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Biomedical subjects

G Alfthan

Publications and source records attributed to G Alfthan.

At least 73 records · Page 4Linked to original sources

Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial in men with low antioxidant status.

We investigated the effect on platelet function of supplementing men with low antioxidant status with 600 mg ascorbic acid, 300 mg alpha-tocopherol, 27 mg beta-carotene, and 75 micrograms selenium in yeast daily. Eighty men were randomly assigned in pairs (matched for smoking, baseline antioxidant status, and time and day of entry) by use of a double-blind design to receive supplement or placebo for 5 mo. Compared with 39 control subjects, 39 antioxidant-supplemented men experienced the following net reductions during the double-blind period: 20% (P = 0.012) in serum lipid peroxides, 24% (P = 0.035) in ADP-induced platelet aggregation, 42% (P = 0.040) in the rate of ATP release during aggregation, 51% (P = 0.018) in serum (platelet-produced) thromboxane B2, and 29% (P = 0.024) in plasma beta-thromboglobulin concentration. The data support our hypothesis that antioxidant supplementation of men with low antioxidant status and high fat intake reduces lipid peroxidation, the capacity of platelets to aggregate and to produce thromboxane A2, and in vivo platelet activation.

Adenosine Triphosphate↗

Role of selenium-dependent glutathione peroxidase in protecting against t-butyl hydroperoxide-induced damage in hepatocytes.

The role of the selenoenzyme glutathione peroxidase (Se-GSHPx) in protecting against oxidative injury was studied in hepatocytes isolated from rats fed either a low-selenium (Se-) or a selenium-adequate (Se+, control) diet. In rats fed Se- diet for eight weeks the selenium content of plasma and liver was lowered to 15 and 8%, respectively. No Se-GSHPx and only 5% of total GSHPx activity was detected in Se- hepatocytes. However, the Se- hepatocytes were as resistant as the Se+ cells to oxidative injury by 0.8 mM tert-butyl hydroperoxide (t-BuOOH), or 0.2 mM t-BuOOH plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of oxidized glutathione (GSSG) reductase. Only at 1.5 mM t-BuOOH or at 0.5 mM t-BuOOH with BCNU were cell damage and lipid peroxidation more evident in Se- cells. At all t-BuOOH concentrations used the depletion of cellular glutathione (GSH) was similar in magnitude in Se- and Se+ cells, but Se+ cells released more glutathione (mainly GSSG), obviously due to their higher Se-GSHPx activity. These results suggest that hepatocytes devoid of Se-GSHPx activity maintain a high capacity to resist peroxidative attack, either via residual (non-Se)GSHPx activity or other compensatory GSH-associated detoxication mechanisms.

Animals↗

Serum selenium and subsequent risk of cancer among Finnish men and women.

The association between the serum selenium level and the subsequent incidence of cancer was investigated in a longitudinal study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. The baseline examinations, including the collection of blood samples, were performed in 1968-1972. During a median follow-up of 10 years, 1,096 new cancer cases were identified from the files of the Finnish Cancer Registry. Selenium concentrations were measured from the stored serum samples collected from these cancer cases and from two controls per case, matched for sex, municipality, and age. The mean serum selenium level was 59.1 micrograms/L among all male cancer cases and 62.5 micrograms/L among controls. The difference was statistically significant (P less than .001). Corresponding values among women were 63.6 and 63.9 micrograms/L, respectively. Low serum selenium levels were associated with an increased risk of developing cancer at several sites, especially cancers of the stomach and lung among men. The relative risk of lung cancer between the highest and lowest decile of serum selenium was 0.11, and it differed significantly from unity (P less than .001). These findings are in agreement with the hypothesis that low selenium intake may increase the risk of some cancers among men.

Adolescent↗

Plasma antioxidants and coronary heart disease: vitamins C and E, and selenium.

