Stress exposure alters brain mRNA expression of the genes involved in insulin signalling, an effect modified by a high fat/high fructose diet and cinnamon supplement.

In occidental societies, high fat and high sugar diets often coincide with episodes of stress. The association is likely to modify brain energy control. Brain insulin signalling is rarely studied in stressed individuals consuming high fat diets. Furthermore the effects of cinnamon supplement are not known in these conditions. Therefore, we exposed rats, over a 12-week period, to a control (C) or a high fat/high fructose (HF/HFr) diet that induces peripheral insulin resistance. A cinnamon supplement (C+CN and HF/HFr +CN) was added or not. After diet exposure, one group of rats was exposed to a 30-min restraint followed by a 10-min open-field test, their combination featuring a moderate stressor, the other rats staying unstressed in their home cages. The insulin signalling in hippocampus and frontal cortex was studied through the mRNA expression of the following genes: insulin receptor (Ir), insulin receptor substrate (Irs1), glucose transporters (Glut1 and Glut3), glycogen synthase (Gys1) and their modulators, Akt1 and Pten. In C rats, stress enhanced the expression of Ir, Irs1, Glut1, Gys1 and Akt1 mRNA. In C+CN rats, stress induced an increase in Pten but a decrease in Gys1 mRNA expression. In HF/HFr rats, stress was associated with an increase in Pten mRNA expression. In HF/HFr+CN rats, stress increased Pten mRNA expression but also decreased Gys1 mRNA expression. This suggests that a single moderate stress favours energy refilling mechanisms, an effect blunted by a previous HF/HFr diet and cinnamon supplement.

Selenium preserves keratinocyte stemness and delays senescence by maintaining epidermal adhesion.

Skin is constantly exposed to environmental factors such as pollutants, chemicals and ultra violet radiation (UV), which can induce premature skin aging and increase the risk of skin cancer. One strategy to reduce the effect of oxidative stress produced by environmental exposure is the application of antioxidant molecules. Among the endogenous antioxidants, selenoproteins play a key role in antioxidant defense and in maintaining a reduced cellular environment. Selenium, essential for the activity of selenoproteins, is a trace element that is not synthesized by organisms and must be supplied by diet or supplementation. The aim of this study is to evaluate the effect of Selenium supplementation on skin aging, especially on keratinocytes, the main cells of the epidermis. Our results demonstrate for the first time to our knowledge, the major role of Selenium on the replicative life span of keratinocytes and on aging skin. Selenium protects keratinocyte stem cells (KSCs) against senescence via preservation of their stemness phenotype through adhesion to the basement membrane. Additionally, Selenium supplementation maintains the homeostasis of skin during chronological aging in our senescent skin equivalent model. Controlled supplementation with Selenium could be a new strategy to protect skin against aging.

Selenium status and fungi in the protein-losing enteropathy of persistent diarrhea.

BACKGROUND AND OBJECTIVES: A vicious cycle of infection, malabsorption, and malnutrition has been implicated in the perpetuation of diarrheal disease. This study examined whether persistent diarrhea is associated with changes in selenium status and stool alpha-1 antitrypsin (AAT) concentration. METHODS AND STUDY DESIGN: This cross-sectional study included 30 children aged 1-12 years with persistent diarrhea who were hospitalized in Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta, and 30 apparently healthy children who were matched by age and sex and lived in a rural area of Jakarta. Clinical examinations, blood routine tests, erythrocyte glutathione peroxidase (GPX) activity and plasma selenium levels as well as AAT in fresh stool samples were performed in all the subjects. RESULTS: Of 30 children with persistent diarrhea, 17 had moderate malnutrition and 13 had severe malnutrition. The mean plasma selenium was significantly lower in children with persistent diarrhea than in children without diarrhea (86.0 µg/L [95% CI: 76.1-95.9] vs 110 µg/L [95% CI: 104-116, p<0.0001). The mean stool AAT concentration was significantly higher in children with persistent diarrhea than in those without diarrhea (115 mg/dL [95% CI: 38.5-191] vs 16 mg/dL [95% CI: 4.0-13.5, p<0.0001]). Selenium correlated with AAT (p=0.05). Fecal fungi were persistently present. CONCLUSIONS: Although selenium status in both groups was optimal for the obtained plasma GPX activity, children with persistent diarrhea exhibited lower plasma selenium levels. This study suggests that the decrease in the plasma selenium level may be the consequence of protein loss and that fungi may be involved.

