Serum vitamin E concentrations at 1 year and risk of atopy, atopic dermatitis, wheezing, and asthma in childhood: the PASTURE study.

BACKGROUND: Prospective studies investigating the role of serum vitamin E concentrations during early life in the development of childhood allergies and asthma are limited. OBJECTIVE: To study the associations between serum vitamin E concentrations at first year of life and longitudinal development of atopy, atopic dermatitis, wheeze, and asthma up to 6 years of age. METHODS: The setting was the PASTURE study, a multicenter prospective birth cohort study in five European rural settings. Children of 1133 mothers recruited during pregnancy were followed from birth with measurement of serum vitamin E levels at year 1 and repeated assessments of serum immunoglobulin E antibodies (year 1, 4.5, 6), atopic dermatitis, wheezing symptoms, and asthma (year 1, 1.5, 2, 3, 4, 5, 6). RESULTS: At 6 years of age, 66% and 82% of the original 1133 subjects underwent blood test for IgE and answered the questionnaire, respectively. We did not observe any statistically significant associations between serum vitamin E concentrations at year 1 and the endpoints, but borderline inverse associations between alpha tocopherol and wheezing without cold (OR 0.45, 95% CI 0.19-1.09) and any wheezing symptom (OR 0.52, 95% CI 0.27-1.02). CONCLUSIONS: Serum vitamin E concentrations at year 1 were not associated with allergies or asthma by 6 years of age. While further prospective studies with repeated assessments of vitamin E during early life may clarify its putative role in the development of the diseases, it is also possible that the antioxidant hypothesis in the development of allergies and asthma does not hold.

The effect of high-fiber rye bread enriched with nonesterified plant sterols on major serum lipids and apolipoproteins in normocholesterolemic individuals.

BACKGROUND AND AIMS: Plant sterols are naturally occurring cholesterol-lowering compounds which are industrially incorporated in various foods. A novel food carrier is rye bread, the intake of which can be monitored in trials utilizing newly defined plasma biomarkers. Our aim was to determine the effects of plant sterols incorporated into high-fiber rye bread on serum total and LDL cholesterol, apoB/apoA1 and total cholesterol/HDL cholesterol ratios and lipophilic (pro)vitamins in healthy free-living normocholesterolemic individuals. METHODS AND RESULTS: In this double-blind, dietary intervention trial the subjects (n=68) were randomized to receive a rye bread (9.3g/d fiber) with added plant sterols (2g/d) (active) or without (control). In the second phase of the study the amount of rye bread was doubled providing 18.6g/d fiber and in the active group 4g/d plant sterols. Compliance was monitored utilizing 3-day food diaries and a novel rye fiber-derived biomarker in plasma. Intake of rye bread enriched with 2g/d of plant sterols during two weeks reduced significantly serum total and LDL cholesterol, apoB/apoA1 and total cholesterol/HDL cholesterol ratios by 5.1%, 8.1%, 8.3% and 7.2%, respectively, compared to controls. Correspondingly, the following two-week treatment with 4g/d of plant sterols resulted in 6.5%, 10.4%, 5.5% and 3.7% difference compared to controls, being most pronounced for LDL (0.33 mmol/L). The treatments did not affect lipophilic (pro)vitamin levels. CONCLUSION: Rye bread enriched with 2-4g/d of nonesterified plant sterols beneficially modifies cardiovascular lipid risk factors in normocholesterolemic subjects compared to controls.

Selenium status and blood lipids: the cardiovascular risk in Young Finns study.

