9Percentage of increments (%) Percentage of increment in BMD and BMC between groups after 1 year of 500 mg Ca supplementation in malesP = .030P = .031P = .007P = .045Percentage of increments (%)Charoenkiatkul, et al. 2542
10Percentage of increments (%) Percentage of increment in BMD and BMC between groups after 1 year of 500 mg Ca supplementation in femalesP = .038P = .033Percentage of increments (%)Charoenkiatkul, et al. 2542
11BMD AND QUARTILES OF CALCIUM INTAKE IN LATE POSTMENOPAUSAL WOMEN .821.1P < 0.05P < 0.05.801.0.78SPBMD (g/cm 2).76FNBMD (g/cm 2).188.8.131.52.70Q1( )Q2( )Q3( )Q4( )Q1( )Q2( )Q3( )Q4( )Quartiles of calcium intake (mg/d)
20Calcium, dairy products, and bone health in children and young adults: a reevaluation of the evidence Lanou AJ et al. Pediatrics 2005 Mar; 115:792-4.Aim: review literature effects of dairy products and total dietary calcium on bone integrity in children and young adults (1-25 yrs)58 studies: 22 cross-sectional, 13 retrospective,10 longitudinal and 13 RCT11: not control for wt, pubertal status, exercise,10 RCT + calcium supplement: 9/10 positive results37 dairy products without calcium supplement27: no relationship between dairy and bone health9 : effects on bone health are “small”1 : no reportConclusion: In clinical, longitudinal, retrospective, and cross-sectional studies, neither increased consumption of dairy products, specifically, nor total dietary calcium consumption has shown even a modestly consistent benefit for child or young adult bone health.
21A Meta-analysis of milk intake and fracture risk Osteoporosis International, 2005 Jul;16(7):799-804 39,563 men and women6 prospective studies (EVOS/EPOS, CaMos, DOES, Rotterdam, Sheffield, Gothernberg)
22Osteoporotic fracture CohortNMean age (years)Age range (years)% FemaleLow calcium intake (%)Any fractureOsteoporotic fractureHip#EVOS/EPOS13,44563.841–91526072045CaMos940162.125–103693758631642DOES206570.457–956140516405104Rotterdam540867.755–94593636473130Sheffield217380.074–961001629224363Gothenburg II707158.921–891444131229Total39,56364.321–1033531912469413A low intake of calcium (less than 1 glass of milk daily) was not associated with a significantly increased risk of any fracture, osteoporotic fracture or hip fracture.
26Dietary Cholesterol and Serum Cholesterol Relationship STUDYPLASMA CHOLESTEROL [mg/dl per 100 mg/day]Ginsberg et al. 19941.5Schnohr et al. 19942.4McComb et al. 19942.3; 0.7Vuoristo & Miettinen 19943.4Kern 19940.7; 0.0Lichtenstein et al. 19943.9; 3.8Jones et al. 19944.1Ginsberg et al. 19952.8Ferrier et al. 19951.9Knopp et al. 19961.6, 3.2AVERAGE2.3(n=142)2.5Bosner MS, Lange LG, Stenson WF, Ostlund RE Jr. Lipid Res 1999, 40: 302-8Cholesterol Absorption Efficiencytwo interesting characteristics of the cholesterol absorption process.One is its variability from one individual to another.Most of us are very efficient in absorbing fat from the diet, but when it comes tocholesterol, there is a marked individual variation in the efficiency of this process. Thishas been demonstrated by a number of detailed studies over the years. One of them iscited here in this diagram. These data are based on a study done at WashingtonUniversity in St. Louis about 4 years ago and they show that the absorption efficiency ofcholesterol in people varies anywhere from about 20% all the way up to almost 90%. Soon the left-hand side of the diagram we see these “low absorbers” of cholesterol, on theright hand side we have what we term “hyper absorbers.” In the middle though, we seethe bulk of the people fall in the range of 40-60% and we routinely work with a figure ofabout 50% for the absorption efficiency of cholesterol. It’s important that we try tounderstand why individuals vary so much in their absorption efficiency of cholesterolbecause if we can resolve this then we will probably learn why certain cholesterollowering drugs do not work very well, or even work at all, in some patients.Dietary Cholesterol and Plasma Cholesterol: Recent StudiesClinical studies of the effects of dietary cholesterol on plasma cholesterol levels are complicated by many factors, not the least of which is the wide range of dietary cholesterol levels fed to study subjects. Other factors include the type and amount of dietary fat and whether the studies use a controlled feeding environment or are carried out in free-living subjects. The following outline summarizes the methodology