Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

Lipoprotein receptor-related protein 1 variants and dietary fatty acids: meta-analysis of European origin and African American studies.

OBJECTIVE: Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids. DESIGN AND METHODS: We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800). RESULTS: After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m(-2) greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m(-2) greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed. CONCLUSION: Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits.

Dietary patterns, insulin sensitivity and inflammation in older adults.

BACKGROUND/OBJECTIVES: Several studies have linked dietary patterns to insulin sensitivity and systemic inflammation, which affect risk of multiple chronic diseases. The purpose of this study was to investigate the dietary patterns of a cohort of older adults, and to examine relationships of dietary patterns with markers of insulin sensitivity and systemic inflammation. SUBJECTS/METHODS: The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3075 older adults. In Health ABC, multiple indicators of glucose metabolism and systemic inflammation were assessed. Food intake was estimated with a modified Block food frequency questionnaire. In this study, dietary patterns of 1751 participants with complete data were derived by cluster analysis. RESULTS: Six clusters were identified, including a 'healthy foods' cluster, characterized by higher intake of low-fat dairy products, fruit, whole grains, poultry, fish and vegetables. In the main analysis, the 'healthy foods' cluster had significantly lower fasting insulin and homeostasis model assessment of insulin resistance values than the 'breakfast cereal' and 'high-fat dairy products' clusters, and lower fasting glucose than the 'high-fat dairy products' cluster (P≤0.05). No differences were found in 2-h glucose. With respect to inflammation, the 'healthy foods' cluster had lower interleukin-6 than the 'sweets and desserts' and 'high-fat dairy products' clusters, and no differences were seen in C-reactive protein or tumor necrosis factor-α. CONCLUSIONS: A dietary pattern high in low-fat dairy products, fruit, whole grains, poultry, fish and vegetables may be associated with greater insulin sensitivity and lower systemic inflammation in older adults.

Dietary fat and cholesterol and risk of cardiovascular disease in older adults: the Health ABC Study.

BACKGROUND AND AIMS: Although dietary fats and cholesterol have previously been associated with risk of cardiovascular disease (CVD) in middle-aged populations, less is known among older adults. The purpose of this study was to determine the association between dietary fats, cholesterol, and eggs and CVD risk among community-dwelling adults aged 70-79 in the Health, Aging and Body Composition Study. METHODS AND RESULTS: Diet was assessed using an interviewer-administered 108-item food frequency questionnaire (n=1941). CVD events were defined as a confirmed myocardial infarction, coronary death, or stroke. Relative rates of CVD over 9 years of follow-up were estimated using Cox proportional hazards models. During follow-up, there were 203 incident cases of CVD. There were no significant associations between dietary fats and CVD risk. Dietary cholesterol (HR (95% CI): 1.47 (0.93, 2.32) for the upper vs. lower tertile; P for trend, 0.10) and egg consumption (HR (95% CI): 1.68 (1.12, 2.51) for 3+/week vs. <1/week; P for trend, 0.01) were associated with increased CVD risk. However, in sub-group analyses, dietary cholesterol and egg consumption were associated with increased CVD risk only among older adults with type 2 diabetes (HR (95% CI): 3.66 (1.09, 12.29) and 5.02 (1.63, 15.52), respectively, for the upper vs. lower tertile/group). CONCLUSIONS: Dietary cholesterol and egg consumption were associated with increased CVD risk among older, community-dwelling adults with type 2 diabetes. Further research on the biological mechanism(s) for the increased CVD risk with higher dietary cholesterol and frequent egg consumption among older adults with diabetes is warranted.

Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults.

BACKGROUND/OBJECTIVES: Vitamin D deficiency is associated with cardiovascular disease, osteoporosis, poor muscle strength, falls, fractures and mortality. Although older adults are at a higher risk of vitamin D deficiency, the relationship of serum 25-hydroxyvitamin D (25(OH)D) with all-cause and cardiovascular disease mortality has not been well characterized in the elderly. We hypothesized that low serum 25(OH)D levels predicted mortality in older adults. SUBJECTS/METHODS: Serum 25(OH)D as well as all-cause and cardiovascular disease mortality were examined in 1006 adults, aged > or =65 years, who participated in the InCHIANTI (Invecchiare in Chianti, Aging in the Chianti Area) study, a population-based, prospective cohort study of aging in Tuscany, Italy. Serum 25(OH)D levels were measured at the time of enrollment in 1998-1999, and participants were followed up for mortality. RESULTS: During 6.5 years of follow-up, 228 (22.7%) participants died, of whom 107 died due to cardiovascular diseases. Compared with participants in the highest quartile of serum 25(OH)D (>26.5 ng/ml) (to convert to nmol/l, multiply by 2.496), those in the lowest quartile (<10.5 ng/ml) had increased risk of all-cause mortality (Hazard Ratio (H.R.) 2.11, 95% Confidence Interval (95% C.I.): 1.22-3.64, P=0.007) and cardiovascular disease mortality (H.R. 2.64, 95% C.I.: 1.14-4.79, P=0.02), in multivariate Cox proportional hazards models that adjusted for age, sex, education, season, physical activity and other potential confounders. CONCLUSIONS: Older community-dwelling adults with low serum 25(OH)D levels are at higher risk of all-cause and cardiovascular disease mortality.

Dietary factors in relation to daily activity energy expenditure and mortality among older adults.

OBJECTIVES: To examine the association between dietary factors to daily activity energy expenditure (DAEE) and mortality among older adults. DESIGN AND SETTING: A sub-study of Health, Aging, and Body Composition study. PARTICIPANTS: 298 older participants (aged 70-82 years) in the Health, Aging, and Body Composition Energy Expenditure sub-study. MEASUREMENTS: Dietary factors, DAEE, and all-cause mortality were measured in 298 older participants. Dietary factors include dietary intake assessed by the Block Food Frequency Questionnaire (FFQ), Healthy Eating Index (HEI), and self-reported appetite and enjoyment of eating. DAEE was assessed using doubly labeled water. All-cause mortality was evaluated over a 9 year period. RESULTS: Participants in the highest tertile of DAEE were more likely to be men and to report having a 'good' appetite; BMI among men, proportion married, IL-6 and CRP levels and energy intake were also higher. Fewer black participants were in the 'good' HEI category. Participants in the 'good' HEI category had higher cognitive scores and a higher education level. Participants who reported improvement in their appetite as well as participants who reported a 'good' appetite were at lower risk for mortality (HR (95% CI): 0.42 (0.24-0.74) and 0.50 (0.26-0.88), respectively) even after adjusting for DAEE, demographic, nutritional and health indices. CONCLUSIONS: We showed an association between DAEE and appetite and mortality among well-functioning, community-dwelling older adults. These findings may have some practical use for the health providers. Inclusion of a question regarding appetite of an elderly patient may provide important information regarding risk for health deterioration and mortality.

Effects of dietary protein on the composition of weight loss in post-menopausal women.

OBJECTIVES: To determine whether a hypocaloric diet higher in protein can prevent the loss of lean mass that is commonly associated with weight loss. DESIGN: An intervention study comparing a hypocaloric diet moderately high in protein to one lower in protein. SETTING: Study measurements were taken at the Wake Forest University General Clinical Research Center (GCRC) and Geriatric Research Center (GRC). PARTICIPANTS: Twenty-four post-menopausal, obese women (mean age = 58 +/- 6.6 yrs; mean BMI = 33.0 +/- 3.6 kg/m2). INTERVENTION: Two 20-week hypocaloric diets (both reduced by 2800 kcal/wk) were compared: one maintaining dietary protein intake at 30% of total energy intake (1.2-1.5 g/kg/d; HI PROT), and the other maintaining dietary protein intake at 15% of total energy (0.5-0.7 g/kg/d; LO PROT). The GCRC metabolic kitchen provided lunch and dinner meals which the women picked up 3 days per week and ate outside of the clinic. MEASUREMENTS: Body composition, including total body mass, total lean mass, total fat mass, and appendicular lean mass, assessed by dual energy x-ray absorptiometry, was measured before and after the diet interventions. RESULTS: The HI PROT group lost 8.4 +/- 4.5 kg and the LO PROT group lost 11.4 +/- 3.8 kg of body weight (p = 0.11). The mean percentage of total mass lost as lean mass was 17.3% +/- 27.8% and 37.5% +/- 14.6%, respectively (p = 0.03). CONCLUSION: Maintaining adequate protein intake may reduce lean mass losses associated with voluntary weight loss in older women.

The association between cheese consumption and cardiovascular risk factors among adults.

