High Polyunsaturated Fat Diet Research Articles

Influence of dietary fat on the promotion of diethylnitrosamine-induced hepatocarcinogenesis in female rats.

The effect of varying the amount and type of dietary fat on the promotion of gamma-glutamyltranspeptidase (GGT)-positive foci and hepatocarcinomas in female rats was studied. In the first study, two-thirds of the rats were first intubated with diethylnitrosamine (DEN, 10 mg/kg) 20 hr after partial hepatectomy; 1 week later, rats were fed one of three purified diets (a low-fat diet similar to the AIN-76 diet, a high saturated fat diet, or a high polyunsaturated fat diet) with or without 0.05% phenobarbital in the diet for 10 months. Increasing the fat level of the diet did not increase the number of GGT-positive foci arising spontaneously or induced by DEN alone. When phenobarbital was present in the diet, feeding the high polyunsaturated fat diet slightly increased the number of GGT-positive foci and the incidence of tumors. The low-fat diet, however, increased the incidence of fatty liver. We therefore reexamined the effect of diet on promotion by phenobarbital, using an additional low-fat diet with cornstarch rather than sucrose as the carbohydrate source. In this experiment, both high-fat diets slightly enhanced the induction of GGT-positive foci; the carbohydrate source had no effect. The incidence of tumors was not affected by diet in this experiment, but the incidence of fatty liver was again enhanced by feeding a diet high in sucrose. We conclude that increasing the fat level of the diet does not promote the development of DEN-initiated GGT-positive foci or carcinomas in female rats. Increasing the dietary fat level, however, may enhance promotion of liver foci by phenobarbital. Finally, increasing the sucrose content of the diet increases the incidence of fatty liver.

Effects of diabetes on the dietary lipid alteration of R3230AC mammary carcinoma growth in rats.

To examine the effects of diabetes on the alteration of R3230AC mammary tumor growth by dietary lipids, streptozotocin-induced diabetic rats were fed diets containing either 20% corn oil (HF), 20% hydrogenated cottonseed oil (HCTO), or 0% fat (FF). Diabetes resulted in lower tumor weights and body weights compared to those of intact animals. Unlike intact animals, relative tumor weight (g tumor/100 g body wt) of diabetic animals fed HF diets were not greater than those from animals fed FF diets. However, in these diabetic animals, growth of tumors in HF-fed rats was faster than in HCTO-fed rats, a relationship similar to that seen in intact rats. A surprising result was the almost twofold greater tumor weight/100 g body wt observed in diabetic FF-fed rats compared to those fed HCTO diets. Insulin binding to tumor plasma membranes from diabetic animals was higher in rats fed HF diets than in rats fed FF or HCTO diets. The tumor plasma membrane fatty acid composition of diabetic rats fed FF and HCTO diets displayed higher proportions of the monounsaturates (C18:1 and C21:1) and decreased amounts of the polyunsaturates (C18:2 and C20:4) compared to the levels observed in membranes from HF-fed rats. These results, as well as the insulin binding data, were similar to those obtained using intact animals. The data presented here indicate that the more rapid growth of the R3230AC mammary tumor seen in intact animals fed high polyunsaturated fat vs fat-free diets did not occur in diabetic animals.

Coffee and Methylxanthines and Breast Cancer: A Case-Control Study<xref ref-type="fn" rid="FN2">2</xref>

A dietary case-control study based on 818 newly diagnosed breast cancer (BC) patients was conducted in Israel between 1975 and 1978. The role of coffee and total methylxanthine intake from coffee, tea, cola, chocolate, and cocoa drinks was evaluated in the BC patients as compared to that in two matched control populations [surgical controls (SC) and neighborhood controls (NC)]. Because it has been suggested that caffeine enhances mammary carcinogenesis in rats fed high polyunsaturated fat diets, analysis was done also in relation to fat consumption. When comparison was done to both matched control groups, a nonsignificant negative association was found between consumption of cups of coffee and BC (odds ratios of greater than or equal to 4 cups of coffee/day vs. less than or equal to 1 per week = 0.6 for BC/NC and 0.7 for BC/SC). This association was observed in all 3 ethnic subgroups studied. The pattern was stronger among the high-fat consumers after controlling for several hormonal confounding factors (two-tailed P-value for linear trend = 0.06 for SC and P = 0.05 for NC). In addition, when the consumption of methylxanthine of BC patients was compared to that of benign breast patients, adjusted by age and ethnic group, a diminished risk was found (odds ratio for BC of the highest level of methylxanthine vs. lowest level = 0.59).

