Mood and cognition in healthy older European adults: the Zenith study.

BACKGROUND: The study aim was to determine if state and trait intra-individual measures of everyday affect predict cognitive functioning in healthy older community dwelling European adults (n = 387), aged 55-87 years. METHODS: Participants were recruited from centres in France, Italy and Northern Ireland. Trait level and variability in positive and negative affect (PA and NA) were assessed using self-administered PANAS scales, four times a day for four days. State mood was assessed by one PANAS scale prior to assessment of recognition memory, spatial working memory, reaction time and sustained attention using the CANTAB computerized test battery. RESULTS: A series of hierarchical regression analyses were carried out, one for each measure of cognitive function as the dependent variable, and socio-demographic variables (age, sex and social class), state and trait mood measures as the predictors. State PA and NA were both predictive of spatial working memory prior to looking at the contribution of trait mood. Trait PA and its variability were predictive of sustained attention. In the final step of the regression analyses, trait PA variability predicted greater sustained attention, whereas state NA predicted fewer spatial working memory errors, accounting for a very small percentage of the variance (1-2%) in the respective tests. CONCLUSION: Moods, by and large, have a small transient effect on cognition in this older sample.

Predictors of taste acuity in healthy older Europeans.

This study aimed to identify factors associated with taste acuity in healthy older European adults aged 55-87 years, employing a factorial independent design to recruit older adults from centres in France, Italy and United Kingdom. Adults aged 70-87 years (N=387) were recruited in Rome (Italy) (n=108) and Grenoble (France) (n=91) and aged 55-70 years in Northern Ireland (United Kingdom) (n=93) and Clermont-Ferrand (C-F) (France) (n=95). A signal detection theory (SDT) approach was used for detection threshold assessment of the four basic tastes (salt; sweet; bitter; and, sour). Trial data were converted to R-indices. Diet was assessed by means of four day food diaries. Dietary data were converted using WISP and then reduced, using a principal components analysis, to four components: Component 1 'high fat and salt'; Component 2 'high vitamins and fibre'; Component 3 'high fat and carbohydrate'; and, Component 4 'high trace elements'. Socio-demographic information was collected by self report survey. Four separate regression analyses were carried out, one for each of the four basic taste qualities (sweet; sour; bitter; salt). Mean ROC scores for each taste quality were the response variables and age, sex, country, social class and dietary components were predictor variables. The main predictors of taste acuity were age, sex, social class and country, which had differential effects for each taste quality. These data suggest that socio-demographic and cultural factors should be taken into account when considering taste acuity in older people.

Supplemented zinc does not alter mood in healthy older European adults--a randomised placebo-controlled trial: the Zenith study.

OBJECTIVE: Older people are vulnerable to zinc deficiency, which may impact upon their mood. This randomised, placebo-controlled, double-blind intervention study aimed to investigate the effect of oral zinc gluconate supplementation (15 mg/d; 30 mg/d; and placebo) on subjective mood (affect) in older Europeans. SUBJECTS: Healthy volunteers (n 387) aged 55-87 years were recruited. SETTING: Volunteers in Rome (Italy; n 108) and Grenoble (France; n 91) were aged 70-87 years and those in Coleraine (Northern Ireland; n 93) and Clermont-Ferrand (France; n 95) were aged 55-70 years. DESIGN: Mood was measured using the Positive and Negative Affect Scale on four occasions per day over 4 d at baseline, 3 and 6 months post-intervention. RESULTS: Mixed ANOVA indicated that neither positive nor negative affect altered in response to zinc (15 mg/d or 30 mg/d) compared to placebo in either the 55-70 years or the ≥70 years age group. CONCLUSIONS: These results suggest that zinc does not benefit mood in healthy older people.

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.

Effect of sub-deficient zinc status on insulin sensitivity after burn injury in rats.

