Vitamin, individual folic acid

In an investigation of the water-soluble vitamins in human skin,71 it was found that 15 individuals showed relatively small ranges (less than 2-fold) for vitamin B12, folic acid, and biotin about 2-fold ranges in the cases of riboflavin, niacin, and thiamine about a 4-fold range in the case of ascorbic acid, and more than a 5-fold range in the case of pantothenic acid. In another study72 it was found that the total choline content of normal skin varied in four individuals over approximately a 10-fold range 127 to 1200 ig. per gm. The variation in the free choline in the same individuals was relatively small. 

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... 

A thorough medical evaluation of an individual wifh anemia is necessary because fhe condition can result from a variefy of diseases as well as from nutritional deficiencies. Vitamin and folic acid deficiencies can also cause anemia. 

Generally, AA is determined individually, and only about a 10% of the published methods determine AA simultaneously with other analytes such as uric acid, glucose, fructose, dopamine, iodate, bromate, hypochlorite, thiourea, glutathione, hydrogen peroxide, acetylsalicylic acid, kojic acid, ascorbyl glucoside, paracetamol, cysteine, and other water soluble vitamins (thiamine [vitamin Bj], folic acid [vitamin B12], niacin [vitamin B3], riboflavin [vitamin B2], and pyridoxine [vitamin B ]). 

The water-soluble vitamins comprise the B complex and vitamin C and function as enzyme cofactors. Fofic acid acts as a carrier of one-carbon units. Deficiency of a single vitamin of the B complex is rare, since poor diets are most often associated with multiple deficiency states. Nevertheless, specific syndromes are characteristic of deficiencies of individual vitamins, eg, beriberi (thiamin) cheilosis, glossitis, seborrhea (riboflavin) pellagra (niacin) peripheral neuritis (pyridoxine) megaloblastic anemia, methyhnalonic aciduria, and pernicious anemia (vitamin Bjj) and megaloblastic anemia (folic acid). Vitamin C deficiency leads to scurvy. 

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. 

In view of the lack of satisfactory data, the evidence for substantial inter-individual differences in milk composition is limited, and satisfactory conclusions must await further study of both inter-individual and intra-individual differences. The available data suggest that interindividual differences may be substantial and important in the case of ascorbic acid, folic acid, and vitamin B12. 

The fact that certain human adults or infants develop types of anemia which respond to small doses of folic acid can be interpreted to mean that, for reasons which doubtless have some genetic basis, these individuals have unusually high demands for this vitamin. Presumably they develop the disease when consuming diets that do not induce the disease in others. Folic acid needs are (for one reason or another) highly variable from individual to individual among patients as is shown by the fact that many patients will respond to as little as 0.5 mg. folic acid per day, whereas others will not respond at all... 

Dietary supplementation with B vitamins is also highly effective in lowering homocysteine in most individuals with mild or moderate hyperhomocysteinemia. A meta-analysis of 12 randomized trials performed prior to folic acid fortification concluded that treatment with folic acid (0.5 to 5 mg daily) decreased homocysteine levels by 25%, and that the addition of... 

Anaemia occurs when there is a decrease in haemoglobin below the appropriate level for the age and sex of the individual. The anaemia maybe due to several factors as lack of iron, vitamin Bi2 and folic acid all affect red cell production, resulting in anaemia. Bi2 deficiency may also cause neurological problems, such as numbness and weakness. Patients with Bi2 deficiency may also report mood swings and seem to suffer more infection and mild gastrointestinal problems than normal, so Maria s moodiness, stomach upsets and colds may be significant. 

In a case-control study in 106 heroin-dependent individuals undergoing an opioid detoxification program (n = 19) or a methadone maintenance treatment program (n = 87) there were large significant differences in the mean values of some vitamins and minerals between the heroin-dependent individuals and the healthy, non-dependent controls (37). Dependent individuals had higher white cell counts and transaminases and lower erythrocyte counts and cholesterol, albumin, tocopherol, folic acid, sodium, selenium, and copper concentrations. 

The pterins include the redox cofactors biopterin and molybdopterin, as well as various insect pigments. Folic acid is a conjugated pterin, in which the pteridine ring is linked to p-aminobenzoyl-poly-y-glutamate it is this linkage that renders folate a dietary essential, because it is the ability to condense p-aminobenzoate to a pteridine, rather than to synthesize the pteridine nucleus itself, which has been lost by higher animals. Biopterin (Section 10.4) and molybdopterin (Section 10.5) are coenzymes in mixed-function oxidases they are not vitamins, but can be synthesized in the body. Rare genetic defects of biopterin synthesis render it a dietary essential for affected individuals. 

