Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstuffs and Cigarette Smoke

Cadmium is a cumulative nephrotoxicant that is absorbed into the body from dietary sources and cigarette smoking. The levels of Cd in organs such as liver and kidney cortex increase with age because of the lack of an active biochemical process for its elimination coupled with renal reabsorption. Recent research has provided evidence linking Cd-related kidney dysfunction and decreases in bone mineral density in nonoccupationally exposed populations who showed no signs of nutritional deficiency. This challenges the previous view that the concurrent kidney and bone damage seen in Japanese itai-itai disease patients was the result of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and calcium. Further, such Cd-linked bone and kidney toxicities were observed in people whose dietary Cd intakes were well within the provisional tolerable weekly intake (PTWI) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives of 1 mug/kg body weight/day or 70 mug/day. This evidence points to the much-needed revision of the current PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is accumulating and Cd effects on reproductive outcomes have begun to emerge.

Promoter-, cell-, and ligand-specific transactivation responses of the VDRB1 isoform

The vitamin D receptor (VDR) mediates the effects of 1,25(OH)(2)D-3, the active form of vitamin D. The human VDRB1 isoform differs from the originally described VDR by an N-terminal extension of 50 amino acids. Here we investigate cell-, promoter-, and ligand-specific transactivation by the VDRB1 isoform. Transactivation by these isoforms of the cytochrome P450 CYP24 promoter was compared in kidney (HEK293 and COS1), tumor-derived colon (Caco-2, LS174T, and HCT15), and mammary (HS578T and MCF7) cell lines. VDRB1 transactivation in response to 1,25(OH)(2)D-3 was greater in Cost and HCT15 cells (145%), lower in HEK293 and Caco-2 cells (70-85%) and similar in other cell lines tested. By contrast, on the cytochrome P450 CYP3A4 promoter, 1,25(OH)(2)D-3-induced VDRB1 transactivation was significantly lower than VDRA in Caco-2 (68%), but comparable to VDRA in HEK293 and COS1 cells. Ligand-dependence of VDRB1 differential transactivation was investigated using the secondary bile acid lithocholic acid (LCA). On the CYP24 promoter LCA-induced transactivation was similar for both isoforms in COS1, whereas in Caco-2 and HEK293 cells VDRB1 was less active. On the CYP3A4 promoter, LCA activation of VDRB1 was comparable to VDRA in all the cell lines tested. Mutational analysis indicated that both the 1,25(OH)(2)D-3 and LCA-regulated activities of both VDR isoforms required a functional ligand-dependent activation function (AF-2) domain. In gel shift assays VDR:DNA complex formation was stronger in the presence of 1,25(OH)(2)D-3 than with LCA. These results indicate that regulation of VDRB1 transactivation activity is dependent on cellular context, promoter, and the nature of the ligand. (c) 2005 Elsevier Inc. All rights reserved.

Season of birth is associated with anthropometric and neurocognitive outcomes during infancy and childhood in a general population birth cohort

The 'season of birth' effect is one of the most consistently replicated associations in schizophrenia epidemiology. In contrast, the association between season of birth and development in the general Population is relatively poorly understood. The aim of this study was to explore the impact of season of birth on various anthropometric and neurocognitive variables from birth to age seven in a large, community-based birth cohort. A sample of white singleton infants born after 37 weeks gestation (n =22,123) was drawn from the US Collaborative Perinatal Project. Anthropometric variables (weight, head circumference, length/height) and various measures of neurocognitive development, were assessed at birth, 8 months, 4 and 7 years of age. Compared to surnmer/autumn born infants, winter/spring born infants were significantly longer at birth, and at age seven were significantly heavier, taller and had larger head circumference. Winter/spring born infants were achieving significantly higher scores on the Bayley Motor Score at 8 months, the Graham-Ernhart Block Test at age 4, the Wechsler Intelligence Performance and Full Scale scores at age 7, but had significantly lower scores on the Bender-Gestalt Test at age 7 years. Winter/spring birth, while associated with an increased risk of schizophrenia, is generally associated with superior outcomes with respect to physical and cognitive development. (c) 2005 Elsevier B.V. All rights reserved.

