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Background: The quality of nutrition-related systematic reviews (SRs) is an unstudied but important factor affecting their usefulness. Objectives: The objectives were to evaluate the reporting quality of published SRs and to identify areas of improvement. Design: Descriptive and exploratory analyses of the reporting quality (7 nutrition items and 28 SR reporting items) of all Englishlanguage SRs published through July 2007 linking micronutrients and health outcomes in humans were conducted. Factors that may be associated with reporting quality were also evaluated. Results: We identified 141 eligible SRs of 21 micronutrients. Ninety SRs that included only interventional studies met a higher proportion of our reporting criteria (median: 62%; interquartile range: 51%, 72%) than did 31 SRs with only observational studies (median: 53%; interquartile range: 47%, 60%) or 20 SRs with both study designs (median: 47%; interquartile range: 39%, 52%) (P , 0.001). SRs published after consensus reporting standards (since 2003) met a higher proportion of the reporting criteria than did earlier SRs (median: 59% compared with 50%; P ¼ 0.01); however, the reporting of nutrition variables remained unchanged (median: 38% compared with 33%; P ¼ 0.7). The least-reported nutrition criteria were baseline nutrient exposures (28%) and effects of measurement errors from nutrition exposures (24%). Only 58 SRs (41%) used quality scales or checklists to assess the methodologic quality of the primary studies included. Conclusions: The reporting quality of SRs has improved 3 y after publication of SR reporting standards, but the reporting of nutrition variables has not. Improved adherence to consensus methods and reporting standards should improve the utility of nutrition SRs. Am J Clin Nutr 2009;89:1099‐113.

Nutrient reference values have significant public health and policy implications. Given the importance of defining reliable nutrient reference values, there is a need for an explicit, objective, and transparent process to set these values. The Tufts Medical Center Evidence-based Practice Center assembled a group of nutrition experts from academic institutions and federal government agencies, led participants in discussions, conducted exercises in formulating questions and evidence review criteria that would be amenable to systematic reviews of the scientific literature, performed a literature search on the questions to identify potentially relevant publications, and identified challenges and limitations of applying this method to support the development of nutrient reference values using vitamin A as an example. The workgroup concluded that the systematic review approach could be productively used to inform the development of reference values. Challenges identified in this exercise include prioritizing and defining research questions when the volume of literature is large, relying on intermediate (surrogate) outcomes when few or no studies directly linking nutrient intake with clinical outcomes are available, and determining reliable nutrient biomarkers. Ultimately, an objective, unbiased systematic review of a defined question could be useful, not only in helping to set nutrient reference values, but also for increasing the transparency of the decision making process.

Observational data have identified associations between carotenoids, folic acid, and vitamin E, or metabolites altered by these nutrients, and cardiovascular disease (CVD) risk. Despite biological plausibility, for the most part, data derived from nutrient supplement trials using moderate to high doses of single nutrients or nutrient combinations (exceeding amounts to avoid nutrient deficiency) have been disappointing. The data for vitamin D is not yet adequate to evaluate; observational data suggest were a relationship to exist it would be related to nutrient insufficiency. There is some evidence that use of nutrient supplements intended to decrease CVD risk has resulted in unanticipated adverse consequences. Potential discrepancies between observational and interventional data include concerns of residual confounding by diet and lifestyle patterns, publication bias against studies with null or negative outcomes, reliance on secondary rather than primary prevention trials, and unaccounted for contribution of genotypic variations. At this time there are insufficient data to recommend the routine use of nutrient supplements to prevent or treat CVD. In the recent past we have learned a great deal about anticipated and unanticipated consequences of nutrient supplementation and cardiovascular outcomes. As a result, we are in a better position to adjudicate new potential relationships as data emerge.

Objective— To investigate mechanisms underlying gender differences in serum lipoprotein concentrations, the kinetic behavior of apoB-100 was assessed. Methods and Results— Twenty subjects (r =−0.59, P r =−0.54, P r =−0.43, P r =−0.44, P Conclusions— These data suggest the mechanism for lower TRL-C and LDL-C concentrations in women was determined predominantly by higher TRL and LDL FCR rather than lower PR. This could explain, in part, the lower CVD risk in premenopausal women relative to men.

Objectives— Extended-release niacin effectively lowers plasma TG levels and raises plasma high-density lipoprotein (HDL) cholesterol levels, but the mechanisms responsible for these effects are unclear. Methods and Results— We examined the effects of extended-release niacin (2 g/d) and extended-release niacin (2 g/d) plus lovastatin (40 mg/d), relative to placebo, on the kinetics of apolipoprotein (apo) A-I and apoA-II in HDL, apoB-100 in TG-rich lipoproteins (TRL), intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), and apoB-48 in TRL in 5 men with combined hyperlipidemia. Niacin significantly increased HDL cholesterol and apoA-I concentrations, associated with a significant increase in apoA-I production rate (PR) and no change in fractional catabolic rate (FCR). Plasma TRL apoB-100 levels were significantly lowered by niacin, accompanied by a trend toward an increase in FCR and no change in PR. Niacin treatment significantly increased TRL apoB-48 FCR but had no effect on apoB-48 PR. No effects of niacin on concentrations or kinetic parameters of IDL and LDL apoB-100 and HDL apoA-II were noted. The addition of lovastatin to niacin promoted a lowering in LDL apoB-100 attributable to increased LDL apoB-100 FCR. Conclusion— Niacin treatment was associated with significant increases in HDL apoA-I concentrations and production, as well as enhanced clearance of TRL apoB-100 and apoB-48.