Although requirements for vitamins and trace elements are known in health (Table 30-1), the effects of illness on these requirements are poorly understood and quantified. However, it is now apparent that as an individual develops progressively more severe depletion in vitamin or trace element status, the person passes through a series of stages with biochemical or physiological consequences. The metabolic or physiological penalty of such suboptimal nutritional status is usually not clear, but the assumption remains that the suboptimal metabolism is likely to have detrimental effects (e.g., subclinical deficiency of folic acid is associated with an increase in serum homocysteine concentration, which is an independent risk factor for coronary artery disease—see Chapter 26). Similarly, subclinical deficiency of chromium may be associated with impaired glucose tolerance in certain types of diabetes. 

Vitamin status also may be affected by drugs (Table 135-15). For example, sulfasalazine therapy has been noted to cause a decrease in folic acid, isoniazid therapy causes pyridoxine deficiency, and furosemide therapy may result in decreased thiamin concentrations. Furthermore, some drug therapy outcomes may be affected by vitamin intake. The ingestion of megadoses of folic acid may decrease methotrexate s therapeutic effect, whereas changes in an individual s usual vitamin K intake may cause variability in warfarin s anticoagulation effects. 

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. 

Besides these studies with individual vitamins, there are studies with rats that had received none of the vitamins of the B group (Morgan and Yudkin, 1957). With 20% sorbitol in the diet, the animals grew well for the 13 weeks of the experiment. The diets were such that they would not produce deficiences of vitamin B12, biotin, or niacin however, we can conclude that sorbitol can spare simultaneously at least thiamine, riboflavin, pantothenic acid, pyridoxine and folic acid. 

The availability of Mg +, K+, and the folate coenzymes may also be considered. The two cations are probably not rate-limiting, although K+ concentrations do fluctuate in cells. Little is known about the concentrations of total folic acid or of individual folate coenzymes, relative to tissue requirements for them. That this cofactor may be in excess was suggested by a recent study (39) in which a 95% decrease in total H4-folate was induced without causing any change in growth rate of the cells concerned. Others have found, however, that dietary deficiency of folate or vitamin Bi2 leads to increased urinary excretion of aminoimidazole carboxamide (40, 4D-... 

Folic acid and vitamins Bg and B12 are essential cofactors in Hey metabolism (Figure 3.1). Folate administration consistently reduces plasma Hey levels even in healthy individuals without homocysteinaemia. It is estimated that oral... 

Existing data on the effects of B vitamins on atheroma progression are conflicting. Folic acid, Bg and B12 administration in middle-aged individuals... 

Some findings of this clinical trial are that daily administration of folic acid, vitamin Bg and vitamin B12 to patients with recent stroke or transient ischemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins (VITATOPS Trial Study Group 2010). 

The homocysteine hypothesis of vascular disease has attracted considerable interest since homocysteine levels are readily lowered by daily dietary supplementation with folic acid, vitamin Bg and vitamin B12 (Homocysteine Lowering Trialists Collaboration 2005), raising the prospect that dietary supplementation with these B vitamins could prevent vascular disease. Indeed, dietary supplementation with B vitamins to lower homocysteine levels of affected individuals is remarkably effective for the prevention of cardiovascular disease and other complications of homocystinuria (Yap et al. 2001). This review examines the evidence from the observational studies of homocysteine and vascular disease and from the randomized trials of B vitamin supplementation for the prevention of vascular disease. 

About 300 individual compounds with antimutagenic properties are known. The frequency of mutations can be reduced by some amino acids (arginine, histidine, methionine, cysteamine etc ), vitamins and provitamins (a-tocopherol, ascorbic acid, retinol, p-carotene, phylloquinone, folic acid), enzymes (peroxidase, NADPH oxidase, glutathione peroxidase, catalase), complex compounds of plant and animal origin, chemical substances with antioxidant properties (derivatives of gallic acid, ionol, oxypyridines, selenium salts and others). 

Table I summarizes the effects of the various deficiencies of the vitamin B complex upon the response to a variety of antigenic stimuli in different test animals. It is the reviewers opinion that, with the exception of the criticisms already made, this table represents the results of well-controlled, adequate experiments. It is quite apparent that the individual members of the vitamin B complex play a very important role in determining antibody response. Their absence may produce a marked impairment in antibody production. Generalizations on this subject are dangerous, but it would appear that pyridoxine, pantothenic acid, and folic acid deficiencies show the most consistent deleterious effects upon antibody production. It is also apparent that the effects of the individual deficiencies may vary widely depending upon the antigen employed.

---