Assessing the Relationship between Vitamin D Status and Impairments in Cognitive and Physical Performance in Older Adults Using a Dual Task Physical Performance Test.

BACKGROUND: Vitamin D deficiency has been associated with an increased risk of falls in older adults. Several studies have demonstrated an association between vitamin D deficiency and gait and cognitive impairments, which are two risk factors for falls in the elderly. There is lack of research about the role of vitamin D in cognitive function in the context of mobility. OBJECTIVE: The purpose of this study was to evaluate the association between vitamin D status with the age-related changes in mobility through higher order cognitive function using a dual task physical performance test. DESIGN: Cross-sectional. SETTING: Community-dwelling older adult population located in Miami, Fl. PARTICIPANTS: Healthy participants over the age of 55 (n=97) who participated in the parent interventional study. MEASUREMENTS: Participants completed assessments that included serum levels of vitamin D, surveys, and dual task physical performance tests. Spearman's correlations, independent t-tests, repeated measures ANOVAs and multiple logistic regressions were used to examine the relationship between vitamin D insufficiency (25-hydroxyvitamin D <30 ng/ml) and sufficiency (≥30 ng/ml) and dual task physical performance variables. The significance level was set at α=0.05. RESULTS: There were no significant associations between vitamin D insufficiency and gait velocity during either task. Using Spearman correlations, slower single (P=0.011) and dual task counting rates (P=0.006) were significantly associated with vitamin D insufficiency. Independent t-tests showed dual and single task counting rates were significantly lower in the vitamin D insufficient group compared to the sufficient group (P=0.018 and P=0.028, respectively). The results for the ANOVAs indicated that velocities and counting rates were not significantly different by vitamin D status (Wilk's Lambda =0.999; F (1, 95) =.11, P=.740) (Wilk's Lambda =.999, F(1,95)=.13, P=.718). Vitamin D status was not significantly associated with dual task physical performance (defined as the difference in dual and single task) in gait velocity (OR=1.00, 95% CI: 0.98; 1.02, P=0.772) and counting rate (OR=1.684, 95% CI: 0.15; 19.57, P=0.677), when controlling for confounders. CONCLUSIONS: Since counting backward is a mental tracking task, which is a component of executive function, our results suggest a relationship between vitamin D insufficiency and executive dysfunction. Executive dysfunction has been previously associated with fall risks in the elderly, and it could be a possible mediator between vitamin D and falls. Our data suggest that cognition may play a significant role in vitamin D's influence on falls, while motor function may play a lesser role.

Role of zinc in the regulation of autophagy during ethanol exposure in human hepatoma cells.

Faulty autophagy has been linked to various diseases including neurodegenerative disorders, diabetes, and cancer. Increasing evidence support the notion that activation of autophagy protects against ethanol-induced steatosis and liver injury. Herein, we investigated the role of zinc in autophagy in human hepatoma cells VL-17A exposed or not to ethanol. LC3II/LC3I ratio, p62, and Beclin-1 expression and autophagosomes number were determined in cells incubated in medium containing various concentrations of zinc with or without ethanol. In addition, labile zinc and mRNA expression of metallothionein and the zinc transporters SLC39A8, SLC39A14, and SLC30A10 were evaluated in cells exposed to ethanol and the autophagy inhibitor 3-methyladenine. Zinc depletion caused a significant suppression of autophagy in cells. Conversely, zinc addition to medium stimulated autophagy in cells. Moreover, cotreatment with ethanol and excess zinc (40 µM) had an additive effect on the induction of autophagy. 3-methyadenine treatment decreased labile zinc, but this effect was more pronounced in cells exposed to ethanol. Lastly, ethanol and 3-methyladenine caused significant changes in the expression of metallothionein and zinc transporters. The results from this study support the hypothesis that zinc is critical for autophagy under basal conditions and during ethanol exposure.

Interactions among indicators of B1, B2, B6 and vitamin C status in university students.

In 209 young university students (109 males and 80 females) with body mass index within the normal range, the activation coefficient of the erythrocyte transketolase (ETKAC) glutathione reductase (EGRAC) and aspartate amino transferase (EASTAC) as well as the circulating levels of vitamin C were determined. Using the usual cutoff points for ETKAC and serum vitamin C and higher than usual cutoff points for EASTAC and EGRAC 99, 95, 92, and 87% of the study subjects exhibited activation coefficients which were compatible with an acceptable status for vitamin B2, B6, C and B1 respectively. A correlation analysis showed a high correlation (r = 0.81) between erythrocyte indicators of B1 and B2 status a lower correlation between indicators of the status of these vitamins and B6 and no correlation between the indicators of B1, B2, and B6 status and serum vitamin C. This study indicated that in this largely nutritionally adequate population, the activation coefficient of the erythrocyte enzymes used here as markers of the nutritional status of B1, B2, and B6 were related between themselves and varied in the same direction. These changes, however, were not associated with circulating levels of vitamin C.

