Medical utility of apoe allele determination in assessing the need for antioxidant therapy.

The APOE varepsilon4 allele is associated with a variety of conditions such as Alzheimer's disease, coronary artery disease, stroke and postoperative cognitive dysfunction. The common pathophysiological feature that appears to explain these positive clinical associations with APOE varepsilon4 allele may relate to the decreased endogenous anti-oxidant capability of an individual. A significant body of existing clinical data supports the assumption that diseases associated with the varepsilon4 allele can be alleviated by antioxidant therapies, such as vitamin E. Therefore, we hypothesize that determination of an individual's APOE allele status has medical utility as an efficient method to identify patient subgroups susceptible to oxidative damage. We suggest that prospective studies are needed to determine if individuals at high risk for diseases characterized by oxidative damage and/or who have an APOE varepsilon4 allele might benefit significantly from available antioxidant intervention at a relatively early and asymptomatic age.

Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study.

The evidence for a protective effect of vegetables, fruits, and legumes against prostate cancer is weak and inconsistent. We examined the relationship of these food groups and their constituent foods to prostate cancer risk in a multicenter case-control study of African-American, white, Japanese, and Chinese men. Cases (n = 1619) with histologically confirmed prostate cancer were identified through the population-based tumor registries of Hawaii, San Francisco, and Los Angeles in the United States and British Columbia and Ontario in Canada. Controls (n = 1618) were frequency-matched to cases on ethnicity, age, and region of residence of the case, in a ratio of approximately 1:1. Dietary and other information was collected by in-person home interview; a blood sample was obtained from control subjects for prostate-specific antigen determination. Odds ratios (OR) were estimated using logistic regression, adjusting for age, geographic location, education, calories, and when indicated, ethnicity. Intake of legumes (whether total legumes, soyfoods specifically, or other legumes) was inversely related to prostate cancer (OR for highest relative to lowest quintile for total legumes = 0.62; P for trend = 0.0002); results were similar when restricted to prostate-specific antigen-normal controls or to advanced cases. Intakes of yellow-orange and cruciferous vegetables were also inversely related to prostate cancer, especially for advanced cases, among whom the highest quintile OR for yellow-orange vegetables = 0.67 (P for trend = 0.01) and the highest quintile OR for cruciferous vegetables = 0.61 (P for trend = 0.006). Intake of tomatoes and of fruits was not related to risk. Findings were generally consistent across ethnic groups. These results suggest that legumes (not limited to soy products) and certain categories of vegetables may protect against prostate cancer.

Reduced LDL particle size in children consuming a very-low-fat diet is related to parental LDL-subclass patterns.

BACKGROUND: A genetically influenced atherogenic lipoprotein phenotype characterized by a predominance of small, dense LDL particles (subclass pattern B) can be induced by low-fat diets in healthy subjects with large LDL particles (pattern A). OBJECTIVE: The aim of this study was to test whether genetic predisposition to subclass pattern B contributes to susceptibility to induction of this trait by a low-fat diet. DESIGN: The prevalence of pattern B in children is relatively low compared with that in older individuals, but genetic susceptibility to this trait in offspring can be inferred by its presence in their parents. Plasma lipoproteins were analyzed 10 d after a change from a usual diet to a very-low-fat (10% fat), high-carbohydrate diet in offspring (mean age: 14 y; range: 7-28 y) of 22 families according to parental LDL-subclass patterns when consuming a low-fat diet: AxA mating (9 families with 19 children), AxB mating (5 families with 10 children), and BxB mating (8 families with 21 children). RESULTS: The very-low-fat, high-carbohydrate diet produced significantly greater decreases in LDL particle size in offspring of BxB parents (f1.gif" BORDER="0"> +/- SE: -0.55 +/- 0.16 nm) and AxB parents (-0.48 +/- 0.19 nm) than in offspring of AxA parents (0.14 +/- 0.20 nm). The number of children expressing pattern B with the 10%-fat diet and the proportion of children converting from pattern A to pattern B was significantly greater in offspring of BxB parents than in those with 1 or 2 pattern A parents. CONCLUSION: A very-low-fat, high-carbohydrate diet can induce expression of LDL-subclass pattern B in genetically predisposed children with low expression of the trait while consuming their usual diets.

