Mg Of Dietary Cholesterol Research Articles

Egg and cholesterol consumption and mortality from cardiovascular and different causes in the United States: A population-based cohort study.

Whether consumption of egg and cholesterol is detrimental to cardiovascular health and longevity is highly debated. Data from large-scale cohort studies are scarce. This study aimed to examine the associations of egg and cholesterol intakes with mortality from all causes, cardiovascular disease (CVD), and other causes in a US population. Overall, 521,120 participants (aged 50-71 years, mean age = 62.2 years, 41.2% women, and 91.8% non-Hispanic white) were recruited from 6 states and 2 additional cities in the US between 1995 and 1996 and prospectively followed up until the end of 2011. Intakes of whole eggs, egg whites/substitutes, and cholesterol were assessed by a validated food frequency questionnaire. Cause-specific hazard models considering competing risks were used, with the lowest quintile of energy-adjusted intake (per 2,000 kcal per day) as the reference. There were 129,328 deaths including 38,747 deaths from CVD during a median follow-up of 16 years. Whole egg and cholesterol intakes were both positively associated with all-cause, CVD, and cancer mortality. In multivariable-adjusted models, the hazard ratios (95% confidence intervals) associated with each intake of an additional half of a whole egg per day were 1.07 (1.06-1.08) for all-cause mortality, 1.07 (1.06-1.09) for CVD mortality, and 1.07 (1.06-1.09) for cancer mortality. Each intake of an additional 300 mg of dietary cholesterol per day was associated with 19%, 16%, and 24% higher all-cause, CVD, and cancer mortality, respectively. Mediation models estimated that cholesterol intake contributed to 63.2% (95% CI 49.6%-75.0%), 62.3% (95% CI 39.5%-80.7%), and 49.6% (95% CI 31.9%-67.4%) of all-cause, CVD, and cancer mortality associated with whole egg consumption, respectively. Egg white/substitute consumers had lower all-cause mortality and mortality from stroke, cancer, respiratory disease, and Alzheimer disease compared with non-consumers. Hypothetically, replacing half a whole egg with equivalent amounts of egg whites/substitutes, poultry, fish, dairy products, or nuts/legumes was related to lower all-cause, CVD, cancer, and respiratory disease mortality. Study limitations include its observational nature, reliance on participant self-report, and residual confounding despite extensive adjustment for acknowledged dietary and lifestyle risk factors. In this study, intakes of eggs and cholesterol were associated with higher all-cause, CVD, and cancer mortality. The increased mortality associated with egg consumption was largely influenced by cholesterol intake. Our findings suggest limiting cholesterol intake and replacing whole eggs with egg whites/substitutes or other alternative protein sources for facilitating cardiovascular health and long-term survival. ClinicalTrials.gov NCT00340015.

Differences in Response to Egg Intake Result in Distinct Lipoprotein Profiles While Plasma Concentrations of Carotenoids and Choline Are Not Affected (P08-102-19)

ObjectivesIt has been demonstrated that some individuals (approximately 1/3 of the population) can be classified as hyper-responders to dietary cholesterol. The objective of this study was to evaluate whether the response to dietary cholesterol (provided by eggs) would affect lipoprotein metabolism and the bioavailability of lutein, zeaxanthin and choline, nutritional components present in eggs. MethodsWe recruited 36 healthy subjects who underwent a two-week washout period in which they consumed zero eggs. Participants were then fed 3 eggs (540 additional mg of dietary cholesterol) for 4 weeks. Plasma lipids were measured by use of an automated chemical clinical analyzer; the number of large and small LDL and HDL particles were measured by Nuclear Magnetic Resonance. Plasma lutein and zeaxanthin were determined by use of HPLC and plasma choline by use of LSM spectroscopy. We classified the normal response to dietary cholesterol as 2.2 mg/dL for each additional 100 mg of dietary cholesterol. Therefore, those individuals who had >12 mg/dL increase in plasma cholesterol after the intervention (n = 12) were considered hyper-responders while the other 24 subjects who presented changes in plasma cholesterol ranging from −16 to 9 mg/dL were considered hypo-responders. ResultsCompared to zero eggs, hyper-responders had significant increases in plasma total, LDL and HDL cholesterol (P < 0.001) with no changes in the LDL/HDL ratio. They also had higher concentrations of large LDL (P < 0.01) with no changes in small LDL. In contrast no changes in plasma total LDL or HDL cholesterol or large LDL were observed in hypo-responders after the consumption of 3 eggs/day. Interestingly, both hypo and hyper-responders had significant increases in large HDL particles (12%), plasma lutein (17%), zeaxanthin (30%) and choline (12%) (P < 0.001) compared to zero egg intake. ConclusionsThese results suggest that egg intake increases the bioavailability of carotenoids and choline present in eggs independently of plasma cholesterol response to dietary cholesterol. Further, the observed increases in large HDL in all individuals could be associated with HDL being a major transporter of lutein and zeaxanthin in plasma. Funding SourcesThe Esperance Family and the Egg Nutrition Center.

Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality

Cholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial. To determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality. Individual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol. Dietary cholesterol (mg/day) or egg consumption (number/day). Hazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors. This analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all P values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, -0.47% [95% CI, -1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, -0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption. Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.

Exclusion of Dietary Cholesterol from The Specific Food Restrictions: A Review in Indonesia

Hypercholesterolemia, the presence of high levels of cholesterol in the blood, is one of the major risk factor for cardiovascular disease (CVD). One of the key recommendation in the Dietary Guidelines for Americans 2010, is to consume less than 300 mg of dietary cholesterol per day. The same amount is also adopted in Indonesia (BPOM, 2016) until today. However, in the latest Dietary Guidelines for Americans 2015-2020, dietary cholesterol is no longer included in the list of specific foods that should be limited. The added sugars, sodium, saturated fats and trans fats remain on the list of food components that should be reduced. Generally, foods that are higher in dietary cholesterol are also higher in saturated fats. But there are also some foods that are higher in cholesterol but not in saturated fats. According to the latest recommendation, this kind of foods can be consumed without any specific restriction. In this review, some of clinical studies related to the association between dietary cholesterol and blood cholesterol levels are selected. The findings from those studies will be summarized to consider whether the same recommendation should be implemented in other countries, especially in Indonesia.

DIETARY CHOLESTEROL LOWERS RISK OF TYPE 2 DIABETES IN THE FRAMINGHAM OFFSPRING STUDY

Beginning in the 1960s, limiting dietary cholesterol (DC) was widely considered a strategy for protecting against cardiovascular disease (CVD) risk. Recently, the 2013 American College of Cardiology/American Heart Association Lifestyle Guidelines for the Reduction of Cardiovascular Disease concluded that the evidence was insufficient to support continued restriction of DC intake for prevention of CVD; the Dietary Guidelines Advisory Committee no longer considers DC to be a “nutrient of concern”. However, questions remain about whether DC is a risk factor for type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the effects of DC alone and in combination with selected markers of a healthy diet (e.g. fruits &amp; vegetables, whole grains, fiber) on fasting glucose (FG) and risk of developing T2DM. Men and women without T2DM who were 35–64 years of age at the time of dietary assessment in the Framingham Offspring Study were included these analyses and followed for 20 years. Three‐day food records were collected at exams 3 and 5. Individuals were classified according to sex‐specific DC intake (low, moderate, and high intakes for men: &lt;200, 200–&lt;400, and ≥400 mg/day; for women: &lt;150, 150–&lt;350, and ≥350 mg/day). Longitudinal mixed models were used to estimate the adjusted mean fasting glucose (FG) at five follow‐up exams, 4 years apart. Cox proportional hazard's models were used to estimate the risk of developing T2DM; final models were adjusted for age, education, physical activity, cigarette smoking, alcohol intake, and baseline body mass index (BMI). At baseline, men consuming ≥400 mg of DC had lower mean FG than those consuming &lt;200 mg (FG: 93.8 vs 96.6, p‐trend: 0.0006); results were similar in women. There was no evidence that higher DC intake had an adverse effect on FG throughout all years of follow‐up. Among both men and women, longitudinal mixed models showed that those consuming the highest (vs. lowest) amounts of DC had the lowest FG levels at baseline (p&lt;0.0001) and lowest throughout the 20 years of follow‐up (p=0.0008). In addition, those subjects with high intakes of DC had a 22% lower risk of developing T2DM (HR: 0.78; 95% CI: 0.52–1.15) over time. To evaluate the combined effects of DC and other healthy diet patterns, we cross‐classified subjects according to their intake of both DC and the particular food serving as a marker of a healthy diet. The foods most strongly associated with a lower risk of T2DM and that modified the effects of DC were whole grains and fiber. Adults consuming ≥300 mg/day of DC and ≥0.5 servings/day of whole grains had a 38% lower risk of developing T2DM (95% CI: 0.41–0.93), while those consuming ≥300 mg/day of DC who had low whole intakes had only a 21% lower risk and those with lower DC intakes but higher intakes of whole grains had a 13% lower risk. These results suggest a positive synergistic effect between DC and whole grain consumption. Dietary fiber also modified the effects of DC on T2DM risk. Subjects consuming ≥300 mg/day of DC and ≥15 grams of dietary fiber had a 43% lower risk of T2DM (95% CI: 0.40–0.83) than those consuming less DC and less fiber. These results suggest that higher intakes of DC do not adversely affect fasting glucose levels or risk of T2DM and may even be beneficial when consumed in combination with a healthy diet.Support or Funding InformationNational Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. HHSN268201500001I) and a small grant from the American Egg Board ‐ Egg Nutrition Center.

