Pramod Khosla

Short-Term Effect of Eggs on Satiety in Overweight and Obese Subjects

Objective: To test the hypotheses that among overweight and obese participants, a breakfast consisting of eggs, in comparison to an isocaloric equal-weight bagel-based breakfast, would induce greater satiety, reduce perceived cravings, and reduce subsequent short-term energy intake. Subjects: Thirty women with BMI’s of at least 25 kg/M2 between the ages of 25 to 60 y were recruited to participate in a randomized crossover design study in an outpatient clinic setting. Design: Following an overnight fast, subjects consumed either an egg or bagel-based breakfast followed by lunch 3.5 h later, in random order two weeks apart. Food intake was weighed at breakfast and lunch and recorded via dietary recall up to 36 h post breakfast. Satiety was assessed using the Fullness Questionnaire and the State-Trait Food Cravings Questionnaire, state version. Results: During the pre-lunch period, participants had greater feelings of satiety after the egg breakfast, and consumed significantly less energy (kJ; 2405.6 ± 550.0 vs 3091.3 ± 445.5, Egg vs Bagel breakfasts, p < 0.0001), grams of protein (16.8 ± 4.2 vs 22.3 ± 3.4, Egg vs Bagel breakfasts, p < 0.0001), carbohydrate 83.1 ± 20.2 vs 110.9 ± 18.7, Egg vs Bagel breakfasts, p < 0.0001), and fat 19.4 ± 5.1 vs 22.8 ± 3.2, Egg vs Bagel breakfasts, p < 0.0001) for lunch. Energy intake following the egg breakfast remained lower for the entire day (p < 0.05) as well as for the next 36 hours (p < 0.001). Conclusions: Compared to an isocaloric, equal weight bagel-based breakfast, the egg-breakfast induced greater satiety and significantly reduced short-term food intake. The potential role of a routine egg breakfast in producing a sustained caloric deficit and consequent weight loss, should be determined.

Dietary trans-monounsaturated fatty acids negatively impact plasma lipids in humans: critical review of the evidence.

Trans fatty acids (t-FA) are geometrical isomers of unsaturated fatty acids that assume a saturated fatty acid-like configuration. Human diets contain t-FA derived from animal sources (e.g., dairy products and ruminant meats), but most are supplied by products containing industrially hydrogenated vegetable oils (e.g., margarines, shortenings and baked goods). Typical intake of t-FA in American diets has been estimated to be between 8-15 g/day, although wide variation exists between individuals. Human clinical studies since 1990 have revealed that relative to cis-monounsaturated fatty acids (i.e., oleic acid), t-FA increase total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), and tend to decrease high density lipoprotein cholesterol (HDL-C) concentrations. Additionally, t-FA tend to increase the atherogenic lipoprotein (a). Thus, t-FA induce an adverse plasma lipid profile (increased ratios of TC/LDL-C and LDL-C/HDL-C), which represents increased risk for coronary heart disease. The effects of t-FA on LDL-C and HDL-C appear to be directly related to intake and clinically measurable above 3%en as t-FA. The cholesterol-raising ability of t-FA is analogous to that of the 12-16 carbon saturated fatty acids, possibly reflecting increased LDL production or delayed LDL clearance. By contrast, t-FA are unlike the saturated fatty acids in their depression of HDL-C. Preliminary evidence suggests that at least part of their impact on lipoproteins reflects increased serum cholesteryl ester transfer protein activity, i.e., increased transfer of cholesteryl esters from HDL to LDL. Since the adverse effects of t-FA on human plasma lipids may be confined to specific isomers, future studies delineating their effects are warranted.

Dietary myristic, palmitic, and linoleic acids modulate cholesterolemia in gerbils.

Previous studies with cebus monkeys and review of published human data indicated that 85% to 90% of the variation in plasma cholesterol (TC) could be explained on the basis of dietary myristic (14:0) and linoleic (18:2) acid intake in the absence of cholesterol, and that 16:0 contributed to cholesterolemia as dietary cholesterol was increased. Because monkeys are a limited resource, a more convenient, sensitive model was sought for investigating these dietary fatty acid and plasma lipid relationships. Accordingly, this report describes the results of multiple regression analysis of the TC response to dietary fatty acids based on 319 young, male Mongolian gerbils fed a total of 59 purified diets supplying about 40% energy as fat from single or blended fat sources. Gerbils (6‐16 animals per dietary group) were fed purified diets (21 with 0.01 to 0.08% cholesterol and 38 cholesterol‐free) for 4‐week periods. When cholesterol‐free diets were fed, dietary 14:0 and 18:2 together accounted for 89% of the observed variation in TC. Although 14:0 consumption increased TC in a linear manner, the independent ability of 18:2 to lower cholesterol was nonlinear and exhibited a threshold effect at 5‐6% dietary energy, above which further lowering of TC was less remarkable. In gerbils consuming cholesterol‐supplemented diets, 87% of the observed variation in TC could be accounted for by a regression equation that included 14:0, palmitic acid (16:0), and a log function of 18:2 plus dietary cholesterol itself. These results demonstrate the applicability of gerbils for such studies and confirm previous observations in monkeys and humans that dietary 14:0 and 18:2 are the main fatty acids modulating plasma cholesterol under normocholesterolemic circumstances (i.e., when consuming low‐cholesterol diets and lipoprotein metabolism is normal) whereas 16:0 also appears modestly hypercholesterolemic when LDL receptors are compromised (i.e., when dietary cholesterol or certain metabolic factors have encumbered lipoprotein metabolism).—Pronczuk, A., Khosla, P., Hayes, K. C. Dietary myristic, palmitic, and linoleic acids modulate cholesterolemia in gerbils. FASEB J. 8, 1191‐1200 (1994)

Prevalence of risk factors to coronary heart disease in an Arab-American population in southeast Michigan.

Although significant advances have been made in the area of cardiovascular disease, few studies have targeted ethnic groups. There is a large and growing Arab-American (AA) population living in Southeast Michigan, whose risk of cardiovascular disease may be on the increase. The objective of this study was to evaluate the prevalence of cardiovascular disease risk factors and associated behavioral factors in an AA community with a large population of emigrants, subjected to significant lifestyle changes. Three hundred and fifty-two AA living in Southeast Michigan, mostly from the Middle East, were screened to determine their eating and smoking habits, body mass index (BMI) body fat analysis, blood pressure, and complete lipid profiling. Overweight was defined as a BMI greater than or equal to the 85th percentile value for age- and sex-specific reference data from the third National Health and Nutrition Examination Survey (NHANES III). Correlation analysis was used to examine factors associated with being overweight, with adjustment for age and sex. Blood cholesterol concentrations were compared with published data for Arabs from the Middle Eastern countries. The overall prevalence of being overweight in subjects aged 35 and older was significantly higher than NHANES III reference data (Men, 27.7% (95% confidence interval, 21.8-34.5); women, 33.7% (95% confidence interval, 27.9-40.1)). A mean cholesterol concentration of 210 ± 4 mg/dl was observed in those over the age of 40. The mean high-density lipoprotein (HDL)-cholesterol levels for men and women were 38 and 48 mg/dl, respectively. Greater than 54.6% of all subjects had a total cholesterol:HDL ratio >4.5. Although being overweight and obesity were prevalent in this population, the mean BMI for men was 25.7 ± 0.34, compared with 27 ± 0.58 for women. Increased BMI was significantly correlated (P < 0.01) with increased blood pressure, increased glucose levels, increased total cholesterol and decreased HDL-cholesterol levels (P < 0.01). Elevation in risk factors to cardivoascular disease is prevalent in this population and indicates a need for programs targeting primary prevention of obesity in men and women. These results, which could be attributed in part to lifestyle changes typical of most emigrant populations, suggest an increase in the risk for developing cardiovascular disease. In addition, this study provides a basis for future intervention to improve the health of this population.

Dietary palmitic acid raises plasma LDL cholesterol relative to oleic acid only at a high intake of cholesterol

Using a crossover design, the effects of exchanging up to 10% dietary energy (%en) between oleic (18:1) and palmitic acid (16:0) on plasma lipoprotein metabolism was investigated in 12 normocholesterolemic cebus monkeys, both in the absence and presence of dietary cholesterol (0.3%, w/w). In all the purified diets, which contained 33%en as fat blends, myristic acid (14:0) and linoleic acid (18:2) were held constant at 0.3%en and 3.7%en, respectively. Cholesterol-free diets containing either high 18:1 (19%en), roughly equivalent levels of 16:0 and 18:1 (12 and 15%en, respectively), or a high level of 16:0 (18%en), generated similar values for total plasma cholesterol (TC), HDL-C and LDL-C. Plasma triacylglycerol concentrations (TG) were significantly higher when monkeys were fed the 16: 0-rich diet than when fed the 18: 1-rich diet (75 +/- 6 vs. 52 +/- 8 mg/dl; P < 0.05). LDL and HDL kinetic parameters (assessed after simultaneous injection of homologous 131I-LDL and 125I-HDL) revealed no significant differences between the 18: 1-rich or 16: 0-rich diets. By contrast, with added dietary cholesterol (0.78 mg/kcal) the 16: 0-rich diet resulted in significantly higher TC (318 +/- 20 vs. 299 +/- 20 mg/dl; P < 0.05) and LDL-C (136 +/- 10 vs. 117 +/- 10 mg/dl; P < 0.05) in comparison to the 18: 1-rich diet. HDL-C was unaffected (159 +/- 8 vs. 156 +/- 5 mg/dl), but plasma TG concentrations also tended to be higher (70 +/- 8 vs. 60 +/- 6 mg/dl, P < 0.08). Kinetic studies revealed that the higher LDL-C concentration was associated with an elevated pool size of LDL apo B (40 +/- 2 vs. 34 +/- 2 mg/kg body weight; P < 0.005), the latter attributed to decreased FCR (1.06 +/- 0.07 vs. 1.27 +/- 0.12 pools/day; P < 0.04) with no effect on the transport rate of LDL apo B (41 +/- 2 vs. 42 +/- 3 mg/kg body weight per day). HDL kinetic parameters were comparable during the 16: 0 and 18: 1 dietary periods, but dietary cholesterol caused an increase in apo A-I pool size and transport rate without impacting FCR. In this study a palmitic acid-rich diet failed to alter plasma or LDL-C when compared to an oleic acid-rich diet, unless the diet also contained cholesterol. In the latter case, 16: 0 increased LDL-C, which reflected a decrease in the efficiency of LDL apo B removal.