The value of genotyping for apolipoprotein E alleles in relation to vitamin E supplementation.

The clinical utility of genotyping individuals for apolipoprotein E alleles remains controversial. The present summary reviews clinical and scientific data that suggest that vitamin E supplementation may be beneficial in individuals who carry the apolipoprotein E4 allele. We propose that early anti-oxidant intervention with vitamin E supplementation may have life-long beneficial effects for individuals who carry one or more apolipoprotein E4 alleles.

Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971-1975 to 1992. National Health and Nutrition Examination Survey.

We analyzed data from the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study to test the hypothesis that vitamin D from sunlight exposure, diet, and supplements reduces the risk of breast cancer. We identified 190 women with incident breast cancer from a cohort of 5009 white women who completed the dermatological examination and 24-h dietary recall conducted from 1971-1974 and who were followed up to 1992. Using Cox proportional hazards regression, we estimated relative risks (RRs) for breast cancer and 95% confidence intervals, adjusting for age, education, age at menarche, age at menopause, body mass index, alcohol consumption, and physical activity. Several measures of sunlight exposure and dietary vitamin D intake were associated with reduced risk of breast cancer, with RRs ranging from 0.67-0.85. The associations with vitamin D exposures, however, varied by region of residence. The risk reductions were highest for women who lived in United States regions of high solar radiation, with RRs ranging from 0.35-0.75. No reductions in risk were found for women who lived in regions of low solar radiation. Although limited by the relatively small size of the case population, the protective effects of vitamin D observed in this prospective study are consistent for several independent measures of vitamin D. These data support the hypothesis that sunlight and dietary vitamin D reduce the risk of breast cancer.

A very low-fat diet is not associated with improved lipoprotein profiles in men with a predominance of large, low-density lipoproteins.

BACKGROUND: We found previously that men with a predominance of large LDL particles (phenotype A) consuming high-fat diets (40-46% fat) show less lipoprotein benefits of low-fat diets (20-24% fat) than do men with a high-risk lipoprotein profile characterized by a predominance of small LDL (phenotype B). Furthermore, one-third of men with phenotype A consuming a high-fat diet converted to phenotype B with a low-fat diet. OBJECTIVE: We investigated effects of further reduction in dietary fat in men with persistence of LDL subclass phenotype A during both high- and low-fat diets. DESIGN: Thirty-eight men who had shown phenotype A after 4-6 wk of both high- and low-fat diets consumed for 10 d a 10%-fat diet (2.7% saturates) with replacement of fat with carbohydrate and no change in cholesterol content or ratio of polyunsaturates to saturates. RESULTS: In 26 men, phenotype A persisted (stable A group) whereas 12 converted to phenotype B (change group). LDL cholesterol did not differ from previous values for 20-24%-fat diets in either group, whereas in the change group there were higher concentrations of triacylglycerol and apolipoprotein B; greater mass of HDL, large LDL-I, small LDL-III and LDL-IV, and HDL3; lower concentrations of HDL cholesterol, apolipoprotein A-I; and lower mass of large LDL-I and HDL2. CONCLUSIONS: There is no apparent lipoprotein benefit of reduction in dietary fat from 20-24% to 10% in men with large LDL particles: LDL-cholesterol concentration was not reduced, and in a subset of subjects there was a shift to small LDL along with increased triacylglycerol and reduced HDL-cholesterol concentrations.

Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men.

