Nutrition Close-Up 14(1), 1997


Volume 14 – Number 2 Summer 1997


BMI: body mass index (kg/m2)
CHD: coronary heart disease
CVD: cardiovascular disease
HDL: high density lipoprotein
LDL: low density lipoprotein
Lp(a): lipoprotein (a)
MI: myocardial infarction
MUFA: monounsaturated fatty acids
NCEP: National Cholesterol Education Program
P:S: dietary polyunsaturated:saturated fat ratio
PUFA: polyunsaturated fatty acids
SFA: saturated fatty acids
TAG: triacylglycerol
VLDL: very low density lipoprotein

Dietary Lipids and Plasma Lipids: Effects of Fat and Cholesterol

The quantitative importance of changes in dietary fat type and amount, and dietary cholesterol, in the treatment of hypercholesterolemia has been a topic of considerable debate over the years. Questions such as whether it is the type or amount of fat in the diet which has the major impact, whether changes in HDL cholesterol should be a concern, whether dietary cholesterol is a significant factor in elevated plasma cholesterol levels, have all been areas of debate in the diet-hyperlipidemia-heart disease discussions. Should the diet be very low in saturated fat but with moderate amounts of total fat? Just how important is it that the diet be low in cholesterol or is this not even an issue? Are there potential problems with very low-fat diets which are not high in grains, fruits and vegetables? These are all questions which need to be answered to have a scientifically sound and research based set of dietary recommendations for the public.

The statistical procedure of meta-analysis provides a valuable tool for the analysis of multiple studies in development of conclusions based on the preponderance of scientific evidence. In the last issue of Nutrition Close-Up (14(1):1, 1997) we reviewed the results of a meta-analysis by Clarke et al. metabolic ward studies investigating the effects of dietary lipids on plasma lipids and lipoproteins. Howell et al. have also now published a meta-analysis on this same question using data from both metabolic ward studies and studies in free-living populations. This analysis included 224 studies in 8,143 subjects. Regression models were developed for estimating effects of dietary fat type and amount, and dietary cholesterol, on plasma total, VLDL, LDL and HDL cholesterol and TAG concentrations. The authors also analyzed the data to determine what interactive effects existed between subject characteristics and dietary variables and the responses to changes in dietary lipids.

The predictive equations developed from this meta-analysis were:
Total cholesterol (mg/dl) = 1.92 SFA – 0.90 PUFA + 0.022 C
LDL cholesterol (mg/dl) = 1.81 SFA – 0.50 PUFA
HDL cholesterol (mg/dl) = 0.29 SFA + 0.19 Fat
Triglyceride (mg/dl) = 0.014 C – 1.07 PUFA -0.92 Fat
[Changes in lipid and lipoprotein concentrations for changes in percent of calories from total Fat, SFA and PUFA, and changes in dietary cholesterol, C (mg/day).]

The authors found no evidence for meaningful dietary interactions between lipids in determining plasma cholesterol and lipoprotein responses. Overall, subject characteristics and study design differences were not major contributors to variations in the plasma lipid responses to dietary interventions.

Based on these predictive models, Howell et al. calculated the average plasma lipid and lipoprotein changes which would be expected upon changing from a diet with 37% of calories as fat (13% SFA, 17% MUFA, 7% PUFA) and 385 mg/day cholesterol to the NCEP Step I diet with 30% of calories as fat (SFA, MUFA and PUFA @10%) and 300 mg/day of cholesterol. This dietary intervention would be predicted to lower plasma total cholesterol levels by an average of 10.4 mg/dl (5.8 mg/dl from the decrease in SFA, 2.7 mg/dl from the increase in PUFA, and 1.9 mg/dl from the decrease in dietary cholesterol). LDL cholesterol levels would decrease by almost 7 mg/dl while HDL cholesterol concentrations would fall by 2 mg/dl. For a hypercholesterolemic individual with LDL cholesterol of 175 mg/dl and HDL cholesterol of 50 mg/dl, the dietary change would lower the LDL to 168 mg/dl and the HDL to 48 mg/dl; the LDL:HDL ratio would not change.

