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Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer.Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment.Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay.RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA.

Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared with controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared with population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.

Background: High whole grain intake has consistently been associated with lowered risk of developing a number of chronic diseases. Among cereals, rye has highest content of dietary fiber, together with a wide variety of bioactive compounds. There is accumulating evidence from intervention studies of physiological effects of rye foods with potential health benefits. Scope and approach: This review summarizes the state of the art of rye and health and identifies future directions for research and innovation, based partly on findings presented at the international conference "The Power of Rye", angstrom land, Finland, 7-8 June 2017. Key findings and conclusions: Rye foods have well-established beneficial effects on insulin metabolism compared with wheat bread under isocaloric conditions and at standardized amounts of available carbohydrates, which may have positive implications for diabetes prevention. Recent findings suggest that alterations in blood glucose flux partly explain these effects. Moreover, several studies have shown beneficial effects of rye-based foods on satiety, which is one plausible mechanism behind recently demonstrated beneficial effects on weight management. Emerging results indicate beneficial effects of rye intake on inflammation and blood lipids. More research is needed to uncover underlying mechanisms for other demonstrated effects and the long-term implications for health. A challenge with rye-based foods is making them palatable and widely acceptable to consumers. Development of innovative and tasty rye products and targeted communication strategies is crucial in increasing awareness and consumption of rye foods. Novel results in this regard are presented in this review.

SummaryMetabolic dysregulation in multiple tissues alters glucose homeostasis and influences risk for type 2 diabetes (T2D). To identify pathways and tissues influencing T2D-relevant glycemic traits (fasting glucose [FG], fasting insulin [FI], two-hour glucose [2hGlu] and glycated hemoglobin [HbA1c]), we investigated associations of exome-array variants in up to 144,060 individuals without diabetes of multiple ancestries. Single-variant analyses identified novel associations at 21 coding variants in 18 novel loci, whilst gene-based tests revealed signals at two genes, TF (HbA1c) and G6PC (FG, FI). Pathway and tissue enrichment analyses of trait-associated transcripts confirmed the importance of liver and kidney for FI and pancreatic islets for FG regulation, implicated adipose tissue in FI and the gut in 2hGlu, and suggested a role for the non-endocrine pancreas in glucose homeostasis. Functional studies demonstrated that a novel FG/FI association at the liver-enriched G6PC transcript was driven by multiple rare loss-of-function variants. The FG/HbA1c-associated, islet-specific G6PC2 transcript also contained multiple rare functional variants, including two alleles within the same codon with divergent effects on glucose levels. Our findings highlight the value of integrating genomic and functional data to maximize biological inference.Highlights23 novel coding variant associations (single-point and gene-based) for glycemic traits51 effector transcripts highlighted different pathway/tissue signatures for each traitThe exocrine pancreas and gut influence fasting and 2h glucose, respectivelyMultiple variants in liver-enriched G6PC and islet-specific G6PC2 influence glycemia

Background Herpes simplex virus (HSV) is thought to play an etiological role in the development of Alzheimer's disease (AD). Methods Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years) and 360 age- and sex-matched dementia-free controls, taken on average 9.6 years before AD diagnosis, were analyzed for anti-HSV antibodies (immunoglobulin G, IgG, and immunoglobulin M, IgM) by enzyme-linked immunosorbent assays. Results In the complete sample group, the presence of anti-HSV IgG and IgM antibodies did not increase the risk of AD significantly (odds ratio (OR) 1.636, P = .069 and OR 1.368, P = .299, respectively). In cases with 6.6 years or more between plasma sampling and AD diagnosis (n = 270), there was a significant association between presence of anti-HSV IgG antibodies and AD (OR 2.250, P = .019). Conclusion Among persons with a follow-up time of 6.6 years or more, HSV infection was significantly associated with AD.

The nested case-control (NCC) design is widely used in epidemiologic studies as a cost-effective subcohort sampling method to study the association between a disease and its potential risk factors. NCC data are commonly analyzed using Thomas' partial likelihood approach under the Cox proportional hazards model assumption. However, the linear modeling form in the Cox model may be insufficient for practical applications, especially when there are a large number of risk factors under investigation. In this paper, we consider a partially linear single index proportional hazards model, which includes a linear component for covariates of interest to yield easily interpretable results and a nonparametric single index component to adjust for multiple confounders effectively. We propose to approximate the nonparametric single index function by polynomial splines and estimate the parameters of interest using an iterative algorithm based on the partial likelihood. Asymptotic properties of the resulting estimators are established. The proposed methods are evaluated using simulations and applied to an NCC study of ovarian cancer.

Background: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. Objective: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. Design: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. Results: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. Conclusion: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity. Am J Clin Nutr 2013;97:1107-20.