We tested whether nutrient intakes estimated from 4-d diet records were associated with plasma lipoprotein subclasses in 103 men who were randomly assigned to a low-fat (24% fat) and a high-fat (46% fat) diet for 6 wk each in a crossover design. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities were also determined in a subset of 43 men. Changes in intake (ie, high fat minus low fat) of total saturated fatty acids, as well as myristic (14:0) and palmitic (16:0) acids, were positively correlated (P < 0.01) with increases in mass of large LDL particles [measured by analytic ultra-centrifugation as mass of lipoproteins of flotation rate (Sf) 7-12] and with LDL peak particle diameter and flotation rate, but not with changes in LDL-cholesterol concentration. Changes in total saturated fatty acids as well as myristic and palmitic acids were also inversely associated with changes in HL activity (P < 0.05). With the high-fat diet only, variation in dietary total saturated fatty acid intake was inversely correlated (P < 0.01) with concentrations of small, dense LDL of Sf 0-5. This correlation was significant specifically for myristic acid (P < 0.001). Stearic acid (18:0), monounsaturates, and polyunsaturates showed no significant associations with lipoprotein concentrations. These data indicate that a high saturated fat intake (especially 14:0 and 16:0) is associated with increased concentrations of larger, cholesterol-enriched LDL and this occurs in association with decreased HL activity.

Diet-gene interactions in human lipoprotein metabolism.

Genetic variation can influence the effects of hypocholesterolemic dietary interventions on lipoproteins involved in coronary artery disease (CAD). Individuals with the E4 allelic variant of the apo E gene exhibit greater low-density lipoprotein (LDL) cholesterol reductions on low-fat, low-cholesterol diets than subjects with other alleles. Another apolipoprotein structural variant, apo A-IV-2, attenuates the response of LDL cholesterol to dietary cholesterol. Other studies have associated lipoprotein response to dietary modifications with DNA polymorphisms in the genes for apo B and the LDL receptor, and in the promoter region of the apo A-I gene. Studies in our laboratory involving variation in dietary fat and carbohydrate intake have demonstrated that alleles at the apo E gene locus are associated with changes in large, buoyant but not smaller, denser LDL subclasses. On the other hand, a low-fat diet induces a reduction in small, dense LDL in individuals with a genetically influenced metabolic profile characterized by a predominance of these particles. Moreover, reductions in LDL cholesterol and apo B in these subjects are greater than in the majority of subjects with larger LDL. Since in humans a predominance of small LDL signifies a higher risk for coronary artery disease than that associated with larger LDL, metabolic and genetic factors contributing to the small LDL trait may account for a substantial portion of the coronary risk benefit attributed to reduced-fat diets. Studies in large population groups or in suitable animal models will be necessary to determine the impact of genetic influences on dietary response affecting lipoprotein metabolism and their interactions with other environmental and hormonal factors.

Variability of plasma HDL subclass concentrations in men and women over time.

Plasma HDL subclasses were examined by gradient gel electrophoresis in repeated samples to assess variability over time. Absorbance of the protein stain was used as an index of mass concentrations at 0.01-nm intervals within five HDL subclasses: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). Three separate longitudinal studies of men showed that repeated samples of HDL over time were correlated most strongly within HDL2b, somewhat less within HDL2a, and more weakly within HDL3a, HDL3b, and HDL3c. As in men, repeated samples in women from two studies were significantly correlated within the HDL2b, HDL2a, and HDL3b intervals. Plasma HDL2b levels were significantly more stable in men than in women. Although the variability of HDL subclass measurements includes both methodological and physiological sources, differences in laboratory measurement error do not appear to explain the differences in correlations among subclasses. Specifically, analysis of 288 replications from frozen aliquots suggested that laboratory error had the least effect on correlations involving HDL3 subclasses and only slightly greater effect on correlations involving HDL2 subclasses. Our results suggest that for plasma sampled over time, the stability of HDL subclass levels increases with particle size. Prior reports of subclass-specific correlations between HDL and other variables (eg, diet, exercise, and other lipids) are unlikely to be artifacts of laboratory precision but could arise from subclass differences in variability that are physiological.

LDL subclass patterns and lipoprotein response to a low-fat, high-carbohydrate diet in women.