Dietary analysis and nutritional behaviour in people with and without age-related macular disease

Background and Aims: Consumption of antioxidant nutrients can reduce the risk of progression of age-related macular degeneration (AMD) - the leading cause of visual impairment in adults over the age of 50 years in the UK. Lutein and zeaxanthin (L&Z) are of particular interest because they are selectively absorbed by the central retina. The objectives of this study were to analyse the dietary intake of a group of AMD patients, assess their ability to prepare and cook healthy food, and to make comparisons with people not affected by AMD. Methods: 158 participants with AMD were recruited via the UK charity The Macular Society, and fifty participants without AMD were recruited from optometric practice. A telephone interview was conducted by trained workers where participants completed a 24 hour food diary, and answered questions about cooking and shopping capabilities. Results: In the AMD group, the average L&Z intake was low in for both males and females. Those able to cook a hot meal consumed significantly more L&Z than those who were not able. Most participants were not consuming the recommended dietary allowance of fibre, calcium, vitamin D and E, and calorific intake was also lower than recommendations for their age-group. The non-AMD group consumed more kilocalories and more nutrients than the AMD group, but the L&Z intake was similar to those with AMD. The main factor that influenced participant’s food choices was personal preference. Conclusion: For an ‘informed’ population, many AMD participants were under-consuming nutrients considered to be useful for their condition. Participants without AMD were more likely to reach recommended daily allowance values for energy and a range of nutrients. It is therefore essential to design more effective dietary education and dissemination methods for people with, and at risk of, AMD.

Cardiovascular risk factors in Turkish immigrants with type 2 diabetes living in the Netherlands

The cross sectional study investigated the association of tobacco smoke, vitamin D status, anthropometric parameters, and kidney function in Turkish immigrants with type 2 diabetes (T2D) living in the Netherlands. Study sample included a total of 110 participants aged 30 years and older (males= 46; females= 64). Serum cotinine, a biomarker for smoke exposure, was measured with a solid-phase competitive chemiluminescent immunoassay. Serum 25-hydroxyvitamin D [25(OH)D] was determined by electrochemiluminescence immunoassay (ECLIA). Measures of obesity including: body weight, body mass index (BMI), waist circumference (WC), and hip circumference (HC) were measured. Waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were calculated. Urine albumin was measured by immunoturbidimetric assay. Urine creatinine was determined using the Jaffe method. All statistical analyses were performed using SPSS, version 19.0 (SPSS Inc., Chicago, IL, USA). Independent samples t-test, chi-squared tests, multiple linear regression and logistic regression analysis were used. Cotinine levels were positively associated with cholesterol to HDL ratio and atherosclerosis-index. Serum 25(OH)D levels were negatively associated with diastolic blood pressure. Gender-specific associations between anthropometric measures and high sensitivity C-reactive protein (hs-CRP) levels were observed. Hs-CRP was positively associated with WC and WHR in males and WHtR in females. Microalbuminuria (MAU), as determined by albumin-to-creatinine ratio, was present in 21% of the Turkish immigrants with T2D. Participants with hypertension were 6.58 times more likely (adjusted odds ratio) to have positive MAU as compared to normotensive participants. Our findings indicate that serum cotinine, 25(OH)D, hs-CRP, and MAU may be assessed as a standard of care for T2D management in the Turkish immigrant population. Further research should be conducted following cohorts to determine the effects of these biomarkers on CVD morbidity and mortality.

Application and evaluation of an Institute of Medicine approach to dietary assessment and planning in long -term care

The primary purpose of these studies was to determine the effect of planning menus using the Institute of Medicine's (IOMs) Simple Nutrient Density Approach on nutrient intakes of long-term care (LTC) residents. In the first study, nutrient intakes of 72 subjects were assessed using Dietary Reference Intakes (DRIs) and IOM methodology. The intake distributions were used to set intake and menu planning goals. In the second study, the facility's regular menus were modified to meet the intake goals for vitamin E, magnesium, zinc, vitamin D and calcium. An experiment was used to test whether the modified menu resulted in intakes of micronutrients sufficient to achieve a low prevalence (<3%) of nutrient inadequacies. Three-day weighed food intakes for 35 females were adjusted for day-to-day variations in order to obtain an estimate of long-term average intake and to estimate the proportion of residents with inadequate nutrient intakes. ^ In the first study, the prevalence of inadequate intakes was determined to be between 65-99% for magnesium, vitamin E, and zinc. Mean usual intakes of Vitamin D and calcium were far below the Adequate Intakes (AIs). In the experimental study, the prevalence of inadequacies was reduced to <3% for zinc and vitamin E but not magnesium. The groups' mean usual intake from the modified menu met or exceeded the AI for calcium but fell short for vitamin D. Alternatively, it was determined that addition of a multivitamin and mineral (MVM) supplement to intakes of the regular menu could be used to achieve goals for vitamin E, zinc and vitamin D but not calcium and magnesium. ^ A combination of menu modification and MVM supplementation may be necessary to achieve a low prevalence of micronutrient inadequacies among LTC residents. Menus should be planned to optimize intakes of those nutrients that are low in an MVM, such as calcium, magnesium, and potassium. A MVM supplement should be provided to fill the gap for nutrients not provided in sufficient amounts by the diet, such as vitamin E and vitamin D. ^

Inadequacy of Micronutrients, Fat, and Fiber Consumption in the Diets of Haitian-, African- and Cuban-Americans with and without Type 2 Diabetes

Micronutrient insufficiency, low dietary fiber, and high saturated fat intake have been associated with chronic diseases. Micronutrient insufficiencies may exacerbate poor health outcomes for persons with type 2 diabetes and minority status. We examined dietary intakes using the Recommended Dietary Allowances (RDAs) of micronutrients, and Adequate Intakes (AIs) of fiber, and Dietary Guidelines for Americans (DGA) for saturated fat in Haitian-, African-, and Cuban- Americans (n = 868), approximately half of each group with type 2 diabetes. Insufficient intakes of vitamins D and E and calcium were found in over 40 % of the participants. Over 50 % of African- and Cuban- Americans consumed over 10 % of calories from saturated fat. Haitian-Americans were more likely to have insufficiencies in iron, B-vitamins, and vitamins D and E, and less likely to have inadequate intake of saturated fat as compared to Cuban-Americans. Vitamin D insufficiency was more likely for Haitian-Americans as compared to African- Americans. Diabetes status alone did not predict micronutrient insufficiencies; however, Haitian-Americans with no diabetes were more likely to be insufficient in calcium. Adjusting for age, gender, energy, smoking, physical activity, access to health care, and education negated the majority of micronutrient insufficiency differences by ethnicity. These findings suggest that policies are needed to ensure that low-cost, quality produce can be accessed regardless of neighborhood and socioeconomic status.

The relationship among serum levels of manganese superoxide dismutase and mitochondrial DNA 8-hydroxy-2'- deoxyguanosine, and dietary antioxidants intake in type 2 diabetes