The authors note that there is a large degree of individual variability in response to dietary interventions and that multiple factors can play a role: genetic influences, type of hyperlipidemia, adiposity and its distribution, physical activity, and interactions with non-lipid components of the diet. What the data do provide is an estimate of the population wide response to implementation of the Step I diet and the responses to specific components of the dietary changes. Both Howell et al. and Clarke et al. found that SFA was the major dietary determinant of the plasma cholesterol response to diet, followed by PUFA content, and finally dietary cholesterol which has a small, but statistically significant effect. It is interesting to note that when the authors calculated the effects of a Step II diet with less than 7% of calories from SFA and 200 mg/day of cholesterol, the reduction in total cholesterol beyond the Step I diet was 8 mg/dl, with 2.2 mg/dl from the 100 mg/day reduction in dietary cholesterol and 5.8 mg/dl from the decrease in SFA.

In the report by Howell et al. the authors compare their results to other predictive models, including those by Keys and Hegsted published in the 1960s. Interestingly, the response factors calculated thirty years ago are not all that different from what these authors found in 1997. Some of the differences could be ascribed to the use of solid food diets in the later studies which would provide more stearic acid which, even though technically a saturated fat, has a neutral effect on plasma cholesterol levels. This would result in a lowering of the SFA response factor. Another difference is that many of the later studies used more physiological levels of dietary cholesterol which could account for the decrease in the dietary cholesterol response factor over the years. The available data does address one question which has been a topic of debate for many years, i.e. metabolic ward versus free-living population studies. In this report these data sets are compared and the findings indicate that the differences are relatively minor. It is also interesting that Howell and colleagues used both metabolic ward and free-living studies while Clarke and coworkers choose only metabolic ward studies. The end results are virtually identical.

The authors of this meta-analysis concluded that “Predictive equations developed from this meta-analysis indicated that compliance with current dietary recommendations (30% of energy from fat, < 10% from saturated fat, and < 300 mg cholesterol/d) will, on average, reduce plasma total and LDL cholesterol concentrations by 5% compared with amounts associated with the average American diet.” Applications of these predictive equations in the design of dietary interventions studies should provide valuable information regarding expected responses and the potential to detect biologically significant changes in plasma lipids and lipoproteins, and in CVD incidence.
[Howell, W.H. , McNamara, D.J., Tosca, M.A. et al. Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis. Am J Clin Nutr 1997;65:1747-1764. ]

Key Messages

  • A 50 mg/day reduction in dietary cholesterol lowers plasma cholesterol by 1 mg/dl.
  • A 1% change from SFA calories to PUFA calories lowers plasma cholesterol by 3 mg/dl.
  • Fat saturation, not cholesterol, is the primary dietary determinant of plasma cholesterol levels.
  • Compliance with the Step I diet will lower the average plasma cholesterol in the population by 5%.

“Meta-analysis begins with scientific studies, usually performed by academics or government agencies, and sometimes incomplete or disputed. The data from the studies are then run through computer models of bewildering complexity, whcih produce results of implausible precision.” B. Davis, Wall Street Journal, 6 August 1992.

Editor’s Comment
This analysis of dietary effects on plasma lipids provides valuable data on the predicted changes in plasma total and lipoprotein cholesterol levels which can be achieved from a population-wide change in dietary lipid intakes. It is also possible to use these data to predict diet-mediated changes in CHD mortality rates based on epidemiological data. Based on data from the Seven Countries Study (see Nutrition Close-Up 12(3): 2, 1995), a 20 mg/dl change in the plasma cholesterol level is associated with a 17% change in CHD risk. Using these data it can be predicted that an 11 mg/dl fall in total cholesterol levels would lower CHD risk by 9%. What is discouraging is that overall, the effects of dietary fat and cholesterol interventions on plasma cholesterol levels are quantitatively relatively small, and seem to have only a small effect on CHD relative risk in the U.S. population, a population with a high CHD absolute risk as compared to other industrialized countries. There appears to be more to CHD risk reduction than simply cutting out the fat and cholesterol in the diet