BACKGROUND: Concern has been recently raised about possible adverse cardio-metabolic effects of high selenium status, such as increased risks of diabetes and hyperlipidaemia. However, most of the evidence comes from selenium-replete populations such as that of the United States. OBJECTIVES: To examine cross-sectional and longitudinal associations of serum selenium with cardiovascular risk factors in Finland where selenium levels were amongst the lowest in the world until the early 1980s before the implementation of a nationwide selenium fertilization programme. METHODS: Serum selenium was measured in 1235 young Finns aged 3-18 years at baseline in 1980 (prefertilization) and in a subgroup (N = 262) at the 6-year follow-up (1986, postfertilization). During the 27-year follow-up, serum lipids, blood pressure, body mass index and smoking were assessed five times (1980, 1983, 1986, 2001 and 2007). RESULTS: Mean (±SD) serum selenium concentrations were 74.3 ± 14.0 ng mL(-1) in 1980 and 106.6 ± 12.5 ng mL(-1) in 1986 (average increase 32.3 ng mL(-1); 95% CI: 30.3 to 34.3, P < 0.0001). In univariate and multivariable cross-sectional models in 1980 and 1986, increased serum selenium levels were consistently associated with increased total, HDL and Low-density lipoprotein (LDL) cholesterol. However, the average longitudinal changes in lipids were -0.20 mmol L(-1) (95% CI: -0.30 to -0.10, P < 0.0001) for total cholesterol, 0.06 mmol L(-1) (95% CI: 0.03 to 0.10, P < 0.0001) for HDL cholesterol, and -0.23 mmol L(-1) (95% CI: -0.31 to -0.14, P < 0.0001) for LDL cholesterol. Selenium measured in 1986 was not associated with lipids assessed in 2001 and 2007. CONCLUSIONS: Cross-sectional findings from the Young Finns study corroborate positive associations of selenium status with serum lipids. However, longitudinal evidence does not support the causality of this link.

Serum and dietary beta-carotene and alpha-tocopherol and incidence of type 2 diabetes mellitus in a community-based study of Swedish men: report from the Uppsala Longitudinal Study of Adult Men (ULSAM) study.

AIMS/HYPOTHESIS: To investigate the association of serum concentrations and dietary intake of beta-carotene and alpha-tocopherol with type 2 diabetes incidence. METHODS: Serum beta-carotene, alpha-tocopherol, lifestyle factors (BMI, physical activity and smoking) and metabolic factors (insulin sensitivity [homeostasis model assessment], acute insulin response and impaired fasting glucose) were analysed in 846 50-year-old non-diabetic Swedish men (participants in the Uppsala Longitudinal Study of Adult Men). Diabetes was identified in 245 participants at reinvestigations after 10, 20 and 27 years. At the 20 year reinvestigation, dietary intake of beta-carotene and alpha-tocopherol, insulin sensitivity (euglycaemic-hyperinsulinaemic clamp) and insulin secretion (early insulin response in OGTT) were determined. RESULTS: The highest tertile of serum beta-carotene at age 50 (>0.335 mumol/l) was associated with 59% lower risk of diabetes during follow-up compared with the lowest tertile (<0.210 mumol/l) after adjustment for lifestyle and metabolic factors (p < 0.01). The highest tertile of lipid-corrected serum alpha-tocopherol at age 50 (>3.67 mumol/mmol) was associated with 46% lower risk of diabetes compared with the lowest tertile (<3.25 mumol/mmol) independently of metabolic factors (p < 0.05). Moreover, lower serum beta-carotene and alpha-tocopherol concentrations were independently associated with impaired insulin sensitivity (p < 0.001), but not with early insulin response, in a subsample of non-diabetic individuals 20 years later. Dietary intake of beta-carotene and alpha-tocopherol independently predicted type 2 diabetes during 7 years of follow-up. CONCLUSIONS/INTERPRETATION: Serum concentrations and dietary intakes of beta-carotene and alpha-tocopherol independently predicted insulin resistance and type 2 diabetes incidence during 27 years of follow-up in a community-based study of men. This result supports the importance of impaired antioxidant status for the development of insulin resistance and type 2 diabetes.

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.

Hyperhomocystinemia: a risk factor or a consequence of coronary heart disease?