Interactions among indicators of B1, B2, B6 and vitamin C status in university students

In 209 young university students (109 males and 80 females) with body mass index within the normal range, the activation coefficient of the erythrocyte transketolase (ETKAC) glutathione reductase (EGRAC) and aspartate amino transferase (EASTAC) as well as the circulating levels of vitamin C were determined. Using the usual cutoff points for ETKAC and serum vitamin C and higher than usual cutoff points for EASTAC and EGRAC 99, 95, 92, and 87 per cent of the study subjects exhibited activation coefficients which were compatible with an acceptable status for vitamin B2, B6, C and B1 respectively. A correlation analysis showed a high correlation (r = 0.81) between erythrocyte indicators of B1 and B2 status a lower correlation between indicators of the status of these vitamins and B6 and no correlation between the indicators of B1, B2, and B6 status and serum vitamin C. This study indicated that in this largely nutritionally adequate population, the activation coefficient of the erythrocyte enzymes used here as markers of the nutritional status of B1, B2, and B6 were related between themselves and varied in the same direction. These changes, however, were not associated with circulating levels of vitamin C.

Effects of intracellular zinc depletion on metallothionein and ZIP2 transporter expression and apoptosis.

Zinc is critical for the functional and structural integrity of cells. We have used the monocytic cell line THP-1 as a model in which to study both the responsiveness of metallothionein and ZIP2 transporter expression to zinc depletion induced by the intracellular zinc chelator TPEN [N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine] and the extent of concomitant apoptosis. Metallothionein expression increased proportionately with the addition of zinc to the medium and decreased with TPEN treatment. When treated with TPEN, both THP-1 cells and human peripheral blood mononuclear cells exhibited marked decreases in cellular zinc concentrations and increases in ZIP2 mRNA expression. These results suggest that cells attempt to homeostatically adjust to zinc depletion. When THP-1 cells were treated with >5 microM TPEN, cell viability decreased, and cells entered the early stages of apoptosis. These data show that metallothionein and ZIP2 expression are inversely related during zinc depletion and that apoptosis is concurrent with these changes.

Differential regulation of zinc transporter 1, 2, and 4 mRNA expression by dietary zinc in rats.

Zinc metabolism is well regulated over a wide range of dietary intakes to help maintain cellular zinc-dependent functions. Expression of transporter molecules, which influence zinc influx and efflux across the plasma and intracellular membranes, contributes to this regulation. We have examined in rats the comparative response of zinc transporters 1, 2, and 4 (ZnT-1, ZnT-2 and ZnT-4) to dietary zinc. ZnT-1 and ZnT-4 are expressed ubiquitously, whereas ZnT-2 is limited to small intestine, kidney, placenta and, in some cases, the liver. When zinc intake was low (<1 mg Zn/kg), ZnT-2 mRNA was extremely low in small intestine and kidney compared with an adequate intake (30 mg Zn/kg). ZnT-1 and ZnT-2 mRNAs were markedly greater in both tissues when a supplemental zinc intake (180 mg Zn/kg) was provided. ZnT-4 was refractory to changes in zinc intake. When zinc was provided as a single oral dose (70 mg/kg body), ZnT-1 and ZnT-2 mRNA levels were increased many fold in small intestine, liver and kidney, whereas ZnT-4 gene expression was not changed. The expression of ZnT-1 and ZnT-2 is comparable to zinc-induced changes in metallothionein mRNA levels, suggesting a similar mode of regulation for these genes. The relative differential in regulation by zinc is ZnT-2 > ZnT-1 > ZnT-4. These data provide evidence that, in an animal model, zinc transporter expression is responsive to zinc under physiologically relevant conditions.

In well-fed young rats, lactose-induced chronic diarrhea reduces the apparent absorption of vitamins A and E and affects preferentially vitamin E status.

To establish the effect of lactose-induced diarrhea on the apparent absorption and status of vitamins-A and E in well-fed young rats, we fed Sprague Dawley rats a balanced diet or a lactose diet (350 g/kg). A group of rats fed the control diet equal to the level measured in the lactose-fed rats (pair-fed) was also included. The experiment lasted 23 d and feces were collected on days 4-6, 10-12, 14-16 and 20-22. Samples of serum and tissues were taken on days 10 and 23. Lactose caused a significant reduction in food intake, had no effect on body weight and produced a diarrhea that persisted during the whole experiment. The severity of diarrhea decreased with time, indicating that the rats partially adapted to lactose feeding. At the onset of diarrhea, the apparent absorption of vitamins A and E in the rats with diarrhea was significantly lower than in the control or pair-fed rats, but the rats with diarrhea recovered gradually, and in the case of vitamin E was normalized by day 15. At day 10 the rats with lactose-induced diarrhea had serum and liver concentrations of vitamins A and E that did not differ from the control or pair-fed rats. However, at day 23 the lactose-fed rats with diarrhea had significantly lower serum and liver concentrations of vitamin E than the control or pair-fed rats. Measured at that time, diarrhea had no effect on liver vitamin A, but lower serum concentrations of this vitamin were detected in both the lactose-fed rats and in the pair-fed rats. In general, in well-nourished rats, the chronic diarrhea associated with excessive dietary lactose reduced the apparent absorption of vitamin A and E and particularly compromised the nutritional status of vitamin E.