Occurrence of selenoprotein enzyme activities and mRNA in bovine mammary tissue.

To elucidate the possible role of selenoproteins for milk formation and mammary gland physiology, the activities of selenoprotein enzymes and the expression of selenoprotein genes were studied in the bovine mammary gland. Messenger RNA was demonstrated for selenoprotein P, thioredoxin reductase 1, and for glutathione peroxidase (GPx) 1, 3, and 4. Significant differences in mRNA expression between the cows were seen for GPx 1 and GPx 3. The enzyme activity of glutathione peroxidase varied approximately 16-fold among cows, and the activity of thioredoxin reductase and the concentration of soluble Se varied approximately 6-fold among cows. There were positive correlations between glutathione peroxidase activity, thioredoxin reductase activity, and soluble Se, the correlation between glutathione peroxidase activity and soluble Se being the strongest. Furthermore, selenoprotein P expression correlated with GPx 1 mRNA expression and with soluble Se. There was also a correlation between glutathione peroxidase activity and the mRNA expression of GPx 1. The general conclusion from the data was that the activity of glutathione peroxidase and thioredoxin reductase and the mRNA expression of selenoprotein P and GPx 1 and 3 were influenced by Se status, but the expression of GPx 4 and thioredoxin reductase 1 were not. These results indicate that the Se status in mammary tissue is an important regulator of selenoprotein activity and expression, but that other factors are also in operation.

Bioavailability of selenium from bovine milk as assessed in subjects with ileostomy.

OBJECTIVE: To assess the absorption of dietary selenium in humans, especially of milk selenium. DESIGN: : 1-day meal studies in subjects with ileostomy. SETTING: Hospital outpatient clinics. SUBJECTS: Three subjects in the pilot study and nine subjects in the main study (eight men/ four women). INTERVENTION: Different beverages, 1 l/day, were given in addition to basal diets (soft drink, 1 week; low-fat milk, 3 weeks; fermented low-fat milk, 3 weeks and soft drink, 1 week). Ileostomy effluents were collected during the last 2 days in each of the four periods. RESULTS: On days when the subjects were given 1 l of low-fat milk, the estimated fractional absorption of total dietary selenium was 65.5 (2.3)% (mean (s.d.), n=18), which was similar to the value when fermented low-fat milk was given (64.1 (3.2)%). However, both the calculated amount of milk selenium absorbed (10.9 (2.4) vs 9.4 (1.7) microg selenium) and its fractional absorption (73.3 (16.1) vs 64.1 (11.2)%, n=18) were significantly higher for milk than for fermented milk. CONCLUSIONS: Selenium from milk and other sources is well absorbed in subjects with ileostomy. The real absorption may be even higher than the values shown.

Plasma levels of selenium, selenoprotein P and glutathione peroxidase and their correlations to fish intake and serum levels of thyrotropin and thyroid hormones: a study on Latvian fish consumers.

OBJECTIVE: To study the relationships between fish intake and different markers of selenium status and thyroid hormone function. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: Sixty-eight men (age 24-79 years) were recruited among coastal fishermen and inland subjects from Latvia. None of the subjects was on selenium medication or had any known endocrine disease. MAIN OUTCOME MEASURES: Correlations between fish intake, plasma levels of selenium, selenoprotein P, glutathione peroxidase, organic mercury in erythrocytes and TSH in serum. RESULTS: Selenium in plasma ranged from 0.30 to 1.56 micromol/l, selenoprotein P from 0.54 to 2.21 arbitrary units relative to pooled plasma, and glutathione peroxidase from 1.20 to 5.73 mg/l. The number of fish meals per month was correlated with plasma selenium, selenoprotein P and glutathione peroxidase (r = 0.63, r = 0.62 and r = 0.50, respectively; P<0.001). Plasma selenium was correlated with selenoprotein P and glutathione peroxidase (r = 0.88 and r = 0.67, respectively; P < 0.001), and also selenoprotein P and glutathione peroxidase were correlated (r = 0.63, P < 0.001). The mean plasma selenium level in those with a high fish intake (21-50 fish meals/month), was 81% higher than in those with lowest fish intake. TSH in serum was inversely correlated with plasma selenium and selenoprotein P. Thyroid hormone levels were not correlated with plasma selenium, selenoproteins or fish intake. CONCLUSIONS: In this study group, selenium from fish intake had a marked impact on all variables studied on selenium status. No impact of selenium status on T3 and T4 levels was observed. The slightly negative correlation of selenium status with TSH levels might indicate a higher TSH secretion at low selenium status.