Dietary fat saturation in rhesus monkey affects LDL concentrations by modulating the independent production of LDL apolipoprotein B

In a recent study from this laboratory, rhesus monkeys fed a 90% palm oil/10% soybean oil-containing diet (PS), rich in 16:0 and 18:1 fatty acids, had decreased total and LDL cholesterol concentrations compared to monkeys fed a 90% coconut oil/10% soybean oil-containing diet (CS), rich in 12:0 and 14:0 fatty acids. To investigate the metabolic basis of these changes, homologous 125I-VLDL and 131I-LDL were injected simultaneously into eight monkeys (four per dietary group). Analysis of apo B specific activity curves revealed that PS monkeys had an increased pool size of VLDL apo B (P less than 0.02), a 3-fold increase in the total VLDL apo B transport rate (P less than 0.001), a decreased pool size of LDL apo B (P less than 0.01) and a 2-fold decrease in the total transport rate of LDL apo B (P less than 0.001), while the irreversible FCR for VLDL apo B and LDL apo B was similar between dietary groups. PS monkeys derived a greater percentage of LDL apo B from VLDL catabolism resulting in a greater transport rate of LDL apo B from VLDL catabolism (P less than 0.055), in comparison to CS monkeys. For CS monkeys the proportion as well as the amount of LDL apo B derived from VLDL-independent catabolism (i.e., LDL apo B derived from sources other than VLDL catabolism) was higher (P less than 0.001) than the values obtained in PS monkeys. In both dietary groups the proportion of VLDL apo B converted to LDL apo B was similar, although the absolute amount was higher for the PS monkeys (P less than 0.06). The proportion of VLDL apo B directly removed from the circulation was similar for both dietary groups, with the absolute amount being higher for the PS monkeys (P less than 0.001). Consistent with the lower pool size of LDL apo B and the higher pool size of VLDL apo B observed in PS monkeys, plasma and LDL cholesterol concentrations tended to be lower, whereas plasma triacylglycerol and VLDL cholesterol concentrations tended to be higher, but these changes were not statistically significant. Although total apo B and VLDL apo B transport rates were increased 2-3-fold in PS monkeys, LDL apo B concentration was reduced by 40% (P less than 0.02) attributed to a significant reduction in the mass and proportion of LDL apo B derived independent of VLDL catabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

A rationale for plasma cholesterol modulation by dietary fatty acids: Modeling the human response in animals

Abstract At low levels of dietary cholesterol intake ( 500 mg/day), the plasma cholesterol response is no longer described accurately by dietary 14:0 and 18:2 alone. In such situations 16:0 appears to contribute to plasma cholesterol elevation. The hypercholesterolemic potential of 16:0, possibly reflecting a synergism between dietary cholesterol and 16:0, is thought to reside, in part, in the ability of 16:0 to increase the transport of very low density lipoprotein (VLDL) apoB. Increased production of VLDL, coupled with impaired LDL receptor activity, results in an expansion of the LDL pool when the ability to clear VLDL remnants is impaired. Evidence is also available to suggest that the position of saturated fatty acids on the TG molecule affects its hypercholesterolemic ability. An argument is made for selecting animal models for investigation of the fat saturation effect based initially on the total plasma cholesterol (TC) response, with subsequent emphasis being placed on lipoproteins and the actual control mechanism(s) once the generic similarity in the TC response with that in humans has been established.

Saturated fatty acids and LDL receptor modulation in humans and monkeys

It has been known for 40 years that dietary saturated fat (SAT FAT) increases plasma cholesterol, including LDL-C and HDL-C. In humans, where LDL-C is typically > 90 mg/dl this SAT FAT effect largely reflects changes in LDL-C pool size. The original human studies suggested that LDL-C expansion during SAT FAT consumption reflected reduced LDL clearance (LDL receptor activity) in hyperlipemics and increased LDL production rates in normolipemics (LDL-C < 100 mg/dl) . This dual explanation is supported by data from several animal models where specific saturated fatty acids (SFAs) have been the focus. However, the situation is complicated by the fact that polyunsaturated fatty acids (PUFAs) oppose SFAs, i.e. PUFAs decrease LDL-C and increase LDL receptor (LDLr) activity, so the effect of SAT FAT intake may represent the combined influence of increased SFAs and decreased PUFAs. In fact, careful scrutiny of primate data suggests a negligible effect of saturated fat on LDL clearance (and receptor activity) in the absence of dietary cholesterol when PUFA intake is adequate (5-10%en) and the lipoprotein profile is relatively normal (LDL-C < 90 mg/dl), i.e. normolipemic situations at the time of dietary intervention. In such cases increases in LDL-C due to SFAs (particularly 12:0+14:0) appear to reflect LDL overproduction associated with a shift in cholesterol from tissues to the plasma cholesteryl ester (CE) pool (both LDL-C and HDL-C) without altering whole-body cholesterol balance. The reason for this shift, which is accompanied by an increase in the plasma oleic/linoleic CE ratio, is unknown but may reflect a decreased rate of CE hydrolysis by the liver. When individuals or animals are rendered hyperlipemic by other factors (e.g. chronic caloric and dietary cholesterol excesses in humans or by cholesterol feeding in animals) specific SFAs (particularly 16:0) can contribute to decreased LDLr activity initiated by a primary factor, such as dietary cholesterol. However, LDLr down-regulation by dietary cholesterol greatly exceeds any contribution from SFAs.

Vitamin E tocotrienol supplementation improves lipid profiles in chronic hemodialysis patients

Purpose Chronic hemodialysis patients experience accelerated atherosclerosis contributed to by dyslipidemia, inflammation, and an impaired antioxidant system. Vitamin E tocotrienols possess anti-inflammatory and antioxidant properties. However, the impact of dietary intervention with Vitamin E tocotrienols is unknown in this population. Patients and methods A randomized, double-blind, placebo-controlled, parallel trial was conducted in 81 patients undergoing chronic hemodialysis. Subjects were provided daily with capsules containing either vitamin E tocotrienol-rich fraction (TRF) (180 mg tocotrienols, 40 mg tocopherols) or placebo (0.48 mg tocotrienols, 0.88 mg tocopherols). Endpoints included measurements of inflammatory markers (C-reactive protein and interleukin 6), oxidative status (total antioxidant power and malondialdehyde), lipid profiles (plasma total cholesterol, triacylglycerols, and high-density lipoprotein cholesterol), as well as cholesteryl-ester transfer protein activity and apolipoprotein A1. Results TRF supplementation did not impact any nutritional, inflammatory, or oxidative status biomarkers over time when compared with the baseline within the group (one-way repeated measures analysis of variance) or when compared with the placebo group at a particular time point (independent t-test). However, the TRF supplemented group showed improvement in lipid profiles after 12 and 16 weeks of intervention when compared with placebo at the respective time points. Normalized plasma triacylglycerols (cf baseline) in the TRF group were reduced by 33 mg/dL (P=0.032) and 36 mg/dL (P=0.072) after 12 and 16 weeks of intervention but no significant improvement was seen in the placebo group. Similarly, normalized plasma high-density lipoprotein cholesterol was higher (P<0.05) in the TRF group as compared with placebo at both week 12 and week 16. The changes in the TRF group at week 12 and week 16 were associated with higher plasma apolipoprotein A1 concentration (P<0.02) and lower cholesteryl-ester transfer protein activity (P<0.001). Conclusion TRF supplementation improved lipid profiles in this study of maintenance hemodialysis patients. A multi-centered trial is warranted to confirm these observations.

Conjugated linoleic acid: effects on plasma lipids and cardiovascular function.

Conjugated linoleic acid is a collective name for mixtures of several positional and geometric conjugated dienoic isomers of linoleic acid, which have been shown to impact favorably on several biological processes, particularly carcinogenesis. Recent studies have clearly established that the c9, t11 andt10, c12 isomers have distinct biological effects. The latter may be of particular importance in affecting blood lipids. Because conjugated linoleic acid has been suggested to be anti-atherogenic, this review is focused on its effects on cardiovascular function. Careful scrutiny of the literature suggests that at present it is premature to assign any beneficial role to conjugated linoleic acid in terms of its ability to impact either blood lipids or atherogenesis.