Zinc effects on nutrient / nutrient interactions and trends in health and ageing.

Inadequate intakes of micronutrients in elderly negatively affect the nutritional status. Zinc (Zn) is an essential micronutrient in the elderly, especially in relation to its impact on immune function, bone mass, cognitive function and oxidative stress. However, data are lacking on Zn interaction with other trace elements during normal aging. In this study, we evaluate the effect of Zn supplementation on trace elements status in late middle-aged and older free-living subjects. Zn, iron (Fe) and copper (Cu) status in 188 middle-aged subjects from Clermont-Ferrand (Fr) and Coleraine (UK), and in 199 older subjects from Grenoble (Fr) and Roma (It) were assessed after 3 and 6 months supplementation with 15 or 30mg/ Zn/d or placebo. In relation to the Zn RDA for people older than 55y, Zn intakes in most of the middle-aged and older subjects (more than 96%) in the present study were adequate. The prevalence of biological Zn deficiency in free-living aging European people was low (<5%). 30mg/d of Zn increased significantly serum and urinary Zn in middle-aged and older people, but no effect of Zn supplementation on erythrocyte Zn has been observed in the middle-aged and older groups. Fe and Cu status were not modified by Zn supplementation in the middle-aged and older groups. In conclusion, our findings suggest that in our population of middle age and older subjects, Zn supplementation had no adverse effects on Fe and Cu status.

The objective of this study was to describe health and lifestyle factors of participants in the ZENITH study. To do so, a prospective multi-centre intervention study employing a randomised double-blind design. Community dwelling older adults (n=387), aged 55-87 years were recruited from regions in France, Italy and the UK. A self-report questionnaire comprising socio-demographic variables, dietary habits, physical activity in the home, at work and recreation. Participants differed with regards dietary habits and physical activity for each region. Recreational activity was higher in France and women generally tend to perform less hours of recreational activity per week than men. The differences found for these regions of Europe in relation to lifestyle factors will affect health and well-being within these countries and may mediate the impact of Zn supplementation on various biological and psychological parameters.

Cortisol effects mood and behaviour as it alters brain cells and some neurotransmitters. Negative mood has been associated with increased cortisol levels (Gold et al 1986), positive mood is associated with lowered cortisol levels (Rudolph and McAuley, 1995). The latter finding is less conclusive and more research is needed (Hubert and de Jong-Meyer, 1990). Zinc (Zn) supplementation may enhance positive mood (Fabris and Macchegiani, 1995) by its effect on tryptophan, which increases levels of serotonin leading to a reduction in cortisol levels (Hambridge and Mills, 1989) and an inhibitory effect on negative affect. Little research has been carried out looking at this in older adults. This study aimed at investigating the effects of Zn supplementation on cortisol levels and mood in healthy older adults. This is a randomised placebo controlled double blind intervention study investigating supplementation of either 15 or 30 mg Zn/day or placebo for six months on mood and cortisol levels. A Northern Ireland sample of 43 older adults, aged 55-70 years were recruited. Baseline and 6 month follow up measures of salivary cortisol, measured using an enzyme immunoassay kit, were obtained twice a day for 7 consecutive days in conjunction with measures of positive and negative affect measured using the PANAS scale (Watson et al, 1988). Evening cortisol was negatively correlated to serum Zn and positive mood. Perceived stress was correlated to negative mood. Zinc supplementation did not effect cortisol levels. Cortisol levels were related to positive mood but Zn does not appear to mediate cortisol levels in healthy adults.

Moderate zinc (Zn) deficiency is often associated with ageing, which might arise due to a reduced Zn intake. An inadequate Zn nutriture might be the cause of ageing associated decline in immune function. This study was performed to evaluate whether Zn supplementation could improve the immune response in elderly Italian subjects (70-85 y) in relation to gender and Zn status. The subjects were supplemented for six months with Zn (15mg/day or 30 mg/day) or with placebo using a placebo-controlled, double-blinded design. Lymphocytes, isolated from peripheral whole blood, were cultured in medium containing autologous serum and were unstimulated or stimulated with PHA. Proliferative capacity, measured by 3H-thymidine incorporation and reported as stimulation index (SI: cpm stimulated cells/unstimulated cells), and cytokine production, measured by ELISA, were analysed before and after the supplementation with Zn or placebo. Any significant difference between males and females was found at M0 and at M6. However, at M6 the lower dose of Zn appeared more effective than the higher one, since the proliferative response of females differed significantly from that of males after 15mg of Zn supplementation. No significant difference of men and women cytokine secretion between M0 and M6 with all doses of Zn supplementation was found. The only exception was a small decrease of IL-8 secretion in males after 15 mg of Zn. At M0 a negative correlation between SI and IL-1b or IL-10 was found. IL-10 appeared also negatively correlated with erythrocyte Zn level in PHA-stimulated lymphocytes in males and with serum Zn unstimulated and PHA-stimulated lymphocytes in females. At M6 a negative correlation was observed between SI and TNF-a of PHA-stimulated lymphocytes of male supplemented with both the two doses of Zn, and between SI and TNF-a of unstimulated lymphocytes of males after the lower dose of Zn. In males, the TNF-a secreted by PHA-stimulated lymphocytes was negatively associated with Zn intake. In females, the IL-1b and TNF-a of unstimulated lymphocytes were negatively associated with red blood Zn. Moreover, a negative association between TNF-a of stimulated and IL-10 of unstimulated cells with serum Zn was found.

