A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk.

OBJECTIVE: To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk. METHODS: A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed. RESULTS: Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event. CONCLUSION: Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs.

Multivitamin-mineral use is associated with reduced risk of cardiovascular disease mortality among women in the United States.

BACKGROUND: Multivitamin-mineral (MVM) products are the most commonly used supplements in the United States, followed by multivitamin (MV) products. Two randomized clinical trials (RCTs) did not show an effect of MVMs or MVs on cardiovascular disease (CVD) mortality; however, no clinical trial data are available for women with MVM supplement use and CVD mortality. OBJECTIVE: The objective of this research was to examine the association between MVM and MV use and CVD-specific mortality among US adults without CVD. METHODS: A nationally representative sample of adults from the restricted data NHANES III (1988-1994; n = 8678; age ≥40 y) were matched with mortality data reported by the National Death Index through 2011 to examine associations between MVM and MV use and CVD mortality by using Cox proportional hazards models, adjusting for multiple potential confounders. RESULTS: We observed no significant association between CVD mortality and users of MVMs or MVs compared with nonusers; however, when users were classified by the reported length of time products were used, a significant association was found with MVM use of >3 y compared with nonusers (HR: 0.65; 95% CI: 0.49, 0.85). This finding was largely driven by the significant association among women (HR: 0.56; 95% CI: 0.37, 0.85) but not men (HR: 0.79; 95% CI: 0.44, 1.42). No significant association was observed for MV products and CVD mortality in fully adjusted models. CONCLUSIONS: In this nationally representative data set with detailed information on supplement use and CVD mortality data ∼20 y later, we found an association between MVM use of >3 y and reduced CVD mortality risk for women when models controlled for age, race, education, body mass index, alcohol, aspirin use, serum lipids, blood pressure, and blood glucose/glycated hemoglobin. Our results are consistent with the 1 available RCT in men, indicating no relation with MVM use and CVD mortality.

Effects of whey protein and resistance exercise on body composition: a meta-analysis of randomized controlled trials.

OBJECTIVES: The objective of the present meta-analysis was to examine the effect of whey protein (WP), with or without resistance exercise, on body weight and body composition in randomized controlled trials (RCTs) conducted in generally healthy adult study populations. METHODS: A comprehensive literature search was conducted to identify RCTs that investigated WP (concentrate, isolate, or hydrolystate) and body weight, body mass index (BMI), body fat, lean body mass (LBM), fat-free mass (FFM), and waist circumference. Random effects meta-analyses were conducted to generate weighted group mean differences (WGMD) for between-group comparisons (WP vs other protein sources or carbohydrates) and within-WP group comparisons (i.e., differences from baseline to trial end). Studies were classified into 2 distinct groups-WP as a supplement without dietary modification (WPS) and WP as a replacement for other sources of calories (WPR)-and were meta-analyzed separately. Subgroup analyses included examining the effect of resistance exercise and type of WP on the relationship between WP and body composition. RESULTS: Fourteen RCTs were included, with a total of 626 adult study completers. Five studies examined the effects of WPR and the remaining 9 studies examined the effects of WPS. Body weight (WGMD: -4.20 kg, 95% confidence interval [CI], -7.67, -0.73) and body fat (WGMD: -3.74 kg, 95% CI, -5.98, -1.50) were significantly decreased from baseline in the WPR within-group analyses. In the between-group analyses, the effects of WP were more favorable when compared with carbohydrates than protein sources other than whey, although findings did not reach statistical significance. Results from the subgroup analyses indicated a statistically significant increase in LBM (WGMD: 2.24 kg, 95% CI, 0.66, 3.81) among studies that included a resistance exercise component along with WP provision. CONCLUSION: The current body of literature supports the use of WP, either as a supplement combined with resistance exercise or as part of a weight loss or weight maintenance diet, to improve body composition parameters.

Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials.

