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Workshops sponsored by the Institute of Medicine (IOM) and the World Health Organization suggested that incorporating systematic (evidence) reviews into the process of updating nutrient reference values would provide a comprehensive and distilled evidence document to decision makers and enhance the transparency of the decision-making process the IOM used in recommending the Dietary Reference Intake values (DRIs) for US and Canadian populations. At the request of the US and Canadian government sponsors of the ongoing review of the 1997 vitamin D and calcium DRI values, the Tufts Evidence-based Practice Center performed a systematic review for the current DRI Committee to use early in its deliberations. We described the approach used to include systematic review into the IOM process for updating nutrient reference values and highlighted major challenges encountered along with the solutions used. The challenges stemmed from the need to review and synthesize a large number of primary studies covering a broad range of outcomes. We resolved these challenges by 1) working with a technical expert panel to prioritize and select outcomes of interest, 2) developing methods to use existing systematic reviews and documenting the limitations by doing so, 3) translating results from studies not designed to address issues of interest by using a transparent process, and 4) establishing tailored quality-assessment tools to assist in decision making. The experiences described in this article can serve as a basis for future improvements in systematic reviews of nutrients and to better integrate systematic review into development of future nutrient reference values. doi: 10.3945/ajcn.2009.29092.

Background: Reduced rank regression (RRR) has been used to derive dietary pattern scores that predict linear combinations of disease biomarkers. The generalizability of these patterns to independent populations remains unknown. Objective: The goal was to examine the generalizability of dietary patterns from the following prior studies using RRR to predict type 2 diabetes mellitus (T2DM): the Nurses' Health Study (NHS), European Prospective Investigation into Cancer and Nutrition Germany (EPIC), and Whitehall II Study (WS). Design: The relative weights of food groups of each dietary pattern were used to generate each dietary pattern score in the Framingham Offspring Study (n = 2879). Each of the external scores (confirmatory scores) was examined to determine whether it could predict incident T2DM during 7 y of follow-up as well as scores developed internally in the Framingham Offspring Study using a Cox-proportional hazard model adjusted for T2DM risk factors. Results: Intakes of meat products, refined grains, and soft drinks (caloric and noncaloric) were found to be common predictive components of all confirmatory scores, but fried foods, eggs, and alcoholic beverages were predictive in some, but not in all, confirmatory scores. On the basis of a continuous increase in the score by 1 SD, the NHS-based confirmatory score predicted T2DM risk (hazard ratio: 1.44; 95% CI: 1.25, 1.66). However, T2DM risk was only weakly predicted by the EPIC-based score (hazard ratio: 1.14; 95% CI: 0.99, 1.32) and the WS-based score (hazard ratio: 1.16; 95% CI: 1.00, 1.35). Conclusions: The study suggested that dietary patterns that predict T2DM risk in different populations may not be generalizable to different populations. Additional dietary pattern studies should be conducted with regard to generalizability.

Background: A premise of the 2005 Dietary Guidelines for Americans (DGA) is chronic disease prevention. Objective: The goal was to determine whether a diet meeting the DGA is associated with less atherosclerotic lesion progression. Design: We used the data from 224 postmenopausal women with established coronary artery disease enrolled in the Estrogen Replacement and Atherosclerosis Study. Atherosclerosis progression was defined by repeated measures of quantitative angiography over a 3-y period. Adherence to the key DGA recommendations was measured by using the DGA Adherence Index (DGAI; possible range: 0-20), with each component weighted equally, and the modified DGAI score (wDGAI; possible range: -0.19-0.51), with each component weighted based on its relation to atherosclerosis progression. Mixed-model regression analyses were performed to assess the association between diet and atherosclerosis progression. Results: No women consumed a diet meeting all of the DGA recommendations. The mean (range) of the DGAI score was 14.1 (8.019.0). DGAI was not associated with atherosclerosis progression (P = 0.44), whereas wDGAI was inversely associated; a 1-SD difference in wDGAI was related to 0.049-mm less narrowing of the coronary arteries (SE = 0.017, P = 0.004). Conclusions: In postmenopausal women with established heart disease, under the assumption that all DGA recommendations are similarly effective, overall adherence was not associated with atherosclerosis progression. However, assigning differential weights to the DGA recommendations, the adherence was significantly associated with slower atherosclerosis progression. Assuming equity of associations between all dietary recommendations and disease outcomes is a limitation in accurately examining the effectiveness of the DGA.

