Folate status

Jacques PF, Bostom AG, Williams RR, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996 93 79. 

Folate deficiency results in a megaloblastic anemia that is microscopically indistinguishable from the anemia caused by vitamin B12 deficiency (see above). However, folate deficiency does not cause the characteristic neurologic syndrome seen in vitamin B12 deficiency. In patients with megaloblastic anemia, folate status is assessed with assays for serum... 

As discussed in Section 10.3.4.2, the metabolic fate of homocysteine arising from methionine is determined not only by the activity of cystathionine synthetase and cystathionase, hut also the rate at which it is remethylated to methionine (which is dependent on vitamin B12 and folate status) and the requirement for cysteine. 

Epidemiological smdies suggest that hyperhomocysteineima is most significantly correlated with low folate status, but there is also a significant association with low vitamin Bg status (SeUiub et al., 1993). Trials of supplementation have shown that whereas folate supplements lower fasting homocysteine in moderately hyperhomocysteinemic subjects, supplements of 10 mg per day of vitamin Bg have no effect, although supplements do reduce the peak plasma concentration of homocysteine after a test dose of methionine (Ubbink et al., 1994 Ubbink, 1997 Dierkes et al., 1998). This can probably be explained on the basis of the kinetics of the enzymes involved the of cystathionine... 

Although folate is widely distributed in foods, dietary deficiency is not uncommon, and a number of commonly used drugs can cause folate depletion. Marginal folate status is a factor in the development of neural tube defects and supplements of 400 fj,g per day periconceptually reduce the incidence of neural tube defects significantly. High intakes of folate lower the plasma concentration of homocysteine in people genetically at risk of hyperhomo-cysteinemia and may reduce the risk of cardiovascular disease, although as yet there is no evidence from intervention studies. There is also evidence that low folate status is associated with increased risk of colorectal and other cancers and that folate may be protective. Mandatory enrichment of cereal products with folic acid has been introduced in the United States and other countries, and considered in others. 

Figure 10.6. Catabolism of histidine - basis of the FIGLU test for folate status. Histidase, EC 4.3.1.3 urocanase, EC 4.2.1.49 FIGLU formiminotransferase, EC 2.1.2.5. THF, tetrahydrofolate.

Deficiency of either folic acid or vitamin B12 results in a clinically similar megaloblastic anemia because of the neurological damage that accompanies the megaloblastic anemia of vitamin B12 deficiency, the condition is generally known as pernicious anemia. Suhoptimal folate status is also associated with increased incidence of neural tube defects (Section 10.9.4), hyperhomocys-teinemia leading to increased risk of cardiovascular disease (Section 10.3.4.2), and undermethylation of DNAleadingto increased cancerrisk (Section 10.9.5). 

Epidemiological studies suggest that suboptimal folate status is associated with an increased risk of colorectal and other cancers. It is difficult to determine the importance of folate per se, because the dietary sources of folate (mainly greenleafy vegetables) are also sources of avariety of other compounds... 

In addition to the methods described here, measurement of urinary ac-etamido p-aminohenzoyl glutamate will reflectfolate turnover (Section 10.2.3) and incorporation of uracil, instead of thymidine into the DNA in leukocytes or lymphocytes may provide a sensitive index of folate status. 

At tbe time that the U. K. and European Union reference intakes of folate shown in Table 10.3 were being discussed, the results of intervention trials for the prevention of neural tube defects (Section 10.9.4) were only just becoming available. At that time, there was no information concerning the effects of folate status onhyperhomocysteinemia (Section 10.3.4.2). TheU.S./Canadianreport (Institute of Medicine, 1998) notes specifically that protective effects with respect to neural tube defects were not considered relevant to the determination of the Dietary Reference Intake of folate, and there was insufficient evidence to associate higher intakes of folate (and lower plasma concentrations of homocysteine) with reduced risk of cardiovascular disease. 

Change A, Potier De Courcy G, Boisson F, Guilland JC, Barbe F, Perrin MO, Christides JP, Rabhi K, Pfister M, Galan P, Hercberg S, and Nicolas JP (2000b) 5,10-Meth-ylenetetrahydrofolate reductase common mutations, folate status and plasma homocysteine in healthy French adults of the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) cohort. British Journal of Nutrition 84, 891-6. 

Green R and Miller JW (1999) Folate deficiency beyond megaloblastic anemia hyperho-mocysteinemia and other manifestations of dysfunctional folate status. Seminars in Hematology 3S, 47-64. 

CataboUsm of histidine - basis of the FIGLU test for folate status. 282... 

Folate status can be assessed by the measurement of serum or red blood ceil folate levels, by the histidine load test, and by hematological methods. 

Scrum contains folate monoglutamates. The normal level of serum folate is 6-0 ng/ml or greater. A value of 3.0 ng/ml or less indicates a folate deficiency. Scrum folate levels are sensitive to recent dietary practices aitd hence may not accurately reflect the amount of folate in tissues. True folate status is closely related to the tissue or cellular level of folate, rather than the serum level. 

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