A dietary cholesterol challenge study to assess Chlorella supplementation in maintaining healthy lipid levels in adults: a double-blinded, randomized, placebo-controlled study.

BackgroundPrevious animal studies suggested that Chlorella, a unicellular green alga, has a preventive role in maintaining serum cholesterol levels against excess dietary cholesterol intake. This study aimed to conduct a pioneering investigation to clarify this issue in healthy subjects by adopting a dietary cholesterol challenge, which has not been used previously in similar studies of Chlorella in hypercholesterolemia.MethodsIn this double blind, randomized, placebo-controlled study, 34 participants ingested 510 mg of dietary cholesterol from three eggs concomitantly with a usual dose of Chlorella (5 g/d) or a matched placebo for 4 weeks.ResultsThe dietary cholesterol challenge induced consistently higher concentrations of serum total cholesterol (TC, P < 0.001), LDL-C (P = 0.004), and HDL-C (P = 0.010) compared with baseline values, suggesting that the challenge was reliable. Thus, we observed a preventive action of Chlorella in maintaining serum TC versus placebo levels (3.5 % versus 9.8 %, respectively; P = 0.037) and LDL-C versus placebo levels (1.7 % versus 14.3 %, respectively; P = 0.012) against excessive dietary cholesterol intake and in augmenting HDL-C versus placebo levels (8.3 % versus 3.8 %, respectively). Furthermore, serum α-carotene showed the best separation between the placebo and Chlorella groups (R2X and R2Y > 0.5; Q2 > 0.4).ConclusionThe results suggest that a fully replicated dietary cholesterol challenge may be useful in assessing the effectiveness of dietary supplements in maintaining the serum lipid profiles of adults whose habitual diets are high in cholesterol.Trial registrationWHO International Clinical Trials Registry Platform (KCT0000258)

The Fifty Year Rehabilitation of the Egg.

The 1968 American Heart Association announced a dietary recommendation that all individuals consume less than 300 mg of dietary cholesterol per day and no more than three whole eggs per week. This recommendation has not only significantly impacted the dietary patterns of the population, but also resulted in the public limiting a highly nutritious and affordable source of high quality nutrients, including choline which was limited in the diets of most individuals. The egg industry addressed the egg issue with research documenting the minimal effect of egg intake on plasma lipoprotein levels, as well as research verifying the importance of egg nutrients in a variety of issues related to health promotion. In 2015 dietary cholesterol and egg restrictions have been dropped by most health promotion agencies worldwide and recommended to be dropped from the 2015 Dietary Guidelines for Americans.

Intake of 2 Eggs or Oatmeal for Breakfast does not Increase Biomarkers for Heart Disease while Eggs Improve Liver Enzymes and Raise HDL Cholesterol in Young Healthy Individuals

