Uncovering the Relationship between Selenium Status, Age, Health, and Dietary Habits: Insights from a Large Population Study including Nonagenarian Offspring from the MARK-AGE Project.

An inadequate selenium (Se) status can accelerate the aging process, increasing the vulnerability to age-related diseases. The study aimed to investigate plasma Se and Se species in a large population, including 2200 older adults from the general population (RASIG), 514 nonagenarian offspring (GO), and 293 GO Spouses (SGO). Plasma Se levels in women exhibit an inverted U-shaped pattern, increasing with age until the post-menopausal period and then declining. Conversely, men exhibit a linear decline in plasma Se levels with age. Subjects from Finland had the highest plasma Se values, while those from Poland had the lowest ones. Plasma Se was influenced by fish and vitamin consumption, but there were no significant differences between RASIG, GO, and SGO. Plasma Se was positively associated with albumin, HDL, total cholesterol, fibrinogen, and triglycerides and negatively associated with homocysteine. Fractionation analysis showed that Se distribution among plasma selenoproteins is affected by age, glucometabolic and inflammatory factors, and being GO or SGO. These findings show that sex-specific, nutritional, and inflammatory factors play a crucial role in the regulation of Se plasma levels throughout the aging process and that the shared environment of GO and SGO plays a role in their distinctive Se fractionation.

Beneficial and adverse effects of vitamin E on the kidney.

This article reviews the beneficial and adverse effects of high-dose vitamin E supplementation on the vitamin E status and renal function in human and rodent studies. The high doses of vitamin E, which can cause renal effects, were compared to upper limits of toxicity (UL) as established by various authorities worldwide. In recent mice studies with higher doses of vitamin E, several biomarkers of tissue toxicity and inflammation were found to be significantly elevated. In these biomarker studies, the severity of inflammation and the increased levels of the biomarkers are discussed together with the need to re-evaluate ULs, given the toxic effects of vitamin E on the kidney and emphasizing oxidative stress and inflammation. The controversy in the literature about vitamin E effects on the kidney is mainly caused by the dose-effects relations that do not give a clear view, neither in human nor animals studies. In addition, more recent studies on rodents with new biomarkers of oxidative stress and inflammation give new insights into possible mechanisms. In this review, the controversy is shown and an advice given on the vitamin E supplementation for renal health.

Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma.

Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling  = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.

The association of vitamin D with survival in colorectal cancer patients depends on antioxidant capacity.

BACKGROUND: Vitamin D plays a role in detoxifying free radicals, which might explain the previously reported lower mortality in colorectal cancer (CRC) patients with higher vitamin D concentrations. OBJECTIVES: We aimed to assess whether the associations of 25-hydroxyvitamin D [25(OH)D] with prognosis in CRC patients differ by total thiol concentration (TTC), a biomarker of antioxidant capacity. METHODS: CRC patients who were diagnosed from 2003 to 2010 and recruited into a population-based study in southern Germany (n = 2,592) were followed over a period of 6 y. 25(OH)D and TTC were evaluated from blood samples collected shortly after CRC diagnosis. Associations of 25(OH)D with all-cause and CRC mortality according to TTC were estimated using multivariable Cox proportional hazards regression. RESULTS: There was a weak positive correlation between 25(OH)D and TTC (r = 0.26, P < 0.001). 25(OH)D was inversely associated with mortality among patients in the lowest and middle TTC tertiles, but no associations were found among patients in the highest TTC tertile (P-interaction = 0.01). Among patients in the lowest/middle TTC tertiles, those in the middle and highest (compared with lowest) 25(OH)D tertiles had 31% and 44% lower all-cause mortality (P < 0.001) and 25% and 45% lower CRC mortality (P < 0.001), respectively. However, in the highest TTC tertile, 25(OH)D was not associated with all-cause (P = 0.638) or CRC mortality (P = 0.395). CONCLUSIONS: The survival advantages in CRC patients with adequate vitamin D strongly depend on antioxidant capacity and are most pronounced in cases of low antioxidant capacity. These findings suggest that TTC and other biomarkers of antioxidant status may be useful as the basis for enhanced selection criteria of patients for vitamin D supplementation, in addition to the conventional judgment based on blood 25(OH)D concentrations, and also for refining selection of patients for clinical trials aiming to estimate the effect of vitamin D supplementation.

