Dietary intake of nitrate and nitrite and risk of renal cell carcinoma in the NIH-AARP Diet and Health Study

Background: Nitrate and nitrite are present in many foods and are precursors of N-nitroso compounds, known animal carcinogens and potential human carcinogens. We prospectively investigated the association between nitrate and nitrite intake from dietary sources and risk of renal cell carcinoma (RCC) overall and clear cell and papillary histological subtypes in the NIH-AARP Diet and Health Study. Methods: Nitrate and nitrite intakes were estimated from a 124-item food frequency questionnaire. Over a mean follow-up of 9 years, we identified 1816 RCC cases (n=498, clear cell; n=115, papillary cell) among 491 841 participants. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Individuals in the highest quintile of nitrite intake from animal sources compared with those in the lowest quintile, had an increased risk of total RCC and clear cell subtype (HR=1.28, 95% CI, 1.10–1.49 and HR=1.68, 95% CI, 1.25–2.27, respectively). Nitrite from processed meats and other animal sources were associated with increased clear cell adenocarcinoma risk (HR=1.33, 95% CI, 1.01–1.76 and HR=1.78, 95% CI, 1.34–2.36, respectively). We found no association for nitrite intake from plant sources or nitrate intake overall. Conclusion: Our findings suggest that nitrite from animal sources may increase the risk of RCC, particularly clear cell adenocarcinomas.

Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study

Background Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons. We comprehensively investigated the association between meat and meat components and bladder cancer. Methods During 7 years of follow-up, 854 transitional cell bladder cancer cases were identified among 300,933 men and women who completed a validated food frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. We estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat using quantitative databases of measured values. We calculated total dietary nitrate and nitrite based on literature values. Results The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth compared to first quintile=1.22, 95% CI=0.96–1.54, p-trend=0.07) and the HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (HR=1.19, 95% CI=0.95–1.48, p-trend=0.06) conferred a borderline statistically significant increased risk of bladder cancer. We observed positive associations in the top quintile for total dietary nitrite (HR=1.28, 95% CI=1.02–1.61, p-trend= 0.06) and nitrate plus nitrite intake from processed meat (HR=1.29 95% CI=1.00–1.67, p-trend= 0.11). Conclusions These findings provide modest support for a role for total dietary nitrite and nitrate plus nitrite from processed meat in bladder cancer. Our results also suggest a positive association between red meat and PhIP and bladder carcinogenesis.

Intake of fiber and fiber-rich plant foods is associated with a lower risk of renal cell carcinoma in a large US cohort

Background: Plant-based and fiber-rich diets high in vegetables, fruit, and whole grains are recommended to prevent cancer and chronic conditions associated with renal cell carcinoma (RCC), such as obesity, hypertension, and diabetes. Diet may play a role in the etiology of RCC directly and/or indirectly. Objective: In a large prospective cohort of US men and women, we comprehensively investigated dietary intake and food sources of fiber in relation to RCC risk. Design: Participants of the NIH-AARP Diet and Health Study (n = 491,841) completed a self-administered questionnaire of demographics, diet, lifestyle, and medical history. Over 9 (mean) years of follow-up we identified 1816 incident cases of RCC. HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. Results: Total dietary fiber intake was associated with a significant 15–20% lower risk of RCC in the 2 highest quintiles compared with the lowest (P-trend = 0.005). Intakes of legumes, whole grains, and cruciferous vegetables were also associated with a 16–18% reduced risk of RCC. Conversely, refined grain intake was positively associated with RCC risk in a comparison of quintile 5 with quintile 1 (HR: 1.19; 95% CI: 1.02, 1.39; P-trend = 0.04). The inverse association between fiber intake and RCC was consistent among participants who never smoked, had a body mass index [BMI (in kg/m2)] <30, and did not report a history of diabetes or hypertension. Conclusions: Intake of fiber and fiber-rich plant foods was associated with a significantly lower risk of RCC in this large US cohort. This trial was registered at clinicaltrials.gov as NCT00340015.

Meat intake and mortality: a prospective study of over half a million people

Context High intakes of red or processed meat may increase risk of mortality. Objective Determine the relations of red, white and processed meat intakes to risk for total, and cause-specific mortality. Design, Setting, and Participants The NIH-AARP Diet and Health Study cohort of half a million people aged 50-71 years at baseline. Meat intake was estimated from a food frequency questionnaire administered at baseline. Cox proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of meat intake. The covariates included in the models were: age; education; marital status; family history of cancer (yes/no) (cancer mortality only); race; body mass index; 31-level smoking history; physical activity; energy intake; alcohol intake; vitamin supplement use; fruit consumption; vegetable consumption; and menopausal hormone therapy among women. Main Outcome Measure Total mortality, deaths due to cancer, CVD, accidents, and other causes. Results There were 47,976 male deaths and 23,276 female deaths during 10 years of follow-up. Men and women in the highest versus lowest quintile of red (HR 1.31, 95% CI 1.27-1.35; HR 1.36, 95% CI 1.30-1.43, respectively) and processed meat intake (HR 1.16, 95% CI 1.12-1.20; HR 1.25, 95% 1.20-1.31, respectively) had elevated risks for overall mortality. Regarding cause-specific mortality, men and women had elevated risks for cancer mortality for red (HR 1.22, 95% CI 1.16-1.29; HR 1.20, 95% CI 1.12-1.30, respectively) and processed meats (HR 1.12, 95% CI 1.06-1.19; HR 1.11, 95% CI 1.04-1.19, respectively). Furthermore, CVD risk was elevated for men and women in the highest quintile of red (HR 1.27, 95% CI 1.20-1.35; HR 1.50, 95% CI 1.37-1.65, respectively) and processed meat (HR 1.09, 95% CI 1.03-1.15; HR 1.38, 95% CI 1.26-1.51, respectively). When comparing the highest to the lowest quintile of white meat intake, there was an inverse association for total mortality, and cancer mortality, as well as all other deaths for both men and women. Conclusion Red and processed meat intakes were associated with modest increases in total mortality, cancer mortality and CVD mortality.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe: results from the Europea...

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.

Diet, Lifestyle, and Acute Myeloid Leukemia in the NIH–AARP Cohort

The relation between diet, lifestyle, and acute myeloid leukemia was assessed in a US cohort of 491,163 persons from the NIH–AARP Diet and Health Study (1995–2003). A total of 338 incident cases of acute myeloid leukemia were ascertained. Multivariate Cox models were utilized to estimate hazard ratios and 95% confidence intervals. Compared with those for never smokers, hazard ratios were 1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32, 2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence interval: 1.38, 3.79) for former smokers who smoked ≤1 or >1 pack/day and for current smokers who smoked ≤1 or >1 pack/day, respectively. Higher meat intake was associated with an increased risk of acute myeloid leukemia (hazard ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first quintile; P for trend = 0.06); however, there were no clear effects of meat-cooking method or doneness level. Individuals who did not drink coffee appeared to have a higher risk of acute myeloid leukemia than those who drank various quantities of coffee. Neither fruit nor vegetable intake was associated with acute myeloid leukemia. This large prospective study identified smoking and meat intake as risk factors for acute myeloid leukemia.

Intensity and timing of physical activity in relation to postmenopausal breast cancer risk: the prospective NIH-AARP Diet and Health Study

Background Despite strong evidence of an inverse association of physical activity with postmenopausal breast cancer risk, whether a certain intensity or time of life of physical activity is most effective for lowering breast cancer risk is not known. Methods In 118,899 postmenopausal women in the prospective NIH-AARP Diet and Health Study, we examined the relations of light and moderate-to-vigorous intensity physical activity during four periods of life ("historical": ages 15-18, 19-29, 35-39 years; "recent": past 10 years) to postmenopausal breast cancer risk. Physical activity was assessed by self-report at baseline, and 4287 incident breast cancers were identified over 6.6 years of follow-up. Results In age-adjusted and multivariate Cox regression models, >7 hours/week of moderate-to-vigorous activity during the past 10 years was associated with 16% reduced risk of postmenopausal breast cancer (RR:0.84; 95%CI:0.76,0.93) compared with inactivity. The association remained statistically significant after adjustment for BMI (RR:0.87; 95%CI:0.78,0.96). Neither moderate-to-vigorous activity during other periods of life nor light intensity activity during any period of life was related to breast cancer risk, and associations did not vary by tumor characteristics. Conclusion A high level of recent, but not historical, physical activity of moderate-to-vigorous intensity is associated with reduced postmenopausal breast cancer risk. More precise recall of recent physical activity than activity in the distant past is one possible explanation for our findings.

Sweetened Beverages, Coffee, and Tea and Depression Risk among Older US Adults

Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995–1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17–1.44) for soft drinks, 1.38 (1.15–1.65) for fruit drinks, and 0.91 (0.84–0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16–1.47) for diet versus 1.22 (1.03–1.45) for regular soft drinks, 1.51 (1.18–1.92) for diet versus 1.08 (0.79–1.46) for regular fruit drinks, and 1.25 (1.10–1.41) for diet versus 0.94 (0.83–1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.

Dietary Fatty Acids and Pancreatic Cancer in the NIH-AARP Diet and Health Study

Background Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive. Methods We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health–AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995–1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided. Results Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; Ptrend  = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; Ptrend < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; Ptrend = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; Ptrend < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively). Conclusion In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.

US medical researchers, the Nuremberg Doctors Trial, and the Nuremberg Code. A review of findings of the Advisory Committee on Human Radiation Expe...

The Advisory Committee on Human Radiation Experiments (ACHRE), established to review allegations of abuses of human subjects in federally sponsored radiation research, was charged with identifying appropriate standards to evaluate the ethics of cold war radiation experiments. One central question for ACHRE was to determine what role, if any, the Nuremberg Code played in the norms and practices of US medical researchers. Based on the evidence from ACHRE's Ethics Oral History Project and extensive archival research, we conclude that the Code, at the time it was promulgated, had little effect on mainstream medical researchers engaged in human subjects research. Although some clinical investigators raised questions about the conduct of research involving human beings, the medical profession did not pursue this issue until the 1960s.

Relationship between funding sources and outcomes of obesity-related research.

This study examined the relationship between funding sources and the outcomes of published obesity-related research. A list of funded projects for human nutrition research linking food intake to obesity in 2001-2005 was drawn from two distinct sources: (a) the federal government's semi-public generic commodity promotion or "checkoff" programs for Fluid Milk and Dairy and (b) the National Institutes of Health (NIH). The Principal Investigator for each funded project was determined. Published literature by that individual was located using an Ovid MEDLINE and PubMed author search. All articles related to both dairy and obesity were included. Financial sponsorship for each article and article conclusions were classified by independent groups of co-investigators. Seventy-nine relevant articles were included in the study. Of these, 62 were sponsored by the checkoff programs and 17 by the NIH. The study did not find consistent evidence that checkoff-funded projects were more likely to support an obesity prevention benefit from dairy consumption. The study did identify a new research methodology for the investigation of bias by source of sponsorship. Copyright © 2012 Elsevier Inc. All rights reserved.

Lead, Mercury, and Arsenic in US- and Indian-Manufactured Ayurvedic Medicines Sold via the Internet

Context Lead, mercury, and arsenic have been detected in a substantial proportion of Indian-manufactured traditional Ayurvedic medicines. Metals may be present due to the practice of rasa shastra (combining herbs with metals, minerals, and gems). Whether toxic metals are present in both US- and Indian-manufactured Ayurvedic medicines is unknown. Objectives To determine the prevalence of Ayurvedic medicines available via the Internet containing detectable lead, mercury, or arsenic and to compare the prevalence of toxic metals in US- vs Indian-manufactured medicines and between rasa shastra and non–rasa shastra medicines. Design A search using 5 Internet search engines and the search terms Ayurveda and Ayurvedic medicine identified 25 Web sites offering traditional Ayurvedic herbs, formulas, or ingredients commonly used in Ayurveda, indicated for oral use, and available for sale. From 673 identified products, 230 Ayurvedic medicines were randomly selected for purchase in August–October 2005. Country of manufacturer/Web site supplier, rasa shastra status, and claims of Good Manufacturing Practices were recorded. Metal concentrations were measured using x-ray fluorescence spectroscopy. Main Outcome Measures Prevalence of medicines with detectable toxic metals in the entire sample and stratified by country of manufacture and rasa shastra status. Results One hundred ninety-three of the 230 requested medicines were received and analyzed. The prevalence of metal-containing products was 20.7% (95% confidence interval [CI], 15.2%–27.1%). The prevalence of metals in US-manufactured products was 21.7% (95% CI, 14.6%–30.4%) compared with 19.5% (95% CI, 11.3%–30.1%) in Indian products (P=.86). Rasa shastra compared with non–rasa shastra medicines had a greater prevalence of metals (40.6% vs 17.1%; P=.007) and higher median concentrations of lead (11.5 μg/g vs 7.0 μg/g; P=.03) and mercury (20 800 μg/g vs 34.5 μg/g; P=.04). Among the metal-containing products, 95% were sold by US Web sites and 75% claimed Good Manufacturing Practices. All metal-containing products exceeded 1 or more standards for acceptable daily intake of toxic metals. Conclusion One-fifth of both US-manufactured and Indian-manufactured Ayurvedic medicines purchased via the Internet contain detectable lead, mercury, or arsenic.

MULTIVITAMIN USE AND RISK OF CANCER AND CARDIOVASCULAR DISEASE IN THE WOMEN’S HEALTH INITIATIVE COHORTS

Context Millions of postmenopausal women use multivitamins, often believing that supplements prevent chronic diseases such as cancer and cardiovascular disease. Objective To examine associations between multivitamin use and risk of cancer, cardiovascular disease and mortality in postmenopausal women. Design, Setting and Participants 161,808 participants from the Women’s Health Initiative Clinical Trials (n=68,132 in three overlapping trials of hormone therapy, dietary modification and calcium-vitamin D) or Observational Study (n=93,676). Detailed data were collected on multivitamin use at baseline and follow-up time points. Study enrollment occurred between 1993–1998; women were followed for a median of 8.0 years in the clinical trials and 7.9 years in the observational study. Disease endpoints were collected through 2005. Outcome Measures Cancers of the breast (invasive), colon/rectum, endometrium, kidney, bladder, stomach, ovary and lung; cardiovascular disease (myocardial infarction, stroke, venous thrombosis); and total mortality. Results 41.5% of participants used multivitamins. After a median of 8.0 years of follow-up in the CT and 7.9 years in the OS, 9,619 cases of breast, colorectal, endometrium, kidney, bladder, stomach lung or ovary cancer; 8,751 CVD events and 9,865 deaths were reported. Multivariate-adjusted analyses revealed no association of multivitamins with risk of cancer (breast HR=0.98, 95%CI 0.91–1.05; colorectal HR = 0.99, 95% CI 0.88–1.11; endometrial HR = 1.05, 95%CI= 0.90–1.21; lung HR = 1.0, 95% CI=0.88–1.13; ovary HR = 1.07, 95%CI =0.88–1.29); CVD (MI HR= 0.96, 95%CI= 0.89–1.03; stroke HR = 0.99, 95%CI =0.91–1.07; VT HR = 1.05, 95%CI =0.85–1.29); or mortality (HR = 1.02, 95% CI=0.97–1.07). Conclusion After a median follow-up of 8.0 and 7.9 years in the CT and OS, respectively, the WHI cohorts provide convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease or total mortality in postmenopausal women. Clinical Trial Registration clinicaltrials.gov identifier: NCT00000611

Monoamine theories of depression: historical impact on biomedical research.

Monoamine theories associate depression with reduced brain monoamine levels. These theories achieved broad popularity in the mid-1960s. The present article reviews the historical development of monoamine theories and their subsequent impact on biomedical research. Alleged divisions between West European and US researchers over competing versions of the theories are investigated using bibliometrics. Subsequently, the application of monoamine theories in the NIMH Collaborative Program on the Psychobiology of Depression is covered. The article argues that the impact of monoamine theories is best explained by the ability of researchers, governmental agencies, and pharmaceutical companies to invoke theories that advance various projects and agendas.

A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

OBJECTIVE: To investigate the possible role of the maternal diet, particularly vegetarianism and consumption of phytoestrogens, in the origin of hypospadias, which is reported to be increasing in prevalence. SUBJECTS AND METHODS: Detailed information was obtained prospectively from mothers, including previous obstetric history, lifestyle and dietary practices, using structured self-completed questionnaires during pregnancy. Previously recognized associations with environmental and parental factors were examined, focusing particularly on the hypothesized hormonal link. Multivariate logistic regression was used to identify independent associations. RESULTS: Of 7928 boys born to mothers taking part in the Avon Longitudinal Study of Pregnancy and Childhood, 51 hypospadias cases were identified. There were no significant differences in the proportion of hypospadias cases among mothers who smoked, consumed alcohol or for any aspect of their previous reproductive history (including the number of previous pregnancies, number of miscarriages, use of the contraceptive pill, time to conception and age at menarche). Significant differences were detected for some aspects of the maternal diet, i.e. vegetarianism and iron supplementation in the first half of pregnancy. Mothers who were vegetarian in pregnancy had an adjusted odds ratio (OR) of 4.99 (95% confidence interval, CI, 2.10-11.88) of giving birth to a boy with hypospadias, compared with omnivores who did not supplement their diet with iron. Omnivores who supplemented their diet with iron had an adjusted OR of 2.07 (95% CI, 1.00-4.32). The only other statistically significant association for hypospadias was with influenza in the first 3 months of pregnancy (adjusted OR 3.19, 95% CI 1.50-6.78). CONCLUSION: As vegetarians have a greater exposure to phytoestrogens than do omnivores, these results support the possibility that phytoestrogens have a deleterious effect on the developing male reproductive system.

Adherence to WCRF/AICR cancer prevention recommendations and risk of post-menopausal breast cancer

Background In 2007 the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) released eight recommendations related to body fatness, physical activity and diet aimed at preventing the most common cancers worldwide. However, limited information exists on the association between meeting these recommendations and risks of specific cancers, including breast cancer. Methods We operationalized six recommendations (related to body fatness, physical activity, foods that promote weight gain, plant foods, red and processed meats, and alcohol) and examined their association with invasive breast cancer incidence over 6.7 years of follow-up in the VITamins And Lifestyle (VITAL) study cohort. Participants included 30,797 post-menopausal women ages 50–76 years at baseline in 2000–2002 with no history of breast cancer. Breast cancers (n=899) were tracked through the Western Washington Surveillance, Epidemiology and End Results (SEER) database. Results Breast cancer risk was reduced by 60% in women who met at least five recommendations compared to those who met none (HR: 0.40; 95% CI: 0.25–0.65; Ptrend<0.001). Further analyses that sequentially removed individual recommendations least associated with reduced risk suggested that this reduction is due to meeting recommendations related to body fatness, plant foods and alcohol (HR for meeting vs. not meeting these three recommendations: 0.38; 95% CI: 0.25–0.58; Ptrend <0.001). Conclusions Meeting the WCRF/AICR cancer prevention recommendations, specifically those related to alcohol, body fatness and plant foods, is associated with reduced post-menopausal breast cancer incidence. Impact Increased adherence to the WCRF/AICR cancer prevention recommendations could substantially reduce post-menopausal breast cancer risk in US women.

Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good

Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin – an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain’s susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of antidepressants are warranted.

Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study.

Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.

Aggressiveness and brain amine concentration in dominant and subordinate finishing pigs fed the beta-adrenoreceptor agonist ractopamine.

Under farm conditions, aggression related to the formation of social hierarchy and competition for resources can be a major problem because of associated injuries, social stress, and carcass losses. Any factor that may affect the regulation and amount of aggression within a farmed system, for instance, feeding the beta-adrenoreceptor agonist ractopamine (RAC), is therefore worthy of investigation. The objectives of this study were to assess the effects of the widely used swine feed additive RAC, considering also the effects of sex and social rank on aggressiveness and concentrations of brain amines, neurotransmitters essential for controlling aggression, in finishing pigs. Thirty-two barrows and 32 gilts (4 pigs/pen by sex) were fed either a control diet or a diet with RAC (Paylean, Elanco Animal Health, Greenfield, IN) added (5 mg/kg for 2 wk, followed by 10 mg/kg for 2 wk). The top dominant and bottom subordinate pigs (16 pigs/sex) in each pen were determined after mixing by a 36-h period of continuous behavioral observation. These pigs were then subjected to resident-intruder tests (maximum 300 s) during the feeding trial to measure aggressiveness. At the end of wk 4, the amygdala, frontal cortex, hypothalamus, and raphe nuclei were dissected and analyzed for concentrations of dopamine (DA); serotonin (5-HT); their metabolites 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA), respectively; norepinephrine; and epinephrine using HPLC. Ractopamine-fed gilts performed more attacks during the first 30 s of testing than pigs in all other subgroups (P < 0.05). By the end of the resident-intruder test (300 s), the dominant control gilts and barrows, and both dominant and subordinate RAC-fed gilts performed the greatest percentage of attacks (P < 0.05). Gilts had decreased norepinephrine and DOPAC concentrations in the amygdala and frontal cortex, and when fed RAC, gilts also had the least 5-HIAA concentration and greatest DA turnover rate in the amygdala (P < 0.05). The 5-HT concentration was less in the frontal cortex of gilts compared with barrows and in the raphe nuclei (single site for brain 5-HT synthesis) of dominant gilts (P < 0.05). Ractopamine may be affecting aggressive behavior through indirect action on central regulatory mechanisms such as the DA system. The aggressive pattern observed in the tested pigs, especially in gilts, is likely linked to brain monoamine profiling of a deficient serotonergic system in the raphe nuclei, amygdala, and frontal cortex, and enhanced DA metabolism in the amygdala, brain areas vital for aggression regulation.

Smoking and lung cancer risk in American and Japanese men: an international case-control study.

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.

Higher Diet Quality Is Associated with Decreased Risk of All-Cause, Cardiovascular Disease, and Cancer Mortality among Older Adults

Increased attention in dietary research and guidance has been focused on dietary patterns, rather than on single nutrients or food groups, because dietary components are consumed in combination and correlated with one another. However, the collective body of research on the topic has been hampered by the lack of consistency in methods used. We examined the relationships between 4 indices—the Healthy Eating Index–2010 (HEI-2010), the Alternative Healthy Eating Index–2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)—and all-cause, cardiovascular disease (CVD), and cancer mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124-item food-frequency questionnaire were used to calculate scores; adjusted HRs and 95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and 29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were associated with a 12–28% decreased risk of all-cause, CVD, and cancer mortality. Specifically, comparing the highest with the lowest quintile scores, adjusted HRs for all-cause mortality for men were as follows: HEI-2010 HR: 0.78 (95% CI: 0.76, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.78), aMED HR: 0.77 (95% CI: 0.75, 0.79), and DASH HR: 0.83 (95% CI: 0.80, 0.85); for women, these were HEI-2010 HR: 0.77 (95% CI: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76 (95% CI: 0.73, 0.79), and DASH HR: 0.78 (95% CI: 0.75, 0.81). Similarly, high adherence on each index was protective for CVD and cancer mortality examined separately. These findings indicate that multiple scores reflect core tenets of a healthy diet that may lower the risk of mortality outcomes, including federal guidance as operationalized in the HEI-2010, Harvard’s Healthy Eating Plate as captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized aMED, and the DASH Eating Plan as included in the DASH score.

What benefit do patients expect from adding second and third antihypertensive drugs?

Aims To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. Methods This was an anonymous questionnaire survey carried out in a single primary care group. A random sample of patients from the practice list stratified by age and gender were surveyed to determine what benefit they required before deciding to receive first and subsequent drugs to treat hypertension. They were asked to indicate the largest number needing treatment for 5 years (NNT5) to prevent myocardial infarction in 1 (smallest benefit) that would persuade them of the need for treatment. Demographic information which might explain variability in enthusiasm for treatment was also collected. Results Participants required far higher benefit to consider drug treatment than expected with a mean NNT5 for the first treatment of 15.0 (95% CI 12.3, 17.8). Marginal benefit demanded for the addition of second and third treatments was at least as great with an NNT5 of 13.2 (95% CI 10.8, 15.7) and NNT5 of 11.0 (95% CI 8.6, 13.4). Additional factors influencing willingness to take treatment were gender with a difference in NNT5 between men and women of 7.1 (95% CI 1.7, 12.5), difficulty in making the decision (very easy vs very difficult) of 14.9 (95% CI 6.0, 23.8), and years in full time education 2.0 (95% CI 0.9, 3.0) for each additional year of education. Any slope of NNT5 with increasing number of tablets disappeared when gender, years in education, and difficulty in reaching a decision were taken into account simultaneously. Conclusions People may have greater expectation of benefit from antihypertensive drug treatment than it provides. They certainly do not view the addition of subsequent drugs as any lesser step than starting the first in terms of the benefit expected. Full understanding of both the risks and benefits may be of critical importance with those spending longer in full time education and those expending more effort in making the decision accepting more treatment. The discrepancy between benefit expected and that available demands further research into methods of determining patients’ expectations and informing individual patient decisions.

Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial

Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.

Egg Consumption and Risk of Type 2 Diabetes in Men and Women

OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.

Epidemilogical trends strongly suggest exposures as etiologic agents in the pathogenesis of sporadic Alzheimer's disease, diabetes mellitus, and no...

Nitrosamines mediate their mutagenic effects by causing DNA damage, oxidative stress, lipid peroxidation, and pro-inflammatory cytokine activation, which lead to increased cellular degeneration and death. However, the very same pathophysiological processes comprise the "unbuilding" blocks of aging and insulin-resistance diseases including, neurodegeneration, diabetes mellitus (DM), and non-alcoholic steatohepatitis (NASH). Previous studies demonstrated that experimental exposure to streptozotocin, a nitrosamine-related compound, causes NASH, and diabetes mellitus Types 1, 2 and 3 (Alzheimer (AD)-type neurodegeneration). Herein, we review evidence that the upwardly spiraling trends in mortality rates due to DM, AD, and Parkinson's disease typify exposure rather than genetic-based disease models, and parallel the progressive increases in human exposure to nitrates, nitrites, and nitrosamines via processed/preserved foods. We propose that such chronic exposures have critical roles in the pathogenesis of our insulin resistance disease pandemic. Potential solutions include: 1) eliminating the use of nitrites in food; 2) reducing nitrate levels in fertilizer and water used to irrigate crops; and 3) employing safe and effective measures to detoxify food and water prior to human consumption. Future research efforts should focus on refining our ability to detect and monitor human exposures to nitrosamines and assess early evidence of nitrosamine-mediated tissue injury and insulin resistance.

A modest proposal for a longitudinal study of dementia prevention (with apologies to Jonathan Swift, 1729).

Many studies have documented the role of risk and protective factors for late life dementing illnesses, particularly Alzheimer's disease. A "Systematic Review" from the US Agency for Healthcare Research and Quality and the National Institute on Aging concluded that because the overall quality of evidence was low, recommendations for public health could not be made. In order to gain evidence for the efficacy of lifestyle interventions, we propose a "Modest Proposal" to study 10,000 subjects over 40 years randomly assigned to groups of low or high saturated fat in the diet, head injury, and high or low levels of mental activity, physical activity, or inactivity as well as smoking or non-smoking. This proposed study cannot be accomplished. The "Modest Proposal" illustrates that the absence of definitive evidence should not restrict physicians from making reasonable recommendations based on the evidence that is available.

Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population.

Urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are a class of PAH metabolites used as biomarkers for assessing human exposure to PAHs. The Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) uses OH-PAHs to establish reference range concentrations for the US population, and to set benchmarks for future epidemiologic and biomonitoring studies. For the years 2001 and 2002, 22 OH-PAH metabolites were measured in urine specimens from 2748 NHANES participants. Percentages of samples with detectable levels ranged from nearly 100% for metabolites of naphthalene, fluorene, phenanthrene, and pyrene, to less than 5% for metabolites from parent compounds with higher molecular weight such as chrysene, benzo[c]phenanthrene, and benz[a]anthracene. The geometric mean for 1-hydroxypyrene (1-PYR)--the most commonly used biomarker for PAH exposure--was 49.6 ng/L urine, or 46.4 ng/g creatinine. Children (ages 6-11) generally had higher levels than did adolescents (ages 12-19) or adults (ages 20 and older). Model-adjusted, least-square geometric means for 1-PYR were 87, 53 and 43 ng/L for children, adolescents (ages 12-19) and adults (ages 20 years and older), respectively. Log-transformed concentrations for major detectable OH-PAHs were significantly correlated with each other. The correlation coefficients between 1-PYR and other metabolites ranging from 0.17 to 0.63 support the use of 1-PYR as a useful surrogate representing PAH exposure.

Sociodemographic and Lifestyle Statistics of Oldest Old People (>80 Years) Living in Ikaria Island: The Ikaria Study

Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the “Blue Zones”. Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the “Blue Zones”. The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study. Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures. Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression. Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the “secrets” of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life.

Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk o...

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% CI: 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.

The Free Radical Theory of Aging Revisited: The Cell Signaling Disruption Theory of Aging

Significance: The free radical theory of aging has provided a theoretical framework for an enormous amount of work leading to significant advances in our understanding of aging. Up to the turn of the century, the theory received abundant support from observations coming from fields as far apart as comparative physiology or molecular biology. Recent Advances: Work from many laboratories supports the theory, for instance showing that overexpression of antioxidant enzymes results in increases in life-span. But other labs have shown that in some cases, there is an increased oxidative stress and increased longevity. The discovery that free radicals can not only cause molecular damage to cells, but also serve as signals; led to the proposal that they act as modulators of physiological processes. For instance, reactive oxygen species (ROS) stimulate physiological adaptations to physical exercise. Critical Issues: A critical blow to the free radical theory of aging came from epidemiological studies showing that antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death. Moreover, recent molecular evidence has shown that increasing generation of ROS, in some cases, increases longevity. Future Directions: Gerontologists interested in free radical biology are at a crossroads and clearly new insights are required to clarify the role of ROS in the process of aging. The hurdles are, no doubt, very high, but the intellectual and practical promise of these studies is of such magnitude that we feel that all efforts will be generously rewarding. Antioxid. Redox Signal. 19, 779–787.

The effect of dietary factors on nitrosoproline levels in human urine.

The effect of dietary components on the levels of nitrosoproline ( NPRO ) excreted over a 24 h period in the urine was examined in volunteers ingesting known amounts of various food products. The ingestion of nitrite-preserved meats (85-170 g per meal), including canned, rolled or Yunnan ham, cured pork, luncheon meat, and various Chinese and European-style sausages, led to urinary NPRO excretion levels ranging from 2.5 to 78.5 micrograms/24 h, whereas the consumption of non-preserved meat and fish products, including chicken, herring, salmon, shrimp, ground beef (hamburger), pork chops and beef liver, led to relatively low NPRO excretion levels, ranging from 0.0 to 0.8 micrograms/24 h. The urinary NPRO levels of 22 vegetarians and 14 lacto-vegetarians averaged 0.8 and 1.4 micrograms/24 h, respectively. A change from a nitrite-preserved meat diet to a vegetarian diet was accompanied by an approximately six-fold reduction in urinary NPRO levels; however, these remained above control levels for at least 3 days following the dietary change. The relatively high NPRO levels following the ingestion of nitrite-preserved meats could not be reduced by nitrite-trapping chemicals, including ascorbic acid, ferulic acid, caffeic acid, or phenolic-containing mixtures such as coffee and tea, which were effective in suppressing endogenous NPRO formation following the intake of nitrate and proline. The high urinary NPRO levels after ingestion of preserved meat products appear to be due to the consumption of preformed NPRO . An understanding of the relative contribution of preformed and endogenously formed nitrosamines appears to be essential when designing dietary intervention programmes.

Review of epidemiologic studies of dietary acrylamide intake and the risk of cancer.

Conjectured associations between dietary acrylamide intake and cancer have been evaluated in more than 15 epidemiologic studies examining almost every major cancer site. We have critically reviewed the epidemiologic studies of estimated dietary acrylamide exposure and cancer. As substantially greater acrylamide exposure occurs through tobacco smoke than dietary exposure, we present the results separately for never smokers or adjusted statistically for smoking status, where possible. After an extensive examination of the published literature, we found no consistent or credible evidence that dietary acrylamide increases the risk of any type of cancer in humans, either overall or among nonsmokers. In particular, the collective evidence suggests that a high level of dietary acrylamide intake is not a risk factor for breast, endometrial, or ovarian cancers, which have generated particular interest because of a conjectured hormonal mechanism of acrylamide. Moreover, the absence of a positive association between smoking and ovarian and endometrial cancers suggests that any association of these cancers with the much lower, more sporadic dietary acrylamide intake is unlikely. In conclusion, epidemiologic studies of dietary acrylamide intake have failed to demonstrate an increased risk of cancer. In fact, the sporadically and slightly increased and decreased risk ratios reported in more than two dozen papers examined in this review strongly suggest the pattern one would expect to find for a true null association over the course of a series of trials. Therefore, continued epidemiologic investigation of acrylamide and cancer risk appears to be a misguided research priority.

Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China study.

Investigators collected and analyzed mortality data for >50 diseases, including 7 different cancers, from 65 counties and 130 villages in rural mainland China. Blood, urine, food samples, and detailed dietary data were collected from 50 adults in each village and analyzed for a variety of nutritional, viral, hormonal, and toxic chemical factors. In rural China, fat intake was less than half that in the United States, and fiber intake was 3 times higher. Animal protein intake was very low, only about 10% of the US intake. Mean serum total cholesterol was 127 mg/dL in rural China versus 203 mg/dL for adults aged 20-74 years in the United States. Coronary artery disease mortality was 16.7-fold greater for US men and 5.6-fold greater for US women than for their Chinese counterparts. The combined coronary artery disease mortality rates for both genders in rural China were inversely associated with the frequency of intake of green vegetables and plasma erythrocyte monounsaturated fatty acids, but positively associated with a combined index of salt intake plus urinary sodium and plasma apolipoprotein B. These apolipoproteins, in turn, are positively associated with animal protein intake and the frequency of meat intake and inversely associated with plant protein, legume, and light-colored vegetable intake. Rates of other diseases were also correlated with dietary factors. There was no evidence of a threshold beyond which further benefits did not accrue with increasing proportions of plant-based foods in the diet.

A survey of placebo use in a general hospital.

Two hundred thirty registered nurses and seventy physicians participated in a retrospective study scrutinizing placebo effects, prescribing patterns, and staff attitudes in a university-based general hospital setting. Despite copious experimental literature devoted to placebo effects over the past thirty years, the medical and surgical use of placebos seems to disregard experimental data. Although 80% of the staff had used placebos in the hospital, their knowledge of placebo effects was in many respects deficient. Within the hospital, 89% of placebo use was directed toward the amelioration of "pain"; the authors believe that emphasis should be placed on the education of staff to perceive emotional, social, and physiological concomitants of pain rather than resorting to a purely physicalistic approach. A need to acknowledge staff conflicts over the ethical use of placebos should be a significant part of this educational approach.

N-Nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study.

BACKGROUND: Humans are exposed to preformed N-nitroso compounds (NOCs) and endogenous NOCs. Several NOCs are potential human carcinogens, including N-nitrosodimethylamine (NDMA), but evidence from population studies is inconsistent. OBJECTIVE: We examined the relation between dietary NOCs (NDMA), the endogenous NOC index, and dietary nitrite and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, United Kingdom, study. DESIGN: This was a prospective study of 23,363 men and women, aged 40-79 y, who were recruited in 1993-1997 and followed up to 2008. The baseline diet was assessed with food-frequency questionnaires. RESULTS: There were 3268 incident cancers after a mean follow-up of 11.4 y. Dietary NDMA intake was significantly associated with increased cancer risk in men and women [hazard ratio (HR): 1.14; 95% CI: 1.03, 1.27; P for trend = 0.03] and in men (HR: 1.24; 95% CI: 1.07, 1.44; P for trend = 0.005) when the highest quartile was compared with the lowest quartile in age- and sex-adjusted analyses but not in multivariate analyses (HR: 1.10; 95% CI: 0.97, 1.24; HR for men: 1.18; 95% CI: 1.00, 1.40; P for trend ≥ 0.05). When continuously analyzed, NDMA was associated with increased risk of gastrointestinal cancers (HR: 1.13; 95% CI: 1.00, 1.28), specifically of rectal cancer (HR: 1.46; 95% CI: 1.16, 1.84) per 1-SD increase after adjustment for age, sex, body mass index, cigarette smoking status, alcohol intake, energy intake, physical activity, education, and menopausal status (in women). The endogenous NOC index and dietary nitrite were not significantly associated with cancer risk. There was a significant interaction between plasma vitamin C concentrations and dietary NDMA intake on cancer incidence (P for interaction < 0.00001). CONCLUSIONS: Dietary NOC (NDMA) was associated with a higher gastrointestinal cancer incidence, specifically of rectal cancer. Plasma vitamin C may modify the relation between NDMA exposure and cancer risk.

Long-term exposure to sodium nitrite and risk of esophageal carcinoma: a cohort study for 30 years.

The objective of this study is to investigate the risk of esophageal carcinoma in a cohort with long-term occupational exposure to sodium nitrite. The method used was a retrospective cohort study. A small wood screw manufacturer was founded in 1977 and closed down in 2000. In their production process, the sodium nitrite solution was used to serve as anticorrosive and coolant fluid. One hundred sixty workers in turning and milling shops had direct exposure to sodium nitrite through skin, mouth, and airway because of lack of occupational protective knowledge (study group), whereas 255 workers from other workshops without direct contact with sodium nitrite served as control group. The incidence, diagnosis, and treatment of esophageal carcinoma as well as other malignant tumors in these two groups were followed until the end of 2007. The sodium nitrite exposure time in the study group ranged from 16 to 23 years, with an average of 22.1 years. During 30 years of follow-up, there were 11 esophageal carcinomas and 10 other malignant tumors (4 hepatic cell carcinomas, 3 lung cancers, 2 breast cancers, and 1 leukemia) documented in the study group, while no cancer developed in the control group. The risk for esophageal carcinoma was significantly increased in the study group compared with the control group (relative risk = 1.26, 95% confidence interval = 1.08-1.46, chi-square = 116.83, P < 0.001). Long-term exposure to sodium nitrite markedly increases the risk of esophageal carcinoma in human body. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals.

BACKGROUND: Abdominal aortic aneurysm (AAA) disease is an insidious condition with an 85% chance of death after rupture. Ultrasound screening can reduce mortality, but its use is advocated only for a limited subset of the population at risk. METHODS: We used data from a retrospective cohort of 3.1 million patients who completed a medical and lifestyle questionnaire and were evaluated by ultrasound imaging for the presence of AAA by Life Line Screening in 2003 to 2008. Risk factors associated with AAA were identified using multivariable logistic regression analysis. RESULTS: We observed a positive association with increasing years of smoking and cigarettes smoked and a negative association with smoking cessation. Excess weight was associated with increased risk, whereas exercise and consumption of nuts, vegetables, and fruits were associated with reduced risk. Blacks, Hispanics, and Asians had lower risk of AAA than whites and Native Americans. Well-known risk factors were reaffirmed, including male gender, age, family history, and cardiovascular disease. A predictive scoring system was created that identifies aneurysms more efficiently than current criteria and includes women, nonsmokers, and individuals aged <65 years. Using this model on national statistics of risk factors prevalence, we estimated 1.1 million AAAs in the United States, of which 569,000 are among women, nonsmokers, and individuals aged <65 years. CONCLUSIONS: Smoking cessation and a healthy lifestyle are associated with lower risk of AAA. We estimated that about half of the patients with AAA disease are not eligible for screening under current guidelines. We have created a high-yield screening algorithm that expands the target population for screening by including at-risk individuals not identified with existing screening criteria.

Purine-rich foods intake and recurrent gout attacks

Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.

Paleolithic nutrition: twenty-five years later.

A quarter century has passed since the first publication of the evolutionary discordance hypothesis, according to which departures from the nutrition and activity patterns of our hunter-gatherer ancestors have contributed greatly and in specifically definable ways to the endemic chronic diseases of modern civilization. Refinements of the model have changed it in some respects, but anthropological evidence continues to indicate that ancestral human diets prevalent during our evolution were characterized by much lower levels of refined carbohydrates and sodium, much higher levels of fiber and protein, and comparable levels of fat (primarily unsaturated fat) and cholesterol. Physical activity levels were also much higher than current levels, resulting in higher energy throughput. We said at the outset that such evidence could only suggest testable hypotheses and that recommendations must ultimately rest on more conventional epidemiological, clinical, and laboratory studies. Such studies have multiplied and have supported many aspects of our model, to the extent that in some respects, official recommendations today have targets closer to those prevalent among hunter-gatherers than did comparable recommendations 25 years ago. Furthermore, doubts have been raised about the necessity for very low levels of protein, fat, and cholesterol intake common in official recommendations. Most impressively, randomized controlled trials have begun to confirm the value of hunter-gatherer diets in some high-risk groups, even as compared with routinely recommended diets. Much more research needs to be done, but the past quarter century has proven the interest and heuristic value, if not yet the ultimate validity, of the model.

Brain rust: recent discoveries on the role of oxidative stress in neurodegenerative diseases.

Oxidative stress (OS) and damages due to excessive reactive oxygen species (ROS) are common causes of injuries to cells and organisms. The prevalence of neurodegenerative diseases (ND) increases with aging and much of the research involving ROS and OS has emerged from works in this field. This text reviews some recent published articles about the role of OS in ND. Since there are many reviews in this field, the focus was centered in articles published recently. The Scientific Journals Directory supported by the Brazilian Ministry of Education Office for the Coordination of Higher Educational Personnel Improvement (CAPES) was used to search, download, and review articles. The search engine looked for the terms 'oxidative stress AND neurodegenerative diseases AND nutrition' in 10 different scientific collections. Biochemical markers for ND lack sensitivity or specificity for diagnosis or for tracking response to therapy today. OS has an intimate connection with ND, albeit low levels of ROS seem to protect the brain. Deleterious changes in mitochondria, OS, calcium, glucocorticoids, inflammation, trace metals, insulin, cell cycle, protein aggregation, and hundreds to thousands of genes occur in ND. The interaction of genes with their environment, may explain ND. Although OS has received much attention over the years, which increased the number of scientific works on antioxidant interventions, no one knows how to stop or delay ND at present. Interventions in vitro, in vivo, and in humans will continue to contribute for a better understanding of these pathologies.

Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, I...

CONTEXT: Alzheimer disease (AD) represents a major and increasing public health problem. If populations were identified with significantly lower or higher incidence rates of AD, the search for risk factors in the genesis of AD could be greatly enhanced. OBJECTIVE: To compare incidence rates of dementia and AD in 2 diverse, elderly community-dwelling populations. DESIGN: The Indianapolis-Ibadan Dementia Project, a longitudinal, prospective population-based study consisting of a baseline survey (1992-1993) and 2 subsequent follow-up waves after 2 years (1994-1995) and 5 years (1997-1998). Each wave followed a 2-stage design, with an in-home screening interview followed by a full diagnostic workup of a subsample of participants based on screening performance. SETTING AND PARTICIPANTS: A total of 2459 community-dwelling Yoruba residents of Ibadan, Nigeria, without dementia, and 2147 community-dwelling African American residents of Indianapolis, Ind, without dementia (all aged 65 years or older). The cohorts were followed up for a mean of 5.1 years and 4.7 years, respectively. MAIN OUTCOME MEASURES: Incident cases of dementia and AD in each of the 2 populations. RESULTS: The age-standardized annual incidence rates were significantly lower among Yoruba than among African Americans for dementia (Yoruba, 1.35% [95% confidence interval [CI], 1.13%-1.56%]; African Americans, 3.24% [95% CI, 2.11%-4.38%]) and for AD (Yoruba, 1.15% [95% CI, 0.96%-1.35%]; African Americans, 2.52% [95% CI, 1.40%-3.64%]). CONCLUSION: This is the first report of incidence rate differences for dementia and AD in studies of 2 populations from nonindustrialized and industrialized countries using identical methods and the same group of investigators in both sites. Further explorations of these population differences may identify potentially modifiable environmental or genetic factors to account for site differences in dementia and AD.

Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population.

This study was designed to ascertain whether individuals with mood disorders are particularly vulnerable to adverse effects of aspartame. Although the protocol required the recruitment of 40 patients with unipolar depression and a similar number of individuals without a psychiatric history, the project was halted by the Institutional Review Board after a total of 13 individuals had completed the study because of the severity of reactions within the group of patients with a history of depression. In a crossover design, subjects received aspartame 30 mg/kg/day or placebo for 7 days. Despite the small n, there was a significant difference between aspartame and placebo in number and severity of symptoms for patients with a history of depression, whereas for individuals without such a history there was not. We conclude that individuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged.

The counseling practices of internists.

OBJECTIVES: To determine the counseling practices of a group of internists in the areas of smoking, exercise, and alcohol and seat belt use, and to determine the associations among physicians' personal health habits and their counseling practices. DESIGN: A random stratified sample of members and fellows of the American College of Physicians in 21 regions selected to represent all areas of the United States. Because of the relatively small proportion of women in this group, they were oversampled. SETTING: Physicians' practices. PARTICIPANTS: One thousand three hundred and forty-nine internists (members or fellows of the College) returned questionnaires, for a response rate of 75%; 52% defined themselves as general internists. INTERVENTIONS: A questionnaire was used to obtain information on internists' use of cigarettes, alcohol, and seat belts and their level of physical activity. Data were obtained on the indications used for counseling and the aggressiveness of counseling about each of these four habits. MEASUREMENTS AND MAIN RESULTS: Bivariate and logistic regression analyses were used to compare the tendencies of internist subgroups both in using various indications for counseling and in the thoroughness of counseling. Generalists were more likely than specialists to counsel at least once all patients who were at risk and to be more aggressive in counseling. Ninety percent of respondents counseled all of their patients who smoked, but 64.5% never discussed the use of seat belts. Only 3.8% of these internists currently smoked cigarettes, 11.3% drank alcohol daily, 38.7% were extremely or quite active, and 87.3% used seat belts all or most of the time. Among men internists, for every habit except alcohol use, personal health practices were substantially associated with counseling patients; for example, nonsmoking internists were more likely to counsel smokers, and very physically active internists were more likely to counsel about exercise. Among women internists, being very physically active was associated with counseling more patients about exercise and alcohol use. CONCLUSIONS: The low level of self-reported counseling among these internists suggests that further emphasis on training in these skills is needed. The association between personal and professional practices suggests that medical schools and housestaff training programs should support health promotion activities for future internists.

Communicating clinical research to reduce cancer risk through diet: Walnuts as a case example

Inflammation is one mechanism through which cancer is initiated and progresses, and is implicated in the etiology of other conditions that affect cancer risk and prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity. Emerging human evidence, primarily epidemiological, suggests that walnuts impact risk of these chronic diseases via inflammation. The published literature documents associations between walnut consumption and reduced risk of cancer, and mortality from cancer, diabetes, and cardiovascular disease, particularly within the context of the Mediterranean Diet. While encouraging, follow-up in human intervention trials is needed to better elucidate any potential cancer prevention effect of walnuts, per se. In humans, the far-reaching positive effects of a plant-based diet that includes walnuts may be the most critical message for the public. Indeed, appropriate translation of nutrition research is essential for facilitating healthful consumer dietary behavior. This paper will explore the translation and application of human evidence regarding connections with cancer and biomarkers of inflammation to the development of dietary guidance for the public and individualized dietary advice. Strategies for encouraging dietary patterns that may reduce cancer risk will be explored.

Exploration of 100 commonly used drugs and supplements on cognition in older adults

Background There are conflicting reports and a lack of evidence-based data regarding effects of medications on cognition in cognitively normal older adults. We explored whether use of 100 common medications taken by older adults is associated with longitudinal cognitive performance. Methods A longitudinal observational cohort was used with analysis of data collected September 2005 through May 2011 and maintained in the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set. Participants were aged 50 years or older and cognitively normal (N=4414). Composite scores were constructed from 10 psychometric tests. Scores for each participant reflecting change in the psychometric composite score from the baseline clinical assessment to the next assessment were calculated. General linear models were used to test whether the mean composite change score differed for participants who reported starting, stopping, continuing, or not taking each of the 100 most frequently-used medications in the NACC sample. Results The average time between assessments was 1.2 years (SD=0.42). Nine medications showed a difference (p<0.05) across the four participant groups in mean psychometric change scores from the first to the second assessment. Medications associated with improved psychometric performance were: naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline. Medications associated with declining psychometric performance were: bupropion, oxybutynin, and furosemide. Conclusions Reported use of common medications is associated with cognitive performance in older adults, but studies are needed to investigate the mechanisms underlying these effects.

Egg consumption and the risk of cancer: a multisite case-control study in Uruguay.

BACKGROUND: Previous studies have suggested that egg consumption may increase the risk of colorectal cancer and some other cancers. However, the evidence is still limited. To further explore the association between egg intake and cancer risk we conducted a case-control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls. RESULTS: In the multivariable model with adjustment for age, sex (when applicable), residence, education, income, interviewer, smoking, alcohol intake, intake of fruits and vegetables, grains, dairy products, fatty foods, meat, energy intake and BMI, there was a significant increase in the odds of cancers of the oral cavity and pharynx (OR= 2.02, 95% CI: 1.19-3.44), upper aerodigestive tract (OR= 1.67, 95% CI: 1.17-2.37), colorectum (OR= 1.64, 95% CI: 1.02-2.63), lung (OR= 1.59, 95% CI: 1.10-2.29), breast (OR= 2.86, 95% CI: 1.66-4.92), prostate (OR= 1.89, 95% CI: 1.15-3.10), bladder (OR= 2.23, 95% CI: 1.30-3.83) and all cancer sites combined (OR= 1.71, 95% CI: 1.35-2.17) with a high vs low egg intake. CONCLUSIONS: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.

Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression.

CONTEXT: The monoamine theory of depression proposes that monoamine levels are lowered, but there is no explanation for how monoamine loss occurs. Monoamine oxidase A (MAO-A) is an enzyme that metabolizes monoamines, such as serotonin, norepinephrine, and dopamine. OBJECTIVE: To determine whether MAO-A levels in the brain are elevated during untreated depression. SETTING: Tertiary care psychiatric hospital. PATIENTS: Seventeen healthy and 17 depressed individuals with major depressive disorder that met entry criteria were recruited from the care of general practitioners and psychiatrists. All study participants were otherwise healthy and nonsmoking. Depressed individuals had been medication free for at least 5 months. MAIN OUTCOME MEASURE: Harmine labeled with carbon 11, a radioligand selective for MAO-A and positron emission tomography, was used to measure MAO-A DVS (specific distribution volume), an index of MAO-A density, in different brain regions (prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, caudate, putamen, thalamus, anterior temporal cortex, midbrain, hippocampus, and parahippocampus). RESULTS: The MAO-A DVS was highly significantly elevated in every brain region assessed (t test; P=.001 to 3x10(-7)). The MAO-A DVS was elevated on average by 34% (2 SDs) throughout the brain during major depression. CONCLUSIONS: The sizable magnitude of this finding and the absence of other compelling explanations for monoamine loss during major depressive episodes led to the conclusion that elevated MAO-A density is the primary monoamine-lowering process during major depression.

Cost-effectiveness of gargling for the prevention of upper respiratory tract infections

Background In Japan, gargling is a generally accepted way of preventing upper respiratory tract infection (URTI). The effectiveness of gargling for preventing URTI has been shown in a randomized controlled trial that compared incidences of URTI between gargling and control groups. From the perspective of the third-party payer, gargling is dominant due to the fact that the costs of gargling are borne by the participant. However, the cost-effectiveness of gargling from a societal perspective should be considered. In this study, economic evaluation alongside a randomized controlled trial was performed to evaluate the cost-effectiveness of gargling for preventing URTI from a societal perspective. Methods Among participants in the gargling trial, 122 water-gargling and 130 control subjects were involved in the economic analysis. Sixty-day cumulative follow-up costs and effectiveness measured by quality-adjusted life days (QALD) were compared between groups on an intention-to-treat basis. Incremental cost-effectiveness ratio (ICER) was converted to dollars per quality-adjusted life years (QALY). The 95% confidence interval (95%CI) and probability of gargling being cost-effective were estimated by bootstrapping. Results After 60 days, QALD was increased by 0.43 and costs were $37.1 higher in the gargling group than in the control group. ICER of the gargling group was $31,800/QALY (95%CI, $1,900–$248,100). Although this resembles many acceptable forms of medical intervention, including URTI preventive measures such as influenza vaccination, the broad confidence interval indicates uncertainty surrounding our results. In addition, one-way sensitivity analysis also indicated that careful evaluation is required for the cost of gargling and the utility of moderate URTI. The major limitation of this study was that this trial was conducted in winter, at a time when URTI is prevalent. Care must be taken when applying the results to a season when URTI is not prevalent, since the ICER will increase due to decreases in incidence. Conclusion This study suggests gargling as a cost-effective preventive strategy for URTI that is acceptable from perspectives of both the third-party payer and society.

Patients' Expectations of Screening and Preventive Treatments

PURPOSE An informed decision to accept a health care intervention requires an understanding of its likely benefit. This study assessed participants' estimates of the benefit, as well as minimum acceptable benefit, of screening for breast and bowel cancer and medication to prevent hip fracture and cardiovascular disease. METHODS Three general practitioners sent questionnaires to all registered patients aged 50 to 70 years. Patients agreeing to participate in the study were asked to estimate the number of events (fractures or deaths) prevented in a group of 5,000 patients undergoing each intervention over a period of 10 years, and to indicate the minimum number of events avoided by the intervention that they considered justified its use. The proportions of participants that overestimated each intervention's benefit were calculated, and univariate and multivariable analyses of predictors of response were performed. RESULTS The participation rate was 36%: 977 patients were invited to participate in the study, and 354 returned a completed questionnaire. Participants overestimated the degree of benefit conferred by all interventions: 90% of participants overestimated the effect of breast cancer screening, 94% overestimated the effect of bowel cancer screening, 82% overestimated the effect of hip fracture preventive medication, and 69% overestimated the effect of preventive medication for cardiovascular disease. Estimates of minimum acceptable benefit were more conservative, but other than for cardiovascular disease mortality prevention, most respondents indicated a minimum benefit greater than these interventions achieve. A lower level of education was associated with higher estimates of minimum acceptable benefit for all interventions. CONCLUSION Patients overestimated the risk reduction achieved with 4 examples of screening and preventive medications. A lower level of education was associated with higher minimum benefit to justify intervention use. This tendency to overestimate benefits may affect patients' decisions to use such interventions, and practitioners should be aware of this tendency when discussing these interventions with patients.

The role of exercise in the treatment of obesity.

The United States is in the midst of a significant public health problem that relates to obesity and inactivity. This epidemic has far-ranging consequences for our workforce and our children and shows no signs of slowing in the near future. Significant research has been performed on the effects of exercise for the reduction of body weight; results of most studies indicate that exercise alone has a small effect on body-weight reduction independent of caloric restriction. However, when combined with dietary restriction, exercise has a synergistic effect and enhances weight loss beyond the effect of diet alone. In addition, exercise has been shown to have significant beneficial effects on cardiovascular and metabolic risk factors independent of actual weight loss, and losing just a small amount of weight can have a significant beneficial effect on these parameters. Genetic factors related to obesity have been found to be positively modified when persons incorporate physical activity into their lifestyle. Sitting time appears to be an independent risk factor for the development of metabolic risk factors; persons who spend more time sitting and watching television have worse metabolic profiles, even if they achieve the recommended amount of physical activity per week, than do those who move about throughout the day. Exercise also is essential for the prevention of weight gain over a life span, although the amount required to prevent weight gain may be closer to twice the amount of exercise recommended by the current Physical Activity Guidelines for Americans (www.health.gov/paguidelines). In many ways, the physiatrist is the most well prepared of all the specialists to address the complex, multidimensional problems of obesity and inactivity. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people

Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.

Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study.

BACKGROUND: Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner. METHODS: Forty-five women were randomly assigned to four interventions: "placebo ingestion" (n = 11), "curcumin ingestion" (n = 11), "exercise training with placebo ingestion" (n = 11), or "exercise training with curcumin ingestion" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms. RESULTS: There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group. CONCLUSIONS: These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.

Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults

Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.

Statin use and risk of breast cancer: a meta-analysis of observational studies.

Emerging evidence suggests that statins' may decrease the risk of cancers. However, available evidence on breast cancer is conflicting. We, therefore, examined the association between statin use and risk of breast cancer by conducting a detailed meta-analysis of all observational studies published regarding this subject. PubMed database and bibliographies of retrieved articles were searched for epidemiological studies published up to January 2012, investigating the relationship between statin use and breast cancer. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Combined relative risk (RR) and 95 % confidence interval (CI) were calculated using a random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. A total of 24 (13 cohort and 11 case-control) studies involving more than 2.4 million participants, including 76,759 breast cancer cases contributed to this analysis. We found no evidence of publication bias and evidence of heterogeneity among the studies. Statin use and long-term statin use did not significantly affect breast cancer risk (RR = 0.99, 95 % CI = 0.94, 1.04 and RR = 1.03, 95 % CI = 0.96, 1.11, respectively). When the analysis was stratified into subgroups, there was no evidence that study design substantially influenced the effect estimate. Sensitivity analysis confirmed the stability of our results. Cumulative meta-analysis showed a change in trend of reporting risk of breast cancer from positive to negative in statin users between 1993 and 2011. Our meta-analysis findings do not support the hypothesis that statins' have a protective effect against breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.

Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis.

Parkinson's disease (PD) is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. Recent epidemiological data demonstrate that environmental risk factors may play a dominant role as compared to genetic factors in the etiopathogenesis of idiopathic Parkinson's disease. Identification of key genetic defects such as alpha-synuclein and parkin mutations in PD also underscores the important role of genetic factors in the disease. Thus, understanding the interplay between genes and environment in PD may be critical to unlocking the mysteries of this 200-year-old neurodegenerative disease. Pesticides and metals are the most common classes of environmental chemicals that promote dopaminergic degeneration. The organochlorine pesticide dieldrin has been found in human PD postmortem brain tissues, suggesting that this pesticide has potential to promote nigral cell death. Though dieldrin has been banned, humans continue to be exposed to the pesticide through contaminated dairy products and meats due to the persistent accumulation of the pesticide in the environment. This review summarizes various neurotoxic studies conducted in both cell culture and animals models following dieldrin exposure and discusses their relevance to key pathological mechanisms associated with nigral dopaminergic degeneration including oxidative stress, mitochondrial dysfunction, protein aggregation, and apoptosis.

Blueberries and neuronal aging.

As the population of people in the United States over the age of 65 years continues to increase, so too will the incidence of age-related pathologies, including decreases in cognitive and motor function. In cases of severe deficits in memory or motor function, hospitalization and/or custodial care would be a likely outcome. This means that unless some way is found to reduce these age-related decrements in neuronal function, health care costs will continue to rise exponentially. Evidence is accumulating that consumption of blueberries may be one strategy to forestall or even reverse age-related neuronal deficits, as well as their subsequent behavioral manifestations, in order to increase healthy aging. Research suggests that the polyphenolic compounds found in blueberries exert their beneficial effects either through their ability to lower oxidative stress and inflammation or directly by altering the signaling involved in neuronal communication. These interventions, in turn, may protect against age-related deficits in cognitive and motor function. Appropriately, the US Department of Agriculture has figured prominently in these discoveries, through the efforts of two USDA researchers who worked for the department 100 years apart. Copyright © 2012 S. Karger AG, Basel.

Omega-3 Fatty Acids and incident Type 2 Diabetes: A Systematic Review and Meta-Analysis

The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.

Systematic review: factors associated with risk for and possible prevention of cognitive decline in later life.

BACKGROUND: Many biological, behavioral, social, and environmental factors may contribute to the delay or prevention of cognitive decline. PURPOSE: To summarize evidence about putative risk and protective factors for cognitive decline in older adults and the effects of interventions for preserving cognition. DATA SOURCES: English-language publications in MEDLINE, HuGEpedia, AlzGene, and the Cochrane Database of Systematic Reviews from 1984 through 27 October 2009. STUDY SELECTION: Observational studies with 300 or more participants and randomized, controlled trials (RCTs) with 50 or more adult participants who were 50 years or older, drawn from general populations, and followed for at least 1 year were included. Relevant, good-quality systematic reviews were also eligible. DATA EXTRACTION: Information on study design, outcomes, and quality were extracted by one researcher and verified by another. An overall rating of the quality of evidence was assigned by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. DATA SYNTHESIS: 127 observational studies, 22 RCTs, and 16 systematic reviews were reviewed in the areas of nutritional factors; medical factors and medications; social, economic, or behavioral factors; toxic environmental exposures; and genetics. Few of the factors had sufficient evidence to support an association with cognitive decline. On the basis of observational studies, evidence that supported the benefits of selected nutritional factors or cognitive, physical, or other leisure activities was limited. Current tobacco use, the apolipoprotein E epsilon4 genotype, and certain medical conditions were associated with increased risk. One RCT found a small, sustained benefit from cognitive training (high quality of evidence) and a small RCT reported that physical exercise helps to maintain cognitive function. LIMITATIONS: The categorization and definition of exposures were heterogeneous. Few studies were designed a priori to assess associations between specific exposures and cognitive decline. The review included only English-language studies, prioritized categorical outcomes, and excluded small studies. CONCLUSION: Few potentially beneficial factors were identified from the evidence on risk or protective factors associated with cognitive decline, but the overall quality of the evidence was low. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and the National Institute on Aging, through the Office of Medical Applications of Research, National Institutes of Health.

Coffee and its consumption: benefits and risks.

Coffee is the leading worldwide beverage after water and its trade exceeds US $10 billion worldwide. Controversies regarding its benefits and risks still exist as reliable evidence is becoming available supporting its health promoting potential; however, some researchers have argued about the association of coffee consumption with cardiovascular complications and cancer insurgence. The health-promoting properties of coffee are often attributed to its rich phytochemistry, including caffeine, chlorogenic acid, caffeic acid, hydroxyhydroquinone (HHQ), etc. Many research investigations, epidemiological studies, and meta-analyses regarding coffee consumption revealed its inverse correlation with that of diabetes mellitus, various cancer lines, Parkinsonism, and Alzheimer's disease. Moreover, it ameliorates oxidative stress because of its ability to induce mRNA and protein expression, and mediates Nrf2-ARE pathway stimulation. Furthermore, caffeine and its metabolites help in proper cognitive functionality. Coffee lipid fraction containing cafestol and kahweol act as a safeguard against some malignant cells by modulating the detoxifying enzymes. On the other hand, their higher levels raise serum cholesterol, posing a possible threat to coronary health, for example, myocardial and cerebral infarction, insomnia, and cardiovascular complications. Caffeine also affects adenosine receptors and its withdrawal is accompanied with muscle fatigue and allied problems in those addicted to coffee. An array of evidence showed that pregnant women or those with postmenopausal problems should avoid excessive consumption of coffee because of its interference with oral contraceptives or postmenopausal hormones. This review article is an attempt to disseminate general information, health claims, and obviously the risk factors associated with coffee consumption to scientists, allied stakeholders, and certainly readers. © Taylor and Francis Group, LLC

Intake of fried meat and risk of cancer: a follow-up study in Finland.

It has been suggested that mutagens in fried meat may be involved in the cancer process. Therefore the relationships between intake of fried meat and subsequent risk of cancers at different sites were studied among 9,990 Finnish men and women, 15-99 years of age and initially free of cancer. The baseline study was carried out in 1966-1972, and cases of cancer were identified through data linkage with the Finnish Cancer Registry. During a 24-year follow-up, 853 cancer cases were diagnosed. The intake of fried meat was estimated from a dietary history interview covering the total diet of the participants during the previous year. There was a positive association between fried meat intake and the risk of female-hormone-related cancers, i.e., cancer of the breast, endometrium and ovary combined. The relative risk of these cancers combined between persons in the highest and lowest tertiles of daily intake of fried meat adjusted for age, personal characteristics and intake of other main food groups was 1.77 (95% confidence interval = 1.11-2.84). Pancreatic and nervous system cancers also presented non-significant suggestive associations. No associations were observed with respect to other single cancer sites studied or to all sites of cancer combined. Further epidemiological efforts are needed to ascertain the potential link between fried-food mutagens and cancer risk.

Empirical evaluation of very large treatment effects of medical interventions.

CONTEXT: Most medical interventions have modest effects, but occasionally some clinical trials may find very large effects for benefits or harms. OBJECTIVE: To evaluate the frequency and features of very large effects in medicine. DATA SOURCES: Cochrane Database of Systematic Reviews (CDSR, 2010, issue 7). STUDY SELECTION: We separated all binary-outcome CDSR forest plots with comparisons of interventions according to whether the first published trial, a subsequent trial (not the first), or no trial had a nominally statistically significant (P < .05) very large effect (odds ratio [OR], ≥5). We also sampled randomly 250 topics from each group for further in-depth evaluation. DATA EXTRACTION: We assessed the types of treatments and outcomes in trials with very large effects, examined how often large-effect trials were followed up by other trials on the same topic, and how these effects compared against the effects of the respective meta-analyses. RESULTS: Among 85,002 forest plots (from 3082 reviews), 8239 (9.7%) had a significant very large effect in the first published trial, 5158 (6.1%) only after the first published trial, and 71,605 (84.2%) had no trials with significant very large effects. Nominally significant very large effects typically appeared in small trials with median number of events: 18 in first trials and 15 in subsequent trials. Topics with very large effects were less likely than other topics to address mortality (3.6% in first trials, 3.2% in subsequent trials, and 11.6% in no trials with significant very large effects) and were more likely to address laboratory-defined efficacy (10% in first trials,10.8% in subsequent, and 3.2% in no trials with significant very large effects). First trials with very large effects were as likely as trials with no very large effects to have subsequent published trials. Ninety percent and 98% of the very large effects observed in first and subsequently published trials, respectively, became smaller in meta-analyses that included other trials; the median odds ratio decreased from 11.88 to 4.20 for first trials, and from 10.02 to 2.60 for subsequent trials. For 46 of the 500 selected topics (9.2%; first and subsequent trials) with a very large-effect trial, the meta-analysis maintained very large effects with P < .001 when additional trials were included, but none pertained to mortality-related outcomes. Across the whole CDSR, there was only 1 intervention with large beneficial effects on mortality, P < .001, and no major concerns about the quality of the evidence (for a trial on extracorporeal oxygenation for severe respiratory failure in newborns). CONCLUSIONS: Most large treatment effects emerge from small studies, and when additional trials are performed, the effect sizes become typically much smaller. Well-validated large effects are uncommon and pertain to nonfatal outcomes.

Biology and function of the aryl hydrocarbon receptor: report of an international and interdisciplinary conference.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor present in many cells. The AhR links environmental chemical stimuli with adaptive responses, such as detoxification, cellular homoeostasis or immune responses. Furthermore, novel roles of AhR in physiological and genetic functions are being discovered. This is a report of a recent meeting in Düsseldorf. The meeting highlighted that AhR research has moved from its focus on toxic effects of dioxins and other environmental pollutants to its biological roles. For instance, it was recently discovered that AhR-responsive elements in retrotransposons contribute to the functional structure of the genome. Other exciting new reports concerned the way plant-derived compounds in our diet are necessary for a fully functioning immune system of the gut. Also, human brain tumours use the AhR system to gain growth advantages. Other aspects covered were neurotoxicology, the circadian rhythm, or the breadth of the adaptive and innate immune system (hematopoietic stem cells, dendritic cells, T cells, mast cells). Finally, the meeting dealt with the discovery of new xenobiotic and natural ligands and their use in translational medicine, or cancer biology and AhR.

Sympathetic nervous system activity and resting metabolic rate in vegetarians.

We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.

A Systematic Review of Body Fat Distribution and Mortality in Older People

We conducted a systematic review investigating body fat distribution in older adults and its association with morbidity and mortality. Our search yielded 2,702 citations. Following three levels of screening, 25 studies were selected to evaluate the association between body fat distribution and comorbidity, and 17 studies were used in the mortality analysis. Most of the selected studies in our analyses used anthropometric measures, e.g., body mass index (BMI), waist circumference, and waist-hip ratio; relatively few studies used direct measures, such as body fat/lean mass, and percentage body fat. Studies reported inconsistent findings regarding the strongest predictor(s) of morbidity and mortality. However, the majority of studies suggested that BMI per se was not the most appropriate predictor of morbidity and mortality in the elderly because of its inability to discern or detect age-related body fat redistribution. In addition, studies using BMI found that the optimal BMI range for the lowest mortality in the elderly was overweight (25 kg/m2 ≤ BMI < 30 kg/m2) or mildly obese (30 kg/m2 ≤ BMI < 35 kg/m2). Our findings suggest that the current clinical guidelines, recommending that overweight and obesity are major risk factors for increased morbidity and mortality are not applicable to this population. Therefore, the central message of this review is to admonish the government to establish new guidelines specifically for this population, using a combination of body fat distribution measurements, and to certify that these guidelines will not be applied to inappropriate populations.

Low-fat dietary pattern and risk of benign proliferative breast disease: a randomized, controlled dietary modification trial

Modifiable factors, including diet, might alter breast cancer risk. We used the WHI Dietary Modification (DM) trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of and considered to be on the pathway to invasive breast cancer. The WHI DM trial was a randomized, controlled, primary prevention trial conducted in 40 US clinical centers from 1993–2005. 48,835 postmenopausal women, aged 50–79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the DM intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to ≥5 servings/day and intake of grain products to ≥6 servings/day, but resulted in smaller, albeit significant changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between DM and benign proliferative breast disease was 1.09 (95%CI, 0.98–1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake does not alter the risk of benign proliferative breast disease.

The link between erectile and cardiovascular health: the canary in the coal mine.

Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.

A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults.

BACKGROUND: Studies of single nutrients on depression have produced inconsistent results, and they have failed to consider the complex interactions between nutrients. An increasing number of studies in recent years are investigating the association of overall dietary patterns and depression. OBJECTIVE: This study aimed to systematically review current literature and conduct meta-analyses of studies addressing the association between dietary patterns and depression. DESIGN: Six electronic databases were searched for articles published up to August 2013 that examined the association of total diet and depression among adults. Only studies considered methodologically rigorous were included. Two independent reviewers completed study selection, quality rating, and data extraction. Effect sizes of eligible studies were pooled by using random-effects models. A summary of the findings was presented for studies that could not be meta-analyzed. RESULTS: A total of 21 studies were identified. Results from 13 observational studies were pooled. Two dietary patterns were identified. The healthy diet pattern was significantly associated with a reduced odds of depression (OR: 0.84; 95% CI: 0.76, 0.92; P < 0.001). No statistically significant association was observed between the Western diet and depression (OR: 1.17; 95% CI: 0.97, 1.68; P = 0.094); however, the studies were too few for a precise estimate of this effect. CONCLUSIONS: The results suggest that high intakes of fruit, vegetables, fish, and whole grains may be associated with a reduced depression risk. However, more high-quality randomized controlled trials and cohort studies are needed to confirm this finding, specifically the temporal sequence of this association.

Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women.

The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15.2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.

Principal component analysis of dietary and lifestyle patterns in relation to risk of subtypes of esophageal and gastric cancer

Purpose To perform pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers. Methods We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression. Results PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing GERD/BMI score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA. Conclusions PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, while fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC.

Effects of Diets High in Walnuts and Flax Oil on Hemodynamic Responses to Stress and Vascular Endothelial Function

Background Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax. Objective To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP). Design Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n = 12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA). Results The ALA and LA diets significantly reduced diastolic blood pressure (−2 to −3 mm Hg) and total peripheral resistance (−4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged. Conclusions These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.

Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies.

BACKGROUND: Regular consumption of fruit and vegetables has been considered to be associated with a reduced risk of dementia and age-associated cognitive decline, although the association is currently unsupported by a systematic review of the literature. METHODS: We searched Medline, Embase, Biosis, ALOIS, the Cochrane library, different publisher databases as well as bibliographies of retrieved articles. All cohort studies with a follow-up of 6 months or longer were included if they reported an association of Alzheimer's disease or cognitive decline in regard to the frequency of fruit and vegetables consumption. FINDINGS: Nine studies with a total of 44,004 participants met the inclusion criteria. Six studies analyzed fruit and vegetables separately and five of them found that higher consumption of vegetables, but not fruit is associated with a decreased risk of dementia or cognitive decline. The same association was found by three further studies for fruit and vegetable consumption analytically combined. CONCLUSION: Increased intake of vegetables is associated with a lower risk of dementia and slower rates of cognitive decline in older age. Yet, evidence that this association is also valid for high fruit consumption is lacking.

Fruit, vegetable, and fish consumption and heart rate variability: the Veterans Administration Normative Aging Study

Background: Higher intakes of fruit, vegetables, and dark fish may prevent sudden cardiac death and arrhythmias, but the exact mechanisms are not fully understood. Objective: We examined whether high consumption of fruit, vegetables, and dark fish would be associated with beneficial changes in heart rate variability (HRV). Design: HRV variables were measured among 586 older men with 928 total observations from November 2000 to June 2007 in the Normative Aging Study, a community-based longitudinal study of aging. Dietary intake was evaluated with a self-administered semiquantitative food-frequency questionnaire and categorized into quartiles. Results: After controlling for potential confounders, intake of green leafy vegetables was positively associated with normalized high-frequency power and inversely associated with normalized low-frequency power (P for trend < 0.05). These significant associations were retained after further adjustment for healthy lifestyle factors, such as physical activity and use of multivitamins. No significant association was seen between HRV measures and intakes of other fruit and vegetables, vitamin C, carotenoids, tuna and dark-meat fish, or n–3 (omega-3) fatty acids. An effect modification of intake of noncitrus fruit by obesity and of total vegetables and cruciferous vegetables by cigarette smoking was seen, which warrants further investigation. Conclusion: These findings suggest that higher intake of green leafy vegetables may reduce the risk of cardiovascular disease through favorable changes in cardiac autonomic function.

VEGETARIAN DIETS AND THE INCIDENCE OF CANCER IN A LOW-RISK POPULATION

Background Cancer is the second leading cause of death in the US. Dietary factors account for at least 30% of all cancers in Western countries. Since people do not consume individual foods but rather combinations of them, the assessment of dietary patterns may offer valuable information when determining associations between diet and cancer risk. Methods We examined the association between dietary patterns (non-vegetarians, lacto, pesco, vegan, and semi-vegetarian) and the overall cancer incidence among 69,120 participants of the Adventist Health Study-2. Cancer cases were identified by matching to cancer registries. Cox-proportional hazard regression analysis was performed to estimate hazard ratios, with “attained age” as the time variable. Results 2,939 incident cancer cases were identified. The multivariate HR of overall cancer risk among vegetarians compared to non-vegetarians was statistically significant (HR=0.92; 95%CI: 0.85, 0.99) for both genders combined. Also, a statistically significant association was found between vegetarian diet and cancers of the gastrointestinal tract (HR=0.76; 95%CI: 0.63, 0.90). When analyzing the association of specific vegetarian dietary patterns, vegan diets showed statistically significant protection for overall cancer incidence (HR=0.84; 95%CI: 0.72, 0.99) in both genders combined and for female-specific cancers (HR=0.66; 95%CI: 0.47, 0.92). Lacto-ovo-vegetarians appeared to be associated with decreased risk of cancers of the gastrointestinal system (HR=0.75; 95%CI: 0.60, 0.92). Conclusion Vegetarian diets seem to confer protection against cancer. Impact Vegan diet seems to confer lower risk for overall and female-specific cancer compared to other dietary patterns. The lacto-ovo-vegetarian diets seem to confer protection from cancers of the gastrointestinal tract.

Emerging issues associated with HIV patients seeking advice from health food stores.

OBJECTIVES: To ascertain the recommendations, training and education of health food store employees and determine how they communicate the costs, benefits and risks associated with natural health products for the HIV/AIDS community. METHODS: Four male research assistants, posing as asymptomatic HIV-positive individuals, inquired of employees of all retail health food stores in a major Canadian city as to what is recommended for their condition. The research assistants asked about product costs, side effects, potential drug interactions and efficacy. They also inquired as to employee education related to Complementary and Alternative Medicine (CAM) and noted whether employees asked about which conventional medications they were taking and whether they recommended that the subjects seek physician or CAM provider advice. RESULTS: A total of 32 stores were included. Eight store employees (25%) offered no advice; eight (25%) inquired whether the subjects were currently taking medications; six (19%) suggested visiting a physician; and eight (25%) suggested visiting a CAM provider. A total of 36 different products (mean 2.3 per employee) were recommended with considerable variability in product evidence and cost. The education of the employees varied from postgraduate education (n=3), to undergraduate degree (n=3), college level (n=5) in CAM, or no formal education in CAM (n=21). CONCLUSION: There was considerable heterogeneity in advice on natural food products provided by employees of natural food stores and, in general, these individuals had limited formal training in CAM. The products they recommended had limited evidence supporting their efficacy and in some instances were potentially harmful and had considerable costs. The findings of this study support the need to further examine how best to regulate this growing component of the health care system.

Breast cancer incidence rates in U.S. women are no longer declining.

BACKGROUND: Several publications reported breast cancer incidence rates continued to decrease among white women, following the decline of about 7% from 2002 to 2003. However, none of these reports exclusively examined the trend after 2003. In this paper, we examined breast cancer incidence rates among non-Hispanic (NH) white women from 2003 to 2007 to determine whether the decrease in breast cancer incidence rates indeed persisted through 2007. In addition, we present breast cancer incidence trends for NH black and Hispanic women and postmenopausal hormone use for all three racial/ethnic groups. METHODS: Breast cancer incidence rates were calculated by race/ethnicity, age and ER status using data from the Surveillance, Epidemiology, and End Results (SEER) 12 registries for 2000 to 2007. Prevalence of postmenopausal hormone use was calculated using National Health Interview Survey data from 2000, 2005, and 2008. RESULTS: From 2003 to 2007, overall breast cancer incidence rates did not change significantly among NH white women in any age group. However, rates increased (2.7% per year) for ER+ breast cancers in ages 40 to 49, and decreased for ER- breast cancers in ages 40 to 49 and 60 to 69. Similarly, overall breast cancer incidence rates did not change significantly for black and Hispanic women. Hormone use continued to decrease from 2005 to 2008 in all groups, although the decreases were smaller compared to those from 2000 to 2005. CONCLUSIONS: The sharp decline in breast cancer incidence rates that occurred from 2002 to 2003 among NH white women did not continue through 2007. IMPACT: Further studies are needed to better understand the recent breast cancer trends. ©2011 AACR.

Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2

Importance Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. Objective To evaluate the association between vegetarian dietary patterns and mortality. Design Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. Setting Adventist Health Study 2 (AHS-2), a large North American cohort. Participants A total of 96 469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73 308 participants remained after exclusions. Exposures Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo–vegetarian, and vegan. Main Outcome and Measure The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. Results There were 2570 deaths among 73 308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82–6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs non-vegetarians was 0.88 (95% CI, 0.80–0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73–1.01); in lacto-ovo–vegetarians, 0.91 (95% CI, 0.82–1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69–0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75–1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. Conclusions and Relevance Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.

A meta-analysis of maternal cured meat consumption during pregnancy and the risk of childhood brain tumors.

OBJECTIVE: N-Nitroso compounds (NOCs) are recognized neural carcinogens in animal models and are suspected human carcinogens. A meta-analysis was performed examining the possible association of maternal intake of cured meat (an important source of dietary NOCs) during pregnancy and the risk of pediatric brain tumors. METHODS: Data from epidemiological studies were pooled using a general variance-based meta-analytic method employing confidence intervals described by Greenland in 1986. The outcome of interest was a summary relative risk (RR) reflecting the risk of childhood brain tumor (CBT) development associated with maternal intake of cured meats during pregnancy. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity. RESULTS: Seven observational studies were found that met the protocol-specified inclusion criteria. Analysis for heterogeneity demonstrated a lack of statistical heterogeneity (p = 0.59), indicating that the data could be statistically combined. Pooling data from the 6 reports containing data on maternal cured meat intake of all types yielded an RR of 1.68 (1.30- 2.17), being a statistically significant result. Analyzing CBT risk by type of cured meat ingested showed that hot dog consumption increased CBT risk by 33% (1.08-1.66), with a similar increase shown by frequent ingestion of sausage, i.e. 44%. CONCLUSION: The data provide support for the suspected causal association between ingestion of NOCs from cured meats during pregnancy and subsequent CBT in offspring. Limitations in study design preclude definitive conclusions, but the relationship warrants exploration via additional observational and laboratory-based studies. Copyright 2004 S. Karger AG, Basel

Epidemiologic Investigation of Immune-Mediated Polyradiculoneuropathy among Abattoir Workers Exposed to Porcine Brain

Background In October 2007, a cluster of patients experiencing a novel polyradiculoneuropathy was identified at a pork abattoir (Plant A). Patients worked in the primary carcass processing area (warm room); the majority processed severed heads (head-table). An investigation was initiated to determine risk factors for illness. Methods and Results Symptoms of the reported patients were unlike previously described occupational associated illnesses. A case-control study was conducted at Plant A. A case was defined as evidence of symptoms of peripheral neuropathy and compatible electrodiagnostic testing in a pork abattoir worker. Two control groups were used - randomly selected non-ill warm-room workers (n = 49), and all non-ill head-table workers (n = 56). Consenting cases and controls were interviewed and blood and throat swabs were collected. The 26 largest U.S. pork abattoirs were surveyed to identify additional cases. Fifteen cases were identified at Plant A; illness onsets occurred during May 2004–November 2007. Median age was 32 years (range, 21–55 years). Cases were more likely than warm-room controls to have ever worked at the head-table (adjusted odds ratio [AOR], 6.6; 95% confidence interval [CI], 1.6–26.7), removed brains or removed muscle from the backs of heads (AOR, 10.3; 95% CI, 1.5–68.5), and worked within 0–10 feet of the brain removal operation (AOR, 9.9; 95% CI, 1.2–80.0). Associations remained when comparing head-table cases and head-table controls. Workers removed brains by using compressed air that liquefied brain and generated aerosolized droplets, exposing themselves and nearby workers. Eight additional cases were identified in the only two other abattoirs using this technique. The three abattoirs that used this technique have stopped brain removal, and no new cases have been reported after 24 months of follow up. Cases compared to controls had higher median interferon-gamma (IFNγ) levels (21.7 pg/ml; vs 14.8 pg/ml, P<0.001). Discussion This novel polyradiculoneuropathy was associated with removing porcine brains with compressed air. An autoimmune mechanism is supported by higher levels of IFNγ in cases than in controls consistent with other immune mediated illnesses occurring in association with neural tissue exposure. Abattoirs should not use compressed air to remove brains and should avoid procedures that aerosolize CNS tissue. This outbreak highlights the potential for respiratory or mucosal exposure to cause an immune-mediated illness in an occupational setting.

Nearwork-induced transient myopia (NITM) and permanent myopia--is there a link?

Myopia is a worldwide public health problem. However, its understanding is incomplete, and many of its preventative and therapeutic aspects remain controversial. Nearwork is a primary, environmentally based factor in the aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM) being a possible contributory component. A relationship between PM and NITM has been suggested, but that connection has remained somewhat indirect and elusive. However, based on recent converging evidence from clinical, laboratory and modelling studies, a five-fold argument will be advanced for a possible link between PM and NITM.

Suicide Mortality in Relation to Dietary Intake of n-3 and n-6 Polyunsaturated Fatty Acids and Fish: Equivocal Findings From 3 Large US Cohort Studies

Intake of n-3 and n-6 polyunsaturated fatty acids (PUFAs) has been implicated in the pathogenesis of depression. We sought to estimate the association between intake of fish and n-3 and n-6 PUFAs and suicide mortality over the course of long-term follow-up. In this prospective cohort study, biennial questionnaires were administered to 42,290 men enrolled in the Health Professionals Follow-up Study (1988–2008), 72,231 women enrolled in the Nurses' Health Study (1986–2008), and 90,836 women enrolled in Nurses' Health Study II (1993–2007). Dietary fish and n-3 and n-6 PUFA intakes were assessed every 4 years using a validated food-frequency questionnaire. Suicide mortality was ascertained through blind physician review of death certificates and hospital or pathology reports. Adjusted relative risks of suicide mortality were estimated with multivariable Cox proportional hazards models and pooled across cohorts using random-effects meta-analysis. The pooled multivariable relative risks for suicide among persons in the highest quartile of intake of n-3 or n-6 PUFAs, relative to the lowest quartile, ranged from 1.08 to 1.46 for n-3 PUFAs (Ptrend = 0.11–0.52) and from 0.68 to 1.19 for n-6 PUFAs (Ptrend = 0.09–0.54). We did not find evidence that intake of n-3 PUFAs or fish lowered the risk of completed suicide.

Antidepressants and the placebo response.

AIMS: To evaluate new generation antidepressants in relation to the placebo response. METHODS: I review meta-analyses in which response to antidepressant medication and response to placebo were calculated. RESULTS: All but one of these meta-analyses included unpublished as well as published trials. Most trials failed to show a significant advantage of SSRIs over inert placebo, and the differences between drug and placebo are not clinically significant for most depressed patients. Documents obtained from the U.S. Food and Drug Administration (FDA) revealed an explicit decision to keep this information from the public and from prescribing physicians. CONCLUSIONS: Because they do not incur drug risks, exercise and psychotherapy, which show at benefits at least equal to those of antidepressants, may be a better treatment choice for depressed individuals.

Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)

Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.

Selective publication of antidepressant trials and its influence on apparent efficacy.

BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set. RESULTS: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall. CONCLUSIONS: We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients. Copyright 2008 Massachusetts Medical Society.

Processed meats and risk of childhood leukemia (California, USA).

The relation between the intake of certain food items thought to be precursors or inhibitors of N-nitroso compounds (NOC) and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California (United States). Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random-digit dialing. Interviews were obtained from 232 cases and 232 controls. Food items of principal interest were: breakfast meats (bacon, sausage, ham); luncheon meats (salami, pastrami, lunch meat, corned beef, bologna); hot dogs; oranges and orange juice; and grapefruit and grapefruit juice. We also asked about intake of apples and apple juice, regular and charcoal broiled meats, milk, coffee, and coke or cola drinks. Usual consumption frequencies were determined for both parents and the child. When the risks were adjusted for each other and other risk factors, the only persistent significant associations were for children's intake of hot dogs (odds ratio [OR] = 9.5, 95 percent confidence interval [CI] = 1.6-57.6 for 12 or more hot dogs per month, trend P = 0.01), and fathers' intake of hot dogs (OR = 11.0, CI = 1.2-98.7 for highest intake category, trend P = 0.01). There was no evidence that fruit intake provided protection. While these results are compatible with the experimental animal literature and the hypothesis that human NOC intake is associated with leukemia risk, given potential biases in the data, further study of this hypothesis with more focused and comprehensive epidemiologic studies is warranted.

An epidemiologic study of thyroid cancer in Hawaii.

A population-based case-control interview study was designed to test the hypothesis that dietary iodine or the consumption of goitrogenic vegetables increases the risk of thyroid cancer. A total of 191 histologically confirmed cases (64 percent female) and 441 matched controls from five ethnic groups in Hawaii were available for analysis. Among women, intake of seafood (especially shellfish), harm ha (a fermented fish sauce), and dietary iodine were associated with an increased risk of cancer, whereas consumption of goitrogenic (primarily cruciferous) vegetables was associated with a decreased risk. Non-dietary risk factors included miscarriage (especially at first pregnancy), use of fertility drugs, family history of thyroid disease, obesity, and work as a farm laborer. The odds ratio for the combined effect of a high iodine intake and a first-pregnancy miscarriage was 4.8 (95 percent confidence interval [CI] = 1.2-19.2); and for high iodine intake and use of fertility drugs 7.3 (95 percent CI = 1.5-34.5). Among men, positive associations were found for obesity, work as a farm laborer, and a past history of benign thyroid disease. Although this study identified several dietary and non-dietary risk factors for thyroid cancer, it could not fully explain the exceptionally high incidence rates among Filipino women in Hawaii.

To Have or Not To Have a Pet for Better Health?

Background Pet ownership is thought to have health benefits, but not all scientific explorations have been founded on proper applications of representative samples or statistically correct methodologies. Databanks have been too small for proper statistical analyses; or, instead of a random sample, participation has been voluntary. The direction of causality has been evaluated incorrectly or control of relevant factors noted deficient. This study examined the associations of pet ownership with perceived health and disease indicators by taking into account socio-demographic background factors together with health risk factors, including exercise. Methodology/Principal Findings The present study used baseline data from the 15-year Health and Social Support Study (the HeSSup Study). The Finnish Population Register Centre was used to draw population-based random samples stratified according to gender and four age groups (20–24, 30–34, 40–44, and 50–54 years). A total of 21,101 working-aged Finns responded to the baseline survey questionnaire of the 15-year HeSSup Study in 1998. Ordinal and binary logistic regression was used to analyze the cross-sectional data. Pet ownership was associated with poor rather than good perceived health. BMI surfaced as the risk factor most strongly associated with pet ownership. Conclusions/Significance Pet owners set in their ways and getting older were found to have a slightly higher BMI than the rest. Additional research is needed for the testing of hypotheses involving effects of pet ownership with various health dimensions within population groups that are composed of different kinds of background characteristics.

Associations between meat consumption and the prevalence of degenerative arthritis and soft tissue disorders in the adventist health study, Califor...

OBJECTIVE: To examine associations between the prevalence of degenerative arthritis and soft tissue disorders and consumption of meat and other foods among participants in the Adventist Health Study. METHODS: Unconditional logistic regression analysis is used to examine cross-sectional associations, adjusting for the effects of age, smoking, alcohol consumption, body mass index, use of sex hormones and parity. RESULTS: The prevalence of degenerative arthritis and soft tissue disorders was 22.60 percent. Women had a higher prevalence than men and prevalence increased greatly with age. Smoking, higher body mass index, never use of contraceptive pills, and current hormone replacement therapy are associated with a higher prevalence of these disorders on multivariate analysis. Multivariate OR's comparing consumption of meat < 1/week; >or= 1/week; with the reference being no meat, were 1.31(95% CI: 1.21,1.43) and 1.49(1.31, 1.70) in women; and 1.19 (95% CI: 1.05,1.34) and 1.43(1.20, 1.70) in men. Dairy fat and fruit consumption were weakly associated with increased risk. There were protective associations with nut and salad consumption. CONCLUSIONS: Greater meat consumption is associated with a higher prevalence of degenerative arthritis and soft tissue disorders in both male and female subjects of this population, as is hormone replacement therapy in women.

Loving-Kindness Meditation practice associated with longer telomeres in women.

Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p=.083); among women, the LKM practitioners had significantly longer RTL than controls, (p=.007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of ascorbic acid and green tea on endogenous formation of N-nitrosodimethylamine and N-nitrosopiperidine in humans.

Many constituents present in the human diet may inhibit endogenous formation of N-nitroso compounds (NOC). Studies with human volunteers showed inhibiting effects of intake of ascorbic acid and green tea consumption on nitrosation using the N-nitrosoproline test. The aim of the present study was to evaluate the effects of ascorbic acid and green tea on urinary excretion of carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) in humans. Twenty-five healthy female volunteers consumed a fish meal rich in amines as nitrosatable precursors in combination with intake of nitrate-containing drinking water at the Acceptable Daily Intake level during 7 consecutive days. During 1 week before and after nitrate intake a diet low in nitrate was consumed. Using the same protocol, the effect of two different doses of ascorbic acid (250 mg and 1 g/day) and two different doses of green tea (2 g and 4 g/day) on formation of NDMA and NPIP was studied. Mean nitrate excretion in urine significantly increased from control (76+/-24) to 167+/-25 mg/24 h. Intake of nitrate and fish resulted in a significant increase in mean urinary excretion of NDMA compared with the control weeks: 871+/-430 and 640+/-277 ng/24 h during days 1-3 and 4-7, respectively, compared with 385+/-196 ng/24 h (p<0.0002). Excretion of NPIP in urine was not related to nitrate intake and composition of the diet. Intake of 250 mg and 1 g of ascorbic acid per day resulted in a significant decrease in urinary NDMA excretion during days 4-7 (p=0.0001), but not during days 1-3. Also, consumption of four cups of green tea per day (2 g) significantly decreased excretion of NDMA during days 4-7 (p=0.0035), but not during days 1-3. Surprisingly, consumption of eight cups of green tea per day (4 g) significantly increased NDMA excretion during days 4-7 (p=0.0001), again not during days 1-3. This increase is probably a result of catalytic effects of tea polyphenols on nitrosation, or of another, yet unknown, mechanism. These results suggest that intake of ascorbic acid and moderate consumption of green tea can reduce endogenous NDMA formation.

Lipid Concentrations and Semen Quality: The LIFE Study

The decline in sperm count rates over the last 50 years appears to parallel the rising prevalence of obesity. As lipids levels are strongly associated with obesity, high lipids levels or hyperlipidemia may thus play an important role in the decline in fertility in addition to other environmental or lifestyle factors. The objective of this population based cohort study was to evaluate the association between men’s serum lipid concentrations and semen quality parameters among 501 male partners of couples desiring pregnancy and discontinuing contraception. Each participant provided prospectively up to two semen samples (94% of men provided one or more semen samples, and 77% of men provided a second sample approximately one month later). Linear mixed effects models were used to estimate the associations between baseline lipid concentrations and semen quality parameters, adjusted for age, body mass index, and race. We found that higher levels of serum total cholesterol, free cholesterol and phospholipids were associated with a significantly lower percentage of sperm with intact acrosome and smaller sperm head area and perimeter. Our results suggest that lipid concentrations may affect semen parameters, specifically sperm head morphology, highlighting the importance of cholesterol and lipid homeostasis for male fecundity.

N-Nitroso compounds in the diet.

N-Nitroso compounds were known almost 40 years ago to be present in food treated with sodium nitrite, which made fish meal hepatotoxic to animals through formation of nitrosodimethylamine (NDMA). Since that time, N-nitroso compounds have been shown in animal experiments to be the most broadly acting and the most potent group of carcinogens. The key role of nitrite and nitrogen oxides in forming N-nitroso compounds by interaction with secondary and tertiary amino compounds has led to the examination worldwide of foods for the presence of N-nitroso compounds, which have been found almost exclusively in those foods containing nitrite or which have become exposed to nitrogen oxides. Among these are cured meats, especially bacon-and especially when cooked; concentrations of 100 micrograms kg(-1) have been found or, more usually, near 10 micrograms kg(-1). This would correspond to consumption of 1 microgram of NDMA in a 100-g portion. Much higher concentrations of NDMA (but lower ones of other nitrosamines) have been found in Japanese smoked and cured fish (more than 100 micrograms kg(-1)). Beer is one source of NDMA, in which as much as 70 micrograms l(-1) has been reported in some types of German beer, although usual levels are much lower (10 or 5 micrograms l(-1)); this could mean a considerable intake for a heavy beer drinker of several liters per day. Levels of nitrosamines have been declining during the past three decades, concurrent with a lowering of the nitrite used in food and greater control of exposure of malt to nitrogen oxides in beer making. There have been declines of N-nitroso compound concentrations in many foods during the past two decades. The small amounts of nitrosamines in food are nonetheless significant because of the possibility-even likelihood-that humans are more sensitive to these carcinogens than are laboratory rodents. Although it is probable that alkylnitrosamides (which induce brain tumors in rodents) are present in cured meats and other potentially nitrosated products in spite of much searching, there has been only limited indirect evidence of their presence. Copyright 1999 Elsevier Science B.V.

Cooked meat and risk of breast cancer--lifetime versus recent dietary intake.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.

Nut consumption, weight gain and obesity: Epidemiological evidence.

BACKGROUND AND AIMS: Short-term trials support that adding tree nuts or peanuts to usual diets does not induce weight gain. We reviewed the available epidemiological evidence on long-term nut consumption and body weight changes. We also report new results from the SUN ("Seguimiento Universidad de Navarra") cohort. METHODS AND RESULTS: Published epidemiologic studies with ≥1-yr follow-up were located. Two published reports from large cohorts (SUN and Nurses Health Study-2) showed inverse associations between frequency of nut consumption and long-term weight changes. A beneficial effect of a Mediterranean diet supplemented with tree nuts on waist circumference was reported after 1-yr follow-up in the first 1224 high-risk participants in the PREDIMED ("PREvencion DIeta MEDiterranea") trial. After assessing 11,895 participants of the SUN cohort, a borderline significant (p value for trend = 0.09) inverse association between baseline nut consumption and average yearly weight gain (multivariate-adjusted means = 0.32 kg/yr (95% confidence interval: 0.22-0.42) and 0.24 (0.11-0.37) kg/yr for participants with no consumption and >4 servings/week, respectively) was found after a 6-yr follow-up. CONCLUSIONS: Consumption of nuts was not associated with a higher risk of weight gain in long-term epidemiologic studies and clinical trials. Copyright © 2010 Elsevier B.V. All rights reserved.

Soy food consumption and breast cancer prognosis.

BACKGROUND: Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis. METHODS: Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model. RESULTS: As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death. CONCLUSION: Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis. IMPACT: These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer. ©2011 AACR.

Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis.

BACKGROUND: Sexual dysfunction (SD) is an important underestimated adverse effect of antidepressant drugs. Patients, in fact, if not directly questioned, tend to scarcely report them. The aim of the present meta-analysis was to quantify SD caused by antidepressants on the basis of studies where sexual functioning was purposely investigated through direct inquiry and specific questionnaires. METHODS: A literature search was conducted using MEDLINE, ISI Web of Knowledge, and references of selected articles. Selected studies performed on patients without previous SD were entered in the Cochrane Collaboration Review Manager (RevMan version 4.2). Our primary outcome measure was the rate of total treatment-emergent SD. Our secondary outcome measures were the rates of treatment-emergent desire, arousal, and orgasm dysfunction. RESULTS: Our analyses indicated a significantly higher rate of total and specific treatment-emergent SD and specific phases of dysfunction compared with placebo for the following drugs in decreasing order of impact: sertraline, venlafaxine, citalopram, paroxetine, fluoxetine, imipramine, phenelzine, duloxetine, escitalopram, and fluvoxamine, with SD ranging from 25.8% to 80.3% of patients. No significant difference with placebo was found for the following antidepressants: agomelatine, amineptine, bupropion, moclobemide, mirtazapine, and nefazodone. DISCUSSION: Treatment-emergent SD caused by antidepressants is a considerable issue with a large variation across compounds. Some assumptions, such as the inclusion of open-label studies or differences in scales used to assess SD, could reduce the significance of our findings. However, treatment-emergent SD is a frequent adverse effect that should be considered in clinical activity for the choice of the prescribed drug.

Plant foods and brain aging: a critical appraisal.

In the 21st century, human aging will be one of the biggest challenges for most societies throughout the world. The decline in human fitness is a typical hallmark of the aging process. Aside from the cardiovascular system, the brain most often suffers significantly from the life-long impact of stressors, such as reactive oxygen and nitrogen species. Oxytosis, i.e. oxidative stress-induced cell death, has been identified to play a major role in the development and onset of chronic diseases. Foods, especially of plant origin, are rich in antioxidants and numerous in vivo data suggest that a diet rich in fruits and vegetables supports the maintenance of animal and human health. These beneficial effects also extend to the central nervous system, which, due to the presence of the blood-brain barrier, tightly controls the influx of metabolites and nutrients. In earlier studies the impact of antioxidant vitamins, such as alpha-tocopherol and ascorbic acid, on brain health has been of interest. Recently, the focus moved to assessing the potential of unsaturated fatty acids and secondary plant metabolites, particularly of polyphenols, to act as neuroprotectants. Considerable experimental evidence suggests that polyphenols and other plant-derived bioactivities affect animal and human brain function not only by directly lowering oxidative stress load but also by modulating various signal transduction pathways.

Why do African Americans get more colon cancer than Native Africans?

The incidence of colorectal cancer (CRC) is dramatically higher in African Americans (AAs) than in Native Africans (NAs) (60:100,000 vs. <1:100,000) and slightly higher than in Caucasian Americans (CAs). To explore whether the difference could be explained by interactions between diet and colonic bacterial flora, we compared randomly selected samples of healthy 50- to 65-y-old AAs (n = 17) with NAs (n = 18) and CAs (n = 17). Diet was measured by 3-d recall, and colonic metabolism by breath hydrogen and methane responses to oral lactulose. Fecal samples were cultured for 7-alpha dehydroxylating bacteria and Lactobacillus plantarum. Colonoscopic mucosal biopsies were taken to measure proliferation rates. In comparison with NAs, AAs consumed more (P < 0.01) protein (94 +/- 9.3 vs. 58 +/- 4.1 g/d) and fat (114 +/- 11.2 vs. 38 +/- 3.0 g/d), meat, saturated fat, and cholesterol. However, they also consumed more (P < 0.05) calcium, vitamin A, and vitamin C, and fiber intake was the same. Breath hydrogen was higher (P < 0.0001) and methane lower in AAs, and fecal colony counts of 7-alpha dehydroxylating bacteria were higher and of Lactobacilli were lower. Colonic crypt cell proliferation rates were dramatically higher in AAs (21.8 +/- 1.1% vs. 3.2 +/- 0.8% labeling, P < 0.0001). In conclusion, the higher CRC risk and mucosal proliferation rates in AAs than in NAs were associated with higher dietary intakes of animal products and higher colonic populations of potentially toxic hydrogen and secondary bile-salt-producing bacteria. This supports our hypothesis that CRC risk is determined by interactions between the external (dietary) and internal (bacterial) environments.