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 English-language 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 = 0.01); however, the reporting of nutrition variables remained unchanged (median: 38% compared with 33%; P = 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.

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.

Background: Poor diet may affect bone status by displacing nutrients involved in bone health. Dihydrophylloquinone, a form of vitamin K present in foods made with partially hydrogenated fat, is a potential marker of a low-quality dietary pattern. Objective: Our objective was to examine the cross-sectional associations between dihydrophylloquinone intake and bone mineral density (BMD) of the hip and spine in men and women. Design: Dihydrophylloquinone intake was estimated with a food-frequency questionnaire, and BMD (in g/[cm.sup.2]) was measured by dual-energy X-ray absorptiometry in 2544 men and women (mean age: 58.5 y) who had participated in the Framingham Offspring Study. General linear models were used to examine the associations between dihydrophylloquinone intake (in tertiles: < 15.5, 15.5-29.5, and >29.5/[micro]g/d) and hip and spine BMD after adjustment for age, body mass index, energy intake, calcium intake, vitamin D intake, smoking status, physical activity score, and, for women, menopause status and estrogen use. Results: Higher dihydrophylloquinone intakes were associated with lower mean BMD at the femoral neck [lowest-to-highest tertiles (95% CI): 0.934 (0.925, 0.942), 0.927 (0.919, 0.935), and 0.917 (0.908, 0.926), P for trend = 0.02], the trochanter [lowest-to-highest tertiles (95% CI): 0.811 (0.802, 0.820), 0.805 (0.797, 0.813), and 0.795 (0.786, 0.804), P for trend = 0.02], and the spine [lowest-to-highest tertiles (95% CI): 1.250 (1.236, 1.264), 1.243 (1.242, 1.229), and 1.227 (1.213, 1.242), P for trend = 0.03] in men and women after adjustment for the covariates. Further adjustment for markers of healthy and low-quality dietary patterns did not affect the observed associations. Conclusions: Higher dihydrophylloquinone intakes are associated with lower BMD in men and women. This association remains significant after adjustment for other markers of diet quality. Am J Clin Nutr 2007;86:504-8. KEY WORDS Dihydrophylloquinone, vitamin K, partially hydrogenated fat, trans fatty acids, diet patterns, bone mineral density, osteoporosis

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. KEY WORDS Evidence-based medicine, systematic review, nutrition, dietary supplements, diet, fatty acids, n--3 fatty acids

Background: There remains no consensus about the optimal dietary composition for sustained weight loss. Objective: The objective was to examine the effects of 2 dietary macronutrient patterns with different glycemic loads on adherence to a prescribed regimen of calorie restriction (CR), weight and fat loss, and related variables. Design: A randomized controlled trial (RCT) of diets with a high glycemic load (HG) or a low glycemic load (LG) at 30% CR was conducted in 34 healthy overweight adults with a mean ([+ or -] SD) age of 35 [+ or -] 6 y and body mass index (kg/[m.sup.2]) of 27.6 [+ or -] 1.4. All food was provided for 6 mo in diets controlled for confounding variables, and subjects self-administered the plans for 6 additional months. Primary and secondary outcomes included energy intake measured by doubly labeled water, body weight and fatness, hunger, satiety, and resting metabolic rate. Results: All groups consumed significantly less energy during CR than at baseline (P < 0.01), but changes in energy intake, body weight, body tat, and resting metabolic rate did not differ significantly between groups. Both groups are more energy than provided (eg, 21% and 28% CR at 3 mo and 16% and 17% CR at 6 mo with HG and LG, respectively). Percentage weight change at 12 mo was -8.04 [+ or -] 4.1% in the HG group and -7.81 [+ or -] 5.0% in the LG group. There was no effect of dietary composition on changes in hunger, satiety, or satisfaction with the amount and type of provided food during CR. Conclusions: These findings provide more detailed evidence to suggest that diets differing substantially in glycemic load induce comparable long-term weight loss. KEY WORDS Glycemic load, caloric restriction, body weight, metabolism

