Serum Alpha-tocopherol Research Articles

Effects of Supplementation with a Combination of Antioxidant Vitamins and Trace Elements, at Nutritional Doses, on Biochemical Indicators and Markers of the Antioxidant System in Adult Subjects

Objective: To test the impact of supplementation with nutritional doses of antioxidant nutrients on biochemical indicators of vitamin and trace element levels.Design: A randomized double-blind trial was performed comparing two groups receiving daily either a combination of vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 30 mg) and trace elements (zinc, 20 mg; and selenium, 100 μg); or a placebo.Subjects: 401 subjects (166 males aged 45 to 60 years and 235 females aged 35 to 60 years).Measure of outcome: Biological markers of vitamin and trace element status and free radical parameters were measured initially, 3 months, and 6 months after supplemention.Results: Mean serum concentrations of alpha-tocopherol, vitamin C, beta-carotene, zinc and selenium increased significantly after 3 months of supplementation in the group receiving multivitamins associated with minerals. At baseline, 18.2% of the men and 5.1% of the women had low concentrations of serum vitamin C (<20 μmol/l); 2.4% of the men and 17% of the women presented low concentrations of serum retinol (<1.4 μmol/l); 18.7% of men and 10% of women had serum beta-carotene <0.30 μmol/l. None of the study subjects had serum alpha-tocopherol concentrations below the limit cut-off point (<9.3 μmol/l). Low serum zinc concentrations (<10.7 μmol/l) were found in 15.1% of men and 23.8% of women. Low serum selenium concentrations (<0.75 μmol/l) were found in 6% of men and 6.4% of women. A significant increase in plasma and red cell GPx activity was observed in groups receiving supplementation. No modifications were observed after 6 months of supplementation for malondyaldehyde.Conclusion: This study demonstrates the efficacy of an intake of antioxidant vitamins and trace elements, given at nutritional doses, on biochemical indicators of vitamin and trace elements status.

Serum antioxidants and risk of non-insulin dependent diabetes mellitus.

To examine whether serum levels of alpha-tocopherol, beta-carotene and retinol were associated with risk of non-insulin dependent diabetes mellitus (NIDDM). The study design was a nested case-control study within a longitudinal population study. Serum levels of antioxidants were determined in 106 incident cases with non-insulin dependent diabetes mellitus detected on follow-up and 201 controls matched for sex, age and study region. The incident cases had lower serum alpha-tocopherol and beta-carotene levels than controls. The relative risk between the highest and lowest tertiles of serum alpha-tocopherol was 0.61 (95% confidence interval (CI) 0.32-1.15), between the highest and lowest tertiles of serum beta-carotene 0.45 (CI 0.22-0.92). Although the relative risk of highest compared with lowest tertile of serum alpha-tocopherol was not statistically significant the inverse trend through the tertiles was (P < 0.05). The decreasing risk of diabetes was particularly evident in the elderly, women, nonsmokers and the obese. However, adjustment for serum cholesterol, obesity, smoking and hypertension abolished the associations. The adjusted relative risks in relation to serum alpha-tocopherol and beta-carotene (between highest and lowest tertiles) were 1.25 (CI 0.54-2.90) and 0.94 (CI 0.38-2.32), respectively. No associations were observed relating to serum retinol. High levels of alpha-tocopherol and beta-carotene were found to be associated with decreased risk of non-insulin dependent diabetes mellitus, but the association disappeared after adjustment for cardiovascular risk factors.

Kinetics of the response of milk and serum beta-carotene to daily beta-carotene supplementation in healthy, lactating women

Changes in concentrations of milk and serum carotenoids, retinol, and alpha-tocopherol of five healthy, well-nourished, lactating women were measured over a 28-d supplementation trial with 30 mg beta-carotene and for 4 wk thereafter. Beta-carotene supplementation increased mean beta-carotene concentrations in milk and serum 6.4- and 7.4-fold, respectively. Concentrations of other major carotenoids, retinol, and alpha-tocopherol did not change substantially in either milk or serum. Uptake of beta-carotene into both serum and milk followed apparent first-order kinetics, occurring more rapidly into serum (t(1/2) = 5.5 d) than into milk (t(1/2) = 9 d). After supplementation, milk and serum beta-carotene concentrations decayed slowly, reaching approximately twofold initial concentrations by 4 wk. Kinetics of uptake and decay in milk beta-carotene concentrations paralleled those in serum. The data show that short-term supplementation of healthy, lactating mothers with purified beta-carotene at approximately fivefold the average daily dietary intake substantially increased milk and serum beta-carotene concentrations while not interfering with concentrations of other carotenoids, retinol, or alpha-tocopherol in milk or serum. Thus, an increased intake of beta-carotene by healthy, lactating women increases the supply of milk beta-carotene available to their breast-feeding infants.

Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States)

To evaluate relationships of serum carotenoids, alpha-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta-cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha- and beta-carotene, alpha-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer.

Effects of supplemental vitamin E and canola oil on tissue tocopherol and liver fatty acid profile of finishing swine.

We conducted a 4 x 3 factorial experiment with finishing pigs for 6 wk to evaluate effects of dietary canola oil and vitamin E on vitamin E status and liver fatty acid profile. Treatments consisted of four supplemental levels of vitamin E (0, 50, 125, and 200 mg/kg) and three of canola oil (0, 5, and 10% of the diet). Serum was collected each week and tissue samples at d 42. Dietary canola oil (P = .02) and vitamin E (P < .001) increased serum alpha-tocopherol. Serum alpha-tocopherol reached a plateau at d 35 of vitamin E and canola oil supplementation. An interaction was observed between canola oil and vitamin E (P = .02) for liver alpha-tocopherol. Liver alpha-tocopherol was greater in pigs fed diets with 10% canola oil and supplemented with 125 or 200 mg/kg of vitamin E than in pigs fed diets with 0 and 5% canola oil. An interaction also occurred between canola oil and vitamin E (P = .01) for alpha-tocopherol in the gluteus medius and obliquus capitis caudalis muscles. A greater magnitude of increase in muscle alpha-tocopherol was observed in pigs fed diets with no canola oil than in pigs fed diets with 5 and 10% canola oil. Highest alpha-tocopherol was in liver, followed by obliquus capitis caudalis and then gluteus medius. Inclusion of 5 or 10% dietary canola oil decreased the amount of saturated fatty acids by 4.1 and 13.5%, increased monounsaturated fatty acids by 10.9 and 39.3%, respectively, and had no effect (P > .10) on total polyunsaturated fatty acids. Canola oil increased linoleic acid [18:2(n-6)] (quadratic, P = .05) and linolenic acid [18:3(n-3)] (linear, P < .001) while decreasing arachidonic acid [20:4(n-6)] and docosadienoic acid (20:2) linearly (P < .001 and P = .02, respectively). Dietary canola oil and vitamin E increased serum and tissue alpha-tocopherol; canola oil increased monounsaturated and decreased saturated fatty acids in liver.

Serum Beta Carotene, Alpha Tocopherol, and Age-Related Maculopathy: the Blue Mountains Eye Study

To assess associations between serum beta carotene, alpha tocopherol, and age-related maculopathy. We studied 156 subjects with age-related maculopathy matched for age, sex, and month of blood collection to 156 control subjects without age-related maculopathy. Subjects were identified from the Blue Mountains Eye Study: those with late age-related macular degeneration and early age-related maculopathy using examination and grading of retinal photographs, and control subjects without age-related maculopathy randomly sampled from the study population. Neither serum alpha tocopherol nor beta carotene was significantly associated with age-related maculopathy. These findings provide no evidence of a protective association between serum alpha tocopherol or beta carotene and age-related maculopathy.

Enteral vitamin E supplementation inhibits the cytokine response to endotoxin.

