Blood folic acid

Patients typically present by 6-12 months with severe developmental retardation, convulsions, microcephaly and homocysteinemia (=50pmol/l) with hypomethioninemia (<20 pmol/1). A few individuals have had psychiatric disturbances. The blood concentration of vitamin B12 is normal, and, unlike individuals with defects of cobalamin metabolism, these patients manifest neither anemia nor methylmalonic aciduria. The blood folic acid level is usually low. 

Growth conditions Tope 35-37 °C (10-40 °C), survive 30 min. temperatures at 60 °C pH 4.6-9 Requirements complexes such as brain heart infusion, blood, folic acid, some strains the same requirements such as LAB ... 

Hydroxymethyl-6-methyluracil (1043) was prepared many years ago from 6-methyl-uracil and formaldehyde, or in other ways. Since 1956 it has received much attention in the USSR under the (transliterated) name pentoxyl or pentoxil. It is used in several anaemic and disease conditions. For example, a mixture of folic acid and pentoxyl quickly reduces the anaemia resulting from lead poisoning pentoxyl stimulates the supply of serum protein after massive blood loss it stimulates wound healing it stimulates the immune response in typhus infection and it potentiates the action of sulfonamides in pneumococcus infections (70MI21300). 

Anemias, reductions in the number of red blood cells or of hemoglobin in the blood, can reflect impaired synthesis of hemoglobin (eg, in iron deficiency Chapter 51) or impaired production of erythrocytes (eg, in folic acid or vitamin Bjj deficiency Chapter 45). Diagnosis of anemias begins with spectroscopic measurement of blood hemoglobin levels. 

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. 

The underlying cause of anemia (e.g., blood loss iron, folic acid, or B12 deficiency or chronic disease) must be determined and used to guide therapy. 

The underlying cause of anemia (e.g., blood loss iron, folic acid, or vitamin B12 deficiency or chronic disease) must be determined and used to guide therapy. As discussed previously, patients should be evaluated initially based on laboratory parameters to determine the etiology of the anemia (see Fig. 63-3). Subsequently, the appropriate pharmacologic treatment should be initiated based on the cause of anemia. 

Growing clinical data also points to the importance of IL-8 in atherogenesis. IL-8 has been found in atheromatous lesions from patients with atherosclerotic disease including carotid artery stenosis (103), CAD (118), abdominal aortic aneurysms (AAA) (103,104,114), and peripheral vascular disease (PVD) (104). Furthermore, studies using plaque explant samples have yielded more direct evidence for IL-8 involvement. Media from cultured AAA tissue induced IL-8-dependent human aortic endothelial cell (HAEC) chemotaxis (122). Homocysteine, implicated as a possible biomarker for CAD, is also capable of inducing IL-8 (123-125) by direct stimulation of endothelial cells (123,124) and monocytes (125). When patients with hyperhomocysteinemia were treated with low-dose folic acid, decreases in homocysteine levels correlated with decreases in IL-8 levels (126). Statins significantly decrease serum levels of IL-6, IL-8, and MCP-1, as well as expression of IL-6, IL-8, and MCP-1 mRNA by peripheral blood monocytes and HUVECs (127). Thus, IL-8 may be an underappreciated factor in the pathogenesis of atherosclerosis. 

Monitor effects by symptomatic improvement, gain of body weight and improved blood tests as indicated hemoglobin, calcium, albumin, iron, B12 and folic acid... 

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). 

A relatively large number of agents have been utilized to treat this intractable disorder folinic acid (5-formyl-tetrahydrofolic acid), folic acid, methyltetrahydrofolic acid, betaine, methionine, pyridoxine, cobalamin and carnitine. Betaine, which provides methyl groups to the beta i ne ho mocystei ne methyltransferase reaction, is a safe treatment that lowers blood homocysteine and increases methionine. 

Anemia may be a common problem where there is significant blood loss from the GI tract. When the patient can consume oral medication, ferrous sulfate should be administered. Vitamin B12 or folic acid may also be required. 

Serum uric acid and folic acid concentrations should be monitored yearly in patients prone to hyperuricemia or folic acid deficiency. Blood glucose must be monitored carefully in diabetic patients. 

J. M. Cooperman, Microbiological assay of folic acid activity in serum and whole blood. In Methods in Enzymology, XVIII, Part B (eds. D. G. McCormick and... 

For every milliliter of citrated blood (Fig. 3) 1 ml of pH 6.1 phosphate buffer is added (see Folic Acid, Section 8.1). The mixture is autoclaved... 

Because of the multiplicity of folic acid factors reported in whole blood (Ul), the microbiologic assay for folic acid in whole blood and serum was regarded as valueless (C2, L8, W9) results based on S. faecalis methods (C2, C3) did not contradict this view. Streptococcus faecalis is inferior to L. casei in its utilization of the PGA polyglutamates... 