Background: The magnitude of the effect of soy protein on lipoprotein concentrations is variable. This discordance is likely attributable to the various forms of soy protein used and to unrecognized shifts in dietary fatty acid, cholesterol, and fiber. Objective: The objective was to evaluate the effect of soybean processing as well as soy consumption relative to animal protein, independent of alterations in major dietary variables, on cardiovascular disease risk factors and vascular endothelial function. Design: Twenty-eight hypercholesterolemic subjects (LDL cholesterol [greater than or equal to] 3.36 mmol/L) aged >50 y consumed each of 4 diets for 6-wk periods according to a randomized crossover design. The diets [55% of energy as carbohydrate, 30% of energy as fat, and 15% of energy as protein--7.5% of energy as experimental protein (37.5 g/d)] were designed to contain products made from either whole soybeans, soyflour, or soymilk and were compared with a diet containing an equivalent amount of animal protein (meat, chicken, and dairy products). The cholesterol, fiber, and fatty acid profiles of the diets were equalized. All food and drink were provided, and body weight was maintained throughout the study. Results: No significant differences in blood pressure, vascular endothelial function, or total cholesterol, VLDL-cholesterol, triacylglycerol, apolipoprotein B, or C-reactive protein concentrations were observed between the diets. Consumption of the soymilk diet resulted in a modest decrease (4%) in LDL-cholesterol concentrations compared with the animal-protein and soyflour diets (P < 0.05) and higher HDL-cholesterol (1%) and apolipoprotein A-I (2%) concentrations compared with the soybean and soyflour diets (P < 0.05). Conclusions: The results suggest that the consumption of differently processed soy-based products and different types of protein (animal and soy) has little clinical effect on cardiovascular disease risk factors, including peripheral endothelial function, when other major dietary variables are held constant. KEY WORDS Soy protein, lipids, lipoproteins, apolipoproteins, cholesterol, endothelial function

Background: A variety of soybean oils were developed with improved oxidative stability and functional characteristics for use as alternatives to partially hydrogenated fat. Objective: The objective was to assess the effect of selectively bred and genetically modified soybean oils with altered fatty acid profiles, relative to common soybean and partially hydrogenated soybean oils, on cardiovascular disease risk factors. Design: Thirty subjects (16 women and 14 men) aged >50 y with LDL-cholesterol concentrations >130 mg/dL at screening consumed 5 experimental diets in random order for 35 d each. Diets contained the same foods and provided 30% of energy as fat, of which two-thirds was either soybean oil (SO), low-saturated fatty acid soybean oil (LoSFA-SO), high-oleic acid soybean oil (HiOleic-SO), low--[alpha]-linolenic acid soybean oil (LoALA-SO), or partially hydrogenated soybean oil (Hydrog-SO). Results: Plasma phospholipid patterns reflected the predominant fat in the diet. LDL-cholesterol concentrations were 3.66 [+ or -] [0.67.sup.b], 3.53 [+ or -] [0.77.sup.b], 3.70 [+ or -] [0.66.sup.b], 3.71 [+ or -] [0.64.sup.a,b], and 3.92 [+ or -] [0.70.sup.a] mol/L; HDL-cholesterol concentrations were 1.32 [+ or -] [0.32.sup.a,b], 1.32 [+ or -] [0.35.sup.b,] 1.36 [+ or -] [0.33.sup.a], 1.32 [+ or -] [0.33.sup.b], and 1.32 [+ or -] [0.32.sup.a,b] mol/L for the SO, LoSFA-SO, HiOleic-SO, LoALA-SO, and Hydrog-SO diets, respectively (values with different superscript letters are significantly different, P < 0.05). No significant effects were observed on VLDL-cholesterol, triacylglycerol, lipoprotein(a), and C-reactive protein concentrations or on ratios of LDL cholesterol to apolipoprotein B (apo B) and HDL cholesterol to apo A-I. Total cholesterol:HDL cholesterol was lower after subjects consumed the unhydrogenated soybean oils than after they consumed the Hydrog-SO diet. Conclusions: All varieties of soybean oils resulted in more favorable lipoprotein profiles than did the partially hydrogenated form. These soybean oils may provide a viable option for reformulation of products to reduce the content of trans fatty acids. KEY WORDS Soybean oils, selective breeding, genetic modification, cardiovascular disease, CVD risk factors, trans fatty acids, LDL cholesterol, HDL cholesterol, triacylglycerol, C-reactive protein, fatty acids

