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Studies that have compared the absorption of phylloquinone from green vegetables and oils have equivocal results. To address differences in approaches used to assess absorption of phylloquinone, a 24-h absorption study was conducted in 18 younger (20-40 y) and 18 older (60-80 y) men and women as part of a larger metabolic study that compared changes in vitamin K status in response to broccoli and phylloquinone-fortified oil (377 +/- 46 and 417 +/- 45 micro g/d, respectively). Absorption was defined as the 24-h area under the curve (AUC) for plasma phylloquinone concentrations (both unadjusted and adjusted for triglyceride concentrations). The mean AUC for plasma phylloquinone concentrations (both unadjusted and adjusted) were significantly greater after consumption of the phylloquinone-fortified oil diet compared with the broccoli diet (P < 0.001). However, there were no differences between the two treatments in 24-h fasting plasma phylloquinone concentrations. Although there were no age differences in the AUC for plasma phylloquinone adjusted for triglycerides, older adults had significantly higher plasma phylloquinone concentrations (both unadjusted and adjusted) at 0 and 24 h than the younger adults (P < 0.001). These data emphasize that the use of different approaches for the assessment of vitamin K absorption can result in disparate conclusions.

This article reviews the literature from 1986 to early 2001 relating to apoB100 and apoB48 kinetics in humans using amino acid precursors labeled with stable isotopes. The following subjects are reviewed: (1) methodology; (2) normal individuals and the effects of aging; (3) diet; (4) hereditary dyslipidemias: familial hypercholesterolemia, familial combined hyperlipidemia, cholesteryl ester storage disease, cholesteryl ester transfer protein deficiency, lipoprotein lipase deficiency, familial hypobetalipoproteinemia, and truncated forms of apoB; (5) hormonal perturbations: estrogen, insulin, diabetes, obesity, and growth hormone; (6) the nephrotic syndrome; and (7) the effects of the statin class of drugs. Because of the advances which have been made in mass spectrometry techniques, the advantages of using non-radioactive tracers in humans have made stable isotope kinetic studies the present day standard in this area of research.

Consumption of diets high in hydrogenated fat/trans fatty acids has been shown to have an adverse affect on lipoprotein profiles with respect to cardiovascular disease risk. Dietary fat and cholesterol play an important role in the regulation of immune and inflammatory responses shown to be involved in atherogenesis. We investigated the effects of diets containing hydrogenated fat on cellular immune response and production of inflammatory cytokines in human subjects with moderately elevated cholesterol levels (LDL cholesterol130 mg/dl). In a double blind cross-over study, 19 subjects consumed three diets, 30% of calories as fat, of which two thirds were provided as soybean oil, soybean oil-based stick margarine, or butter for 32 days, each in a randomized order. Production of proinflammatory mediators, prostaglandin (PG)E(2), interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha); delayed type hypersensitivity (DTH) response, in vitro lymphocyte proliferation, and production of IL-2 were determined. Production of IL-6 and TNF-alpha was significantly higher after consumption of stick margarine diet compared with soybean oil diet. IL-1beta and TNF-alpha production correlated positively with ratios of total cholesterol to HDL cholesterol (r = 0.499, P0.001 and r = 0.291, P = 0.04, respectively). There was no significant difference in DTH response, lymphocyte proliferation, or levels of IL-2 and PGE(2) produced among three groups. Our results indicate that consumption of a diet high in hydrogenated fat does not adversely affect cellular immunity but increases production of inflammatory cytokines that have been associated with the pathophysiology of atherosclerosis.

Lifestyle modification to decrease cardiovascular disease (CVD) risk has recently been reaffirmed by both the National Cholesterol Education Program and American Heart Association (AHA). Using a randomized crossover design, the Therapeutic Lifestyle Change (TLC)/Step 2 diet relative to a typical Western diet was assessed in 36 moderately hypercholesterolemic subjects in a clinical setting under isoweight conditions. Mean lipoprotein and apolipoprotein levels (fasting and non-fasting), fatty acid profiles, parameters of HDL metabolism, and glucose homeostasis were determined. Relative to the Western diet, the TLC/Step 2 diet resulted in 11% and 7% lower LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), respectively, with no significant change in TG levels or total cholesterol-HDL-C ratio. Similar responses were observed in the non-fasting state. Linoleic (18:2n-6c) and alpha-linolenic (18:3n-3) acids increased at the expense of oleic acid (18:1n-9c) in the cholesteryl ester, TG, and phospholipid subfractions. The dietary changes had no significant effect on fractional esterification rate of HDL, phospholipid transfer protein (PLTP), or cholesterol ester transfer protein activities, or glucose and insulin levels. Female and male subjects responded similarly. The TLC/Step 2 diet resulted in a decrease in some CVD risk factors and no apparent adverse effects in others.

Plant sterols have recently been recommended by the National Cholesterol Education Panel for use with the more traditional approaches of limiting saturated fat and cholesterol intakes, maintaining a healthy body weight and engaging in regular exercise, as a non-pharmacological approach to reduce low-density lipoprotein cholesterol levels. Recent data confirm the original observation that approximately 1.6 g of plant sterol esters per day results in a maximal low-density lipoprotein cholesterol lowering of approximately 10%. Few side-effects of plant sterols have been reported, with the exception of decreased levels of circulating carotenoids.

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 +/- 2.6 mg/L in TRL and 2.2 +/- 3.2 mg/L in plasma with the baseline diet; these values were 37.7% (P < 0.001) and 19.4% (P < 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 < 0.001) and between TRL apo A-IV pool size and TRL-cholesterol concentrations (r = 0.48, P < 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.

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.

Conference Planning and Writing Committee:Penny Kris-Etherton, PhD, Stephen R. Daniels, MD, PhD, Robert H. Eckel, MD, Marguerite Engler, PhD, RN, Barbara V. Howard, PhD, Ronald M. Krauss, MD, Alice H. Lichtenstein, DSc, Frank Sacks, MD, Sachiko St. Jeor, PhD, Meir Stampfer, MD, DrPH, For the American Heart Association Nutrition Committee Speakers and Discussants:, Robert H. Eckel, MD, Scott M. Grundy, MD, PhD, Lawrence J. Appel, MD, MPH, Tim Byers, MD, Hannia Campos, PhD, Greg Cooney, PhD, Margo A. Denke, MD, Barbara V. Howard, PhD, Eileen Kennedy, DSc, Ronald M. Krauss, MD, Penny Kris-Etherton, PhD, Alice H. Lichtenstein, DSc, Peter Marckmann, MD, DSc, Thomas A. Pearson, MD, PhD, Gabriele Riccardi, MD, Lawrence L. Rudel, PhD, Mike Rudrum, PhD, Frank Sacks, MD, Daniel T. Stein, MD, Russell P. Tracy, PhD, Virginia Ursin, PhD, Robert A. Vogel, MD, Peter L. Zock, PhD, AHA Members:, Terry L. Bazzarre, PhD and Julie Clark, AHA Staff

To assess the validity of two techniques used to measure human cholesterol synthesis, the rate of uptake of deuterium (D) into plasma free cholesterol (FC), and plasma cholesterol precursor (squalene, lanosterol, desmosterol and lathosterol) levels were compared in 14 women [65-71 yr with low density lipoprotein-cholesterol (LDL-C)or = 3.36 mmol x L(-1)]. Subjects consumed each of six diets for 5-wk periods according to a randomized crossover design. The experimental diets included a baseline diet (39% energy as fat, 164 mg chol x 4.2 MJ(-1)) and five reduced-fat diets (30% of energy as fat), where two-thirds of the fat was either soybean oil; squeeze, tub or stick margarines; or butter. Fractional and absolute synthesis rates (FSR and ASR) of FC were determined using the deuterium incorporation (DI) method, while cholesterol precursor levels were measured using gas-liquid chromatography. Data were pooled across diets for each variable and correlation coefficients were calculated to determine if associations were present. There was good agreement among levels of the various cholesterol precursors. In addition, FSR in pools/d (p x d(-1)) and ASR in grams/d (g x d(-1)) were strongly associated with lathosterol (r= 0.72 and 0.71, P= 0.0001), desmosterol (r= 0.75 and 0.75, P = 0.0001), lanosterol (r = 0.67 and 0.67), and squalene (r = 0.69 and 0.68) when levels of the precursors were expressed as micromol x mmol(-1) C. Significant but lower correlations were observed between the D uptake and plasma cholesterol precursor levels when the latter were expressed in absolute amounts (micromol x L(-1)). The wide range of fatty acid profiles of the experimental diets did not influence the degree of association between methods. In conclusion, the DI method and levels of some cholesterol precursors correspond as methods for shortterm measurement of cholesterol synthesis.

Trans fatty acids are unsaturated fatty acids that contain at least one double bond in the trans configuration. In the diet they occur at relatively low levels in meat and dairy products as a by-product of fermentation in ruminant animals or in hydrogenated fats as a consequence of the hydrogenation process. In general, dietary hydrogenated fat/trans fatty acids have been reported to increase LDL cholesterol levels relative to oil in the natural state or cis fatty acids. In contrast, dietary hydrogenated fat/trans fatty acids have been reported have to have little effect or decrease HDL cholesterol levels, the later observation restricted to relatively high intakes of trans fatty acids. These two effects result in higher, therefore less favorable, total or LDL cholesterol/HDL cholesterol ratios. Significant increases in Lp(a) levels have been reported after consumption of diets relatively high in trans fatty acids compared with either unsaturated or saturated fatty acids. However, the magnitude of the change is for the most part small and the physiological significance of this observation has yet to be resolved. Data related to the mechanism by which hydrogenated fat/trans fatty acids alter serum lipid levels and other risk factors for cardiovascular disease are in the nascent stages. At this time it would appear prudent that public health recommendations should be aimed at encouraging the moderate consumption of products low in saturated fat or minimally hydrogenated. Trans fatty acids intake should not be stressed at the expense of saturated fat but should augment it.

Abstract —The purpose of our study was to investigate high density lipoprotein (HDL) apolipoprotein (apo) A-I and apoA-II kinetics in a state of constant feeding after a primed-constant infusion of [5,5,5- 2 H 3 ] l -leucine in 32 normolipidemic older men and postmenopausal women (aged 41 to 79 years). ApoA-I and apoA-II were isolated from plasma HDL, and enrichment was determined by gas chromatography/mass spectrometry. The fractional secretion rate was obtained by using a monoexponential equation calculated with the SAAM II program (Department of Bioengineering, University of Washington, Seattle). Mean HDL cholesterol (HDL-C) and total triglyceride levels were 23% higher and 27% lower, respectively, in women than in men. Mean plasma apoA-I levels were 10% greater in women than in men, whereas mean apoA-II levels were similar. HDL size, estimated by gradient-sizing gels and by the HDL-C/apoA-I+apoA-II ratio, was significantly higher in women than in men. Mean apoA-I secretion rates (SRs) were similar in men and women (12.28±3.64 versus 11.96±2.92 mg/kg per day), whereas there was a trend toward a lower (−13%) apoA-I fractional catabolic rate (FCR) in women compared with men (0.199±0.037 versus 0.225±0.062 pools per day, P =0.11). Mean apoA-II SRs (2.21±0.57 versus 2.27±0.91 mg/kg per day) and FCRs (0.179±0.034 versus 0.181±0.068 pools per day) were similar in men and women. For the group as a whole, there was an inverse association between the HDL-C/apoA-I+apoA-II ratio and apoA-I FCR and between the ratio and triglyceride levels. Plasma levels of apoA-I and apoA-II were correlated with their respective SRs but not FCRs. These data suggest a major role for apoA-I and apoA-II SRs in regulating the plasma levels of these proteins, whereas apoA-I FCR might be an important factor contributing to the differences in apoA-I levels between men and postmenopausal women. Moreover, plasma triglyceride levels are important determinants of HDL size and apoA-I catabolism.

The effects of soy protein and isoflavones on blood cholesterol in humans has been variable. Maximal low- density lipoprotein cholesterol lowering appears to be modest and consistently ranges from 5% to 7%. Preliminary evidence suggests a potentially beneficial effect of the isoflavone fraction of soybeans on arterial compliance. The isoflavone fraction has been demonstrated to decrease the in vitro susceptibility of low-density lipoprotein to oxidation; the significance of this finding in vivo is unknown. It is difficult to definitively say at this time whether increased consumption of soy based products will result in a decreased risk of CHD beyond their ability to displace foods high in saturated fat and cholesterol from the diet.

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 >/=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 < 0.05) and zeaxanthin by 142% (P < 0.001); supplementation of the corn oil diet increased plasma lutein by 50% (P < 0.05) and zeaxanthin by 114% (P < 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 < 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.

Metabolic studies suggest that fatty acids containing at least one double bond in the trans configuration, which are found in hydrogenated fat, have a detrimental effect on serum lipoprotein cholesterol levels as compared with unsaturated fatty acids containing double bonds only in the cis configuration. We compared the effects of diets with a broad range of trans fatty acids on serum lipoprotein cholesterol levels.Eighteen women and 18 men consumed each of six diets in random order for 35-day periods. The foods were identical in each diet, and each diet provided 30 percent of calories as fat, with two thirds of the fat contributed as soybean oil (0.5 g of trans fatty acid per 100 g of fat), semiliquid margarine (0.5 g per 100 g), soft margarine (7.4 g per 100 g), shortening (9.9 g per 100 g), or stick margarine (20.1 g per 100 g). The effects of those diets on serum lipoprotein cholesterol, triglyceride, and apolipoprotein levels were compared with those of a diet enriched with butter, which has a high content of saturated fat.The mean (+/-SD) serum low-density lipoprotein (LDL) cholesterol level was 177+/-32 mg per deciliter (4.58+/-0.85 mmol per liter) and the mean high-density lipoprotein (HDL) cholesterol level was 45+/-10 mg per deciliter (1.2+/-0.26 mmol per liter) after subjects consumed the butter-enriched diet. The LDL cholesterol level was reduced on average by 12 percent, 11 percent, 9 percent, 7 percent, and 5 percent, respectively, after subjects consumed the diets enriched with soybean oil, semiliquid margarine, soft margarine, shortening, and stick margarine; the HDL cholesterol level was reduced by 3 percent, 4 percent, 4 percent, 4 percent, and 6 percent, respectively. Ratios of total cholesterol to HDL cholesterol were lowest after the consumption of the soybean-oil diet and semiliquid-margarine diet and highest after the stick-margarine diet.Our findings indicate that the consumption of products that are low in trans fatty acids and saturated fat has beneficial effects on serum lipoprotein cholesterol levels.

Abstract —We examined the mechanisms responsible for the decrease in HDL cholesterol (HDL-C) levels after the consumption of a diet low in total fat, saturated fat, and cholesterol. Twenty-one subjects with a mean age of 58±12 years were placed on a baseline isocaloric diet (15% protein, 49% carbohydrate, 36% fat, and 150 mg/1000 kcals of cholesterol) and then switched to an NCEP Step 2 diet (15% protein, 60% carbohydrate, 25% fat, and 45 mg/1000 kcals of cholesterol). After 6 or 24 weeks on each diet, subjects received a 15-hour primed-constant infusion of [5,5,5– 2 H 3 ]-L-leucine. HDL apoA-I and apoA-II tracer curves were determined by gas chromatography-mass spectrometry and fitted to a monoexponential equation. Compared with the baseline diet, consumption of the Step 2 diet lowered HDL-C mean levels by 15% (1.03±0.23 to 0.88±0.16 mmol/L, P P P =0.91) but HDL apoA-I secretion rate decreased by 8% (12.26±3.07 to 10.84±2.11 mg · kg −1 · day −1 , P =0.03) during consumption of the Step 2 diet. There was no effect of diet on apoA-II fractional catabolic rate or secretion rate. Our results indicate that the decrease in HDL-C and apoA-I levels during the isocaloric consumption of a Step 2 diet paralleled the reductions in apoA-I secretion rate.

The effect of the fatty acid composition of reduced-fat diets on the in vitro oxidation of LDL was examined in 14 moderately hypercholesterolemic [low density lipoprotein (LDL) > 3.36 mmol/L] postmenopausal female and male subjects (age 44-78 y). Each subject consumed each of five reduced-fat diets [30 energy percent (E%) fat, 17 E% protein and 53 E% carbohydrate] enriched in beef tallow, canola oil, corn oil, olive oil or rice bran oil (20 E%) for 32-d periods. In vitro oxidation of LDL was assessed by incubating LDL with hemin and hydrogen peroxide, and measuring the time required for the reaction to reach maximum velocity (lag time). LDL lag times were 93.2 +/- 25.8, 95.9 +/- 26.4, 104.2 +/- 32.7, 108.0 +/- 26.6 and 113.1 +/- 24.0 min for corn oil, beef tallow, rice bran oil, canola oil and olive oil periods, respectively. When the data from all dietary phases were pooled, LDL alpha-tocopherol level (r = 0.30, P = 0.01) and plasma 18:1/18:2 ratio (r = 0.22, P = 0.08) were positively related to resistance of LDL to oxidation. Differences induced by the dietary perturbations in LDL content of beta-cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-carotene or beta-carotene, and LDL particle size were not related to resistance of LDL to oxidation. In conclusion, in middle-aged and elderly moderately hypercholesterolemic subjects, the consumption of reduced-fat diets enriched in animal fat or vegetable oils with a relatively wide range of fatty acid profiles did not alter the in vitro susceptibility of LDL to oxidation. The advantages of reducing the saturated fat content of the diet were reflected in lower total and LDL cholesterol levels.

Current dietary guidelines from both the American Heart Association1 and the National Cholesterol Education Program2 recommend restricting consumption of fat to an upper limit of 30% of daily caloric intake. This limit translates into 67 g of fat for small or sedentary individuals who need 2000 calories per day and 100 g of fat for larger or more active individuals who need 3000 calories per day. With the exception of the World Health Organization Study Group,3 which recommends that 15% of total calories be derived from fat, current guidelines do not specify a lower limit on fat intake. Recommending a lower limit is controversial4 5 because of the difficulty in balancing the efficacy of a very low fat diet in decreasing plasma cholesterol levels against the risks of nutrient inadequacy or other adverse effects. Some population subgroups, such as growing children, pregnant women, lactating women, and the elderly, have special needs for essential fatty acids and caloric density. Because weight loss frequently accompanies the initial adoption of a very low fat diet and independently affects blood lipid levels and cardiovascular risk, assessing the effect of the very low fat diet alone is difficult. Step 1 and Step 2 diets are effective in lowering blood cholesterol levels6 7 8 and consequently are advocated as the primary dietary strategy for reducing cardiovascular risk.1 2 This statement summarizes the evidence regarding the association of very low fat intake with reduced cardiovascular risk, the quality and quantity of results bearing on this issue, and the effect of very low fat diets on blood lipid levels in the context of potential body weight changes. The statement also contrasts the benefits of very low fat diets with the potentially harmful effects on certain subgroups. For the purposes of this statement, …

We examined the effects of a high fat diet rich in monounsaturated fat (MUFA-diet) and a moderate fat diet rich in polyunsaturated fat (PUFA-diet) on the susceptibility of LDL to oxidation.29 subjects with impaired glucose tolerance.After consuming a run-in diet [37% of energy (E%) fat, 18 E% saturated fat] for three weeks, subjects were randomly assigned either to a MUFA-diet (40 E% fat, 19 E% monounsaturated fatty acids) or a PUFA-diet (34 E% fat, 10 E% polyunsaturated fat) for eight weeks. The susceptibility of LDL to oxidation was measured by challenging LDL with hemin and H2O2 and measuring the time for the reaction to reach maximum velocity. Results are expressed as lag time to oxidation in minutes.In the PUFA-diet group (n = 15) lag time tended to decrease during the experimental diet (97 +/- 28 vs 90 +/- 25 min, mean +/- s.d., P = 0.073), whereas in the MUFA-diet group (n = 14) there was no significant change (lag time 96 +/- 24 vs 100 +/- 16 min, P = 0.408). The mean change in lag time was -7 +/- 14 min (-7.2%) in the PUFA-diet group and +4 +/- 16 min (+4.0%) in the MUFA-diet group (P = 0.029, PUFA-diet group vs MUFA-diet group). The alpha-tocopherol concentration in LDL increased significantly (P0.01) in both diet groups relative to the run-in diet period, but LDL particle score did not change in either of the diet groups during the dietary intervention. In subjects with impaired glucose tolerance a PUFA-rich diet with a moderate amount of fat tended to increase the susceptibility of LDL to oxidation as compared to a higher fat diet rich in MUFA. Furthermore, the negative mean change in lag time to oxidation found in the PUFA-diet group differed significantly from the slightly positive mean change found in the MUFA-diet group.

Subjects with apoA-I(Lys107--0) deletion mutation have reduced levels of plasma HDL cholesterol, apoA-I, apoA-II and Lp(AI:AII). In the present study were describe the postprandial responses of apoA-I(Lys107--0) subjects (n=6) to the ingestion of a fat rich meal compared to the responses of their unaffected family members (n=6). The postprandial plasma triglyceride responses were comparable in the two groups of subjects. Plasma postprandial HDL cholesterol levels fell in both groups; patients (0.89+/-0.05-0.76+/-0.06 mmol/l, P=0.0032) and control subjects (1.32+/-0.25-1.18+/-0.21 mmol/l; P=0.0022). HDL2 cholesterol levels tended to rise, but the changes were not significant. By contrast, in both patients and control subjects, the HDL3 cholesterol levels fell; patients (0.52+/-0.15-0.37+/-0.11 mmol/l, P=0.0068) and control subjects (0.63+/-0.10-0.49+/-0.08 mmol/l, P=0.0078), respectively. In both patients and control subjects the plasma HDL2 mass increased in response to the fat meal; patients (94.7+/-37.3-114.3+/-28.8 mg/dl, P=0.0397) and control subjects (142.1+/-32.8-168.1+/-29.8 mg/dl, P=0.0298), whereas HDL3 mass decreased; patients (162.3+/-36.8-131.4+/-28.9 mg/dl, P=0.0251) and control subjects (185.5+/-34.1-161.1+/-29.0 mg/dl, P=0.0021), respectively. In control subjects the triglyceride levels increased in both HDL2 (0.10+/-0.06-0.17+/-0.06 mmol/l; P=0.0005) and to a lesser extent in HDL3 (0.10+/-0.03-0.12+/-0.02 mmol/l, P=0.0017). In patients, triglyceride levels in both HDL subclasses remained unchanged. Changes in the concentration of Lp(AI) in HDL2 and HDL3 were comparable in the two groups of subjects. The Lp(AI:AII) concentration in HDL2 remained unchanged in the patients, but increased in control subjects (change+27%. P=0.0026). Consequently, the 20% difference at baseline in the concentration of Lp(AI:AII) in HDL2 between the patients and control subjects increased postprandially to 45% (P=0.0240). The Lp(AI:AII) concentration in HDL3 decreased in both groups, but the changes were non-significant. Our findings show that in postprandial state, no accumulation of triglycerides in HDL subclasses occurs in patients with apoA-I(Lys[107]--0) and that these patients appear to lack the ability to respond to fat feeding by increasing the Lp(AI:AII) concentration in HDL2.

Fifty-five patients with advanced multiple myeloma received purified CD34-selected peripheral blood progenitor cell transplants following myeloablative chemotherapy. A median of 4.1 x 10(6) CD34 cells/kg (range 1.2-30.7) were infused after busulfan (14 mg/kg) and cyclophosphamide (120 mg/kg); granulocyte-macrophage colony-stimulating factor was used until hematopoietic recovery. Median time to neutrophils0.5 x 10(9)/l and platelets20 x 10(9)/l were 12 days (range 10-16 and 8-184 days, respectively). Median follow-up of survivors from the time of transplantation is 33 months (range 7 to 44 months). Thirty-one patients are alive, 19 progression-free. Median progression-free survival is 14 months. Actuarial 3-year progression-free and overall survival are 29+/-14% and 47+/-17%. CD34-selection of peripheral blood progenitor cells provides effective hematopoietic support with significant progression-free and overall survival.

Abstract The behavior of apolipoprotein (apo) A-I in lipoprotein (Lp) AI and LpAI:AII was studied in 11 postmenopausal females and 11 males matched for plasma triglyceride and total cholesterol levels. Subjects consumed a baseline diet [35% fat (14% saturated, 15% monounsaturated, and 7% polyunsaturated), 15% protein, 49% carbohydrate, and 147 mg cholesterol/1000 kcal] for 6 weeks before the start of the kinetic study. At the end of the diet period, using a primed-constant infusion of [5,5,5- 2 H 3 ]leucine, residence times (RT) and secretion rates (SR) of apoA-I were determined in 2 subpopulations of high-density lipoprotein (HDL) particles, LpAI and LpAI:AII. Plasma total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations were similar in males and females. The mean plasma HDL cholesterol concentration in males (1.14± 0.23 mmol/L; mean±SD) was lower than in females (1.42±0.18 mmol/L; P =.0034). Similarly, the mean plasma concentration of apoA-I in males (130±21 mg/dL) was lower than that in females (150±19 mg/dL; P =.0421). The RT of apoA-I in either LpAI or LpAI:AII was similar between men and women. Despite the higher plasma apo A-I levels in female compared with male subjects, total apoA-I and apoA-I in LpAI and LpAI:AII pool sizes were similar between the two groups, attributable to the lower body weight of the female subjects. The mean SR of total apoA-I in males (8.5±2.7 mg · kg −1 · d −1 ) was 22% lower than in females (10.9±2.3 mg · kg −1 · d −1 ; P =.0389). The SR of both apoA-I in LpAI and LpAI:AII was lower in males than females, although the differences did not reach statistical significance. These data suggest that the difference observed in HDL cholesterol concentration between males and females is attributable to SR of apoA-I and not the catabolic rate.

Abstract The effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, on the kinetics of de novo cholesterol synthesis and apolipoprotein (apo) B in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) was investigated in five male patients with combined hyperlipidemia. Subjects were counseled to follow a Step 2 diet and were treated with lovastatin and placebo in randomly assigned order for 6-week periods. At the end of each experimental period, subjects were given deuterium oxide orally and de novo cholesterol synthesis was assessed from deuterium incorporation into cholesterol and expressed as fractional synthesis rate (C-FSR) and production rate (C-PR). Simultaneously, the kinetics of VLDL, IDL, and LDL apo B-100 were studied in the fed state using a primed-constant infusion of deuterated leucine to measure fractional catabolic rates (FCR) and production rates (PR). Drug treatment resulted in significant decreases in total cholesterol (−29%), VLDL cholesterol (−40%), LDL cholesterol (−27%), and apo B (−16%) levels and increases in HDL cholesterol (+13%) and apolipoprotein (apo) A-I (+11%) levels. Associated with these plasma lipoprotein responses was a significant reduction in both de novo C-FSR (−40%; P =.04) and C-PR (−42%; P =.03). Treatment with lovastatin in these patients had no significant effect on the FCR of apoB-100 in VLDL, IDL, or LDL, but resulted in a significant decrease in the PR of apoB-100 in IDL and LDL. Comparing the kinetic data of these patients with those of 10 normolipidemic control subjects indicates that lovastatin treatment normalized apoB-100 IDL and LDL PR. The results of these studies suggest that the declines in plasma lipid levels observed after treatment of combined hyperlipidemic patients with lovastatin are attributable to reductions in the C-FSR and C-PR of de novo cholesterol synthesis and the PR of apoB-100 containing lipoproteins. The decline in de novo cholesterol synthesis, rather than an increase in direct uptake of VLDL and IDL, may have contributed to the decline in the PR observed.

Dietary guidelines for the general population and individuals with hyperlipidemia specify upper limits for total fat, saturated fat, and cholesterol intake.1 2 The term trans fatty acids does not appear in dietary guidelines or on nutrient labels; however, it appears frequently in the scientific and lay press. Current issues of controversy are whether trans fatty acids should be listed on nutrient labels and whether this is the appropriate time to issue public health guidelines with respect to intake. Trans fatty acids contain at least one double bond in the trans configuration. The carbon/carbon double bonds of fatty acids can exist in either the cis or trans configuration. When the two hydrogen atoms are on opposite sides of the double bond, the configuration is termed trans ; when the two hydrogen atoms are on the same side of the double bond, the configuration is termed cis . Lack of rotational mobility precludes interconversion of configurations under normal circumstances. The bond angle is larger for a trans than a cis double bond. Therefore, the presence of a trans , relative to a cis , double bond results in acyl chains that can pack together more tightly. Trans double bonds occur in nature as such. They are the result of anaerobic bacterial fermentation in ruminant animals and are thereby introduced into the food chain.3 Humans consume them in the form of meat and dairy products. Trans double bonds are also formed during the hydrogenation of either vegetable or fish oils. Oils are hydrogenated to increase their plasticity and chemical stability, hence their potential use in food products. It is important to note that hydrogenation results in a number of changes in the acyl chain of the fatty acid moiety, all of which can impact physiological parameters: conversion of cis to trans …

Malhotra questions the wisdom of continuing public health recommendations to limit dietary saturated fat for the prevention of cardiovascular disease and went on to suggest that dietary saturated fat may decrease the risk of cardiovascular disease. …

Dihydro-vitamin K1 is a dietary form of vitamin K1 (phylloquinone) produced during the hydrogenation of vegetable oils. To determine if dihydro-vitamin K1 is present in plasma following dietary intake of a hydrogenated fat, eight healthy adults consumed each of two diets containing 30% of calories from fat, of which 20% was either soybean oil or a partially hydrogenated soybean oil-based stick margarine. Of the fats and oils analyzed, dihydro-vitamin K1 was only found in the hydrogenated products. The soybean oil diet contained 180 +/- 12 micrograms (mean +/- SD) of vitamin K1/day and nondetectable levels of dihydro-vitamin K1, whereas the stick margarine diet contained 199 +/- 7 micrograms of vitamin K1/day and 23 +/- 2 micrograms of dihydro-vitamin K1/day. After consuming each diet for five weeks, plasma dihydro-vitamin K1 concentrations were higher (P = 0.002) in all eight subjects when consuming the stick margarine diet (0.56 +/- 0.33 nmol/L) compared to the soybean oil diet (0.12 +/- 0.11 nmol/L). There was no significant change in plasma vitamin K1 concentrations when the two diets were compared. In conclusion, dihydro-vitamin K1 is detectable in plasma following dietary intake of a hydrogenated vitamin K1-rich vegetable oil.

Reactivity of aortic and carotid strip from control; hypertensive; hypercholesterolemic; and hypertensive/hypercholesterolemic rabbits were studied. Maximal stress was less in strips from hypertensive/hypercholesterolemic animals. Norepinephrine sensitivity was increased in the carotid artery from hypertensive/hypercholesterolemic animals (EC50: 0.11 microM; 0.35 microM control). CaCl2 sensitivity during norepinephrine-induced contractions was enhanced by hypertension and hypercholesterolemia (carotid EC50: 0.10 mM; 0.38 mM control; aorta EC50: 0.12 mM; 0.82 mM control). Similar results were obtained during membrane depolarization. 5-hydroxytryptamine sensitivity (EC50: 0.15 microM carotid; 0.18 microM aorta) was decreased during hypertension (EC50: 0.51 microM carotid; 1.13 microM aorta) and by hypercholesterolemia (EC50: 1.76 microM carotid; 1.53 microM aorta). Our results support the hypothesis that hypertension and hypercholesterolemia increase vascular sensitivity by increasing Ca2+ permeability. Our results also suggest that hypertension and hypercholesterolemia selectively decrease 5-hydroxytryptamine-induced contractions.

Abstract We tested the effects of a National Cholesterol Education Program (NCEP) Step 2 diet (30% of calories or less as total fat, less than 7% saturated fat, and less than 200 mg cholesterol per day) on plasma lipid levels in normocholesterolemic and hypercholesterolemic middle-aged and elderly men and women. Thirty-two subjects were studied. Eight normolipidemic subjects (6 men and 2 women, mean age 56±13 years) with LDL cholesterol levels of less than 4.14 mmol/L (160 mg/dL) were given a baseline diet similar in composition to the diet currently consumed in the United States (35% of calories as total fat and 14% as saturated fat, with 147 mg cholesterol per 1000 kcal) for 6 weeks. Subjects were then placed on an NCEP Step 2 diet (26% total fat, 4% saturated fat, 45 mg cholesterol per 1000 kcal) for 24 weeks. In addition, 24 subjects (12 men and 12 women, mean age 62±12 years) with moderate hypercholesterolemia (LDL cholesterol levels of 4.14 mmol/L or above) were given a baseline diet for 6 weeks and then the NCEP Step 2 diet for 6 weeks. Energy intakes were adjusted to keep body weight constant throughout the study. In both normolipidemic and hypercholesterolemic subjects, consumption of the NCEP Step 2 diet was associated with significant changes in levels of total cholesterol (−20% and −16%, respectively), LDL cholesterol (−21% and −18%, respectively), and HDL cholesterol (−16% and −15%, respectively). The plasma total cholesterol/HDL cholesterol ratio and plasma triglyceride, VLDL cholesterol, and lipoprotein(a) levels were not affected by the diet in either group. Similar responses were seen in men and women. The range of diet responsiveness in the 32 subjects was very large, with LDL cholesterol changes ranging from +5% to −40%. Thus, an NCEP Step 2 diet is effective in significantly reducing total and LDL cholesterol levels without changing the total cholesterol/HDL cholesterol ratio under controlled isoweight conditions in middle-aged and elderly normolipidemic and hypercholesterolemic men and women. The wide individual variation in diet responsiveness may indicate genetic variability.

We have investigated the effects of a low-fat, high-fiber diet on plasma lipid and lipoprotein levels and serum sex hormone concentrations in 22 normal premenopausal women (mean age, 25.8 +/- 3.8 years). Participants consumed a baseline diet for 4 weeks (40% of calories as fat, 16% as saturated fatty acids, 8% as polyunsaturated fatty acids, 400 mg/d cholesterol, and 12 g/d dietary fiber) and then a low-fat, high-fiber diet for 8 to 10 weeks (16% to 18% of calories as fat, 4% as saturated fatty acids, 4% as polyunsaturated fatty acids, 150 mg/d cholesterol, and 40 g/d fiber). Blood samples for determination of plasma lipids and serum hormones were obtained during the follicular and luteal phases of the menstrual cycle during both diets. Compared with the baseline diet, the low-fat, high-fiber diet resulted in significant decreases in total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations during both the follicular and luteal phases (TC, -14% and -16%; LDL cholesterol, -14% and -17%; and HDL cholesterol, -15% and -18%, respectively). During the follicular phase but not the luteal phase on the low-fat, high-fiber diet, women exhibited significant increases in plasma triglyceride ([TG] 22%) and very-low-density lipoprotein (VLDL)-TG (36%) concentrations. During the follicular phase, serum estrone sulfate concentrations decreased by 25% (P < .0001) when subjects were fed the low-fat, high-fiber diet.(ABSTRACT TRUNCATED AT 250 WORDS)

In this issue, Angell and colleagues report on the effect of the New York City regulation that has restricted the use of trans fat in the preparation of foods that are sold by chain restaurants. Th...

The relationships between six body girths (shoulder, midarm, waist, hip, thigh, and calf) and cardiovascular risk factors (systolic and diastolic blood pressures and glucose, triglyceride, lipoprotein cholesterol, and apolipoprotein levels) were examined in 407 healthy Chinese urban workers in Taipei, Taiwan who were between 40 to 59 years old. Canonical correlation analysis revealed significant associations of upper body adiposity (shoulder, midarm, and waist firths) with cardiovascular risk factors in all subgroups assessed: men, premenopausal women, and postmenopausal women. Waist girth and hip girth were consistent and important variables, and weighted in the opposite direction. Waist-hip ratio (WHR) was the best descriptor of centralized adiposity. Centralized fat distribution was positively associated with blood pressure and glucose, triglyceride, and apolipoprotein (apo) B levels, and negatively associated with high-density-lipoprotein (HDL) cholesterol and apo A-I levels in this population. Body fat distribution had an effect independent of body mass index and accounted for some of the differences in triglyceride, HDL cholesterol, apo A-I, and apo B concentrations among men, premenopausal women, and postmenopausal women. Our findings in a Chinese population are similar to data from other studies in Western populations, and are consistent with the hypothesis that centralized adiposity is related to cardiovascular risk factors independent of general obesity.

The effect of rice bran oil, and oil not commonly consumed in the United States, on plasma lipid and apolipoprotein concentrations was studied within the context of a National Cholesterol Education Panel (NCEP) Step 2 diet and compared with the effects of canola, corn, and olive oils. The study subjects were 15 middle-aged and elderly subjects (8 postmenopausal women and 7 men; age range, 44 to 78 years) with elevated low-density lipoprotein (LDL) cholesterol (C) concentrations (range, 133 to 219 mg/dL). Diets enriched in each of the test oils were consumed by each subject for 32-day periods in a double-blind fashion and were ordered in a Latin square design. All food and drink were provided by the metabolic research unit. Diet components were identical (17% of calories as protein, 53% as carbohydrate, 30% as fat [< 7% as saturated fat], and 80 mg cholesterol/1000 kcal) except that two thirds of the fat in each diet was contributed by rice bran, canola, corn, or olive oil. Mean +/- SD plasma total cholesterol concentrations were 192 +/- 19, 194 +/- 20, 194 +/- 19, and 205 +/- 19 mg/dL, and LDL-C concentrations were 109 +/- 30, 109 +/- 26, 108 +/- 31, and 112 +/- 29 mg/dL after consumption of the rice bran, canola, corn, and olive oil-enriched diets, respectively. Plasma cholesterol and LDL-C concentrations were similar and statistically indistinguishable when the subjects consumed the rice bran, canola, and corn oil-enriched diets and lower than when they consumed the olive oil-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of plasma lipoproteins and apolipoproteins of replacing corn oil with corn-oil margarine in stick form as two thirds of the fat in the National Cholesterol Education Program (NCEP) Step 2 diet were assessed in 14 middle-aged and elderly women and men (age range, 44-78 years) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-C] range, 133-219 mg/dl [3.45-5.67 mmol/l] at screening). During each 32-day study phase, subjects received all their food and drink from a metabolic kitchen. Subjects were first studied while being fed a diet approximating the composition of the current US diet (baseline), which contained 35% of calories as fat (13% saturated fatty acids [SFAs], 12% monounsaturated fatty acids [MUFAs; 0.8% 18:1n-9 trans], and 8% polyunsaturated fatty acids [PUFAs]) and 128 mg cholesterol/1,000 kcal. This baseline phase was followed by a corn oil-enriched diet containing 30% fat (6% SFA, 11% MUFA [0.4% 18:1n-9 trans], and 10% PUFA) and 83 mg cholesterol/1,000 kcal, and then a corn-oil margarine-enriched diet containing 30% fat (8% SFA, 12% MUFA [4.2% 18:1n-9 trans], and 8% PUFA) and 77 mg cholesterol/1,000 kcal. All diets were isocaloric. Mean fasting LDL-C and apolipoprotein (apo) B levels were 153 mg/dl (3.96 mmol/l) and 101 mg/dl on the baseline diet, 17% and 20% lower (both p < 0.001) on the corn oil-enriched diet, and 10% and 10% lower (both p < 0.01) on the margarine-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary long-chain PUFA, both n-3 and n-6, have unique benefits with respect to CVD risk. The aim of the present study was to determine the mechanisms by which n-3 PUFA (EPA, DHA) and n-6 PUFA (linoleic acid (LA), arachidonic acid (AA)) relative to SFA (myristic acid (MA), palmitic acid (PA)) alter markers of inflammation and cholesterol accumulation in macrophages (MPhi). Cells treated with AA and EPA elicited significantly less inflammatory response than control cells or those treated with MA, PA and LA, with intermediate effects for DHA, as indicated by lower levels of mRNA and secretion of TNFalpha, IL-6 and monocyte chemoattractant protein-1. Differences in cholesterol accumulation after exposure to minimally modified LDL were modest. AA and EPA resulted in significantly lower MPhi scavenger receptor 1 mRNA levels relative to control or MA-, PA-, LA- and DHA-treated cells, and ATP-binding cassette A1 mRNA levels relative to control or MA-, PA- and LA-treated cells. These data suggest changes in the rate of bidirectional cellular cholesterol flux. In summary, individual long-chain PUFA have differential effects on inflammatory response and markers of cholesterol flux in MPhi which are not related to the n position of the first double bond, chain length or degree of saturation.