Animal and human studies have shown that zinc (Zn) deficiency is associated with decreases in circulating thyroid hormone levels, in the ratio T3/T4 and in Basal Metabolic Rate (BMR). It is postulated that iodothyronine deiodinase expression is Zn sensitive and that the production of T3 is therefore reduced in Zn deficiency. No recent studies have addressed or confirmed this hypothesis in human subjects. The objectives of this work were to investigate whether Zn supplementation might affect thyroid hormone levels and consequently affect the BMR. A sub-sample of 70 middle-aged (aged 55-70y) volunteers (35 men and 35 women recruited in Clermont-Ferrand, France) and 108 older (aged 70-85y) volunteers (56 men and 52 women recruited in Rome, Italy) was selected for BMR measurement and body composition; thyroid hormone levels were measured on all volunteers (n=387) participating in the survey. Volunteers were assigned to receive placebo (0mg) or 15mg or 30mg of Zn per day for six months. At the beginning and at the end of the supplementation period, serum Zn levels, BMR, body composition and thyroid hormone levels were determined. At baseline Italian older volunteers had a significantly lower FFM than middle-aged French volunteers (-7% P<0.01). A negative correlation between BMR and age (men, r-0.64; women, r-0.62; both P<0.0001) was observed: BMR was significantly (P<0.00001) lower in Italian elderly volunteers (4.03±0.46kJ/min and 3.29±0.42kJ/min for men and women, respectively) than in middle-aged French volunteers (4.84±0.45kJ/min and 3.87±0.38kJ/min for men and women respectively), even after adjustment for FFM (-12%). No correlation has been observed between BMR and thyroid hormones both in French and Italian subjects. Total T4 (TT4) concentrations were lowest in middle-aged population (-10%; P<0.0001). A moderate negative correlation has been found with TT4 and red blood cell Zn (r=-0.12, P<0.02; slope -0.026). However, after three and six months of supplementation there was no significant effect of Zn on serum concentrations of thyroid hormones. The results of this study confirm the age related decline in BMR, which cannot entirely be explained by body composition or thyroid hormones differences. This study also shows that older individuals have a moderately higher serum concentration of total T4, suggesting an age-related impairment in the normal mechanisms that regulates energy expenditure. Although a possible role of Zn was postulated at baseline no effect was found after six months of Zn supplementation.

A reduction of muscular performance with advancing age has been demonstrated in several studied. Zinc (Zn) has been reported to improve the muscular strength, effect due to the participation of Zn in the formation of several enzymes of energy metabolism such as carbon anhydrase and lactate dehydrogenase in intermediary metabolism during exercise. Moreover Zn facilitates the trasduction of food energy in to energy for work and enhances physical performance. However little is known about the relationship between muscle strength and Zn status. The aims of this part of the ZENITH study were to explore the influence of the Zn supplementation on muscle strength and to evaluate associations between changes in muscle strength, physical performance and spontaneous physical activity in an Italian older population. Hundred eight apparently healthy volunteers 56 men and 52 women, aged 70-85 years were enrolled in Italy. Volunteers were assigned to receive placebo (0mg) or 15mg or 30mg of Zn. At the beginning, after three and six months of the supplementation grip strength (HG), knee extension, anthropometry, body composition, performance of the lower extremities and physical activity were evaluated. The variables studied at baseline were not significantly different between the supplemented and un-supplemented volunteers. Significant differences between sexes were observed in all parameters (P<0.0001). No differences between sex were observed in mean physical activity level: most of subjects (88% of men and 65% of women) had a sedentary lifestyle. HGmax was significantly correlated with body weight (r=0.61, p<0.0001), and AMA (r=0.52, p<0.0001), the higher correlation was found with FFM (r =0.73, p<0.0001) and Forearm Muscle Area (FMA: r =0.71, p<0.0001). Moreover improved strength has been associated with improved skeletal muscle mass (r = 0.79, p<0.0001), bone mass (BMC: r= 0.64 P<0.0001; BMD r= 0.48 P<0.0001), performance score (r=0.31 P<0.001) but not with physical activity level. When association with indices of Zn nutritive status was considered, only a moderate positive correlation between muscle strength (as absolute value) and Zn intake (r=0.19, p<0.04) was observed. After six months of Zn supplementation no significant differences were observed in body composition parameters and muscle strength.