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Effectiveness of a Prepared Meal Plan vs. Self-Selected Diet in Managing Cardiovascular Risk Factors

The Campbell’s Center for Nutrition and Wellness (CCNW) Dietary Intervention study investigated the effectiveness of prepackaged meals verus self-selected diet in subjects with chronic illnesses. In this randomized multi-center clinical trial, 560 participants (314 women and 246 men) were followed for 14 weeks. During the first 4 weeks, baseline data on participants weight, blood pressure, two 3-day food records, and 2 sets of quality-of-life questionnaires were collected weekly. Blood samples were collected and analyzed for lipid, lipoprotein, insulin, hemoglobin A1c. Subjects consumed their regular diet during this period. Starting at week five, 314 subjects received prepackaged meals and 214 began consuming self-selected (SS) diets based on nutrition recommendations of NCEP. All subjects received nutrition counseling at week 5 and week 7.

Composition of both diets consisted of 17% calories from fat, 63% calories from carbohydrate, and 21% calories from protein. However, only the CCNW group received 100% RDA for vitamins and minerals since their meals were fortified. Also, CCNW meals were formulated to meet the daily nutrition guidelines for intake of sodium, total cholesterol, saturated fat, sugar, fiber, and complex carbohydrate. Subject caloric needs were calculated using the Harris Benedict formula with adjustments made for desired weight loss or weight maintenance. And based on their caloric need, subjects were instructed to eat appropriate numbers of CCNW meals per day or servings from the ADA and American Diabetes Association exchange list. The actual study period lasted a total of 10 weeks.

Based on analysis of food records, researchers reported that subjects from both groups decreased their caloric intake (CCNW men, 1541 ± 2401 kJ, SS men 2263 ± 2864 kJ, CCNW women 1373 ± 1949 kJ, SS women 1625 ± 1814 kJ) and percent of energy intake from fat (CCNW men 17 ± 7%, women 14 ± 7%, SS men 10 ± 8%, women 10 ± 7%). The percentage of energy intake from carbohydrate and protein increased. In spite of the greater caloric decrease by self-selected group, subjects on CCNW program lost significantly more weight (men 3.5 ± 3.3 kg, women 4.8 ± 3.0 kg). This weight loss in the CCNW group could partially explain the greater drop in blood pressure for the CCNW group.

Researchers also observed a significant decline in subjects plasma cholesterol, HDL, LDL, VLDL, TAG, and LDL:HDL ratio with both diets. However, when CCNW and self-selected diets were compared, CCNW resulted in greater decline in plasma cholesterol levels while TAG level decreased more on self selected diet. The plasma glucose and hemoglobin A1c levels decreased on both diets but the difference between the two diets was not significant. For example, plasma glucose level decreased by 11.7 ± 34.0 mg/dl on CCNW, while glucose levels on self-selected diet decreased by 13.5 ± 36.6 mg/dl. Hemoglobin A1c level decreased by 0.4 ± 0.8% and 0.3 ± 0.7% on CCNW and self-selected diet, respectively.

Compliance was better on the CCNW diet (86%) than self-selected diet (73%), however, all subjects reported improvement in “mental health, general perceived health, daily activities, and work performance, nutrition hassels, nutritional health perceptions, nutritional effect, social function, and sexual function.”

Therefore, in conclusion, researchers speculated that it is possible for free-living individual to follow a complete diet that meets both macronutrients and micronutrients recommendations from the major US health organization with improved cardiovasular risk factors.