This review provides a scientific assessment of current knowledge of health effects of soybean oil (SBO) and sunflower oil (SFO). SBO and SFO both contain high levels of polyunsaturated fatty acids (PUFA) (60.8 and 69%, respectively), with a PUFA:saturated fat ratio of 4.0 for SBO and 6.4 for SFO. SFO contains 69% C18:2n-6 and less than 0.1% C18:3n-3, while SBO contains 54% C18:2n-6 and 7.2% C18:3n-3. Thus, SFO and SBO each provide adequate amounts of C18:2n-6, but of the two, SBO provides C18:3n-3 with a C18:2n-6:C18:3n-3 ratio of 7.1. Epidemiological evidence has suggested an inverse relationship between the consumption of diets high in vegetable fat and blood pressure, although clinical findings have been inconclusive. Recent dietary guidelines suggest the desirability of decreasing consumption of total and saturated fat and cholesterol, an objective that can be achieved by substituting such oils as SFO and SBO for animal fats. Such changes have consistently resulted in decreased total and low-density-lipoprotein cholesterol, which is thought to be favorable with respect to decreasing risk of cardiovascular disease. Also, decreases in high-density-lipoprotein cholesterol have raised some concern. Use of vegetable oils such as SFO and SBO increases C18:2n-6, decreases C20:4n-6, and slightly elevated C20:5n-3 and C22:6n-3 in platelets, changes that slightly inhibit platelet generation of thromboxane and ex vivo aggregation. Whether chronic use of these oils will effectively block thrombosis at sites of vascular injury, inhibit pathologic platelet vascular interactions associated with atherosclerosis, or reduce the incidence of acute vascular occlusion in the coronary or cerebral circulation is uncertain. Linoleic acid is needed for normal immune response, and essential fatty acid (EFA) deficiency impairs B and T cell-mediated responses. SBO and SFO can provide adequate linoleic acid for maintenance of the immune response. Excess linoleic acid has supported tumor growth in animals, an effect not verified by data from diverse human studies of risk, incidence, or progression of cancers of the breast and colon. Areas yet to be investigated include the differential effects of n-6- and n-3-containing oil on tumor development in humans and whether shorter-chain n-3 PUFA of plant origin such as found in SBO will modulate these actions of linoleic acid, as has been shown for the longer-chain n-3 PUFA of marine oils.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of dietary supplementation with fish oil was investigated in the Watanabe heritable hyperlipidemic (WHHL) rabbit. Rabbits were fed Maxepa (1 g/kg body weight) from weaning for a 6-month period and were compared to controls. Fish oil supplements resulted in significant decreases in plasma triglyceride and cholesterol at 4 weeks after the start of the study, and these differences persisted over the 6-month period. No differences in the distribution of cholesterol or triglyceride among lipoprotein particles were found, nor were there differences in low density lipoprotein particle size. The decreases in plasma cholesterol and triglyceride were accompanied by significant increases in the percent of eicosapentaenoic and docosahexaenoic acids in both plasma and platelets. Fish oil supplementation resulted in a decrease in platelet count and response to the aggregating agents adenosine diphosphate, arachidonic acid, and collagen. Systolic blood pressure was significantly lower in the rabbits fed fish oil. At the end of the study period, aortic free and esterified cholesterol and intimal surface area covered with plaque were determined in the arch and in the descending and abdominal aorta. Significantly less cholesterol was found in the descending and abdominal aorta. These differences were mirrored by decreased activities of acid lipase and N-acetyl-beta-glucosaminidase. In contrast, no differences in the intimal surface area covered with plaque were found. In conclusion, dietary fish oil resulted in a decrease in aortic lipid deposition in the WHHL rabbit, which may have been due to decreases in plasma triglyceride and cholesterol, platelet count and aggregability, and systolic blood pressure.

We thank Kleefstra et al. for their comments (1) on our review (2), and we appreciate the opportunity to respond. We agree that the available trials on chromium supplementation are of poor quality and have heterogeneous results. Our approach toward systematic review is to not exclude studies based on what are inevitably subjective decisions about quality, applicability, or heterogeneity. A subanalysis of the chromium picolinate trials excluding Anderson et al. (3), because of its …

Objective. —To assess the effects of a diet restricted in fat, saturated fat, and cholesterol, under weight-maintenance and ad libitum conditions on body weight and plasma lipid levels in hypercholesterolemic subjects. Design. —Dietary intervention study. Setting and Participants. —Twenty-seven free-living, healthy middle-aged and elderly men (n=13, age range, 41 to 81 years) and women (n=14, age range, 52 to 79 years) with moderate hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] ≥3.36 mmol/L [130 mg/dL]) participated in the study. Intervention. —Subjects underwent three dietary phases. First, subjects were provided with a diet similar to the average US diet (baseline diet; 35.4% total fat, 13.8% to 14.1% saturated fat, and 30 to 35 mg/1000 kJ [128 to 147 mg/1000 kcal] cholesterol). During the second dietary phase, subjects consumed a low-fat diet (15.1% total fat, 5.0% saturated fat, 17 mg/1000 kJ [73 mg/1000 kcal] cholesterol). During the baseline and low-fat diet phases, which lasted 5 to 6 weeks each, the energy intake was adjusted to keep body weight constant. During the third diet phase (low-fat ad libitum diet) subjects were given the same low-fat diet for 10 to 12 weeks, but could adjust their intake between 66% and 133% of the energy required to maintain body weight. Main Outcome Measures. —Body weight and plasma lipid levels. Results. —Consumption of the low-fat diet under weight-maintenance conditions had significant lowering effects on plasma total cholesterol (TC), LDL-C, and highdensity lipoprotein cholesterol (HDL-C) levels (mean change, -12.5%, -17.1%, and -22.8%, respectively). This diet significantly increased plasma triglyceride levels (+47.3%) and the TC/HDL-C ratio (+14.6%). In contrast, consumption of the low-fat ad libitum diet was accompanied by significant weight loss (-3.63 kg), by a mean decrease in LDL-C (-24.3%), and by mean triglyceride levels and TC/HDL-C ratio that were not significantly different from values obtained at baseline. Conclusions. —Our results indicate that a low-fat ad libitum diet promotes weight loss and LDL-C lowering without adverse effects on triglycerides or the TC/HDL-C ratio in middle-aged and elderly men and women with moderate hypercholesterolemia. (JAMA. 1995;274:1450-1455)