Nutrition for the ageing brain: Towards evidence for an optimal diet.

As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline.

Cinnamon intake alleviates the combined effects of dietary-induced insulin resistance and acute stress on brain mitochondria.

Insulin resistance (IR), which is a leading cause of the metabolic syndrome, results in early brain function alterations which may alter brain mitochondrial functioning. Previously, we demonstrated that rats fed a control diet and submitted to an acute restraint stress exhibited a delayed mitochondrial permeability transition pore (mPTP) opening. In this study, we evaluated the combined effects of dietary and emotional stressors as found in western way of life. We studied, in rats submitted or not to an acute stress, the effects of diet-induced IR on brain mitochondria, using a high fat/high fructose diet (HF(2)), as an IR inducer, with addition or not of cinnamon as an insulin sensitizer. We measured Ca(2+) retention capacity, respiration, ROS production, enzymatic activities and cell signaling activation. Under stress, HF(2) diet dramatically decreased the amount of Ca(2+) required to open the mPTP (13%) suggesting an adverse effect on mitochondrial survival. Cinnamon added to the diet corrected this negative effect and resulted in a partial recovery (30%). The effects related to cinnamon addition to the diet could be due to its antioxidant properties or to the observed modulation of PI3K-AKT-GSK3ß and MAPK-P38 pathways or to a combination of both. These data suggest a protective effect of cinnamon on brain mitochondria against the negative impact of an HF(2) diet. Cinnamon could be beneficial to counteract deleterious dietary effects in stressed conditions.

Acute stress delays brain mitochondrial permeability transition pore opening.

Since emotional stress elicits brain activation, mitochondria should be a key component of stressed brain response. However, few studies have focused on mitochondria functioning in these conditions. In this work, we aimed to determine the effects of an acute restraint stress on rat brain mitochondrial functions, with a focus on permeability transition pore (PTP) functioning. Rats were divided into two groups, submitted or not to an acute 30-min restraint stress (Stress, S-group, vs. Control, C-group). Brain was removed immediately after stress. Mitochondrial respiration and enzymatic activities (complex I, complex II, hexokinase) were measured. Changes in PTP opening were assessed by the Ca(2+) retention capacity. Cell signaling pathways relevant to the coupling between mitochondria and cell function (adenosine monophosphate-activated protein kinase, phosphatidylinositol 3-kinase, glycogen synthase kinase 3 beta, MAPK, and cGMP/NO) were measured. The effect of glucocorticoids was also assessed in vitro. Stress delayed (43%) the opening of PTP and resulted in a mild inhibition of complex I respiratory chain. This inhibition was associated with significant stress-induced changes in adenosine monophosphate-activated protein kinase signaling pathway without changes in brain cGMP level. In contrast, glucocorticoids did not modify PTP opening. These data suggest a rapid adaptive mechanism of brain mitochondria in stressed conditions, with a special focus on PTP regulation. In a rat model of acute restraint stress, we observed substantial changes in brain mitochondria functioning. Stress significantly (i) delays (43%) the opening of permeability transition pore (PTP) by the calcium (Ca(2+) ), its main inductor and (ii) results in an inhibition of complex I in electron transport chain associated with change in AMPK signaling pathway. These data suggest an adaptive mechanism of brain mitochondria in stressed condition, with a special focus on PTP regulation.