The Mediterranean diet has been widely promoted and may be associated with chronic disease prevention and a better overall health status. The aim of this study was to evaluate whether the Mediterranean diet score inversely predicted total or cause-specific mortality in a prospective population study in Northern Sweden (Västerbotten Intervention Program). The analyses were performed in 77,151 participants (whose diet was measured by means of a validated FFQ) by Cox proportional hazard models adjusted for several potential confounders. The Mediterranean diet score was inversely associated with all-cause mortality in men [HR = 0.96 (95% CI = 0.93, 0.99)] and women [HR = 0.95 (95% CI = 0.91, 0.99)], although not in obese men. In men, but not in women, the score was inversely associated with total cancer mortality [HR = 0.92 (95% CI = 0.87, 0.98)], particularly for pancreas cancer [HR = 0.82 (95% CI = 0.68, 0.99)]. Cardiovascular mortality was inversely associated with diet only in women [HR = 0.90 (95% CI = 0.82, 0.99)]. Except for alcohol [HR = 0.83 (95% CI = 0.76, 0.90)] and fruit intake [HR = 0.90 (95% CI = 0.83, 0.98)], no food item of the Mediterranean diet score independently predicted mortality. Higher scores were associated with increasing age, education, and physical activity. Moreover, healthful dietary and lifestyle-related factors additively decreased the mortality likelihood. Even in a subarctic region, increasing Mediterranean diet scores were associated with a longer life, although the protective effect of diet was of small magnitude compared with other healthful dietary and lifestyle-related factors examined.

BACKGROUND: The glycemic potential of a diet is associated with chronically elevated insulin concentrations, which may augment breast cancer (BC) risk by stimulating insulin receptor or by affecting insulin-like growth factor I (IGF-I)-mediated mitogenesis. It is unclear whether this effect differs by BC phenotype. OBJECTIVE: The objective was to investigate the relation between glycemic index (GI), glycemic load (GL), and total carbohydrate intake with BC by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: We identified 11,576 women with invasive BC among 334,849 EPIC women aged 34-66 y (5th to 95th percentiles) at baseline over a median follow-up of 11.5 y. Dietary GI and GL were calculated from country-specific dietary questionnaires. We used multivariable Cox proportional hazards models to quantify the association between GI, GL, and carbohydrate intake and BC risk. BC tumors were classified by receptor status. RESULTS: Overall GI, GL, and carbohydrates were not related to BC. Among postmenopausal women, GL and carbohydate intake were significantly associated with an increased risk of estrogen receptor-negative (ER(-)) BC when extreme quintiles (Q) were compared [multivariable HR(Q5-Q1) (95% CI) = 1.36 (1.02, 1.82; P-trend = 0.010) and HR(Q5-Q1) = 1.41 (1.05, 1.89; P-trend = 0.009), respectively]. Further stratification by progesterone receptor (PR) status showed slightly stronger associations with ER(-)/PR(-) BC [HR(Q5-Q1) (95% CI) = 1.48 (1.07, 2.05; P-trend = 0.010) for GL and HR(Q5-Q1) = 1.62 (1.15, 2.30; P-trend = 0.005) for carbohydrates]. No significant association with ER-positive BC was observed. CONCLUSION: Our results indicate that a diet with a high GL and carbohydrate intake is positively associated with an increased risk of developing ER(-) and ER(-)/PR(-) BC among postmenopausal women.

Background: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. Objective: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Design: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. Results: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% Cl: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. Conclusion: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer. Am J Clin Nutr 2012;96:150-63.

Epidemiological studies have reported associations between circulating inflammation markers and risk of chronic diseases. It is of interest to examine whether risk factors for these diseases are associated with inflammation. We conducted a cross-sectional analysis to evaluate whether reproductive and lifestyle factors and circulating vitamin D were associated with inflammation markers, including C-reactive protein, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα), and cytokine modulators (IL-1RA, sIL-lRII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1/R2), among 616 healthy women. We confirmed associations of several inflammation markers with age and BMI. We also observed significantly higher levels of certain inflammation markers in postmenopausal versus premenopausal women (TNFα, sIL-1RII, sIL-2Ra), with increasing parity (IL-12p40), and with higher circulating 25(OH) vitamin D (IL-13) and lower levels among current users of non-steroidal anti-inflammatory drugs (NSAIDs) (IL-1β, IL-2, IL-10, IL-12p70, and IL-12p40), current smokers (IL-4, IL-13, IL-12p40), and women with a family history of breast or ovarian cancer (IL-4, IL-10, IL-13). Our findings suggest that risk factors for chronic diseases (age, BMI, menopausal status, parity, NSAID use, family history of breast and ovarian cancer, and smoking) are associated with inflammation markers in healthy women.