BACKGROUND: Mild hyperhomocystinemia has been suggested as an indicator of an increased risk of cardiovascular disease. OBJECTIVE: To examine whether serum homocysteine concentration is a predictor of coronary heart disease (CHD) events. METHODS: A case-control study, nested in a population-based cohort study was used. During a follow-up of 13 years, 166 major coronary events (death from CHD or nonfatal myocardial infarction) occurred in men with evidence of heart disease at baseline and 272 events in men without a history of heart disease. Two controls per case were selected by individual matching. RESULTS: Among men with known heart disease at baseline, the relative risk (95% confidence interval) of CHD events adjusted for age, smoking, hypertension, diabetes mellitus, serum cholesterol level, body mass index, and alcohol consumption was 2.23 (95% confidence interval, 1.03-4.85) in the highest serum homocysteine quintile compared with the lowest quintile. Among the men free of heart disease at baseline, the corresponding relative risk was 0.90 (95% confidence interval, 0.51-1.60). CONCLUSIONS: This prospective study does not support the hypothesis that a high concentration of serum homocysteine is a risk factor for coronary events in a population free of heart disease. However, it does suggest that mild hyperhomocystinemia predicts secondary coronary events in men with heart disease, possibly as a consequence of atherosclerotic changes.

Antibody against oxidized low-density lipoprotein predicting myocardial infarction.

BACKGROUND: Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of atherosclerosis. The purpose of the present study was to determine whether antibody against oxidized low-density lipoprotein, reported to be associated with the progression of carotid atherosclerosis, is predictive of cardiac death and nonfatal myocardial infarction. METHODS: Serum samples from 135 cases and their controls, drawn at entry from middle-aged dyslipidemic men participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil, were tested for immunoglobulin G class antibodies against oxidized low-density lipoprotein by enzyme-linked immunosorbent assay. RESULTS: The mean antibody level, expressed in optical density units, was significantly higher in cases than in controls (0.412 vs 0.356, P = .002). After adjustment for age, smoking, blood pressure, and high-density lipoprotein cholesterol level, there was a 2.5-fold increased risk (95% confidence interval, 1.3 to 4.9) of a cardiac end point in the highest tertile of antibody level vs the lowest tertile (P = .005 for trend). CONCLUSIONS: Elevated levels of antibodies against oxidized low-density lipoprotein were predictive of myocardial infarction. The effect was independent of low-density lipoprotein cholesterol levels, and the joint effect was additive. Elevated antibody levels modified the effects of classic coronary risk factors.

Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite, and selenate.

The mean dietary selenium intake in Finland increased from 40 to 100 micrograms/d in 1987 because of the addition in 1985 of selenium to fertilizers. A selenium-supplementation study was performed in 1987 on the same men as were followed in a 1981 study that had a similar design (200 micrograms Se/d). Selenite and selenate, but not selenium yeast increased platelet glutathione peroxidase (GSHPx) activity by 30% compared with placebo, much less than the 70% found in the previous study. Selenium yeast and selenite increased plasma selenium after 11 wk from 1.39 mumol/L to peak values of 2.15 and 1.58 mumol/L, respectively. Only yeast selenium was incorporated into red cells. From a regression plot based on present and literature data, it was estimated that the plasma selenium concentration needed to achieve maximal platelet GSHPx activity was 1.25-1.45 mumol/L. At the present selenium intake in Finland, 100 micrograms/d, GSHPx activity is saturated in plasma and red cells and almost saturated in platelets.

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.

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.

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.

Toenail selenium as an indicator of selenium intake among middle-aged men in an area with low soil selenium.

Toenail selenium concentration has been proposed as a long-term (6-12 mo) indicator of human selenium status. This study investigated the association between toenail selenium concentration and selenium intake and other dietary factors among 166 urban men aged 55-69 y. The dietary information was collected by food records covering a 6-mo period. Toenail clippings were collected by mail 9-10 mo after food recording. The mean selenium intake from food was 42.5 micrograms/d and the dietary intake was equal to that of users and nonusers of selenium supplements. The mean toenail selenium concentration was 0.47 mg/kg. The mean selenium intake from supplements was 29.7 micrograms/d among supplement users. In the analysis of covariance the best predictors of toenail selenium concentration were selenium intake from supplements and food, and among supplement users dietary beta-carotene also.

Bioavailability of selenium to Finnish men as assessed by platelet glutathione peroxidase activity and other blood parameters.

Three groups of 10 men of low selenium status were given 200 micrograms Se/day as Serich wheat, Se-rich yeast, or sodium selenate for 11 wk. Twenty unsupplemented subjects served as controls. Plasma Se levels increased steadily in the wheat and yeast groups for 11 wk without plateauing, whereas in the selenate group, plasma Se plateaued around 110 ng/ml after 4 wk. Platelet glutathione peroxidase (GSH-Px) activities increased rapidly in the wheat and selenate groups for 4 wk and then plateaued. Platelet GSH-Px increased more slowly in the yeast group. Ten weeks after the supplements were discontinued, platelet GSH-Px was higher in the wheat and yeast groups than in the selenate group. Assessment of Se bioavailability requires a short-term platelet GSH-Px measurement to determine immediate availability, a medium-term plasma Se measurement to estimate retention, and a long-term platelet GSH-Px measurement after supplements are discontinued to determine the covertibility of tissue Se stores to biologically active Se.

Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study.

The relation of serum total homocysteine and lipoprotein(a) (Lp(a)) with the incidence of atherosclerotic disease was investigated among 7424 men and women aged 40-64 years free of atherosclerotic disease at baseline in 1977. During the 9-year follow-up, 134 male and 131 female cases with either myocardial infarction or stroke were identified. For each case a control subject was selected belonging to the same sex and 5-year age group. Serum samples collected in 1977 were stored at -20 degrees C and analyzed in 1991. The mean serum homocysteine concentration of male cases and controls was 9.99 mumol/l and 9.82 mumol/l at baseline and that of female cases and controls 9.58 mumol/l and 9.24 mumol/l, respectively. The median serum Lp(a) concentration of male cases and controls was 73 mg/l and 108 mg/l and that of female cases and controls 113 mg/l and 91 mg/l, respectively. The differences between cases and controls were not statistically significant. There was also no significant association between either homocysteine or Lp(a) and atherosclerotic disease, myocardial infarction or stroke in logistic regression analyses. The odds ratios varied from 1.00 to 1.26 for homocysteine and from 0.81 to 1.06 for Lp(a). The results of this prospective population-based study do not support the hypotheses that serum homocysteine or Lp(a) are risk factors for atherosclerotic disease. The lack of association between serum homocysteine and atherosclerotic disease may be due to the exceptionally low gene frequency predisposing to homocysteinemia in Finland.

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.

Relation of inflammation to vascular function in patients with coronary heart disease.

Endothelium plays a pivotal role in the regulation of vascular relaxation. Inflammation may in turn induce endothelial dysfunction and thus increase the risk of atherothrombosis. We investigated 31 men with angiographically verified coronary heart disease, aged 57. 7+/-5.3 years, in regard to endothelium-dependent, acetylcholine-induced, and to endothelium-independent, sodium nitroprusside-induced vasodilatation in the forearm vasculature by strain-gauge plethysmography. Logistic regression analysis served to determine the relation between forearm vascular function and the inflammatory factors measured, concentration of C-reactive protein, subtypes of peripheral blood T-lymphocytes, and other factors potentially affecting endothelial function (lipoprotein and glucose levels). Concentration of C-reactive protein was an independent determinant of endothelium-dependent vascular function (P<0.001 for low dose acetylcholine, P=0.01 for high dose acetylcholine). Other determinants of endothelium-dependent vascular dysfunction were CD8-lymphocytes expressing ICAM-1 (P=0.001), antibodies to oxidized low-density lipoprotein (P<0.001), and body weight (P=0.007). The present data showed an association between inflammatory risk factors linked to atherothrombosis and endothelial dysfunction in coronary heart disease patients. It is possible that endothelial dysfunction in coronary heart disease patients is related to the chronic inflammation or infection coexisting with atherosclerosis.

Serum fatty acids, apolipoproteins, selenium and vitamin antioxidants and the risk of death from coronary artery disease.

The independent association of serum concentrations of saturated and polyunsaturated fatty acids, apolipoproteins AI and B, selenium and vitamins A and E with the risk of death from coronary artery disease (CAD) was studied in 92 persons with no previous myocardial infarction, who died from CAD during a 5-year follow-up, and their 92 1-to-1 matched controls. Case-control pairs came from a randomly drawn population sample of approximately 12,000 persons aged 30 to 64 years from 2 provinces of eastern Finland, an area with exceptionally high CAD mortality. Control subjects were matched for sex, age, serum cholesterol, mean arterial pressure, tobacco consumption and history of cardiovascular diseases. The persons who died of CAD had lower serum esterified arachidonic acid concentrations before follow-up than the control subjects (41 vs 48 mg/liter, p = 0.05), and this difference was greater for pairs with no chest pain on effort (36 vs 50 mg/liter, p less than 0.05). The adjusted risk of CAD death in persons with a serum polyunsaturated to saturated (P/S) fatty acid ratio of 0.28 or less (in the lowest tertile) was 3.5-fold (95% confidence interval [CI], 1.5 to 8.2) compared with those with higher serum P/s ratios in a multivariate logistic model and 5.6-fold (95% CI 1.6 to 19.8) for pairs with no chest pain on effort. A low serum apolipoprotein AI concentration (1.25 g/liter or less, in the lowest tertile) was associated with a 2.5-fold (95% CI 1.1 to 5.7) adjusted risk of CAD death among the chest pain-free persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular risk factor changes in Finland, 1972-1997.

BACKGROUND: The cardiovascular risk factor levels of the population have been assessed in Finland since 1972. In the beginning the surveys were done to evaluate the North Karelia Project, which was a community-based preventive programme. A national cardiovascular disease (CVD) prevention strategy was developed and implemented during the late 1970s. Subsequently, a national cardiovascular risk factors monitoring system was developed to assess the effectiveness of the national strategy. METHODS: Cross-sectional population samples were studied in 1972 and 1977 in North Karelia and Kuopio provinces in eastern Finland. An area in southwestern Finland was included in 1982, followed by the Helsinki metropolitan area in 1992 and Oulu province in northern Finland in 1997. A total of 19 761 men and 20 761 women aged 30-59 participated in the six surveys (1972, 1977, 1982, 1987, 1992, 1997). RESULTS: The serum cholesterol levels of both genders have continuously declined. Systolic blood pressure levels have declined since 1972, but no further decline in diastolic blood pressure was found in 1997. Smoking prevalence among men continued to decline mainly due to an increase in the percentage of never-smokers. For the first time the increase in smoking prevalence among women levelled off and started to decline, mainly because the number of female quitters had increased. CONCLUSIONS: These data suggest that the cardiovascular health programme in Finland has succeeded in decreasing the general risk factor level of the population.

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.

Effects of selenium supplementation on blood and urine selenium levels and liver function in patients with primary biliary cirrhosis.

To study the mechanism of the reduced serum selenium concentration in patients with liver damage we administered 200 micrograms (2.53 mumol) selenium daily as selenium-rich yeast to 8 patients with primary biliary cirrhosis and 8 healthy controls over 16 weeks. Initially selenium concentrations in serum were 24% lower (P less than 0.001) in patients than controls. During supplementation serum selenium levels increased in both groups but the difference between them persisted. Throughout the study whole blood selenium levels and glutathione peroxidase activities were also somewhat lower (P = NS) in patients than controls. Selenium supplementation had no effect on whole blood glutathione peroxidase activities in either group. The basal 24 h urinary excretion of selenium was similar in both groups but was increased more by supplementation in patients than controls. Selenium administration did not influence the liver function of the patients. We conclude that impaired hepatic production of selenium-containing serum compounds is the most likely explanation for the reduced serum selenium concentration in patients with primary biliary cirrhosis.