Influence of vitamin D on key bacterial taxa in infant microbiota in the KOALA Birth Cohort Study.

Vitamin D has immunomodulatory properties giving it the potential to affect microbial colonization of the intestinal tract. We investigated whether maternal vitamin D supplemention, maternal plasma 25-hydroxyvitamin D concentration, or direct supplementation of the infant influences key bacterial taxa within microbiota of one month old infants. Infant and maternal vitamin D supplement use was ascertained via questionnaires. Maternal plasma 25-hydroxyvitamin D was determined at approximately the 36th week of pregnancy. In 913 one month old infants in the prospective KOALA Birth Cohort Study, fecal Bifidobacterium spp., Escherichia coli, Clostridium difficile, Bacteroides fragilis group, Lactobacillus spp. and total bacteria were quantified with real-time polymerase chain reaction assays targeting 16S rRNA gene sequences. The association between vitamin D exposure and prevalence or abundance of a specific bacterial group or species was analyzed using logistic or linear regression, respectively. There was a statistically significant negative linear trend between counts of Bifidobacterium spp. and levels of maternal vitamin D supplementation and maternal 25-hydroxyvitamin D quintiles, respectively. In addition, a positive linear trend between quintile groups and B. fragilis group counts was observed. Lower counts of C. difficile were associated with vitamin D supplementation of breast fed infants whose mothers were more likely to adhere to an alternative lifestyle in terms of, e.g., dietary habits. These data suggest that vitamin D influences the abundance of several key bacterial taxa within the infant microbiota. Given that intestinal microbiotic homeostasis may be an important factor in the prevention of immune mediated diseases and that vitamin D status is a modifiable factor, further investigation of the impact of postnatal vitamin D supplementation should be conducted in older infants.

The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.

Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.

Vitamin E supplementation in chronically hemodialyzed patients - influence on blood hemoglobin and plasma (anti)oxidant status.

Background: Disturbed oxidant/antioxidant status is involved in pathogenesis of anemia in end stage renal disease. There is evidence that vitamin E supplementation can increase blood hemoglobin in chronically hemodialyzed patients. However, the interindividual variation in response to the supplementation has not been fully addressed. Methods: 24 chronically hemodialyzed patients were supplemented with vitamin E (400 IU/day) in a period of two months. They had already been treated with erythropoiesis stimulating agents (ESA) and iron on a long-term basis, which was continued during the study period. A group of 20 healthy volunteers served as control subjects. Complete blood count, general biochemistry assays, the redox status by total thiols, oxidative stress by reactive oxygen metabolites, antioxidant status by biological antioxidant potential, and vitamin E (α- and γ- tocopherol) were measured before the start of supplementation, one month and two months later. Results: Overall, the vitamin E supplementation did not cause an increase of blood hemoglobin, hematocrit or red blood cells. However, 50 % of the patients with basal blood hemoglobin below 12.0 g/dL (N = 10) responded to the supplementation with its continuous increase. In addition, vitamin E exhibited a slight prooxidant effect only in the subgroup of patients with basal blood hemoglobin of ≥ 12.0 g/dL, two months after the start of supplementation (decreased total thiols: 300 ± 31 vs. 277 ± 36 µmol/L, p < 0.05; increased reactive oxygen metabolites: 183 ± 140 vs. 287 ± 112 CARR U, p > 0.05; decreased biological antioxidant potential: 2278 ± 150 vs. 2171 ± 126 µEq/L, p < 0.025), which coincided with their significantly increased serum α-tocopherol concentrations in comparison to the patients with basal blood hemoglobin below 12.0 g/dL (41.3 ± 7.2 vs. 59.9 ± 19.2 µmol/L, p < 0.025). Conclusions: When treated with ESA and iron on a long-term basis, the response to the vitamin E supplementation in chronically hemodialyzed patients is largely dependent on their basal blood hemoglobin and serum vitamin E concentrations.