To compare the efficacy of single versus multiple doses of plant sterols on circulating lipid level and cholesterol trafficking.A randomized, placebo-controlled, three-phase (6 days/phase) crossover, supervised feeding trial was conducted in 19 subjects. Subjects were provided (i) control margarine with each meal; (ii) 1.8 g/day plant sterols in margarine with breakfast (single-BF) and control margarine with lunch and supper or (iii) 1.8 g/day plant sterols in margarine divided equally at each of the three daily meals (three times per day).Relative to control, end point plasma low-density lipoprotein (LDL) cholesterol concentrations were lower (P0.05) after consuming plant sterols three times per day but were not different when consumed once per day (3.43+/-0.62, 3.22+/-0.58 and 3.30+/-0.65 mmol/l, control, three times per day and single-BF, respectively). Relative to the control, end point LDL level was 0.21+/-0.27 mmol/l (6%) lower (P0.05) at the end of the three times per day phase. Cholesterol fractional synthesis rate was highest (P0.05) after the three times per day phase (0.0827+/-0.0278, 0.0834+/-0.0245 and 0.0913+/-0.0221 pool/day, control, single-BF and three times per day, respectively). Cholesterol-absorption efficiency decreased (P0.05) by 36 and 39% after the three times per day and single-BF phase, respectively, relative to control.Present data indicate that to obtain optimal cholesterol-lowering impact, plant sterols should be consumed as smaller doses given more often, rather than one large dose.

The waist-to-height ratio is an anthropometric measure of central adiposity that has emerged as a significant predictor of cardiovascular disease risk factors in children and adolescents. However, the simple waist-to-height ratio retains residual correlation with height, which could cause the measure to over- or under-adjust for the effect of height at certain ages. We investigated the dependence of waist-to-height ratio on height in the representative US National Health and Nutrition Examination Survey 1999-2004. We stratified 11 270 subjects aged 2-18 years by age and sex. There was considerable residual correlation between height and the waist-to-height ratio, ranging from -0.29 to 0.36. Thus, simply dividing waist circumference by height (WC/Ht1) might not be appropriate to "adjust for height" during periods of growth. We fitted a log-log regression of waist circumference on height to determine which exponent for height ensures that the log of the ratio is uncorrelated with the log of height, which we call the optimal exponent for WC/Ht(p). This optimal power for height in the age- and sex-specific waist-to-height ratio varies from 0.5 to 2.0, with similar patterns for males and females. The value peaks at age 8, and is close to 1 at age 18. Future research should investigate how this affects relationships between central adiposity and cardiovascular disease risk factors across these ages, and how using a power other than 1 might reduce bias and improve precision.

The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of [5,5,5,-2H3]leucine, [4,4,4,-2H3]valine, and [6,6-2H2,1,2-13C2]lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine) mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine, and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol.

The handling of cholesterol by the intestine involves a balance between absorption, excretion and metabolism by gut microflora. Between 34-57% of dietary cholesterol is absorbed from the human intestine. Variables effecting the efficiency of cholesterol absorption include the absolute amount of cholesterol consumed, the presence of plant sterols, the fiber content of the diet, transit time and possibly the relative proportions of fatty acids in the diet. On average, 150 mg/day of cholesterol is excreted in the feces. Fecal cholesterol derives from biliary secretions into the intestine, sloughing of epithelial cells and unabsorbed dietary cholesterol. The major metabolic products of cholesterol in the gut are coprostanol, coprostanone, cholestanol, cholestanone and epicoprostanol. Bacterial metabolism of cholesterol can be influenced by diet as evidenced by significant variations among different population groups with different dietary habits. Altered patterns of intestinal bacterial metabolism of cholesterol may place persons at a higher risk of developing colonic disorders. Dairy products have been reported to influence the bacterial metabolism of cholesterol and possibly plasma cholesterol levels although the significance of these findings to overall cholesterol balance needs to be further defined.

In 1999 we proposed a Modified Food Guide Pyramid for adults aged 70+ y. It has been extensively used in a variety of settings and formats to highlight the unique dietary challenges of older adults. We now propose a Modified MyPyramid for Older Adults in a format consistent with the MyPyramid graphic. It is not intended to substitute for MyPyramid, which is a multifunctional Internet-based program allowing for the calculation of individualized food-based dietary guidance and providing supplemental information on food choices and preparation. Pedagogic issues related to computer availability, Web access, and Internet literacy of older adults suggests a graphic version of MyPyramid is needed. Emphasized are whole grains and variety within the grains group; variety and nutrient density, with specific emphasis on different forms particularly suited to older adults' needs (e.g. frozen) in the vegetables and fruits groups; low-fat and non-fat forms of dairy products including reduced lactose alternatives in the milk group; low saturated fat and trans fat choices in the oils group; and low saturated fat and vegetable choices in the meat and beans group. Underlying themes stress nutrient- and fiber-rich foods within each group and food sources of nutrients rather than supplements. Fluid and physical activity icons serve as the foundation of MyPyramid for Older Adults. A flag to maintain an awareness of the potential need to consider supplemental forms of calcium, and vitamins D and B-12 is placed at the top of the pyramid. Discussed are newer concerns about potential overnutrition in the current food landscape available to older adults.