Effect of a high-fat--high-fructose diet, stress and cinnamon on central expression of genes related to immune system, hypothalamic-pituitary-adrenocortical axis function and cerebral plasticity in rats.

The intake of a high-fat/high-fructose (HF/HFr) diet is described to be deleterious to cognitive performances, possibly via the induction of inflammatory factors. An excess of glucocorticoids is also known to exert negative effects on cerebral plasticity. In the present study, we assessed the effects of an unbalanced diet on circulating and central markers of inflammation and glucocorticoid activity, as well as their reversal by dietary cinnamon (CN) supplementation. A group of male Wistar rats were subjected to an immune challenge with acute lipopolysaccharide under a HF/HFr or a standard diet. Another group of Wistar rats were fed either a HF/HFr or a control diet for 12 weeks, with or without CN supplementation, and with or without restraint stress (Str) application before being killed. We evaluated the effects of such regimens on inflammation parameters in the periphery and brain and on the expression of actors of brain plasticity. To assess hypothalamic-pituitary-adrenocortical axis activity, we measured the plasma concentrations of corticosterone and the expression of central corticotrophin-releasing hormone, mineralocorticoid receptor, glucocorticoid receptor and 11ß-hydroxysteroid dehydrogenase. We found that the HF/HFr diet induced the expression of cytokines in the brain, but only after an immune challenge. Furthermore, we observed the negative effects of Str on the plasma concentrations of corticosterone and neuroplasticity markers in rats fed the control diet but not in those fed the HF/HFr diet. Additionally, we found that CN supplementation exerted beneficial effects under the control diet, but that its effects were blunted or even reversed under the HF/HFr diet. CN supplementation could be beneficial under a standard diet. [corrected].

Effects of di(2-ethylhexyl)phthalate on testicular oxidant/antioxidant status in selenium-deficient and selenium-supplemented rats.

Di(ethylhexyl)phthalate (DEHP), the most widely used plasticizer, was investigated to determine whether an oxidative stress process was one of the underlying mechanisms for its testicular toxicity potential. To evaluate the effects of selenium (Se), status on the toxicity of DEHP was further objective of this study, as Se is known to play a critical role in testis and in the modulation of intracellular redox equilibrium. Se deficiency was produced in 3-weeks-old Sprague-Dawley rats feeding them ≤0.05 mg Se /kg diet for 5 weeks, and Se-supplementation group was on 1 mg Se/kg diet. DEHP-treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and thus the GSH/GSSG redox ratio; and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP was found to induce oxidative stress in rat testis, as evidenced by significant decrease in GSH/GSSG redox ratio (>10-fold) and marked increase in TBARS levels, and its effects were more pronounced in Se-deficient rats with ∼18.5-fold decrease in GSH/GSSG redox ratio and a significant decrease in GPx4 activity, whereas Se supplementation was protective by providing substantial elevation of redox ratio and reducing the lipid peroxidation. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting testicular tissue from the oxidant stressor activity of DEHP.

Cinnamon counteracts the negative effects of a high fat/high fructose diet on behavior, brain insulin signaling and Alzheimer-associated changes.

Insulin resistance leads to memory impairment. Cinnamon (CN) improves peripheral insulin resistance but its effects in the brain are not known. Changes in behavior, insulin signaling and Alzheimer-associated mRNA expression in the brain were measured in male Wistar rats fed a high fat/high fructose (HF/HFr) diet to induce insulin resistance, with or without CN, for 12 weeks. There was a decrease in insulin sensitivity associated with the HF/HFr diet that was reversed by CN. The CN fed rats were more active in a Y maze test than rats fed the control and HF/HFr diets. The HF/HFr diet fed rats showed greater anxiety in an elevated plus maze test that was lessened by feeding CN. The HF/HFr diet also led to a down regulation of the mRNA coding for GLUT1 and GLUT3 that was reversed by CN in the hippocampus and cortex. There were increases in Insr, Irs1 and Irs2 mRNA in the hippocampus and cortex due to the HF/HFr diet that were not reversed by CN. Increased peripheral insulin sensitivity was also associated with increased glycogen synthase in both hippocampus and cortex in the control and HF/HFr diet animals fed CN. The HF/HFr diet induced increases in mRNA associated with Alzheimers including PTEN, Tau and amyloid precursor protein (App) were also alleviated by CN. In conclusion, these data suggest that the negative effects of a HF/HFr diet on behavior, brain insulin signaling and Alzheimer-associated changes were alleviated by CN suggesting that neuroprotective effects of CN are associated with improved whole body insulin sensitivity and related changes in the brain.

