Jackilen Shannon

Nutrient Biomarker Patterns, Cognitive Function, and Mri Measures of Brain Aging

Objective: To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders. Methods: Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n = 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes. Results: Mean age was 87 ± 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine ω-3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine ω-3 pattern and white matter hyperintensity volume. Conclusion: Distinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population. Neurology® 2012;78:241–249

Uric Acid as a CNS Antioxidant

Oxidative damage is a consistent finding in a number of central nervous system (CNS) disorders. Uric acid (UA) is a potent hydrophilic antioxidant that is modified by diet and drug. Several lines of evidence suggest that plasma UA may modulate outcomes in neurologic disease, but little attention has been paid to CNS levels of UA. Our objective was to test the hypothesis that cerebrospinal fluid (CSF) UA is determined by plasma UA, modified by blood-brain barrier (BBB) integrity and associated with rate of cognitive decline in Alzheimers disease (AD). Also, since UA and ascorbic acid may act as antioxidants for one another, we also explored a potential interaction between them in the brain. Thirty-two patients with mild to moderate AD (Mini-Mental Status Exam 19 +/- 5) participated in a longitudinal biomarker study for one year involving standardized clinical assessments. CSF and blood were collected at baseline for UA, ascorbic acid, and albumin. Cognitive measures were collected at baseline and again one year later. CSF UA was independent of age, gender, and AD severity. CSF and plasma UA were positively correlated (r=0.669, p=0.001) and BBB impairment was associated with higher CSF levels of UA (p=0.028). Neither plasma nor CSF UA reached significant association with rates of cognitive decline over 1 year. CSF UA and CSF ascorbic acid were positively correlated (r=0.388, p=0.001). The hypothesis that CSF UA is determined by plasma UA and BBB integrity is supported, as is the hypothesis that UA and ascorbic acid are associated in CSF but not plasma. Adequately powered prospective studies would help assess any role for UA in primary and secondary prevention of AD.

Dietary risk factors for invasive and in-situ cervical carcinomas in Bangkok, Thailand

OBJECTIVE: Although human papillomavirus (HPV) may be a necessary cause of cervical cancer, most women with HPV infections do not develop this disease. This study was conducted to evaluate the possible effects of specific dietary factors on cervical carcinogenesis.METHODS: Fifty hospitalized in-situ cases and 125 controls were identified from family planning or gynecologic clinics associated with Siriraj hospital in Bangkok, Thailand, and 134 hospitalized invasive cases and 384 hospitalized controls from the public wards of Siriraj Hospital were administered a food-frequency questionnaire and tested for HPV DNA in exfoliated cervical cells. Odds ratios in relation to intake of foods high in vitamin C, folate, vitamin E, vitamin A, β-carotene, retinol, and cruciferous vegetables were estimated using logistic regression in case–control comparisons and in case–case comparisons adjusted for HPV status.RESULTS: High intake of foods rich in vitamin A, and particularly high-retinol foods, were associated with a reduced risk of in-situ disease and less strongly also with a reduced risk of invasive as compared to in-situ disease. No association was found between intake of cruciferous vegetables, foods high in vitamin C, folate, vitamin E, and β-carotene and risk of either in-situ or invasive cervical cancer.CONCLUSIONS: Increasing intake of foods rich in total vitamin A, and particularly high-retinol foods, may reduce risk of in-situ cervical cancer, and at the highest level of intake may inhibit progression to invasion. If others confirm these results they suggest means of reducing the risk of cervical cancer that are amenable to public health action.

Plasma Isoflavones and Fibrocystic Breast Conditions and Breast Cancer Among Women in Shanghai, China

Background: Proliferative benign breast conditions are associated with elevated risk of breast cancer, whereas nonproliferative conditions are not strongly associated with risk. Factors acting before onset of hyperplasia might be associated with both benign conditions and breast cancer, whereas those on the proliferative disease-to-cancer pathway would be associated only with cancer. Soy isoflavone exposure may influence breast cancer risk, but little is known of its association with benign conditions. Materials and Methods: We examined possible relationships between plasma genistein and daidzein concentrations and risk of breast disease in women, in a breast self-examination trial in Shanghai, China, diagnosed with breast cancer (n = 196) or a benign breast condition (n = 304), and 1,002 age-matched controls with no known breast disease. Benign conditions were classified as nonproliferative (n = 131) or proliferative with or without atypia (n = 173). Results: Isoflavone concentrations were inversely associated with risk of nonproliferative and proliferative benign fibrocystic conditions, as well as with breast cancer, both with and without concomitant proliferative changes in ipsilateral noncancerous mammary epithelium (Ptrend < 0.01 for all comparisons with controls). Women in the highest quartile of plasma genistein (>76.95 ng/mL) were less likely to have breast cancer (odds ratio, 0.26; 95% confidence interval, 0.13-0.50) or benign conditions (odds ratio, 0.40; 95% confidence interval, 0.23-0.70) compared with women in the lowest quartile (<9.42 ng/mL). Observed risks for breast cancer with and without surrounding proliferative changes were not different, respectively, from observed risks for benign proliferative and nonproliferative conditions alone. Conclusion: Isoflavone exposure was inversely associated with fibrocystic breast conditions and breast cancer, and the results suggest that effects on cancer risk occur early in carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2579–86)