BACKGROUND: Although a large body of literature has been devoted to examining the relationship between eicosapentaenoic and docosahexaenoic acids (EPA+DHA) and blood pressure, past systematic reviews have been hampered by narrow inclusion criteria and a limited scope of analytical subgroups. In addition, no meta-analysis to date has captured the substantial volume of randomized controlled trials (RCTs) published in the past 2 years. The objective of this meta-analysis was to examine the effect of EPA+DHA, without upper dose limits and including food sources, on blood pressure in RCTs. METHODS: Random-effects meta-analyses were used to generate weighted group mean differences and 95% confidence intervals (CIs) between the EPA+DHA group and the placebo group. Analyses were conducted for subgroups defined by key subject or study characteristics. RESULTS: Seventy RCTs were included. Compared with placebo, EPA+DHA provision reduced systolic blood pressure (-1.52 mm Hg; 95% confidence interval (CI) = -2.25 to -0.79) and diastolic blood pressure (-0.99 mm Hg; 95% CI = -1.54 to -0.44) in the meta-analyses of all studies combined. The strongest effects of EPA+DHA were observed among untreated hypertensive subjects (systolic blood pressure = -4.51 mm Hg, 95% CI = -6.12 to -2.83; diastolic blood pressure = -3.05 mm Hg, 95% CI = -4.35 to - 1.74), although blood pressure also was lowered among normotensive subjects (systolic blood pressure = -1.25 mm Hg, 95% CI = -2.05 to -0.46; diastolic blood pressure = -0.62 mm Hg, 95% CI = -1.22 to -0.02). CONCLUSIONS: Overall, available evidence from RCTs indicates that provision of EPA+DHA reduces systolic blood pressure, while provision of ≥2 grams reduces diastolic blood pressure.

A systematic review of multivitamin-multimineral use and cardiovascular disease and cancer incidence and total mortality.

Multivitamin-multimineral (MVM) supplements are the most frequently used dietary supplements in the United States, with one third or more of the population using at least one daily. However, the health-related implications of MVM use are unclear. Thus, we systematically reviewed and summarized the prospective studies of MVM supplementation and all-cause and cause-specific mortality, as well as cardiovascular disease (CVD) and cancer incidence, to critically evaluate the current evidence on this topic. We included studies of generally healthy adult populations that evaluated multivitamin (the most commonly used dietary supplement) and/or multimineral supplement use or simultaneous use of 3 or more vitamins and minerals. We did not evaluate individual supplements. A total of 12 cohort studies and 3 primary prevention randomized controlled trials met our inclusion criteria. The majority of the studies were conducted in the United States (n = 11), and the remaining were conducted in European countries (n = 3) and Japan (n = 1). Although between-study methodological variation was present, most relative risks hovered closely around or slightly below the null value. No clear patterns of associations by study country, gender, smoking status, or frequency of use were observed. Based upon the available scientific evidence to date, supplementation with MVMs does not appear to increase all-cause mortality, cancer incidence or mortality, or CVD incidence or mortality and may provide a modest protective benefit.

Association of dietary and supplemental folate intake and polymorphisms in three FOCM pathway genes with colorectal cancer in a population-based case-control study.

Previous research has shown that greater intakes of dietary folate are associated with reduced risk for colorectal cancer (CRC) and that single nucleotide polymorphisms (SNPs) in genes involved in folate-mediated one-carbon metabolism (FOCM) also may be involved in altering CRC risk. The objective of this study was to evaluate the role of folate intake (and intakes of related dietary components such as methionine), 35 SNPs in three FOCM pathway genes (MTHFD1, MTHFR, and TYMS), and their interactions on CRC risk in a population-based case-control study in Pennsylvania (686 cases, 740 controls). Diet and supplement use was assessed for the year before diagnosis or interview for cases and controls, respectively, with a modified Diet History Questionnaire from the National Cancer Institute. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. Using a dominant model for the variant allele, several SNPs were significantly associated with CRC including MTHFD1 rs8003379 (OR = 1.65; 95% CI = 1.00-2.73) and rs17824591 (OR = 1.98; 95% CI = 1.14-3.41) and the TYMS rs2853533 SNP (OR = 1.38; 95% CI = 1.05-1.80). Using a nondominant model, the AA genotype for MTHFR rs1476413 exhibited a marginally significant (OR = 1.56; 95% CI = 1.00-2.44) association with CRC. Two TYMS SNPs (rs16948305 and rs495139) exhibited significant (P = 0.024 and P = 0.040, respectively) gene-diet interactions with folate intake. One MTHFD1 (P = 0.019) and one MTHFR (P = 0.042) SNP exhibited gene-diet interactions with methionine intake. These findings suggest that allelic variants in genes involved in FOCM interact with dietary factors including folate and methionine to modify risk for CRC.

