Life Extension Magazine




May 5, 2000

 

References


 

181. Selenium.
Barceloux DG
dgbarcelou@aol.com
J Toxicol Clin Toxicol, 1999, 37:2, 145?72

The 4 natural oxidation states of selenium are elemental selenium (0), selenide (?2), selenite (+4), and selenate (+6). Inorganic selenate and selenite predominate in water whereas organic selenium compounds (selenomethionine, selenocysteine) are the major selenium species in cereal and in vegetables. The principal applications of selenium include the manufacture of ceramics, glass, photoelectric cells, pigments, rectifiers, semiconductors, and steel as well as use in photography, pharmaceutical production, and rubber vulcanizing. High concentrations of selenium in surface and in ground water usually occur in farm areas where irrigation water drains from soils with high selenium content (Kesterson Reservoir, California) or in lakes receiving condenser cooling water from coal?fired electric power plants (Belews Lake, North Carolina). For the general population, the primary pathway of exposure to selenium is food, followed by water and air. Both selenite and selenate possess substantial bioavailability. However, plants preferentially absorb selenates and convert them to organic compounds. Aquatic organisms (e.g., bivalves) can accumulate and magnify selenium in the food chain. Selenium is an essential component of glutathione peroxidase, which is an important enzyme for processes that protect lipids in polyunsaturated membranes from oxidative degradation. Inadequate concentrations of selenium in the Chinese diet account, at least in part, for the illness called Keshan disease. Selenium deficiency occurs in the geographic areas where Balkan nephropathy appears, but there is no direct evidence that selenium deficiency contributes to the development of this chronic, progressive kidney disease. Several lines of scientific inquiry suggest that an increased risk of cancer occurs as a result of low concentrations of selenium in the diet; however, insufficient evidence exists at the present time to recommend the use of selenium supplements for the prevention of cancer. The toxicity of most forms of selenium is low and the toxicity depends on the chemical form of selenium. The acute ingestion of selenious acid is almost invariably fatal, preceded by stupor, hypotension, and respiratory depression. Chronic selenium poisoning has been reported in China where changes in the hair and nails resulted from excessive environmental exposures to selenium. Garlic odor on the breath is an indication of excessive selenium exposure as a result of the expiration of dimethyl selenide. The US National Toxicology Program lists selenium sulfide as an animal carcinogen, but there is no evidence that other selenium compounds are carcinogens.

182. Selenium and cardiovascular diseases??an update.
Huttunen JK
National Public Health Institute, Helsinki, Finland.
Biomed Environ Sci, 1997 Sep, 10:2?3, 220?6

Dietary deficiency of selenium has been incriminated in the etiology of cardiovascular diseases. Thus, cardiomyopathy associated with low selenium intake has been described in areas of exceptionally low selenium intake and in patients receiving total parenteral nutrition. Epidemiological studies have provided some evidence for the role of selenium deficiency in the etiology of atherosclerotic disease. An inverse association between the incidence of ischaemic heart disease and selenium intake has been described in population comparisons. The results of longitudinal studies within populations are conflicting. While some investigations have observed a relationship between low serum?selenium levels and the risk of coronary disease, others have not. Final evidence for the role of selenium in preventing atherosclerotic disease can be obtained only from controlled prevention trials.

183. Selenium and cardiovascular pathology
Neve J
UnitÆe de Toxicologie et de Chimie Bioanalytique, FacultÆe de MÆedecine et de Pharmacie,
UniversitÆe Libre de Bruxelle, Belgique.
Pathol Biol (Paris), 1989 Dec, 37:10, 1102?6

Selenium deficiency has established implications in cardiovascular diseases, particularly on cardiac muscle integrity. The essential trace element takes part not only in the direct protection of endothelial cells against the accumulation of aggressive oxygen species, but also in the biosynthesis of arachidonic acid derivatives involved in platelet and leucocyte functions, or in the regulation of cholesterol. Moreover, it prevents toxic effects of cadmium and mercury, and modulates the active transport of calcium. Some clinical investigations have underlined its importance in the cardiac function and the prevention of coronary atherosclerosis, and several recent prospective epidemiological studies have attributed to selenium deficiency a greater incidence of cardiovascular diseases. Further studies should be devoted to the influence of marginal deficiency in this trace element whose optimal requirement does not seem to be met by the usual dietary intake.