Plasma Carotenoids, Tocopherols, and Retinol in the Age-Stratified (35-74 Years) General Population: A Cross-Sectional Study in Six European Countries.

Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/ß-carotene and higher ß-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene (r = -0.248), α-tocopherol (r = 0.208), α-carotene (r = -0.112), and ß-cryptoxanthin (r = 0.125; all p < 0.001). Age was inversely associated with lycopene (-6.5% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m²)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7% vs. 2.4% per five-year age increase). The association of higher ß-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (-4.8% vs. -3.8% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene.

Tissue-Specific Effects of Vitamin E Supplementation.

A multivitamin and mineral supplementation study of 6 weeks was conducted with male and female mice. The control group received a standard dose of vitamins and minerals of 1× the Recommended Daily Intake (RDI), whereas a second group received 3× RDI. A third group received a high dose of vitamin E (25× RDI), close to the upper limit of toxicity (UL), but still recommended and considered to be harmless and beneficial. The high dose of vitamin E caused a number of beneficial, but also adverse effects. Different biomarkers of tissue toxicity, oxidative stress related processes and inflammation were determined. These biomarkers did not change in plasma and erythrocytes to a large extent. In the liver of male mice, some beneficial effects were observed by a lower concentration of several biomarkers of inflammation. However, in the kidney of male mice, a number of biomarkers increased substantially with the higher dose of vitamin E, indicating tissue toxicity and an increased level of inflammation. Since this dose of vitamin E, which is lower than the UL, cause some adverse effects, even after a short exposure period, further studies are required to reconsider the UL for vitamin E.

Iron Supplements and Magnesium Peroxide: An Example of a Hazardous Combination in Self-Medication.

The use of self-medication, which includes dietary supplements and over-the-counter drugs, is still on the rise, while safety issues are not well addressed yet. This especially holds for combinations. For example, iron supplements and magnesium peroxide both produce adverse effects via the formation of reactive oxygen species (ROS). This prompted us to investigate the effect of the combination of three different iron supplements with magnesium peroxide on ROS formation. Hydroxyl radical formation by the three iron supplements either combined with magnesium peroxide or alone was determined by performing a deoxyribose assay. Free iron content of iron supplements was determined using ferrozine assay. To determine hydrogen peroxide formation by magnesium peroxide, a ferrous thiocyanate assay was performed. Finally, electron spin resonance spectroscopy (ESR) was performed to confirm the formation of hydroxyl radicals. Our results show that magnesium peroxide induces the formation of hydrogen peroxide. All three iron supplements induced the formation of the extremely reactive hydroxyl radical, although the amount of radicals formed by the different supplements differed. It was shown that combining iron supplements with magnesium peroxide increases radical formation. The formation of hydroxyl radicals after the combination was confirmed with ESR. All three iron supplements contained labile iron and induced the formation of hydroxyl radicals. Additionally, magnesium peroxide in water yields hydrogen peroxide, which is converted into hydroxyl radicals by iron. Hence, iron supplements and magnesium peroxide is a hazardous combination and exemplifies that more attention should be given to combinations of products used in self-medication.

Methylene blue attenuates mitochondrial dysfunction of rat kidney during experimental acute pancreatitis.

OBJECTIVE: The disturbance of mitochondrial functions has been considered as one of the mechanisms of pathogenesis of acute pancreatitis (AP) followed by kidney failure. This study was aimed to investigate the effects of methylene blue (MB) on pancreas and kidney mitochondrial respiratory functions during experimental acute pancreatitis in rats. METHODS: AP was induced by administrating sodium taurocholate into the pancreatic duct of male Wistar rats. The rats were divided into three groups: the MB group, MB (5 mg/kg) was injected intravenously 10 min prior to AP induction; the AP group, saline solution was injected intravenously 10 min prior to AP induction; and the sham operation group, isotonic sodium chlorine was used instead of sodium taurocholate. The animals were sacrificed after 24 h. The pancreas and kidney were removed for mitochondrial assay by oxygraphic and spectrophotometric methods. RESULTS: Intravenous injection of MB did not prevent AP-induced inhibition of pancreatic mitochondrial respiration; however, MB significantly improved kidney mitochondrial respiratory functions with complex I-dependent substrates glutamate and malate. The activity of complex I of mitochondria isolated from AP-damaged kidney was increased after pretreatment with MB. However, MB did not affect AP-inhibited kidney mitochondrial respiration with succinate. MB had no protective effects on amylase activity or on urea content in serum in AP. CONCLUSION: The disturbances of kidney mitochondrial energy metabolism in experimental model of severe AP can be ameliorated by MB administration.

Anticholinergic Accumulation: A Slumbering Interaction between Drugs and Food Supplements.

Many compounds display anticholinergic effects which might give rise to cognitive impairment and even delirium. These side effects are caused by their ability to bind to muscarinic receptors in our brain. Especially with combination of compounds, these serious effects are seen. This phenomenon, known as anticholinergic accumulation, is especially seen in the elderly. A classification of drugs for anticholinergic side effects has been made based on clinical observations, the ACB score. Here, we aimed to substantiate this classification by comparing the affinity of numerous drugs for the muscarinic receptors to the ACB score. Additionally, a number of supplements were screened. The affinity of the compounds was determined by their ability to displace the radioligand [(3)H]pirenzepine of the muscarinic receptor induced by these compounds. Our results show that the affinity of a compound for the muscarinic receptors correlated with its ACB score. Also food supplements appeared to bind to these muscarinic receptors. Moreover, several drug-drug, supplement-supplement and supplement-drug combinations had an affinity that is higher than the affinity of single compounds. This explains the phenomenon of anticholinergic accumulation. In conclusion, care should be taken to drug-drug and supplement-drug combinations with respect to anticholinergic accumulation.

Biomarkers of oxidative stress and redox status in a short-term low-dosed multivitamin and mineral supplementation study in two human age groups.

A 60-day intervention study was conducted in which the participants took a low dose of a multivitamin and mineral supplement. The study consists of a final number of 66 volunteers (30 males and 36 females), divided into two age groups of 30-35 and 60-65 years. For 30 days they took a multivitamin and mineral supplement with 1× the recommended daily intake (RDI) followed by another 30 days with 2× the RDI. The aim of the study was to monitor oxidative stress and redox status of both young and old age groups. In serum, the expected increase of the water-soluble vitamins folate and vitamin B12 was observed with a concomitant decrease in homocysteine. Serum biomarkers of oxidative stress, the reactive oxygen metabolites, of the antioxidant status, the biological antioxidant potential did not change. However, the total thiol levels in serum, biomarker of the redox status, decreased significant, only in both groups of elderly after 60 days. In erythrocytes, there was a change in the glutathione metabolism as observed by an increase in glutathione reductase and to a lower extend in glutathione peroxidase, indicating an increase in oxidative stress in all groups. It is concluded that a low-dosed multivitamin and -mineral supplementation have different effects on the redox status in young versus old. It remained to explain why a low dose of a multivitamin and -mineral supplement cause increased oxidative stress.

The shifting perception on antioxidants: the case of vitamin E and ß-carotene.

Antioxidants are vital for aerobic life, and for decades the expectations of antioxidants as health promoting agents were very high. However, relatively recent meta-analyses of clinical studies show that supplementation of antioxidants does not result in the presumed health benefit, but is associated with increased mortality. The dilemma that still needs to be solved is: what are antioxidants in the end, healthy or toxic? We have evaluated this dilemma by examining the presumed health effects of two individual antioxidants with opposite images i.e. the "poisonous" ß-carotene and the "wholesome" vitamin E and focused on one aspect, namely their role in inducing BPDE-DNA adducts. It appears that both antioxidants promote DNA adduct formation indirectly by inhibition of the protective enzyme glutathione-S-transferase π (GST π). Despite their opposite image, both antioxidants display a similar type of toxicity. It is concluded that, in the appreciation of antioxidants, first their benefits should be identified and substantiated by elucidating their molecular mechanism. Subsequently, the risks should be identified including the molecular mechanism. The optimal benefit-risk ratio has to be determined for each antioxidant and each individual separately, also considering the dose.

The supplement-drug interaction of quercetin with tamsulosin on vasorelaxation.

The food supplement quercetin is used as self-medication for prostate disorders and is known to induce vasorelaxation. The drug tamsulosin is used in the treatment of benign prostatic hyperplasia. A major side effect of tamsulosin is orthostatic hypotension, mediated by vasorelaxation resulting from α1-adrenoceptor blockade. The overlapping profile prompted us to investigate the pharmacodynamic interaction of quercetin with tamsulosin. Since quercetin is extensively metabolized in the intestines and the liver, the metabolites quercetin-3-glucuronide and 4'O-methyl-quercetin were also examined. Vasorelaxation induced by the compounds was tested in rat mesenteric arteries (average diameter: 360±µm) constricted by the α1-adrenoceptor agonist phenylephrine. Tamsulosin (0.1nM) decreased phenylephrine sensitivity 17-fold (n=10). Quercetin (5, 10 and 20µM) also caused a decrease (2-, 4- and 6-fold respectively) of phenylephrine sensitivity, while 10µM of quercetin-3-glucuronide and 4'O-methyl-quercetin decreased this sensitivity (1.5- and 2-fold) only slightly (n=6). The combination of tamsulosin with quercetin or quercetin metabolites proved to be far more potent than the compounds in isolation. The combination of quercetin, quercetin-3-glucuronide or 4'O-methyl-quercetin with tamsulosin decreased the phenylephrine sensitivity approximately 200-, 35- and 150-fold (n=6). The strong pharmacodynamic interaction between the food supplement quercetin and tamsulosin underlines the potential of the impact of supplement-drug interactions that warrant more research.

Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States.

OBJECTIVE: To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences. DESIGN: Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US. SETTING: General population. PARTICIPANTS: 26,018 men and women aged 50-79 years. MAIN OUTCOME MEASURES: All-cause, cardiovascular, and cancer mortality. RESULTS: 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses. CONCLUSIONS: Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

Biological effects of add-on eicosapentaenoic acid supplementation in diabetes mellitus and co-morbid depression: a randomized controlled trial.

BACKGROUND: Eicosapentaenoic acid (EPA) may reduce increased risks for (cardiovascular) morbidity and mortality in patients with diabetes mellitus (DM) and comorbid major depressive depression (MDD). Yet, effects of EPA-supplementation on biological risk factors for adverse outcomes have not been studied in DM-patients with MDD. METHODS: We performed a randomized, double-blind trial (n = 25) comparing add-on ethyl-EPA-supplementation to placebo on (I) oxidative stress, (II) inflammatory, (III) hypothalamic-pituitary-adrenal (HPA)-axis, (IV) one-carbon-cycle, (V) fatty acid metabolism and (VI) lipoprotein parameters during 12-weeks' follow-up. RESULTS: Besides increases in supplemented α-tocopherol [estimate (95% CI); 3.62 (1.14-6.11) µmol/l; p = 0.006] and plasma and erythrocyte EPA, the intervention did not influence other oxidative stress, inflammatory or one-carbon-cycle parameters compared to placebo. HPA-axis reactivity significantly decreased in the EPA-group (N = 12) [AUC(i): -121.93 (-240.20--3.47) min×nmol/l; p = 0.045], not in the placebo-group (N = 12). Furthermore, EPA-supplementation increased erythrocyte and plasma docosapentaenoic acid, and decreased plasma arachidonic acid (AA) concentrations [-1.61 (-3.10--0.11) %; p = 0.036]. Finally, EPA had a multivariate influence on lipoprotein concentrations (p = 0.030), reflected by relative increases in high density lipoprotein [HDL; 0.30 (0.02-0.58) mmol/l; p = 0.039] and total cholesterol concentrations [1.01 (0.29-1.72) mmol/l; p = 0.008]. CONCLUSION: Overall, add-on EPA-supplementation had limited effects on biological risk factors for adverse outcome in this sample of DM-patients with comorbid MDD. Besides increases in concentrations of supplemented α-tocopherol and EPA, AA decreased, and inconclusive effects on HPA-axis (re)activity and lipoprotein concentrations were observed. Therefore, further studies on the alleged beneficial effects of EPA-supplementation on biological risk factors for adverse outcome in DM-patients with comorbid MDD seem warranted, preferably using clinical outcomes such as (cardiovascular) DM-complications.