A predominance of small, dense LDL particles (subclass pattern B) characterizes a metabolic trait that is associated with higher levels of triglyceride-rich lipoproteins and lower levels of HDL compared with those of individuals with predominantly larger LDL (pattern A). This trait appears to be under the influence of one or more genes, with maximal expression in adult males and reduced expression in premenopausal females. In a previous study, men with LDL subclass pattern B had significantly greater reductions in LDL cholesterol (LDL-C) and apolipoprotein B than men with pattern A. We hypothesized that despite the low prevalence of pattern B in premenopausal women, genetic predisposition to this trait could affect dietary responsiveness. Specifically, we predicted that LDL-C reduction on a low-fat, high-carbohydrate diet would be greatest in daughters of two pattern B parents, intermediate in daughters with one pattern B parent, and least in daughters with no pattern B parents. When 72 premenopausal women were placed on a 20% fat diet for 8 weeks, the changes in LDL-C (mmol/L) compared with levels on basal diets were significantly related to the number of pattern B parents (two B parents: -0.92 +/- 0.61, one B parent: -0.23 +/- 0.10, no B parents: -0.05 +/- 0.06) and could not be explained by diet adherence or baseline characteristics including initial lipoprotein profile or body mass index. The number of pattern B parents was also related to reductions in plasma mass concentrations of IDL, total LDL, and large LDL and to increases in plasma triglycerides. There was a significant inverse correlation between changes in triglyceride and LDL-C induced by the low-fat, high-carbohydrate diet. Thus, genetic and metabolic factors underlying LDL subclass pattern B may result in enhanced LDL and triglyceride responsiveness to substitution of dietary carbohydrate for fat in premenopausal women.

Serum androgens and sex hormone-binding globulins in relation to lifestyle factors in older African-American, white, and Asian men in the United States and Canada.

Differences in endogenous androgen levels have been hypothesized to explain ethnic differences in prostate cancer risk. To examine this hypothesis, we gathered data on serum concentrations of androgens and sex hormone-binding globulin (SHBG) in healthy older men from four ethnic groups at different levels of prostate cancer risk. As part of a population-based case-control study of prostate cancer we conducted in California, Hawaii, and Vancouver, Canada, 1127 African-American, white, Chinese-American, and Japanese-American control men, mostly ages 60 years or older (mean age, 69.9 years) provided information on various lifestyle factors and donated an early morning fasting blood sample between March 1990 and March 1992. We used these data to examine the distributions of serum androgens [testosterone (total, free, and bioavailable), dihydrotestosterone (DHT)], the ratio of DHT to total testosterone (DHT:testosterone ratio), and SHBG in these four ethnic groups. We also assessed correlations between concentrations of these measures with age, body size, physical activity, and other personal characteristics, and we evaluated ethnic differences in concentrations of androgens and SHBG after adjusting for these characteristics. In each of the four ethnic groups, concentrations of free and bioavailable testosterone declined with age, whereas SHBG concentrations increased with age. Age-adjusted concentrations of all androgen measures and SHBG decreased with increasing levels of Quetelet's index. After adjustment for age and Quetelet's index, androgens and SHBG showed no clear and consistent relationships to physical activity, alcohol consumption, or tobacco use. DHT:testosterone ratio was higher in men reporting a history of benign prostate disease than in men without such a history, and higher in vasectomized men than in nonvasectomized men. SHBG concentrations were higher in men reporting one or more first-degree relatives with prostate cancer than in men without such a family history. After adjustment for age and Quetelet's index, the levels of total and bioavailable testosterone were highest in Asian-Americans, intermediate in African-Americans, and lowest in whites. However, the DHT:testosterone ratio was highest in African-Americans, intermediate in whites, and lowest in Asian-Americans, corresponding to the respective incidence rates in these groups and providing indirect evidence for ethnic differences in 5alpha-reductase enzyme activity.

Low-density-lipoprotein subclasses and response to a low-fat diet in healthy men.