Plasma selenoprotein P levels of healthy males in different selenium status after oral supplementation with different forms of selenium.

OBJECTIVE: To assess changes in selenoprotein P levels in plasma from subjects who had received oral supplements of different selenium forms. DESIGN: The same study group participated in two similar selenium supplementation trials, Trial I in 1981 (Levander et al, 1983) and Trial II in 1987 (Alfthan et al, 1991). During Trial II the mean baseline intake of selenium in Finland was higher compared to that during Trial I (100 and 40 microg/d, respectively), due to a nationwide supplementation of fertilisers which started in 1985. SUBJECTS: Fifty healthy Finnish men, 36-60 y old. INTERVENTION: The study group received daily placebo or oral supplements consisting of 200 microg selenium as selenium-enriched yeast, sodium selenate or selenium-enriched wheat (Trial I) or selenium-enriched yeast, sodium selenate or sodium selenite (Trial II). The duration of supplementation periods was 11 (Trial I) and 16 (Trial II) weeks. RESULTS: In Trial I the mean plasma selenoprotein P values in all the supplemented groups increased significantly, approaching a plateau at 2 weeks and reaching maxima at 4 weeks (mean increase 34%, P < 0.05). In Trial II the mean selenoprotein P levels of the supplemented groups were not significantly different from each other or from the placebo group at the start or at any time point of the supplementation period. CONCLUSIONS: At a low selenium status the selenoprotein P levels increased in a similar fashion after supplementation with different forms of selenium, but at a high selenium status no significant effects of supplementation with the same amount of selenium were observed. No differences in selenoprotein P levels were observed for inorganic and organic selenium supplements.

Interactions between essential and toxic elements in lead exposed children in Katowice, Poland.

OBJECTIVES: To determine the influence of the essential element status on blood concentrations of lead and other toxic metals. DESIGN AND METHODS: A group of 157 children from Katowice, an industrial area in Poland, was investigated for concentrations of lead and cadmium in whole blood, and mercury, selenium, zinc, copper, and magnesium in whole blood and serum. Relations between these elements, serum ferritin, hematological parameters, as well as serum selenoprotein P and glutathione peroxidase (GSH-px) were examined. Conversion factors for element concentrations (mumol to microgram): lead 207.19, cadmium 112.41, mercury 200.59, selenium 78.96, magnesium 24.31, copper 63.55, and zinc 65. RESULTS: Blood lead was negatively associated with concentrations of selenium in whole blood and serum as well as selenoprotein P and glutathione peroxidase in serum. The association was mainly apparent at low blood lead concentrations, which may indicate an influence of selenium on the kinetics of lead, rather than an effect of lead on the selenium status. Children with low serum ferritin levels had statistically higher blood cadmium levels and a tendency for higher blood lead levels, indicating increased gastrointestinal absorption of these metals at reduced iron stores. Blood lead was negatively correlated with mean corpuscular hemoglobin concentration, which may reflect the effect of lead on hemoglobin synthesis. There was an association between blood mercury and selenium, indicating a common source of intake through fish consumption. CONCLUSIONS: The results indicate that selenium and iron status may influence the kinetics of lead.

Extracellular glutathione peroxidase and ascorbic acid in aqueous humor and serum of patients operated on for cataract.

Patients operated on for cataract (32 men/75 women, aged 50-93 years) were studied with respect to antioxidative agents in aqueous humor and serum. Extracellular glutathione peroxidase (eGSHPx) was demonstrated in aqueous humor for the first time by a radioimmunoassay, the concentration of eGSHPx being 0.66(0.18) mg/l (mean(S.D.)). The concentration of eGSHPx in serum was 3.81(0.84) mg/l, and its level in aqueous humor was 18(7)% of that level. Serum selenium had positive correlations with both serum eGSHPx (r = 0.34, P < 0.001) and aqueous humor eGSHPx (r = 0.25, P = 0.011). However, there was no relation between the concentrations of eGSHPx in aqueous humor and in serum, suggesting that the maintenance of eGSHPx levels in the two fluids is controlled by different mechanisms beside selenium status. There was an inverse correlation between age and serum eGSHPx but not with aqueous humor eGSHPx. The concentration of ascorbic acid in aqueous humor was 2.04(0.58) mmol/l, and it was closely correlated to the level of ascorbic acid in serum (0.052(0.032) mmol/l), r = 0.58 (P < 0.001). The ratio between the level of ascorbic acid in aqueous humor and that in serum was 39(17). There was no significant difference among patients with nuclear (n = 39), cortical (n = 20), posterior-subcapsular (n = 23) or mixed (n = 23) lens opacity with respect to levels of eGSHPx and ascorbic acid in serum and aqueous humor. Since serum ascorbic acid is related to ascorbic acid intake, its association to aqueous humor ascorbic acid indicates that dietary habits are important for maintaining that level which could play an important role in protecting ocular tissue against oxidative damage. The role of eGSHPx secreted into aqueous humor in the oxidant defence system needs further study.

