B Vitamins and Disease

Alcoholism affects about 10% of the drinking population and alcohol (ethanol) abuse has been implicated in at least 20% of admissions to general hospitals. This chronic disease exhibits high mortality due to a wide variety of factors. Ethanol produces effects in virtually every organ system. The biochemical effects of ethanol are due to increased production of NADH that decreases the [NAD ]/[NADH] ratio in the cytoplasm of liver cells at least tenfold from the normal value of about 1000. Increased production of lactate and inhibition of gluconeo-genesis (Chapter 15) result. The hyperuricemia associated with ethanol consumption has been attributed to accelerated turnover of adenine nucleotides and their catabolism to uric acid (Chapter 27). Alcohol increases hepatic fatty acid and triacylglycerol synthesis and mobilization of fat from adipose tissue, which can lead to fatty liver, hepatitis, and cirrhosis. These effects are complicated by a deficiency of B vitamins and protein. 

Coverage includes B vitamins and folate in the context of a historical background, disease, cardiovascular effects and the importance of vitamins in biochemistry as illustrated by a single vitamin. Thereafter there are chapters on the chemistry and biochemistry of thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folate and cobalamin. Methodical aspects include characterization and assays of B vitamins and folate in foods of all kinds, dietary supplements, biological fluids and tissues. The techniques cover solid-phase extraction, spectrofluorimetry, mass spectrometry, HPLC, enzymatic assay, biosensor and chemiluminescence. In terms of fimction and effects or... 

Dangour, A.D., Whitehouse, P.J., Rafferty, K., Mitchell, S.A., Smith, L., Hawkesworth, S., and Vellas, B., 2010. B vitamins and fatty acids in the prevention and treatment of Alzheimer s disease and dementia a systematic review. Journal of Alzheimer s Disease. 22 205-224. 

Heinz, J., Kropf, S., Domrose, U., Westphal, S., Borucki, K., Luley, C., Neumann, K.H., and Dierkes, J., 2010. B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease results of a randomized controlled trial. Circulation. 121 1432-1438. 

Robinson, K., 2000. Homocysteine, B vitamins, and risk of cardiovascular disease. Heart. 83 127 130. 

McCully made the first connection between homocysteine levels and cardiovascular disease in 1969. Since then there have been many studies showing that higher plasma homocysteine levels are associated with a higher risk of cardiovascular, cerebrovascular and peripheral arterial disease. (This topic is developed in the chapter Cardiovascular effects of B vitamins and folate in the context of fortification ). 

Galan, P., Kesse-Guyot, E., Czernichow. S., et al, 2010. Effects of B-vitamins and omega-3 fatty acids on cardiovascular diseases a randomised placebo-controlled trial. British Medical Journal. 341 c6273. 

Qualified health claims for dietary supplements recognized by the FDA as part of its enforcement discretion include such examples as the relationships between phosphatidylserine and cognitive function, B vitamins and cardiovascular disease, omega-3 fatty acids and cardiovascular disease, selenium and cancer, and antioxidant vitamins and cancer. 

Homocysteine arises from dietary methionine. High levels of homocysteiae (hyperhomocysteinemia) are a risk factor for occlusive vascular diseases including atherosclerosis and thrombosis (81—84). In a controlled study, semm folate concentrations of <9.2 nmol/L were linked with elevated levels of plasma homocysteiae. Elevated homocysteine levels have beea associated also with ischemic stroke (9). The mechanism by which high levels of homocysteine produce vascular damage are, as of yet, aot completely uaderstood. lateractioa of homocysteiae with platelets or eadothehal cells has beea proposed as a possible mechanism. Clinically, homocysteine levels can be lowered by administration of vitamin B, vitamin B 2> foHc acid. 

The typical U.S. daily diet contains 1.1—3.6 mg of vitamin B, most coming from meats and vegetables. Poor diets may provide less than half of these amounts and less than the RDA. Some populations require higher amounts persons with high protein intakes, pregnant and lactating women, users of oral contraceptives, alcohoHcs, users of dmgs which interfere with vitamin B function, and those afflicted with some diseases. Several reviews have examined the relationship of vitamin B and specific diseases in more detail (4,23). 

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. 

Both statements are valid but the second statement, (b), states more accurately why it is that we need vitamins. Vitamin-deficiency diseases, Such as scurvy, result when certain catabolic and anabolic reactions are not able to proceed efficiently in the absence of these important nutrients. 

Wheat germ is the embryo of wheat berry. It is a good source of coenzyme Q10, vitamin E, choline, most of the B vitamins, the minerals calcium, magnesium, phophorus, and several trace elements. This chapter provides information only on coenzyme Q10, which is useful in the treatment of the pleiotropic manifestation of the following diseases ... 

Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006 354(15) 1567-1577. 

Li JY Taylor PR, Li B, et al. Nutrition intervention trial in Linxian, China multiple vitamin/mineral supplementation, cancer incidence, and disease specific mortality among adults with esophageal displasia. J Natl Cancer Inst 1993 85 1492-1498. 

Measurement of blood tHcy is usually performed for one of three reasons (1) to screen for inborn errors of methionine metabolism (2) as an adjunctive test for cobalamin deficiency (3) to aid in the prediction of cardiovascular risk. Hyperhomocysteinemia, defined as an elevated level of tHcy in blood, can be caused by dietary factors such as a deficiency of B vitamins, genetic abnormalities of enzymes involved in homocysteine metabolism, or kidney disease. All of the major metabolic pathways involved in homocysteine metabolism (the methionine cycle, the transsulfuration pathway, and the folate cycle) are active in the kidney. It is not known, however, whether elevation of plasma tHcy in patients with kidney disease is caused by decreased elimination of homocysteine in the kidneys or by an effect of kidney disease on homocysteine metabolism in other tissues. Additional factors that also influence plasma levels of tHcy include diabetes, age, sex, lifestyle, and thyroid disease (Table 21-1). 

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