Lipid and lipoprotein responses to reduced dietary fat intake were investigated in relation to differences in distribution of low-density-lipoprotein (LDL) subclasses among 105 healthy men consuming high-fat (46% fat) and low-fat (24% fat) diets in random order for 6 wk each. With high-fat diets, 87 subjects had predominantly large, buoyant LDL (pattern A), whereas the remainder had primarily smaller, denser LDL (pattern B). With low-fat diets, 36 men changed from pattern A to B. Compared with the 51 men with pattern A with both diets (stable A group), men in the stable B group (n = 18) had significantly greater reductions in plasma LDL cholesterol, apolipoprotein B, and mass of mid-sized (LDL II) and small (LDL III) LDL subfractions. In both the stable A and change groups, there was a shift in LDL particle mass from larger, lipid-enriched (LDL I and II) to smaller, lipid-depleted (LDL III and IV) subfractions, suggestive of change in LDL composition with minimal change in particle number, and consistent with the observation of reduced plasma LDL cholesterol without reduced apolipoprotein B. Stable B subjects had significantly greater increases in the largest very-low-density-lipoprotein subfraction with the low-fat diet than the stable A group, and also had greater decreases in the high-density-lipoprotein (HDL) subclass HDL3 but smaller reductions in HDL2. Genetic and environmental factors influencing LDL subclass distributions thus may also contribute substantially to interindividual variation in plasma lipoprotein response to a low-fat diet.

Effects of dietary fat on high-density-lipoprotein subclasses are influenced by both apolipoprotein E isoforms and low-density-lipoprotein subclass patterns.

We examined the effects of replacing dietary fat with carbohydrates on high-density-lipoprotein (HDL) subclasses as measured by nondenaturing polyacrylamide-gradient-gel electrophoresis. One hundred five men received a 6-wk low-fat diet (24% of total energy) and a 6-wk high-fat diet (46% of energy) in a crossover design. Absorbency of protein stain was measured within five HDL subclasses: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). The low-density-lipoprotein-(LDL) subclass pattern was determined by gradient-gel electrophoresis, with pattern B men defined as having an LDL-predominant peak diameter < or = 25.5 nm and an LDL distribution skewed toward larger size particles. On the high-fat diet, 18 men exhibited LDL-subclass pattern B and 87 men exhibited the alternative LDL pattern A. Twelve men had the apolipoprotein (apo) epsilon 2 allele. Replacing dietary fat with carbohydrates 1) significantly decreased HDL3a, HDL2a, and HDL2b; 2) reduced HDL2b significantly more in pattern A than in pattern B men; and 3) increased plasma HDL3b concentrations significantly more in those men with the epsilon 2 allele. Our results suggest that unfavorable HDL changes were significantly more likely to occur in men who had LDL-subclass pattern A or the apo epsilon allele than in men who had pattern B or lacked the epsilon 2 allele.

Vasectomy and prostate cancer: results from a multiethnic case-control study.

BACKGROUND: Vasectomy, a widely used form of contraception, has been associated in some studies with increased prostate cancer risk. PURPOSE: We assessed this association on the basis of data collected in a large multiethnic case-control study of prostate cancer that was conducted in the United States (Los Angeles, San Francisco, and Hawaii) and Canada (Toronto and Vancouver). METHODS: In home interviews conducted with newly diagnosed prostate cancer case patients and population control subjects, we obtained information on the participants' medical history, including a history of vasectomy and the age at which the procedure was performed, as well as other potential risk factors. Blood samples were collected from control subjects only and were assayed for concentration of sex hormones and sex hormone-binding globulin. RESULTS: The present analysis was based on 1642 prostate cancer patients and 1636 control subjects. A history of vasectomy was not significantly associated with prostate cancer risk among all racial/ethnic groups combined (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 0.83-1.3), whites (OR = 0.94; 95% CI = 0.69-1.3), blacks (OR = 1.0; 95% CI = 0.59-1.8), or Chinese-Americans (OR = 0.96; 95% CI = 0.42-2.2). Among Japanese-Americans, the OR was 1.8 (95% CI = 0.97-3.4), but the statistically nonsignificant elevation in risk was limited to more educated men and those with localized cancers. ORs did not vary significantly by age at vasectomy or years since vasectomy. We found a lower serum concentration of sex hormone-binding globulin and a higher ratio of dihydrotestosterone to testosterone among vasectomized control subjects than among nonvasectomized control subjects. CONCLUSIONS: The findings of this study do not support previous reports of increased prostate cancer risk associated with vasectomy. However, the altered endocrine profiles of vasectomized control subjects seen in this cross-sectional comparison warrant further evaluation in longitudinal studies.

PIP: Vasectomy has been associated in some studies with increased prostate cancer risk. This association was assessed on the basis of data collected in a large multiethnic case control study of prostate cancer that was conducted in the United States (Los Angeles, San Francisco, and Hawaii) and Canada (Toronto and Vancouver). In home interviews conducted with newly diagnosed prostate cancer case patients (diagnosed between January 1, 1989 and December 31, 1991 as well as January 1, 1987 and December 31, 1988) and control subjects, information was obtained on the participants' medical history, including a history of vasectomy and the age at which the procedure was performed as well as other potential risk factors. Blood samples were collected from control subjects only and were assayed for concentration of total testosterone, percent of free testosterone, percent of bioavailable testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) using an automated, polyclonal-monoclonal immunochemiluminometric prostate-specific antigen (PSA) assay. The analysis was based on 1642 prostate cancer patients and 1636 control subjects. The analysis of PSA, androgens, and SHBG by vasectomy status was based on 850 control subjects with normal PSA concentrations. A history of vasectomy was not significantly associated with prostate cancer risk among all racial/ethnic groups combined (odds ratio [OR] = 1.1; Whites OR = 0.94; Blacks OR = 1.0; or Chinese-Americans OR = 0.96). Among Japanese-Americans, the OR was 1.8, but the statistically significant elevation in risk (OR = 4.1) was limited to more educated men with a history of vasectomy and those with localized cancers (OR = 5.3). ORs did not vary significantly by age at vasectomy or years since vasectomy. Lower serum concentration of SHBG and a higher ratio of DHT to testosterone was found among vasectomized control subjects than among nonvasectomized control subjects. The findings do not support previous reports of increased prostate cancer risk associated with vasectomy. However, the altered endocrine profiles of vasectomized control subjects warrant further evaluation in longitudinal studies.

Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada.

BACKGROUND: International and interethnic differences in prostate cancer incidence suggest an environmental, potentially modifiable etiology for the disease. PURPOSE: We conducted a population-based case-control study of prostate cancer among blacks (very high risk), whites (high risk), and Asian-Americans (low risk) in Los Angeles, San Francisco, Hawaii, Vancouver, and Toronto. Our aim was to evaluate the roles of diet, physical activity patterns, body size, and migration characteristics on risk in these ethnic groups and to assess how much of the interethnic differences in risk might be attributed to interethnic differences in such lifestyle characteristics. METHODS: We used a common protocol and questionnaire to administer personal interviews to 1655 black, white, Chinese-American, and Japanese-American case patients diagnosed during 1987-1991 with histologically confirmed prostate carcinoma and to 1645 population-based control subjects matched to case patients by age, ethnicity, and region of residence. Sera collected from 1127 control subjects were analyzed for levels of prostate-specific antigen (PSA) to permit comparison of case patients with control subjects lacking serological evidence of prostate disease. Odds ratios were estimated using conditional logistic regression. We estimated the proportion of prostate cancer attributable to certain risk factors and the proportion of interethnic risk differences attributable to interethnic differences in risk-factor prevalence. RESULTS: A positive statistically significant association of prostate cancer risk and total fat intake was found for all ethnic groups combined. This association was attributable to energy from saturated fats; after adjusting for saturated fat, risk was associated only weakly with monounsaturated fat and was unrelated to protein, carbohydrate, polyunsaturated fat, and total food energy. Saturated fat intake was associated with higher risks for Asian-Americans than for blacks and whites. In all ethnic groups combined, the risk tended to be higher when only case patients with advanced disease were compared with control subjects with normal PSA levels. Among foreign-born Asian-Americans, risk increased independently with years of residence in North America and with saturated fat intake. Crude estimates suggest that differences in saturated fat intake account for about 10% of black-white differences and about 15% of white-Asian-American differences in prostate cancer incidence. Risk was not consistently associated with intake of any micronutrients, body mass, or physical activity patterns. CONCLUSIONS: These data support a causal role in prostate cancer for saturated fat intake but suggest that other factors are largely responsible for interethnic differences in risk.