Selenoprotein P concentration in plasma is an index of selenium status in selenium-deficient and selenium-supplemented Chinese subjects.

Selenoprotein P, a selenium-rich plasma protein, is an index of selenium status in rats. Antibodies against human selenoprotein P were raised to study the protein and to develop a radioimmunoassay for it. A single collection of plasma from a healthy person in the United States contained 1.84 mumol selenium/L and was defined as containing 1 Unit (U) selenoprotein P/L. Removal of selenoprotein P from the reference plasma by an antibody column indicated that 0.81 mumol selenium/L, or 44% of the plasma selenium, was present as selenoprotein P. Work by others had determined that glutathione peroxidase accounted for 12% of plasma selenium. Stored plasma samples from selenium-deficient (Dechang County) and selenium-supplemented (Mianning County) populations in China were assayed for selenoprotein P. Boys aged 8-12 y had selenoprotein P concentrations of 0.10 +/- 0.04 U/L (n = 22) in Dechang and 0.39 +/- 0.17 U/L (n = 17) in Mianning. Supplementation with 100 micrograms selenium as selenate per day for 14 d raised those levels to 0.51 +/- 0.13 U/L in Dechang and to 0.76 +/- 0.27 U/L in Mianning. Similar results were obtained in men, and plasma selenium concentrations correlated with selenoprotein P concentrations. A study comparing indices of selenium status was conducted in the two counties. Selenoprotein P concentration in Dechang subjects (n = 79) was 36% of that in Mianning subjects (n = 117). For plasma glutathione peroxidase activity the value was 54%; for plasma selenium, 47%; and for whole blood selenium, 64%. We conclude that selenoprotein P is the major selenoprotein in human plasma and that its concentration is an index of selenium nutritional status that appears to be as sensitive as other indices in common use.

Fish consumption and exposure to persistent organochlorine compounds, mercury, selenium and methylamines among Swedish fishermen.

OBJECTIVES: This study assessed dietary habits and exposure to selenium, persistent organochlorine compounds, methylmercury, and methylamines among Swedish fishermen. METHODS: Two hundred and fifty randomly selected subjects from a cohort of 2896 fishermen from the Swedish east coast (Baltic Sea) and 8477 fishermen from the west coast (Skagerrak and Kattegatt) were interviewed along with 250 referents. Subgroups of fishermen and referents from different coastal areas were also selected for blood and urine sampling. RESULTS: The interview data showed that fishermen ate almost twice as much fish as the 250 referents from the general population. The blood levels of mercury were twice as high, and the plasma selenium levels were 10-15% higher in the fishermen than in the referents. There was, however, no difference between the fishermen's cohorts with respect to these variables. Fishermen from the east coast ate more fatty fish than fishermen from the west coast, and they also had higher blood levels of persistent organochlorine compounds such as polychlorinated biphenyls and polychlorinated dibenzo p-dioxins and furans (present in fatty fish species in the Baltic Sea) than both the westcoast fishermen and the referents. CONCLUSIONS: A cohort of Swedish eastcoast fishermen might be a suitable study base for epidemiologic studies on the mortality and cancer morbidity associated with dietary exposure to persistent organochlorine compounds.

Selenoprotein P and glutathione peroxidase (EC 1.11.1.9) in plasma as indices of selenium status in relation to the intake of fish.

