Plasma folates

Alfthan, G., Laurinen, M. S., Valsta, L. M., Pastinen, T., Aro, A. (2003). Folate intake, plasma folate and homocysteine status in a random Finnish population. Eur. J. Clin. Nutr., 57, 81-88. 

Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of L-folinic or folic acid. Kidney Int 62 2246-2249... 

L. M. Wallock et al., Low Seminal Plasma Folate Concentrations Are Associated with Low Sperm Density and Count in Male Smokers and Non-smokers, Fertil. Steril. 75 (2001) 252-59. 

Hall, M Gamble, M Slavkovich, V. et al. (2007) Determinants of arsenic metabolism Blood arsenic metabolites, plasma folate, cobalamin, and homocysteine concentrations in maternal-newborn pairs. Environmental Health Perspectives, 115 (10), 1503-9. 

Several studies have demonstrated an association between plasma tHcy levels and extent of CAD in populations not exposed to fortification of flour products with folic acid, even after controlling for conventional risk factors (26,27). In contrast, Brilakis et al. (28) found no association between plasma tHcy and angiographic CAD in a North American population consuming cereal grain flour fortified with folic acid. Silberberg et al. (29) found an association between plasma folate and CAD independent of tHcy. 

Silberberg JS, et al. Association between plasma folate and coronary disease independent of homocysteine. Am J Cardiol 2001 87(8) 1003-1004 A5. 

Methyl-tetrahydrofolate from the intestinal mucosa circulates bound to albumin and is the main vitamer for uptake by extrahepatic tissues. Small amounts of other one-carbon substituted folates also circulate (about 10% to 15% of plasma folate is 10-formyl-tetrahydrofolate) and are also available for tissue uptake. There are two mechanisms for tissue uptake of folate ... 

Demethylated tetrahydrofolate monoglutamate is released hy extrahepatic tissues and is transported hound to a plasma folate binding protein similar to that in milk. It has a very low affinity for methyl-tetrahydrofolate and other one-carbon substituted derivatives. It functions mainly to return folate to the liver, where it is either conjugated for storage or methylated to 5-methyl-tetrahydrofolate that is secreted in the bile. 

The amount of vitamin B12 in the serum sample is determined as follows. The amount of radioactive [ Co]cobalamin bound to the beads is measured. The purpose of using the beads is to facilitate the separation of bound P CoJcobalamin from the nonbound [ Co]cobalamin remaining in solution (floating around versus sinking to the bottom of the test tube). High levels of bound radioactivity indicate that the scrum sample contains low vitamin levels. Low levels of bound radioactivity indicate that the scrum contains high levels of vitamin. Plasma folate is... 

Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999 340(19) 1449-54. 

Drugs that inhibit folate metabolism increase the likelihood of serious adverse reactions to methotrexate, particularly hematological toxicity. Bone marrow suppression and reduced plasma folate concentrations resulted from the concomitant administration of triamterene with methotrexate (145). 

A study of 1401 subjects involved measuring plasma homocysteine and measuring the lesions in the carotid artery, one of the arteries in the body that tends to acquire atherosclerotic lesions. The thickness of the lesions were measured by ultrasonography. Plasma folate, vitamin Bg, and vitamin B12 were also measured. A correlation was found between narrowing of the artery and homocysteine levels at above 15 xM homocysteine. A correlation with narrowing of the artery was also found with folate levels below 2.5 ng/ml, and with vitamin Bg levels below 30 nM (Selhub et al, 1995). A study of 231 normal subjects and 304 patients with atherosclerosis (coronary artery under 30% normal diameter) revealed a striking correlation between plasma homocysteine of 12 pM, or greater, and atherosclerosis (Robinson et al, 1995). These studies help define an upper limit of acceptable plasma homocysteine levels. 

Erythrocyte and plasma folate concentrations are reduced in protein-calorie malnutrition, but the serum vitamin Bj2 concentration is unaffected or may even be slightly increased. The plasma concentrations of vitamins A and E are much reduced. Although the blood hemoglobin concentration is reduced, the serum iron concentration is initially little affected by malnutrition. 

Protein-free plasma folate is filtered at the glomerulus and most is reabsorbed by the proximal renal tubules. Consequently, intact urinary folate is only a small percentage of intake. Folate is predominantly excreted by catabolism foUowing cleavage of the C9-N10 bond to produce p-aminobenzoylpolyglutamates, which are then hydrolyzed to monoglutamates and hT-acetylated before excretion. Biliary excretion of folate has been estimated at about 100 Xg/day, but much of this is reabsorbed in an enterohepatic circulation. Fecal losses have been studied by radiolabeling and have been found to be similar in type and quantity to urinary losses. ... 