Background: Partially hydrogenated fat has an unfavorable effect on cardiovascular disease risk. Palm oil is a potential substitute because of favorable physical characteristics. Objective: We assessed the effect of palm oil on lipoprotein profiles compared with the effects of both partially hydrogenated fat and oils high in monounsaturated or polyunsaturated fatty acids. Design: Fifteen volunteers aged [greater than or equal to]50 y with LDL cholesterol [greater than or equal to] 130 mg/dL were provided with food for each of 4 diets (35 d/phase) varying in type of fat (partially hydrogenated soybean, soybean, palm, or canola; two-thirds fat, 20% of energy). Plasma fatty acid profiles, lipids, lipoproteins, apolipoprotein A-I, apolipoprotein B, lipoprotein(a), glucose, insulin, HDL subfractions, and indicators of lipoprotein metabolism (HDL-cholesterol fractional esterification rate, cholesteryl ester transfer protein, phospholipid transfer protein, and paraoxonase activities) were measured at the end of each phase. Results: Plasma fatty acid profiles reflected the main source of dietary fat. Partially hydrogenated soybean and palm oils resulted in higher LDL-cholesterol concentrations than did soybean (12% and 14%, respectively; P < 0.05) and canola (16% and 18%; P < 0.05) oils. Apolipoprotein B (P < 0.05) and A-I (P < 0.05) concentrations mirrored the pattern of LDL- and HDL-cholesterol concentrations, respectively. No significant effect on the total-to-HDL cholesterol ratio was observed for palm oil compared with the other dietary fats. HDL3 cholesterol was higher after palm oil than after partially hydrogenated and soybean oils (P < 0.05). Differences in measures of glucose and HDL intravascular processing attributable to dietary fat were small. Conclusion: Palm and partially hydrogenated soybean oils, compared with soybean and canola oils, adversely altered the lipoprotein profile in moderately hyperlipidemic subjects without significantly affecting HDL intravascular processing markers. KEY WORDS Cardiovascular disease, trans fatty acids, lipoproteins, palm oil, partially hydrogenated soybean oil, LDL cholesterol, HDL cholesterol, insulin, glucose, cholesteryl ester transfer protein, phospholipid transfer protein

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 [greater than or equal to] 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. KEY WORDS n-3 Fatty acids, eicosapentaenoic acid, docosahexaenoic acid, fish oil, linolenic acid, cardiovascular disease, adverse events, systematic review

Background: 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. Objective: The objective was to evaluate the independent effects of soy protein and soy-derived isoflavones on plasma antioxidant capacity and biomarkers of oxidative stress. Design: Forty-two hypercholesterolemic (LDL cholesterol > 3.36 mmol/L) subjects aged >50 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.sub.2]-isoprostanes were measured at the end of each dietary phase. Results: 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.sub.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 F2isoprostanes, or protein carbonyl groups, although, paradoxically, the plasma malondialdehyde concentration was significantly higher after the isoflavone-rich diets (P = 0.04). Conclusions: Diets relatively high in soy protein or soy-derived isoflavones have little effect on plasma antioxidant capacity and biomarkers of oxidative stress. Am J Clin Nutr 2005;81:43-9. KEY WORDS Animal protein, antioxidants, antioxidant capacity, cardiovascular disease, isoflavones, oxidative stress, soy protein

Background: Higher intakes of fish and n--3 fatty acids are associated with a reduced risk of cardiovascular events and mortality. However, limited data exist on the effect of fish intake on actual measures of progression of coronary artery atherosclerosis. Objective: The aim was to examine the association between fish intake and the progression of coronary artery atherosclerosis in women with coronary artery disease. Design: This was a prospective cohort study of postmenopausal women (n = 229) participating in the Estrogen Replacement and Atherosclerosis trial. Usual fish intake was estimated at baseline with a food-frequency questionnaire. Quantitative coronary angiography was performed at baseline and after 3.2 [+ or -] 0.6 (bar.x [+ or -] SD) y to evaluate changes in the mean minimum coronary artery diameter, the mean percentage of stenosis, and the development of new coronary lesions. Results: Compared with lower fish intakes, consumption of [greater than or equal to] 2 servings of fish or [greater than or equal to] 1 serving of tuna or dark fish per week was associated with smaller increases in the percentage of stenosis (4.54 [+ or -] 1.37% compared with -0.06 [+ or -] 1.59% and 5.12 [+ or -] 1.48% compared with 0.35 [+ or -] 1.47%, respectively; P < 0.05 for both) in diabetic women after adjustments for age, cardiovascular disease risk factors, and dietary intakes of fatty acids, cholesterol, fiber, and alcohol. These associations were not significant in nondiabetic women. Higher fish consumption was also associated with smaller decreases in minimum coronary artery diameter and fewer new lesions. Conclusions: Consumption of fish is associated with a significantly reduced progression of coronary artery atherosclerosis in women with coronary artery disease. Am J Clin Nutr 2004;80:626-32. KEY WORDS Fish, atherosclerosis, angiography, women, diet, n-3 fatty acids, diabetes mellitus

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 < 0.001). Cholesterol concentrations in large (> 260 [Angstrom]) and medium-sized (255-260 [Angstrom]) 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. KEY WORDS trans Fatty acids, hydrogenated fat, LDL particle size, diet, cholesterol

Background: Hydrogenation of vegetable oils affects blood lipid and lipoprotein concentrations. However, little is known about the effects of hydrogenation on other components, such as vitamin K. Low phylloquinone (vitamin [K.sub.1] intake is a potential risk factor for bone fracture, although the mechanisms of this are unknown. Objective: The objective was to compare the biological effects of phylloquinone and its hydrogenated form, dihydrophylloquinone, on vitamin K status and markers of bone formation and resorption. Design: In a randomized crossover study in a metabolic unit, 15 young adults were fed a phylloquinone-restricted diet (10 [micro]g/d) for 15 d followed by 10 d of repletion (200 [micro]g/d) with either phylloquinone or dihydrophylloquinone. Results: There was an increase and subsequent decrease in measures of bone formation (P = 0.002) and resorption (P = 0.08) after dietary phylloquinone restriction and repletion, respectively. In comparison with phylloquinone, dihydrophylloquinone was less absorbed and had no measurable biological effect on measures of bone formation and resorption. Conclusion: Hydrogenation of plant oils appears to decrease the absorption and biological effect of vitamin K in bone. Am J Clin Nutr 2001;74:783-90. KEY WORDS Vitamin K, osteoporosis, hydrogenated oils, diet, bone turnover, trans fatty acids, phylloquinone, dihydrophylloquinone

Effects of butter and 2 types of margarine on blood lipid and lipoprotein concentrations were compared in a controlled diet study with 23 men and 23 women. Table spreads, added to a common basal diet, provided 8.3% of energy as fat. Diets averaged 34.6% of energy as fat and 15.5% as protein. Each diet was fed for 5 wk in a 3 x 3 Latin-square design. One margarine (TFA-M) approximated the average trans monoene content of trans fatty acid-containing margarines in the United States (17% trans fatty acids by dry wt). The other margarine (PUFA-M) was free of trans unsaturated fatty acids; it contained approximately twice the polyunsaturated fatty acid content of TFA-M (49% compared with 27% polyunsaturated fatty acids). The tub-type margarines had similar physical properties at ambient temperature. Fasting blood lipids and lipoproteins were determined in 2 samples taken from the subjects during the fifth week of each dietary treatment. Compared with butter, total cholesterol was 3.5% lower (P = 0.009) after consumption of TFA-M and 5.4% lower (P [is less than] 0.001) after consumption of PUFA-M. Similarly, LDL cholesterol was 4.9% lower (P = 0.005) and 6.7% lower (P [is less than] 0.001) after consumption of TFA-M and PUFA-M, respectively. Neither margarine differed from butter in its effect on HDL cholesterol or triacylglycerols. Thus, consumption of TFA-M or PUFA-M improved blood lipid profiles for the major lipoproteins associated with cardiovascular risk when compared with butter, with a greater improvement with PUFA-M than with TFA-M. Am J Clin Nutr 1998;68:768-77.