In Sweden fish is considered to be an important source of dietary Se. Therefore Se status was assessed in forty-one middle-aged men with widely varying fish consumption. Glutathione peroxidase (EC 1.11.1.9) and selenoprotein P in plasma were measured by radioimmunoassay. Plasma Se among the men increased slightly with increasing consumption of fish, but no such increases in the concentrations of glutathione peroxidase and selenoprotein P in plasma were observed. Moreover, no correlation was found between plasma Se and glutathione peroxidase or selenoprotein P. Instead, glutathione peroxidase was significantly correlated with selenoprotein P (r 0.73, P < 0.001), indicating that both glutathione peroxidase and selenoprotein P were functional indicators of Se status in this group. The proportion of plasma Se located in glutathione peroxidase decreased with increasing plasma Se. The results suggest that the Se consumed from fish had no apparent effect on the amount of Se incorporated into the functional selenoproteins of plasma. It is concluded that in some cases selenoproteins may be better biological markers of Se status than the total concentration of Se.

Selenoprotein P in serum as a biochemical marker of selenium status.

Some characteristics of a radioimmunoassay of selenoprotein P (a major selenoprotein in human serum) are described. Polyclonal antibodies generated in rabbits were used and goat anti-rabbit-IgG antiserum was used as a second antibody. Depending on the concentration of selenoprotein P, 1-10 microliters of human serum were used in the assay. The relative standard deviation for the concentration of selenoprotein P was 6.3% between assays and 7.7% within assays. Different animal sera gave no significant interference, indicating that the antibodies did not react with non-human analogues of selenoprotein P. No indication of cross-reactivity could be found concerning extracellular glutathione peroxidase (another selenoprotein in serum). Addition of increasing amounts of normal human serum and partially purified selenoprotein P to the radioimmunoassay resulted in parallel curves. Incubation at 4 degrees C gave somewhat higher binding of labelled selenoprotein P than incubation at room temperature. The epitope, recognized by the antibodies, was apparently stable after storage of serum (in the frozen state for years, and in the cold for months). No significant amount of selenoprotein P could be demonstrated in red blood cells, and analysis of haemolysed whole blood gave expected data. Investigations of selenium status in different study groups indicated that in most cases the concentration of selenoprotein P in serum was positively correlated to that of glutathione peroxidase and serum selenium. In an intervention study, where subjects decreased their selenium intake to 50%, the serum levels of glutathione peroxidase and selenium decreased, but no significant decrease of selenoprotein P could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Trace element concentrations in hair of subjects from two South Pacific Islands, Atafu (Tokelau) and Kitava (Papua New Guinea).

The concentrations of trace elements in hair were measured in 108 healthy subjects (60 males and 48 females, mean age 46-years) resident on Atafu (Tokelau) and in 83 subjects (63 males and 20 females, mean age 26-years) living on Kitava island (Papua New Guinea). On Kitava, a traditional subsistence lifestyle uninfluenced by Western dietary habits is still maintained, but on Atafu the dietary habits have been modified by the inclusion of such imported foods as rice, flour, sugar and canned meat and fish. The concentrations of zinc and magnesium in hair were significantly higher in the Kitava than in the Atafu subjects, whereas those of copper were similar in both groups, and those of selenium, mercury, lead and cadmium were higher in Atafu subjects. The levels of serum copper, magnesium and selenium concentrations in Kitava subjects were not so low as to indicate any trace element deficiency. The higher hair content of mercury, lead and cadmium found among Atafu subjects might be due to consumption of marine foods contaminated with metals, consumption of canned foods, or frequent cigarette smoking, though it is difficult to single out any specific factor.

Purification of selenoprotein P from human plasma.

Selenoprotein P was partially purified (> 1000-fold) from human plasma in four chromatographic steps using 75Se-labeled selenoprotein P secreted by HepG2 cells in culture as a marker. The purified preparation was injected into mice and monoclonal antibodies, which precipitated the labeled protein, were generated. Neither of two different monoclonal antibodies had cross-reactivity with plasma from five animal species. Antibodies were coupled to agarose, and selenoprotein P was purified from human plasma by immunoaffinity chromatography followed by chromatography on heparin agarose. With two different matrix-bound monoclonal antibodies, the purification procedure gave two bands on SDS-PAGE with mobilities corresponding to 61 and 55 kDa. Both bands stained for carbohydrate and showed increased electrophoretic mobility after enzymatic deglycosylation. Immunoaffinity chromatography removed approx. one-third of the selenium from plasma or 0.4 mumol Se/l at a total selenium concentration of 1.1 mumol/l, indicating that selenoprotein P constituted this proportion of total plasma selenium in healthy US blood donors.