BACKGROUND: Although current dietary guidelines recommend limiting foods high in fat and saturated fat, such as high-fat dairy, the effect of cheese consumption on body composition and cardiovascular risk factors is largely unknown. METHODS: Participants from a US population-based survey, NHANES III, aged 25-75 years who completed a food frequency questionnaire and had measures of body composition and cardiovascular risk factors were included (n = 10 872). Linear regression was used to compare anthropometrics, blood lipids, blood pressure and blood glucose across categories of cheese consumption (combined full and low-fat). RESULTS: In women, more frequent cheese consumption was associated with higher HDL-C and lower LDL-C (p for trend, < 0.05). However, in men, more frequent cheese consumption was associated with a higher body mass index (BMI), waist circumference, HDL-C and LDL-C, and diastolic blood pressure (p for trend, < 0.05). Men consuming 30 + servings/month had significantly higher BMI, waist circumference, and diastolic blood pressure compared to nonconsumers (P < 0.05). CONCLUSIONS: More frequent cheese consumption was associated with less favourable body composition and cardiovascular risk profile in men, but with a more favourable cardiovascular risk profile in women. However, the type of cheese consumed by men and women may have differed resulting in opposing trends on body composition and cardiovascular risk factors.

The association between weight history and physical performance in the Health, Aging and Body Composition study.

OBJECTIVE: Although the association between current obesity and physical disability is well known, the cumulative effect of obesity is unknown. Using data from the Health, Aging and Body Composition study, we examined the association between weight history in young and middle adulthood and weight status in late adulthood with physical performance in late adulthood. DESIGN: Longitudinal cohort study. SUBJECTS: White and black men and women aged 70-79 years at study baseline (n=2803). MEASURES: Body mass index (BMI; kg/m(2)) was calculated using recalled height at age 25 and weight at age 25 and 50 and measured height and weight at ages 70-79. Physical performance at ages 70-79 was assessed using a short physical performance battery (SPPB) and a 400-m walk test. RESULTS: In this well-functioning cohort, approximately 24% of men and 8% of women reported being overweight or obese (BMI > or =25 kg/m(2)) at age 25, 51% of men and 37% of women reported being overweight or obese at age 50, and 69% of men and 66% of women were overweight or obese at ages 70-79. Men and women who were obese (BMI > or =30 kg/m(2)) at ages 25, 50 and 70-79 had significantly worse SPPB scores and 400-m walk times than those who were normal weight. Women who were overweight (BMI 25-29.9 kg/m(2)) at ages 25, 50 and 70-79 also had significantly worse physical performance. Furthermore, men and women who had a history of being overweight or obese at ages 25 or 50 had worse physical performance compared to those who were normal weight throughout or who were overweight or obese at ages 70-79 but not in midlife or earlier. CONCLUSIONS: Maintaining a healthy body weight throughout adulthood may play a role in preventing or delaying the onset of physical disability.

Abdominal fat distribution and functional limitations and disability in a biracial cohort: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To examine the associations of abdominal fat and obesity with functional limitations and disability in late adulthood. DESIGN: Longitudinal, cohort study. PARTICIPANTS: African American and white men and women aged 45-64 y at baseline with measured waist circumference, waist-to-hip ratio (WHR), and body mass index (BMI) who participated in the Atherosclerosis Risk in Communities (ARIC) Study (n = 9416). OUTCOME MEASURES: Self-reported functional limitations, activities of daily living (ADLs), and instrumental activities of daily living (IADLs) at ages 52-75 y. RESULTS: Waist circumference, WHR, and BMI were positively associated with functional limitations and ADL and IADL impairment approximately 9 y later among African American and white men and women. For example, in African American women the odds ratios (95% CI) associated with a one standard deviation (s.d.) increment in waist circumference (13.3 cm) for severe functional limitations and ADL and IADL impairment were 2.36 (2.00-2.79), 1.41 (1.25-1.58), and 1.49 (1.34-1.66), respectively. In white women, the odds ratios (95% CI) were 2.66 (2.39-2.96), 1.60 (1.47-1.74), and 1.42 (1.31-1.53), respectively. Similar associations were found in men. A 1 s.d. increment in WHR (0.08 U) and BMI (5.06 kg/m2) produced similar results. The associations of waist circumference and WHR with functional limitations and ADL and IADL impairment were attenuated but, in general, remained statistically significant when BMI was added to the models. CONCLUSIONS: Maintaining a healthy body weight and avoiding increases in abdominal fat should be investigated for their potential to reduce the risk of functional limitations and disability in an aging population.

Does vitamin C intake protect against lead toxicity?

Although several animal studies suggest a protective relationship between blood lead concentrations and ascorbic acid, there are inconclusive results regarding the beneficial effect of ascorbic acid on lead concentrations in human studies. Data from the Third National Health and Nutrition Examination Survey examined the association between ascorbic acid and blood lead concentrations in 19,578 participants ages 6-90 years without a history of lead poisoning. Elevated blood lead concentrations were found in 0.4% of adults and 0.5% of youths. Serum ascorbic acid concentrations were inversely associated with the prevalence of elevated blood lead concentrations. However, there was no significant relationship between dietary ascorbic acid intake and blood lead concentrations. This study suggests that there may be a protective relationship between ascorbic acid and lead. Questions remain regarding the unique roles of dietary vitamin C versus supplemental vitamin C in explaining this relationship.