Mechanism of growth enhancement of 7,12-dimethylbenz[a]-anthracene-induced mammary tumors in rats given high polyunsaturated fat diet.

The mechanism of growth enhancement of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors by high fat diet was investigated in 169 female Sprague-Dawley rats fed a semisynthetic diet containing 0, 8 or 40% corn oil by weight. The animals, most of which were intubated with 10 mg of DMBA twice during the 8th week of age, were fed an unsupplemented or fat-supplemented diet for 2 months from the 12th to the 21st week of age and finally killed during the 21st week of age. Compared to the rats fed a fat-free diet, a significantly increased yield of mammary adenocarcinoma with a shorter latency was observed in the rats fed a 40% corn oil diet. DNA synthesis of the biopsied mammary tumors more than 1 month after diet switch-over was estimated in terms of the rate of [3H]thymidine incorporation into the tissue. Significantly higher DNA synthesis of the mammary tumors biopsied from proestrous hosts was found, as compared with the tumors in similar hosts at other stages of the estrous cycle. The greatest enhancement of DNA synthesis in small and rapidly growing tumors was observed in the 40% corn oil diet group. Feeding with 40% corn oil diet always resulted in elevation of the weight percentage of linoleic acid in both simple lipids and phospholipids of the mammary tumors. These data indicate that the effects of dietary fat on mammary tumor growth might be mediated by the enhancement of tumor response to certain hormones, and that the enhanced responsiveness of tumors was associated with increased linoleic acid in tumor lipids.

The effect of variable fat diets and cholesterol-lowering drugs on antithrombin III levels in hyperlipoproteinemic and normal subjects

Functional and immunological Antithrombin III (AT III) levels were studied in normal and hyperlipoproteinemic subjects undergoing crossover therapeutic trials of either diets or hypocholesterolemic drugs. The diet trial subjects, 7 hyperlipoproteinemics and 15 normals, were randomly assigned to crossover between a high saturated fat diet (P/S ratio 1:8) and a high polyunsaturated fat diet (P/S ratio 4:1) for periods of 6–8 weeks, preceded by a baseline period on regular American diet (P/S ratio 1:1). For the drug trials, 33 type II A or B hyperlipoproteinemics were treated in random and double-blind fashion with Colestipol (20 gm/day) or Probucol (1 gm/day) or both, for periods of 3 months, preceded by a double placebo period. Mean low density lipoprotein cholesterol levels were significantly different (p<0.001) between high saturated and high polyunsaturated fat diets (157 ± 37 mg/dl vs 137 ± 31 mg/dl respectively, mean ± S.D.) and between placebo and drug treatment periods (226 ± 51 mg/dl vs 183 ± 44 mg/dl respectively, mean ± S.D.). There was no difference in basal functional or immunological AT III levels between normals and hyperlipoproteinemics. AT III levels did not correlate significantly with cholesterol or triglyceride levels and remained unchanged despite significant reductions in serum cholesterol related to the diet and drug therapy. There appears to be no significant association between baseline or post treatment serum cholesterol levels and functional or immunological AT III. Thus, changes in AT III are unlikely to play a role in the link between hypercholesterolemia and thrombosis.

Dietary vitamin E intake and mammary carcinogenesis in rats.