Prostate cancer (PC) is the most common cancer in the Western world and the second most important cancer causing male deaths, after lung cancer, in the United States and Britain. Lifestyle and dietary changes are recommended for men diagnosed with early-stage PC. It has been shown that a diet rich in whole grain (WG) rye reduces the progression of early-stage PC, but the underlying mechanism is not clear. This study sought to identify changes in the metabolic signature of plasma in patients with early-stage PC following intervention with a diet rich in WG rye and rye bran product (RP) compared with refined white wheat product (WP) as a tool for mechanistic investigation of the beneficial health effects of RP on PC progression. Seventeen PC patients received 485 g RP or WP in a randomized, controlled, crossover design during a period of 6 wk with a 2-wk washout period. At the end of each intervention period, plasma was collected after fasting and used for (1)H NMR-based metabolomics. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. A metabolomics analysis of plasma showed an increase in 5 metabolites, including 3-hydroxybutyric acid, acetone, betaine, N,N-dimethylglycine, and dimethyl sulfone, after RP. To understand these metabolic changes, fasting plasma homocysteine, leptin, adiponectin, and glucagon were measured separately. The plasma homocysteine concentration was lower (P = 0.017) and that of leptin tended to be lower (P = 0.07) after RP intake compared to WP intake. The increase in plasma 3-hydroxybutyric acid and acetone after RP suggests a shift in energy metabolism from anabolic to catabolic status, which could explain some of the beneficial health effects of WG rye, i.e., reduction in prostate-specific antigen and reduced 24-h insulin secretion. In addition, the increase in betaine and N,N-dimethylglycine and the decrease in homocysteine show a favorable shift in homocysteine metabolism after RP intake.

Objectives: Our objectives were to study the relationship between iron stores, HFE genotypes and the risk for first-ever myocardial infarction. Methods: First-ever myocardial infarction cases (n=61 ...

Background: Risk factors for rare gynecological cancers are largely unknown. Initial research has indicated that the metabolic syndrome (MetS) or individual components could play a role. Materials and methods: The Metabolic syndrome and Cancer project cohort includes 288 834 women. During an average follow-up of 11 years, 82 vulvar, 26 vaginal and 43 other rare gynecological cancers were identified. Hazard ratios (HRs) were estimated fitting Cox proportional hazards regression models for tertiles and standardized z-scores [with a mean of 0 and a standard deviation (SD) of 1] of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and MetS. Risk estimates were corrected for random error in the measurement of metabolic factors. Results: The MetS was associated with increased risk of vulvar [HR 1.78, 95% confidence interval (CI) 1.30-2.41) and vaginal cancer (HR 1.87, 95% CI 1.07-3.25). Among separate MetS components, 1 SD increase in BMI was associated with overall risk (HR 1.43, 95% CI 1.23-1.66), vulvar (HR 1.36, 95% CI 1.11-1.69) and vaginal cancer (HR 1.79, 95% CI 1.30-2.46). Blood glucose and triglyceride concentrations were associated with increased risk of vulvar cancer (HR 1.98, 95% CI 1.10-3.58 and HR 2.09, 95% CI 1.39-3.15, respectively). Conclusion: The results from this first prospective study on rare gynecological cancers suggest that the MetS and its individual components may play a role in the development of these tumors.

Background: Lymphoid neoplasms are a heterogeneous group of cancers that originate in the lymphatic cells of the immune system. Several risk factors have been identified or suggested, but they all account for only a small proportion of the lymphoid neoplasm incidence. It has been hypothesised that regular exercise may modulate the immune system and thereby reduce the risk of developing the disease. Design and methods: The European Investigation into Cancer and Nutrition (EPIC) cohort consists of 521,457 adults, recruited by 23 centres in 10 European countries. The analytical cohort included 343,756 participants, with 778 non-Hodgkin lymphoma (NHL) cases (376 men and 402 women) and 690 B-cell non-Hodgkin lymphoma (B-NHL) cases (326 men and 364 women). Multivariate Cox regression models were used to calculate hazard ratios (HR) for the association between total, recreational, occupational, and household physical activity and NHL and B-NHL risk, as well as the risk for several B-NHL subtypes. Models were stratified by study centre and age at recruitment and adjusted for various potential confounding factors. Results: We found no evidence of any effect of total physical activity on NHL (adjusted p-trend = 0.76 and 0.30 for men and women, respectively) and B-NHL risk (adjusted p-trend = 0.99 and 0.21 for men and women, respectively) for either men or women. Also no robust results were found for B-NHL subtype analyses among men or women. Conclusions: This study provided no consistent evidence for an association between various physical activity measures and the risk of lymphoid neoplasms or any of the B-NHL subtypes. © 2010 Elsevier Ltd. All rights reserved.

A beneficial role of fish consumption on the risk of myocardial infarction (MI) has been reported and is mostly ascribed to n-3 (omega-3) fatty acids. However, fish also contains methylmercury, which may increase the risk of MI.The objective was to determine how fish consumption and erythrocyte concentrations of mercury (Ery-Hg) and selenium (Ery-Se) are related to the risk of MI and whether n-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) in plasma phospholipids (P-EPA+DHA) are protective.This was a case-control study nested within the northern Sweden cohort, in which data and samples were collected prospectively. The study included 431 cases with an MI after data and sample collection, including 81 sudden cardiac deaths (SCDs) and 499 matched controls. Another 69 female cases with controls from a breast cancer screening registry were included in sex-specific analyses.Odds ratios for the third compared with the first tertile were 0.65 (95% CI: 0.46, 0.91) for Ery-Hg, 0.75 (95% CI: 0.53, 1.06) for Ery-Se, and 0.78 (95% CI: 0.54, 1.11) for P-EPA+DHA. Ery-Hg and P-EPA+DHA were intercorrelated (Spearman's R = 0.34). No association was seen for reported fish consumption. Multivariate modeling did not change these associations significantly. Sex-specific analyses showed no differences in risk associations. High concentrations of Ery-Se were associated with an increased risk of SCD.The biomarker results indicate a protective effect of fish consumption. No harmful effect of mercury was indicated in this low-exposed population in whom Ery-Hg and P-EPA+DHA were intercorrelated.

Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to ~50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of -14% (P = 0.04). Additionally, fasting plasma insulin and 24-h urinary C-peptide excretion were lower after treatment with RP compared with WP (P < 0.01 and P = 0.01, respectively). Daily excretion of 5 lignans was higher after the RP treatment than after the WP treatment (P < 0.001). We conclude that whole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion.

Physical activity has beneficial effects on cardiovascular disease but the mechanisms are still somewhat unclear. One possible pathway may be through the anti-inflammatory effects attributed to regular physical activity. Our primary aim was to study the effects of endurance physical exercise on C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNFalpha) during the acute and recovery phases. Secondarily, we studied the impact of diet on these inflammatory markers.Twenty men, aged 18-55 years, participated in a 14 days cross-country skiing tour. They traveled 12-30km per day corresponding to about 10h of heavy physical activity. The participants were randomized to a diet with either 30 or 40% of energy derived from fat. Inflammatory variables were analysed at week 0, after 1 and 2 weeks and during the recovery phase at week 6 and 8.CRP and TNFalpha increased significantly during the two weeks of exercise (1.4-5.0mg/l, p=0.00 and 6.8-8.4pg/ml, p=0.00). CRP levels were significantly lower during recovery (median 0.7mg/l) compared to baseline (median 1.4mg/l) and did not correlate to metabolic variables. There were no significant changes in IL-6 levels during the study period. For dietary groups significant CRP changes were observed only in the high fat group during recovery.CRP and TNFalpha increased significantly but reacted differently during heavy physical activity while there seemed to be no significant changes in IL-6. No significant differences regarding inflammatory variables were found between the dietary groups.

Background: Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, requires substitution of other macronutrients to maintain energy balance. Objective: We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. Design: This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. Results: During 4–10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. Conclusion: The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes. Am J Clin Nutr 2009;89:1–8.

Alkylresorcinols (AR), phenolic lipids exclusively present in the outer parts of wheat and rye grains, have been proposed as concentration biomarkers of whole-grain wheat and rye intake. A key feature of a good biomarker is high reproducibility, which indicates how accurately a single sample reflects the true mean biomarker concentration caused by a certain intake. In this study, the short- to medium-term reproducibility of plasma AR was determined using samples from a crossover intervention study, where men with prostate cancer (n = 17) were fed rye whole-grain/bran or refined wheat products for 6-wk periods. AR homologs C17:0 and C21:0 differed between the treatments (P < 0.001). The reproducibility determined by the intraclass correlation coefficient (ICC) was high (intervention period 1: ICC = 0.90 [95% CI = 0.82-0.98], intervention period 2: ICC = 0.88 [95% CI = 0.78-0.98]). The results show that a single fasting plasma sample could be used to estimate the mean plasma AR concentration during a 6-wk intervention period with constant intake at a precision of +/- 20% (80% CI). This suggests that the plasma AR concentration can be used as a reliable short- to medium-term biomarker for whole-grain wheat and rye under intervention conditions where intake is kept constant.

Chromosomal instability (CIN) is a major characteristic of many cancers. We investigated whether putatively functional single nucleotide polymorphisms (SNPs) in genes related to CIN (CENPF, ESPL1, NEK2, PTTG1, ZWILCH, ZWINT) affect breast cancer (BC) risk and clinical outcome in a Swedish cohort of 749 incident BC cases with detailed clinical data and up to 15 years of follow-up and 1493 matched controls. As a main observation, carriers of the A allele of the CENPF SNP rs438034 had a worse BC-specific survival compared to the wild type genotype GG carriers (hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.19-5.90), although they were less likely to have regional lymph node metastases (odds ratio (OR) 0.71, 95% CI 0.51-1.01) and tumours of stage II-IV (OR 0.73, 95% CI 0.54-0.99). As there is increasing evidence that CENPF is associated with poor prognosis in patients with primary BC, further independent studies are needed to clarify the importance of genetic variation in the CENPF gene in the clinic.