The objective of this study was to evaluate of some immune markers in Italian elderly population in relation to Zn status, gender and antioxidant defence. An observational study in Italian apparently healthy, free-living subjects, 56 men and 52 women, aged 70-85 years, enrolled in Italy. Lymphocytes were unstimulated or stimulated with the mitogen phytohemoagglutinin (PHA). The proliferative capacity was measured as incorporation of [3H]-thymidine and reported as stimulation index (SI). Cytokine secretion by lymphocytes was determined by ELISA. The antioxidant enzyme activities were measured using commercial kits. Dietary Zn intake, as well, Zn in serum , red blood and urine were on the normal range of values and did not show any difference between men and women. The proliferative response showed a high variability without significant differences between men and women. The amount of secreted pro- and anti-inflammatory cytokines was similar in men and women. No differences were found in the activity of antioxidant enzymes in lymphocytes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT), between men and women. An association between SI and serum Zn level in men was found. SI resulted negatively correlated with IL-1b (R2 = 0.036 and P = 0.012) and IL-10 (R2 = 0.34 and P = 0.040) only in men. IL-10 of PHA-stimulated lymphocytes was negatively correlated with red blood Zn in men (R2 = 0.41 and P = 0.008), while IL-10 of unstimulated and PHA-stimulated lymphocytes was negatively correlated with serum Zn in women (R2 = 0.38 and P = 0.020; R2 = 0.31 and P = 0.040 respectively). No correlation was observed between immune markers and antioxidant enzyme activities. Only weak differences on immune response between men and women were observed. However, Zn status appears to have more influence on the ability of lymphocytes to proliferate in men than in women.

The effects of zinc (Zn) supplementation on mood level and variability were assessed in this study. Positive and negative affect was measured for 4-7 days at three time points of this intervention study. Moods were measured at baseline and again at three and six month intervals. Participants were from four European centres, with approximately half of the sample aged between 55 and 70 and the remainder 70-87 (total n=387). The sample was randomly allocated to three groups, one received no Zn supplement, one group received 15mg/day, and the third received 30mg/day. Repeated measures ANOVAs were computed to determine the effects of Zn supplementation on the moods experienced. No major changes in moods occurred in response to supplementing diet with Zn. This is interpreted to suggest that whilst moods were not improved with the supplement, nor did supplementation produce any deleterious effects during the study.

The objective of this study was to investigate the relationship between indices of Zn nutritive status and biochemical markers of bone turnover in older adult European subjects. The baseline data from a multi-centre prospective Zn intervention (ZENITH) study was used from France, Italy and Northern Ireland. In total 387 healthy adults, aged 55-87 y participated in this study. Zn intake was assessed by 4-d recall records. Circulating and urinary biochemical Zn status measures were assessed by atomic absorption spectrophometry. Serum bone-specific alkaline phosphatase and osteocalcin were assessed by ELISA and urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) by HPLC. Zn intake was positively correlated with serum (r=0.129; P<0.05) and urinary (r=0.143; P<0.05) Zn, but not with erythrocyte Zn. Serum Zn was positively correlated with urinary Zn (r=0.200; P<0.0001). Zn intake was negatively correlated with urinary Pyr and Dpyr (r=-0.298 and -0.304, respectively; P<0.0001), but was not correlated with bone formation markers. There was a tendency for serum Zn to be negatively correlated with urinary Dpyr (r=-0.211; P=0.080). Erythrocyte Zn was negatively correlated with serum osteocalcin (r=-0.090; P<0.0001). None of the other correlations were significant. After adjustment for confounder (age, gender and research centre) the only significant association, which remained was between serum osteocalcin and erythrocyte Zn (b=-0.124; P=0.011). There was some, albeit inconsistent, evidence of a relationship between Zn nutritive status and bone turnover in the older adults participants of the ZENITH study.

The objective of this study was to determine Zn status and age-related changes in immune function of healthy late-middle-aged men and women (aged 55-70y). Observational study was performed in Northern Ireland apparently healthy, free-living individuals (45 men, 48 women) aged 55 -70y. Zn status markers were analysed by flame atomic absorption spectrometry and commercially available kits. Immune function was assessed by flow cytometry. Serum and erythrocyte Zn concentrations were 13.0 (SD 1.40)µmol/l and 222 (SD 48.2)µmol/l, respectively. Serum alkaline phosphatase (ALP) concentrations were 76.8 (16.1 SD) U/l; women showed significantly higher concentrations of ALP (P=0.011). Women demonstrated: a significant inverse correlation in naive T-lymphocytes, specifically naive T-helper lymphocytes (% expression, r = -0.364 P=0.007 & absolute count, r = -0.275 P = 0.036) with age; and significant positive correlation between late activation of T-lymphocytes (% expression, r = 0.299 P = 0.019 & absolute count, r = 0.260 P=0.039) with advancing age. Men demonstrated a significant positive correlation in the % expression of (CD3-/CD16+/CD56+) natural killer (NK) cells with age (r = 0.316 P=0.017). Between the ages of 55-70 years, healthy individuals experience significant alterations in immune function; however, such changes appear largely sex-specific. Given the reported importance of adequate Zn status in maintaining optimal immune function, further studies are required to explore the effect of enhanced Zn status on emerging immune deficiencies in cell-mediated immunity in healthy 55-70y olds.