Macronutrients, Diet Quality, and Frailty in Older Men

BACKGROUND Frailty, a phenotype of multisystem impairment and expanding vulnerability, is associated with higher risk of adverse health outcomes not entirely explained by advancing age. We investigated associations of macronutrients, dietary fiber, and overall diet quality with frailty status in older community-dwelling men. METHODS Participants were 5,925 men aged ≥ 65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study at six U.S. centers. Diet was assessed at baseline with a food frequency questionnaire. We assessed frailty status (robust, intermediate, or frail) at baseline and at a second clinic visit (a mean of 4.6 years later) using a slightly modified Cardiovascular Health Study frailty index. We used multinomial logistic regression to assess associations between macronutrient intake, dietary fiber, and the Diet Quality Index Revised with frailty status at baseline and at the second clinic visit. RESULTS At baseline, 2,748 (46.4%) participants were robust, 2,681 (45.2%) were intermediate, and 496 (8.4%) were frail. Carbohydrate, fat, protein, and dietary fiber showed no consistent associations with frailty status. Overall diet quality exhibited fairly consistent associations with frailty status. The Diet Quality Index Revised was inversely associated with frail status relative to robust status at the baseline visit (odds ratio for Q5 vs Q1 = 0.44, 95% confidence interval: 0.30, 0.63; p for trend < .0001) and at the second clinic visit (odds ratio for Q5 vs Q1 = 0.18, 95% confidence interval: 0.03, 0.97; p for trend = .0180). CONCLUSIONS Overall diet quality was inversely associated with prevalent and future frailty status in this cohort of older men.

Dietary and other risk factors in women having fibrocystic breast conditions with and without concurrent breast cancer: A nested case‐control study in Shanghai, China

Risk of breast cancer is increased in women with proliferative benign breast conditions. Most of these conditions, however, do not progress to breast cancer. The purpose of our study was to identify factors possibly associated with this progression. Women with proliferative fibrocystic breast conditions alone (214), and women with proliferative fibrocystic breast conditions and concurrent breast cancer (130), were compared to each other, and each of these groups of women were also compared to 1,070 controls; and 176 women with non‐proliferative benign breast conditions alone, and 155 also with breast cancer, were similarly compared. All study subjects were selected from a cohort of women enrolled in a trial of breast self‐examination in Shanghai. Women were interviewed to ascertain information on suspected risk factors for breast cancer and dietary habits. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Increased risks of both proliferative fibrocystic breast conditions alone, and with breast cancer, were associated with low parity, a prior benign breast lump and breast cancer in a first‐degree relative. Decreasing trends in the risk of both conditions with increasing intake of fruits and vegetables were observed. No factors were significantly associated with risk of breast cancer relative to risk of proliferative changes. Similar, but in some instances weaker, associations were observed for non‐proliferative fibrocystic conditions with and without breast cancer. The possible risk or protective factors that were observed in our study most likely alter the risk of breast cancer at an early stage in the carcinogenic process, and probably do not alter risk of progression from proliferative fibrocystic breast conditions to breast cancer.

Absorption and chemopreventive targets of sulforaphane in humans following consumption of broccoli sprouts or a myrosinase-treated broccoli sprout extract

SCOPE Sulforaphane (SFN), an isothiocyanate derived from crucifers, has numerous health benefits. SFN bioavailability from dietary sources is a critical determinant of its efficacy in humans. A key factor in SFN absorption is the release of SFN from its glucosinolate precursor, glucoraphanin, by myrosinase. Dietary supplements are used in clinical trials to deliver consistent SFN doses, but myrosinase is often inactivated in available supplements. We evaluated SFN absorption from a myrosinase-treated broccoli sprout extract (BSE) and are the first to report effects of twice daily, oral dosing on SFN exposure in healthy adults. METHODS AND RESULTS Subjects consumed fresh broccoli sprouts or the BSE, each providing 200 μmol SFN daily, as a single dose and as two 100-μmol doses taken 12 h apart. Using HPLC-MS/MS, we detected ∼3 x higher SFN metabolite levels in plasma and urine of sprout consumers, indicating enhanced SFN absorption from sprouts. Twelve-hour dosing retained higher plasma SFN metabolite levels at later time points than 24-hour dosing. No dose responses were observed for molecular targets of SFN (i.e. heme oxygenase-1, histone deacetylase activity, p21). CONCLUSION We conclude that the dietary form and dosing schedule of SFN may impact SFN absorption and efficacy in human trials.