Physical activity is associated with improved fibrinolytic activity and reduced risk for cardiovascular disease. High levels of leptin and low levels of adiponectin, both adipocyte-derived hormones, or adipokines, are related to dysfibrinolysis and risk for cardiovascular disease. In this study, we explored if improved fibrinolytic activity during exercise could be linked to changes in leptin and adiponectin levels.Twenty healthy men (mean age 36 years) participated in a 14-day long skiing expedition in the Swedish mountains. They were randomly assigned to either a 40% or a 30% fat-based diet. Anthropometry, lipids, fibrinolytic activity (PAI-1 activity, tPA activity and mass) and adipokines (leptin and adiponectin) were measured before, during and six weeks after the expedition.PAI-1 activity and circulating levels of leptin decreased whereas levels of adiponectin increased during exercise. The fall in PAI-1 activity showed a strong linear association with changes in leptin and adiponectin levels (p = 0.001 and p0.001, respectively). Changes in leptin and adiponectin levels were independent of decreasing waist circumference. However, the association between anthropometric measures and adipokines changed considerably during the expedition. Adiponectin was weakly and negatively associated with BMI at baseline. In contrast, there was a strong positive association between adiponectin and BMI after two weeks of exercise, whereas the association between leptin and BMI became less pronounced. In addition, increasing leptin and decreasing adiponectin levels were associated with increasing PAI-1 activity during the six weeks following the expedition. After six weeks of normal activity, fibrinolytic activity and hormone levels returned towards baseline levels.Heavy exercise induced improved fibrinolytic activity, which was associated independently with changes in circulating levels of the adipocyte-derived hormones leptin and adiponectin. Improved fibrinolytic activity (and reduced risk for cardiovascular disease) related to physical activity could possibly be mediated by leptin and adiponectin.

Contains fulltext : 52703.pdf (Publisher’s version ) (Closed access) BACKGROUND: Previous studies suggest that high plasma concentrations of carotenoids, retinol, or tocopherols may reduce the risk of prostate cancer. OBJECTIVE: We aimed to examine the associations between plasma concentrations of 7 carotenoids, retinol, alpha-tocopherol, and gamma-tocopherol and prostate cancer risk. DESIGN: A total of 137,001 men in 8 European countries participated. After a mean of 6 y, 966 incident cases of prostate cancer with plasma were available. A total of 1064 control subjects were selected and were matched for study center, age, and date of recruitment. The relative risk of prostate cancer was estimated by conditional logistic regression, which was adjusted for smoking status, alcohol intake, body mass index, marital status, physical activity, and education level. RESULTS: Overall, none of the micronutrients examined were significantly associated with prostate cancer risk. For lycopene and the sum of carotenoids, there was evidence of heterogeneity between the associations with risks of localized and advanced disease. These carotenoids were not associated with the risk of localized disease but were inversely associated with the risk of advanced disease. The risk of advanced disease for men in the highest fifth of plasma concentrations compared with men in the lowest fifth was 0.40 (95% CI: 0.19, 0.88) for lycopene and 0.35 (95% CI: 0.17, 0.78) for the sum of carotenoids. CONCLUSIONS: We observed no associations between plasma concentrations of carotenoids, retinol, or tocopherols and overall prostate cancer risk. The inverse associations of lycopene and the sum of carotenoids with the risk of advanced disease may involve a protective effect, an association of dietary choice with delayed detection of prostate cancer, reverse causality, or other factors.

Elevated circulating insulin-like growth factor I (IGF-I) levels increasingly are being implicated as a potential risk factor for the development of some cancers; however, relatively few epidemiologic studies have focused on potential relationships between circulating IGF-I levels and cardiovascular risk factors or cardiovascular disease. Hence, our objective is to examine relationships between IGF-I levels; body mass index (BMI); fasting insulin level; IGF binding protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 levels; and an array of traditional cardiovascular risk factors.Our analysis included 715 men and women aged 30 to 62 years who participated in the Västerbotten Intervention Project cohort. IGF-I and IGFBP-1, -2, and -3 were measured in stored plasma samples. Cardiovascular risk factors of interest included glucose level (fasting and 2-hour postload), lipid levels (total cholesterol, high-density lipoprotein cholesterol, and triglycerides), blood pressure (systolic and diastolic), and hypertension status. All presented results were adjusted for age, sex, and laboratory batch.IGF-I quartile was associated inversely with 2-hour glucose level and diastolic blood pressure. There was a stepwise inverse graded association between increasing IGF-I quartile and hypertension, with an odds ratio of 0.51 (95% confidence interval, 0.29-0.90) for hypertension comparing the fourth IGF-I quartile with the first. Further adjusting for BMI and IGFBP-3 level simultaneously strengthened the inverse association, with an odds ratio of 0.42 (95% confidence interval, 0.22-0.80) for hypertension comparing the fourth with the first IGF-I quartile.Contrary to positive associations between IGF-I levels and some cancers, our results suggest that IGF-I level may be related inversely to prevalent hypertension, a risk factor for cardiovascular disease.