[McCarron, D.A., Oparil, S., Chait, a., et al. Nutritional management of cardiovascular risk factors. A randomized clinical trial. Arch Intern Med. 1997;157:169-177. ]

Editor’s Comment
This study uses a nutritionally complete diet which meets standards of low-fat (18% of calories, 6% SFA) and low-cholesterol (<150 mg/day) rarely tested in free-living populations. The authors note that the meals meet the recommendations of national health organizations yet I have not seen recommendations for less than 20% of calories as fat. That aside, let ask about the effectiveness of this very-low-fat diet in lowering plasma lipids. The 18% fat diet resulted in an average 12 mg/dl fall in total cholesterol whereas the self-selected diet group with 25% of calories as fat (8% SFA) had a 11 mg/dl fall. It should also be noted that in both groups there were average weight losses over the 10 week period of 4.6 kg in the CCNW group and 3.1 kg in the self-selected group. The differential effects of the diet and the weight loss on plasma cholesterol levels cannot be estimated from the data in the paper but one can apply the equations from the meta-analysis presented in this issue of Nutrition Close-Up to estimate the diet effect. The predicted decrease in total cholesterol for the CCNW diet group is 12 mg/dl and in the self-selected group 7 mg/dl. It is rather disappointing that a decrease of 400 kcal per day, a weight loss of 0.3-0.4 kg/wk, and intake of less than 25% of calories as fat, SFA < 8% of calories and < 150 mg/day of cholesterol that one only gets a plasma cholesterol lowering of 10-12 mg/dl.

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Genetic Determinant of the LDL Cholesterol Response to Dietary Cholesterol

Many studies have shown that an individual genetic make-up plays an integral role in regulating both the baseline plasma cholesterol level and the plasma lipid response to changes in dietary lipids. Previous studies have shown that a sub-set of the population is more sensitive to dietary cholesterol than the general population. However, the mechanisms and genetic characteristics associated with this phenomenon are not yet defined. Gylling et al. measured the effects of increased cholesterol intake in 29, fifty year old men with different polymorphisms for genes involved in the regulation of lipid metabolism.

For the first 6 weeks of the study, subjects consumed a low-fat, low-cholesterol diet compatible with the NCEP Step 2 diet. According to the dietary records, subjects consumed 53 gm of fat and 208 mg of cholesterol per day. During the second 6 weeks of the study, volunteers consumed a low-fat, high-cholesterol diet. Three egg yolks were added to the first diet to increase the cholesterol content by 670 mg/day and total fat grams to 69 gm per day. During the fourth week of each dietary intervention, researcher measured plasma lipid and lipoprotein levels along with measures of cholesterol absorption and metabolism. The apo E phenotypes of subjects were determined and DNA tested for apolipoprotein restriction fragment length polymorphisms (RFLP).

All groups, except for apo E2, had similar concentrations of plasma total and LDL cholesterol on the low-fat, low-cholesterol diet. Apo E2 subjects had lower levels of plasma total and LDL cholesterol than E3 and E4 patients. When dietary cholesterol intake was increased, the majority of study participants exhibited an increase in plasma LDL levels. However, LDL levels in subjects with the apo B R+ (Eco R1 RFLP) allele exhibited the greatest increase while apo E2 subjects had the smallest increase.

During intake of the high cholesterol diet, LDL cholesterol levels were related to cholesterol absorption and inversely with cholesterol and bile acid synthesis rates. With the high cholesterol diet the fractional catabolic rate (FCR) for LDL apo B decreased and bile synthesis increased in all genetic subgroups while LDL apo B transport rates (TR) and cholesterol synthesis rates were unaffected.

During the two dietary studies, LDL cholesterol concentration was significantly correlated with apo E phenotype and TR for LDL apo B and inversely with FCR for LDL apo B but not with apo B Xba I or EcoRI or LDL receptor gene PvuII RFLPs. During high cholesterol intake, LDL cholesterol concentration was correlated with cholesterol absorption efficiency and inversely with bile acid and cholesterol synthesis. During the latter diet, apo E polymorphism was correlated with FCR for LDL apo B, and apo B EcoRI genotypes with cholesterol absorption efficiency.