The effects of National Cholesterol Education Program (NCEP) Step 2 diets on plasma lipoprotein profiles in men [mean ([+ or -] SD) age: 44 [+ or -] 15 y, range: 19-81 y] and 48 women (mean age: 50 [+ or -] 21 y, range: 19-81 y) participating in five previously published studies were examined. Subjects were placed on a baseline diet similar to an average American diet (35-41% total fat, 13-16% saturated fat, 31-45 mg cholesterol/MJ) and then on an NCEP Step 2 diet (18-29% total fat, 4-7% saturated fat, 11-20 mg cholesterol/MJ) under isoenergetic conditions. All food and drink were provided. Compared with the baseline diet, consumption of the NCEP Step 2 diets was associated with significant decreases in concentrations of low-density-lipoprotein (LDL) cholesterol (-18.9% and - 15.6%, respectively) and high-density-lipoprotein (HDL) cholesterol (-17.0% and -11.2%, respectively) in both men and women. Men with the apolipoprotein (apo) E 3,4 phenotype had a significantly greater decrease in LDL cholesterol (-24.2%) with the NCEP Step 2 diets than men with the apo E 3,3 phenotype (-17.7%). Men with the apo A-IV 1,2 phenotype tended to have less LDL cholesterol lowering (-12.8%) than men with the apo A-IV 1,1 phenotype (-19.6%), but this difference was not significant. No differences were seen by apo E and A-IV phenotype in women. A large variability in lipid response to the diet was observed, with changes in LDL cholesterol ranging from +3% to -55% in men and and from +13% to -39% in women. Forty-eight percent of the variability in LDL-cholesterol response (in mmol/L) to the diet could be accounted for by baseline LDL concentrations and age in men, and 13% by age in women.

The effects of two National.] Cholesterol Education Program (NCEP) Step 2 diets ([less than or equal to] 30% of energy as total fat, < 70% of energy as saturated fat, and < 200 mg cholesterol/d), one relatively high and the other relatively low in fish-derived fatty acids, on plasma lipoprotein concentrations and blood pressure were compared in 22 men and women with a mean ([+ or -] SD) age of 63[+ or -] 10 y. Subjects were placed on a baseline diet similar to the diet currently consumed in the United States (35% of energy as total fat, 14% of energy as saturated fat, 35 mg cholesterol/MJ) for 6 wk and then on either an NCEP Step 2 diet relatively high in fish (Step 2 high-fish, n = 1 1 ) or relatively low in fish (Step 2 low-fish, n = I I ) for 24 wk. All food and drinks were provided. Compared with baseline values, consumption of both the Step 2 high-fish and the Step 2 low-fish diets under weight-stable condihons was associated with significant decreases in plasma concentrations of total cholesterol ( - 14% and--19%, respectively), low-density-lipoprotein (LDL) cholesterol ( - 15% and--20%, respectively), and high-density-lipoprotein (HDL) cholesterol (-11% and-17%, respectively). Postprandial, but not fasting, triacylglycerol concentrations were significantly reduced during consumption of the Step 2 high-fish diet. There were no significant changes in these indexes after consumption of the Step 2 low-fish diet compared with the baseline diet. LDL particle size decreased significantly (-12%) only in subjects on the Step 2 low-fish diet. Both Step 2 diets caused small but significant reductions in diastolic blood pressure. Our results indicate that NCEP Step 2 diets relatively high or relatively low in fish are both effective in significantly reducing total and LDL-cholesterol concentrations without changes in the ratio of total cholesterol to HDL cholesterol under controlled weight-stable conditions in middle-aged and elderly subjects. A beneficial effect on diastolic blood pressure was also observed.