To evaluate the effect of short-term, high-dose enteral supplementation of 3 different vitamin E derivatives: free alpha-tocopherol (VE), alpha-tocopherol succinate (VES), and alpha-tocopherol acetate (VEA) on macrophage and monocyte activation. Sprague-Dawley rats (weight, 150-200 g) were assigned to 1 of 5 experimental groups: saline (control), ethanol (control), VES (100 mg/kg), VEA (100 mg/kg), or VE (100 mg/kg). Rats underwent oral gavage once per day for 5 days with 0.5 mL of their assigned solution. All vitamin E derivatives were diluted in 75% ethanol. Rats were then killed and whole-blood and peritoneal macrophages were harvested and stimulated with lipopolysaccharide (10 microg/mL) in vitro. Tumor necrosis factor (TNF) production was measured by enzyme-linked immunosorbent assay. Additional serum samples were analyzed for alpha-tocopherol concentration by high-performance lipid chromatography. Whole-blood TNF production was maximal in the control groups after 3 hours of incubation and began to decline by 6 hours. Supplementation with all 3 vitamin E derivatives resulted in suppression of lipopolysaccharide-induced TNF production at both time points when compared with both ethanol and saline controls (P<.05, analysis of variance [ANOVA]). All 3 vitamin E derivatives also resulted in significant inhibition of lipopolysaccharide-induced TNF production by peritoneal macrophages when compared with their ethanol-carrier control but not with the saline control (P<.05, ANOVA). The degree of TNF suppression correlated directly with serum alpha-tocopherol levels. Our data demonstrate that a short-term, high-dose enteral supplementation of vitamin E can modulate the monocyte and macrophage response to endotoxin. These data, along with other animal studies showing a protective effect of vitamin E treatment in sepsis and ischemia-reperfusion injury, suggest a potential role for vitamin E supplementation in patients at risk of the systemic inflammatory response syndrome.

Determinants of the nutritional status of vitamin E in a non-smoking Mediterranean population. Analysis of the effect of vitamin E intake, alcohol consumption and body mass index on the serum alpha-tocopherol concentration

Study was conducted in order to investigate the association of vitamin E intake and other factors with plasma alpha-tocopherol concentration in a non-smoking Mediterranean population. A cross-sectional study was conducted in a subsample of a representative sample of the Catalan population. Sample size was 143 men and women, aged between 18 and 75 y, and final response rate reached 61.9% of the initial sample. Serum alpha-tocopherol concentration standardized by serum total lipids was used as a proxy of the nutritional status of vitamin E. Vitamin E intake and alcohol consumption were estimated by a replicated 24 h recall method. Dietary data were collected in two different periods, winter and summer, in order to account for seasonal variation in nutrient intake, and were corrected for random within-person variability in order to account for day-to-day variation in nutrient intake. Multivariate linear regression models were fitted in order to estimate the determinants of serum alpha-tocopherol concentration. In this population study, for each one mg increase in vitamin E intake, serum alpha-tocopherol concentration increased, on average, 0.66 micromol/L, after adjusting for age, gender, Body Mass Index (BMI), alcohol consumption and energy intake. BMI also influenced significantly serum alpha-tocopherol concentration, whereas alcohol intake, age and gender did not show significant associations with serum alpha-tocopherol. The study showed that vitamin E nutritional status was associated to vitamin E intake and BMI in non-smokers.

4.P.172 The alpha and gamma tocopherol levels in serum depend on the dietary fat quality

4.P.172 The alpha and gamma tocopherol levels in serum depend on the dietary fat quality

Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment

We conducted a double-blind placebo-controlled trial to evaluate the chemopreventive potential of either vitamin A alone or beta carotene alone in subjects with oral leukoplakia in Kerala, India. We randomised 160 fishermen and women with oral precancerous lesions to receive oral vitamin A (retinyl acetate 300,000 IU/week x 12 months, n = 50), or beta carotene (360 mg/week x 12 months, n = 55), or placebo (n = 55). Blood, saliva and urine samples were collected at baseline and at exit to study serum micronutrients and mutagenicity assays. Biopsies of the mucosal lesions at entry were performed for histopathological exclusion of malignancy. The subjects were examined once every 2 months to establish clinical response of lesions and toxicity, if any. The results are based on 43 complaint subjects on placebo, 42 on vitamin A and 46 on beta carotene. The complete regression rates were: 10% in the placebo arm, 52% with vitamin A and 33% with beta carotene (P < 0.0001). Homogeneous leukoplakias and smaller lesions responded better than non-homogeneous and larger lesions. No major toxicities were observed. Half of the responders with beta carotene and two thirds with vitamin A relapsed after stopping supplementation. Serum beta carotene concentration increased substantially with beta carotene administration while with vitamin A supplementation there was no change in serum retinol levels. In the vitamin A treated group there was a significant decrease in serum alpha tocopherol. Vitamin A administration resulted in a significant remission of oral leukoplakia without any side effects of prolonged vitamin A supplementation. The results of this study, as well as those from previous studies, appear to provide strong supporting evidence to justify long term trials with vitamin A in subjects with high-risk leukoplakias with oral cancer as an endpoint.