This study is one of the first to assess the associations of common RFLP of lipid-regulatory genes with cholesterol and LDL metabolism during changes in dietary cholesterol. Individuals possessing the E2 allele were nonresponders to increased cholesterol intake irrespective of genetic polymorphism. The presence of the R-allele combined with apo E4 was associated with the greatest elevation of plasma LDL levels.

Plasma Cholesterol Response (mg/dl per 100 mg/day cholestetrol)

Apo E Phenotype Apo B EcoRI RFLP
R+ R-
Apo E2 0.7 (n=8)
Apo E3 1.8 (n=5) 2.3 (n=4)
Apo E4 1.6 (n=8) 5.8 (n=4)

[Gylling, H., Konula, K., Koivisto, U.M., et al. Polymorphisms of the genes encoding apoproteins A-I, C-III,and E and LDL receptor, and cholesterol and LDL metabolism during increased cholesterol intake. Common alleles of the apoprotein E gene show the greatest regulatory impact. Arterioscler Thromb Vasc Biol 1997;17:38-44. ]

Editor’s Comment
The data from the study by Gylling et al. provide a new understanding of the strong genetic influences controlling the plasma lipid responses to changes in dietary cholesterol. As shown in the attached table, apo E2, E3, and E4 subjects with the R+ RFLP (86% of the study group) have a very low plasma cholesterol response to dietary cholesterol (1.5 mg/dl per 100 mg/day) whereas apo E4 subjects with the R- RFLP (14%) are much more dietary cholesterol sensitive (5.8 mg/dl per 100 mg/day). Interestingly, the average response for the group is 2.1 mg/dl per 100 mg/day which is virtually identical to the response factor of 2.2 mg/dl per 100 mg/day determined in the meta-analysis by Howell et al. It should be noted that the estimate of the distribution of sensitivity to dietary cholesterol in the population is between 15 and 20%. The complexity regarding responders and non-responders to dietary cholesterol is becoming more defined, and opens the possibility of targeting dietary restrictions to those who gain some benefit as opposed to population wide restrictions which, if this report is an example, does little for some 85% of the population.

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Efficacy of the National Cholesterol Education Program Step 2 Diet in Males and Females

In nutrition research, results from metabolic studies provide stronger results than epidemiological studies since these studies are designed to control for environmental factors such as food composition, compliance, and associated variables. However, one major disadvantage of this type of study is that the population size is usually limited. Therefore, statistical errors can be a confounding factor in the interpretation of the data. To compensate for this limitation, Schaefer et al. pooled data from five previously published metabolic studies to quantitate the efficacy of the NCEP Step 2 diet in men and women, and to determine the variability in LDL and HDL cholesterol levels in response to the diet. The food compositions in all five studies were very similar and the responses to the diet were similar in all five studies.

There was a total of 120 volunteers, 72 males and 48 females. The male subjects were between 19 and 81 years old, while females were between 21 and 78 years old. All subjects were in good health with no diagnosis of liver, kidney, or thyroid disease, diabetes, or on lipid lowering medication. The baseline diet, which resembled an average American diet, consisted of 35-41% energy from total fat, 13-16% in saturated fat, and 31-45 mg cholesterol/MJ were consumed by test subjects for 4.5 weeks to 10 weeks. The experimental diet (18-29% in total fat, 4-7% in saturated fat, and 11-20 mg cholesterol/MJ) period lasted between 4.5 weeks and 24 weeks. Total calories were adjusted to maintain constant body weight throughout the study period. All meals were prepared in a metabolic kitchen and subjects were encouraged to eat more than 4 meals per week at the research facility. However, packaged meals were provided for home or office consumption.

Compared to the baseline diet, the NCEP Step 2 diet was effective in lowering plasma cholesterol by 16.7% in males, and 13.6% in females, LDL by 18.9% in males, and 15.6% in females, and HDL by 17.0% in males, and 11.2% in females. However, the ratio of total cholesterol to HDL cholesterol was not significantly affected by the experimental diet due to similar reductions in total and HDL cholesterol levels. Male subjects experienced greater diet-related decreases in total, LDL, and HDL cholesterol and diet-related increases in TAG levels than females. The degree of LDL lowering was dependent on subjects baseline LDL level. Male subjects with LDL cholesterol ò 130 mg/dl had an average decrease of 35 mg/dl of LDL while male subjects with baseline LDL < 130 mg/dl decreased LDL by 19 mg/dl. LDL cholesterol levels in females with LDLò130 mg/dl decreased by 27 mg/dl while LDL cholesterol levels in females with LDL < 130 mg/dl decreased by 14 mg/dl. Changes in TAG concentrations were inversely correlated to baseline TAG levels in both men and women. When subjects were separated based on phenotypes, men with an apo E 3,4 phenotype experienced a greater drop in LDL cholesterol than men with an apo E3,3 phenotype on the Step 2 diet. However, this was not the case in female subjects. Also, apo E3,4 men had greater changes in total cholesterol than apo E3,3 men. Women with apo E3,4 had greater changes in TAG concentrations than women with apo E3,3 while on the experimental diet. Unlike apo E, “Apo A-IV phenotype was not a major determinant of plasma lipid lowering response to a Step 2 diet.” According to the results of multivariate analysis, baseline LDL cholesterol concentrations and a subject age were significant predictors of LDL cholesterol responses to the diet in men. In women, age was the only predictor of the LDL cholesterol responses to the Step 2 diet.

These results indicate that the Step 2 diet is effective in lowering plasma lipoprotein levels in both males and females. However, elderly male subjects with high baseline LDL and an apo E 3,4 phenotype obtained the most benefit on the Step 2 diet. Effectiveness of the Step 2 diet in females is much less evident than for males.

[Schaefer, D.J., Lamon-Fava, S., Ausman, L.M., et al. Individual variability in lipoprotein cholesterol response to National Cholesterol Education Program Step 2 diets. Am J Clin Nutr 1997;65:823-30.]

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HDL Cholesterol and Risk of Stroke and CHD Mortality

Using data obtained from the Israeli Ischemic Heart Disease Study, Tanne et al. and Goldbourt et al. investigated the relationships between HDL levels and mortality rates from ischemic stroke and CHD, respectively. HDL cholesterol measurements were available for 8586 men who participated in a 21 year prospective study. Minimum age for the participants at the onset of the study was 42 years old. All subjects held tenured government and municipal positions in Israel.

There were a total of 2,865 deaths during the study period; 295 (10%) men died of stroke, 912 (32%) died of CHD, 603 (21%) died of cancer, and 1055 (37%) died of other causes. Of the 295 who died of stroke, 82% were attributed to ischemic stroke.

The mean age of subjects who died of stroke was 5.5 years older than survivors. Mean diastolic and systolic blood pressure, BMI, and baseline total cholesterol levels were higher in men who suffered stroke than the survivors. The incidence of diabetes was three times higher in the stroke population. The mortality rate from ischemic stroke was inversely related to the HDL concentration. Based on the age adjusted ischemic stroke mortality rates, subjects in the highest tertile of HDL cholesterol (21.9% HDL cholesterol) had the lowest death rate [11.8 per 10,000] while the other two groups with percent HDL cholesterol levels of 17.6-21.9 and < 17.6 had mortality rate of 14.0 and 14.6 per 10,000, respectively.

When HDL cholesterol level deceased by 10 mg/dl, relative risk for mortality due to ischemic stroke and CHD was increased to 1.17 and 1.28, respectively. However, when total cholesterol level increases by 53 mg/dl, relative risk for ischemic stroke and CHD increased by 1.11 and 1.37, respectively. Based on this study, a low HDL level is a greater risk than an increased LDL for ischemic stroke. However, lifestyle changes such as lowering blood pressure and quitting smoking can decrease the incidence of stroke since the relative risk due to high blood pressure, diabetes, smoking, and age were 1.68, 1.78, 1.67, and 1.72, respectively; values much higher than the relative risk from a low HDL level.

According to the report of Goldbourt et al., of the 8586 initial volunteers, 1494 men (17.4%) fell into the isolated low group (HDLó35 mg/dl and TCó200 mg/dl); 2557 men (29.8%) fell into high-low group (HDL > 35 mg/dl and TCó200 mg/dl); 3357 men (39.1%) fell into the high-high group (HDL > 35 mg/dl and TC > 200 mg/dl); and 1178 men (13.7%) fell into the low-high group (HDL> 35 mg/dl and TC > 200 mg/dl). Men in the high-low group were leaner and more physically active at work than the other three groups.

Of the 7686 men free of MI and angina pectoris, 2434 (31.6%) died during the 21 year study period. Six hundred ninety-seven deaths were due to CHD. The age adjusted CHD rate among the different groups was 3.8%, 2.8%, 4.9%, 6.6% for isolated low, high-low, high-high, and low-high, respectively. The age adjusted all-cause death rate was 14.1% for isolated low, 13.9% for high-low, 15.3% for high-high, and 18.0% for low-high groups. In addition, Goldbourt et al. reported that subjects with low HDL levels had increased risk of CHD when their risk profile was further complicated by diabetes, smoking, high blood pressure, and elevated BMI.

Results from both studies show that a low plasma HDL level is an independent risk factor for both stroke and CHD mortality. Thus, HDL concentrations should be measured even if the total cholesterol level is less than 200 mg/dl in order to establish an accurate risk profile for the patient.

[Tanne, D., Yaari, S., Goldbourt, U. High-density lipoprotein cholesterol and risk of ischemic stroke mortality. A 21-year follow-up of 8586 men from the Israeli Ischemic Heart Disease Study. Stroke 1997;28:83-87.
Goldbourt, U., Yaari, S., Medalie, J.H. Isolated low HDL cholesterol as a risk factor for coronary heart disease mortality. A 21-year follow-up of 8000 men. Arterioscler Thromb Vasc Biol 1997;17:107-113.]

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BMI and CHD Risk Factors in Men and Women

In the past several decades, the number of overweight Americans have steadily increased. According to the latest report, one third of the U.S. population is overweight. Scientists have suggested many causes for this problem; however, all agree that it is a major health risk. Using data from the Framingham Offspring Study, Lamon-Fava et al. investigated the role of BMI in CHD risk. The data included 1566 men and 1627 women and the researchers used the 1995 USDA Dietary Guideline and World Health Organization definition of overweight as BMI greater than 25.

The results indicated that 72% of men and 42% of women had BMI value greater than 25 and that the increase in BMI was strongly related to age. For example, BMI increased linearly with age in women until 70 years of age, while men BMI increased linearly with age until 50 years then plateaued. Men and women between the ages of 50-59 years were 2 times and 3 times, respectively, more likely to have BMI values greater than 30. Smoking had a negative impact on BMI levels in that smokers of all age, except females younger than 30 years, had lower BMI than nonsmokers. When nonsmoking subjects were stratified according to their BMI , there was a clear linear association between subject blood pressure, glucose level, plasma TAG, total cholesterol, VLDL, and LDL cholesterol. However, BMI and plasma HDL cholesterol levels exhibited an inverse relationship. Unlike Lp(a) levels, which were not affected by BMI, plasma apo B and apo AI levels followed the same trend observed for LDL cholesterol and HDL cholesterol, respectively. Subjects with a high BMI had more small dense LDL particles than thinner subjects.

Therefore, using these data, the researchers estimated that subjects in the highest BMI group (ò30 kg/m2) had approximately three times greater risk for developing CHD within 10 years than subjects in the lowest BMI group (<21 kg/m2). The risk decreased to 2-fold when age was factored into the calculations. Finally, contrary to common belief, increases in BMI had significant effects on hypertension, diabetes, high TAG, and low HDL than on total and LDL cholesterol levels. Lamon-Fava et al. concluded that “BMI is highly correlated with most risk factors for CHD and that prevention of overweight is an important public health issue.”

Subjects in the highest BMI group (>30 kg/m²) had approximately three times higher risk for developing CHD within 10 years than subjects in the lowest BMI group (<21 kg/m²).

[Lamon-Fava, S., Wilson, P.W., Schaefer, E.J. Impact of body mass index on coronary heart disease risk factors in men and women. The Framingham Offspring Study. Arterioscler Thromb Vasc Biol. 1996;16:1509-1515. ] .

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The More Things Change, the More Things Stay The Same

The recent publication of two meta-analysis of the available data relating changes in dietary lipids and changes in plasma total and lipoprotein cholesterol levels provides a unique opportunity to consider what we have learned over the past thirty years relative to dietary fat and cholesterol and plasma cholesterol levels. In 1965-66 Drs. Keys and Hegsted published their well known equations for predicting the average plasma cholesterol change in response to changes in dietary fat saturation and cholesterol. In 1997, reports by Clarke et al. and Howell et al. present the latest set of equations for predicting dietary lipid effects on plasma cholesterol and specific lipoproteins. Just how much have we learned in the last thirty years?

A comparison of the predictive response factors show that the responses to saturated and polyunsaturated fatty acids really haven changed very much: from an average of 2.33 per 1% change in saturated fat calories in the 60s to 1.97 in the 90s. For polyunsaturated fat the response factor per 1% change in calories has gone from -1.45 in the original equations to -0.95 in the most recent studies. The only real inconsistency is the predicted plasma cholesterol response to changes in dietary cholesterol. In his original estimates of dietary lipid effects on plasma cholesterol, Keys in 1957 didn’t even include dietary cholesterol in his predictive model since he considered it to have little effect. Later, Keys estimated a relatively small dietary cholesterol effect on plasma cholesterol while Hegsted had a much larger response factor. Over the years Hegsted has progressively lowered his estimates of the effect of dietary cholesterol and the predicted changes have settled around a factor of 0.027 mg/dl per mg dietary cholesterol (in a 2,000 kcal diet). Other estimates of the plasma cholesterol response to dietary cholesterol indicate that a reduction in dietary cholesterol from 350 mg/day to 250 mg/day in a 2000 kcal diet would, on average, lower plasma cholesterol by 2.5 mg/dl. And while this is statistically significant, it probably has little, if any, biological meaning in terms of CHD risk reduction. And even the concerns about responders and non-responders are beginning to become clearer as the quantitative differences are defined. In the fifteen to twenty percent of the population classified as dietary cholesterol responders, the response factor is fairly small. In studies of genetic variances non-responders change by 1-2 mg/dl per 100 mg/day increase in dietary cholesterol while responders vary by 3-5 mg/dl per 100 mg/day. Compared to dietary fat, the average subject would need to lower dietary cholesterol intake by 87 mg/day to achieve the same plasma cholesterol lowering effect as a 1% reduction in saturated fat or a 2% increase in calories from polyunsaturated fat.

So forty years after Dr. Ancel Keys considered dietary cholesterol to be an insignificant determinant of plasma cholesterol we have come full circle to the point where we now know that the effect of dietary cholesterol is statistically significant, it just too small an effect to really matter very much. In a recent interview in Eating Well magazine (March/April 1997) when asked about dietary cholesterol and heart disease risk, Dr. Keys was quoted as saying “… there no connection whatsoever between cholesterol in food and cholesterol in the blood. None. And we’ve known that all along” Now I guess we have the evidence to prove it.

Donald J. McNamara, Ph.D.
Executive Editor, Nutrition Close-Up

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Executive Editor: Donald J. McNamara, Ph.D.
Writer/Editor: Linda Min, M.S., R.D.

Nutrition Close-Up is published quarterly by the Egg Nutrition Center. Nutrition Close-Up presents up-to-date reviews, summaries and commentaries on the latest research investigating the role of nutrition in health promotion and disease prevention, and the contributions of eggs to a nutritious and healthful diet. Nutrition and health care professionals can receive a FREE subscription for the newsletter by contacting the ENC.

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