The purpose of this study was to examine whether changes in cholesterol metabolism after weight loss were affected by single nucleotide polymorphisms (SNPs) in ABCG5 and ABCG8 genes. Thirty-five hypercholesterolemic women lost 11.7 +/- 2.5 kg (P < 0.001). Cholesterol kinetics were assessed using stable isotope techniques. TaqMan PCR was used to detect SNPs in ABCG5/G8. Homozygous Q604E variants in ABCG5 had larger (P < 0.05) reductions in cholesterol absorption and greater increases (P < 0.05) in synthesis in contrast to heterozygous and homozygous wild-type carriers. Heterozygous C54Y carriers had smaller declines (P = 0.047) in synthesis compared with homozygous variant individuals. The presence of at least one Y54 variant was associated with higher (P = 0.042) post-weight-loss synthesis compared with carriers of the C54 genotype. The direction of the results is consistent with cross-sectional studies on the effects of Q604E and C54Y polymorphisms on plasma cholesterol. SNPs in ABCG5/G8 were found to be associated with the response of cholesterol metabolism to weight loss. The evidence for associations between SNPs in ABCG5/G8 and various parameters of cholesterol metabolism indicates the potential effectiveness of establishing genetic screening tools to determine optimal lipid-lowering treatment routes for individuals during weight reduction.

The effect of body mass index (BMI) and obesity on apolipoprotein (apo) A-I levels and kinetics was examined by gender. Apo A-I kinetics were determined with a primed, constant infusion of deuterated leucine in the fed state in 19 men and 13 postmenopausal women. Compared with nonobese men, nonobese women had a higher level of high-density lipoprotein cholesterol (HDL-C) and apo A-I due to a 48% higher apo A-I production rate (PR) (P = .05). Obesity had no significant effects on apo A-I kinetics in women. In contrast, compared with nonobese men, obese men had a 9% lower apo A-I level due to a 64% higher fractional catabolic rate (FCR) partially offset by a 47% higher PR. Obese women had a 52% higher HDL-C than obese men (50 vs 33 mg/dL, respectively; P = .012), a finding related to the faster apo A-I FCR in obese men. BMI was directly correlated with apo A-I FCR (r = 0.84, P < .001) and PR (r = 0.79, P < .001) in men but not in women. Sixty-two percent of the variability in PR and 71% of the variability in FCR were due to BMI in men and only 3% and 23%, respectively, in women. In conclusion, BMI has a significant effect on apo A-I PR and FCR in men but not in women.

Evidence-based systematic reviews evaluating dietary intake and nutritional interventions are becoming common but are relatively few compared with other applications. Concerns remain that systematic reviews of nutrition topics pose several unique challenges. We present a successful collaboration to systematically review the health effects of a common nutrient, n-3 (or omega-3) fatty acids, across a wide range of clinical conditions. More generally, we discuss the challenges faced and the lessons learned during the review, the benefits of systematic review of nutritional topics, and recommendations for conducting and reviewing nutrition-related studies. Through a structured but flexible process, 3 Evidence-based Practice Centers in the Agency for Healthcare Research and Quality program produced 11 reports on a wide range of n-3 fatty acid-related topics. An important resource has been created, through which nutrition and dietetics researchers, clinical dietitians and nutritionists, clinicians, and the general public can understand the state of the science. The process identified challenges and problems in evaluating the health effects of n-3 fatty acid consumption, highlighted challenges to reviewing the human nutrition literature, and yielded recommendations for future research. The goals of these systematic reviews, the processes that were used, the benefits and limitations of the collaboration, and the conclusions of the reviews, including recommendations for future research, are summarized here.

The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.

Studies on the relation between dietary n-3 fatty acids (FAs) and cardiovascular disease vary in quality, and the results are inconsistent. A systematic review of the literature on the effects of n-3 FAs (consumed as fish or fish oils rich in eicosapentaenoic acid and docosahexaenoic acid or as alpha-linolenic acid) on cardiovascular disease outcomes and adverse events was conducted. Studies from MEDLINE and other sources that were of > or =1 y in duration and that reported estimates of fish or n-3 FA intakes and cardiovascular disease outcomes were included. Secondary prevention was addressed in 14 randomized controlled trials (RCTs) of fish-oil supplements or of diets high in n-3 FAs and in 1 prospective cohort study. Most trials reported that fish oil significantly reduced all-cause mortality, myocardial infarction, cardiac and sudden death, or stroke. Primary prevention of cardiovascular disease was reported in 1 RCT, in 25 prospective cohort studies, and in 7 case-control studies. No significant effect on overall deaths was reported in 3 RCTs that evaluated the effects of fish oil in patients with implantable cardioverter defibrillators. Most cohort studies reported that fish consumption was associated with lower rates of all-cause mortality and adverse cardiac outcomes. The effects on stroke were inconsistent. Evidence suggests that increased consumption of n-3 FAs from fish or fish-oil supplements, but not of alpha-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke. The evidence for the benefits of fish oil is stronger in secondary- than in primary-prevention settings. Adverse effects appear to be minor.

Improving diet and lifestyle is a critical component of the American Heart Association’s strategy for cardiovascular disease risk reduction in the general population. This document presents recommendations designed to meet this objective. Specific goals are to consume an overall healthy diet; aim for a healthy body weight; aim for recommended levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides; aim for normal blood pressure; aim for a normal blood glucose level; be physically active; and avoid use of and exposure to tobacco products. The recommendations are to balance caloric intake and physical activity to achieve and maintain a healthy body weight; consume a diet rich in vegetables and fruits; choose whole-grain, high-fiber foods; consume fish, especially oily fish, at least twice a week; limit intake of saturated fat to trans fat to

Recommendations for decreasing the risk of developing cardiovascular disease include increasing the intake of plant sterols and fish oil. The cholesterol-lowering action of plant sterols, when provided in a fish-oil fatty acids vehicle, remains to be investigated in humans. A randomized, crossover-feeding, single-blind trial was conducted in 30 subjects with mild-to-moderate hypercholesterolemia to study the effects on plasma lipids of 2 novel forms of plant sterols: those combined with, or esterified to, fish-oil fatty acids. The treatments were margarine (control), free plant sterols, plant sterols esterified to fatty acids from sunflower oil, plant sterols esterified to very long-chained fatty acids from fish oil, and plant sterols combined with the same amount of very long-chained fatty acids from fish oil. Each sterol-containing food (1.0-1.8 g plant sterols/d) was consumed for 29 d as a single dose with breakfast under staff supervision. Compared with the control treatment, none of the plant sterol preparations reduced plasma total cholesterol or LDL cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, lipoprotein (a), or C-reactive protein concentration. Relative to the control phase, all plant sterols treatment increased the plasma HDL cholesterol concentration (P < 0.05) by approximately 8%. In conclusion, because standard forms of plant sterols did not reduce plasma cholesterol concentrations, the efficacy of the new formulation of plant sterols cannot be confirmed from the present study design, where plant sterols were given as a single morning dose.