Using the dimethylbenz[a]anthracene-induced mammary tumor model, the present study demonstrated that a low vitamin E intake (7.5 mg/kg of diet) had minimal effect on carcinoma development in rats fed a 5% stripped corn oil diet, but resulted in a marked enhancement in tumor incidence and yield in those rats fed a 25% stripped corn oil ration. Control animals in this experiment received an adequate supply of vitamin E (30 mg/kg as DL-alpha-tocopheryl acetate). Thus, the effect of vitamin E deficiency on mammary carcinogenesis was accentuated in rats maintained on a high polyunsaturated fat diet, an observation similar to that of selenium deficiency which was reported by the author in a previous publication. In view of the biochemical interaction between vitamin E and selenium as endogenous antioxidants, another experiment was conducted to determine whether supranutritional supplementation of vitamin E (1000 mg/kg) was able to block the enhancement in mammary tumorigenesis due to selenium deprivation. Results of this experiment indicated that vitamin E excess failed to overcome the augmented tumor yield in selenium-deficient rats, nor did it provide any protection in rats that received an adequate supply of selenium. In summary, vitamin E deficiency may increase the risk of neoplastic development, especially when coupled with a high polyunsaturated fat intake; however, a high vitamin E supplementation does not seem to have any prophylactic effect on tumorigenesis by itself.

Effects of butylated hydroxytoluene and acetylaminofluorene on NADPH-cytochrome P-450 reductase activity in rat liver microsomes

Cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity were measured in liver microsomes prepared from male weanling rats fed low-fat, high-saturated fat or high-polyunsaturated fat diets with or without butylated hydroxytoluene (BHT) and 2-acetylaminofluorene (AAF). The inclusion of BHT and/or AAF in the diets consistently produced marked decreases in cytochrome P-450 reductase activity, regardless of the amount and type of dietary fat. In contrast, there was no inhibition of reductase activity when the compounds were added in vitro to liver microsomes.

The effect of a high cholesterol and saturated fat diet on serum high-density lipoprotein-cholesterol, apoprotein A-I, and apoprotein E levels in normolipidemic humans

The effects of a high cholesterol, high saturated fat diet on serum high density lipoprotein cholesterol, apo A-I, and apo E levels were studied in six normolipidemic subjects. The study was done on an outpatient basis and mixed natural foods normally consumed by humans were used. When compared with a low cholesterol (98 mg/day) high polyunsaturated fat (P/S ratio 1.6) diet, the high cholesterol (1021 mg/day), high saturated fat (P/S ratio 0.4) diet increased serum cholesterol (23%) by raising the cholesterol concentration in very low-density lipoproteins (59%), low-density lipoproteins (15%), and high-density lipoproteins (30%). The low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol ratio fell significantly from 1.78 to 1.58. The increased high-density lipoprotein-cholesterol was associated with an elevation of serum apo A-I but not apo E. Serum triglycerides did not change significantly.

The effect of oral calcium carbonate administration on serum lipoproteins of children with familial hypercholesterolaemia (type II-A)

The effect of oral calcium carbonate on serum lipoprotein concentrations was tested in 50 children with familial hypercholesterolemia (type II-A) consuming a low cholesterol high polyunsaturated fat diet, using a cross-over design versus a placebo. Cholesterol was measured in serum and in the individual lipoprotein density classes. Serum apolipoprotein B (the protein moiety of low density lipoprotein) and apolipoprotein A-I (the main protein of high density lipoprotein) were measured by specific immunoassays. Calcium carbonate treatment induced only a slight increase in serum apolipoprotein A-I (+ 4%) and a slight decrease in low density lipoprotein cholesterol (-4%), both changes being significant at the P = 0.05 level.

The methanol extraction residue of Bacillus Calmette-Guerin protects against 7,12-dimethylbenz(alpha)anthracene-induced rat mammary carcinoma.

SummarySprague-Dawley female rats were placed on a low-fat diet, a high saturated fat diet, or a high polyunsaturated fat diet at time of weaning (21 days of age). Half of the rats in each dietary group were given an intraperitoneal injection of MER (0.5 mg) on Day 28 and again on Day 35. On Day 50, all rats were given 10 mg of DMBA in 1 ml of stripped corn oil via stomach tube. Tumor incidence was determined weekly by palpation and confirmed by histological analysis upon completion of the experiment. In each dietary group, rats immunized with MER had a lower tumor incidence, a longer latent period, and smaller tumors compared to non-immunized rats. In other experiments, rats were placed on the high polyunsaturated fat diet at time of weaning, exposed to DMBA on Day 50, and maintained on this diet for either 3 or 4 weeks after DMBA. At those times, some rats were placed on the low-fat diet while other rats were maintained on the high polyunsaturated fat diet. Half of the rats from each group were treated ...