Correlation of repressed transcription of alpha-tocopherol transfer protein with serum alpha-tocopherol during hepatocarcinogenesis.

Using a subtraction-enhanced display technique, we identified a rodent alpha-tocopherol transfer protein (alpha-TTP) cDNA which exhibited markedly lower messenger RNA (mRNA) amounts in rat hepatocellular carcinoma (HCC) than in healthy controls. Several lines of evidence have substantiated that abnormal alpha-TTP results in isolated vitamin E deficiency. In this study, we investigated the hepatic mRNA amounts of alpha-TTP during rat hepatic carcinogenesis and liver regeneration on Northern blot, localization of alpha-TTP mRNA in HCC of rats and humans by in situ hybridization, and we analyzed the correlation between alpha-TTP mRNA and alpha-tocopherol. alpha-TTP mRNA concentrations of the rats were decreased at the early stage of hepatic carcinogenesis, and remained 3-5-fold reduced as the tumor progressed. In parallel, serum alpha-tocopherol concentrations were significantly decreased to 40% of those in the controls at the early stages of rat hepatic carcinogenesis (p < 0.01). The 2 data sets were strongly correlated (r = 0.834, p < 0.001). In situ hybridization revealed that a decrease of alpha-TTP mRNA was preferentially localized in the tumor nodules of rats and humans with HCC. Our data suggest that repressed transcription of alpha-TTP is associated with a decrease of serum alpha-tocopherol and with hepatic carcinogenesis.

Increased serum and low-density-lipoprotein antioxidant potential after antioxidant supplementation in endurance athletes

We studied the effect of antioxidant supplementation on acute exercise-induced lipid peroxidation and antioxidant potential measured in serum and low-density-lipoprotein (LDL) samples. Eight endurance athletes repeated a 31-km running exercise twice with an interval of 4 wk. During the 4 wk before the runs, the subjects took in a single-blind randomized order either a combination of antioxidant supplements (the antioxidant trial; 294 mg vitamin E, 1000 mg vitamin C, and 60 mg ubiquinone daily) or placebo (the placebo trial). Venous blood samples were taken before and immediately after the 31-km run in both trials. Antioxidant supplementation raised the LDL antioxidant potential (TRAP) (40% and 30%, P = 0.0031), serum TRAP (9% and 10%, P = 0.0037), and serum alpha-tocopherol concentration (by 59% and 66%, P = 0.0004) in both pre- and postexercise samples, respectively. The supplementation did not, however, affect the concentration of LDL diene conjugation (DC) or of serum DC. Physical exercise increased serum DC (by 18% and 10%, P = 0.0004) but not LDL-DC, and the quantity of the increment of serum DC was not affected by antioxidant intervention. The major cause for the increased LDL-TRAP and serum TRAP after antioxidant supplementation is apparently the elevation of the serum alpha-tocopherol concentration.

Biodiscrimination of alpha-tocopherol stereoisomers in humans after oral administration

We investigated changes in the concentrations of the stereoisomers of alpha-tocopherol in serum and lipoproteins in seven normal, healthy women aged 21-37 y who had received oral administration of natural and synthetic alpha-tocopheryl acetate. This study was conducted in three separate periods of 28 d each; there was a 3-mo washout period between each experimental period. During the first period the subjects were administered a daily dose of 100 mg RRR-alpha-tocopherol/d, whereas in the second and third periods 100 mg all-rac-alpha-tocopheryl acetate/d and 300 mg all-rac-alpha-tocopheryl acetate/d were given, respectively. Blood samples were collected 3 d before each treatment and 1, 3, 7, 14, and 28 d after treatment. alpha-Tocopherol stereoisomer concentrations in serum and lipoproteins (very-low-, low-, and high-density lipoproteins) were determined by the chiral HPLC method. The bioavailability of RRR-alpha-tocopherol was greater than that of all-rac-alpha-tocopheryl acetate. When bioavailability was estimated from the increase in the concentration of RRR- or all-rac-alpha-tocopherol in serum, bioavailability of RRR-alpha-tocopherol administered at 100 mg/d was not different from that of all-rac-alpha-tocopheryl acetate administered at 300 mg/d. 2R-Isomers and small amounts of 2S-isomers were detected in the serum lipoproteins of subjects administered all-rac-alpha-tocopheryl acetate.

Effect of injected vitamin A and level of dietary vitamin E on α-tocopherol status in gestating swine

A 2 x 2 trial was conducted to determine the effects of injected vitamin A and dietary level of vitamin E on blood serum and tissue concentrations of alpha-tocopherol during early gestation of gilts. Thirty-two crossbred gilts were fed a corn soybean meal basal diet supplemented with DL-alpha tocopheryl acetate to provide either 25 or 500 IU of vitamin E/kg of diet. Gilts were fed daily 1.9 kg/gilt beginning 7 days before breeding until day 25 of gestation. Sixteen gilts were injected (i.m.) with 350,000 IU of retinol palmitate 7 days before breeding, at the time of breeding (d0), and 7 days after breeding. Blood samples were collected on day -7, 0, 7, and 24, and all gilts were slaughtered on day 25 of gestation. Supplemental vitamin E at 500 IU/kg of diet increased alpha-tocopherol concentrations (P < 0.01) in blood serum in all tissues examined, including reproductive and embryonic, except fat. Vitamin A injections had no effect (P > 0.10) on blood serum alpha-tocopherol concentrations except on day 7 when a small increase (P < 0.06) was noted. Vitamin A injections had no effect (P > 0.10) on tissue alpha-tocopherol concentrations. Increasing dietary level of vitamin E increased blood serum and tissue alpha-tocopherol concentrations, and vitamin A injections had little or no effect on these concentrations during the early gestation of gilts.

Circulating autoantibodies recognizing peroxidase-oxidized low density lipoprotein. Evidence for new antigenic epitopes formed in vivo independently from lipid peroxidation.

Oxidatively modified LDLs are antigenic and elicit the generation of autoantibodies often detected in plasma and within plaques of atherosclerotic patients. Although Cu(2+)-oxidized LDL and malondialdehyde (MDA)-modified LDL are usually used as antigens in immunoassays, other, still unrecognized epitopes may be formed in vivo during LDL oxidation and may induce antibody production. Antibodies recognizing LDL oxidatively modified by Cu2+, 2,2'-azobis-(2-amidino propane) hydrochloride (AAPH), and the combination of horseradish peroxidase and H2O2 (HRP) were detected in serum of a group of 90 unselected patients. HRP-oxidized LDL was the antigen that revealed the highest IgG titers, although the extent of LDL oxidation (evaluated as conjugated diene formation, loss of tryptophan fluorescence, production of fluorescent aldehydic adducts, and change in electrophoretic mobility) was comparable to that obtained with Cu2+ and AAPH. There was a highly statistically significant correlation between the IgG titers detected using Cu(2+)- and AAPH-oxidized LDLs as antigens, but no correlation was found between the IgG titers revealed by HRP and Cu2+ or AAPH. In addition, the antibody titers against MDA-modified LDL exhibited a significant correlation with those against Cu(2+)- or AAPH-oxidized LDL but did not correlate with those against HRP-oxidized LDL. Finally, immunocompetition experiments revealed that IgG recognizing HRP-oxidized LDL did not cross-react with Cu(2+)-oxidized LDL and vice versa. The possibility that lipid peroxidation-independent modifications could play a role in HRP-induced formation of antigenic epitopes in LDL was supported by two lines of evidence. First, in probucol-enriched LDL, despite the complete inhibition of lipid peroxidation, HRP, but not Cu2+ and AAPH, was still able to generate epitopes that were recognized by the same sera reacting with HRP-oxidized native (not probucol-enriched) LDL. In addition, the presence of autoantibodies against Cu(2+)- and AAPH-oxidized LDLs was negatively correlated with serum alpha-tocopherol concentration, whereas the titers against HRP-oxidized LDL did not exhibit any statistically relevant correlation with alpha-tocopherol levels. Together, these findings indicate that peroxidase(s)-dependent mechanisms can trigger peculiar lipid peroxidation-independent modifications of LDL in vivo.

Permissive role of alpha-tocopherol in the stimulation of aldosterone by sodium depletion in the guinea pig.

To investigate the role of vitamin E in aldosterone synthesis, in vivo and in vitro studies were done in alpha-tocopherol-depleted guinea pigs. Seventy-one days of low vitamin E intake ( < 5 mg/kg feed) reduced the concentration of alpha-tocopherol in serum, liver and adrenals to low levels with no signs of hypovitaminosis. Aldosterone secretion was stimulated by 15 days on a low sodium diet (200 mg/kg feed) in controls and vitamin E-depleted animals. Sodium depletion in controls stimulated plasma aldosterone by 335%. Vitamin E depletion reduced the stimulation of plasma aldosterone to only 112% (p < 0.05). In vitro aldosterone secretion by adrenal cells from sodium-depleted animals was 252% higher than secretion by cells from controls. This enhancement of in vitro aldosterone secretion following in vivo sodium depletion was abolished completely by combined in vivo vitamin E and sodium depletion (p < 0.05). No significant differences between groups were found for plasma renin activity, adrenocorticotrophin and serum potassium, suggesting that intra-adrenal mechanisms like damage by enhanced lipid peroxidation in alpha-tocopherol-depleted animals rather than changes in humoral aldosterone-regulating factors are the cause of the attenuated aldosterone response to sodium depletion.

Evaluation of retinol, alpha-tocopherol, and carotenoids in serum of men with cancer of the larynx before and after commercial enteral formula feeding.

Both epidemiologic and in vitro studies have indicated the inverse correlation between intake and/or blood concentrations of different carotenoids, retinol, and tocoferol with different chronic and degenerative disturbances (cancer, cardiovascular diseases, cataracts, aging). The purpose of this study was to determine the fat-soluble vitamin and carotenoid levels in men with recently diagnosed cancer of the larynx (n = 51) who had undergone total or partial laryngectomy and compare them with those of an age- and sex-matched control group (n = 51). In addition, the effects of commercial enteral formula feeding were assessed in a subgroup of these patients (n = 35). A validated high-performance liquid chromatography method was used to determine the concentrations of six carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene), retinol, and alpha-tocopherol in serum. Commercial, rather than blender prepared, enteral formulas were supplied to the patients as the only food source for an average period of 12 days. The statistical analysis was based on nonparametric methods (Mann-Whitney and Wilcoxon). The levels of all compounds analyzed were significantly lower in men with laryngeal cancer than in the control group. Retinol and tocopherol increased significantly after enteral formula feeding, although they continued to be significantly lower than those of the controls. The carotenoid levels decreased after enteral nutrition. The retinol and carotenoid concentrations should be monitored on a routine basis in these patients because of their relationship to this type of cancer. Moreover, it would be of interest to assess the effects of the addition of carotenoids to enteral formulas because they may offer protection from oxidative damage and potentiate the immune system.

Alpha-tocopherol, selenium and polyunsaturated fatty acid concentrations in the serum and feed of spring-calving dairy heifers

The objectives of this study were to provide baseline data for alpha-tocopherol, selenium and polyunsaturated fatty acid concentrations in the serum and feed of New Zealand dairy cattle, and to assess the likelihood that abnormal peroxide metabolism has a role in the impaired lactational and reproductive performance noted in selenium-deficient cattle. Twenty-four Friesian heifers were randomly allocated one of four winter diets consisting of hay with or without selenium supplementation, or pasture and silage with or without selenium supplementation. A winter diet consisting exclusively of hay (alpha-tocopherol concentration 19 mg/kg of dry matter) resulted in a pre-calving serum alpha-tocopherol concentration of 1.2 mg/l compared to 4.5 mg/l for pastured heifers (p<0.01). The pre-calving alpha-tocopherol concentration for the heifers fed hay fell into the range considered deficient (<2.0 mg/l), whereas heifers fed pasture and silage remained in the range considered adequate throughout the study period. Serum fatty acid concentration, and the proportion of fatty acids that were polyunsaturated, were lowest in the hay-fed heifers before calving (1.0 mg/ml, 37.1% respectively), and remained unchanged following re-introduction to pasture after calving in late July and August. Serum fatty acid concentration did not increase following the re-introduction of the heifers to pasture because of the unexpectedly low fatty acid concentration (4.8 g/kg of dry matter) of the mature winter pasture. In October, however, the proportion of fatty acids in serum that were polyunsaturated increased (50%) as did serum cy-tocopherol concentrations (greater than 13 mg/l). Mean serum selenium concentrations in the unsupplemented heifers ranged from 139 to 204 nmol/l, being lowest in October (p<0.01). Supplementation with intraruminal selenium pellets (two pellets delivering about 3 mg of selenium/day) increased serum selenium concentration and glutathione peroxidase activity (p<0.01) whereas the type of winter diet had no effect (p>0.05). These results suggest that dairy cattle wintered on hay can become Vitamin E-depleted, whereas the feeding of pasture and silage should provide adequate Vitamin E. The pasture offered following calving during July and August provided a low dietary polyunsaturated fatty acid challenge, suggesting that abnormal peroxide metabolism is unlikely to be an important mechanism in the impaired performance of selenium-deficient adult cattle which calve at this the of year.

