Cardiovascular disease folates

Supplements of 400 Ig/d of folate begun before conception result in a significant reduction in the incidence of neural mbe defects as found in spina bifida. Elevated blood homocysteine is an associated risk factor for atherosclerosis, thrombosis, and hypertension. The condition is due to impaired abihty to form methyl-tetrahydrofolate by methylene-tetrahydrofolate reductase, causing functional folate deficiency and resulting in failure to remethylate homocysteine to methionine. People with the causative abnormal variant of methylene-tetrahydrofolate reductase do not develop hyperhomocysteinemia if they have a relatively high intake of folate, but it is not yet known whether this affects the incidence of cardiovascular disease. 

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. 

Folate deficiency is associated with the increased risk of neural tube defects (spina bifida, anencephaly), cardiovascular diseases, megaloblastic anemia, and some cancers (Bailey et al., 2003 Finglas et al., 2006 Scott et al, 1999). Unfortunately, folate intake is suboptimal in most of the world s populations, even in developed countries (Scott et al., 2000). Therefore there is an urgent need to increase folate content and bioavailability in staple foods. Because of its large consumption worldwide, potato is an appealing target for enrichment. 

Moat SJ, Lang D, McDowell IF, Clarke ZL, Madhavan AK, Lewis MJ, Goodfellow J (2004) Folate, homocysteine, endothelial function and cardiovascular disease. J Nutr Biochem 15 64-79... 

Vitamins B6, B12, and folate An elevated plasma homocysteine level is associated with increased cardiovascular risk (see p. 263). Homocysteine, which is thought to be toxic to the vascular endothelium, is converted into harmless amino acids by the action of enzymes that require the B vitamins—folate, B6 (pyridoxine), and B12 (cobalamin). Ingesting foods rich in these vitamins can lower homocysteine levels and possibly decrease the risk of car diovascular disease. Folate and B6 are found in leafy green veg etables, whole grains, some fruits, and fortified breakfast cereals. B12 comes from animal food, for example, meat, fish, and eggs. 

JB Ubbink, PJ Becker, and WJH Vermaak. Will an increased dietary folate intake reduce the incidence of cardiovascular disease Nutr Rev 54 213-216, 1996. 

There exists an inverse association between folate and cardiovascular disease. Folic acid deficiency may result from ... 

Evidence that a diet rich in fruits and vegetables may protect against coronary heart disease is accumulating. It is unclear exactly which substances in fruits and vegetables are responsible for the observed inverse association with cardiovascular disease. The inverse association may be attributed to folate, antioxidant vitamins, or other constituents such as fiber, potassium, fla-vonoids, or other phytochemicals. The protective effect of folate may be attributed to its role as a cosubstrate in homocysteine metabolism (Eichholzer et al., 2001). 

The observed associations between folate, antioxidant vitamins, and cardiovascular disease may be confounded by other substances in fruits and vegetables, as the following examples of studies show Flavonoids (see Chapter 31) are naturally occurring, water-soluble antioxidants found widely distributed in vegetables, fruits, tea, and wine. There is an inverse relationship between flavonoids and decreased risk of coronary heart disease. Lycopene, the key antioxidant in tomatoes, shows an inverse association with myocardial infarctions. There is an inverse association between folate and cardiovascular disease. 

Eichholzer, M. et al., The role of folate, antioxidant vitamins and other constituents in fruit and vegetables in the prevention of cardiovascular disease the epidemiological evidence, Int. J. Vitam. Nutr. Res., 71, 5-17, 2001. 

Morgan SL, et al. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm,low dose methotrexate therapy for rheumatoid arthritis implications for cardiovascular disease prevention. J Rheumatol 1998 25(3) 44l-446. 

A rich source of iron and vitamins C and A, parsley also yields fatty acids and an essential or volatile oil. The essential oil of the leaves is considered superior to that from the seeds and is used in condiments and seasonings. Parsley seed oil is used in fragrances for perfumes, soaps and creams. Parsley has a very high content of vitamins (/i-carotene, thiamin, riboflavin and vitamins C and E) and is a rich source of calcium, iron and folate (Athar et al., 1999). A high proportion of the carotene is 9-cis-P-carotene, which is considered effective against cancer and cardiovascular disease (Ben-Amotz and Fishier, 1998). 

Possibly beneficial effects of intakes more than adequate to meet requirements the promotion of optimumhealth and life expectancy. There is evidence that relatively high intakes of vitamin E and possibly other antioxidant nutrients (Section 4.6.2) may reduce the risk of developing cardiovascular disease and some forms of cancer. High intake of folate during early pregnancy reduces the risk of neural tube defects in the fetus (Section 10.9.4). 

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. 

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). 

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. 

Surv eys designed to lest the possible connection between a history of eating foods rich (or poor) in folate, rich (or poor) in vitamin He, and the eventual diagnosis of cardiovascular disease. 

An epidemiological study supports the connection between low intakes of folate and of vitamin with cardiovascular disease. The study involved 80,082 women who were followed for 14 years. Vitamin intake was estimated by questionnaires, while the eventual acquisition of disea.se was determined by physicians who reviewed medical records. Although no biochemical tests were perfomned, it should be noted that this and other epidemiological studies acquire their power by their large number of subjects, as w ell as by small pilot studies that validate the accuracy of the questionnaires fkimm cf al., 1998). 

Folate, 492,493-494 adenoma rislt, 90S assessment of status, 508-514 biochenrustiy, 495-49fr cardiovascular disease and, 553 colorectal career, 09B hcumocysleire and, 515 metabolism... 

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... 

Some of the dreaded nutritional diseases of the past — such as scurvy, pellagra, and pernicious anemia — are discussed in this book. Such contemporary problems as infectious diarrhea, xerophthalmia, protein/energy malnutrition, and folate deficiency are discussed, as are diabetes and cardiovascular disease, two of the most sigf cant nutrition-related diseases. The last two conditions can be controlled in part by dietary intervention. 

There are several vitamin Bg-responsive inborn errors of metabolism that include (1) cases of infantile convulsions in which the apoenzyme for glutamate decarboxylase has a poor affinity for the coenzyme (2) a type of chronic anemia in which the number but not morphological abnormality of erythrocytes is improved by pyridoxine supplementation (3) xanthurenic aciduria in which affinity of the mutant kynureninase for PLP is decreased (4) primary cystathion-inuria caused by similarly defective cystathionase and (5) homocystinuria in which there is less of the normal cystathionine synthetase. In these cases increased levels (200 to lOOOmg/day) of administered vitamin Bg are required for life. Low vitamin Bg status (together with low vitamin B12 and folate status) in humans has been linked to hyperho-mocysteinemia and as an independent risk factor for cardiovascular disease. ... 

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