Zinc (Zn) supplementation may be beneficial for health. Assessing the exchangeable Zn pools may be a useful approach for evaluating Zn status. We undertook this study to evaluate the long-term supplementation effects of two moderate doses of Zn on the mass of the exchangeable Zn pools. Design: three groups of healthy late middle-aged male subjects (n = 16/group) participated in a stable isotope Zn kinetic study following 6 months of daily supplementation with placebo (0mg) or 15mg or 30mg of supplemental Zn. At the end of the supplementation period, each subject received an intravenous injection of 1mg of 70Zn, and the plasma Zn disappearance curve was monitored for the next 10d. Two approaches have been applied to determine the characteristics of exchangeable Zn pools: 1) formal tri-compartmental modelling, and 2) a simplified determination of the total mass of the rapidly exchangeable Zn pool (EZP). The exchangeable Zn pool masses for the three considered pools were as follows: 2.15, 12.7 and 100.5mg Zn. Rapidly exchangeable Zn pool mass was 143mg Zn. Zn supplementation significantly increased exchangeable Zn pool masses regardless of the approach employed to determine these pools. In addition, these data confirmed that Zn exchangeable pool masses correlate positively with total Zn intake and negatively with subject age, but do not correlate with plasma Zn. Our data demonstrated that a long-term supplementation with two moderate doses of Zn is efficient to increase exchangeable Zn pool masses in late middle-aged subjects.

Zinc (Zn) is essential for a great number of biochemical activities and biological functions. Long-term marginal intakes of Zn and a decreased absorptive efficiency could severely compromise Zn status in older individuals. Zinc plays an important role in the antioxidant defence and Zn deficiency has been associated with increased reactive oxygen-induced damage in various tissues and with alteration in antioxidant enzymes. The aim of this work was to explore the effect of long-term supplementation with two moderate dose of Zn (15mg/day or 30mg/day) on oxidative stress parameters and on cellular stress and oxidative markers in 108 healthy elderly (70-85yrs) recruited in Rome. Plasma carotenoids and lymphocytes a-tocopherol, B-carotene and coenzyme Q10 (coQ10) were determined by high-performance liquid chromatography. Lymphocytes were isolated from whole blood using ficoll gradient. Nitric Oxide (NO) assay were performed spectrophotometrically. The measurement of the absorbance due this azo-chromophore accurately determines NO2- concentration. For the determination of SOD, GPx and catalase (CAT) activity in lymphocytes and to test the erythrocytes levels of GSH/RSH and MDA were used spectrophotometric kits provided by Oxis (Oxis International, inc. Portland, USA). The percentage of haemolysis in erythrocytes was determined spettrophotometrically at 540nm. The methemoglobin (Methb), an oxidant product pf haemoglobin, was tested using a Kit by Pokler Italia. The dietary intakes of micronutrients (carotenoids, retinol, vitamin E) and minerals (Zn, copper and iron) were statistically similar before and after Zn supplementation for both sexes and no significant changes in fruits and vegetables consumption were noted during the entire period of study. Zn supplementation, after the 6-mo period, had no significant effects on all the measured parameters either in both genders considered separately or in a gender combined analysis. All the results were in a range of normality. The results of this study provide further information regarding the age-related oxidative stress in free-living healthy elderly in Rome, and on the effects of nutritional Zn supplementation on the red-ox status. Our data showed that long-term supplementation with two moderate doses of Zn had no significant effects on the markers of oxidative stress measured. In conclusion, it appears that, differently from unhealthy populations, this kind of supplementation is an inefficient way to increase antioxidant defence in a healthy population.

A randomised double-blind placebo-controlled design was employed to investigate the effects of zinc (Zn) supplementation on cognitive function in 387 healthy adults aged 55-87 years. Several measures of visual memory, working memory, attention and processing speed were obtained using the Cambridge Automated Neuropsychological Test Battery (CANTAB) at baseline and then after 3 and 6 months of 0 (placebo), 15 or 30mg of Zn per day. Younger adults (<70 years) performed significantly better on all tests than older adults (>70 years), and performance improved with practice on some measures. However, there was no clear evidence of interactions indicating any systematic effects of Zn supplementation for either dose in comparison with placebo and this was the case for both younger and older adults. It is concluded that, at least in this large sample of healthy older adults, Zn supplementation is neither beneficial nor detrimental to cognitive function.

Effect of zinc supplementation on biochemical markers of bone turnover in older European adults

The objective of this study was to report selected dietary intake and vitamin status at baseline of volunteers participating in the ZENITH study and the correlation of vitamin status with Zn. A multi-centre prospective intervention study employing a randomised double-blind design was performed in Clermont-Ferrand, Theix (France), Coleraine (Northern Ireland), Grenoble (France) and Rome (Italy). 387 healthy middle-aged (55-70y) and older (70-87y) men and women participated in this study. Dietary intake was assessed by means of a validated 4-d recall record. Fasting blood samples were simultaneously analysed for retinol and a-tocopherol by HLPC method. Erthrocyte folates were measured by a competitive immunoassay with direct chemiluminescence detection on an automatised immunoanalyzer. In all centres, men had a significantly (P<0.0001) higher mean nutrient intake than women. Comparison between age groups showed that older individuals had significantly lower intakes of macro- and selected micronutrients than middle-aged subjects (P<0.0001). A high fat intake (from 36% to 40% of total energy) was observed in all examined groups. In relation to biochemical measures of vitamin status, all parameters were above their respective cut-off values for normality and thus, none of the subjects had biochemical evidence of deficiency of these selected vitamins. A moderate correlation has been found with plasma vitamin A and serum Zn (r=0.12, P<0.05) or red blood cell Zn (r=0.12, P<0.01) and with erythrocyte folates and red blood cell Zn (r=0.11, P<0.05). There were only moderate differences in the nutrient intake of the ZENITH study volunteers among the four European centres. Their biochemical status for retinol, a-tocopherol and folate appeared adequate.