Associations of hepatic and lipoprotein lipase activities with changes in dietary composition and low density lipoprotein subclasses.

To test whether lipoprotein lipase or hepatic lipase activities are associated with lipoprotein subclasses, and to assess the effects of dietary manipulations on these associations, enzyme activities were measured in postheparin plasma (75 U heparin/kg) from 43 healthy men who were randomly allocated to a low-fat (24% fat, 60% carbohydrate) and a high-fat (46% fat, 38% carbohydrate) diet for 6 weeks each in a cross-over design. The high-fat diet significantly increased both lipoprotein lipase (+20%, P = 0.02) and hepatic lipase (+8%, P = 0.007) activities. On both diets, hepatic lipase activity was significantly positively correlated (P < 0.01) with plasma apolipoprotein (apo)B concentrations, and with levels of small dense low density lipoprotein (LDL) III, measured by analytic ultracentrifugation as mass of lipoproteins of flotation rate (Sof) 3-5, while lipoprotein lipase activity was inversely associated with levels of LDL III (P < 0.05). Despite the cross-sectional correlations, increased hepatic lipase activity was not significantly correlated with the reduction in LDL III mass observed on the high-fat diet. Rather, changes in hepatic lipase were correlated inversely with changes in small very low density lipoproteins (VLDL) of Sof 20-40, and small intermediate density lipoproteins (VLDL) of Sof 10-16. Moreover, changes in lipoprotein lipase activity were not significantly correlated with changes in small LDL, but were positively associated with changes in small IDL of Sof 10-14, and large LDL I of Sof 7-10. Thus, while increased levels of small dense LDL are associated with a metabolic state characterized by relatively increased hepatic lipase and decreased lipoprotein lipase activity, changes in these enzymes do not appear to be primary determinants of diet-induced changes in levels of this LDL subfraction. On the other hand, increased lipoprotein lipase activity induced by high-fat feeding may contribute to the accumulation in plasma of both large LDL I and small IDL, whereas increased hepatic lipase may promote catabolism or clearance of triglyceride-rich lipoprotein remnants.

Apolipoprotein E isoform phenotype and LDL subclass response to a reduced-fat diet.

We investigated the association of apolipoprotein (apo) E isoform phenotype with lipoprotein response to reduced dietary fat intake in 103 healthy men (apoE3/2, n = 10; apoE3/3, n = 65; and apoE4/3, 4/4, n = 28). In a randomized, crossover design, subjects consumed high-fat (46%) and low-fat (24%) diets for 6 weeks each. High-fat LDL cholesterol differed among phenotypes, with apoE4/3, 4/4 > apoE3/3 > apoE3/2. Reduction of LDL cholesterol on the low-fat diet was greater for apoE4/3, 4/4 than apoE3/3 (P < .05). There was no significant change in plasma apoB level within any of the apoE phenotype groups on the low-fat diet. This result, together with measurements of LDL subfraction mass by analytical ultracentrifugation, indicated that the primary basis for the diet-induced reduction in LDL cholesterol was not reduced LDL particle number but rather a shift from large, buoyant, cholesterol-rich LDL particles (flotation rate, 7 to 12) to smaller, denser LDL particles (flotation rate, 0 to 7). The magnitude of this effect was related to apoE phenotype, with progressively greater reductions in levels of large LDL (P < .01) from apoE3/2 to apoE3/3 to apoE4/3, 4/4. These results indicate that reduced dietary fat lowers levels of large, buoyant LDL particles by an apoE-dependent mechanism.