Although zinc status is an important parameter in insulin sensitivity, data concerning its implication in noxious burn-induced insulin resistance are scarce. The present study was designed to evaluate the impact of zinc status before burn on the recovery of injury with focus on plasma insulin and glucose levels. The experiment was performed in male adult Wistar rats fed from weaning with a zinc normal diet (80 ppm) or a depleted zinc diet (10 ppm) for 8 weeks and burned to third degree on 20% of their total body surface area. Blood and tissue samples were collected 3, 6, and 24 h after injury in order to study biochemical parameters and the glucose/insulin response in relation with the zinc status. After burn, zinc-depleted rats presented an exacerbated decrease in plasma zinc level. In addition, the burn-induced insulin resistance, leading to protein catabolism, was emphasized, with higher plasma insulin, glucose, and leptin levels in zinc-deficient animals versus normal-fed rats. Our experimental results underlined the interest to early control the zinc status in order to limit the deleterious effects of oxidative stress and insulin resistance in burned patients.

No antioxidant beneficial effect of zinc supplementation on oxidative stress markers and antioxidant defenses in middle-aged and elderly subjects: the Zenith study.

OBJECTIVE: The aim of the study was to investigate whether zinc supplementation affects antioxidant status in European middle-aged and elderly people. DESIGN: Multicentre prospective intervention study, randomized, double-blind, placebo-control. SETTING: France (Clermont-Ferrand/Theix, and Grenoble), Italy (Rome), Northern Ireland (Coleraine). SUBJECTS: A total of 387 healthy middle-aged (55-70 yrs) and free-living older aged (70-85 yrs) subjects were randomly allocated to three groups: 0, 15 or 30 mg zinc gluconate/d in addition to usual dietary intake during 6 months. METHODS: Oxidative stress status was evaluated by measurement of protein oxidation (plasma thiol groups), lipid peroxidation (plasma thio-barbituric acid reactants, TBARS), whole blood glutathione levels, erythrocyte copper/zinc superoxide dismutase activity and plasma antioxidant status (ferric reducing antioxidant power assay), at baseline and after 3 and 6 months. RESULTS: Zinc supplementation did not alter oxidative stress markers and antioxidant defenses in elderly, after 3 or 6 months, except an increase in Cu/Zn superoxide dismutase activity. CONCLUSIONS: In apparently healthy free living elderly people, a single zinc supplementation had no effects on oxidative stress status.

Burn-induced oxidative stress is altered by a low zinc status: kinetic study in burned rats fed a low zinc diet.

As an initial subdeficient status of zinc, considered as an essential antioxidant trace element, is frequent in burned patients, we aim to assess the effects of low zinc dietary intakes on burn-induced oxidative stress, in an animal model. After 8 weeks of conditioning diets containing 80 ppm (control group) or 10 ppm of zinc (depleted group), Wistar rats were 20% TBSA burned and sampled 1-10 days after injury. Kinetic evolutions of zinc status, plasma oxidative stress parameters, and antioxidant enzymes were also studied in blood and organs. The zinc-depleted diet induced, before injury, a significant decrease in zinc bone level and the increase of oxidative stress markers without stimulation of antioxidant enzyme activity. After burn, more markedly in zinc depleted animals than in controls, zinc levels decreased in plasma and bone, while increasing in liver. The decrease of thiol groups and GSH/GSSG ratio and the depression of GPx activity in liver are also moderately emphasized. Nevertheless, depleted zinc status could not be considered as determining for oxidative damages after burn injury. Further investigations must also be done to enlighten the mechanism of beneficial effects of zinc supplementation reported in burned patients.

Toxic effects of iterative intraperitoneal administration of zinc gluconate in rats.