Epidemiological studies have demonstrated that elderly sectors of population have higher rates of nutritional deficiency, in particular marginal zinc (Zn) deficiency and/or low levels of vitamins; this deficiency can contribute to various chronic and degenerative diseases associated with aging. The overall objective of this study was to investigate the effect of Zn supplementation on vitamin status in the middle-aged and older European volunteers. Dietary intake was assessed by means of a validated 4-d recall record. Fasting blood samples were simultaneously analysed for retinol and a-tocopherol by HLPC method. Erythrocyte folates were measured by a competitive immunoassay with direct chemiluminescence detection on an automatised immunoanalyzer. Results show that there are moderate differences in the vitamin intake and nutritional status for both middle-aged and old-aged volunteers and evidence of inadequate dietary intakes is generally lacking. Moreover, the biochemical indicators for the vitamins suggest that the circulating levels are in the cut-off point of normality and that any deficiency is observed. Vitamin A levels are significantly increased proportionally with Zn dose (for 30mg Zn/day p<0.05; for 15mg Zn/day p <0.0001), and the effect of Zn is more important after 6 months than 3 months of supplementation; no significant changes are observed in the placebo group. This effect is not noticed for vitamin E/cholesterol and erytrocyte folates. In conclusion, it is necessary to underline the importance of the dietary adequacy for macro and micronutrients and in presence of micronutrient deficiency, supplementation is strongly recommended to improve health status in elderly. Particularly, any deficiency was observed for the volunteers regarding vitamin status. Zn supplementation influences significantly vitamin A plasma levels, confirming the role of Zn on vitamin A metabolism.

Adjustments in intestinal absorption and losses of zinc (Zn) are thought to maintain Zn homeostasis when dietary intakes levels are altered. Zn status may also influence efficiency of intestinal Zn absorption. The objectives of this work were to determine the impact of dietary intake and status of some micronutrients on Zn absorption in late middle-aged men. Dietary intake and status of Zn, Cu, Fe, vitamin A, C and fibre, and absorption of Zn were measured in 48 men, aged 58-68yr, confined to a metabolic unit and consuming a typical French diet. Dietary intake was estimated using 4-d food-intake records (including the weekend) and the GENI program. To assess Zn status, plasma, erythrocyte, urine Zn levels and plasma alkaline phosphatase activity were determined. Zn absorption was determined using the isotope double labelling method. Zn stable isotopic ratios were measured in plasma samples collected before and 48 hours after isotope administration using ICP/MS. Zn intake within the group of men varied from 5.7 to 20.5mg/day and averaged 12.9mg/day. Plasma Zn level varied from 10 to 18µmol/l and averaged 12.9µmol/l. Zn absorption varied from 12 to 46% and averaged 29.7%. Zn absorption was not significantly (p>0.05) correlated with Zn intake or with any of the Zn status parameters. Zn absorption was only slightly negatively correlated with plasma and erythrocyte Zn levels and with serum Fe and ferritin levels in this study. In conclusion, although dietary intake was low, Zn absorption was satisfactory and led to an adequate Zn status in this population.

Age-related decline in taste acuity may be both a cause and an effect of depleted Zn and/or increased Zn requirement. The aim of this study has been to explore associations between Zn status and taste acuity in healthy older European adults aged 55-90. Volunteers were recruited within Italy (n=108 aged 70-90 years), the United Kingdom (UK) (n=93 aged 55-70) and two regions of France (n=186), Grenoble (aged 70-90 years) and Clermont-Ferrand (aged 55-70). A Signal Detection Theory (SDT) approach was adopted, employing a three-alternative, forced-choice procedure. The data were converted to R-indices and bivariate correlations computed to explore relationships between serum Zn, erythrocyte Zn and taste acuity. ANOVA was undertaken to determine regional differences in Zn status. Higher erythrocyte Zn status was associated with better acuity for salt (sodium chloride) taste in the sample as a whole (P=0.012) (n=385). Higher serum Zn levels were associated with greater sensitivity to sour (citric acid) (P=0.015) only in the older groups (aged 70-90). There were no apparent associations between serum or erythrocyte Zn status and acuity for bitter (quinine) or sweet (sucrose) tastes irrespective of age. These results agree with those previously suggesting that age-related detriment in sensitivity for salt taste may be associated with depleted Zn.