Background: Epidemiologic studies have suggested a lower risk of coronary heart disease (CHD) at higher intakes of fruit, vegetables, and whole grain. Whether this association is due to antioxidant vitamins or some other factors remains unclear. Objective: We studied the relation between the intake of antioxidant vitamins and CHD risk. Design: A cohort study pooling 9 prospective studies that included information on intakes of vitamin E, carotenoids, and vitamin C and that met specific criteria was carried out. During a 10-y follow-up, 4647 major incident CHD events occurred in 293 172 subjects who were free of CHD at baseline. Results: Dietary intake of antioxidant vitamins was only weakly related to a reduced CHD risk after adjustment for potential nondietary and dietary confounding factors. Compared with subjects in the lowest dietary intake quintiles for vitamins E and C, those in the highest intake quintiles had relative risks of CHD incidence of 0.84 (95% CI: 0.71, 1.00; P = 0.17) and 1.23 (1.04, 1.45; P = 0.07), respectively, and the relative risks for subjects in the highest intake quintiles for the various carotenoids varied from 0.90 to 0.99. Subjects with higher supplemental vitamin C intake had a lower CHD incidence. Compared with subjects who did not take supplemental vitamin C, those who took >700 mg supplemental vitamin C/d had a relative risk of CHD incidence of 0.75 (0.60, 0.93; P for trend < 0.001). Supplemental vitamin E intake was not significantly related to reduced CHD risk. Conclusions: The results suggest a reduced incidence of major CHD events at high supplemental vitamin C intakes. The risk reductions at high vitamin E or carotenoid intakes appear small.

Cervical intraepithelial neoplasia (CIN) is associated with human papillomaviruses (HPV) and the HLA genes. The MICA (MHC class I chain-related gene A) is expressed by keratinocytes and epithelial cells and interacts with gamma delta T cells. It is therefore possible that MICA might influence the pathogenesis of CIN and cervical cancer through presentation of viral or tumor antigens. To investigate this, we determined the MICA transmembrane allele frequencies in a prospective population-based cohort study from the Västerbotten County in northern Sweden. 74 women developed CIN. 153 control women who remained healthy during follow up were matched for age. Five polymorphic microsatellite alleles of MICA were identified by a polymerase chain reaction-based (PCR) technique using fluorescent-labeled primers. MICA A5 and A5.1 were the most common alleles in this population. None of the alleles of MICA were associated with disease. The frequency of MICA allele A5 was higher among HPV 18 seropositive than HPV 18 seronegative patients but this difference was not significant after the correction of p value. In conclusion, microsatellite allele polymorphism of MICA transmembrane part is not associated with cervical intraepithelial neoplasia.

The purpose of this investigation was to study the degradation of beta-glucan in the small intestine and the molecular weight of beta-glucan in the excreta of nine ileostomy subjects after consumption of different diets based on bread made with oat bran (oat bread), a fiber-rich barley fraction (barley bread), or wheat flour (wheat bread) as the main ingredients. Oat bread with enzymatically degraded beta-glucan was also used (oat + enzyme bread). The beta-glucan intake from the four diets was 12.5, 12.9, 1.1, and 4.0 g/d, respectively. On the basis of dry matter, the night effluents accounted for approximately 15% of the total amount of the excreta, with the highest proportion (22%) being for the wheat-bread diet. A notable loss of beta-glucan (0.7-2.4 g/d, or 13-64%) was found when intake was compared with excretion. In vitro, a higher viscosity development with time for dispersions of oat bread compared with barley bread was noted, which could be related to the higher molecular weight of the beta-glucan in this bread. There seemed to be a depolymerization of the beta-glucan both during bread making and transit through the upper gastrointestinal tract.

This study was undertaken to determine whether milk with its high calcium content adversely affects the absorption of nonheme iron from the diet as greatly as single-meal studies indicate. Nine ileostomy subjects ate a low-fiber, low-phytate diet for 8 consecutive weeks. During the first and eighth weeks they drank a 250-mL soft drink with three main meals and an evening snack each day (0.16 g Ca/d). During the two intervening 3-wk periods, they drank the same amount of low-fat milk or fermented low-fat milk (Verum ; Halsofil, Norrmejerier, Umea, Sweden) according to a formally randomized crossover design (1.4 g Ca/d). During the last 2 d in each of the four periods, apparent iron absorption (balance) from a test diet together with that period's beverage was measured and the plasma ferritin concentration was determined. There was no decrease in apparent iron absorption during the milk diet periods.