Low-density lipoprotein subclass patterns and lipoprotein response to a reduced-fat diet in men.

Low-density lipoprotein (LDL) subclass pattern B is a common genetically influenced lipoprotein profile characterized by a predominance of small, dense LDL particles, and associated with increased levels of triglyceride-rich lipoproteins, reductions in high-density lipoprotein cholesterol (HDL-C), and increased risk of coronary artery disease compared to individuals with a predominance of larger LDL (pattern A). We sought to determine whether LDL subclass patterns are associated with response of plasma lipoprotein levels to changes in dietary fat and carbohydrate content. In a randomized cross-over study, 105 men consumed, for six weeks each, high-fat (46%) and low-fat (24%) solid food diets, with replacement of fat by carbohydrate. Diet-induced changes in subjects who exhibited pattern B (n = 18) following the high-fat diet differed significantly from those in subjects with pattern A (n = 87): in pattern B subjects LDL cholesterol (LDL-C) reductions were two-fold greater and plasma apolipoprotein (apo) B levels decreased significantly. These differences remained significant after adjustment for levels of plasma LDL-C, apo B, HDL-C, and body mass index. Thus, LDL subclass pattern is a factor that contributes significantly to interindividual variation of plasma lipoprotein response to a low-fat, high-carbohydrate diet.

Use of NHANES data to assign nutrient densities to food groups in a multiethnic diet history questionnaire.

In epidemiological studies of diet and chronic disease, a brief yet comprehensive diet history questionnaire must aggregate some foods into food groups. A nutrient density is assigned to each food group by averaging the densities of its constituent foods. A person's intake of a given nutrient is then estimated by multiplying the reported consumption of each food group by its average nutrient density and summing over food groups. These calculations could introduce bias in multiethnic studies, if the average nutrient densities assigned to food groups are inappropriate for some ethnic populations. This issue is examined here for intakes of total fat, saturated fat, and vitamin A for U.S. blacks and whites. We used 24-hour diet recall data from the Second National Health and Nutrition Examination Survey (NHANES II) to assess black-white differences in relative frequency of consumption of foods within food groups of a diet history questionnaire. We also calculated ethnic-specific average nutrient densities for each food group by weighting the densities of its foods in proportion to their frequency of consumption by black and white NHANES II participants. We found black-white differences in the frequency of consumption of foods within 14 food groups. However, blacks and whites had different average total fat densities for only 1 of the 14 food groups, no difference in saturated fat densities for any food group, and different vitamin A densities for 2 food groups. Among blacks and whites, there is no advantage to calculating ethnic-specific average nutrient densities for food groups comprised of foods with similar densities.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of polyunsaturated fat vs monounsaturated fat on plasma lipoproteins.

The effect on plasma lipoproteins of exchanging fat type within currently recommended reduced-fat diets was studied in a free-living group of 19 men and 20 women who consumed both a polyunsaturated fat-enriched diet and a monounsaturated fat-enriched diet, each for a 12-week period, with saturated fat and cholesterol held constant. Mean plasma concentrations of low-density lipoprotein cholesterol and low-density lipoprotein total mass (analytic ultracentrifuge), and high-density lipoprotein (HDL) cholesterol and HDL total mass, did not change significantly on exchanging fat type. However, HDL2 cholesterol concentration was 50% higher and HDL3 cholesterol concentration was 7% lower for polyunsaturated compared with monounsaturated fat. Mean total mass of HDL2 was also 23.5% higher and concentration of apolipoprotein B was 5.4% lower on transfer to the polyunsaturated fat diet. Contrary to frequent assertions, we find no advantage with respect to plasma HDL concentrations in using predominantly monounsaturated rather than polyunsaturated fats in subjects who consumed reduced-fat, solid-food diets.