184. Association between beta?carotene and acute myocardial infarction depends on polyunsaturated fatty acid status. The EURAMIC Study. European Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast.
Kardinaal AF; Aro A; Kark JD; Riemersma RA; van t Veer P; Gomez Aracena J; Kohlmeier L; Ringstad J; Martin BC; Mazaev VP; et al
Department of Epidemiology, TNO Nutrition and Food Research, Zeist, Netherlands.
Arterioscler Thromb Vasc Biol, 1995 Jun, 15:6, 726?32

Because antioxidants may play a role in the prevention of coronary heart disease by inhibiting the peroxidation of polyunsaturated fatty acids (PUFAs), the combined association of diet?derived antioxidants and PUFAs with acute myocardial infarction (MI) was investigated. This multicenter case?control study included 674 patients and 725 control subjects in eight European countries and Israel. Fatty acid composition and alpha?tocopherol and beta?carotene levels were determined in adipose tissue; selenium level was determined in toenails. For alpha?tocopherol no association with MI was observed at any PUFA level. The overall multivariate odds ratio (OR) for low (10th percentile) versus high (90th percentile) beta?carotene was 1.98 (95% confidence interval [CI], 1.39 to 2.82). The strength of this inverse association with MI was dependent on PUFA levels (in tertiles): for low PUFA, the OR for low versus high beta?carotene was 1.79 (95% CI, 0.98 to 3.25), for medium PUFA the OR was 1.76 (95% CI, 1.00 to 3.11), and for high PUFA 3.47 (95% CI, 1.93 to 6.24). For selenium increased risk was observed only at the lowest PUFA tertile (OR, 2.49; 95% CI, 1.22 to 5.09). This interaction between selenium and PUFAs was not significant and may at least partly be explained by a higher proportion of smokers at the low PUFA level. These findings support the hypothesis that beta?carotene plays a role in the protection of PUFAs against oxidation and subsequently in the protection against MI. No evidence was found that alpha?tocopherol or selenium may protect against MI at any level of PUFA intake.

185. Antioxidants and coronary heart disease.
van Poppel G; Kardinaal A; Princen H; Kok FJ
Department of Epidemiology, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Ann Med, 1994 Dec, 26:6, 429?34

This review briefly summarizes the scientific evidence for a possible role of antioxidants in the prevention of coronary heart disease (CHD). Antioxidants in our diet include vitamins E, C, and beta?carotene, whereas selenium is an integral part of the antioxidant enzyme glutathione peroxidase (GSHPx). Experimental evidence suggests that free?radical damage and antioxidant defence may play an important role in the development of coronary heart disease. Epidemiological studies have produced some intriguing results, but have not indicated unequivocally that a high intake of antioxidants leads to a decreased cardiovascular disease risk. We conclude that the antioxidant atherosclerosis hypothesis is promising, but that the results of long?term intervention studies are still to be awaited. Preventive action based on antioxidant supplementation is therefore not justifiable as yet. Nevertheless, the findings so far certainly do support the recommendations for a varied diet rich in vegetables and fruit.

186. Selenium, glutathione peroxidase, peroxides and platelet functions
Vitoux D; Chappuis P; Arnaud J; Bost M; Accominotti M; Roussel AM
Laboratoire central de biochimie, hÈopital LariboisiÄere, Paris, France.
Ann Biol Clin (Paris), 1996, 54:5, 181?7

In the last five years, there has been a renewal of interest in the protective role of selenium in vascular disorders, inspired by experimental evidence that this trace element could modulate leukotriene and prostaglandin synthesis in both endothelial cells and platelets. In people living in low?selenium areas, a relationship has been established between a decrease in plasma selenium and an increase in the risk of coronary disease, atherosclerosis, platelet hyperaggregability and synthesis of proaggregant and proinflammatory compounds like thromboxane A2 and leukotrienes. Selenium, as an essential part of glutathione peroxidase, takes part in the reduction of hydrogen peroxides and lipid peroxides. The concentration of these peroxides, in turn, regulates the activities of cyclooxygenase and lipooxygenase pathways, ultimately influencing the production of eicosanoids and modulating the balance between a proaggregatory and antiaggregatory state.Recent evidence shows that selenium, via its action on glutathione peroxidase activity, may be primarily responsible for the regulation of the endogenous hydroperoxide level. In human platelets, the activity of glutathione peroxidase is particularly high and is very sensitive to the requirement of selenium. This sensitivity could explain why platelets of selenium?deficient subjects show increased aggregation, thromboxane B2 production and synthesis of the lipoxygenase?derived compounds. In these deficient subjects, selenium administration increases platelet glutathione peroxidase activity and inhibits platelet hyperaggregation and leukotriene synthesis. These results support the hypothesis that selenium supplementation has a positive effect on platelet aggregation in selenium?deficient subjects. In France, more than 10% of the population is selenium?deficient and long?term supplementation with low doses of selenium could have a beneficial effect on the prevention of both thrombosis and coronary heart disease in these subjects.