Quantitative PCR for glucose transporter and tristetraprolin family gene expression in cultured mouse adipocytes and macrophages.

Quantitative real-time PCR (qPCR) such as TaqMan and SYBR Green qPCR are widely used for gene expression analysis. The drawbacks of SYBR Green assay are that the dye binds to any double-stranded DNA which can generate false-positive signals and that the length of the amplicon affects the intensity of the amplification. Previous results demonstrate that TaqMan assay is more sensitive but generates lower calculated expression levels than SYBR Green assay in quantifying seven mRNAs in tung tree tissues. The objective of this study is to expand the analysis using animal cells. We compared both qPCR assays for quantifying 24 mRNAs including those coding for glucose transporter (Glut) and mRNA-binding protein tristetraprolin (TTP) in mouse 3T3-L1 adipocytes and RAW264.7 macrophages. The results showed that SYBR Green and TaqMan qPCR were reliable for quantitative gene expression in animal cells. This result was supported by validation analysis of Glut and TTP family gene expression. However, SYBR Green qPCR overestimated the expression levels in most of the genes tested. Finally, both qPCR instruments (Bio-Rad's CFX96 real-time system and Applied Biosystems' Prism 7700 real-time PCR instrument) generated similar gene expression profiles in the mouse cells. These results support the conclusion that both qPCR assays (TaqMan and SYBR Green qPCR) and both qPCR instruments (Bio-Rad's CFX96 real-time system and Applied Biosystems' Prism 7700 real-time PCR instrument) are reliable for quantitative gene expression analyses in animal cells but SYBR Green qPCR generally overestimates gene expression levels than TaqMan qPCR.

Thyroidal effects of di-(2-ethylhexyl) phthalate in rats of different selenium status.

This study was designed to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on thyroid hormone levels and oxidant/antioxidant parameters in the rat and to evaluate the effects of selenium status. Selenium deficiency was produced by feeding 3-week-old Sprague-Dawley rats with <0.05 mg selenium/kg body weight for 5 weeks, and the supplementation group received a diet of 1 mg selenium/kg body weight. DEHP-treated groups received the compound at a dose of 1000 mg/kg by gavage during the last 10 days of the feeding period. Levels of thyroid hormone levels as well as selenoenzyme (glutathione peroxidase 1, thioredoxin reductase), catalase, and superoxide dismutase (SOD) activity and thiobarbituric acid reactive substance (TBARS) were measured. Total thyroxine (TT4) levels decreased significantly with DEHP exposure (~25%), whereas TT3 level was not altered. The TT4 lowering effect of DEHP exposure was not affected by selenium deficiency but was observed when animals exposed to DEHP received a selenium supplement. DEHP was found to alter the antioxidant status and induce oxidative stress in rat thyroid by increasing SOD activity (~30%) and TBARS levels (~35%). The effects of DEHP were much more pronounced in selenium-deficient rats, as evidenced by significant increases in SOD activity (~65%) and TBARS levels (~55%) compared with the control levels. Thus, these results show the thyroid-disrupting effect of DEHP in rats and protection by selenium.

Di(2-ethylhexyl)phthalate-induced renal oxidative stress in rats and protective effect of selenium.

This study was designed to examine the oxidative stress potential of di(2-ethylhexyl)phthalate (DEHP) on rat kidney and to evaluate possible protective effect of selenium (Se) status. Se deficiency (SeD) was produced in 3-week old Sprague-Dawley rats by feeding them ≤ 0.05 Se mg/kg diet for 5 weeks; Se supplementation group (SeS) was on 1 mg Se/kg diet. DEHP treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations of total glutathione (GSH), thiols and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP treatment was found to induce oxidative stress in rat kidney, as evidenced by significant decreases in GPx1 (~20%) and SOD (~30%) activities and GSH levels (~20%), along with marked decrease in thiol content (~40%) and increase in TBARS (~30%) levels. The effects of DEHP was more pronounced in SeD rats, whereas Se supplementation was protective by providing substantial elevations of GPx1 and GPx4 activities and GSH levels. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting renal tissue from the oxidant stressor activity of DEHP.

Cinnamon increases liver glycogen in an animal model of insulin resistance.

The objective of this study was to determine the effects of cinnamon on glycogen synthesis, related gene expression, and protein levels in the muscle and liver using an animal model of insulin resistance, the high-fat/high-fructose (HF/HFr) diet-fed rat. Four groups of 22 male Wistar rats were fed for 12 weeks with (1) HF/HFr diet to induce insulin resistance, (2) HF/HFr diet containing 20 g cinnamon per kilogram of diet, (3) control diet, and (4) control diet containing 20 g cinnamon per kilogram of diet. In the liver, cinnamon added to the HF/HFr diet led to highly significant increases of liver glycogen. There were no significant changes in animals consuming the control diet plus cinnamon. In the liver, cinnamon also counteracted the decreases of the gene expressions due to the consumption of the HF/HFr diet for the insulin receptor, insulin receptor substrates 1 and 2, glucose transporters 1 and 2, and glycogen synthase 1. In muscle, the decreased expressions of these genes by the HF/HFr diet and glucose transporter 4 were also reversed by cinnamon. In addition, the overexpression of glycogen synthase 3ß messenger RNA levels and protein observed in the muscle of HF/HFr fed rats was decreased in animals consuming cinnamon. These data demonstrate that, in insulin-resistant rats, cinnamon improves insulin sensitivity and enhances liver glycogen via regulating insulin signaling and glycogen synthesis. Changes due to cinnamon in control animals with normal insulin sensitivity were not significant.

Plasma selenium and risk of dysglycemia in an elderly French population: results from the prospective Epidemiology of Vascular Ageing Study.

BACKGROUND: A preventive role of selenium on the risk of diabetes has been reported and ascribed to the "insulin-like" activity of selenium and the antioxidant properties of the selenoenzymes. By contrast, data from cross-sectional studies and clinical trials have suggested an adverse effect of high selenium status and selenium supplementation on type-2 diabetes risk. Given these controversial results, we investigated prospectively the relationship between baseline plasma selenium concentration and occurrence of dysglycemia (impaired fasting glucose or type 2 diabetes) in an elderly French cohort. METHODS: The Epidemiology of Vascular Ageing (EVA) study (n = 1389, 59-71 years) is a 9-year longitudinal study in which, fasting plasma glucose was measured at baseline, 2, 4 and 9 years. Analyses were performed on 1162 participants with complete data. RESULTS: At baseline plasma selenium mean levels were 1.08 (0.21) mumol/l in men and 1.10 (0.20) mumol/l in women. During the 9-year follow-up, 127 cases of dysglycemia occurred. A significant interaction was found between plasma selenium and sex. Risk of dysglycemia was significantly lower in men with plasma selenium in the highest tertile (T3:1.19-1.97) compared to those in the lowest tertile (T1:0.18-1.00) [HR = 0.48 (0.25-0.92)], but no significant relationship was observed in women. After controlling for socio-demographic factors, lifestyle factors, cardiovascular diseases, body mass index, hypertension and lipid profile, plasma selenium remained marginally significantly associated with occurrence of dysglycemia in men [T3 vs. T1, HR = 0.50 (0.24-1.04)] and unrelated in women. CONCLUSIONS: This prospective study suggests a sex-specific protective effect of higher selenium status at baseline on later occurrence of dysglycemia.