Many investigations have been reported in which the effects of varying the concentration of a single factor in grain diets on the availabilities of minerals for absorption have been studied. The purpose of this study in rats was to determine the effects on iron, zinc and cadmium availability of substituting whole grain wheat, oats, barley or rye for iron-supplemented endosperm wheat in a composite diet with one part grain flour and one part non-fat, dried milk with maize oil and vitamins. Iron concentrations varied by a factor of 3 among these diets, zinc by 1.5, cadmium by 5, and both fiber and phytate by a factor of 3.5. The absorption of 59 Fe and 65 Zn from test meals of the diets and the concentrations of iron, zinc and cadmium in selected tissues and body fluids after five weeks on the grain diets were used as independent measures of the mineral availabilities from these diets. Absorption of iron from endosperm wheat and, to a lesser extent, zinc from oats and rye appears to have been overestimated, most likely due to incomplete exchange of the radioisotopes with the supplemented or endogenous minerals in the grains. The variations in the concentrations of iron and cadmium among the diets were by far the most important factors determining the availabilities of these minerals to the rats. The fractional availabilities of iron and zinc were negatively related to the diet phytate concentration and the fractional availability of cadmium was negatively related to the iron status of the rats. The results indicate that substitution of whole grain wheat for endosperm wheat in the diet will increase cadmium accumulation considerably while substitution of oats, barley or rye should result in nearly the same or lower cadmium accumulation. Due to the low availability of iron in barley and rye, substitution of either grain for iron-supplemented endosperm wheat may compromise iron status. As the diets in this study are similar to baby formulas and breakfast cereals, porridge or a sandwich with milk, the probability that these results in rats are applicable to humans strongly suggests that studies similar to this be carried out in humans.

The study was conducted to determine if the excretion of starch and dietary fiber components varies in ileostomy subjects consuming diets high or low in dietary fiber. Excretion of starch, enzyme-resistant starch and dietary fiber components was studied in nine human subjects with ileostomies, who consumed (in a crossover design) a wheat bread-based diet (daily intake 274 g starch, 2.4 g enzyme-resistant starch and 14.4 g total dietary fiber) and a high fiber diet based on oat-bran bread (daily intake 243 g starch, 2.7 g enzyme-resistant starch and 40.2 g total dietary fiber). Food and excreta were collected on d 3 and 17. No significant differences in excretion of starch, enzyme-resistant starch or dietary fiber components were found on these 2 d in each dietary period. When subjects consumed the wheat bread-based diet they excreted (mean +/- SD) 3.3 +/- 1.7 g starch and 2.4 +/- 0.4 g enzyme-resistant starch daily, whereas when consuming the oat bran-based diet they excreted 4.5 +/- 3.1 g starch and 2.5 +/- 0.4 g enzyme-resistant starch. During both dietary periods subjects excreted significantly greater amounts of certain dietary fiber polysaccharide residues (fucose, galactose and uronic acid) than they ingested. This indicates a contribution of endogenous and/or microbial material to the dietary fiber value in ileostomy effluents. However, significantly less excretion of some dietary fiber polysaccharide residues, especially glucose residues, during the oat-bran bread-based dietary period was also noted. This was presumably caused by a degradation of mixed-linked (1,3),(1,4)-beta-D-glucans.

Currently there is no biomarker to link consumption of whole grain cereals and their observed health benefits. A candidate for a biomarker of whole grain wheat and rye intake is a class of phenolic lipids, the alkylresorcinols (AR). Studies to determine the uptake of AR in humans were carried out with a low fiber diet based on white wheat bread (AR free) and a high fiber diet based on rye bran-enriched bread (AR rich). For each diet, two meal frequencies were used: nibbling (7 small meals/d) and ordinary (3 large meals/d). Ten human ileostomy-operated subjects started with the AR-free diet for 2 wk, wk 1 on either nibbling or ordinary and wk 2 on the other meal frequency in a crossover design, followed by a 1-wk washout period, before the AR-rich diet performed as the AR-free diet. Food and ileostomy samples were analyzed for AR. Approximately 40% of AR were recovered in effluent from the small intestine, indicating that 60% of AR are taken up from or converted in the small intestine (ileal digestibility) with no difference between nibbling and ordinary meal frequencies. AR absorbed by humans may be of importance as bioactive compounds, or as a biomarker of whole grain wheat and rye intake.

Excretion of total dietary fiber and dietary fiber components was studied in 10 human subjects with ileostomies, consuming in a crossover design a low fiber diet (15 g total dietary fiber/d) or this diet supplemented with 62 g/d of brewer's spent grain. Food and excreta were collected and analyzed on d 2, 3 and 7 of each dietary period. No significant differences in excretion of total dietary fiber or dietary fiber components were found on the three days. Excreta from subjects consuming the low fiber diet contained significantly more total dietary fiber than was ingested (20%, P < 0.01), indicating the importance of endogenous and microbial material, contributing to the total dietary fiber value, in ileostomy effluents. Analysis of specific dietary fiber components showed that this increased excretion was mainly due to fucose, mannose, galactose and uronic acid residues. When the high-fiber diet was consumed, there was a significantly greater excretion of the same non-starch polysaccharide residues as for consumption of the low fiber diet, but with a simultaneous decrease in excretion of arabinose, xylose and glucose residues (12%, P < 0.01), which were the major fiber components in the diet.

The purpose of the present study was to determine to what extent the accumulation of cadmium in rats with low, marginal and high iron status is affected by the presence of bran in the diet. High iron status caused the total and fractional accumulation of cadmium from both the wheat endosperm and wheat bran diets to be decreased by almost half compared to that in the low iron status rats. The inclusion of wheat bran in the diet increased the total accumulation of cadmium in the liver by approximately the same proportion in all three iron status groups. While the results do not exclude the possibility that the availability of cadmium for absorption from wheat bran is less than that from wheat endosperm in rats with high iron status, no appreciable effect of mineral binding factors in bran on the fractional cadmium accumulation in the liver could be demonstrated in the low and marginal iron status groups. Thus, for rats with less than adequate iron status, the inclusion of wheat bran in the diet should increase the cadmium intake and its accumulation in the body by the same proportion.

A crossover design studying lipid and apoprotein levels in serum and excretion of sterols, ni trogen and fat in ileostomy effluent was performed in 10 subjects fed diets with or without supplementation with brewer's spent grain, which is the residue of barley after the brewing of beer. More cholesterol, nitrogen, fat and energy were excreted in the ileostomy effluents when the subjects consumed a brewer's spent grain supple mented, high fiber diet than when they consumed a low fiber diet. No significant change was found in the daily net sterol excretion. The six subjects with low daily excretion of bue acids (< 1000 mg/24 h) had increased cholesterol and net cholesterol and decreased bile acid excretion per day, and lowered serum LDL-cholesterol and apoprotein B levels after supplementation with brewer's spent grain. We propose that subjects with low daily bile acid excretion are suitable models for studying the effect of dietary changes on sterol excretion and serum lipid levels. Increased fecal cholesterol excretion is suggested to be the primarymechanism for the serum LDL-cholesterol lowering effect of brewer's spent grain. J. Nutr. 121: 778-784, 1991.

Two experiments were conducted to investigate the effect of soy and rye on the development of Dunning R3327 prostatic adenocarcinoma in rats.

The healing of experimental palatal defects and its influence on maxillary growth was studied in 14 beagles operated at 6 to 8 weeks of age. Analogous defects involving the removal of palatal bone and the overlying oral mucoperiosteum were made on each side of the midline. The defect on one side of the midline was covered with an autogenous full-thickness skin graft while that on the opposite side was left to heal by second intention. Healing and maxillary growth were evaluated for up to 46 weeks postoperatively using histological, scanning electron microscopical and biometric techniques. From the time of surgery to the age of 1 year the uncovered area decreased 36 % in size while the area of the skin graft increased 155 %. The presence in the skin graft of hair follicles with the ability to grow hair indicates that the principal structure of the skin graft did not change during the observation period. Nearly complete bone regeneration occurred in the side left uncovered and the palatine suture was in all dogs displaced towards this side. Beneath the skin graft, large bone defects remained and in eight of 10 dogs, a new suturelike structure parallel to the palatine suture was found in the middle. of this side. It is hypothesized that transverse growth on the uncovered side was inhibited due to wound contraction and nearly complete bone regeneration, while translation of bones adjacent to the defect was possible beneath the skin graft due to lower resistance in the skin graft, slow bone formation beneath it and the formation of the suturelike structure. Compensatory growth mechanisms in the dentoalveolar regions permitted the maintenance of proper occlusion.

Serum lipids, lipoprotein (a), plasminogen activator inhibitor and tissue plasminogen activator levels were measured in 260 subjects, constituting a cross-section sample of 30–60-year-old men and women. For Lp(a), there were positive correlations with age and cholesterol, but not with any of other measured parameters. Triglyceride, cholesterol, and HDL-cholesterol (inversely) levels were associated with waist-to-hip girth circumference ratio: this variable remained significant in a multiple regression model. PAI-1 activity and tPA antigen levels were positively associated with triglycerides and inversely associated with HDL-cholesterol. Moreover, tPA antigen was positively related to total cholesterol level. In multiple regression analysis, however, only triglycerides were found to contribute significantly to the variance of tPA antigen and PAI-1 activity levels, when BMI (in men) and abdominal skinfold thickness (in women) were entered into the model. Insulin or glucose postload responses to an OGTT were not independently related to any lipid or fibrinolytic variable. These data demonstrate the importance of anthropometric variables both for fibrinolytic variables and traditional lipid risk factors. Only Lp(a) was found to be largely unrelated to the endocrine-metabolic and anthropometric variables.

Levels of the fibrinolytic variables, tissue plasminogen activator (tPA) antigen concentration and plasminogen activator inhibitor (PAI-1) activity, were measured in a cross sectional sample of 260 subjects aged 30, 40, 50, or 60 years. There was a significant increase of tPA with age in both sexes, but PAI-1 increased only in women. Linear regression analysis was used to assess relations between tPA or PAI-I and the anthropometric data. In men, tPA levels were related to body mass index and waist-to-hip ratio, whereas in women, it was also related to systolic and diastolic blood pressures and with abdominal or triceps skinfold thicknesses. PAI-1 levels were related to body mass index and waist-to-hip ratio in men, and in women it was in addition related to systolic and diastolic blood pressures and to abdominal and triceps skinfold thicknesses. These data offer new insight into pathophysiological mechanisms whereby age, sex, blood pressure, and body composition variables such as body mass index or waist-to-hip ratio, might act as cardiovascular risk factors.