markers of osteoporosis risk. Alternatively, markers of exposure may also indicate the benefit from a functional food by demonstrating bioavailability, such as increased serum levels of vitamins or carotenoids. Some components will be measurable in both ways. For instance, effects of a folic acid-fortified food could be measured via decrease in plasma homocysteine levels, or increase in red blood cell folate. 

New derivatives of 4-amino and 2,4-diaminopteridines have been synthesized and their capability to inhibit neuronal nitric oxide synthase evaluated <99JMC4108>. The synthesis of folic acid multiply labeled with stable isotopes, for bioavailability studies in human nutrition, has been reported <99JCS(P1)1311>, Synthesis and antiviral evaluation of several 6-(methylenecarbomethoxy)pteridine-4,7-diones have been described <99JHC435>. Synthesis and biochemical evaluation of bis(6,7-dimethyl-8-D-ribityllumazines) as potential bisubstrate analog inhibitors of riboflavin synthase have been reported <99JOC4635>. Synthesis and cyclization of novel lumazine-enediyne chimeras have been reported <99H13>. 

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. 

Folacin bioavailability varies among the vitamers (120,125). Folic acid is more readily available than the naturally occurring food folates but may be less available from fortified foods than in aqueous solution or tablet form. Food folates have been reported to be 30-80% as available as folic acid. Folacin availability, absorption, and metabolism were recently reviewed (20,120,122). 

Nutritionally, the most important water-soluble vitamins in citrus fruits are ascorbic acid, folic acid and pyridoxine. Clinical studies on the bioavailability of these vitamins, as well as basic research on the absorption and chemistry of these vitamins, have yielded valuable information adding to our overall understanding of the nutritional quality and bioavailability of these vitamins found in citrus fruits. 

Canola meal is a good source of choline, niacin and riboflavin, but not folic acid or pantothenic acid. It contains one of the highest levels of biotin found typically in North American feed ingredients. Total biotin in canola meal was found to average 1231 pg/kg with a bioavailability for growing broilers of 0.66 compared with 0.17 for wheat, 0.2 for triticale, 0.21 for barley, 0.39 for sorghum, 0.98 for soybean meal and 1.14 for maize (Blair and Misir, 1989). 

The mechanism of absorption must always be evaluated when a sustained-release dosage form is considered. A drug that is passively absorbed throughout the GI tracts is an ideal candidate for sustained release. Drugs such as riboflavin, folic acid, aminopenicillins, amino-p-lactams and nucleoside analogs, which have windows of absorption due to site-specific and/or active transport processes, may have incomplete bioavailability when formulated in oral, sustained-release dosage forms. 

Magnesium silicate may decrease the oral bioavailability of drugs such as mebeverine hydrochloride, sucralfate, and tetracycline, via chelation or binding, when they are taken together. The dissolution rate of folic acid, erythromycin stearate, paracetamol, " and chloroquine phosphate, " may be retarded by adsorption onto magnesium silicate. Antimicrobial preservatives, such as parabens, may be inactivated by the addition of magnesium silicate. ... 

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. 

It has been repeatedly shown that intestinal transport of folic acid and of its derivatives has a pH-optimum of 6. Folic acid bioavailability is reduced in certain clinical situations where human jejunal pH deviates from this value, such as sodium hydro-gencarbonate dosing, prolonged administration of... 

Gregory III, J. R, Bhandari, S. D., Bailey, L. B., Toth, J. P., Baumgartner, T.G., and Cerda, J.J. 1992. Relative bioavailability of deuterium-labeled monoglutamyl tetrahy-drofolates and folic acid in human subjects. Am. J. Clin. Nutr. 55 1147-1153. 

Figure 3.2 Beneficial effects of folic acid on vascular wall. Folic acid circulates in human body as 5-methyltetrahydrofolate (5-MTHF). 5-MTHF lowers circulating homocysteine (Hey) levels, thus reducing systemic oxidative stress and Hcy-induced activation of prothrombotic mechanisms. In addition, vascular 5-MTHF has a favourable effect on intracellular Hey metabolism, attenuating Hcy-induced activation of NADPH oxidase isoforms (NOXs) in the vascular wall. Furthermore vascular 5-MTHF scavenges per se peroxynitrite (ONOO ) radicals in the vascular wall preventing the oxidation of vascular tetrahydrobiopterin (BH4) associated with endothelial nitric oxide synthase (eNOS) uncoupling and diminished vascular nitric oxide (NO) bioavailability. In total through these effects 5-MTHF lowers vascular oxidative and nitrosative stress. Thus by modulating vascular redox, 5-MTHF inhibits activation of proinffammatory pathways which orchestrate vascular wall inflammation and perpetuate endothelial dysfunction and atherogenesis development (unpublished).

Melse-Boonstra, A., Verhoef, P., West, C.E., van Rhijn, J.A., van Breemen, R.B., Lasaroms, J.J.P., Garbis, S.D., Katan, M.B., and Kok, F.J., 2006. A dual-isotope-labeling method of studying the bioavailability of hexaglutamyl folic acid relative to that of monoglutamyl folic acid in humans by using multiple orally administered low doses. The American Journal of Clinical Nutrition. 84 1128-1133. 

DFE reflects the higher bioavailability of synthetic folic acid found in supplements and fortified foods compared to that of naturally occurring food folate (Combs 2000 Food and Nutrition Board 1998). 

JF Gregory, SD Bhandari, LB Bailey, JP Toth, JJ Cerda. Bioavailability of deuterium-labeled monoglutamyl forms of folic acid and tetrahydrofolates in human subjects. Am J Clin Nutr 55 1147-1153, 1992. 

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