The possibility of a relation between plasma antioxidants such as vitamins C and E and selenium, and mortality from coronary heart disease (CHD) was examined. A cross-sectional survey was undertaken of random population samples of apparently healthy middle-aged men in four European regions with differing mortalities from CHD [rate/100,000 for men aged 40-49]: north Karelia (eastern Finland) (n = 99) [212/100,000]; south-west Finland (n = 85) [146/100,000]; Scotland (n = 131) [140/100,000]; and south Italy (n = 80) [43/100,000]. Median (5th-95th percentile) plasma vitamin C concentrations were lower in Scotland: 18.2 (5.7-61.3) microM than in other regions: north Karelia 28.4 (6.2-85.2); south-west Finland 33.5 (5.7-76.6); south Italy 38.0 (10.2-69.8) microM (P less than 0.001). The median levels in the four areas did not however reflect the regional CHD mortality rates. Regional differences in plasma vitamin E levels were also observed: Scottish levels were low 20.0 (12.1-29.3) microM (P less than 0.001) and did not differ between the other areas: 23.0 (16.7-35.1), 22.5 (13.7-31.6) and 23.9 (15.6-41.3) microM respectively. The vitamin E gradient could be explained in part by differences in serum cholesterol. However, cholesterol-adjusted vitamin E levels were low in the three high CHD areas: Scotland 3.41 (2.41-4.62); north Karelia 3.53 (2.67-5.18); south-west Finland 3.53 (2.58-4.92); Italy 4.81 (3.25-5.99) mumol/mmol cholesterol (P less than 0.001). Cholesterol-adjusted vitamin E was not lower in north Karelia, the higher CHD mortality area in Finland. Serum selenium values also varied with the area examined and reported low levels in Finland were confirmed. Nevertheless, selenium levels did not correlate with the reported mortality rates of CHD. Thus in our small cross-cultural study the evidence did not support our hypothesis that plasma antioxidants explain regional differences in CHD mortality.

Adipose Tissue↗

Vitamin A, vitamin E and selenium status in an aged Finnish male population.

Vitamin A (retinol), vitamin E (alpha-tocopherol) and selenium concentrations in serum were studied during the autumn season (October and November) in two Finnish male populations aged 65-84 years and living either in eastern or southwestern Finland. The mean vitamin A concentration was higher in south-western, but the mean selenium concentration was higher in eastern Finland. Mean vitamin A concentrations did not differ between age groups, but in the south-west highest vitamin E and selenium concentrations were found among the youngest population. A severe vitamin A deficiency (below 300 micrograms/l) was found only in 3 (1%) men in the east and 4 (1%) men in the south-west, and a mild deficiency (300-399 micrograms/l) in 11 (4%) men in the east and 16 (4%) men in the south-west. Vitamin E deficiency after the correction by serum total cholesterol (below 2 mg/l/g/l) was found only in 3 (1%) men in the east and 1 (0%) man in the south-west, and low values (2.0-2.9 mg/l/g/l) were found in 13 (4%) men in the east and 34 (9%) men in the south-west. A severe deficiency of selenium (below 46 micrograms/l) was found in 10 (3%) men in the east and 15 (4%) men in the south-west, while a mild deficiency (46-69 micrograms/l) was found in 140 (45%) men in the east and 197 (52%) men in the south-west. The overall vitamin A and vitamin E status of elderly Finnish men was relatively adequate, while severe or mild deficiencies of selenium were common.

Aged↗

Biochemical indicators related to antioxidant status and bone metabolic activity in Finnish elderly men.

Serum concentrations of vitamins A, D and E, osteocalcin, calcium, selenium, cholesterol and HDL-cholesterol were measured in 270 elderly Finnish men aged from 65 to 84 years. alpha-Tocopherol and selenium decreased with aging as did 25-hydroxyvitamin D. Low serum levels were found especially for 25-hydroxyvitamin D (19% less than 8 micrograms/l), selenium (45% less than 70 micrograms/l) and osteocalcin (52% less than 1.8 micrograms/l). Men living in institutions for the aged had lower serum 25-hydroxyvitamin D levels than those living at home. Smoking was associated with decreased and alcohol consumption with increased serum levels of 25-hydroxyvitamin D. Those men who reported having most weekly working hours had highest serum levels of 25-hydroxyvitamin D. Serum osteocalcin correlated with 25-hydroxyvitamin D at normal or high serum vitamin levels but not at low vitamin levels; neither did it correlate with age or consumption of tobacco, alcohol or multivitamin pills.

Aged↗

Serum vitamin E, serum selenium and the risk of gastrointestinal cancer.

