Cholesterol Journal Articles

Record 4201 to 4220

Dietary fish oil decreases C-reactive protein, interleukin-6, and triacylglycerol to HDL-cholesterol ratio in postmenopausal women on HRT
Ciubotaru, I., Y. S. Lee, et al. (2003), J Nutr Biochem 14(9): 513-21.
Abstract: BACKGROUND: Atherogenesis is a complex process involving both a low-grade inflammation and a disturbed lipid profile. Although dietary fish and fish oil improve the latter of these two risk factors, their impact on the former is less clear. OBJECTIVE: This study addressed the effect of supplementation with fish oil in doses achievable with diet on serum C-reactive protein (CRP), interleukin-6 (IL-6), and the lipid profile. METHODS AND RESULTS: Thirty healthy subjects taking HRT were randomly divided into three groups and supplemented for five weeks with 14 g/day safflower oil (SO), 7 g/day of both safflower oil and fish oil (LFO), or 14 g/day fish oil (HFO). Measurements included serum high-sensitivity CRP, IL-6 in plasma and in cell culture supernatant collected from 24-hr lipopolysaccharide (LPS)-stimulated whole blood, and lipid profile markers. CRP and IL-6 were adjusted for body mass index (BMI). Fish oil supplementation significantly decreased CRP and IL-6 compared to SO, with a greater effect in the LFO than HFO groups. Plasma triacylglycerol (TG) and the TG/HDL-C ratio were significantly lower in the HFO compared to the SO group. CONCLUSIONS: These results suggest that dietary fish oil may decrease the risk for cardiovascular disease through the modulation of both plasma lipids and inflammatory markers in healthy postmenopausal women.

Dietary fish oil effects on biliary lipid secretion and cholesterol gallstone formation in the African green monkey
Scobey, M. W., F. L. Johnson, et al. (1991), Hepatology 14(4 Pt 1): 679-84.
Abstract: We studied two groups of adult male African green monkeys to assess the effects of dietary fish oil on biliary lipid secretion and cholesterol gallstone formation. One group was fed 0.8 mg cholesterol/kcal and 42% of calories as fat with half of the fat calories derived from lard; the other group was fed a similar diet except for the isocaloric substitution of menhaden oil for lard. After 2 1/2 to 3 yr, necropsies were performed and the presence of gallstones was determined. Gallbladder bile specimens were analyzed for cholesterol saturation index, as well as for bile acid species and biliary phospholipid fatty acid composition. Our results showed that 67% of animals fed the lard diet had cholesterol gallstones compared with only 22% of animals in the group fed the fish oil diet (p = 0.08). The cholesterol saturation index of gallbladder bile also tended to be higher in the lard-fed group (1.15 +/- 0.11) compared with the fish oil-fed group (0.86 +/- 0.09, p = 0.06). No differences between the two dietary groups were noted in the percentages of the various types of bile acids. However, a greater percentage of omega-3 fatty acids and a lesser percentage of 18:1, 18:2 and 20:4 fatty acids were found in the biliary phospholipids from the fish oil-fed group compared with the lard-fed group. Biliary lipid secretion rates were then measured during isolated recirculating liver perfusion performed with a constant sodium taurocholate infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary fish oil inhibits cholesterol monohydrate crystal nucleation and gallstone formation in the prairie dog
Magnuson, T. H., K. D. Lillemoe, et al. (1995), Surgery 118(3): 517-23.
Abstract: BACKGROUND. Epidemiologic studies suggest that populations consuming a diet rich in fish oil have lower rates of both atherosclerotic heart disease and gallstones. The mechanisms underlying this inhibitory effect on cholesterol gallstone formation remain unclear. We therefore studied the effect of dietary fish oil on bile composition and cholesterol precipitation in an animal model of gallstone disease. METHODS. Adult male prairie dogs were fed a standard control diet (n = 12) or a lithogenic 1.2% cholesterol diet (n = 16). One half of the animals in each group had their diet supplemented with concentrated fish oil. RESULTS. After 14 days animals receiving the cholesterol diet all developed biliary cholesterol monohydrate crystals and gallstones. When fish oil was added to this high cholesterol diet, solid cholesterol crystal precipitation and gallstone formation were completely inhibited. This inhibition of gallstone formation was accompanied by a significant decrease in biliary calcium and total protein concentration. Microscopic cholesterol liquid crystals were evident in the bile of all of the animals fed the cholesterol plus fish oil diet. Dietary fish oil also significantly prolonged cholesterol monohydrate crystal observation time in animals receiving the lithogenic diet. CONCLUSIONS. These data suggest that dietary fish oil exerts a potent antilithogenic effect on cholesterol gallstone disease and may induce a stable liquid crystalline phase retarding nucleation.

Dietary fish oil potentiates bile acid-induced cholesterol secretion into bile in rats
Smit, M. J., H. J. Verkade, et al. (1994), J Lipid Res 35(2): 301-10.
Abstract: Recently we demonstrated that dietary fish oil (FO) causes changes in intrahepatic cholesterol transport and hypersecretion of cholesterol into bile in rats (J. Clin. Invest. 88: 943-951, 1991). We have now investigated in more detail the relationship between cholesterol and bile acid secretion in rats with chronic bile diversion fed purified diets supplemented (9% wt/wt) with either FO or corn oil (CO) for 2 weeks. Effects of FO on biliary cholesterol secretion (+ 400% as compared to CO after 14 days) were much more pronounced than previously observed in rats with intact enterohepatic circulation (+50%). Biliary bile acid (+30%) and phospholipid (+120%) secretion were increased to a much lesser extent than that of cholesterol resulting in the formation of bile supersaturated with cholesterol. The biliary cholesterol/bile acid molar ratio was 0.069 and 0.032 in FO- and CO-fed rats, respectively, at noon of day 14. This ratio increased to 0.108 in FO-fed rats at midnight, when bile acid output was maximal, but remained unchanged in CO-fed rats during the day-night cycle. Intravenous administration of taurochenodeoxycholic acid (15 mumol/kg) resulted in a 2-fold increase in bile acid output and a simultaneous 1.6-fold stimulation of cholesterol secretion in both groups, implying that administration of the bile acid induced the secretion of 2-3 times as much cholesterol in FO- than in CO-fed rats. Likewise, administration of bilirubin ditaurate (30 mumol/kg), an inhibitor of bile acid-induced biliary lipid secretion, reduced cholesterol output in both groups by about 50% while bile acid output remained unchanged. It is concluded that, in rats, dietary fish oil increases the disposition of cholesterol into bile by potentiating bile acid-dependent cholesterol secretion, presumably by facilitating the recruitment of bile-destined cholesterol.

Dietary fish oil reduces cholesterol and arachidonic acid levels in chick plasma and very low density lipoprotein
Castillo, M., F. Amalik, et al. (1999), Mol Cell Biochem 200(1-2): 59-67.
Abstract: The mechanisms involved in the hypolipidemic effects of fish oil have not been clearly established. This study shows that supplementation of 10% menhaden oil to the chick diet for 7 days produced a significant hypocholesterolemia and hypotriglyceridemia. Fatty acid composition of chick plasma drastically changed by the same dietary manipulation. Percentages of 20:5 and 22:6 n-3 fatty acids strongly increased, while percentages of 20:4 n-6, 18:2 n-6, and 18:1 n-9 significantly decreased. Changes observed in the relative percentages were parallel to those obtained in the amount of each fatty acid. Ratio of n-3/n-6 clearly decreased in plasma by fish oil feeding. Total cholesterol and triacylglycerol contents decreased in high density lipoprotein (HDL) but did not change in low density lipoprotein (LDL). All chemical constituents of very low density lipoprotein (VLDL) significantly decreased after the first week of menhaden oil supplementation to the diet. Similar modifications in fatty acid composition of the three lipoprotein fractions were also found. Our results suggest that the hypocholesterolemic effects of fish oil may be mediated by the depletion in VLDL synthesis and secretion into the chick plasma. On the other hand, the strong decrease found in the arachidonic acid (AA) content of chick plasma and lipoproteins may contribute to the beneficial effects of fish oil consumption by lowering the production of its derived eicosanoids.

Dietary fish oil reduces microthrombi over atherosclerotic lesions in hyperlipidemic swine even in the absence of plasma cholesterol reduction
Kim, D. N., J. Schmee, et al. (1993), Exp Mol Pathol 59(2): 122-35.
Abstract: We have investigated in swine the effect of fish oil additives to a butter-cholesterol hyperlipidemic diet (BT) on atherogenesis and thrombogenesis when average plasma cholesterol levels were kept similar in fish oil-treated and untreated BT groups. The studies included evaluation of lesion sizes and cell numbers, counts of adherent monocytes over lesions, and counts of platelet clumps (microthrombi) over lesions either attached directly to endothelium or to adherent monocytes. Anatomic sites studied for lesion development were the left anterior descending coronary artery (LAD), the distal 1/5 of the abdominal aorta, and a proximal portion of the thoracic aorta. Counts of attached monocytes and platelet clumps were made by scanning electron microscopy only for the LAD and expressed per mm2 of surface. The most striking new result was in regard to the platelet clumps. These were reduced by the fish oil from 996 +/- 295/mm2 in the untreated BT group to 313 +/- 59 and 364 +/- 105 in BT+cod liver oil and BT+menhaden oil groups, respectively. Most of the platelet clumps were adherent to attached monocytes in all groups and the number of attached monocytes were greatly reduced by the fish oil additive. Thus there were close relationships among platelet clumps, monocytes, and lesion endothelium. Numbers of attachments over nonlesion endothelium were much less than those over lesions in all dietary groups. The most surprising result was the lack of retardation of lesion growth by the fish oil additives in spite of the reduction in attached monocytes and platelet clumps. In previous studies where the high plasma cholesterol levels in the BT swine had been modestly reduced (about 25%) there had been a marked retardation of lesion growth. The current result suggests that plasma cholesterol is the major factor controlling lesion growth in this model through under milder conditions and longer observation periods other factors might become apparent.

Dietary fish oil up-regulates cholesterol 7alpha-hydroxylase mRNA in mouse liver leading to an increase in bile acid and cholesterol excretion
Berard, A. M., M. F. Dumon, et al. (2004), FEBS Lett 559(1-3): 125-8.
Abstract: To investigate the molecular events controlling reverse cholesterol transport, we compared gene expression of normal mouse liver to that of mice fed a long chain (LC) omega-3 fatty acid-enriched diet. Using cDNA microarrays, we assessed expression levels of 1176 genes, and we found that D-site binding protein (DBP) was three-fold increased in mice on a LC omega-3 fatty acid-rich diet compared to controls. DBP is known to increase transcriptional level of cholesterol 7alpha-hydroxylase (C7alpha), the rate-limiting enzyme for bile acid production and cholesterol excretion, and we found that C7alpha mRNA was also up-regulated by LC omega-3 fatty acids. Moreover, liver X receptor-alpha, another transcription factor up-regulating C7alpha, was three- to four-fold increased in liver of treated mice. On the other hand, we demonstrated that bile acid and cholesterol excretion were two-fold increased. These results show that LC omega-3 fatty acids control cholesterol metabolism in mice at a new endpoint.

Dietary fish oil-induced changes in intrahepatic cholesterol transport and bile acid synthesis in rats
Smit, M. J., A. M. Temmerman, et al. (1991), J Clin Invest 88(3): 943-51.
Abstract: Hepatic cholesterol metabolism was studied in rats fed purified diets supplemented (9% wt/wt) with either fish oil (FO) (n-3 fatty acids) or corn oil (CO) (n-6 fatty acids) for 4 wk. Rats were equipped with permanent catheters in heart, bile duct, and duodenum to allow studies under normal feeding conditions. 3H-cholesteryl oleate-labeled small unilamellar liposomes, which are rapidly endocytosed by hepatocytes, were intravenously injected to label intrahepatic cholesterol pools, and plasma and bile were collected. FO as compared to CO induced a lowering of plasma cholesterol levels by 38% and of triglyceride levels by 69%. This reduction in plasma lipids in FO rats was accompanied by: (a) an increased bile acid pool size (28%); (b) a fourfold increase in the ratio cholic acid/chenodeoxycholic acid in bile; (c) increased biliary excretion of cholesterol (51%); (d) accelerated excretion of endocytosed free cholesterol into bile; (e) accelerated incorporation of endocytosed cholesterol in bile acids; (f) a significant increase in the bile acid-independent fraction of bile flow; and (g) a threefold increase in hepatic alkaline phosphatase activity. The results show that FO induces changes in transport and metabolic pathways of cholesterol in the rat liver, which result in a more rapid disposition of plasma-derived cholesterol into the bile.

Dietary fish protein modulates high density lipoprotein cholesterol and lipoprotein lipase activity in rabbits
Bergeron, N., Y. Deshaies, et al. (1992), J Nutr 122(8): 1731-7.
Abstract: To explore the pathways by which fish protein feeding influences HDL metabolism, postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured in rabbits fed fish protein or soybean protein combined with corn oil or coconut oil in a 2 x 2 factorial arrangement. In addition to greater serum total and LDL-cholesterol concentrations, the elevated HDL cholesterol concentration caused by feeding fish protein, compared with soybean protein, was accompanied by lower VLDL triglycerides and parallel higher lipoprotein lipase activity in fish protein-fed rabbits. These results suggest an enhanced assembly of circulating HDL through promoted lipoprotein lipase activity in rabbits fed fish protein. Moreover, dietary proteins and lipids interacted with one another to alter HDL triglycerides and liver cholesterol concentrations. Diet-induced changes in lipoprotein lipase activity were, however, not related to insulinemia, which was unaltered by purified diet feeding. The present results suggest that fish protein may affect HDL metabolism through the modulation of lipoprotein lipase activity in rabbits.

Dietary fish proteins and cholesterol metabolism
Zhang, X. Z. and A. C. Beynen (1990), Monogr Atheroscler 16: 148-52.

Dietary free and esterified cholesterol absorption in cholesterol esterase (bile salt-stimulated lipase) gene-targeted mice
Howles, P. N., C. P. Carter, et al. (1996), J Biol Chem 271(12): 7196-202.
Abstract: The involvement of pancreatic cholesterol esterase (bile salt-stimulated lipase) in cholesterol absorption through the intestine has been controversial. We have addressed this issue by using homologous recombination in embryonic stem cells to produce mice lacking a functional cholesterol esterase gene. Cholesterol esterase knockout mice and their wild type counterparts were fed a bolus dose of 3Hcholesterol and a trace amount of beta-14Csitosterol by gavage. The ratio of the two radiolabels excreted in the feces over a 24-h period was found to be similar in the control and cholesterol esterase-null mice. Similar results were observed when the radiolabeled sterols were supplied in an emulsion with phospholipid and triolein or in lipid vesicles with phosphatidylcholine. Cholesterol absorption results were similar between the control and cholesterol esterase-null mice regardless of whether the animals were fed a low fat diet or a high fat/high cholesterol diet. The rate of 3Hcholesterol appearance in the serum of the gene-targeted mice paralleled that observed in control animals. In contrast to these results, when experiments were performed with 3Hcholesteryl oleate instead of 3Hcholesterol, a higher amount of the 3H radiolabel was found excreted in feces and dramatically less of the radiolabel was detected in the serum of the cholesterol esterase-null mice in comparison with that detected in control animals. Serum cholesterol levels were not significantly different between control and cholesterol esterase-null mice fed either control or an atherogenic diet. These results indicate that cholesterol esterase is responsible for mediating intestinal absorption of cholesteryl esters but does not play a primary role in free cholesterol absorption.

Dietary gamma-linolenic acid lowers blood pressure and alters aortic reactivity and cholesterol metabolism in hypertension
Engler, M. M., M. B. Engler, et al. (1992), J Hypertens 10(10): 1197-204.
Abstract: OBJECTIVE: To determine the effects of dietary gamma-linolenic acid upon blood pressure, aortic reactivity and cholesterol metabolism in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. DESIGN: Randomized parallel-group study. METHODS: SHR and WKY rats were fed a purified diet containing either sesame or borage oil rich in gamma-linolenic acid for 7 weeks. Blood pressure measured by the tail-cuff method and weight were monitored weekly. At the end of the study, intra-arterial pressor responses to norepinephrine and angiotensin II, and reactivity of isolated aortic rings to norepinephrine, angiotensin II, KCl and acetylcholine were determined. Serum cholesterol and triglycerides were measured. Hepatic and intestinal enzymes and receptors of cholesterol metabolism were also measured. RESULTS: Dietary borage oil significantly decreased blood pressure in SHR and WKY rats compared with sesame oil-fed rats. Pressor responses to norepinephrine and angiotensin II, and aortic reactivity to norepinephrine, angiotensin II, KCl and acetylcholine were not significantly different. The borage oil diet increased serum cholesterol levels in WKY rats and hepatic B-hydroxy-3-methylglutaryl coenzyme A reductase in SHR. CONCLUSION: These data indicate that dietary borage oil has a blood pressure lowering effect in hypertensive and normotensive rats. However, the effect cannot be explained by altered sensitivity to humoral and neural vasoconstrictors or changes in cholesterol metabolism. Other mechanisms should be investigated.

Dietary glycemic load assessed by food-frequency questionnaire in relation to plasma high-density-lipoprotein cholesterol and fasting plasma triacylglycerols in postmenopausal women
Liu, S., J. E. Manson, et al. (2001), Am J Clin Nutr 73(3): 560-6.
Abstract: BACKGROUND: In metabolic studies, both greater carbohydrate intakes and higher glycemic indexes (GIs) raise fasting triacylglycerol concentrations. In epidemiologic studies, dietary glycemic load (GL) is positively associated with risk of coronary artery disease and type 2 diabetes. OBJECTIVE: We examined both the physiologic relevance of GI and GL and the ability of dietary questionnaires to measure these variables. DESIGN: In the Nurses' Health Study, we measured plasma triacylglycerol concentrations in fasting blood samples from 185 healthy postmenopausal women and HDL-cholesterol concentrations in an additional 95 nonfasting samples. Dietary carbohydrate, GI, and GL were assessed by use of semiquantitative food-frequency questionnaires. The cross-sectional associations between these 3 variables and plasma triacylglycerol and HDL were assessed, with adjustment for potential confounding factors. RESULTS: For the lowest and highest quintiles of GL, the multivariate-adjusted geometric mean triacylglycerol concentrations were 0.98 and 1.75 mmol/L (87 and 155 mg/dL; P for trend < 0.001). Both overall GI (P for trend = 0.03) and carbohydrate (P for trend < 0.01) contributed independently to the strong positive association between GL and fasting triacylglycerol concentrations. GL was also inversely associated with HDL-cholesterol concentrations. For the lowest and highest quintiles of GL, the mean HDL-cholesterol concentrations were 1.50 and 1.34 micromol/L (58 and 52 mg/dL; P for trend = 0.03). The relation between GL and fasting triacylglycerol concentrations differed significantly by body mass index (BMI; in kg/m(2)) categories (P < 0.001 for interaction). For the lowest to the highest quintiles of GL, the mean triacylglycerol concentrations were 0.92 and 2.24 mmol/L (81 and 198 mg/dL) in women with BMIs > 25 (P for trend < 0.001) and 1.02 and 1.42 mmol/L (90 and 126 mg/dL) in women with BMIs < or = 25 (P for trend < 0.001). CONCLUSION: These data support the physiologic relevance of the GL as a potential risk factor for coronary artery disease in free-living women, particularly those prone to insulin resistance. These findings also document the ability of a semiquantitative food-frequency questionnaire to assess dietary GIs and GLs.

Dietary guidelines with particular emphasis on nutritional intake of fat and cholesterol
Lifshitz, F. (1997), J Am Coll Nutr 16(6): 507-9.

Dietary induction of cholesterol gallstones in the owl monkey: preliminary findings in a new animal model
Pekow, C. A., R. E. Weller, et al. (1995), Lab Anim Sci 45(6): 657-62.
Abstract: The owl monkey (Aotus nancymae) is a primate with a bile acid and biliary lipid profile resembling that of humans. Aotus spp. are among the rare species, including humans, that spontaneously develop cholesterol gallstones. With dietary induction the owl monkey proved a rapid, reliable model of cholesterol cholelithiasis. Six owl monkeys, three of each sex, were fed a diet supplemented with 1.5% cholesterol for 5 weeks. Each week blood samples were drawn for cholesterol determination, and bile samples were obtained by ultrasound-guided percutaneous aspiration of the gallbladder. Weekly ultrasound imaging documented development of gallbladder sludge in all animals, with eventual stone formation in five of six. At necropsy after 5 weeks consuming the diet, all animals had distinct sludging and/or small stones in the gallbladder, correlating with the ultrasound findings. Plasma cholesterol values remained lower in females but increased markedly in some males to > 1,400 mg/dl. Histologic examination revealed mild, diffuse hepatocellular lipidosis and degeneration in four of six animals. Detailed examination of the gallbladder indicated that transhepatic needle punctures induced minimal focal abnormalities, judged inconsequential. In contrast to rodent models commonly in use, owl monkeys have liver and digestive tract anatomy and bile physiology that is similar to that in humans. These similarities give this model the potential to substantively improve understanding of the pathogenesis, treatment, and prevention of human cholesterol gallstones. This model can provide sequential, simultaneous correlation of plasma and biliary lipids, imaging of gallbladder contents, and physiologic processes.

Dietary induction of pancreatic cholesterol esterase: a regulatory cycle for the intestinal absorption of cholesterol
Lopez-Candales, A., J. Grosjlos, et al. (1996), Biochem Cell Biol 74(2): 257-64.
Abstract: Atherosclerosis has a strong dietary basis without a proven molecular mechanism for cholesterol absorption. To investigate the potential role of pancreas in this process and its interaction with the two dietary forms of cholesterol (free and esterified), we undertook to study the role of pancreatic cholesterol esterase in cholesterol absorption. The results showed that (i) cholesterol esters contribute a disproportionately high fraction of absorbed dietary cholesterol, (ii) rates of intestinal cholesterol absorption are related to pancreatic cholesterol esterase activity, (iii) mRNA specific for pancreatic cholesterol esterase is induced 15-fold by dietary sterol esters and 10-fold by free sterol, (iv) the induction of cholesterol esterase mRNA is reversible, and (v) free cholesterol transport into cultured human intestinal cells is enhanced 300% by pancreatic cholesterol esterase. These data implicate pancreatic cholesterol esterase as pivotal in a metabolic loop under positive feedback control for the absorption of dietary cholesterol, whether free or esterified.

Dietary intake as a risk factor for pancreatic cancer in Japan: high cholesterol and low vitamin C diet
Takeyama, Y. (2005), J Gastroenterol 40(3): 324-5.

Dietary intake of Americans reporting adherence to a low cholesterol diet (NHANES II)
Schectman, G., W. P. McKinney, et al. (1990), Am J Public Health 80(6): 698-703.
Abstract: We studied the dietary intake of persons age 18 and over participating in the 1976-80 National Health and Nutrition Examination Survey (NHANES II). We compared the diets of those on a "low cholesterol" diet (dieters, n = 296) with the diets of individuals not following a special diet (non-dieters, n = 10,052). Dietary intakes were assessed by 24-hour recall and food frequency reports and were adjusted for differences in age, sex, race, education, smoking, and socioeconomic status by multivariate statistical techniques. Dieters consumed 16 percent (99% confidence interval(-) -24, -9 fewer calories than non-dieters, and had decreased intake of saturated fat by 25 percent (-34, -15) and cholesterol by 21 percent (-32, -10). However, their intake of vitamin A, thiamine, riboflavin, niacin, calcium, and iron were not significantly different from non-dieters and their ascorbic acid intake was 18 percent (1, 36) higher. The nutrient density (nutrient/1000 kcal) among dieters was increased over non-dieters by 35 percent (-3, 72) for vitamin A, 35 percent (1, 70) for thiamine, 30 percent (-4, 65) for riboflavin, 27 percent (9, 44) for niacin, 60 percent (40, 80) for vitamin C, 14 percent for calcium (-5, 32), and 15 percent for iron (6,25). Compared with non-dieters, dieters consumed 27 percent (9, 45) more poultry and 39 percent (12, 66) more fish, but consumed 30 percent (-44, -16) less eggs and 15 percent (-24, -6) less meat.