Frequency of soy food consumption and serum isoflavone concentrations among Chinese women in Shanghai

OBJECTIVE The food-frequency questionnaire (FFQ) can be an efficient tool to evaluate dietary intake in large, population-based studies, especially for specific foods. The objective of this study was to validate the assessment of soy and isoflavone (daidzein and genistein) intakes, measured by an FFQ, by comparing intakes with serum isoflavone concentrations. DESIGN AND SETTING Soy and isoflavone intakes and serum isoflavone concentrations were determined as part of a case-control study of dietary factors and risks of benign breast disease and breast cancer. The FFQ, administered during an in-person interview, included six soy-specific line items. Blood was drawn within one week of FFQ completion. SUBJECTS In total, 1823 women living in Shanghai, Peoples Republic of China. RESULTS In this population, soybean milk, fresh bean curd and other bean foods were eaten once per week, and fermented bean curd, fried bean curd puff and soybeans were eaten less than once per week. A significant linear trend (P<0.01) in serum isoflavone concentrations across increasing categories of soy and isoflavone intakes was observed, indicating that soy and isoflavone intakes, measured by the FFQ, well distinguished serum isoflavone concentrations. Linear trends were also observed in both case and control groups in stratified analyses, suggesting little differential bias by case-control status. CONCLUSIONS The results suggest that the FFQ provides a useful marker of soy food consumption and isoflavone exposure in this population.

Serum and dietary vitamin D and cardiovascular disease risk in elderly men: A prospective cohort study

BACKGROUND AND AIM Recent research suggests that low vitamin D may be associated with cardiovascular disease (CVD). METHODS AND RESULTS We prospectively evaluated the association of dietary plus supplemental vitamin D intake and serum 25(OH) vitamin D with CVD incidence in the Osteoporotic Fractures in Men (MrOS) Study. Vitamin D intake was measured using a food frequency questionnaire and self-reported supplemental intake in 3094 men (mean age 76.4 years). From a subset of this population, we measured 25(OH) vitamin D in 813 men. Median 25(OH) vitamin D was 25.3 ng/mL. During a median follow-up of 4.4 years, there were 472 CVD cases, including 371 from coronary heart disease (CHD) and 101 from cerebrovascular attack (CVA). In the 25(OH) vitamin D sub-cohort, there were 140 cases of CVD including 115 from CHD and 25 from CVA. We used a Cox proportional hazards regression to calculate hazard ratios (HR) for CVD by vitamin D quartile. After adjusting for age, season, and standard CVD risk factors, the lowest quartile of 25(OH) vitamin D (HR, 1.18; 95% CI, 0.69-2.03) and vitamin D intake (HR, 0.76; 95% CI, 0.56-1.04) were not significantly associated with CVD incidence, compared to the highest vitamin D quartiles. When 25(OH) vitamin D was further analyzed by sufficiency (≥30 ng/mL), insufficiency (≥15-29.9 ng/mL), and deficiency (<15 ng/mL), vitamin D deficiency was not significantly associated with CVD incidence compared to sufficiency (HR 1.34; 95% CI 0.65-2.77). CONCLUSION Vitamin D intake and serum 25(OH) vitamin D were not associated with CVD risk.

Assessment of Genetic Determinants of the Association of γ′ Fibrinogen in Relation to Cardiovascular Disease

Objective—&ggr;′ fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of &ggr;′ fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort. Methods and Results—A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for &ggr;′ fibrinogen levels from the cycle 7 examination. Fifty-four SNPs in or near the fibrinogen gene locus demonstrated genome-wide significance (P<5.0×10−8) for association with &ggr;′ fibrinogen levels. The top-signal SNP was rs7681423 (P=9.97×10−110) in the fibrinogen gene locus near FGG, which encodes the &ggr; chain. Conditional on the top SNP, the only other SNP that remained genome-wide significant was rs1049636. Associations between SNPs, &ggr;′ fibrinogen levels, and prevalent CVD events were examined using multiple logistic regression. &ggr;′ fibrinogen levels were associated with prevalent CVD (P=0.02), although the top 2 SNPs associated with &ggr;′ fibrinogen levels were not associated with CVD. These findings contrast those for total fibrinogen levels, which are associated with different genetic loci, particularly FGB, which encodes the B&bgr; chain. Conclusion—&ggr;′ fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus.