Supplements, folate vitamin

The homocystinurias are a group of disorders involving defects in the metabolism of homocysteine. The diseases are inherited as autosomal recessive illnesses, characterized by high plasma and urinary levels of homocysteine and methionine and low levels of cysteine. The most common cause of homocystinuria is a defect in the enzyme cystathionine /3-synthase, which converts homocysteine to cystathionine (Figure 20.21). Individuals who are homozygous for cystathionine [3-synthase deficiency exhibit ectopia lentis (displace ment of the lens of the eye), skeletal abnormalities, premature arte rial disease, osteoporosis, and mental retardation. Patients can be responsive or non-responsive to oral administration of pyridoxine (vitamin B6)—a cofactor of cystathionine [3-synthase. Bg-responsive patients usually have a milder and later onset of clinical symptoms compared with B6-non-responsive patients. Treatment includes restriction of methionine intake and supplementation with vitamins Bg, B, and folate. 

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. 

Folate Is a generic term referring to a family of related compounds. All of these compounds represent modifications of the simplest form of the vitamin, folic acid (pteroylglutamic add, PlcGlu). Folic add does not occur in nature in appreciable amounts, though it is readily assimilated by the body and converted to the active cofactor forms of the vitamin. Folic acid is the form of the vitamin used in folate supplements. Folates are modified by reduction and by a poly glutamyl chain or tail. The reduced folates include dlhydrofolate and tetrahydrofolate. 

A study of 2K human subjects revealed that treatment with three vitamins together (folate, vitamin and vitamin Bu) can provoke a decline of plasma homt>cysteine from an initial level of about 12 piM to the lower level of 8 xM (Naurath ei a]., 1995). A study of 100 men with moderate levels of plasma homocysteine (18-40 pM) involved separate supplements of placebo, folic acid, vitamin 15i2, or vitamin E. Folic add alone resulted in a 40% decline in plasma homocysteine. Vitamin B] alone provoked a 15% decrease in the amino acid, while vitamin... 

Vtamin A supplementation, 564-565 Vitamin B(, 493, 541-542 aminotranK/ei ase, 209 assessmenl of status, 546-550 biochcinistry, 542-545 cardiovascular disease and, 553 homocysteine and, 550-554 homocysbnuria, 550,554 toxidty, 550 water solubility, 27 Vitamin Bs deficiency, 545-546 Vitamin supplements, 551 Vitamin Bu, 493,507, 516 absorption, 81-82 assessment of status, 522-524 biocbemistry, 516-517 chemical structure, 517 Cobalt and, 4t homocystBine and, 553 Vitamin Bij dehdency, 517-524 causes of, 518-522 elderly population, 521,553 folate deficiency and, 507, 511-312, 518 hematologic signs, 513... 

Sources Dietary Reference Intakes for Calcium, Phosphorous, Magnesium, Vitamin D, and Huoride (1997) Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin 85, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998) EHetary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids (2000) Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc (2001) Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate (2005) and EHetary Reference Intakes for Calcium and Vitamin D (2011). These reports may be accessed via www.nap.edu A Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population. Unless otherwise specified, the UL represents total intake from food, water, and supplements. Due to a lack of suitable data, ULs could not be established for vitamin K, thiamin, riboflavin, vitamin B12, pantothenic acid, biotin, and carotenoids. In the absence of a UL, extra caution may be warranted in consuming levels above recommended intakes. Members of the general population should be advised not to routinely exceed the UL. The UL is not meant to ply to individuals who are treated with the nutrient under medical supervision or to individuals with predisposing conditions that modify their sensitivity to the nutrient... 

Clinical observations suggest that pyridoxine supplements have no effects on seizure frequency. Like folate, vitamin Bg has a specialized transport system into the cerebrospinal fluid. 

Bryan, J., Calvaresi, E, and Hughes, D., 2002. Short-term folate, vitamin B12, or vitamin B6 supplementation slightly affects memory performance but not mood in women of various ages. The Journal of Nutrition. 132 1345-1356. 

Metabolism In a prospective controlled study in 74 patients taking isotretinoin for cystic acne, blood concentrations of homocysteine, vitamin B12, and folate were assessed before and after 45 days of isotretinoin therapy [39 ]. The control group consisted of 80 individuals. Homocysteine concentrations were significantly higher in those who took isotretinoin. The vitamins were unaffected, but serum lipids and liver enzymes increased significantly. These effects may have been due to inhibition of cystathionine-beta-synthase, an enzyme required for the metabolism of homocysteine by either the drug or liver dysfunction. Daily supplementation with vitamin B12 and folate can lower plasma concentrations of homocysteine, and the authors therefore recommended the use of these vitamins in patients taking isotretinoin. 