Radioimmunoassay of glutathione peroxidase in human serum.

Glutathione peroxidase (GSHPx) was purified from human serum and used for immunization of rabbits. Antiserum bound up to 75% of added 125I-GSHPx after precipitation with a second antibody. Human serum, but not sera from eight animal species, inhibited the binding of labelled GSHPx, indicating that the antiserum did not react with GSHPx from these species. GSHPx could be measured in less than 10 microliters of human serum by radioimmunoassay. In sera with widely varying selenium concentrations (0.1-2.9 mumol/l) the amount of GSHPx protein (0.3-6.3 mg/l) was strongly correlated with GSHPx activity (r = 0.94) and it was also correlated with serum selenium concentrations (r = 0.64). This indicates that GSHPx protein may be a valuable biological marker of selenium status. In samples with serum selenium concentrations of 0.8-1.2 mumol/l, the concentration of GSHPx was 3.3 (0.4) mg/l (mean (S.D.)), or 0.04 (0.005) mumol/l. This corresponded to 0.16 (0.02) mumol/l of GSHPx selenium and 16% (2.8)% of total serum selenium. The data suggest that the method can be used to measure the proportion of serum selenium that is located in GSHPx. Following storage of serum at room temperature, both serum GSHPx protein and activity declined, but addition of glutathione protected both GSHPx protein and activity.

Fatty acid composition of serum phosphatidylcholine in healthy subjects consuming varying amounts of fish.

Fatty acid composition of serum phosphatidylcholine was studied in subjects living in the same area and selected for high consumption of fat fish, high consumption of lean fish, moderate or no consumption of fish. The proportion of eicosapentaenoic acid (20:5) in serum phosphatidylcholine was fourfold higher, and that of docosahexaenoic acid (22:6) twofold higher among high consumers of fish compared to non-consumers, and these proportions were also higher in fat fish consumers than in high consumers of lean fish, and in moderate consumers compared to non-consumers. In the whole group the intake of fat fish was correlated to the proportions of 20:5, 22:6 and total n-3 fatty acids in serum phosphatidylcholine. The estimated intake of total n-3 fatty acids from fish was highly correlated to the proportions of these fatty acids in serum phosphatidylcholine (r = 0.87). Plasma triglyceride concentration was lower among high fat fish consumers than in other groups, but no differences between groups were observed for concentration of cholesterol, LDL cholesterol, and HDL cholesterol. It is concluded that subjects who consume high amounts of fat fish in their normal diet attain approximately the same proportions of n-3 fatty acids in serum phosphatidylcholine as reported for subjects taking fish oil supplements, and that fatty acid composition of serum lipids can be used as a marker of intake of fat fish.

Fish as a source of exposure to mercury and selenium.

In a total of 395 subjects with varying fish consumption habits, mercury levels in whole blood (B-Hg), and selenium levels in plasma (P-Se) were studied. Also, in subcohorts, mercury levels in blood cells (Ery-Hg; n = 79), plasma (P-Hg; n = 158) and urine (U-Hg; n = 125) were analysed. There were statistically significant associations between fish intake on the one hand, and B-Hg, Ery-Hg and P-Hg, on the other, but not so with U-Hg. In subjects who never had fish, the average B-Hg was 1.8 ng/g, in subjects who had at least two fish meals each week, 6.7 ng/g. Ery-Hg, and to a less extent P-Hg, were associated with levels of marine n-3 polyunsaturated fatty acids (PUFA) in serum phosphatidylcholine. P-Hg and U-Hg were associated with numbers of teeth with amalgam fillings. P-Se also correlated with fish intake. In subjects who never had fish, P-Se averaged 80 micrograms/l, in subjects who had at least two fish meals per week, 91 micrograms/l. There was an association between PUFA and P-Se. Further, there were statistically significant associations between P-Se on the one hand, and B-Hg, Ery-Hg and P-Hg on the other. The data clearly demonstrate the importance of fish for the exposure to methylmercury and selenium in the Swedish diet, and the impact of amalgam as a source of exposure to inorganic mercury.

Trace element status in healthy subjects switching from a mixed to a lactovegetarian diet for 12 mo.