Since the American Heart Association last presented nutrition guidelines for children, significant changes have occurred in the prevalence of cardiovascular risk factors and nutrition behaviors in children. Overweight has increased, whereas saturated fat and cholesterol intake have decreased, at least as percentage of total caloric intake. Better understanding of children's cardiovascular risk status and current diet is available from national survey data. New research on the efficacy of diet intervention in children has been published. Also, increasing attention has been paid to the importance of nutrition early in life, including the fetal milieu. This scientific statement summarizes current available information on cardiovascular nutrition in children and makes recommendations for both primordial and primary prevention of cardiovascular disease beginning at a young age.

Soy protein and isoflavones (phytoestrogens) have gained considerable attention for their potential role in improving risk factors for cardiovascular disease. This scientific advisory assesses the more recent work published on soy protein and its component isoflavones. In the majority of 22 randomized trials, isolated soy protein with isoflavones, as compared with milk or other proteins, decreased LDL cholesterol concentrations; the average effect was &3%. This reduction is very small relative to the large amount of soy protein tested in these studies, averaging 50 g, about half the usual total daily protein intake. No significant effects on HDL cholesterol, triglycerides, lipoprotein(a), or blood pressure were evident. Among 19 studies of soy isoflavones, the average effect on LDL cholesterol and other lipid risk factors was nil. Soy protein and isoflavones have not been shown to lessen vasomotor symptoms of menopause, and results are mixed with regard to soy’s ability to slow postmenopausal bone loss. The efficacy and safety of soy isoflavones for preventing or treating cancer of the breast, endometrium, and prostate are not established; evidence from clinical trials is meager and cautionary with regard to a possible adverse effect. For this reason, use of isoflavone supplements in food or pills is not recommended. Thus, earlier research indicating that soy protein has clinically important favorable effects as compared with other proteins has not been confirmed. In contrast, many soy products should be beneficial to cardiovascular and overall health because of their high content of polyunsaturated fats, fiber, vitamins, and minerals and low content of saturated fat.

Background and aims Dietary patterns high in fruits and vegetables have been associated with lower risk of cardiovascular diseases. It is difficult to assess whether individuals are following a dietary pattern recommended for cardiovascular disease prevention in large population based studies. Therefore, the association between phylloquinone (vitamin K1) intake, derived mainly from green vegetables, and risk of cardiovascular diseases [total and fatal coronary heart disease (CHD), non-fatal myocardial infarction, total and ischemic stroke] was prospectively assessed. Methods and results The study was conducted in 40,087 men who participated in the Health Professionals' Follow-up Study during 1986–2000. There were 1857 CHD events and 617 strokes. After adjustment for lifestyle factors, the relative risks of total CHD events in increasing quintile categories of phylloquinone intake were 1 (reference), 0.84, 0.87, 0.82 and 0.84, respectively (P for trend 0.05). However, the risk of CHD events and strokes did not remain significantly associated with phylloquinone intake after adjustment for lifestyle and other dietary factors. Conclusion These results suggest that although not an independent risk factor, high phylloquinone intake may be a marker of dietary patterns associated with lower CHD risk and useful when used within that context.

Background In the United States, >50% of dietary calcium is provided by milk and milk products. Calcium intakes in the United States are inadequate for many children, and a large proportion do not drink milk or consume dairy products. However, no studies have addressed whether dairy-free diets can provide adequate calcium while meeting other nutrient recommendations. Objective To determine the highest calcium intake for adolescents obtained from dairy-free diets, and to examine the relationship between intakes of calcium-fortified foods, using citrus juice as an example, and maximal calcium intakes. Design In the National Health and Nutrition Examination Survey 2001 to 2002, 65 females and 62 males, aged 9 to 18 years, reported no intake of dairy. We used linear programming to generate diets with maximal calcium intake, while meeting Dietary Reference Intakes for a set of nutrients, limiting energy and fat intakes, and not selecting food quantities exceeding amounts usually eaten in the population. Results With food use and energy and fat constraints, diets formulated by linear programming provided 1,150 and 1,411 mg/day of calcium for girls and boys, respectively. With the Dietary Reference Intakes constraints, these decreased to 869 and 1,160 mg/day. When we introduced 1.5 servings of fortified juice to the diets, the highest calcium intake increased to 1,302 mg/day for girls and to 1,640 mg/day for boys. Conclusions Adequate intake for calcium cannot be met with dairy-free diets while meeting other nutrient recommendations. To meet the adequate intake for calcium without large changes in dietary patterns, calcium-fortified foods are needed. In addition, greater physical activity and responsible sunlight exposure should be encouraged to promote vitamin D adequacy.