We hypothesized that consuming 2 eggs per day for breakfast would not increase biomarkers of heart disease in a young healthy population. We recruited 26 women and 24 men aged 18‐30 y old with healthy plasma lipid profiles and plasma glucose, a BMI of 23.3 ± 3.2 kg/m2 in addition to normal systolic and diastolic blood pressure. Participants were randomly allocated to consume a breakfast of either 2 eggs per day or a packet of oatmeal per day for 4 weeks. Following a 3 week washout participants were allocated to the alternate dietary treatment. Blood was collected at the end of each period to assess plasma lipid profiles, plasma glucose, liver enzymes and C‐reactive protein (CRP). In spite of the additional 460 mg of dietary cholesterol per day during the egg period, we observed no changes in total cholesterol, LDL cholesterol, LDL/HDL ratio, plasma triglycerides, systolic or diastolic blood pressure, body weight, plasma glucose or CRP when compared to the oatmeal breakfast. However, liver enzymes alanine amino transferase and aspartate amino transferase were lower (p &lt; 0.05) during the egg period. Further, we observed that HDL cholesterol consistently increased after the egg period (p &lt; 0.05) while HDL cholesterol decreased following the oatmeal period. These results indicate that for healthy young men and women consumption of two eggs per day appears to be a healthy breakfast in that eggs did not impact plasma lipids or glucose negatively but in contrast were beneficial for liver enzymes and HDL cholesterol.

Egg intake increases peripheral blood mononuclear cell expression of ATP‐binding cassette transporter A1 in parallel with toll‐like receptor 4 as a potential mechanism to reduce cellular inflammation in metabolic syndrome

We investigated the effects of excess dietary cholesterol from eggs on peripheral blood mononuclear cell (PBMC) expression of inflammatory mediators and HDL‐associated lipid transporters in metabolic syndrome (MetS). Thirty‐seven men and women consumed either 3 eggs (EGG, additional 534 mg of dietary cholesterol) or the equivalent amount of a cholesterol‐free egg substitute (SUB, 0 additional mg of cholesterol) in combination with a carbohydrate‐restricted diet for 12 weeks. All participants reduced body weight an average of 4.0 ¡Ó 2.8% with no difference between groups. While PBMC mRNA expression of tumor necrosis factor ƒÑ (TNF‐ƒÑ), interleukin 6 (IL‐6), and interleukin 1ƒÒ (IL‐1ƒÒ) did not change, toll‐like receptor 4 (TLR4) increased in EGG only (+75.3% vs. −6.2% in SUB). Changes in TLR4 expression were positively correlated with nuclear factor £eB (NF‐£eB) p65 DNA binding activity. ATP‐binding cassette transporter A1 (ABCA1) expression increased in EGG only (+127.0% vs. +31.5% in SUB) while ABCG1 did not change. Interestingly, changes in ABCA1 were positively correlated with changes in IL‐6, IL‐1ƒÒ, and TLR4 in EGG only, as were changes in ABCG1 and IL‐6 and IL‐1ƒÒ. These findings suggest that the increase in PBMC ABCA1 expression from egg intake is potentially due to an effort to reduce cellular inflammation in MetS. Supported by the American Egg Board and USDA Grant No. 2012–67011‐19914Grant Funding Source: USDA Grant No. 2012–67011‐19914

Changes induced by diet and nutritional intake in the lipid profile of female professional volleyball players after 11 weeks of training

BackgroundThe relationship between cardiovascular disease and lipid profile is well known. Apart from a heart-healthy diet, exercise is the primary factor that can modify this lipid-associated cardiovascular risk. The aim of the study was to evaluate potential changes in the levels of triglycerides, total cholesterol (TC), low-density lipoprotein-cholesterol (LDLc), and high-density lipoprotein-cholesterol (HDLc), as well as atherogenic indices (TC/HDLc and LDLc/HDLc), and also to analyse the diet over 11 weeks of training in female professional volleyball players.MethodsThe lipid profile of 22 female professional volleyball players was analysed on Day T0 (pre-preseason) and Day T11 (after 11 weeks of training). The consumption of fats by the players was estimated using a food frequency questionnaire, confirmed by seven days of full dietary records.ResultsBy the end of the study, the LDLc levels and both atherogenic indices of the players had decreased (p < 0.05) compared to the values obtained at baseline. In addition, the diet of the players contained 35.5 ± 3.2% of fats (saturated fatty acid: 11.1 ± 1.2%, monounsaturated fatty acid: 14.3 ± 1.9%, and polyunsaturated fatty acid: 7.0 ± 1.1%) and 465 ± 57 mg of dietary cholesterol. Their score for the (monounsaturated + polyunsaturated fatty acid)/saturated fatty acid ratio was 1.9 ± 0.4, less than the recommended ≥ 2.ConclusionThese data indicate that the activity of the female professional volleyball players during the first 11 weeks of training in the season was heart healthy, because their lipid profile improved, despite an inadequate intake of fats.

