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Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption.
Brickman, AM, Yeung, LK, Alschuler, DM, Ottaviani, JI, Kuhnle, GGC, Sloan, RP, Luttmann-Gibson, H, Copeland, T, Schroeter, H, Sesso, HD, et al
Proceedings of the National Academy of Sciences of the United States of America. 2023;120(23):e2216932120
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“Cognitive aging” is a term used to describe how some of our cognitive abilities decline during the aging process, independent of late-life cognitive diseases. Because cognitive aging is meaningfully disruptive to our lives, it is biomedically justified to identify its etiologic factors. The current study was ancillary to COSMOS and termed COSMOS-Web. COSMOS was designed to examine the effects of cocoa extract and multivitamin supplementation on total cardiovascular disease and total invasive cancer. For this study, the focus is on the cocoa extract intervention only. Participants were randomly assigned to a 3-year intervention of cocoa extract or a placebo. Results showed that a flavanol intervention-based restoration of memory was observed in the lower tertile of habitual diet quality and in the subset of participants with lower habitual flavanol consumption. The improvement in memory was apparent after 12 months of intervention and appeared to be sustained over the 3 years of follow-up. Additionally, diet quality is a key lifestyle factor linked to the hippocampal and not to the prefrontal component of cognitive aging. Authors concluded that habitual flavanol consumption and diet quality at baseline are positively and selectively correlated with hippocampal-dependent memory. Improvements in the flavanol biomarker over the trial were associated with improving memory.
Abstract
Dietary flavanols are food constituents found in certain fruits and vegetables that have been linked to cognitive aging. Previous studies suggested that consumption of dietary flavanols might specifically be associated with the hippocampal-dependent memory component of cognitive aging and that memory benefits of a flavanol intervention might depend on habitual diet quality. Here, we tested these hypotheses in the context of a large-scale study of 3,562 older adults, who were randomly assigned to a 3-y intervention of cocoa extract (500 mg of cocoa flavanols per day) or a placebo [(COcoa Supplement and Multivitamin Outcomes Study) COSMOS-Web, NCT04582617]. Using the alternative Healthy Eating Index in all participants and a urine-based biomarker of flavanol intake in a subset of participants [n = 1,361], we show that habitual flavanol consumption and diet quality at baseline are positively and selectively correlated with hippocampal-dependent memory. While the prespecified primary end point testing for an intervention-related improvement in memory in all participants after 1 y was not statistically significant, the flavanol intervention restored memory among participants in lower tertiles of habitual diet quality or habitual flavanol consumption. Increases in the flavanol biomarker over the course of the trial were associated with improving memory. Collectively, our results allow dietary flavanols to be considered in the context of a depletion-repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging.
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Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors.
Merino, J, Jablonski, KA, Mercader, JM, Kahn, SE, Chen, L, Harden, M, Delahanty, LM, Araneta, MRG, Walford, GA, Jacobs, SBR, et al
Diabetes. 2020;69(1):112-120
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Individual risk of Coronary Artery Disease (CAD) and type 2 diabetes reflects the interplay between lifestyle behaviours acting on a backdrop of genetic predisposition. The aim of this study was to examine whether type 2 diabetes prevention strategies, either an intensive lifestyle intervention (ILS) or metformin treatment (MET), modify the association between CAD genetic risk and cardiometabolic risk factors (CRFs) in participants at high risk of type 2 diabetes. The study is a randomised controlled trial were participants were randomly allocated to one of the three groups; ILS (n = 1,079), MET (850 mg twice daily [n = 1,073]), or placebo (n = 1,082). Results indicate that there weren’t major significant differences in baseline characteristics, except for lower high-density lipoprotein and higher triglyceride in the placebo individuals compared with individuals assigned to MET or ILS. In fact, either an ILS or MET has a beneficial effect on 1-year change in different CRFs. Authors conclude that type 2 diabetes–preventive strategies for individuals at high risk of type 2 diabetes provide beneficial effects on CRFs regardless of CAD genetic risk profile.
Abstract
Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.
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A prospective study of meat and meat mutagens and prostate cancer risk.
Cross, AJ, Peters, U, Kirsh, VA, Andriole, GL, Reding, D, Hayes, RB, Sinha, R
Cancer research. 2005;65(24):11779-84
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Meat cooked at high temperatures is a source of carcinogens (heterocyclic amines and polycyclic aromatic hydrocarbons). The formation of these substances depends on the meat type, and is highest in meats cooked by high-temperature cooking methods. The aim of the study was to determine whether meat intake or meat-related mutagens was associated with increased prostate cancer risk. This was a prospective cohort study of 29,361 men aged between 55 and 74. Results show that a consumption of more than 10 g per day of very well done meat was associated with a 42% increased risk for prostate cancer and a 69% increased risk for incident disease. A high intake of the carcinogens under study was associated with a 22% increased risk for prostate cancer and a 28% increased risk for incident disease. The study concluded that there is a positive association between prostate cancer risk and a high intake of very well done meat.
Abstract
High-temperature cooked meat contains heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP). In rodents, a high intake of PhIP induces prostate tumors. We prospectively investigated the association between meat and meat mutagens, specifically PhIP, and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Diet was assessed using a 137-item food frequency questionnaire and a detailed meat-cooking questionnaire linked to a database for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and PhIP. During follow-up, we ascertained a total of 1,338 prostate cancer cases among 29,361 men; of these, 868 were incident cases (diagnosed after the first year of follow-up) and 520 were advanced cases (stage III or IV or a Gleason score of > or =7). Total, red, or white meat intake was not associated with prostate cancer risk. More than 10 g/d of very well done meat, compared with no consumption, was associated with a 1.4-fold increased risk of prostate cancer [95% confidence interval (95% CI), 1.05-1.92] and a 1.7-fold increased risk (95% CI, 1.19-2.40) of incident disease. Although there was no association with MeIQx and DiMeIQx, the highest quintile of PhIP was associated with a 1.2-fold increased risk of prostate cancer (95% CI, 1.01-1.48) and a 1.3-fold increased risk of incident disease (95% CI, 1.01-1.61). In conclusion, very well done meat was positively associated with prostate cancer risk. In addition, this study lends epidemiologic support to the animal studies, which have implicated PhIP as a prostate carcinogen.
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Effects of alcohol on insulin-like growth factor I and insulin-like growth factor binding protein 3 in postmenopausal women.
Lavigne, JA, Baer, DJ, Wimbrow, HH, Albert, PS, Brown, ED, Judd, JT, Campbell, WS, Giffen, CA, Dorgan, JF, Hartman, TJ, et al
The American journal of clinical nutrition. 2005;81(2):503-7
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Both alcohol and the endocrine hormone insulin-like growth factor (IGF-1) have been linked to increased breast cancer risk. However, the link with breast cancer is stronger in pre-menopausal women but most studies have not distinguished between pre and post-menopausal individuals. This randomly controlled, crossover study looked at how IGF-1 and its major binding protein IGFBP-3 were affected by alcohol in 31 pre-menopausal women, it also considered if levels were affected by the menstrual cycle. The study concluded that there is a link between alcohol and the reduction of IGF-1 but no effect on IGFBP-3 They also found that IGF-1 serum levels significantly increase during the later stages of the menstruation cycle regardless of alcohol intake. Further studies are needed to understand the balance of alcohol intake and how that alters an increase or decrease in breast cancer risk.
Abstract
BACKGROUND Increased circulating insulin-like growth factor I (IGF-I) concentrations, frequently adjusted for IGF binding protein 3 (IGFBP-3), have been associated with increased risk of several types of cancer, including colon, prostate, and breast. Studies have suggested that alcohol may affect IGF-I or IGFBP-3; however, controlled feeding studies to assess alcohol's effects on IGF-I or IGFBP-3 have not been conducted. OBJECTIVE To determine whether chronic, moderate alcohol intake affects serum IGF-I or IGFBP-3 concentrations, we performed a controlled, crossover feeding study. DESIGN Fifty-three postmenopausal women were randomly assigned to consume 0 g (control), 15 g (one drink), or 30 g (2 drinks) alcohol daily for 8 wk and were rotated through the other 2 intake levels in random order. All foods and beverages were provided during the intervention. Individuals were monitored and calories adjusted to maintain constant weight, and serum was collected at the end of each diet period. RESULTS Compared with the effects of 0 g alcohol/d, IGF-I concentrations were nearly unchanged by 15 g alcohol/d (0.8%; 95% CI: -3.2%, 3.5%) but decreased significantly by 4.9% (95% CI: -8.0%, -1.6%) with 30 g alcohol/d. IGFBP-3 concentrations significantly increased by 3.0% (95% CI: 0.4%, 5.6%) with 15 g alcohol/d but did not increase significantly with 30 g/d (1.8%; 95% CI: -0.9%, 4.5%). CONCLUSIONS To our knowledge, this is the first published controlled diet study to find that in postmenopausal women, when weight is kept constant, alcohol consumption reduces the amount of serum IGF-I potentially available for receptor binding. These findings suggest that the effect of alcohol intake should be considered in studies of IGF-I, IGFBP-3, and cancer in postmenopausal women.
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Effects of a 2-year randomized soy intervention on sex hormone levels in premenopausal women.
Maskarinec, G, Franke, AA, Williams, AE, Hebshi, S, Oshiro, C, Murphy, S, Stanczyk, FZ
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2004;13(11 Pt 1):1736-44
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Countries that have a high consumption of soy, such as Japan and China, tend to have lower breast cancer rates. Soy contains isoflavones, phytoestrogens which may have oestrogenic and antieostrogenic effects. The aim of this trial was to examine the effect of soy foods on menstrual cycle length and circulating sex hormone levels. 189 healthy premenopausal women completed the 2-year study, during which the treatment group consumed two daily servings of soy foods (tofu, soy milk, roasted soy nuts, soy protein powder or soy protein bars) containing a total of 50 mg of isoflavones. The control group maintained their regular diet. Blood samples were taken 5 days after ovulation in months 0, 3, 6, 12 and 24. Soy did not have any significant effects on the levels of circulating sex hormones or length of menstrual cycle. The authors concluded that any preventative effects of soy on breast cancer risk may be mediated by mechanisms other than its effect on circulating sex hormone levels.
Abstract
OBJECTIVE Several epidemiologic studies have described protective effects of soy consumption against breast cancer. The goal of this trial among premenopausal women was to examine the effect of soy foods on menstrual cycle length and circulating sex hormone levels. METHODS This 2-year dietary intervention randomized 220 healthy premenopausal women. The intervention group consumed two daily servings of soy foods containing approximately 50 mg of isoflavones; the control group maintained their regular diet. Five blood samples (obtained in months 0, 3, 6, 12, and 24) were taken 5 days after ovulation as determined by an ovulation kit. The serum samples were analyzed for estrone, estradiol, sex hormone binding globulin, androstenedione, and progesterone by immunoassay. RESULTS At baseline, both groups had similar demographic, anthropometric, and nutritional characteristics. The dropout rates of 15.6% (17 of 109) in the intervention group and 12.6% (14 of 111) in the control group did not differ significantly. According to soy intake logs, 24-hour recalls, and urinary isoflavone excretion, the women closely adhered to the study regimen. Menstrual cycles became slightly shorter in both groups but did not differ by group. Mixed general linear models indicated no significant intervention effect on any of the serum hormones. However, androstenedione and progesterone decreased significantly over time in both groups. CONCLUSIONS The results of this study suggest that the preventive effects of soy on breast cancer risk in premenopausal women may not be mediated by circulating sex hormone levels. Different mechanisms of actions or effects of exposure earlier in life are alternate hypotheses that require further investigation.
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Antioxidant supplementation and nasal inflammatory responses among young asthmatics exposed to high levels of ozone.
Sienra-Monge, JJ, Ramirez-Aguilar, M, Moreno-Macias, H, Reyes-Ruiz, NI, Del Río-Navarro, BE, Ruiz-Navarro, MX, Hatch, G, Crissman, K, Slade, R, Devlin, RB, et al
Clinical and experimental immunology. 2004;138(2):317-22
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Exposure to air pollution has been related to an increased occurrence and severity of asthma. In this double-blind, randomised trial, a group of asthmatic children in Mexico City were given either a daily supplement containing 250mg of vitamin C and 50mg of vitamin E, or a placebo pill, for 12 weeks. Scientists measured inflammatory markers in the nasal passages of the children after being exposed to air pollution. Children who received the vitamin supplement did not experience an increase in inflammation after being exposed to air pollution, whereas children given the placebo did. The authors concluded that supplementation with antioxidants such as vitamin C and vitamin E might decrease nasal inflammation in children with asthma who are exposed to air pollution.
Abstract
The inflammatory response to ozone in atopic asthma suggests that soluble mediators of inflammation are released in response to oxidant stress. Antioxidants may alleviate additional oxidative stress associated with photochemical oxidant pollution. This study investigates the impact of antioxidant supplementation on the nasal inflammatory response to ozone exposure in atopic asthmatic children. We conducted a randomized trial using a double-blinded design. Children with asthma (n = 117), residents of Mexico City, were given randomly a daily supplement of vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin C) or placebo. Nasal lavages were performed three times during the 4-month follow-up and analysed for content of interleukin-6 (IL-6), IL-8, uric acid and glutathione (GSx). IL-6 levels in the nasal lavage were increased significantly in the placebo group after ozone exposure while no increase was observed in the supplement group. The difference in response to ozone exposure between the two groups was significant (P = 0.02). Results were similar for IL-8, but with no significant difference between the groups (P = 0.12). GSx decreased significantly in both groups. Uric acid decreased slightly in the placebo group. Our data suggest that vitamin C and E supplementation above the minimum dietary requirement in asthmatic children with a low intake of vitamin E might provide some protection against the nasal acute inflammatory response to ozone.
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Partial purification and characterization of extrinsic pathway inhibitor (the factor Xa-dependent plasma inhibitor of factor VIIa/tissue factor).
Warn-Cramer, BJ, Maki, SL, Zivelin, A, Rapaport, SI
Thrombosis research. 1987;48(1):11-22
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Green tea (GT) consumption has been associated with the prevention and control of type 2 diabetes, cardiovascular and metabolic disease as well as having a positive effect on body weight and composition. However, the polyphenols in GT have been shown to interact with mineral distribution within the body and those minerals have been shown to be deficient in obesity. Studies to measure mineral status in obese subjects supplementing with GT have been inconclusive and this study aimed to measure the serum concentrations of minerals (calcium, copper, iron, zinc, magnesium), body mass index, total antioxidant status (TAS), lipid profile and glucose concentration. 46 obese patients were randomised into 2 groups, one group were supplemented with 279mg of green tea extract (GTE) and 208mg of the polyphenol epigallocatechin-3-gallate (EGCG) and the other group were issued with a placebo for 3 months. The study concluded that GTE improved Zn and Mg, however decreased levels of FE. The results confirmed a positive effect on body mass, lipid profile, glucose and TAS. It was concluded that more studies are required on a larger population over a longer period of time.
Abstract
We report a procedure to purify partially from plasma (approximately 1200 fold) the factor Xa-dependent inhibitor of factor VIIa/tissue factor (i.e., the extrinsic pathway inhibitor or EPI) and describe some of its properties. An assay for EPI was developed based upon inhibition of factor VIIa/tissue factor induced release of activation peptide from tritiated factor IX by a test sample in the presence but not in the absence of factor Xa. Approximately 50% of the total EPI activity in plasma was found in the lipoprotein fraction, which was used as the starting material for purification. Total lipoproteins (isolated by density ultracentrifugation) were delipidated and the urea soluble apoproteins gel filtered on Sephacryl S-200. The inhibitory activity co-eluted with the major protein peak, which primarily contained apoprotein A-I. Inhibitory activity was separated from apoprotein A-I by anion-exchange chromatography on Q-Sepharose and was further resolved from higher and lower molecular weight contaminating proteins by polypreparative disc gel electrophoresis in the presence of 0.1% SDS. Functional inhibitory activity eluted from the polypreparative disc gel in two discrete pools of different molecular weights (approximately 34,000 and approximately 43,000 D). Apoprotein E was identified by immunological techniques as the major protein present in both of these pools. However, incubation with a monospecific polyclonal antibody to human apoprotein E did not decrease EPI activity either in plasma or in the partially purified polypreparative disc gel fractions. A rabbit antiserum was prepared against material from the polypreparative disc gel. The IgG fraction neutralized approximately 95% of the total inhibitory activity present in plasma. Therefore, EPI in the lipoprotein fraction and in the non-lipoprotein fraction of plasma appears to be antigenically similar.