and results of dietary cholesterol - plasma cholesterol studies published between 1994 and In order to more accurately compare the various cholesterol feeding studies carried out over the past two years, the plasma cholesterol changes (mg/dl) have been normalized per 100 mg per day change in dietary cholesterol to give a dose adjusted value as mg/dl per 100 mg/day.1994Ginsberg et al A dose-response study of the effects of dietary cholesterol on fasting and postprandial lipid and lipoprotein metabolism in healthy young men. Arterioscler. Thrombosis 14:For these controlled feeding studies twenty-four young men were fed 30% fat diets (NCEP Step I) with addition of zero (128 mg cholesterol/day), one (283 mg/day), two (468 mg/day) or four (858 mg/day) eggs per day to the basal diet. Each diet was fed for eight weeks. Average plasma cholesterol levels in the twenty-four subjects were 155, 161, 162, and 166 mg/dl for the zero, one, two and four eggs per day feeding periods. Plasma total cholesterol increased 1.5 mg/dl per 100 mg/day added dietary cholesterol. There was no evidence that changes in dietary cholesterol intakes altered the postprandial plasma lipoprotein profile (lipoproteins thought to be involved in the development of atherosclerosis) and thus did not alter the atherogenic potential of the plasma lipoproteins. The data indicate that in the majority of healthy young men addition of two eggs per day to a low-fat diet has little effect on plasma cholesterol levels.Schnohr et al Egg consumption and high-density-lipoprotein cholesterol. J. Intern. Med. 235:To determine the effects of egg consumption on plasma HDL cholesterol levels, twenty-four adults added two eggs per day to their usual diets for six weeks. Total cholesterol levels were increased by 4% while HDL cholesterol levels increased 10%. The dose adjusted response to the change in dietary cholesterol was 2.4 mg/dl per 100 mg/day. The authors concluded that "a moderate egg intake should not be rigorously restricted in healthy individuals."McComb et al Attenuated hypercholesterolemic response to a high-cholesterol diet in subjects heterozygous for the apolipoprotein A-IV-2 allele.N. Engl. J. Med. 331:Genetic factors contribute to the variability of the plasma lipid responses to dietary cholesterol and in this study it was shown that subjects with the apolipoprotein A-IV-2 allele have an attenuated response to a dietary cholesterol challenge. Subjects were fed a low-cholesterol diet and one with 1100 mg/day added cholesterol. The change in plasma cholesterol in subjects without the apo A-IV-2 allele (n=12) was 22 mg/dl (dose adjusted: 2.3 mg/dl per 100 mg/day) while for those with the apo A-IV-2 allele (n=11) the change was 6 mg/dl (dose adjusted: 0.7 mg/dl per 100 mg/day). It is estimated that one in every seven individuals in the United States has the apo A-IV-2 allele and, based on the data from this study, has a genetic resistance to the plasma cholesterol raising effects of very high intakes of dietary cholesterol. These findings are a breakthrough in beginning to understand the role of genetic factors in the variability of plasma lipid responses to dietary cholesterol.Vuoristo & Miettinen Absorption, metabolism, and serum concentrations of cholesterol in vegetarians: effects of cholesterol feeding. Am. J. Clin. Nutr. 59:Dietary cholesterol feeding studies were carried out in five vegetarians to determine if there were any differences in responses as compared to non-vegetarians. Addition of three egg yolks per day (690 mg cholesterol) to the diet for two months increased the average plasma cholesterol level by 23 mg/dl (dose adjusted: 3.4 mg/dl per 100 mg/day). Surprisingly, HDL cholesterol levels were increased by 10 mg/dl with addition of egg yolks to the diet and the LDL:HDL ratio was unaffected by cholesterol feeding. The authors concluded that the metabolic responses to dietary cholesterol are similar for vegetarians and non-vegetarian subjects.Kern Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones. J. Clin. Invest. 