Supplements are not needed by healthy persons ingesting a balanced diet. In this regard, the American Institute of Nutrition, the American Society for Clinical Nutrition, and the American Dietetic Association issued a formal joint statement that supplements of vitamins and minerals were not needed by well-nourished, healthy individuals except for some specific exceptions, e.g. folate and iron for pregnant women and vitamin K for the newborn [50]. 

Other nutrients and their deficiencies that can impact iron status, utilization, or anemia include vitamin A, folate, vitamin B12, riboflavin, and ascorbic acid (vitamin C). Improving iron status can also increase the utilization of iodine and vitamin A from supplements. On the other hand, it is increasingly recognized that simultaneous provision of iron and zinc in supplements may decrease the benefit of one or both of these nutrients. These complex micronutrient interactions and their implications for nutritional interventions are incompletely imderstood but have significant implications for population-based supplementation strategies. 

A deficiency of folate, vitamin B12, or vitamin Bg may increase the level of homocysteine, an amino acid normally found in the blood. Evidence indicates that a high homocysteine level increases the risk for CVD and stroke, possibly by either damaging coronary arteries or making it easier for blood platelets to clump together and form a clot. However, no evidence is available to suggest that lowering homocysteine through vitamin supplementation will reduce the risk of CVD. Clinical intervention trials to test the effects of vitamin supplementation on CVD and stroke are needed. 

Folate supplements will rectify the megaloblastic anemia of vitamin Bj2 deficiency but may hasten the development of the (irreversible) nerve damage found in B,2 deficiency. There is also antagonism between fohc acid and the anticonvulsants used in the treatment of epilepsy. 

Elevated homocysteine concentrations have been associated with an increased risk for cardiovascular disease in both epidemiologic and clinical studies.43 Several studies have evaluated the benefit of lowering homocysteine levels with folic acid supplementation. One study reported a reduction in major cardiac events with the combination of folic acid, vitamin B12, and vitamin B6 following PCI.44 However, a more recent study found an increased risk of instent restenosis and the need for target-vessel revascularization with folate supplementation following coronary stent placement.45 The role of folate in the management of IHD is currently unclear. 

The risk of colon cancer appears to be inversely related to calcium and folate intake. Calciums protective effect may be related to a reduction in mucosal cell proliferation rates or through its binding to bile salts in the intestine, whereas dietary folate helps in maintaining normal bowel mucosa. Additional micronutrient deficiencies have been demonstrated through several studies to increase colorectal cancer risk and include selenium, vitamin C, vitamin D, vitamin E, and 3-carotene however, the benefit of dietary supplementation does not appear to be substantial.11... 

The fibroblasts do not convert cyanocobalamin or hydroxocobalamin to methylcobalamin or adenosyl-cobalamin, resulting in diminished activity of both N5-methyltetrahydrofolate homocysteine methyltransferase and methylmalonyl-CoA mutase. Supplementation with hydroxocobalamin rectifies the aberrant biochemistry. The precise nature of the underlying defect remains obscure. Diagnosis should be suspected in a child with homocystinuria, methylmalonic aciduria, megaloblastic anemia, hypomethioninemia and normal blood levels of folate and vitamin B12. A definitive diagnosis requires demonstration of these abnormalities in fibroblasts. Prenatal diagnosis is possible. 

Folic acid supplements are given to pregnant women to decrease the risk of neural tube defects such as spina bifida. Prenatal vitamin preparations that contain higher concentrations of folic acid must be dispensed under a health care worker s guidance because high folate intakes can mask the symptoms of pernicious anemia. 

Replenish other vitamin stores with folate, B-complex, and multivitamin supplements. 

Folic acid deficiency, unlike vitamin B12 deficiency, is often caused by inadequate dietary intake of folates. Patients with alcohol dependence and patients with liver disease can develop folic acid deficiency because of poor diet and diminished hepatic storage of folates. Pregnant women and patients with hemolytic anemia have increased folate requirements and may become folic acid-deficient, especially if their diets are marginal. Evidence implicates maternal folic acid deficiency in the occurrence of fetal neural tube defects, eg, spina bifida. (See Folic Acid Supplementation A Public Health Dilemma.) Patients with malabsorption syndromes also frequently develop folic acid deficiency. Patients who require renal dialysis develop folic acid deficiency because folates are removed from the plasma during the dialysis procedure. 

Folic acid (or folate) deficiency, one of the most common vitamin deficiencies in the population consuming few dietary fruits and vegetables, causes chromosome breaks in humans,34 analogous to those caused by radiation. Folate supplementation above... 

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