Coronary heart disease (CHD) risk increases markedly with age in both men and women. Major risk factors for CHD in addition to diet and lifestyle factors include age, family history of CHD, cigarette smoking, hypertension, diabetes, elevated low-density-lipoprotein (LDL) cholesterol ([greater than or equal to] 4.1 mmol/L, or 160 mg/dL), and decreased high-density-lipoprotein (HDL) cholesterol (< 0.9 mmol/L, or 35 mg/dL). A diet containing < 30% of energy from fat, < 10% from saturated fat, and < 300 mg cholesterol/d for the general population for CHD risk reduction, and a further restriction of > 7% of energy from saturated fat and < 200 mg cholesterol/d for hypercholesterolemic subjects has been recommended. Such diets have been shown to reduce CHD risk. Age-adjusted CHD mortality rates have declined by 50% over the past four decades, probably because of decreases in animal fats in the diet, better control of hypertension, and efforts at smoking cessation. Am J Clin Nutr 1995;61(suppl):726S-40S

To test the hypothesis that diet may exert differential effects on apolipoprotein (apo) A-I containing high-density-lipoprotein (HDL) particles with (w) and without (w/o) apo A-II [Lp(A-I w A-II) and Lp(A-I w/o A-II), the effects of a diet low in saturated fatty acids and cholesterol [National Cholesterol Education Panel (NCEP) Step 2 diet! on these lipoproteins were determined in eight normolipidemic subjects, aged 53-74 y, in both the fasting and nonfasting states. Compared with a diet high in saturated fatty acid and cholesterol, consumption of an NCEP diet (6 mo) lowered fasting plasma, low-density-lipoprotein, and HDL cholesterol, and nonfasting plasma cholesterol, triglyceride, and HDL cholesterol (P < 0.05-< 0.005) Phospholipid in fasting and nonfasting LP (A-I w A-11) I w/o A-II) was lower during the NCEP diet (P < 0.05-0.0001), but reductions in apo A-I or A-II were observed only in LP(A-I w A-II). In contrast, differences in particle-size profiles were detected in Lp(A-I w/o A-II) but not in Lp(A-I w A-II). These observations provide further evidence that Lp(A-I) w A-II) and Lp(A-I w/o A-II) are distinct metabolic entities.

To determine whether the lower rates of heart disease in Taiwan than in the United States could be related to associations between plasma lipoproteins and dietary intake, we assessed these indexes in 423 adults in Taipei matched with 420 adults in Framingham, MA. Concentrations of LDL cholesterol were 14% lower, HDL cholesterol 9% higher, and LDL cholesterol: HDL cholesterol 27% lower in Taipei than in Framingham. Dietary intakes of total fat (34%), saturated fatty acids, and cholesterol (338 mg) were, respectively, 16%, 41%, and 19% lower in Taipei men, whereas polyunsaturated fatty acid intake was 89% higher than in Framingham men. Similar differences were seen for women except for total fat and cholesterol intakes, which were similar. From stepwise analyses of all subjects, we observed significant associations of lower LDL cholesterol: HDL cholesterol with higher polyunsaturated fatty acid intakes and lower body mass indexes in both men and women. Our data indicate that the more favorable lipoprotein profiles observed in Taipei subjects may be partly due to differences in type of dietary fat consumption as well as in body mass index. Am J Clin Nutr 1994;60:765-74.

Background: Apolipoprotein (apo) A-IV is a major component of triacylglycerol-rich lipoprotein (TRL) apolipoproteins. Objective: We investigated the effects of dietary saturated fat and cholesterol restriction on the metabolism of TRL and plasma apo A-IV. Design: We assessed TRL and plasma apo A-IV kinetics in 16 and 4 subjects, respectively, consuming an average US (baseline) diet for 6 wk and a National Cholesterol Education Program Step II diet for 24 wk, respectively. At the end of each diet period, all subjects received a primed, constant infusion of deuterated leucine for 15 h with hourly feeding. Ratios of stable-isotope tracer to tracee were measured by using gas chromatography--mass spectrometry, and kinetic data were modeled by using SAAM II. Results: Mean apo A-IV concentrations during the isotope infusion period were 6.9 [+ or -] 2.6 mg/L in TRL and 2.2 [+ or -] 3.2 mg/L in plasma with the baseline diet; these values were 37.7% (P [is less than] 0.001) and 19.4% (P [is less than] 0.01) lower with the Step II diet. Similar changes were observed in the fasting state between the 2 diets. The mean apo A-IV secretion rate decreased significantly from baseline by 59.6% in TRLs and by 40.2% in plasma. Significant correlations were observed between TRL apo A-IV concentrations and the secretion rate (r = 0.94, P [is less than] 0.001) and between TRL apo A-IV pool size and TRL-cholesterol concentrations (r = 0.48, P [is less than] 0.01). Conclusions: Our data indicate that the National Cholesterol Education Program Step II diet significantly decreases TRL and plasma apo A-IV concentrations compared with the average US diet and that this decrease is due to a decreased secretion rate. Am J Clin Nutr 2001;74:308-14. KEY WORDS Apolipoprotein A-IV, kinetics, National Cholesterol Education Program Step II diet, NCEP, metabolism, stable-isotope tracer, triacylglycerol-rich lipoproteins