93:Sixteen women, eight controls and eight with cholesterol gallstones, were fed moderate- and high-cholesterol (5 eggs/day = 939 mg/day cholesterol) diets for days and various parameters of cholesterol metabolism were measured. In control subjects the plasma cholesterol level increased by 6 mg/dl with cholesterol feeding (0.7 mg/dl per 100 mg/day) while in the gallstone subjects the plasma total cholesterol level was decreased by 8 mg/dl with intake of the high cholesterol diet. The study also found that in both groups cholesterol absorption and cholesterol synthesis were decreased on the high cholesterol diet. In both groups of patients, the body's response to a large increase in dietary cholesterol was sufficient to compensate for the increase resulting in little or no increase in plasma cholesterol levels.Lichtenstein et al Hypercholesterolemic effect of dietary cholesterol in diets enriched in polyunsaturated and saturated fat. Dietary cholesterol, fat saturation, and plasma lipids. Arterioscler. Thromb. 14:Studies in fourteen men (n=8) and women (n=6) fed either corn oil (polyunsaturated fat) or beef tallow (saturated fat) with or without addition of mg cholesterol per 1000 kcal, documented little effect of dietary fat saturation on the plasma cholesterol response to dietary cholesterol. In the corn oil fed group the addition of cholesterol increased plasma cholesterol 11 mg/dl (dose adjusted: 3.9 mg/dl per 100 mg/day) and in the beef tallow group the increase was the same, 11 mg/dl (dose adjusted: 3.8 mg/dl per 100 mg/day). The findings are consistent with other studies which indicate that with a 30% fat diet, the plasma cholesterol response to dietary cholesterol is independent of the fatty acid composition of the diet. The study also provides evidence which suggests that resistance to the effects of dietary cholesterol occurs in older men and women and is not limited to only young, healthy volunteers.Jones et al Interaction of dietary fat saturation and cholesterol level on cholesterol synthesis measured using deuterium incorporation. J. Lipid Res. 35:These investigators tested the effects of dietary fat and cholesterol on the regulation of cholesterol synthesis in older men (n=6) and women (n=8). The study subjects were fed diets high in either polyunsaturated fat, corn oil, or saturated fat, beef tallow, with and without addition of 120 mg cholesterol per 1000 kcal. Dietary cholesterol increased plasma cholesterol levels by 12 mg/dl (dose adjusted response = 4.1 mg/dl per 100 mg/day change in dietary cholesterol) and there was no difference between the dietary polyunsaturated and saturated fat groups. The results from this study provide evidence that one effect of an increase in dietary cholesterol is a decease in cholesterol synthesis by the body to compensate for the change. The precision of this mechanisms helps maintain plasma cholesterol levels constant.1995Ginsberg et al Increases in dietary cholesterol are associated with modest increases in both LDL and HDL cholesterol in healthy young women. Arterioscler. Thromb. Vasc. Biol. 15:A controlled dietary cholesterol feeding study in thirteen young women tested the effects of feeding zero, one, or three eggs per day on plasma lipids and lipoproteins. The data indicated that the dose adjusted plasma cholesterol response was 2.8 mg/dl per 100 mg/day dietary cholesterol (a value higher than that obtained in males in the 1994 study). In women, however, the increase in total plasma cholesterol with dietary cholesterol occurred in both the atherogenic LDL cholesterol (2.1 mg/dl per 100 mg/day) and the anti-atherogenic HDL cholesterol (0.6 mg/dl per 100 mg/day). As found in the previous study in healthy young men, young women have the ability to compensate for an increased intake of cholesterol by adjusting the way cholesterol is handled by the body. The data show that addition of two eggs per day to the diet of healthy young women has little effect on plasma cholesterol levels in the majority of study subjects.Ferrier et al Alpha-linolenic acid- and docosahexanaenoic acid-enriched eggs from hens fed flaxseed: influence on blood lipids and platelet phospholipid fatty acids in humans. Am. J. Clin. Nutr. 62:81-86.This study compared the effects of feeding four regular or omega-3 fatty acid enriched eggs per day for two weeks on plasma lipids in twenty-eight males. Eggs were obtained from hens fed either zero, ten or twenty percent flax seed diets. Addition of four eggs per day (720 mg of cholesterol) to the diet increased plasma total cholesterol levels an average of 13 mg/dl and there were no differences between the sources of eggs tested. The dose adjusted change in plasma cholesterol levels was 1.9 mg/dl per 100 mg/day change in dietary