Oxidative stress plays a key role in the development of Type 2 Diabetes (T2D). This cross-sectional study examined the relationship among serum levels of manganese superoxide dismutase (MnSOD), 8-hydroxy-2’-deoxyguanosine (8OHdG), dietary antioxidant intakes and glycemic control in African Americans (n=209) and Haitian Americans (n=234) with and without T2D. ^ African Americans had higher BMI (32.8 vs. 29.3 kg/m2), higher energy intake (2148 vs. 1770 kcal), and were more educated as compared to Haitian Americans; all variables were significant at p < .001. Serum levels of 8OHdG and MnSOD for African Americans (1691.0 ± 225.1 pg/ml, 2538.0 ± 1091.8 pg/ml; respectively) were significantly higher than for Haitian Americans (1626.2 ± 222.9, 2015.8 ± 656.3 pg/ml; respectively). 8OHdG was negatively correlated with MnSOD ( r = -.167, p < .001) in T2D. Having T2D was negatively correlated with MnSOD (r = -.337; p < .01) and positively correlated with 8OHdG (r = .500; p < .01). African Americans and Haitian Americans with T2D had fasting plasma glucose (FPG) levels of 143.0 ± 61.0 mg/dl and 157.6 ± 65.5 mg/dl, and A1C of 7.5 ± 1.8 % and 8.4 ± 2.4 %, respectively. African Americans and Haitian Americans without T2D had FPG levels of 95.8 ± 13.2 mg/dl and 98.7 ± 16.9 mg/dl, and A1C of 5.9 ± 0.4% and 6.0 ± 0.5%, respectively. Dietary intakes of vitamin C and vitamin D were negatively correlated with FPG (r = -.21; r = -.19, p < .05) respectively. Carotenoids negatively correlated with A1C (r = -.19, p < .05). Lower levels of MnSOD were associated with lower levels of zinc, r = .10, p < .05, and higher levels of carotenoids r = -.10, p < .05. Higher levels of 8OHdG were associated with lower levels of Vitamin D, r = -.14, p < .01, and carotenoids, r = -.09, p < .05. ^ The results demonstrate greater oxidative mtDNA damage in persons with T2D compared to those without T2D and in African Americans compared with Haitian Americans. The inverse relationship between dietary intake of antioxidants and oxidative stress implies a potential to reduce oxidative stress with diet. ^

Smoking and dietary inadequacy among Inuvialuit women of child bearing age in the Northwest Territories, Canada

Objective. The prevalence of smoking in Aboriginal Canadians is higher than non-Aboriginal Canadians, a behavior that also tends to alter dietary patterns. Compared with the general Canadian population, maternal smoking rates are almost twice as high. The aim of this study was to compare dietary adequacy of Inuvialuit women of childbearing age comparing smokers versus non-smokers. Research methods & procedures. A cross-sectional study, where participants completed a culturally specific quantitative food frequency questionnaire. Non-parametric analysis was used to compare mean nutrient intake, dietary inadequacy and differences in nutrient density among smokers and non-smokers. Multiple logistic regression analyses were performed for key nutrients inadequacy and smoking status. Data was collected from three communities in the Beaufort Delta region of the Northwest Territories, Canada from randomly selected Inuvialuit women of childbearing age (19-44 years). Results: Of 92 participants, 75% reported being smokers. There were no significant differences in age, BMI, marital status, education, number of people in household working and/or number of self employed, and physical activity between smokers and non-smokers. Non-parametric analysis showed no differences in nutrient intake between smokers and non-smokers. Logistic regression however revealed there was a positive association between smoking and inadequacies of vitamin C (OR = 2.91, 95% CI, 1.17-5.25), iron (OR = 3.16, 95% CI, 1.27-5.90), and zinc (OR = 2.78, 95% CI, 1.12-4.94). A high percentage of women (>60%), regardless of smoking status, did not meet the dietary recommendations for fiber, vitamin D, E and potassium. Conclusions: This study provides evidence of inadequate dietary intake among Inuvialuit of childbearing age regardless of smoking behavior.

The relationship among serum levels of manganese superoxide dismutase and mtDNA 8-hydroxy-2'-deoxyguanosine, and dietary antioxidants intake in Type 2 Diabetes

Oxidative stress plays a key role in the development of Type 2 Diabetes (T2D). This cross-sectional study examined the relationship among serum levels of manganese superoxide dismutase (MnSOD), 8-hydroxy-2’-deoxyguanosine (8OHdG), dietary antioxidant intakes and glycemic control in African Americans (n=209) and Haitian Americans (n=234) with and without T2D. African Americans had higher BMI (32.8 vs. 29.3 kg/m2), higher energy intake (2148 vs. 1770 kcal), and were more educated as compared to Haitian Americans; all variables were significant at p < .001. Serum levels of 8OHdG and MnSOD for African Americans (1691.0 ± 225.1 pg/ml, 2538.0 ± 1091.8 pg/ml; respectively) were significantly higher than for Haitian Americans (1626.2 ± 222.9, 2015.8 ± 656.3 pg/ml; respectively). 8OHdG was negatively correlated with MnSOD (r = -.167, p < .001) in T2D. Having T2D was negatively correlated with MnSOD (r = -.337; p < .01) and positively correlated with 8OHdG (r = .500; p < .01). African Americans and Haitian Americans with T2D had fasting plasma glucose (FPG) levels of 143.0 ± 61.0 mg/dl and 157.6 ± 65.5 mg/dl, and A1C of 7.5 ± 1.8 % and 8.4 ± 2.4 %, respectively. African Americans and Haitian Americans without T2D had FPG levels of 95.8 ± 13.2 mg/dl and 98.7 ± 16.9 mg/dl, and A1C of 5.9 ± 0.4% and 6.0 ± 0.5%, respectively. Dietary intakes of vitamin C and vitamin D were negatively correlated with FPG (r = -.21; r = -.19, p < .05) respectively. Carotenoids negatively correlated with A1C (r = -.19, p < .05). Lower levels of MnSOD were associated with lower levels of zinc, r = .10, p < .05, and higher levels of carotenoids r = -.10, p < .05. Higher levels of 8OHdG were associated with lower levels of Vitamin D, r = -.14, p < .01, and carotenoids, r = -.09, p < .05. The results demonstrate greater oxidative mtDNA damage in persons with T2D compared to those without T2D and in African Americans compared with Haitian Americans. The inverse relationship between dietary intake of antioxidants and oxidative stress implies a potential to reduce oxidative stress with diet. African Americans were significantly younger (53.3 vs. 55.6 years), had higher BMI (32.8 vs. 29.3 kg/m2), higher energy intake (2148 vs. 1770 kcal), and were more educated as compared to Haitian Americans; all variables were significant at p < .001. Serum levels of 8OHdG and MnSOD for African Americans (1691.0 ± 225.1 pg/ml, 2538.0 ± 1091.8 pg/ml; respectively) were significantly higher than for Haitian Americans (1626.2 ± 222.9, 2015.8 ± 656.3 pg/ml; respectively). 8OHdG was negatively correlated with MnSOD (r = -.167, p < .001) in T2D. Having T2D was negatively correlated with MnSOD (r = -.337; p < .01) and positively correlated with 8OHdG (r = .500; p < .01). African Americans and Haitian Americans with T2D had fasting plasma glucose (FPG) levels of 143.0 ± 61.0 mg/dl and 157.6 ± 65.5 mg/dl, and A1C of 7.5 ± 1.8 % and 8.4 ± 2.4 %, respectively. African Americans and Haitian Americans without T2D had FPG levels of 95.8 ± 13.2 mg/dl and 98.7 ± 16.9 mg/dl, and A1C of 5.9 ± 0.4% and 6.0 ± 0.5%, respectively. Dietary intakes of vitamin C and vitamin D were negatively correlated with FPG (r = -.21; r = -.19, p < .05) respectively. Carotenoids negatively correlated with A1C (r = -.19, p < .05). Lower levels of MnSOD were associated with lower levels of zinc, r = .10, p < .05, and higher levels of carotenoids r = -.10, p < .05. Higher levels of 8OHdG were associated with lower levels of Vitamin D, r = -.14, p < .01, and carotenoids, r = -.09, p < .05. The results demonstrate greater oxidative mtDNA damage in persons with T2D compared to those without T2D and in African Americans compared with Haitian Americans. The inverse relationship between dietary intake of antioxidants and oxidative stress implies a potential to reduce oxidative stress with diet.