The association between levels of alpha-tocopherol and selenium in serum and subsequent risk of gastrointestinal cancer was investigated in a longitudinal study based on 36,265 Finnish men and women, aged 15-99 and initially free of cancer. Serum alpha-tocopherol and serum selenium levels at entry into the study were measured from stored serum samples of 150 incident gastrointestinal cancer cases diagnosed during a follow-up of 6-10 years and for 276 controls who were matched for sex, age and place of residence. Subjects with a low level of alpha-tocopherol or selenium had an elevated subsequent risk of cancer of the upper gastrointestinal tract. This association persisted among men after adjustment for various confounding factors and after the exclusion of those with cancer diagnosed during the first 2 years of follow-up. The relative risk of cancer of the upper gastrointestinal tract among men who fell in the lowest quintile of serum selenium was 3.3 (95% confidence limits, 1.3 and 9.1) while among those who fell in the 3 lowest quintiles of alpha-tocopherol it was 2.2 (95% confidence limits 0.9 and 5.6) compared with those in the higher quintiles. Serum levels of selenium or alpha-tocopherol in general were not inversely associated with colorectal cancer risk. These findings indicate that high selenium intake and possibly also high vitamin E intake, especially among men, may provide protection against cancer of the upper gastrointestinal tract but not against colorectal cancer.

Aged↗

Effect of fat on human liver selenium concentration.

Liver samples from 94 adult men and eight fetuses were obtained at autopsy from the Helsinki region. After lyophilization, the samples were analyzed for selenium (Se) both before and after extraction of fat with hexane/isopropanol. An inverse exponential relationship (R2 = 0.63) existed between unextracted adult liver Se concentration and the corresponding liver fat concentration. The relationship ceased to exist when Se was determined on the defatted tissue. The mean defatted adult liver Se concentration, 16.8 microM/kg dry wt, was significantly higher (p less than 0.001) than that of unextracted samples, 12.1 microM/kg. The Se concentration of fetal liver was not affected by the fat extraction. An age relationship (p less than 0.01) was found between subjects under 25 y and those over 40 y when the Se concentration was expressed per unextracted liver tissue but when expressed per defatted liver tissue the difference between age groups widened to comprise subjects over 60 y. Hepatic fat (mean Se concentration 2.7 microM/kg) thus constitutes a diluting factor. We conclude that the Se concentration of fatty human liver results in an underestimation of the selenium status of subjects who have an unphysiologically high liver fat concentration.

Adult↗

Relationship of serum selenium and antioxidants to plasma lipoproteins, platelet aggregability and prevalent ischaemic heart disease in Eastern Finnish men.

In a cross-sectional population study of 1132 unselected Eastern Finnish men aged 54 years, serum selenium concentration had a weak positive association with plasma HDL cholesterol (standardised partial regression coefficient, beta = 0.061, P = 0.019) and a fairly strong inverse relationship (beta = -0.223, P less than 0.001) with the extent of ADP-induced platelet aggregation. Neither plasma ascorbate concentration nor alpha-tocopherol to total cholesterol ratio had any association with plasma lipoproteins, platelet aggregability or prevalent ischaemic heart disease (IHD). When a covariance-correction was applied, men with ischaemic ECG findings at exercise had a lower mean serum selenium than others (81.5 micrograms/l vs. 85.9 micrograms/l, P less than 0.01 for difference). This difference was equally large for men with neither symptoms nor previous diagnosis of IHD.

Antioxidants↗

Selenium intake and serum selenium in Finland: effects of soil fertilization with selenium.

Since fall 1984 all agricultural multinutrient fertilizers in Finland have been supplemented with sodium selenate in an attempt to improve the nutritional quality of local foodstuffs known to be exceptionally low in selenium. The intervention has been effective from the growing season 1985 and it has affected practically all domestic agricultural products. From 1984 to 1986 the mean Se concentration of different foods increased. The mean Se intake of the population, calculated on the basis of food consumption statistics and from the data of urinary Se excretion, as well as the average serum Se concentration of both urban and rural people increased also during the same period. Enrichment of fertilizers with sodium selenate seems an efficient and predictable way of increasing the Se concentration of foods and the Se intake of people in low-Se areas.