187. Selenium as a risk factor for cardiovascular diseases.
Nève J
UniversitÆe Libre de Bruxelles, Institut de Pharmacie, Belgium.
J Cardiovasc Risk, 1996 Feb, 3:1, 42?7

Selenium is a powerful antioxidant regulating the activity of the glutathione peroxidase enzymes, which catalyse the detoxification of hydrogen peroxide and organic hydroperoxides. Selenium deficiency has been implicated in the aetiopathogeny of Keshan disease, an endemic cardiomyopathy observed in China, and in other cases of congestive cardiomyopathy in subjects on artificial nutrition. However, the evidence from case?control and prospective studies for an association between low selenium status and cardiovascular diseases remains controversial. Mechanisms whereby selenium protects against such diseases include increased resistance of
low?density lipoproteins against oxidative modification, modulation of prostaglandin synthesis and platelet aggregation, and protection against toxic heavy metals. The therapeutic benefit of selenium administration in the prevention and treatment of cardiovascular diseases still remains insufficiently documented.

188. Natural antioxidants for the prevention of atherosclerosis.
Odeh RM; Cornish LA
Department of Pharmacy Services, University of Michigan Medical Center and College of Pharmacy, Ann Arbor 48109, USA.
Pharmacotherapy, 1995 Sep, 15:5, 648?59

Hypercholesterolemia, cigarette smoking, hypertension, and obesity are known contributing risk factors for the development of atherosclerotic coronary artery disease (CAD). However, they account for only half of all cases of CAD, and the complete pathologic process underlying atherosclerosis remains unknown. Growing evidence suggests that oxidative modification of low?density lipoprotein (LDL) may be of particular importance in the pathogenesis. Oxidized LDL exhibits proatherogenic effects. Therefore, current research has focused on inhibiting the oxidation of LDL as a means of inhibiting the atherosclerotic process. One such approach is to enhance the endogenous antioxidant defense systems within the LDL particle with lipophilic antioxidants such as alpha?tocopherol and beta?carotene, or by supplementing the aqueous?phase antioxidant capacity with ascorbic acid. Observational data suggest a protective effect of antioxidant supplementation on the incidence of CAD; however, specific doses cannot be recommended since the data are inconclusive.

189. Nutrition in the prevention of ischemic heart disease
Ginter E
Bratisl Lek Listy, 1989 Mar, 90:3, 203?21

The survey presents current knowledge on the role of nutrition in prevention of
hypercholesterolemia and ischemic heart disease. From the standpoint of their role in atherogenesis, nutritional factors can be divided into protective and risk factors. The group of protective factors includes n?3 and n?6 polyunsaturated fatty acids, oleic acid, plant sterols, plant lecithins, some fiber components (e.g. pectin), plant proteins (e.g. soybean), vitamin C, vitamin E, magnesium, potassium, calcium, chromium, and selenium. The group of risk factors comprises saturated fatty acids, cholesterol, sucrose, sodium, vitamin D, and ethanol. After World War II the development of food consumption in Czechoslovakia resulted in an imbalanced state persisting for some decades now which is characterized by a high involvement of risk factors (high consumption of meat, sausages, animal fats, eggs, common salt, and alcoholic beverages) and by a low involvement of protective factors (low consumption of vegetables, fruit, potatoes, legumes, fish, and roughly milled grain). The imbalance of risk and protective factors in nutrition is conceivably one of the main causes of the extremely high mortality from cardiovascular diseases in Czechoslovakia. The current unfavorable trend in the rate of ischemic heart disease and in life expectancy of the population in Czechoslovakia can not be reversed without substantial changes in the composition of nutrition.

190. Recent nutritional approaches to the prevention and therapy of cardiovascular disease.
Kendler BS
Manhattan College, NY, USA.
Prog Cardiovasc Nurs, 1997 Sum, 12:3, 3?23

Nutritional factors play an important role in the development and treatment of cardiovascular disease (CVD). However, health care professionals may overlook, or even disregard, some of these factors for several reasons, including inadequate training and conflicting reports in the biomedical literature. This review provides a synopsis of more than two?dozen nutritional approaches to primary and secondary prevention and therapy of CVD. Favorable cardiovascular effects have been reported with the use of unsaturated fatty acids, vegetarian and semi?vegetarian diets, dietary fiber, plant sterols, alcoholic beverages, vitamins (niacin, E, C, B6, B12, folate), minerals (potassium, calcium, magnesium, selenium), conditionally?essential nutrients (coenzyme Q10, L?carnitine, taurine) and botanical agents (garlic, hawthorn, gugulipid). In contrast, trans?fatty acids, oxysterols, homocysteinemia, carbohydrate intolerance, and excessive sodium chloride and iron have been associated with undesirable cardiovascular effects. A nutritional approach to CVD provides a pivotal adjuvant to traditional pharmaceutical and/or surgical interventions by maximizing the likelihood of success in decreasing CVD morbidity and mortality and minimizing the economic and social costs associated with this disease.

 




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