Prospective study of serum micronutrients and ovarian cancer.

Antioxidant micronutrients, such as alpha-tocopherol (vitamin E), the carotenoids, and selenium, may protect against the development of cancer by preventing free radical damage at the cellular level. A nested case--control study was conducted among donors to a serum bank to examine the association between levels of serum micronutrients and/or cholesterol and the development of ovarian cancer. In 1974, sera were collected from 20,305 residents of Washington County, MD, over a 4-month period and stored at -70 degrees C. Serum micronutrient concentrations of women who developed ovarian cancer (case subjects, n = 35) were compared with those of women who remained free of cancer and who were matched to case subjects on age and menopausal status (control subjects, n = 67). Serum levels of retinol (vitamin A), alpha- and beta-carotene (the major provitamin A), lycopene (a carotenoid), and alpha- and gamma-tocopherol were measured using high-performance liquid chromatography. Serum selenium was measured by neutron activation analysis. Cholesterol was measured by enzymatic assay. The data were categorized into thirds and conditional logistic regression analyses were performed to determine the association between prediagnostic serum cholesterol and micronutrient levels and the development of ovarian cancer; matched odds ratios (ORs) were determined from these regression analyses. P values for trend and for interaction were calculated with the use of two-sided likelihood ratio tests. Higher serum alpha-tocopherol levels were associated with an increased risk of ovarian cancer (P for trend = .04); however, this association diminished after adjustment for cholesterol. Women with higher serum cholesterol levels had an increased risk of ovarian cancer compared with women in the lowest third of cholesterol levels (OR = 3.2; 95% confidence interval = 0.9-11.3). The association between serum cholesterol levels and the risk of ovarian cancer was examined, stratifying by micronutrient level. The general pattern observed was an increased risk of ovarian cancer associated with cholesterol levels greater than 200 mg/dL, regardless of the micronutrient level. Serum selenium was associated with a decreased risk of ovarian cancer only among case participants diagnosed 4 or more years after blood collections (P for trend = .02). Concentrations of carotenoids and retinol were not associated with the development of ovarian cancer. Selenium may have a protective role against the development of ovarian cancer. Higher serum cholesterol levels were associated with an increased risk of developing ovarian cancer; an association that persisted regardless of serum micronutrient level. Given the small size of this study and the inconsistency of results among the few prospective studies of ovarian cancer conducted to test these associations, replications of these findings are highly desirable.

N-3 fatty acid intake and lipid peroxidation. 2. An Assessment of Docosahexaenoic Acid(DHA) Intake with Special Reference to Lipid Metabolism in Rats.

In order to determine the appropriate intake of docosahexaenoic acid (22:6n-3, DHA), the potential changes in lipid peroxidation and antioxidant defense in serum and tissue as well as the changes in serum lipid levels were examined in rats by giving them diets containing graded levels of purified DHA (0, 1.0, 3.4 and 8.7 energy % in the diets) for 2 weeks. Serum alpha-tocopherol concentration decreased slightly but significantly even at the 1.0 energy %. Liver lipid peroxide levels as assessed by the thiobarbituric acid (TBA) value and chemiluminescence intensity augmented at the 3.4 energy % and more, and the alpha-tocopherol content significantly decreased in response to the increase in lipid peroxide levels. In the kidney, a slight but significant increase in TBA value was observed even at 1.0 energy % and higher. All the serum lipid levels as analyzed by total cholesterol, HDL-cholesterol, triacylglycerol (TG) and phospholipids (PLs) decreased as the dietary DHA level increased. These experimental results suggest that the dietary intake of DHA should be less than 1 energy % to avoid promoting deleterious influences such as serum and tissue lipid peroxidation and to ameliorate serum lipid levels.