B2. Baker, H., Erdberg, R., Pasher, I., and Sobotka, H., Study of folic acid and vitamin B12 in blood and mine during normal pregnancy. Proc. Soc. Exptl. Biol. Med. 94, 513-515 (1957). 

H12. Hoogstraten, B., Baker, H., and Reizenstein, P., Correlation between serum folic acid activity and response to antifolate therapy. Blood 17, 787 (1961). 

R12. Ross, J. F., Belding, H. W., and Paegel, B. L., Development and progression of subacute combined degeneration of spinal cord in patients with pernicious anemia treated with synthetic pteroyl glutamic (folic) acid. Blood 3, 68-90 (1948). 

T3. Toennies, G, Usdin, E., and Phillips, P. M., Precursors if the folic acid-active factors of blood. J. Biol. Chem. 221, 855-863 (1956). 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

In a totally different field, studies were being carried out on children who had a deficiency of methionine synthase and an impaired ability to convert homocysteine to methionine, so that they had increased blood levels of homocysteine. It was noted that these children had an increased incidence of thrombosis in cerebral and coronary arteries. This led to a study which eventually showed that an increased level of homocysteine was a risk factor for coronary artery disease in adults. Since methionine synthase requires the vitamins, folic acid and B12, for its catalytic activity, it has been suggested that an increased intake of these vitamins could encourage the conversion of homocysteine to methionine and hence decrease the plasma level of homocysteine. This is particularly the case for the elderly who are undernourished (see Chapter 15 for a discussion of nutrition in the elderly). 

Orotic acid in the diet (usually at a concentration of 1 per cent) can induce a deficiency of adenine and pyridine nucleotides in rat liver (but not in mouse or chick liver). The consequence is to inhibit secretion of lipoprotein into the blood, followed by the depression of plasma lipids, then in the accumulation of triglycerides and cholesterol in the liver (fatty liver) [141 — 161], This effect is not prevented by folic acid, vitamin B12, choline, methionine or inositol [141, 144], but can be prevented or rapidly reversed by the addition of a small amount of adenine to the diets [146, 147, 149, 152, 162]. The action of orotic acid can also be inhibited by calcium lactate in combination with lactose [163]. It was originally believed that the adenine deficiency produced by orotic acid was caused by an inhibition of the reaction of PRPP with glutamine in the de novo purine synthesis, since large amounts of PRPP are utilized for the conversion of orotic acid to uridine-5 -phosphate. However, incorporation studies of glycine-1- C in livers of orotic acid-fed rats revealed that the inhibition is caused rather by a depletion of the PRPP available for reaction with glutamine than by an effect on the condensation itself [160]. 

Folate, the anion of folic acid, is made up of three different components—a pteridine derivative, 4-aminobenzoate, and one or more glutamate residues. After reduction to tetrahydrofolate (THF), folate serves as a coenzyme in the Q metabolism (see p. 418). Folate deficiency is relatively common, and leads to disturbances in nucleotide biosynthesis and thus cell proliferation. As the precursors for blood cells divide particularly rapidly, disturbances of the blood picture can occur, with increased amounts of abnormal precursors for megalocytes megaloblastic anemia). Later, general damage ensues as phospholipid... 

Pharmacology Exogenous folate is required for nucleoprotein synthesis and maintenance of normal erythropoiesis. Folic acid stimulates production of red and white blood cells and platelets in certain megaloblastic anemias. 

Drug/Lab test interactions Methotrexate, pyrimethamine, and most antibiotics invalidate folic acid and vitamin Bi2diagnostic microbiological blood assays. 

Renal stones Triamterene has been found in renal stones with other usual calculus components. Use cautiously in patients with histories of stone formation. Hematologic effects Triamterene is a weak folic acid antagonist. Because cirrhotics with splenomegaly may have marked variations in hematological status, it may contribute to the appearance of megaloblastosis in cases where folic acid stores have been depleted. Perform periodic blood studies in these patients. 

Blood levels of folic acid may become inadequate due to dietary insufficiency or poor absorption due to Intestinal problems or alcoholism. 

Cyanocobalamin, or vitamin B12, is in small amounts required for red blood cell production and for the formation of nucleoproteins and proteins. It is also needed for the proper functioning of the nervous system. Folic acid supplements can correct the anemia associated with vitamin B12 deflciency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B12 deficiency. Vitamin B12 is only found in animal sources such as liver and other organs. Some vitamin B12 is obtained from fish, eggs and milk. Folic acid and cyanocobalamin have been discussed in more detail in Chapter 22. 

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