The consequences of a change from a mixed to a lactovegetarian diet for 12 mo on trace element concentrations in plasma, hair, urine, and feces were studied in 16 women and 4 men. After the diet shift, intakes of zinc and magnesium did not change but that of selenium decreased by 40%. Three months after the diet shift, plasma and hair concentrations of zinc, copper, and selenium had decreased but those of magnesium had increased and the concentrations of mercury, lead, and cadmium in hair were lower. Also, the excretion of zinc, copper, and magnesium in urine, and that of selenium in urine and feces had decreased. Only small changes occurred during the remaining lactovegetarian-diet period. Three years later trace element concentrations had reverted towards baseline concentrations; copper values were similar to baseline concentrations but data for magnesium were slightly higher, and more complex patterns were observed for zinc and selenium. It is concluded that a shift to a lactovegetarian diet changes trace element status.

Effect of six months of fish oil supplementation in stable rheumatoid arthritis. A double-blind, controlled study.

Therapeutic effects of fish oil (10 g/day) in rheumatoid arthritis were investigated in a randomized, controlled, double-blind study. Forty-three patients completing the study were evaluated at 0, 3 and 6 months. The nutrient intake in the fish oil group and in the control group was essentially similar. In the fish oil group, the percentage of n-3 fatty acids in serum phosphatidylcholine increased by 9.6 (range 2.6-16.1). Patients in the fish oil group reported a significantly decreased consumption of NSAID at 3 and 6 months, and the status of global arthritic activity improved at 3 months in physician's assessment. Control patients reported an increased global arthritic activity at 6 months. No change was found in patient assessment of pain, duration of morning stiffness or functional capacity. Essentially no change occurred in biochemical markers of inflammation. We conclude that fish oil has small anti-inflammatory effects with at most a NSAID-saving potential. The value of prolonged supplementation remains to be evaluated.

Chromatography of selenoproteins in human serum using matrix-bound heparin.

Since previous experiments indicated that a major selenoprotein in human serum interacts with heparin, chromatography of serum on matrix-bound heparin was studied. When human serum was applied to heparin-agarose columns, approximately half of the applied selenium was not retained on the columns. Approx. 40% of the selenium could then be eluted either with increasing concentrations of heparin or ammonium acetate. Using a scaled-down version of this procedure, selenoproteins from 0.5 ml serum were separated into the heparin-binding and non-heparin-binding fractions. In an experiment where healthy subjects were given supplements of yeast selenium (200 micrograms/d) for eight weeks, the concentration of selenium in serum was almost doubled and then approached the original concentration 16 weeks after the end of the supplementation. During supplementation, no change in the concentration of heparin-binding selenoproteins was observed, and instead the increase in serum selenium occurred in non-heparin-binding proteins. This suggests that the need for selenium by the heparin-binding proteins was saturated already at the starting serum selenium level (1.0 mumol/l). Since interaction with heparin has been observed also for selenoprotein P isolated from rat plasma, the protein in the heparin-binding fraction, demonstrated in this paper, may be a human analogue to selenoprotein P.

Correlation of fatty acid composition of adipose tissue lipids and serum phosphatidylcholine and serum concentrations of micronutrients with disease duration in rheumatoid arthritis.

To establish the concentrations of micronutrients in serum, fatty acid composition in serum phosphatidylcholine and in adipose tissue, and their correlation with inflammation and disease duration in rheumatoid arthritis (RA), 21 consecutive patients with recently diagnosed disease (mean duration eight months), 21 patients with longstanding disease (mean duration 15 years), and 57 controls were examined. In the patients with RA low concentrations of the essential fatty acids, linoleic acid (18:2) and linolenic (18:3) acid, and high concentrations of total saturated fatty acids, both in serum phosphatidylcholine and in adipose tissue, were found, abnormalities that increased with disease duration. The proportion of 18:2 in serum phosphatidylcholine correlated inversely with such acute phase proteins as orosomucoid and C reactive protein. It is proposed that the decreases in essential fatty acids are related to increased activity in the desaturase/elongation enzymes, increased production of eicosanoids, or metabolic changes secondary to cytokine mediated inflammatory reaction. When the micronutrients were studied it was found that serum concentrations of selenium were lower in patients than in controls, but not those of ascorbic acid, alpha-tocopherol, retinol, folic acid, or cobalamine. Ascorbic acid concentrations tended to be lower in RA, however, and correlated inversely with those of haptoglobin, orosomucoid, and C reactive protein, indicating a relation between the ascorbic acid concentration and the degree of inflammation.