Association of dietary and supplemental iron and colorectal cancer in a population-based study.

We evaluated the role of dietary iron, heme iron, and supplemental iron on colorectal cancer (CRC) risk in a population-based case-control study in Pennsylvania, including 1005 incident cases and 1062 controls. Diet was assessed through a modified food frequency questionnaire that included supplement use and a meat-specific module. Cases reported intakes for the year before diagnosis, whereas controls reported intakes for the year before interview. Heme iron intake was calculated using a new heme database developed by the US National Cancer Institute. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. After multivariate adjustment, there were no significant associations between heme iron or total iron intake and CRC incidence. Dietary iron intake was inversely associated with CRC among women (OR Q5 vs. Q1=0.45; 95% CI=0.22-0.92), but not among men. Supplemental iron intake of more than 18 mg/day versus none was positively associated with CRC incidence (OR=2.31; 95% CI=1.48-3.59; P-trend<0.001), an effect that was observed in both men (OR=2.56; 95% CI=1.30-5.05) and women (OR=2.46; 95% CI=1.34-4.52). These findings suggest that consumption of more than 18 mg/day of supplemental iron may increase risk for CRC.

Why US adults use dietary supplements.

BACKGROUND: Dietary supplements are used by more than half of adults, although to our knowledge, the reasons motivating use have not been previously examined in US adults using nationally representative data. The purpose of this analysis was to examine motivations for dietary supplement use, characterize the types of products used for the most commonly reported motivations, and to examine the role of physicians and health care practitioners in guiding choices about dietary supplements. METHODS: Data from adults (≥20 years; n = 11 956) were examined in the 2007-2010 National Health and Nutrition Examination Survey, a nationally representative, cross-sectional, population-based survey. RESULTS: The most commonly reported reasons for using supplements were to "improve" (45%) or "maintain" (33%) overall health. Women used calcium products for "bone health" (36%), whereas men were more likely to report supplement use for "heart health or to lower cholesterol" (18%). Older adults (≥60 years) were more likely than younger individuals to report motivations related to site-specific reasons like heart, bone and joint, and eye health. Only 23% of products were used based on recommendations of a health care provider. Multivitamin-mineral products were the most frequently reported type of supplement taken, followed by calcium and ω-3 or fish oil supplements. Supplement users are more likely to report very good or excellent health, have health insurance, use alcohol moderately, eschew cigarette smoking, and exercise more frequently than nonusers. CONCLUSIONS: Supplement users reported motivations related to overall health more commonly than for supplementing nutrients from food intakes. Use of supplements was related to more favorable health and lifestyle choices. Less than a quarter of supplements used by adults were recommended by a physician or health care provider.

Phytochemicals and cancer risk: a review of the epidemiological evidence.

A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of ß-carotene and renal cell cancer, ß-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.

Dietary patterns and colorectal adenoma and cancer risk: a review of the epidemiological evidence.