Baseline data are reported from a study of the effects of Zn supplementation on cognitive function in older adults as assessed by the CANTAB computerised test battery. This is a multi-centre prospective intervention study employing a randomised double blind design. There are 387 healthy adults aged 55-87 years from centres in France, Italy and Northern Ireland. Measures of visual memory, working memory, and attention were obtained at baseline (prior to supplementation Younger adults (<70 years) performed significantly better than older adults (>70 years) on all tests, with minimal differences between centres. In addition, men outperformed women on tests of spatial span, pattern recognition memory, and reaction times, although these gender differences varied somewhat between centres. The results are generally consistent with previous age- and gender-related effects on cognitive functioning.

Oxidative stress has been reported to increase with aging in relation with an increased production of free radicals by the mitochondria and/or a decreased level of antioxidant defences. In aging, uncontrolled oxidative stress results in an increased risk of oxidative pathologies such as CVD, dementia and diabetes. Zinc (Zn), as biological antioxidant, could act in preventing increased oxidative stress in Elderly. This study is aiming to investigate the effects on health of a Zn supplementation in free-living subjects in late middle-aged (55-70yrs) and older aged (70-85yrs). In the present work, we measured the effect of a Zn supplementation on oxidative stress parameters monitored by plasma SH groups, TBAR's and blood total glutathione. Zinc status was measured in plasma, urines and erythrocytes. Subjects received 15mg/d or 30mg/d Zn as gluconate or a placebo form for 6 months. Measurements were carried out at the entry (T0), and after 3 (T3) and 6 months (T6). At the entry, only 5.6% of the older subjects and 4.8% of middle aged exhibited a biological Zn deficiency (plasma Zn < 10.7µmol/L). At baseline, when we compared oxidative status between men and women, significant differences were observed, TBAR's levels were higher and GSHt levels lower in women. But no antioxidant beneficial effects of Zn supplementation were observed after 3 or 6 months. In Zn deficient subjects, Zn status was restored but no significant antioxidant effect of Zn supplementation was observed. It seems that oxidative status was higher in women compared to men. Our data point out the limits of a single antioxidant supplementation in older to counteract oxidative stress. Other beneficial effects of Zn supplementation (immunity, cognitive functions, osteoporosis) can be expected but regarding oxidative stresses a single Zn supplementation failed to show beneficial effects.

Oxidative stress has been reported to increase with ageing. However, the data in healthy humans remain controversial and studies in free-living elderly people are scarce. The objective of the present study was to compare age-related oxidative stress in late middle-aged and older free-living subjects. The effect of ageing on oxidative stress and antioxidant parameters was investigated in 188 middle-aged subjects from Clermont-Ferrand (France) and Coleraine (UK), and in 199 older subjects from Grenoble (France) and Roma (Italy). Plasma thiol (SH) groups, define definition (TBAR's) and total glutathione (GSH), define definition (FRAP) and superoxide dismutase (SOD) activity were measured at baseline of the ZENITH study. Plasma SH groups and FRAP and, surprisingly, TBAR's were significantly lower in free-living older subjects compared to younger subjects (p<0.001, p<0.001, p<0.01, respectively), but there was no significant differences in GSH levels. European free-living healthy older do not appear to be exposed to an acute oxidative stress. However, the highly significant positive correlation between plasma SH group oxidation or decreased FRAP and ageing is predictive of an increased risk of oxidative stress in older subjects. Moreover, the comparison between middle-aged and older subjects regarding oxidative stress parameters suggests also a progressive and slow decline of antioxidant status in healthy free-living older elderly and underline the impact on life-style factors on successful ageing.

Zn has been shown to possess antioxidant properties in vitro and in vivo. However, little is known about the antioxidant effects of Zn supplementation in late middle-aged and elderly subjects. 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 this study to evaluate the long-term supplementation effects of two moderate doses of Zn on in vitro Cu-induced LDL oxidation in both men and women. Three groups of 16 healthy late middle-aged subjects from each sex participated in the study. Each group received, for six months either 0mg/d, 15mg/d or 30mg/d of supplemental Zn. At the beginning and at the end of the supplementation period, dietary intakes of Zn, Cu, Fe and vitamin E were estimated using 4-d food-intake records (including the weekend) and the GENI program as well as their status. In vitro LDL oxidizability (conjugated diene content on extraction, and rate of diene formation and lag time on application of oxidant stress) and lipid parameters were also determined at the beginning and at the end of the supplementation period. Dietary intakes of Zn, Cu, Fe and vitamin E were overall satisfactory. Zn supplementation significantly increased serum Zn levels but did not modify significantly Cu, Fe or vitamin E status. However, Zn supplementation had no effect on in vitro LDL oxidation parameters not were there any sex-related differences in vitro LDL oxidizability. This study showed that long-term Zn supplementation in late middle-aged subjects had no effect on in vitro Cu-induced LDL oxidation under the study conditions.

Immune status was determined in a representative sample of healthy late-middle aged individuals (5570 years), by measuring leukocyte and lymphocyte subpopulations in whole-blood samples. Venepuncture was undertaken in 93 individuals that met a defined inclusion criteria, including health and lifestyle and psychosocial questionnaires, and blood screening for determinants of healthy ageing. There were significant age effects (P<0.1) on eosinophils, monocyte phagocytic activity, and CD3/HLA-DR late-activated T-lymphocytes. There was a significant (P<0.1) age x sex interaction in the absolute counts (x109/l) of CD3CD8 total T-cytotoxic lymphocytes, the CD4 T-helper to CD8 T-cytotoxic lymphocytes ratio, the CD4/CD45RA naive T-helper to CD4/CD45RO memory T-helper lymphocytes ratio, and the % expression of IL-1b by activated monocytes. In conclusion, the results show that a number of alterations in immune function occur between the ages of 5570 years, and that these are largely sex specific. The study provides reference values for the lymphocyte measures, which have previously been unreported for healthy men and post-menopausal women in this age group.

This report describes baseline data on basal metabolic rate (BMR), thyroid hormone levels and body composition of middle aged and older people participating in the ZENITH project and the correlation of thyroid hormone levels with Zn status. A multi-centre prospective intervention study employing a randomised double blind design was performed in Clermont-Ferrand, Theix (France), Coleraine (Northern Ireland), Grenoble (France) and Rome (Italy). BMR has been measured on a sub-sample of 70 middle-aged volunteers (35 men and 35 women recruited in Clermont-Ferrand, France, aged 55-70 y) and 108 older volunteers (56 men and 52 women recruited in Rome, Italy, aged 70-85 y). Thyroid hormone levels were evaluated in the entire group of ZENITH volunteers (n 387). BMR was measured by indirect calorimetry. Fat free mass (FFM) was derived by four skinfold thickness using Durnin and Womersley's equations. Concentrations of thyroid hormones (total T3 and T4) were measured using a competitive immunoassay with an enhanced chemiluminescence endpoint. Italian older volunteers had a significantly lower FFM than middle-aged French volunteers (-7% P<0.01). A negative correlation between BMR and age (men, r-0.64; women, r-0.62; both P<0.0001) was observed: BMR was significantly (P<0.000001) lower in Italian elderly volunteers (4.03±0.46kJ/min and 3.29±0.42kJ/min for men and women, respectively) than in middle-aged French volunteers (4.84±0.45kJ/min and 3.87±0.38kJ/min for men and women respectively), even after adjustment for FFM (-12%). No correlation has been observed between BMR and thyroid hormones both in French and Italian subjects. Total T4 (TT4) concentrations were lowest in middle-aged population (-10%; P<0.0001). A moderate negative correlation has been found with TT4 and red blood cell Zn (r=-0.12, P<0.02; slope -0.026). The results confirm an age-related decline in BMR not entirely explained by body composition or thyroid hormones differences.

Inadequate intakes of micronutrients in elderly negatively affect the nutritional status. Zn is an essential micronutrient in the elderly, especially in relation to its impact on immune function, bone mass, cognitive function and oxidative stress. However, data are lacking on Zn intake and status during normal aging. In this study, we evaluate the intake and status of Zn in late middle-aged and older free-living subjects. Dietary Zn intake and Zn status in 188 middle-aged subjects from Clermont-Ferrand (Fr) and Coleraine (UK), and in 199 older subjects from Grenoble (Fr) and Roma (It) were assessed at the entry in the ZENITH study. In relation to the Zn RDA for people older than 55 yr, Zn intakes in most of the middle-aged and older subjects (more than 96%) in the present study were adequate. Older people had significantly lower (P<0.01) energy intakes as compared to middle-aged. Zn intake expressed per MJ was also significantly (P<0.01) higher in older people compared to middle-aged. Erythrocyte and urinary Zn concentrations were significantly (P<0.001) higher in middle-aged subjects compared to older ones. The prevalence of biological Zn deficiency in free-living aging European people was low (<5%). The results of the present study showed a relatively low prevalence of Zn deficiencies in healthy free-living late middle age and older subjects. These results should be useful for health professionals to have reference data on Zn intake and status for a healthy aging.

Older individuals (>55 years) are at risk of developing age-associated immune deficiencies that may be exacerbated by inadequate Zinc (Zn) status. Maintenance of optimal Zn status with advancing age may mitigate against the effect of immunosenescence and allow for successful ageing. The current study aimed to explore the associations between Zn status and marker of immunity and determine if 15mg or 30mg of Zn (as Zn gluconate) per day for six months affected the immune function of 93 individuals (45 men & 48 women) aged 55-70 years. Zn status was assessed by dietary intakes, and putative biochemical indices of Zn. Multiple flow cytometric methods were used to assess immune function. At baseline mean ± SD, serum and erythrocyte Zn concentrations, and dietary Zn intake were 13.0 (±1.4)µM/l and 22.2 (±4.8)µM/l, 9.28 (± 3.28)mg/d, respectively. Serum and erythrocyte Zn concentrations were associated with increased numbers of lymphocyte subpopulations and T-lymphocyte activation. Treatment effect was determined using repeated-measures ANOVA. A significant time x treatment interaction was observed for monocyte count (P = 0.030), total naive T-lymphocytes (% expression P = 0.036), and B-lymphocytes absolute count P = 0.028). B-lymphocytes were significantly lower in individuals receiving 30mg Zn/ d compared to 15 mg Zn/d and control groups, month 3 only. In conclusion, these findings indicate that Zn intakes of up to 40mg Zn/d do not appear to affect immune function in apparently healthy 55-70 year olds.

Mood quality has important implications for both physical and mental wellbeing. Poor quality moods are associated with deficits in the diverse areas of cognitive function, health, and social relationships. The ageing process presents a number of potential challenges to successful mood regulation that could have wider implications. The objective of the present study was to assess the quality of positive and negative affect (mood) in an ageing European sample. The current study examines the quality of positive and negative affect in 387 healthy participants from three European countries. Moods were measured four times a day for 4-7 d with the Positive and Negative Affect Schedule (PANAS) mood scales. Measures of Zn status were taken also. Two centres concentrated on 55-70 yr olds (Coleraine, N.Ireland, n = 93 and Clermont-Ferrand, France, n = 95), and two centres concentrated on 70-87 yr olds (Rome, Italy, n = 108, and Grenoble, France, n = 91) participated in this study. Positive affect scores for the centre in Rome were significantly (P < 0.01) lower than for the other three centres, and the Grenoble centre had significantly (P < 0.05) higher scores on negative affect than the other three centres. Mood was not related to measures of Zn status (all Ps > 0.05). The two centres with the oldest participants showed deficits in mood quality that may have implications for broader well-being.

The objective of this study was to report the rational, design, recruitment, baseline characteristics and preliminary overview of volunteers in the ZENITH study. A multi-centre prospective intervention study employing a randomised double-blind design was performed in Clermont-Ferrand, Theix (France), Coleraine (Northern Ireland), Grenoble (France) and Rome (Italy). Healthy men and women middle-aged (55-70 years) and older volunteers (70-87 years) participated in this study. At baseline (prior to Zn supplementation), all volunteers underwent a full clinical examination, anthropometric measurements, health and lifestyle questionnaire, Mini Mental State Examination, Geriatric Depression Scale, biochemistry profile. In total 842 volunteers (378 men and 464 women) were invited to take part in the study. 49% of these volunteers were excluded on the basis of inclusion/exclusion criteria. 433 participants were admitted to the Zn supplementation for six months. During this period about 10% of volunteers dropped out from the study. A total of 387 subjects (197 males and 190 females) successfully completed the supplementation phase of the ZENITH study.

Taste acuity declines with age and may be dependent upon zinc (Zn) status. The aim of this double-blind, randomised controlled intervention trial has been to determine taste acuity in response to Zn (15 or 30mgs per day). Healthy older European adults aged 55-87 years were recruited to the European Commission funded Zenith project within Italy (n = 108, 70-87 years), the United Kingdom (UK) (n = 93, 55-70 years) and two regions of France, Grenoble (n = 91, 70-87 years) and Clermont-Ferrand (n=95, 55-70 years). A Signal Detection Theory (SDT) approach was adopted for taste threshold assessment. The data were converted to R-indices and analysed by repeated measures ANOVA controlling for baseline Zn status. Serum Zn status improved post-intervention in all four samples. Sweet taste acuity improved in response to Zn 30mgs in the group recruited in Rome (aged 70-87 years). Salt taste acuity improved in response to Zn 30mgs in those (aged 70-87 years) sampled in Grenoble. In younger individuals (aged 55-70 years) recruited in Clermont Ferrand, sweet taste acuity appeared to decline in response to Zn (30mgs). Supplemented Zn had no affect upon taste acuity in those individuals (aged 55-70 years) recruited in Northern Ireland. There appear to be regional differences in taste response to Zn, which appear independent of differences in baseline Zn status. Further research is required to determine the degree to which these differences are dietary related.

Zinc (Zn) deficiency alters protein metabolism. Inadequate Zn intake has been observed in elderly, whose protein turnover is deregulated. Zinc supplementation could have an effect on protein metabolism in elderly. We determined whether moderate Zn supplementation modifies whole-body protein turnover and albumin and fibrinogen synthesis rates in late-middle-aged men. Three groups of 16 healthy late-middle-aged men received for 6 mo either 0mg.d-1, 15mg.d-1or 30mg.d-1 of supplemental Zn. At the end of the supplementation period, each subject received an intravenous infusion of L-[1-13C] leucine to quantify whole-body leucine fluxes and synthesis rates of albumin and fibrinogen. In the placebo group, whole-body leucine fluxes to protein synthesis, to oxidation and from protein degradation were 1.46, 0.40 and 1.73µmol.kg.-1min-1, respectively. Zinc supplementation did not change significantly whole-body leucine fluxes. In the placebo group, plasma concentration and fractional rate of protein synthesis were 45g.L-1 and 8.2%.d-1 for albumin and 3.6g.L-1 and 16.7%.d-1 for fibrinogen, respectively. Zinc supplementation did not change significantly this parameter neither absolute rates of synthesis of these proteins. Zinc supplementation did not modify whole-body leucine fluxes neither rates of synthesis of albumin and fibrinogen. It is likely that dietary supply of Zn is sufficient for sustaining whole-body protein metabolism and acute phase protein synthesis rates in the studied population.

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