Adult↗

Serum selenium and risk of cancer. A prospective follow-up of nine years.

The association between serum selenium concentration and the risk of cancer was studied in 1110 men aged 55 to 74 years in two rural areas of Finland. The men were followed-up prospectively for 9 years and there were 109 new cases of cancer, with the cases of the first follow-up year excluded. The serum selenium concentrations were adjusted for age, area, smoking, serum cholesterol, and alcohol intake. The patients had a slightly lower adjusted mean serum selenium than the subjects without cancer at the end of the follow-up (+/- standard error of mean) 53.9 +/- 1.5 and 55.3 +/- 0.5 micrograms/l, respectively. The relative risks of cancer were essentially the same when these were calculated in the tertiles of the serum selenium distribution. Thirty-seven men had a history of cancer at baseline or had cancer diagnosed during the first follow-up year and their adjusted mean serum selenium was 49.4 +/- 2.6 micrograms/l, which was significantly lower (P less than 0.05) than that of the subjects without cancer during the follow-up.

Aged↗

Blood and liver selenium concentrations in patients with liver diseases.

To study the relation between blood and liver selenium levels in hepatic disorders we measured the selenium concentrations of whole blood, serum and liver tissue obtained at laparoscopy in 17 patients with different kinds of liver diseases. As compared to healthy controls the mean concentration of selenium was decreased by 24% (p less than 0.001) in the whole blood of the patients (n = 15). Similarly, the mean concentration of selenium in serum was 35% lower in the patients than in the controls (p less than 0.001). As compared to the control samples obtained at autopsy the selenium content of liver was decreased by 13% (p less than 0.05) in the patients. Significant positive correlations were found between the selenium content of the liver and the whole blood (r = 0.62, p less than 0.05) as well as also between liver and serum (r = 0.52, p less than 0.05) selenium concentrations. In conclusion, the present study suggests that in patients with liver disorders the selenium concentrations are decreased not only in the blood but also in the liver tissue. Whether this means a decreased activity of hepatic glutathione peroxidase and, further, an increased possibility of oxidative cell injury, remains open.

Adult↗

Employed problem drinkers: a nutritional risk group?

Nutritional assessment was made in 26 employed Finnish men drinking excessively and in 49 control men. Because of their greater alcohol consumption, daily intake of energy of case men significantly exceeded that of control men; other dietary differences were negligible. Compared with control men, case men had thicker fatfolds but reduced mean body mass and arm muscle circumference. Mean circulating levels of vitamin C and alpha-tocopherol were normal and equal in case and control men, but serum retinol was raised and beta-carotene was reduced in case men. Serum concentration and 24-h urinary excretion of selenium were significantly lower in case than in control men. Serum levels of magnesium and zinc were similar in both groups, but urinary excretions were higher in case men. Heavy drinking does not result in florid nutritional deficiencies in socially intact men, but its role in subtle nutritional alterations deserves further studies.

Adult↗

Selenium in pregnancy: effect of maternal drinking.

To study the effect of drinking alcohol during pregnancy on serum selenium, selenium concentrations were measured in 41 women (ten abstinent, 31 problem drinkers) throughout pregnancy as well as in 24 nonpregnant abstinent women. In abstinent pregnant women, serum selenium decreased with advancing gestational age, a pattern not affected by moderate maternal drinking (42 to 126 g of ethanol weekly, N = 14). Seventeen women drank heavily (more than 140 g of ethanol weekly), and nine of them (53%) gave birth to infants with fetal alcohol syndrome. The women with infants having fetal alcohol syndrome had higher (P less than 0.05) selenium levels than the abstinent controls both at the 25th to 32nd (63.3 +/- 6.2 versus 56.6 +/- 4.4 micrograms/L) and at the 33rd to 40th gestational weeks (58.6 +/- 3.4 versus 53.5 +/- 5.9 micrograms/L). The selenium levels in umbilical serum were 20 and 33% lower than in maternal serum of abstinent and drinking women, respectively. However, alcohol-damaged newborns did not demonstrate any further decrease in selenium levels. Thus, heavy maternal drinking is accompanied by increased maternal and decreased umbilical concentration of selenium.

Alcohol Drinking↗