A number of studies exploring associations between individual dietary components and colorectal adenoma or cancer risk have yielded conflicting results. The study of food-based dietary patterns in relation to chronic disease risk represents an alternative approach to the evaluation of single dietary exposures in epidemiological investigations. Results from prospective cohort and population-based case-control studies examining associations between dietary patterns and colorectal cancer or adenoma risk were evaluated and described in this review. Despite notable differences in population characteristics, study design, and methods used for characterizing dietary patterns across the different studies, two general dietary patterns were found to modestly predict colorectal adenoma and cancer risk. A healthier pattern consisting of greater intakes of fruits and vegetables, and lower intakes of red and processed meat, appeared protective against colorectal adenoma and cancer incidence. Findings also suggest that a less healthy pattern characterized by higher intakes of red and processed meat, as well as potatoes and refined carbohydrates, may increase risk. Continued research efforts are needed to evaluate the cumulative and interactive effects of numerous dietary exposures on colorectal cancer risk.

Dietary screening tool identifies nutritional risk in older adults.

BACKGROUND: No rapid methods exist for screening overall dietary intakes in older adults. OBJECTIVE: The purpose of this study was to develop and evaluate a scoring system for a diet screening tool to identify nutritional risk in community-dwelling older adults. DESIGN: This cross-sectional study in older adults (n = 204) who reside in rural areas examined nutrition status by using an in-person interview, biochemical measures, and four 24-h recalls that included the use of dietary supplements. RESULTS: The dietary screening tool was able to characterize 3 levels of nutritional risk: at risk, possible risk, and not at risk. Individuals classified as at nutritional risk had significantly lower indicators of diet quality (Healthy Eating Index and Mean Adequacy Ratio) and intakes of protein, most micronutrients, dietary fiber, fruit, and vegetables. The at-risk group had higher intakes of fats and oils and refined grains. The at-risk group also had the lowest serum vitamin B-12, folate, beta-cryptoxanthin, lutein, and zeaxanthin concentrations. The not-at-nutritional-risk group had significantly higher lycopene and beta-carotene and lower homocysteine and methylmalonic acid concentrations. CONCLUSION: The dietary screening tool is a simple and practical tool that can help to detect nutritional risk in older adults.

Dietary supplement use in adult cancer survivors.

PURPOSE/OBJECTIVES: To assess dietary supplement use and its association with demographic and health-related characteristics among cancer survivors and to investigate differences in supplement use patterns by cancer site. DESIGN: A cross-sectional survey. SETTING: Computer-assisted telephone survey. SAMPLE: 1,233 adult (ages 30-69) survivors participating in the Penn State Cancer Survivor Study who underwent an interviewer-administered questionnaire. METHODS: Descriptive statistics with multivariate logistic regression to determine demographic, disease, and health-related predictors of supplement use. MAIN RESEARCH VARIABLES: Use of dietary supplements and types of supplements taken. FINDINGS: Supplement use ranged from 50% among blood cancer survivors to 85% among melanoma skin cancer survivors, with an overall prevalence rate of 73%. Multivariate logistic regression revealed statistically significant associations (p values < 0.05) between supplement use and older age (>or= age 50), higher levels of education and physical activity, female gender, lower body mass index, and white ethnicity. CONCLUSIONS: Overall, a wide variety of supplements were reported, although multivitamins, calcium and vitamin D combinations, and antioxidant vitamin combinations were the most prevalent. Seventy-eight percent of supplement users took more than one supplement. IMPLICATIONS FOR NURSING: The findings support continued efforts by oncology nurses to identify the types of supplements cancer survivors are using. Nurses should caution against the use of individual supplements as well as combinations of different supplements containing nutrient quantities above recommended daily intake levels. Furthermore, oncology nurses and other healthcare professionals should be receptive to questions and prepared to initiate conversations with patients about their use of dietary supplements.

Dietary supplement use among elderly, long-term cancer survivors.

INTRODUCTION: The purpose of the present study was to assess dietary supplement use and its association with micronutrient intakes and diet quality among older (>or=65 years), long-term survivors (>or=5 years post-diagnosis) of female breast, prostate, and colorectal cancer. METHODS: The sample included 753 survivors who participated in telephone screening interviews to determine eligibility for a randomized diet and physical activity intervention trial entitled RENEW: Reach-out to ENhancE Wellness in Older Cancer Survivors. Telephone surveys included two 24-hour dietary recalls and items regarding supplement use (type, dose, and duration). Nutrient intakes were compared to Dietary Reference Intakes (DRIs). Diet quality was assessed using the revised Healthy Eating Index (HEI). Descriptive statistics and multivariate logistic regression were used in this cross-sectional study. RESULTS: A majority of survivors (74%) reported taking supplements, with multivitamins (60%), calcium/vitamin D (37%), and antioxidants (30%) as the most prevalent. Overall proportions of the total sample with dietary intakes below Estimated Average Requirements (EARs) were substantial, although supplement users had more favorable mean HEI scores (P < 0.01) and nutrient intakes for 12 of the 13 vitamins and minerals investigated (P values < 0.05). Supplement use was positively associated with older age (>or=70 years) (odds ratio (OR)=1.70; 95% confidence interval (95% CI)=1.17, 2.46) and female gender (OR=1.49; 95% CI=1.04, 2.13), and negatively associated with current smoking (OR=0.40, 95% CI=0.21, 0.76). Individuals scoring higher on the Total Fruit (OR=1.12, 95% CI=1.01, 1.23), Whole Grain (OR=1.14, 95% CI=1.04, 1.25), and Oil (OR=1.10, 95% CI=1.01, 1.11) components of the HEI were significantly more likely to take supplements, while those scoring higher on the Meat and Beans category (OR=0.81, 95% CI=0.71, 0.93) were significantly less likely to take supplements. Compared to those with less than a high school education, survivors with a professional or graduate degree were significantly more likely to use supplements (OR=2.18, 95% CI=1.13, 4.23). DISCUSSIONS/CONCLUSIONS: Demographic, disease, and health-related correlates of supplement use follow similar trends observed in the general population as well as previous reports from other cancer survivor populations. Supplement use may reduce the prevalence of nutrient inadequacies in this population, though survivors who use supplements are the least likely to need them. IMPLICATIONS FOR CANCER SURVIVORS: Supplement use may be an effective means for many survivors to achieve adequate nutrient intakes; however, open communication between healthcare providers and survivors is needed to ensure potential concerns are addressed as supplement use may not always be beneficial.

Childhood cancer survivors' perceived barriers to improving exercise and dietary behaviors.

PURPOSE/OBJECTIVES: To determine childhood cancer survivors' barriers to increasing exercise and consuming less fat and more fruits and vegetables, whole grains, and calcium-rich foods. DESIGN: Mailed survey. SETTING: Cases from a comprehensive cancer center. SAMPLE: Convenience sample of 144 childhood cancer survivors aged 13-35 years identified through previous research. Surveys were returned by 118 participants (82% response rate). METHODS: Descriptive statistics with chi-square tests were performed between subgroups defined by age (< 18 years and < or = 18 years) and diagnosis (leukemia, lymphoma, and central nervous system cancers). MAIN RESEARCH VARIABLES: Barriers to exercise, consuming less fat, and eating more fruits and vegetables, whole grains, and calcium-rich foods. FINDINGS: Proportionately more childhood cancer survivors reported barriers to exercise and following a low-fat diet than to consuming more fruits and vegetables, whole grains, and calcium-rich foods. Primary barriers to exercise included being too tired (57%), being too busy (53%), and not belonging to a gym (48%), whereas barriers for restricting high-fat foods were commercials that make high-fat foods look so appealing (58%) and having friends who eat a lot of high-fat foods (50%). Difficulty associated with ordering healthy foods when dining out also was a leading barrier to following a low-fat diet (50%), as well as eating more whole grains (31%), fruits and vegetables (30%), and calcium-rich foods (15%). CONCLUSIONS: Childhood cancer survivors report several barriers to exercise and consuming a low-fat diet with more fruits and vegetables, whole grains, and calcium-rich foods. IMPLICATIONS FOR NURSING: This study's findings may be helpful to nurses, health educators, and allied health professionals in developing effective interventions that promote healthful lifestyle change among childhood cancer survivors.