Although zinc is an essential trace element involved in many physiological functions, toxicological data concerning acute exposure are scarce. The aim of our study was to determine the maximal iterative dose of zinc that can be administrated in rats without any adverse effect. Saline (control group) or zinc gluconate at 1, 2 or 4 mg/kg were intraperitoneally injected in animals daily during 7 days. The tolerance of zinc treatments was evaluated by the observation of clinical symptoms, haematological parameters and biochemistry, in relation to the zinc and copper levels in blood, liver, pancreas and faeces. We found no serious adverse effect within 1 week in rats injected intraperitoneally with 1 or 2 mg/kg/day of zinc gluconate, which tends to indicate that those doses could be useful in future therapeutic research. In contrast, the therapeutic treatment of adult rats with repeated intraperitoneal injections of a 4 mg/kg/day zinc dose should be cancelled, due to the occurrence of clinical adverse effects within a few days, as intraperitoneal local intolerance or major growth underdevelopment.

Interleukin-6, TNF-alpha and interleukin-1 beta levels in blood and tissue in severely burned rats.

Previous studies have demonstrated the early appearance of inflammatory cytokines in the systemic circulation after thermal injury both in humans and animals. The aim of this study was to evaluate the time course of several cytokines, IL-6, TNF-alpha and IL-1beta in serum, lung, liver and brain of severely burned rats during the first week after thermal injury. Cytokine measurements were performed by enzyme-linked immunosorbent assay (ELISA). The comparison between the sham-burned animals and animals with third-degree burns on 20% or 40% of their total body surface area allowed for the study of the inflammatory process relative to the size of the injury. Serum IL-6 levels, which were undetectable in sham-treated animals, peaked during the first hours after injury and were proportionate to the size of the area burned. After a few days, IL-6 increased once more, but only in the most severely burned rats. In lung, liver and brain, low but measurable basal levels of TNF-alpha and IL-1 were detected in sham-burned animals. Strikingly, IL-1beta levels remained significantly elevated in the lung after injury in animals having 20% and 40% burned skin area. Unexpectedly, both TNF-alpha and IL-1beta production decreased gradually in liver and brain after burn injury. Also, the inflammatory response after a burn injury appeared to be biphasic. The first period corresponded to the early release of IL-6 into the circulation, proportional to the severity of the injury. After a few days, a second period was marked by the extension of the inflammatory processes from the injured area to the rest of the body, particularly to lung, which could be considered as at potential risk of involvement in severely burned patients.

Taste acuity in response to zinc supplementation in older Europeans.

Taste acuity declines with age and may be dependent upon Zn status. The aim of the present double-blind, randomised controlled intervention trial has been to determine taste acuity in response to Zn supplementation (placebo, or 15 or 30 mg Zn/d). Healthy older European adults aged 70-87 years were recruited within Italy (Rome) (n 108) and France (Grenoble) (n 91) to the European Commission-funded Zenith project. A signal detection theory approach was adopted for taste assessment. The data were converted to R indices and analysed by repeated-measures ANOVA controlling for baseline taste acuity as well as serum and erythrocyte Zn. Serum Zn increased post-intervention, indicating compliance with the intervention. Results differed across geographical region. Salt taste acuity was greater in response to Zn (30 mg) than placebo post-intervention among those recruited in Grenoble. There was no apparent change in acuity for sweet, sour or bitter taste in response to Zn. Supplemented Zn may have potential to enhance salt taste acuity in those over the age of 70 years. Further research is required to determine if enhanced salt taste acuity is reflected in the eating experiences of older individuals.

Food chromium content, dietary chromium intake and related biological variables in French free-living elderly.

Trivalent chromium (Cr3+) is an essential trace element involved in insulin function. Cr deficiencies result in decreased insulin sensitivity, glucose intolerance and an increased risk of diabetes. Cr status decreases with age suggesting that the elderly may be at high risk of Cr deficiency. This study aimed to provide information about the Cr content of foods in France and the Cr intake in French free-living elderly. We measured the food Cr content and daily Cr intake of freely chosen diets for 3 d in twelve French free-living elderly people and their Cr excretion and plasma hormonal related variables, leptin, insulin and cortisol. Considering the relationship between insulin resistance and oxidative stress, we also determined plasma thiobarbituric acid reactive substance, thiol groups and total and reduced glutathione. Although these subjects had well-balanced diets, their daily Cr intakes did not reach the French recommendations. The low Cr intakes were due to the low Cr density of the foods. We found a negative correlation between Cr intakes and insulin, BMI and leptin.