cholesterol. HDL cholesterol levels were increased 2 mg/dl with the addition of eggs. It would appear from this study that the fatty acid composition of the egg has no relationship to the effects of dietary cholesterol on plasma cholesterol levels.1996Knopp et al A double-blind, randomized trial of the effects of two eggs per day in moderately hypercholesterolemic and combined hyperlipidemic subjects consuming the NCEP Step I diet. (Reported in abstract at the November 1995 American Heart Association meeting in Anaheim, CA)Studies in middle-aged men and women with either moderate hypercholesterolemia (n=44) or combined hyperlipidemia (elevated plasma cholesterol and triglyceride, n=31) were fed either no eggs or two eggs per day as part of a NCEP Step I diet. Subjects with moderate hypercholesterolemia were found to have a dose adjusted plasma cholesterol response to added dietary cholesterol of 1.6 mg/dl per 100 mg/day whereas combined hyperlipidemic individuals are more sensitive to dietary cholesterol and have an average dose response factor of 3.2 mg/dl per 100 mg/day change in dietary cholesterol. The authors concluded that middle aged men and women with elevated plasma cholesterol levels were not more sensitive to dietary cholesterol compared to subjects with normal cholesterol levels. In contrast, middle aged patients with combined hyperlipidemia appear to be more sensitive to dietary cholesterol and in their case dietary cholesterol restrictions appear more appropriate.DATA SUMMARY:STUDYPLASMA CHOLESTEROL [mg/dl per 100 mg/day]Ginsberg et al Schnohr et al McComb et al ; 0.7Vuoristo & Miettinen Kern ; 0.0Lichtenstein et al ; 3.8Jones et al Ginsberg et al Ferrier et al Knopp et al , 3.2AVERAGE (n=142)2.5SUMMARYThe dietary cholesterol feeding studies carried out during the past two years add to a growing body of evidence demonstrating that the majority of study subjects have relatively small plasma cholesterol changes in response to changes in dietary cholesterol intake. These findings are consistent with data from over thirty years of clinical investigations on this question and indicate that the average response to a 100 mg/day change in dietary cholesterol intake is a 2.5 mg/dl change in plasma cholesterol levels. While some individuals are more sensitive to the effects of dietary cholesterol (15-20% of the population), the dose adjusted response factor in this group is still relatively small (3.2 vs 1.6 for sensitive vs resistant study subjects). For example, it can be estimated that reducing dietary cholesterol intake from 400 mg/day to 300 mg/day results in a plasma cholesterol reduction of 3.2 mg/dl in cholesterol sensitive individuals and as little as 1.6 mg/dl in cholesterol insensitive individuals. What becomes essential for effective dietary interventions to lower an elevated plasma cholesterol level is an understanding of the extensive variability of individual responses to dietary changes and the need to determine the most effective dietary intervention for the high risk patient.
27Dietary cholesterol Independent effect on TC, increased risk of CVD Men: + TC 1.47 mg/dl every 100mg chol added,// +LDL Arterioscler Thromb 14(4):Women: + TC 2.81, +LDL 2.08 mg/dl every 100mg chol added, Arterioscler Thromb Vasc Biol 15(2):Egg consumption 1 egg/d not increased risk of cardiovascular disease in healthy>1 egg/d increased risk in diabetic men(2.02), women (1.49)
29Egg consumption, serum cholesterol, and cause-specific and allcause mortality: the National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged, 1980 (NIPPON DATA80)Egg consumption>2/d1/d1/2/d1-2/wkSeldomP-valueWomenTotal cholesterol5.114.984.894.834.84<0.0001All cause death14.887.514.5IHD death184.108.40.2060.008Men4.764.784.790.9811.912.910.213.30.160.70.23
30Dose response of cholesterol and egg consumed Egg consumption, serum cholesterol, and cause-specific and allcause mortality: the National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged, 1980 (NIPPON DATA80)WomenDose response of cholesterol and egg consumedAge adjusted RR of consume egg> 1-2/wk compare with 1/dtendencies for lower mortality due to stroke, IHD, and cancerAm J Clin Nutr 2004;80:58–63.
31Digestibility of Cooked and Raw Egg Protein in Humans as Assessd by Stable Isotope N, recover over 24 hrIngested N.EndogenousexogenousTrue ileal digestibility %Cooked4000RawEvenepoel P, et al. J Nutr 1998; 128: