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PubMed1990

Postprandial levels of prolactin and gut hormones in breast cancer patients: association with stage of disease, but not dietary fat.

Previous studies of the relationship between dietary fat and breast cancer have produced conflicting results and have provided no definitive evidence of a mechanistic link between fat and breast tumorigenesis. We conducted a study to compare postprandial levels of prolactin (Prl), a hormone suspected of promoting the growth of some human breast cancer, and several gut hormones, i.e., gastrin (Gs), vasoactive intestinal polypeptide (VIP), neurotensin (Nt), and cholecystokinin (CCK), following high- and low-fat isocaloric test meals. Data were obtained in the posttreatment period from 13 patients with breast cancer (nine stage I and four stage II), who were disease free clinically, and nine healthy controls. Subjects admitted to the research unit on 2 days were given the high-fat meal on day 1 and the low-fat meal on day 2. Blood samples were drawn before (i.e., fasting) and after test meal consumption. All hormone analyses were performed by radioimmunoassay. Results indicated a significant rise in postprandial Prl levels for stage II patients, but not for stage I patients or the controls. Postprandial Gs levels were also elevated, whereas VIP levels were markedly reduced in patients versus controls; these differences were most marked in stage II patients. No significant intergroup differences were noted in postprandial levels of Nt and CCK. Hormone levels of patients and controls did not differ between the test meal situations, which indicated that some other component of the test meals might have been responsible for altered Prl and Gs levels. The differences observed between the stage I and II patients indicated that diet may influence the aggressiveness of tumor behavior and development through alterations in postprandial hormone release.

Breast Neoplasms↗

PubMed2001

The cholesterolaemic effects of dietary fats in cholesteryl ester transfer protein transgenic mice.

In order to investigate the role of cholesteryl ester transfer protein (CETP) in the cholesterolaemic response to dietary fats, we analysed plasma lipid profiles of CETP-transgenic and control C57BL/6 mice fed standard chow (AIN-93G; AIN), a low-fat diet, and diets high in butter (saturated fatty acids; SFA), high-oleic acid safflower oil (monounsaturated fatty acids; MUFA), and safflower oil (polyunsaturated fatty acids; PUFA) for 5 weeks. Each group contained four or five mice. There were significant diet and dietxgenotype effects on plasma total cholesterol (TC; and respectively), liver TC ( and respectively), and esterified cholesterol (EC; and respectively); diet effects on plasma triacylglycerol liver free cholesterol and body weight a genotype effect on body-weight gain and a dietxgenotype effect on energy intake In transgenic mice the SFA diet caused significantly higher plasma TC than the PUFA diet In control mice MUFA and PUFA diets, but not the SFA diet, caused significantly higher plasma TC than the low-fat and AIN diets Transgenic mice fed PUFA had lower plasma TC while transgenic mice fed MUFA had lower LDL+VLDL-cholesterol than controls in the same dietary groups. Transgenic mice fed MUFA and PUFA diets also had significantly higher liver TC and respectively) and EC and respectively) than controls fed the same diets. In the present study we showed that: (1) CETP transgenic mice had a cholesterolaemic response to dietary fats similar to that in human subjects; (2) CETP transgenic mice fed PUFA showed significantly lower plasma TC, while those fed MUFA had lower LDL+VLDL-cholesterol than controls; (3) hepatic accumulation of cholesterol, possibly resulting from the combination of the enhanced cholesteryl ester transfer to apolipoprotein B-containing lipoproteins and increased hepatic uptake of cholesterol, may contribute to the cholesterol-lowering effect of MUFA and PUFA in CETP-transgenic mice; (4) CETP may play a role in appetite and/or energy regulation.

Animal Nutritional Physiological Phenomena↗

PubMed1992

Effect of dietary fats on some membrane-bound enzyme activities, membrane lipid composition and fatty acid profiles of rat heart sarcolemma.