Background: There is limited information regarding the associations of lifestyle factors and sex with HDL subclasses containing apolipoprotein (apo) A-I (Lp A-I) and both apo A-I and apo A-II (Lp A-I:A-II). Objective: We sought to examine the relations between 2 major HDL subclasses and sex, menopausal status, nutrient intakes, and adiposity. Design: We conducted interviews and measured blood variables in 409 government employees aged 40-59 y in Taiwan. Results: Women (n = 203) had significantly higher concentrations of HDL cholesterol, Lp A-I, and Lp A-I:A-II than did men (n = 206). Postmenopausal women (n = 72) had higher concentrations of HDL cholesterol, Lp A-I, and Lp A-I:A-II than did premenopausal women (n = 131). Body mass index and waist-to-hip ratio were strong predictors of and exerted an independent additive effect on Lp A-I concentrations in both men and women. However, body adiposity was associated with Lp A-I:A-II concentrations only in men. Waist-to-hip ratio was an independent determinant of Lp A-I but not of Lp A-I:A-II in men and postmenopausal women after adjustment for age, body mass index, smoking, and diet. Although there were relatively weak associations between dietary factors and both HDL subclasses (r = 0.01-0.26) in men and women according to bivariate analyses, multiple regression models showed that total fat, saturated fat, and cholesterol intakes were significantly correlated with HDL cholesterol and both Lp A-I and Lp A-I:A-II in men, but not in women. Conclusion: Our data suggest that body adiposity and dietary fat consumption affect 2 major HDL subclasses differently depending on subject sex and menopausal status. Am J Clin Nutr 2001;74:64-71. KEY WORDS Cardiovascular disease, HDL cholesterol, high-density-lipoprotein cholesterol, HDL subclasses, body mass index, BMI, waist-to-hip ratio, adiposity, body fat, diet, dietary fat, sex, menopausal status, Chinese population, Taiwan

Background: The food matrix in which carotenoids are found affects their bioavailability. Lutein and zeaxanthin are abundant in egg yolks and accumulate in the macular region of the retina, where they may affect visual function. Objective: We sought to determine whether plasma lutein and zeaxanthin concentrations are elevated after dietary supplementation with egg yolk. Design: Eleven moderately hypercholesterolemic men and women consumed 2 separate baseline diets, which contained 29-33% of energy as total fat, with 20% of energy as either beef tallow or corn oil. These diets were supplemented with cooked chicken egg yolks (1.3 egg yolks/d for an intake of 10.4 MJ). Each subject consumed all 4 diets. Each diet was consumed for 4.5 wk, with a washout period of [equal to or greater than] 2 wk between diet phases. At the end of each diet phase, fasting morning plasma samples were collected and stored for carotenoid analysis by HPLC. Commercial chicken egg yolks were analyzed for carotenoids and cholesterol. Results: Egg yolk supplementation of the beef tallow diet increased plasma lutein by 28% (P [less than] 0.05) and zeaxanthin by 142% (P [less than] 0.001); supplementation of the corn oil diet increased plasma lutein by 50% (P [less than] 0.05) and zeaxanthin by 114% (P [less than] 0.001). Changes in plasma lycopene and [Beta]-carotene were variable, with no consistent trend. Egg yolk supplementation increased plasma LDL-cholesterol concentrations by 8-11% (P [less than] 0.05). Conclusions: Egg yolk is a highly bioavailable source of lutein and zeaxanthin. The benefit of introducing these carotenoids into the diet with egg yolk is counterbalanced by potential LDL-cholesterol elevation-from the added dietary cholesterol. Am J Clin Nutr 1999;70:247-51.