Supplement of an egg‐containing formula in Thai elderly does not adversely affect blood lipid profiles

We developed (low carbohydrate, egg‐containing) formulas in a blended diet (BD) and determined their effects on blood lipoproteins and proteins after continuous six‐week feeding. 51 older participants (mean age 70.7±1.8 years), living at an elderly care center were randomly assigned into 3 groups: control (N=11), low‐carbohydrate‐low‐cholesterol‐formula group (LCL; n=25) and low‐carbohydrate‐high‐cholesterol‐formula group (LCH; n=15) Anthropometric and laboratory measurements were performed at wk‐1, wk‐3, wk‐6 with 8‐week‐run‐in period. Our data showed that 100 ml of BD in LCL arm provided 80.57 kcal (45%carb, 27%prot and 28%fat) with 17.01 mg of dietary cholesterol (dC), while the LCH arm provided 73.04 kcal (44%carb, 27%prot and 29% fat) with 50.87 mg of dC. When other items of daily dC were added, LCL received up to 223 mg/day while LCH received 373 mg/day, equivalent to 1–1.5 egg/day. There were no statistical differences in blood level of total cholesterol, triacylglycerol, LDL‐C, albumin and prealbumin (p &gt;0.05) after BD diet. There were no differences in lipid and protein levels between LCL and LCH formula. However, BD diet continuously increased HDL levels by 1.38 mg every 3 weeks (95% CI: 0.204, 2.561). We conclude that in Thai elderly, addition of egg‐containing, low‐carbohydrate blenderized supplement improves HDL cholesterol levels without affecting LDL levels.Supported by NRCT Grant No. 2550‐299No conflict of interest.Email: Drkorapat@hotmail.com

Plasma lipoprotein paticle size and carotenoid content are positively influenced by egg consumption and the response to dietary cholesterol in an elderly population

29 postmenopausal women (50–68y) and 13 men (60–80y) were assigned to either 3 eggs (EGG, 640 mg cholesterol /d) or an equal volume of cholesterol-free egg substitute (SUB, 0 mg cholesterol/d) for 30d. Following a 3 wk wash out, subjects crossed over to the alternate diet. Individuals with a response to dietary cholesterol > 2.2 mg/dL for each additional 100 mg of dietary cholesterol were classified as hyper-responders (HYPER) while hypo-responders (HYPO) were those with a response ≤ to 2.2 mg/dL. HYPER had higher concentrations of both LDL and HDL cholesterol (HDL-C) but maintained their LDL/HDL ratio after EGG. In contrast, the concentrations of plasma LDL-C and HDL-C did not differ between the EGG and SUB for the HYPO. NMR spectroscopy determined LDL and HDL size & particle concentrations. After EGG, HYPER experienced an increase in the larger (≥ 21.2 nm) less atherogenic LDL particle (P < 0.001) and in the largest HDL particle (> 8.8 nm) (P < 0.01), associated with reverse cholesterol transport. HPLC was used to analyze plasma carotenoids. All individuals had an increase in plasma lutein (from 32.4 ± 15.2 to 46.4 ± 23.3 ng/L) and zeaxanthin (from 8.8 ± 4.8 to 10.7 ± 5.8 ng/L) during EGG, yet HYPER displayed higher concentrations of carotenoids when compared to HYPO. These findings suggest that the increases in LDL-C and HDL-C due to increased egg consumption in HYPER are related to increases in the lipoprotein subfractions associated with less atherogenic particles. Also, increases in plasma caroteniods after EGG may provide a valuable dietary source for this population. [Supported by the American Egg Board/Egg Nutrition Center and USDA NRI]

Plasma LDL and HDL characteristics and carotenoid content are positively influenced by egg consumption in an elderly population1