Age- and sex-dependent effects of long-term zinc supplementation on essential trace element status and lipid metabolism in European subjects: the Zenith Study.

Given the key role of Zn in many physiological functions, optimal Zn status could be a predictive parameter of successful ageing. However, the benefit of Zn supplementation is still a matter of debate since Zn supplementation has been reported to be associated with the alteration of Cu status and lipid metabolism. As part of the Zenith Project, the present study aimed to investigate, in free-living healthy European middle-aged and older subjects, the effect of Zn supplementation on the biochemical status of Zn, Fe and Cu and on lipid profile. Volunteers aged 55-70 (n 188) and 70-85 (n 199) years old participated in a double-blinded, randomised study and received a daily placebo, or Zn as 15 or 30 mg for 6 months. Zn supplementation did not significantly modify erythrocyte Zn levels or erythrocyte Cu,Zn-superoxide dismutase activity. But Zn supplementation at 15 or 30 mg/d for 6 months increased significantly serum Zn levels and Zn urinary excretion with no major adverse effects on Fe and Cu status or on lipid metabolism. However, Zn supplementation at 30 mg/d showed some age- and sex-dependent alterations in Fe status or lipid profile. Therefore, with respect to the key role of an optimal Zn status in successful ageing, Zn supplementation at 15 mg/d, when necessary, could be safely proposed regarding lipids and the risk of interaction with Fe and Cu.

Effects of zinc supplementation on cognitive function in healthy middle-aged and older adults: the ZENITH study.

A randomised double-blind placebo-controlled design was employed to investigate the effects of Zn supplementation on cognitive function in 387 healthy adults aged 55-87 years. Several measures of visual memory, working memory, attention and reaction time were obtained using the Cambridge Automated Neuropsychological Test Battery at baseline and then after 3 and 6 months of 0 (placebo), 15 or 30 mg Zn/d. Younger adults (< 70 years) performed significantly better on all tests than older adults (> 70 years), and performance improved with practice on some measures. For two out of eight dependent variables, there were significant interactions indicating a beneficial effect (at 3 months only) of both 15 and 30 mg/d on one measure of spatial working memory and a detrimental effect of 15 mg/d on one measure of attention. Further work is required to establish whether these findings generalise to older adults in poorer mental and physical health and with less adequate Zn intake and status than the present sample.

Effect of zinc supplementation on in vitro copper-induced oxidation of low-density lipoproteins in healthy French subjects aged 55-70 years: the Zenith Study.

Zn has been shown to possess antioxidant properties in vitro and in vivo. As inadequate dietary Zn intake has been reported in these populations, Zn supplementation may protect against oxidative stress and thereby limit the progression of degenerative diseases in such populations. We conducted the present study to evaluate the long-term supplementation effects of two moderate doses of Zn on in vitro Cu-induced LDL oxidation in French men and women. Three groups of sixteen healthy subjects aged 55-70 years from each sex participated in this randomized double-blind, placebo-controlled study. Each group received for six months either 0, 15 or 30 mg supplemental Zn per d. At the beginning and at the end of the supplementation periods, dietary intakes of Zn, Cu, Fe and vitamin E were estimated using 4 d food-intake records (including the weekend) and the GENI program. Zn, Cu, Fe and vitamin E status were also determined. In vitro LDL oxidizability (basal conjugated diene level, maximal conjugated diene formation and lag time) and lipid parameters were also determined. Dietary intakes of Zn, Cu, Fe and vitamin E were adequate in this population. Zn supplementation significantly increased serum Zn levels but did not significantly modify Cu, Fe or vitamin E status. However, Zn supplementation had no effect on in vitro LDL oxidation parameters, nor were there any sex-related differences in in vitro LDL oxidizability. The present study showed that long-term Zn supplementation of healthy subjects aged 55-70 years had no effect on in vitro Cu-induced LDL oxidation under the study conditions.