As was mentioned earlier, reports by Shojania et al. (Sll, S12) of decreased plasma and red blood cell folate concentrations in users of OCAs first drew attention to this subject. Luhby et al. (LIO) also found evidence of folate deficiency in some women taking OCAs, and Wertalik et al. (W6) found lower plasma folate levels in women on the pill than in controls. It was felt (S12) that a large number of subjects given these agents for long periods of time needed to be studied in order to demonstrate a statistically significant difference, because folate concentrations were seldom profoundly depressed in such women. 

A number of subsequent articles described no significant differences in plasma folate levels between users of oral contraceptive and normal... 

Folate can be measured in plasma or serum by microbiological assay using L. casei as the test organism, but this test can be confounded if the subject is on antibiotic treatment. Serum folate values reflect recent dietary intake and a vitamin deficiency is ascribed only where serum folate remains low over a period of time. Plasma folate levels are thought to reflect the day-to-day variations in dietary folate levels while red blood cell folate is a better indicator of long-term tissue storage levels. 

Shrubsole, M.J., Yang, G., and Gao, Y.T., et al., 2009. Dietary B vitamin and methionine intakes and plasma folate are not associated with colorectal cancer risk in Chinese women. Cancer Epidemiol Biomarkers Prev. 18 1003-1006. 

The liver rapidly absorbs from 10 to 20% of dietary folate, with a preference for non-methylated and non-reduced derivatives, while peripheral tissues are enriched in reduced and methylated functional derivatives. Folate is mainly stored in the liver. Hepatic folates are partly excreted into the bile enterohepatic circulation and reabsorbed (Steinberg et al. 1979). This is one of the mechanisms involved in the recirculation of folate. Regarding renal elimination, folate is filtered by the glomerulus and reabsorbed into the proximal tubule. The daily urinary excretion of intact folates is between 1 to 12 pg. When the serum plasma folate concentration is very high, it is possible to overwhelm the renal reabsorption capacity in this case, folate derivatives are excreted in the urine. Due to the possible production by the gut microflora, fecal folate levels are quite high. 

The pre-treatment plasma folate concentration was substantially higher in fortified populations compared with that in non-fortified populations, and allocation to B vitamin treatment was associated with a greater proportional reduction in homocysteine concentrations in non-fortified compared with that in fortified populations (Clarke et al. 2010). The meta-analysis assessed the effects of B vitamins on risk of vascular and non-vascular events assodated with about a 25% reduction in homocysteine levels for about five years (Clarke et al. 2010). 

Nutrition The effect of warfarin therapy for 6 months on folate status has been studied in 114 patients, using measurements of erythrocyte folate and 5-methyltetrahydro-folate and plasma folate, total homocysteine, phylloquinone, vitamin B12, and methylmalonic acid [ll. There were significant falls in total erythrocyte folate and 5-methyltetrahydrofolate and a concurrent increase in plasma phylloquinone, attributed to altered vitamin K metabolism. 

Extraction of plasma folates, which are present as folylmonoglutamates, ean be earried out with several extraction methods. Kohashi and Inoue (42) used aeetone extraction of serum protected with 2-mercaptoethanol for HPLC determination... 

Mild heat extraction was applied by Bohlman and Nau (56) in the analysis of rat plasma folates. Plasma was mixed with 0.1 M acetate buffer (pH 5.5) containing ascorbic acid (1%) and 2-mercaptoethanol (0.2M), after flushing with argon, the mixture was heated for 5 min at 80°C. Kelly et al. (45) described an assay for serum folate involving HPLC fractionation of deproteinized serum prior to Lactobacillus rhamnosus assay of the collected peaks. The method was validated particularly for the determination of unmetabolized folic acid in human plasma. The limit of detection for folic acid using L. rhamnosus microtitration plate assay was 1 ng/mL serum. 

LM Rogers, CH Pfeiffer, LB Bailey, JF Gregory. A dual-label stable-isotopic protocol is suitable for determination of folate bioavailabihty evaluation of urinary excretion and plasma folate kinetics of intravenous and oral doses of and H2 fohc acid. J Nutr 127 2321-2327, 1997. 

The introduction of 140 pg of folic acid per 100 g of flour in the USA, calculated to increase individual consumption of folic acid by 100 pgday , has reduced the incidence of abnormally low plasma folate from 21% to less than 2%, the incidence of mild hyperhomocysteinemia from 21% to 10%, and, most importantly, the incidence of NTD by about 20% over the first years of universal fortification. Because 30% of the population takes vitamin supplements and presumably would not be expected to derive significant benefit from fortification, the actual effect may be closer to a 30% decrease due to fortification. Recent calculations suggest that, for a variety of reasons, the overall fortification amount was about twice the mandatory amount. 

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