BackgroundApproximately 1/3 of individuals have a high plasma response to dietary cholesterol (hyper-responders). Although increases in both LDL and HDL cholesterol have been observed, limited data exist regarding effects of egg consumption on lipoprotein subclasses and circulating carotenoids.Methods29 postmenopausal women (50–68 y) and 13 men (60–80 y) were assigned to either 3 eggs (EGG, 640 mg cholesterol/d) or an equal volume of cholesterol-free egg substitute (SUB, 0 mg cholesterol/d) for 30 d. Following a 3 wk wash out, subjects crossed over to the alternate diet. Individuals with a response to dietary cholesterol > 2.2 mg/dL for each additional 100 mg of dietary cholesterol were classified as hyper-responders while hypo-responders were those with a response ≤ to 2.2 mg/dL. Nuclear Magnetic Resonance (NMR) spectroscopy determined LDL and HDL size & particle concentrations. Dietary records were used to evaluate carotenoid consumption.ResultsHyper-responders had higher concentrations of both LDL (LDL-C) and HDL (HDL-C) cholesterol after EGG. In contrast, the concentrations of plasma LDL-C and HDL-C did not differ between the EGG and SUB for the hypo-responders. After EGG, hyper-responders had larger (≥ 21.2 nm) less atherogenic LDL particle (P < 0.001) and larger HDL particle (> 8.8 nm) (P < 0.01), with no significant difference in the total number of LDL or HDL particles. Regardless of response classification, all individuals had an increase in plasma lutein (from 32.4 ± 15.2 to 46.4 ± 23.3 ng/L) and zeaxanthin (from 8.8 ± 4.8 to 10.7 ± 5.8 ng/L) during EGG, yet hyper-responders displayed higher concentrations of carotenoids when compared to hypo-respondersConclusionThese findings suggest that the increases in LDL-C and HDL-C due to increased egg consumption in hyper-responders are not related to an increased number of LDL or HDL particles but, to an increase in the less atherogenic lipoprotein subfractions. Also, increases in plasma carotenoids after EGG may provide a valuable dietary source for this population.

Men Classified as Hypo- or Hyperresponders to Dietary Cholesterol Feeding Exhibit Differences in Lipoprotein Metabolism

The purpose of this study was to evaluate the differences that occur within the plasma compartment of normolipidemic men, classified on the basis of their response to prolonged consumption of additional dietary cholesterol. Using a crossover design, 40 men aged 18-57 y were randomly allocated to an egg (640 mg/d additional dietary cholesterol) or placebo group (0 mg/d additional dietary cholesterol), for two 30-d periods, which were separated by a 3-wk washout period. Subjects were classified as hypo- [increase in plasma total cholesterol (TC) of <0.05 mmol/L for each additional 100 mg of dietary cholesterol consumed] or hyperresponders (increase in TC of > or =0.06 mmol/L for each additional 100 mg of dietary cholesterol consumed) on the basis of their plasma reaction to the additional dietary cholesterol provided. Male hyporesponders did not experience an increase in LDL cholesterol (LDL-C) or HDL cholesterol (HDL-C) during the egg period, whereas both lipoproteins were significantly (P < 0.0001 and P < 0.05, respectively) elevated in hyperresponders. Although the LDL/HDL ratio was increased in male hyperresponders after the high cholesterol period, the mean increase experienced by this population was still within National Cholesterol Education Program guidelines. Furthermore, male hyperresponders had higher lecithin cholesterol acyltransferase (P < 0.05) and cholesteryl ester transfer protein (P < 0.05) activities during the egg period, which suggests an increase in reverse cholesterol transport. These data suggest that additional dietary cholesterol does not increase the risk of developing an atherogenic lipoprotein profile in healthy men, regardless of their response classification.

Pre-Menopausal Women, Classified as Hypo- or Hyper-Responders, do not Alter their LDL/HDL Ratio Following a High Dietary Cholesterol Challenge

Background: Cholesterol is the dietary component that has elicited the most public interest in conjunction with coronary heart disease. However, the impact of excess dietary cholesterol intake on plasma cholesterol levels cannot be accurately predicted; therefore, its role in disease progression is not straightforward. Individual response variation can be due to factors such as ethnicity, hormonal status, obesity and genetic predisposition.Objective: The purpose of this study was to evaluate the differences that occur within the plasma compartment of normolipidemic pre-menopausal women, classified based on their response to a high dietary cholesterol challenge.Design: We recruited 51 pre-menopausal women (29 Caucasian and 22 of Hispanic origin) aged 18 to 49 years with initial plasma cholesterol concentrations ranging from 3.62 to 5.17 mmol/L. Using a cross-over research design, women were randomly allocated to an egg (640 mg additional dietary cholesterol per day) or placebo group (0 mg additional dietary cholesterol per day) initially, and the two 30 day periods were separated by a three-week washout.Results: An initial evaluation of the ethnicity effects revealed elevations in both plasma LDL-C (p < 0.0001) and HDL-C (p < 0.001) concentrations in both Hispanics and Caucasians during the high dietary cholesterol period. However, these increases were not accompanied by a change in the LDL/HDL ratio. Subjects were then classified as hypo- (< 0.05 mmol/L increase in total plasma cholesterol per each additional 100 mg of dietary cholesterol consumed per day) or hyper-responders (≥0.06 mmol/L increase in total blood cholesterol per each additional 100 mg of dietary cholesterol consumed per day), based on their reaction to the additional dietary cholesterol provided. Hypo-responders did not experience an increase in LDL-C or HDL-C during the egg period, while both lipoproteins were elevated in hyper-responders. However, the LDL/HDL ratio, an important parameter of coronary heart disease risk, was maintained for all subjects during the egg period independent of response. Furthermore, hyper-responders had higher concentrations of apo C-III (p < 0.001), apo B (p < 0.001) and cholesterol ester transfer protein (CETP) (p < 0.05) during this period.Conclusion: These data revealed that excess dietary cholesterol does not increase the risk of developing an atherogenic lipoprotein profile in pre-menopausal women, regardless of their response classification. Although the addition of 640 mg of cholesterol to the diet did result in an increase in plasma cholesterol in hyper-responders, the LDL/HDL ratio was maintained. This result, accompanied by increases in CETP activity, leads to the speculation that hyper-responders may process the excess cholesterol in the plasma compartment through an enhancement of the reverse cholesterol transport pathway. With this mechanism identified, further measurement of additional parameters is needed to verify this conclusion.

Genetic basis of sitosterolemia.

The molecular mechanisms regulating the amount of dietary cholesterol retained by the body, as well as the body's ability to exclude other dietary sterols selectively, are poorly understood. An average Western diet will contain approximately 250-500 mg of dietary cholesterol and approximately 200-400 mg of non-cholesterol sterols, of which plant sterols are the major constituents. Approximately 50-60% of dietary cholesterol is absorbed and retained by the normal human body, but less than 1% of the non-cholesterol sterols are retained. There thus exists a subtle mechanism that allows the body to distinguish between cholesterol and non-cholesterol sterols. In sitosterolemia, a rare autosomal recessive disorder, affected individuals hyperabsorb and retain not only cholesterol but also all other sterols, including plant and shellfish sterols from the intestine. Consequently, patients with this disease have very high levels of plant sterols in the plasma, and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. The STSL locus has been mapped to human chromosome 2p21. Mutations in two tandem ABC genes, ABCG5 and ABCG8, encoding sterolin-1 and -2, respectively, are now known to be mutant in sitosterolemia. The identification of these genes should now lead to a better understanding of the molecular mechanism(s) governing the highly selective absorption and retention of cholesterol by the body. Indeed, it is the very existence of this disease that has given credence to the hypothesis that there is a molecular pathway that regulates dietary cholesterol absorption and sterol excretion by the body.

Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption.

The molecular mechanisms regulating the amount of dietary cholesterol retained in the body, as well as the body's ability to exclude selectively other dietary sterols, are poorly understood. An average western diet will contain about 250-500 mg of dietary cholesterol and about 200-400 mg of non-cholesterol sterols. About 50-60% of the dietary cholesterol is absorbed and retained by the normal human body, but less than 1% of the non-cholesterol sterols are retained. Thus, there exists a subtle mechanism that allows the body to distinguish between cholesterol and non-cholesterol sterols. In sitosterolemia, a rare autosomal recessive disorder, affected individuals hyperabsorb not only cholesterol but also all other sterols, including plant and shellfish sterols from the intestine. The major plant sterol species is sitosterol; hence the name of the disorder. Consequently, patients with this disease have very high levels of plant sterols in the plasma and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. We previously mapped the STSL locus to human chromosome 2p21 and further localized it to a region of less than 2 cM bounded by markers D2S2294 and D2S2291 (M.-H.L. et al., manuscript submitted). We now report that a new member of the ABC transporter family, ABCG5, is mutant in nine unrelated sitosterolemia patients.