Dietary intake of selected fatty acids, cholesterol and carotenoids and estrogen receptor status in premenopausal breast cancer patients
Jakovljevic, J., M. S. Touillaud, et al. (2002), Breast Cancer Res Treat 75(1): 5-14.
Abstract: Although a wealth of research has focused on the influence of diet on breast cancer risk, the relationships between dietary factors and tumor characteristics of breast cancer, like estrogen receptor (ER) status, are not well characterized. In a case-case study, we evaluated self-reported dietary intake for five individual carotenoids, selected fatty acids, and cholesterol 1 year before diagnosis in 34 premenopausal breast cancer patients with ER-negative tumors and 86 premenopausal breast cancer patients with ER-positive tumors from The University of Texas M. D. Anderson Cancer Center. In multivariate logistic regression analysis adjusted for age, body mass index, and ethnicity, high intakes of linoleic acid were associated with more than a threefold greater risk of ER-negative disease than ER-positive disease (odds ratio (OR) = 3.48, 95% confidence interval (CI) = 1.42-8.54), whereas high cholesterol intake was associated with lower risk of ER-negative disease (OR = 0.35, 95% CI = 0.14-0.92). In a model evaluating carotenoids, selected fatty acids, and cholesterol together, the association with high intake of linoleic acid remained statistically significant (OR = 3.96,95% CI = 1.53-10.25), while those for high intake of cholesterol (OR = 0.38, 95% CI = 0.14-1.03) and low intake of cryptoxanthin (OR = 0.43, 95% CI = 0.17-1.06) were of marginal significance. While no striking associations were observed for the intakes of total carotenoids, selected fatty acids, and cholesterol, our analysis revealed an association for the consumption of a specific fatty acid (i.e., linoleic acid), suggesting dietary influence of this factor on ER status in premenopausal breast cancer patients. However, larger studies are needed to clarify the role of micronutrients in ER status in breast cancer.

Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration
Arai, Y., S. Watanabe, et al. (2000), J Nutr 130(9): 2243-50.
Abstract: The intake of flavonols, flavones and isoflavones by Japanese women was calculated from our food-phytochemical composition table. The relationship between intake of these phytochemicals and various anthropometric and blood chemistry data was analyzed in a cross-sectional study. The subjects were 115 women volunteers, aged 29-78 y, living in the northern part of Japan. Each subject completed a 3-d dietary record and received a health check up, including urine and blood sampling for biochemical analysis. Total mean intakes of flavonoids (sum of flavonols and flavones) and isoflavones were 16.7 and 47.2 mg/d, respectively. The major source of flavonoids was onions (45.9%) and that of isoflavones was tofu (37.0%). Total intake of isoflavones exceeded that of other dietary antioxidants, such as flavonoids, carotenoids (3.5 mg/d) and vitamin E (8.2 mg/d), and was approximately one half of the vitamin C intake (109 mg/d). The total intake of flavonoids was inversely correlated with the plasma total cholesterol concentration (TC) (r = -0.236, P: < 0.05) and plasma LDL cholesterol concentration (LDL-C) (r = -0.220, P: < 0.05), after the adjustment for age, body mass index and total energy intake. As a single component, quercetin was inversely correlated with both TC (r = -0.261, P: < 0.01) and LDL-C (r = -0. 263, P: < 0.01). Among Japanese, flavonoid and isoflavone intake is the main component among nonnutrient phytochemicals with antioxidant potential in the diet. These results suggest that a high consumption of both flavonoids and isoflavones by Japanese women may contribute to their low incidence of coronary heart disease compared with women in other countries.

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