Dependence of the effects of dietary cholesterol and experimental conditions on serum lipids in man II. Effects of dietary cholesterol in a linoleic acid-poor diet

In this experiment the effect of dietary cholesterol on serum cholesterol levels was tested in a linoleic acid-poor diet. In a cross-over design 34 healthy students received a linoleic acid-poor diet for 6 weeks at two levels of dietary cholesterol for 3 weeks each. The visible fat was supplied in the form of margarine so that the diet contained only 5 energy% linoleic acid. The high-cholesterol diet was obtained by providing two egg yolks a day. During the experimental period an intestinal infection was noticed, based on their diaries, in 16 subjects. Because of the expected influence on serum cholesterol levels all suspected individuals were removed from the records by independent experts and treated separately. Only the results of the 18 healthy persons are discussed in this paper. Supplementation of two eggs a day caused a highly significant (P < 0.01) rise in serum cholesterol levels of 26 ± 20 mg/100 ml (0.65 mmole/liter) in the two experimental groups. After correction for differences in the fat content of the diets an effect of 21 mg (0.54 mmole/liter) remained. As noticed in the first experiment (part 1) the rise in serum cholesterol levels in groups fed a high-cholesterol, high-polyunsaturated fat diet was only 11 mg/100 ml (0.29 mmole/liter). Comparing the two results it is concluded that the effect of dietary cholesterol is clearly dependent on the type of fat present in the diet. Eggs will have a rather important elevating effect in a saturated fat diet, which is the more deleterious as the saturated fat already induces high cholesterol levels. However, linoleic acid-rich fat reduces serum cholesterol levels markedly, while the opposing effect of dietary cholesterol in this case is much smaller. The results of this study emphasize the importance of considering the complexity and interrelations of all constituents of a diet in affecting health parameters. By substituting the type of fat and changing the amount of egg cholesterol, it seems feasible to influence serum cholesterol levels of young healthy men in the range of 145 to 210 mg/100 ml (3.7 to 5.4 mmole/liter).

Fats and atheroma: an inquest.

All well-controlled trials of cholesterol-reducing diets and drugs have failed to reduce coronary (CHD) mortality and morbidity. Nevertheless, commercial, professional, and even government-sponsored propaganda continues. Experimentally some vegetable oils and hardened fats can be more damaging to arteries than butter. There are other hazards to heart muscle from vegetable oils. Israelis consume a high polyunsaturated fat diet equal to that recommended for prevention of CHD in USA but their CHD incidence is very high. Urban Bedouins are also affected. The primary clofibrate prevention trial underlines unacceptable risks which could apply also to diets. Official medical endorsement of these cholesterol reducing measures should be withdrawn.

Reduction in blood pressure associated with high polyunsaturated fat diets that reduce blood cholesterol in man

Ten male and 11 female subjects in the 40–60 age group were fed a 25% fat-calorie diet (Period I) with a P/S ratio of 1. The diet consisted of foods commonly eaten in the U.S.A. and was fed for 40 days, followed by a second 40-day feeding period of 35% fat calories (Period II) with a P/S ratio of 1. A significant decrease in systolic pressure for males and females was observed at the end of the 25% fat-calorie period. The lowered levels of systolic pressure were maintained throughout the 35% fat-calorie period. The diastolic pressure also decreased significantly during Period I; it showed a slight increase, however, during Period II. Plasma cholesterol was also significantly decreased during the first phase of the study and remained lowered during the second phase. Beta cholesterol response paralleled that of total cholesterol, while alpha cholesterol response paralleled that of percentage alpha lipoprotein lipid. Plasma lipoproteins reflected the changes in diet; percentage of pre-beta lipoprotein lipid rose during Period I, while percentage of alpha lipoprotein lipid fell. These results were reversed during Period II. No significant changes in percentage of beta lipoprotein lipid were observed. Blood urea nitrogen was significantly decreased during Period I, followed by a rise after Period II. Blood glucose tended to fall during Period II but rose above prestudy levels after the study. No significant changes were observed in body weights or plasma triglycerides. These results suggest that dietary fat may be one more important factor in elevated blood pressure in otherwise healthy subjects, and its influence should be investigated further in a larger controlled trial with both normo- and hypertensive subjects.