Polymorphisms in thioredoxin reductase and selenoprotein K genes and selenium status modulate risk of prostate cancer.

Increased dietary intake of Selenium (Se) has been suggested to lower prostate cancer mortality, but supplementation trials have produced conflicting results. Se is incorporated into 25 selenoproteins. The aim of this work was to assess whether risk of prostate cancer is affected by genetic variants in genes coding for selenoproteins, either alone or in combination with Se status. 248 cases and 492 controls from an EPIC-Heidelberg nested case-control study were subjected to two-stage genotyping with an initial screening phase in which 384 tagging-SNPs covering 72 Se-related genes were determined in 94 cases and 94 controls using the Illumina Goldengate methodology. This analysis was followed by a second phase in which genotyping for candidate SNPs identified in the first phase was carried out in the full study using Sequenom. Risk of high-grade or advanced stage prostate cancer was modified by interactions between serum markers of Se status and genotypes for rs9880056 in SELK, rs9605030 and rs9605031 in TXNRD2, and rs7310505 in TXNRD1. No significant effects of SNPs on prostate cancer risk were observed when grade or Se status was not taken into account. In conclusion, the risk of high-grade or advanced-stage prostate cancer is significantly altered by a combination of genotype for SNPs in selenoprotein genes and Se status. The findings contribute to explaining the biological effects of selenium intake and genetic factors in prostate cancer development and highlight potential roles of thioredoxin reductases and selenoprotein K in tumour progression.

Protective effect of selenium on aluminium-induced oxidative stress in mouse liver in vivo.

The aim of the study was to evaluate possible protective effects of selenium (Se) against systemic aluminium (Al) toxicity and the redox status of mouse liver after short-term (16 h) exposure to Al in vivo. BALB/c mice were injected i.p. with AlCl(3) (25mg Al(3+) per kg of body mass) or/and Na(2)SeO(3) (1.25mg Se per kg of body mass). The 4-fold increased activity of ALT in serum showed systemic hepatotoxicity that Se could not prevent by competitive mechanisms. The protective effects of Se could only be observed on intracellular oxidative stress events as determined by glutathione status. Exposure to Al leads to the decrease in the total glutathione (GSH(tot)) and GSH/GSSG redox ratio to about 50% of the control. Upon co-exposure to Se+Al, the concentration of GSH(tot) and the redox ratio was restored to the control values. Our results indicate that Se did not have a protective effect on Al-linked liver toxicity, but did ameliorate intracellular oxidative stress processes mediated by glutathione.

Supplementation with eicosapentaenoic omega-3 fatty acid does not influence serum brain-derived neurotrophic factor in diabetes mellitus patients with major depression: a randomized controlled pilot study.

BACKGROUND: Low brain-derived neurotrophic factor (BDNF) levels are observed in both depressed and diabetes patients. Animal research has shown that omega-3 polyunsaturated fatty acids increase BDNF levels. In this exploratory randomized double-blind placebo-controlled study in diabetes patients with major depression, we tested whether (a) omega- 3 ethyl-eicosapentaenoic acid (E-EPA) leads to increased serum BDNF levels and (b) whether changes in BDNF levels are associated with corresponding changes in depression. METHODS: Patients received 1 g/day E-EPA (n = 13) or placebo (n = 12) for 12 weeks, in addition to ongoing antidepressant therapy. At baseline and 12-week follow-up, we determined serum BDNF levels and depression severity, using the Montgomery-Åsberg Depression Rating Scale. RESULTS: We found no effect of E-EPA on BDNF levels (t = -0.144, p = 0.887), and changes in BDNF levels and depression severity were not significantly associated (Spearman's ρ = -0.115, p = 0.593). CONCLUSION: Our study does not provide evidence that supplementation with E-EPA improves BDNF levels in depressed diabetes patients already using antidepressants.