Chromium III histidinate exposure modulates gene expression in HaCaT human keratinocytes exposed to oxidative stress.

While the toxicity of hexavalent chromium is well established, trivalent chromium is an essential nutrient involved in insulin and glucose homeostasis. To study the antioxidant effects of Cr(III)His, cDNA arrays were used to investigate the modulation of gene expression by trivalent chromium histidinate (Cr(III)His) in HaCaT human keratinocytes submitted to hydrogen peroxide (H2O2). Array was composed by a set of 81 expressed sequences tags (ESTs) essentially represented by antioxidant and DNA repair genes. HaCaT were preincubated for 24 h with 50 microM Cr(III)His and were treated with 50 muM H2O2. Total RNAs were isolated immediately or 6 h after the stress. In Cr(III)His preincubated cells, transcripts related to antioxidant family were upregulated (glutathione synthetase, heme oxygenase 2, peroxiredoxin 4). In Cr(III)His preincubated cells and exposed to H2O2, increased expressions of polymerase delta 2 and antioxidant transcripts were observed. Biochemical methods performed in parallel to measure oxidative stress in cells showed that Cr(III)His supplementation before H2O2 stress protected HaCaT from thiol groups decrease and thiobarbituric acid reactive substances increase. In summary, these results give evidence of antioxidant gene expression and antioxidant protection in HaCaT preincubated with Cr(III)His and help to explain the lack of toxicity reported for Cr(III)His.

Antioxidant effects of a cinnamon extract in people with impaired fasting glucose that are overweight or obese.

OBJECTIVE: To determine the effects of a dried aqueous extract of cinnamon on antioxidant status of people with impaired fasting glucose that are overweight or obese. METHODS: Twenty-two subjects, with impaired fasting blood glucose with BMI ranging from 25 to 45, were enrolled in a double-blind placebo-controlled trial. Subjects were given capsules containing either a placebo or 250 mg of an aqueous extract of cinnamon (Cinnulin PF) two times per day for 12 weeks. Plasma malondialdehyde (MDA) concentrations were assessed using high performance liquid chromatography and plasma antioxidant status was evaluated using ferric reducing antioxidant power (FRAP) assay. Erythrocyte Cu-Zn superoxide (Cu-Zn SOD) activity was measured after hemoglobin precipitation by monitoring the auto-oxidation of pyrogallol and erythrocyte glutathione peroxidase (GPx) activity by established methods. RESULTS: FRAP and plasma thiol (SH) groups increased, while plasma MDA levels decreased in subjects receiving the cinnamon extract. Effects were larger after 12 than 6 weeks. There was also a positive correlation (r = 0.74; p = 0.014) between MDA and plasma glucose. CONCLUSION: This study supports the hypothesis that the inclusion of water soluble cinnamon compounds in the diet could reduce risk factors associated with diabetes and cardiovascular disease.

EDTA chelation therapy, without added vitamin C, decreases oxidative DNA damage and lipid peroxidation.

Chelation therapy is thought to not only remove contaminating metals but also to decrease free radical production. However, in standard ethylene diamine tetracetic acid (EDTA) chelation therapy, high doses of vitamin C with potential pro-oxidant effects are often added to the chelation solution. The authors demonstrated previously that the intravenous administration of the standard chelation cocktail, containing high amounts of vitamin C, resulted in an acute transitory pro-oxidant burst that should be avoided in the treatment of pathologies at risk of increased oxidative stress such as diabetes and cardiovascular disease. The current study was designed to determine the acute and chronic biochemical effects of chelation therapy on accepted clinical, antioxidant variables. An EDTA chelation cocktail not containing ascorbic acid was administered to six adult patients for five weeks (10 sessions of chelation therapy); antioxidant indicators were monitored. Immediately after the initial chelation session, in contrast with the data previously reported with the standard cocktail containing high doses of vitamin C, none of the oxidative stress markers were adversely modified. After five weeks, plasma peroxide levels, monitored by malondialdehyde, decreased by 20 percent, and DNA damage, monitored by formamidopyrimidine-DNA glycosylase (Fpg) sensitive sites, decreased by 22 percent. Remaining antioxidant-related variables did not change. In summary, this study demonstrates that multiple sessions of EDTA chelation therapy in combination with vitamins and minerals, but without added ascorbic acid, decreases oxidative stress. These results should be beneficial in the treatment of diseases associated with increased oxidative stress such as diabetes and cardiovascular diseases.

Zinc supplementation does not alter plasma homocysteine, vitamin B12 and red blood cell folate concentrations in French elderly subjects.

BACKGROUND/AIMS: In ageing, low folates and vitamin B12 status are frequent and can explain the increase of plasma homocysteine level. Zinc is involved in the folates and vitamin B12 metabolism with opposite actions. The aim of this study was to investigate the effects of zinc supplementation on homocysteine and vitamin B12 plasma levels as well as red blood cell folate level in French ageing subjects participating in the ZENITH study. METHODS: Apparently healthy middle-aged (55-70 years) and free-living older (70-85 years) subjects were enrolled. They were randomly allocated to three groups: 0, 15 or 30 mg Zn per day for 6 months as zinc gluconate in addition to their usual dietary intake. RESULTS: At baseline, plasma homocysteine levels (15.2+/-3.5 micromol/L) in older people were higher than in the middle-aged subjects (12.7+/-2.7 micromol/L) and was negatively correlated with vitamin B12 values (p=0.0036, r=-0.215) and with RBC folate levels (p<0.0001, r=-0.30). These results are in agreement with previous data. However, we found no correlation between the biomarkers of zinc status and homocysteine, vitamin B12 or folate levels at baseline. Moreover, 6-month zinc supplementation did not modify homocysteine, vitamin B12 and RBC folate values in either of the groups. CONCLUSIONS: Zinc supplementation at moderate doses do not lead to deleterious effect on folate or vitamin B12 status in ageing healthy free-living people, but does not have any beneficial effects on homocysteine metabolism either.

Fibrates but not statins increase plasma selenium in dyslipidemic aged patients--the EVA study.

This secondary analysis of "Etude du Vieillissement Artériel" (EVA) study reports the effect of fibrates and statins on plasma selenium concentration and its 9-year change in free-living dyslipidemic elderly. Dyslipidemic patients were categorized in three sub-groups according to final low-density lipoprotein (LDL)-cholesterol level or hypolipidemic treatment: non-treated dyslipidemic (LDL-cholesterol >4.41 mmol/L, n=84); dyslipidemics who were treated exclusively by fibrates (n=47) or by statins (n=25) whatever their serum LDL-cholesterol concentration. The influence of lipid-lowering treatments on plasma selenium concentrations and its 9-year change was evaluated by analysis of variance (ANOVA) and multivariate linear regression models taking into account cardiovascular risk and changes in lipid-profile parameters. Multivariate linear regression indicated that the plasma selenium decline was associated with the longitudinal variation in LDL (beta=-0.039+/-0.019, p=0.04) and high-density lipoprotein (HDL)-cholesterol concentrations (beta=0.187+/-0.059, p=0.002) but not with triglycerides (beta=-0.018+/-0.031, p=0.57). During the 9-year follow-up, similar plasma selenium declines were observed in all the sub-groups (p=0.33) despite plasma selenium levels being higher in fibrate users and lower in statin users (p=0.0004). The mechanisms underlying these data are not yet totally understood, but considering the risk of selenium deficiency in the elderly and its relationship with poor health status further clinical trial is needed to verify the proposed hypotheses.