Greater fish oil consumption has been associated with reduced CVD risk, although the mechanisms are unclear. Plant-source oil omega-3 fatty acids (ALA) have also been studied regarding their cardiovascular effect. We conducted a systematic review of randomized controlled trials that evaluated the effect of consumption of fish oil and ALA on commonly measured serum CVD risk factors, performing meta-analyses when appropriate. Combining 21 trials evaluating lipid outcomes, fish oil consumption resulted in a summary net change in triglycerides of -27 (95% CI -33, -20)mg/dL, in HDL cholesterol of +1.6 (95% CI +0.8, +2.3)mg/dL, and in LDL cholesterol of +6 (95% CI +3, +8)mg/dL. There was no effect of fish oil on total cholesterol. Across studies, higher fish oil dose and higher baseline levels were associated with greater reductions in serum triglycerides. Overall, the 27 fish oil trials evaluating Hgb A(1c) or FBS found small non-significant net increases compared to control oils. Five studies of ALA were inconsistent in their effects on lipids, Hgb A(1c) or FBS. Four studies investigating the effects of omega-3 fatty acids on hs-CRP were also inconsistent and non-significant. The evidence supports a dose-dependent beneficial effect of fish oil on serum triglycerides, particularly among people with more elevated levels. Fish oil consumption also modestly improves HDL cholesterol, increases LDL cholesterol levels, but does not appear to adversely affect glucose homeostasis. The evidence regarding the effects of omega-3 fatty acids on hs-CRP is inconclusive, as are data on ALA.

The consumption of adequate levels and proper balance of essential nutrients is critical for maintaining health. The identification, isolation, and purification of nutrients in the early 20th century raised the possibility that optimal health outcomes could be realized through nutrient supplementation. Recent attempts using this approach for cardiovascular disease and lung cancer have been disappointing, as demonstrated with vitamin E and beta carotene. Moreover, previously unrecognized risks caused by nutrient toxicity and nutrient interactions have surfaced during intervention studies. The most promising data in the area of nutrition and positive health outcomes relate to dietary patterns, not nutrient supplements. These data suggest that other factors in food or the relative presence of some foods and the absence of other foods are more important than the level of individual nutrients consumed. Finally, unknown are the implications on public health behavior of shifting the emphasis away from food toward nutrient supplements. Notwithstanding the justification for targeting recommendations for nutrient supplements to certain segments of the population (eg, the elderly), there are insufficient data to justify an alteration in public health policy from one that emphasizes food and diet to one that emphasizes nutrient supplements.

Commercial hydrogenation results in the formation of trans fatty acids. An unintended consequence of the hydrogenation process is conversion of phylloquinone (vitamin K1) to dihydrophylloquinone. Plasma dihydrophylloquinone concentrations have yet to be characterized in population-based studies. Dietary determinants of plasma dihydrophylloquinone were estimated using a semi-quantitative food frequency questionnaire in 803 men and 913 women in the Framingham Offspring Study. Geometric mean dihydrophylloquinone intake was 21·3 (95 % CI 20·4, 22·3) μg/d in men and 19·4 (95 % CI 18·5, 20·2) μg/d in women. Detectable (>0·05 nmol/l) plasma dihydrophylloquinone concentrations were measured in 41 % and 30 % of men and women, respectively. The multivariate odds ratio (OR) of detectable plasma dihydrophylloquinone from the lowest to the highest quartile category of dihydrophylloquinone intake were 1 (referent), 1·13 (95 % CI 0·83, 1·53), 1·66 (95 % CI 1·21, 2·26) and 1·84 (95 % CI 1·31, 2·58), P for trend trans fatty acid intake was associated with higher multivariate OR for detectable plasma dihydrophylloquinone (OR comparing extreme quartiles 2·41 (95 % CI 1·59, 3·64), P for trend trans fatty acid intake.

Epidemiological studies and clinical trials report the beneficial effects of fish or fish oil consumption on cardiovascular disease outcomes including sudden death. We performed a systematic review of the literature on controlled animal studies that assessed the effects of omega-3 fatty acids on selected arrhythmia outcomes. On the basis of predetermined criteria, 27 relevant animal studies were identified; 23 of these were feeding studies, and 4 were infusion studies. Across species, fish oil, eicosapentaenoic acid, and/or docosahexaenoic acid appear to have beneficial effects on ventricular tachycardia (VT) and fibrillation (VF) in ischemia- but not reperfusion-induced arrhythmia models; no effect on the incidence of death and infarct size; and inconsistent results with regard to arrhythmia score, VF threshold, ventricular premature beats or length of time in normal sinus rhythm, compared to omega-6, monounsaturated, or saturated fatty acids, and no treatment controls. In a meta-analysis of 13 studies using rat models, fish oil but not alpha-linolenic acid supplementation showed a significant protective effect for ischemia- and reperfusion-induced arrhythmias by reducing the incidence of VT and VF. It is not known whether omega-3 fatty-acid supplementation has antiarrhythmic effects in other disease settings not related to ischemia.

Children with Hutchinson-Gilford Progeria Syndrome (HGPS) die of severe premature atherosclerosis at an average age of 13 years. Although the LMNA gene defect responsible for this "premature aging syndrome" has been identified, biological mechanisms underlying the accelerated atherosclerosis are unknown. We determined whether children with HGPS demonstrate abnormalities in known biomarkers for cardiovascular disease (CVD) risk.We quantified serum lipids, lipoproteins, C-reactive protein (CRP), and adiponectin in children with HGPS and age-matched control children.HDL cholesterol (P.0001) and adiponectin (P.001) concentrations decreased significantly with increasing age in HGPS but not in control children. There was a positive correlation between these variables in HGPS ( P.0001) but not control children. Mean total cholesterol, LDL and HDL cholesterol, triglyceride, and median CRP levels were similar between HGPS and control children (all P.05).Declining HDL cholesterol and adiponectin with advancing age may contribute to accelerated atherosclerotic plaque formation in HGPS. Several factors frequently associated with CVD risk in normal aging (elevated CRP, total and LDL cholesterol) showed no difference and are unlikely to influence CVD risk in HGPS. HDL and adiponectin may represent significant mediators and potential therapeutic targets for atherosclerosis in HGPS.

Consumption of soy protein has been associated with altered risk of developing endocrine-regulated cancers. This study was designed to assess the independent effect of soy relative to animal protein and soy-derived isoflavones on circulating estrogen and androgen concentrations in postmenopausal women and older men. Forty-two subjects (> 50 yr) with low-density lipoprotein cholesterol levels of > or = 3.36 mmol/l were fed each of 4 diets in randomized order for 6 wk/phase. All food and drink were provided. Diets contained 25 g soy or common sources of animal protein/4.2 MJ containing trace or 50 mg isoflavones/4.2 MJ. At the end of each diet phase, concentrations of estrone sulfate, estrone, estradiol, testosterone, androstendione, dihydrotestosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were measured. In postmenopausal women, concentrations of estrone were higher and its precursor, dehydroepiandrosterone, lower after consuming the soy compared with animal protein diets (P = 0.0396 and 0.0374, respectively). There was no significant effect of isoflavones on any of the hormones measured. In older men, dehydroepiandrosterone sulfate concentrations were lower after consuming the isoflavone (P = 0.0106) and higher after soy, compared with the animal protein diets (P = 0.0118). These data suggest that relatively large amounts of soy protein or soy-derived isoflavones had modest and limited sex-specific effects on circulating hormone levels.

Observational studies suggested a negative association between vegetable protein and cardiovascular disease risk, whereas intervention studies have been less consistent. The majority of interventional studies that have evaluated the effects of soy protein compared to animal protein have used casein. Relative to casein, the effect of soy protein on lipids and lipoprotein appears to be variable and less dramatic than originally reported. When compared to animal proteins other than casein, relatively large intakes of soy protein (>/=25 g/d) appear to have a consistent, albeit small ( asymptotically equal to 5%), hypocholesterolemic effect. When assessed, no consistent additional benefit of soy protein on other cardiovascular disease risk factors; Lp(a), inflammatory markers, biomarkers of oxidative stress and endothelial function, has been reported. The data available on the effect of dietary protein on plasma lipids, lipoprotein levels, and cardiovascular disease risk factors is difficult to interpret and insufficient to account for the discrepancy between the observational and interventional studies.

Several clinical trials have suggested that soy intake decreases oxidative stress. Soy isoflavones have antioxidant properties in vitro, but results of supplementation in clinical trials are inconclusive.The objective was to evaluate the independent effects of soy protein and soy-derived isoflavones on plasma antioxidant capacity and biomarkers of oxidative stress.Forty-two hypercholesterolemic (LDL cholesterol3.36 mmol/L) subjects aged50 y were provided with each of 4 diets in random order in a crossover design. Diets varied in protein source (10% of energy, soy or animal) and isoflavone content (trace or 50 mg/1000 kcal) and were consumed for 42 d each. Plasma antioxidants, protein carbonyls, malondialdehyde, total antioxidant performance, LDL oxidizability, and urinary F(2)-isoprostanes were measured at the end of each dietary phase.Plasma antioxidant concentrations were not significantly different, regardless of dietary treatment, except for isoflavones, which were higher after isoflavone supplementation (P = 0.0001). Although plasma total antioxidant performance was 10% higher with soy protein intake, regardless of dietary isoflavones (P = 0.0003), soy protein did not significantly affect most individual markers of oxidative stress (LDL oxidizability, urinary F(2)-isoprostanes, malondialdehyde, or protein carbonyls in native plasma). However, soy protein was associated with modestly lower concentrations of protein carbonyls in oxidized plasma. There was no significant effect of isoflavones on LDL oxidation, urinary F(2)-isoprostanes, or protein carbonyl groups, although, paradoxically, the plasma malondialdehyde concentration was significantly higher after the isoflavone-rich diets (P = 0.04).Diets relatively high in soy protein or soy-derived isoflavones have little effect on plasma antioxidant capacity and biomarkers of oxidative stress.

Prevention of disease is a core public health mission. Food-borne illness is a major source of preventable morbidity and mortality. Each year, an estimated 76 million illnesses, 325,000 hospitalizations, and 5200 deaths due to food-borne illness occur in the United States. Research findings show that irradiating food can both greatly reduce illness from food-borne pathogens and extend food shelf life by delaying ripening, inhibiting spoilage, and minimizing contamination. However, because the food industry has historically been reluctant to sell irradiated foods, food irradiation remains an underutilized technology.

The objective of this study was to assess the effects of omega-3 fatty acid supplementation on various kidney transplant-related outcomes. A systematic review and meta-analysis was performed of published randomized, controlled trials (RCT). There were 16 kidney transplant RCT with a total of 812 patients. All trials evaluated fish oil with dosages that ranged from 1.2 to 5.4 g/d. No consistent benefits were observed for any outcome with the exception of a modest benefit on triglycerides. A meta-analysis of rejection episodes found no significant benefit on either early (

Greater omega-3 fatty acid consumption is associated with reduced cardiovascular disease risk. Though the mechanisms of their effect are unclear, they may involve lesion formation and heart function. We conducted a systematic review of the clinical literature on the effect of omega-3 fatty acids on measures of vascular structure and function. We included studies that assessed fish and plant sources of omega-3 fatty acids on coronary artery restenosis after angioplasty, carotid IMT, and exercise capacity. Compared to placebo, the summary risk ratio of coronary artery restenosis with fish oil is 0.87 (95% CI 0.73, 1.05) across 12 randomized controlled trials. Two prospective studies reported increased carotid IMT, whereas two cross-sectional studies reported a reduction of IMT, with fish, fish oil or ALA consumption. Three randomized trials and three uncontrolled studies reported small non-significant improvements in exercise capacity with fish oil. Overall, little or no effect of fish oil was found for a variety of markers of cardiovascular disease risk. There are insufficient studies to draw conclusions about the effect of ALA. The dearth of long term data on fish consumption or omega-3 fatty acid supplementation on measures of cardiovascular disease risk severely limits our ability to draw definitive conclusions at this time.

Objective: To examine the feasibility of using phylloquinone intake as a marker for coronary heart disease (CHD) and stroke risk in women. Design and setting: Nurses' Health Study, a prospective cohort study during 1984–2000. Dietary data were collected in 1984, 1986, 1990, and 1994 using a validated semiquantitative food frequency questionnaire. Subjects: A total of 72 874 female nurses, aged 38–65 y, without previously diagnosed angina, myocardial infarction (MI), stroke, or cancer at baseline. Main outcome measures: Incidence of nonfatal MI, CHD deaths, total CHD events, ischemic, and total strokes. Results: There were 1679 CHD events (1201 nonfatal) and 1009 strokes (567 ischemic). After adjustment for age and lifestyle factors associated with cardiovascular disease risk, the multivariate relative risks (RR) (95% CI) of total CHD from the lowest to the highest quintile category of phylloquinone intake were 1 (reference), 0.80 (0.69–0.94), 0.86 (0.74–1.00), 0.77 (0.66–0.99), and 0.79 (0.68–0.92), P for trend=0.01. Further adjustment for dietary intakes of saturated fat, polyunsaturated fat, trans fatty acids, eicosapentaenoic, and docosahexaenoic acids, cereal fiber, and folate attenuated the association (RR comparing extreme quintiles 0.84 [0.71–1.00], P for trend=0.12). Incidence rates of total or ischemic strokes were not associated with phylloquinone intake. Conclusion: The data suggest that high phylloquinone intake may be a marker for low CHD risk. Dietary and lifestyle patterns associated with phylloquinone intakes, rather than intake of the nutrient itself, might account for all or part of the weak association. Sponsorship: US Department of Agriculture, National Institute of Health and Academy of Finland.

A heritable deficiency of hepatic lipase (HL) provides insights into the physiologic function of HL in vivo. The metabolism of apolipoprotein B (apoB)-100 in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) and of apoA-I and apoA-II in high-density lipoprotein (HDL) particles lipoprotein (Lp)(AI) and Lp(AI:AII) was assessed in 2 heterozygous males for compound mutations L334F/T383M or L334F/R186H, with 18% and 22% of HL activity, respectively, compared with 6 control males. Subjects were provided with a standard Western diet for a minimum of 3 weeks. At the end of the diet period, apo kinetics was assessed using a primed-constant infusion of [5,5,5- 2 H 3 ] leucine. Mean plasma triglyceride (TG) and HDL cholesterol levels were 55% and 12% higher and LDL cholesterol levels 19% lower in the HL patients than control subjects. A higher proportion of apoB-100 was in the VLDL than IDL and LDL fractions of HL patients than control subjects due to a lower VLDL apoB-100 fractional catabolic rate (FCR) (4.63 v 9.38 pools/d, respectively) and higher hepatic production rate (PR) (33.24 v 10.87 mg/kg/d). Delayed FCR of IDL (2.78 and 6.31 pools/d) and LDL (0.128 and 0.205 pools/d) and lower PR of IDL (3.67 and 6.68 mg/kd/d) and LDL 4.57 and 13.07 mg/kg/d) was observed in HL patients relative to control subjects, respectively. ApoA-I FCR (0.09 and 0.13 pools/d) and PR (4.01 and 6.50 mg/kg/d) were slower in Lp(AI:AII) particles of HL patients relative to control subjects, respectively, accounting for the somewhat higher HDL cholesterol levels. HL deficiency may result in a lipoprotein pattern associated with low heart disease risk.

We assessed the independent effect of soy protein relative to animal protein and of isoflavones on various electrophoretic characteristics of LDL particles. LDL particles were characterized by polyacrylamide gradient gel electrophoresis in 36 moderately hypercholesterolemic men and women (LDL cholesterol3.36 mmol/L). All subjects consumed in random order each of the four diets (soy protein depleted of isoflavones, soy protein enriched in isoflavones, animal protein with no added isoflavones, and animal protein with added isoflavones) for 6 wk. Consumption of soy protein was associated with a larger LDL peak particle size relative to animal protein (P0.01). Soy protein also decreased the cholesterol levels in LDL25.5 nm by 12.3% (P0.001) and increased cholesterol levels in LDL26.0 nm by 14.3% (P0.05) relative to animal protein. Isoflavones did not affect these LDL particle characteristics. Soy protein shifted LDL particle distribution to a less atherogenic pattern and this effect is independent of soy's isoflavone component.

A diet restricted in saturated fat and cholesterol is recommended for subjects with elevated LDL cholesterol concentrations before and during drug therapy. Gender differences in lipoprotein subspecies response to such diets have not been studied in detail. We examined the effects of a diet low in total fat, saturated fat and cholesterol (Therapeutic Lifestyle Changes, TLC, diet: 26% of energy as fat, 4% as saturated fat, and 45 mg cholesterol/4.2 MJ), compared with an average American diet (AAD: 35% of energy as fat, 14% as saturated fat, and 147 mg cholesterol/4.2 MJ), on plasma lipoprotein subspecies in men and women. Each diet period lasted 6 wk. Body weight was kept constant during each diet period. Men (n = 19) and postmenopausal women (n = 14) >40 y old with moderate hypercholesterolemia participated in this study. Plasma lipoprotein concentrations were assessed by standardized methodology, and lipoprotein sizes were determined by gradient gel electrophoresis and NMR spectroscopy. The TLC diet resulted in greater reductions in total cholesterol and plasma apolipoprotein B concentrations in men than in women (-19% vs. -12%, P < 0.05, and -18% vs. -9%, P < 0.05, respectively). Postprandial triacylglycerol and LpAI:AII concentrations were reduced in men, but not in women (-15% vs. 8%, P < 0.05, and -9% vs. -2%, respectively, P < 0.05). Similar decreases in LpAI concentrations and LDL and HDL particle size were observed in men and women. These data are consistent with the concept that middle aged/elderly men may have a more favorable lipoprotein response to a low fat, low cholesterol diet than postmenopausal women.

Background: Dietary trans fatty acids (FAs), which are formed during the process of hydrogenating vegetable oil, are known to increase plasma LDL-cholesterol concentrations. However, their effect on LDL particle size has yet to be investigated. Objective: We investigated the effect of trans FA consumption on the electrophoretic characteristics of LDL particles. Design: Eighteen women and 18 men each consumed 5 experimental diets in random order for 35-d periods. Fat represented 30% of total energy intake in each diet, with two-thirds of the fat in the form of semiliquid margarine (0.6 g trans FAs/100 g fat), soft margarine (9.4 g trans FAs/100 g fat), shortening (13.6 g trans FAs/100 g fat), stick margarine (26.1 g trans FAs/100 g fat), or butter, which was low in trans FAs (2.6 g trans FAs/100 g fat) but rich in saturated fat. LDL particle size and distribution were characterized by nondenaturing, 2‐16% polyacrylamide gradient gel electrophoresis. Results: Relative to the LDL particle size observed after consumption of the butter-enriched diet, LDL particle size decreased significantly and in a dose-dependent fashion with increasing amounts of dietary trans FAs (P 260 A) and medium-sized (255‐260 A) LDL particles also increased proportionately to the amount of trans FAs in the diet. Conclusion: Consumption of dietary trans FAs is associated with a deleterious increase in small, dense LDL, which further reinforces the importance of promoting diets low in trans FAs to favorably affect the lipoprotein profile. Am J Clin Nutr 2003;78:370‐5.

To examine the effects of protein source and isoflavones on triglyceride (TG) fatty acid (TGFA) and cholesterol biosynthesis, subjects (>50 years, LDL cholesterol >130 mg/dl) underwent a four-phase randomized cross-over feeding trial. Diets contained either isolated soy protein or common sources of animal protein (25 g/1000 kcal), without or with isoflavones (49 mg/1000 kcal) and were each fed for 6 weeks. Blood samples from 20 hyperlipidemic subjects (6M, 14F, 62 ± 9 years, BMI 26 ± 3 kg/m², LDL cholesterol >160 mg/dl after feeding animal protein without isoflavones) were selected to measure TGFA fractional synthetic rate (TGFA-FSR) and free cholesterol fractional synthetic rate (FC-FSR) over 24 h as deuterium oxide uptake into TGFA and free cholesterol. Soy protein reduced TG by 12.4% (P < 0.0001), total cholesterol by 4.4% (P < 0.001), and LDL cholesterol by 5.7% (P = 0.003) compared to animal protein. The TGFA-FSR was reduced by13.3% (P = 0.018) and FC-FSR was increased by 7.6% (P = 0.017) after the soy protein relative to the animal protein. Isoflavones had no significant effect on TG and TGFA-FSR. Isoflavones reduced total cholesterol levels by 3.1% (P = 0.009) but had no significant effect on LDL, HDL cholesterol levels, or FC-FSR. These data demonstrate that dietary protein type modulates circulating TG and cholesterol levels in hypercholesterolemic individuals by distinct mechanisms., available, unlimited, public

The immunologic effects of isocaloric reduced- and low-fat diets and a voluntary calorie-restricted low-fat diet resulting in weight loss were compared to the immunologic effects of an average American diet in hyperlipidemic individuals.Ten hyperlipidemic subjects were studied during three six-week weight maintenance phases: baseline (BL) [35% fat [14% saturated fat (SFA), 13% monounsaturated fat (MUFA), 8% polyunsaturated fat (PUFA)] and 147 mg cholesterol (C)/1000 kcal], reduced-fat (RF) [26% fat (4% SFA, 11% MUFA, 11% PUFA) and 45 mg C/1000 kcal], and low-fat (LF) [15% fat (5% SFA, 5% MUFA, 3% PUFA) and 35 mg C/1000 kcal] diets followed by 12-week, low-fat calorie reduced phase (LFCR).During the last phase, the subjects' weight significantly decreased (p = 0.005). Cholesterol levels were significantly reduced during all phases, compared to BL diet (p0.05). Delayed-type hypersensitivity (DTH) was assessed using Multi-test CMI. Maximum induration diameters were 22.7, 25.4, 30.5, 34.5 mm for BL, RF, LF and LFCR diets, respectively. Subjects on the LFCR diets had significantly higher DTH compared to the BL diet (p = 0.005). No significant effect of diet was observed on lymphocyte proliferation or interleukin (IL)-1, IL-2 and prostaglandin (PG) E(2) production.These data suggest that low-fat diets (15% energy), under conditions which result in weight loss, do not compromise and may enhance the immune response of middle-aged and elderly hyperlipidemic subjects. The results of this study provide support for the hypothesis that moderate caloric restriction in humans may have a beneficial effect on cell-mediated immunity such as those reported in calorie-restricted rodents.