The effect of various dietary fats on membrane lipid composition, fatty acid profiles and membrane-bound enzyme activities of rat cardiac sarcolemma was assessed. Four groups of male weanling Charles Foster Young rats were fed diets containing 20% of groundnut, coconut, safflower or mustard oil for 16 weeks. Cardiac sarcolemma was prepared from each group and the activities of Na+, K(+)-ATPase, 5'-nucleotidase, Ca(2+)-ATPase and acetylcholinesterase were examined. ATPase activities were similar in all groups except the one fed coconut oil, which had the highest activities. Acetylcholinesterase activity was also similar in all the groups, however, it was significantly higher in the group fed mustard oil. No significant changes were observed among the groups in 5'-nucleotidase activity, in the cholesterol-to-phospholipid molar ratio and in sialic acid content. The coconut, safflower and mustard oil diets significantly increased cholesterol and phospholipid contents and the lipid-to-protein ratio of cardiac sarcolemma as compared to feeding the groundnut oil diet. The fatty acid composition of membrane lipids was quite different among the various groups, reflecting the type of dietary fat given. The total unsaturated-to-saturated fatty acid ratio was not different among the various groups; however, the levels of some major fatty acids such as palmitic (16:0), oleic (18:1) and linoleic (18:2) acids were significantly different. Cardiac sarcolemma of the group fed safflower oil had the highest polyunsaturated fatty acid content. The results suggest that dietary fats induce changes not only in the fatty acid composition of the component lipids but also in the activities of sarcolemmal enzymes involved in the regulation of cardiac function.

Animals↗

PubMed1999

Difficulties in changing the diet in relation to dietary fat intake among patients with coronary heart disease.

OBJECTIVE: To study barriers in following nutritional advice among coronary heart disease patients in relation to dietary fat intake. DESIGN: A cross-sectional study using 4-day food records and a questionnaire with regard to barriers to or difficulties in following dietary advice. SUBJECTS: Altogether, 362 male subjects with coronary heart disease from two separate patient populations (91 + 271) were included in the study, with the mean age of 50 years and 60 years, respectively. The patients were classified into low (< or = 30 E%) or high (> 30 E%) fat intake groups. The patients with low dietary fat intake obtained on an average 10 E% less energy from fat as compared to the high dietary fat intake group. RESULTS: Overall, most patients with coronary heart disease reported difficulties in following nutritional advice when eating in social situations. Patients with high dietary fat intake reported more frequently than patients with low fat intake that they eat like other people without thinking about what they eat. On the other hand, there were no differences between the high and low fat intake groups in the barriers: eating at work, food price, shopping, taste or knowledge of nutrition. CONCLUSIONS: Our results suggest that the sensitivity to social influence is an important factor explaining noncompliance with dietary advice among patients with high dietary fat intake.

Coronary Disease↗

PubMed1983

Hormones and dietary fat as promoters in mammary carcinogenesis.

Hormones, particularly ovarian steroids and pituitary prolactin, promote mammary carcinogenesis in rats treated with a carcinogen. Hormones also play a critical role during the initiation process as demonstrated by mammary carcinogenesis in ovariectomized rats. A diet high in fat content, especially polyunsaturated fat, promotes mammary tumorigenesis when it is fed to carcinogen-treated rats for a prolonged period of time. Although a high fat diet is not essential for neoplastic transformation of the mammary cells, its effect on initiation is demonstrated when it is fed to rats for a long duration. Thus, both hormones and high dietary fat play a dual function in mammary carcinogenesis. There are indications that dietary fat may modulate endocrine activities, but a relationship between dietary fat and endocrine function remains to be conclusively demonstrated.

Animals↗

PubMed1996

Estimating the effect of dietary fat on the risk of lung cancer in nonsmoking women.

In 1992, approximately 13 000 lung cancers occurred in nonsmoking U.S. women but the cause of these highly fatal tumors is not well understood. As the rate of smoking declines in many developed countries, the interest in identifying lung cancer risk factors other than tobacco smoking is increasing. A population-based, case-control study of incident lung cancer among nonsmoking women in Missouri was conducted between 1986 and 1992 to assess the effect of a comprehensive list of potential risk factors. Dietary information on 429 case subjects and 1021 control subjects was obtained by personal interview, or next-of-kin interviews (36% and 64%, respectively) and the relationship of diet to lung cancer risk is the focus of this investigation. Odds ratios and population attributable risks (PAR) for dietary fat and dietary saturated fat were computed among lifetime nonsmokers and long-term ex-smokers. The mean age at lung cancer diagnosis was 71 years old, and nearly 50% of the lung cancers were histologically confirmed adenocarcinomas. Dietary intake of saturated fat was the leading identified cause of lung cancer among lifetime nonsmokers and former smokers in Missouri. The etiologic link between dietary saturated fat and lung cancer has not been examined in many other studies and the studies published to date are not completely consistent with the hypothesis so a cautious interpretation of the population attributable risks for these exposures is warranted. Nonetheless, a growing number of studies arising from around the world purport to show a link between fat, saturated fat and/or cholesterol or food groups containing relatively high amounts of these macronutrients (i.e. dairy products, eggs and/or red meat consumption) and lung cancer, and these recent studies add support to this hypothesis. If the results from Missouri are valid and applicable to other Americans, 23% of lung cancer cases among lifetime nonsmokers in the United States could be prevented if the saturated fat consumption of the upper half of saturated fat intake continuum could be reduced to the level consumed by the lower half. Even greater reductions in risk could be achieved if saturated fat consumption were reduced to even lower levels (i.e. 20th percentile of consumption as shown in this paper). However, additional etiologic research and evaluation is needed before specific dietary recommendations concerning fat and saturated fat and lung cancer prevention can be made.

Adult↗

PubMed1977

Effect of dietary fat level on growth and lipogenesis in the colostrum deprived neonatal pig.

Thirty male neonatal pigs were obtained by cesarean section and randomly allotted from littermate groups to three diets containing 2%, 17%, and 32% fat on a dry matter basis. Butterfat was used to replace glucose in the isoenergetic liquid, semipurified diets. Each pig was placed in a sterile isolator and fed ad libitum five times daily. After 14 days, pigs were weighed, killed, and samples of liver and backfat were obtained. The carcass of each pig was ground and samples obtained for determination of total body fat and protein. An increase in the level of dietary fat resulted in a significant increase in 14 day weight gain and a tendency for improved feed efficiency. These results demonstrate not only that the neonatal pig can utilize semipurified liquid diets high in butterfat content, but also that energy from butterfat appears to be used as efficiently as energy from glucose from growth purposes. Increasing dietary fat level decreased the activity of fatty acid synthetase and citrate cleavage enzyme in adipose tissue and liver, and decreased the activity of malic enzyme in adipose tissue. The specific activities of these three enzymes were higher in adipose tissue than in liver.

Animals↗

PubMed1983

Faecal excretion of bile acids and neutral steroids on diets differing in type and amount of dietary fat in young healthy persons.

The effect of different amounts and types of dietary fat on faecal steroid excretion in healthy volunteers was examined. In the first experiment with sixty volunteers four diets which differed in type and amount of dietary fat only were compared during a test-period of 5 weeks. Faeces were collected during 7 days before and at the end of the test period and analysed individually. In the second experiment with thirty-five volunteers, a low fat diet containing 22% of energy as total fat (4% as polyunsaturated fatty acids) was compared with a moderate fat diet (30% of energy as total fat; 11% as polyunsaturated fatty acids) during 13 weeks. Faeces were collected during the first 7 days of the test period and during 7 consecutive days near the end of the test period and pooled per dietary group. Excretion of faecal neutral steroids and bile acids was not significantly influenced by amounts of total fat ranging from 22% to 40% of daily energy or by differences in polyunsaturated to saturated fatty acids ratio from 0 . 2 to 1 . 7. The only exception was the excretion of bile acids in the second experiment which was 0 . 19 mmol/24 h (75 mg/24 h) higher on the low fat diet than on the moderate fat, high polyunsaturated fat diet (P less than 0 . 01).

Adult↗

PubMed1997

Effect of dietary fat reduction and increased aerobic exercise on cardiovascular risk factors.

1. The combined effect of dietary fat reduction and increased aerobic exercise on coronary heart disease (CHD) risk factors was investigated in healthy, normolipidaemic, normotensive, sedentary individuals. 2. After a baseline period of 2 weeks, 21 subjects were randomly allocated to one of two intervention groups (low fat exercise (LFEX) or low fat control (LFC)) for 8 weeks. Both groups were counselled to reduce their dietary fat intake to 20-25% energy from fat. The LFEX group was also required to commence an aerobic exercise programme (4 x 45 min per week). 3. In both groups, the falls in total cholesterol seen at week 4 were not maintained at the end of the study; however, the LFEX group maintained a fall in low-density lipoprotein (LDL) of 0.21 +/- 0.11 mmol/L. At the end of the study, the LFC group experienced a fall in high-density lipoprotein (HDL)-cholesterol of 0.16 +/- 0.05 mmol/L, due to a 0.19 +/- 0.07 mmol/L fall in the HDL2 subfraction. The LFEX group experienced no change in HDL (-0.09 +/- 0.06 mmol/L) or HDL2 (-0.09 +/- 0.05 mmol/L). 4. At the end of the study the LFEX and LFC groups experienced a 7 +/- 3 and 5 +/- 1 mmHg fall in systolic blood pressure, respectively, while the LFEX group also observed a 4 +/- 2 mmHg fall in diastolic blood pressure. 5. The benefits of a low-fat diet combined with aerobic exercise include a reduction in LDL and blood pressure, while maintaining HDL through the HDL2 subfraction.

Adult↗

PubMed1986

Effects of dietary fat on mammary development relative to age and hormones in BALB/c mice.

Earlier studies reported that mammary ducts grew faster if the 10% fat in the diet was composed of oils containing polyunsaturated fatty acids (corn oil: CO) compared to hydrogenated cottonseed oil (HCTO), which is devoid of such fatty acids. These experiments were primarily carried out in immature mice and left unanswered questions regarding the effects of dietary fats on more differentiated stages of mammary development. The use of transplanted ducts permitted the study of mammary growth rates in adult mice. If the diet was started when the animals were adults, there was no difference in the growth rate of those fed HCTO diet compared to those fed CO diet. However, when the diets were fed to immature mice, the mammary gland grew slower in mice fed the HCTO diet, confirming our earlier observations. The HCTO and CO diets caused no difference in the growth rate or morphology of fine ducts and alveoli that developed during pregnancy. Furthermore, no differences were seen in female mice following 6 weeks of progesterone administration begun at 3 weeks of age. Experiments that used male mice to examine the initial stages of mammary duct growth also showed that the effect of dietary fat was not observed when estrogen (E) or E and progesterone (P) were injected. In addition, there was no effect of dietary fat in ovariectomized 3-week-old females when any dose of E was administered from 0.01 to 1 microgram/day. Examination of the ovaries from mice fed either HCTO or CO diets from 3 to 9 weeks or 3 to 13 weeks of age showed that mice fed HCTO diet did not develop corpora lutea, while those fed CO diet had normal appearing ovaries. The HCTO diet inhibits normal maturation of the follicle and corpus luteum formation. We conclude that the effect of the dietary fat on the developing mouse is on the maturation of the ovary and subsequently on mammary growth.

Age Factors↗

PubMed2005

Substitution of high monounsaturated fatty acid avocado for mixed dietary fats during an energy-restricted diet: effects on weight loss, serum lipids, fibrinogen, and vascular function.

OBJECTIVE: First, we wanted to dispel the myth that avocados are fattening and therefore should be avoided in energy-restricted diets. Second, we examined the effects of avocados, a rich source of monounsaturated fatty acids, as part of an energy-restricted diet on weight loss, serum lipids, fibrinogen, and vascular function in overweight and obese subjects. METHODS: Sixty-one free-living volunteers (13 men and 48 women), with body mass index of 32 +/- 3.9 kg/m(2) (mean +/- standard deviation) participated in this randomized, controlled, parallel study. Subjects were paired and randomly assigned to one of two groups. The experimental group consumed 200 g/d of avocado (30.6 g of fat), which substituted for 30 g of other mixed dietary fats such as margarine or oil, and the control group excluded avocado from their energy-restricted diet for 6 wk. Seven-day isoenergetic menus were planned according to mean energy requirements of both sexes to provide total energy intakes consisting of 30% fat, 55% carbohydrates, and 15% protein. Anthropometric measurements, physical activity, blood pressure, and arterial compliance were measured with standard methods at the beginning and end of the intervention. Fasting blood samples were drawn at the beginning and end of the intervention. RESULTS: Fifty-five subjects completed the study. The compliance rate to avocado intake in the experimental group was 94.6%. The percentage of plasma oleic acid increased significantly with the consumption of avocado in the experimental group, whereas a decrease was seen in the percentage of myristic acid from baseline to the end of the intervention in both groups but was significant only in the experimental group. Anthropometric measurements (body mass, body mass index, and percentage of body fat) decreased significantly in both groups during the study (P < 0.001), and the change was similar in both groups. Serum lipid concentrations (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triacylglycerols), fibrinogen, blood pressure, and arterial compliance did not change significantly within or between groups. CONCLUSION: The consumption of 200 g/d of avocado within an energy-restricted diet does not compromise weight loss when substituted for 30 g of mixed dietary fat. Serum lipid concentrations, plasma fibrinogen, arterial compliance, and systolic and diastolic blood pressures were not affected by weight loss or avocado intake.

Adult↗

PubMed1992

Postnatal dietary fat influences mRNAS involved in myelination.

The synthesis and composition of myelin in the developing mouse central nervous system can be influenced by diet. Postnatal maternal fat intake altered nursing pup brain and liver fatty acid composition. Peak (day 21) proteolipid protein (PLP) and myelin basic protein (MBP) mRNA levels were reduced when pups were nursed by mothers fed a fat-free or 5% coconut oil diet. This effect was reversed by feeding a corn oil based diet. Oleic acid accounts for about 30% of myelin fatty acids. mRNA levels of stearoyl CoA desaturase (SCD), the rate-limiting step in oleic acid synthesis, increase in neonatal mouse brain. Postnatal maternal fat-free feeding reduced day 21 pup brain SCD and LDL receptor, but not apolipoprotein (Apo E) E mRNA levels. In contrast to brain, nursing pup hepatic SCD mRNA levels were induced, LDL receptor mRNA levels were unaffected and Apo E mRNA levels were reduced by postnatal maternal fat-free feeding. Myelin-specific mRNA levels are developmentally regulated and influenced by dietary fat. Neonatal brain SCD and LDL receptor mRNA levels are also altered by neonatal fat intake. The neonatal response to dietary fat is tissue-specific at the mRNA level.

Animals↗

PubMed1979

Effect of dietary fat and vitamin E on mouse lung lipids.

To examine the effect of dietary fat on lung lipids, male weanling mice (CD-1 strain) were fed purified diets containing 5% stripped lard or corn oil and kept in chambers supplied with air filtered free of airborne bacteria. Vitamin E was fed at 0, 10.5 or 105 mg dl-alpha-tocopheryl acetate/kg diet. Dietary fat and vitamin E (0 or 10.5 mg/kg) had no significant effects on the lung levels of triacylglycerol (TG) or phospholipid (PL) molecular species through 4 weeks of intake. Alterations in lung fatty acid composition were followed through 6 weeks of intake at 0, 10.5 and 105 mg vitamin E/kg diet. Vitamin E, at all levels of supplementation, had no significant effect on mouse lung fatty acid composition. Saturated fatty acids of the lung also showed little alteration by diet, but feeding the lard diet significantly elevated oleic and palmitoleic acids. In mice fed the corn oil diet the levels of linoleic acid (18:2) were twice those of lard-fed mice, and arachidonic acid (20:4) was elevated by 15.8%. The diet elevated the mean peroxidizability index (PI) on lung tissue in corn oil-fed mice.

Animals↗

PubMed2005

Effects of the type of dietary fat on acetylcholine-evoked amylase secretion and calcium mobilization in isolated rat pancreatic acinar cells.

Olive oil is a major component of the Mediterranean diet, and its role in human health is being actively debated. This study aimed to clarify the mechanism of pancreatic adaptation to dietary fat. For this purpose, we examined whether dietary-induced modification of pancreatic membranes affects acinar cell function in response to the secretagogue acetylcholine (ACh). Weaning male Wistar rats were assigned to one of two experimental groups and fed for 8 weeks with a commercial chow (C) or a semisynthetic diet containing virgin olive oil as dietary fat (OO). The fatty acid composition of pancreatic plasma membranes was determined by gas-liquid chromatography. For assessment of secretory function, viable acini were incubated with ACh and amylase of supernatant was further assayed with a substrate reagent. Changes in cytosolic Ca(2+) concentration in response to ACh were measured by fura-2 AM fluorimetry. Compared to C rats, pancreatic cell membranes of OO rats had a higher level of monounsaturated fatty acids and a lower level of both saturated and polyunsaturated fatty acids, thus, reflecting the type of dietary fat given. Net amylase secretion in response to ACh was greatly enhanced after OO feeding, although this was not paralleled by enhancement of ACh-evoked Ca(2+) peak increases. In conclusion, chronic intake of diets that differ in the fat type influences not only the fatty acid composition of rat pancreatic membranes but also the responsiveness of acinar cells to ACh. This mechanism may be, at least in part, responsible for the adaptation of the exocrine pancreas to the type of fat available.

Acetylcholine↗

PubMed2001

Dietary fats and cancer.

The present review addresses the evidence for a possible link between dietary fat and cancer. International comparisons suggest that a high-fat diet may increase cancer risk, and this hypothesis is supported by animal experiments. However, epidemiological studies within populations show little or inconsistent associations. Taken together, the available evidence for a relation between dietary fat and cancer is weak.

Animals↗

PubMed1991

Influence of dietary fat on nutritive utilization of protein in intestinally resected rats.

The effects of different types of dietary fat on the digestive and metabolic utilization of protein were studied in rats with 50% resection of the distal small intestine and in sham-operated controls one month after surgery. The digestive utilization of protein was not significantly affected in intact animals when olive oil was replaced by butter as the dietary source of fat. In resected rats given either type of diet the apparent digestibility coefficient of protein declined significantly in comparison to intact controls. Intestinal resection decreased the retention of nitrogen significantly in rats given olive oil. The replacement of 2/3 of the dietary supply of olive oil with 1/3 medium chain triglycerides and 1/3 sunflower seed oil improved the metabolic utilization of protein in comparison to resected rats fed olive oil or butter as the only source of dietary fat. However, the addition of ursodeoxycholic acid to the diet containing equal parts of olive oil, medium chain triglycerides and sunflower seed oil failed to improve the metabolic utilization of protein in comparison to that seen in rats given olive oil only. Serum concentrations of total protein, urea and creatinine, albeit with slight changes in the first, remained within normal limits. Despite the lower retention of nitrogen in resected rats, these animals maintained homeostasis without resorting to muscular protein.

Animals↗

PubMed1998

Relationships between dietary fat, body fat, and serum lipid profile in prepubertal children.

OBJECTIVE: The purpose of the study was to test the hypothesis that dietary fat components were associated with the serum lipid profile independent of ethnicity, body fat, and fat distribution in prepubertal children. RESEARCH METHODS AND PROCEDURES: Sixty-six children (45 African American and 21 Caucasian), aged from 4 to 10 years, were recruited into the study. Dietary total fat, saturated fat, monounsaturated fat, and polyunsaturated fat were estimated by averaging two 24-hour diet recalls. Fasting serum triacylglycerol, total cholesterol, and high-density lipoprotein cholesterol were analyzed, and low-density lipoprotein cholesterol (LDL-C) was calculated by the method of Friedewald. Body composition and fat distribution were measured by dual energy X-ray absorptiometry and computed tomography. RESULTS: Children in both ethnic groups tended to overreport their dietary intake relative to total energy expenditure by 18%. African American children consumed more energy from total fat (35.3% vs. 31.5%, p<0.05), saturated fat (13.7% vs 12.2%, p<0.05), protein (16.4% vs. 13.2%, p=0.02), and less from carbohydrate (48% vs. 57.1%, p<0.01) than Caucasian children. There was no significant correlation between dietary fat and either serum lipids or body fat indices after adjusting for nonfat energy intake and total lean tissue mass. Total body fat (r=0.32), subcutaneous abdominal adipose tissue (r=0.39), and intra-abdominal adipose tissue (r=0.42) were positively related to serum triacylglycerol; these associations remained significant in a multiple linear regression model in which body fat indices were adjusted for ethnicity, total lean tissue, dietary total fat, and nonfat intake. DISCUSSION: Our results do not support a link between dietary fat and serum lipids; instead, our data suggest that body fat may play a more important role than dietary fat in the course of cardiovascular disease development in prepubertal children.

Adipose Tissue↗

PubMed1998

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation.

Previous studies have shown that the A to G transition occurring at position -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals were prepared and consumed at the study sites. Lipoproteins were measured at the end of each diet period. The allele frequency for the A allele was 0.13. Subjects carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantly greater plasma total (P = 0.003) and LDL-C decreases (P = 0.001) in G/A women (-1.62 and -1.32 mmol/l, respectively) than in G/G subjects (-0.87 and -0.74 mmol/l for plasma and LDL-C, respectively). Multiple regression analysis demonstrated that in women, the variability in LDL-C response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the major determinant of this response was smoking (21.4%). In conclusion, the G/A polymorphism appears to have a small but significant effect on plasma LDL-C responsiveness to changes in dietary fat saturation specially in women.

Adult↗