Lead as a risk factor for hypertension in women.

The relation between blood lead concentrations and hypertension, although suggestive, remains controversial. A recent case-control study examined the relation of blood and bone lead concentrations, used as a measure of long-term low-level lead exposure, to the risk of hypertension in women. An increase in patella lead concentrations from the 10th to the 90th percentile was associated with increased odds of hypertension of 1.86 using a backward-elimination logistic regression after adjusting for age, body mass index, dietary sodium intake, and family history of hypertension. Although more studies are needed, this study suggests that associations between lead and blood pressure do occur in women.

Age-related hearing loss, vitamin B-12, and folate in elderly women.

BACKGROUND: Hearing impairment is 1 of the 4 most prevalent chronic conditions in the elderly. However, the biological basis of age-related hearing loss is unknown. OBJECTIVE: The objective was to test the hypothesis that age-related hearing loss may be associated with poor vitamin B-12 and folate status. DESIGN: A thorough audiometric assessment was conducted in 55 healthy women aged 60-71 y. Hearing function was determined by the average of pure-tone air conduction thresholds at 0.5, 1, 2, and 4 kHz and was categorized into 2 groups for logistic regression analyses: normal hearing (<20 dB hearing level; n = 44) and impaired hearing (> or = 20 dB hearing level; n = 11). RESULTS: Mean age was the same (65 y) for the normal hearing and impaired hearing groups. Pure-tone averages were inversely correlated with serum vitamin B-12 (r = -0.58, P = 0.0001) and red cell folate (r = -0.37, P = 0.01). Women with impaired hearing had 38% lower serum vitamin B-12 (236 compared with 380 pmol/L, respectively, P = 0.008) and 31% lower red cell folate (425 compared with 619 nmol/L, respectively, P = 0.02) than women with normal hearing. Among participants who did not take supplements containing vitamin B-12 or folate, women with impaired hearing had 48% lower serum vitamin B-12 (156 compared with 302 pmol/L, respectively, P = 0.0007) and 43% lower red cell folate (288 compared with 502 nmol/L, respectively, P = 0.001) than women with normal hearing. CONCLUSION: Poor vitamin B-12 and folate status may be associated with age-related auditory dysfunction.

Health and dietary characteristics of supplement users in an elderly population.

The purpose of this study was to investigate the association of health and dietary characteristics with the use of vitamin and mineral supplements in community-dwelling, cognitively intact elders aged in their 60s (n = 89), 80s (n = 92), and 100s (n = 76) who resided in Georgia in the southeastern United States. Elders who were physically active (p = 0.008), had stomach problems (p = 0.042), or used arthritis medication (p = 0.015) were more likely to take a nutritional supplement than elders without these characteristics. Physically active elders were more likely to take calcium (p = 0.004), vitamin E (p = 0.022), and vitamin C (p = 0.046) than non-physically active elders. Compared to non-users, supplement users were also more likely to comply with nutritional health seeking behaviors such as avoiding too much salt, fat, cholesterol, sugar, caffeine, and eating enough fiber, vitamins and minerals from food or supplements, and calcium in foods or supplements. The observation that the use of certain vitamin or mineral supplements is associated with dietary fat intakes, dietary protein intakes, and patterns of alcohol, decaffeinated coffee, and tea consumption suggests that supplement use is one of a cluster of health behaviors. Thus, it may be important that future investigations concerning the impact of supplement use on diseases, such as heart disease or cancer, control for the effects of dietary patterns and physical activity.

Individual foods and food group patterns of the oldest old.

This study compares the dietary patterns of centenarians (n = 85) with sexagenarians (n = 76) and octogenarians (n = 83). A Daily Diet Diary was developed to code the responses of the 24-hour dietary recalls. Centenarians and octogenarians consumed a more varied (P < 0.05) diet, with higher (P < 0.01) consumption frequencies of milk and grains, and fewer (P < 0.01) skipped breakfasts than sexagenarians. However, centenarians also consumed high fat foods (P < 0.01), such as whole milk and biscuits, and coffee (P < 0.5) more frequently than the two younger cohorts. Several of the variations found in the food patterns among the three age groups may reflect cohort differences, rather than true antecedents for longevity.