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The dietary fat--breast cancer hypothesis is alive.

Data from animal experiments and human correlation studies strongly support the dietary fat-breast cancer hypothesis. Moreover, a causal relation between dietary fat and breast malignancy is biologically plausible. Negative findings from recent analytic epidemiologic studies of dietary fat and breast cancer, however, have fueled the notion that the hypothesis is no longer viable. We argue that only limited conclusions should be drawn from epidemiologic studies to date because of the narrow range of dietary fat intake among subjects and the substantial measurement error in dietary assessment. Although many doubts remain about the dietary fat--breast cancer hypothesis, the question is of such importance that intensive efforts at designing better studies of the hypothesis are urgently needed. Such studies might include (1) laboratory investigations in humans that examine possible mechanisms for the effects of fat, (2) large, prospective epidemiologic studies, and (3) randomized, controlled diet trials.

Animals↗

Influence of dietary fat on the lipid composition of perirenal adipose tissue in rats.

The influence of dietary fat on the composition of perirenal adipose tissue was studied in Wistar rats fed three experimental semisynthetic, isocaloric diets containing different qualities of fat (olive oil, butter and medium chain triglycerides + corn oil). Under these experimental conditions, the saturation index reflects the percentage of fatty acids supplied by each diet; this index was highest in animals fed the diet containing butter and lowest in the group in which olive oil was the dietary fat source. The amount of linoleic acid (the major component of the diunsaturation index) supplied by the diet is directly paralleled by levels of this fatty acid in perirenal adipose tissue, whereas the monounsaturation index in adipose tissues, considered an indicator of the dietary supply of monounsaturated fatty acids in the rat, failed to show a clearly proportional relationship between intake and perirenal adipose tissue levels.

Adipose Tissue↗

Energy balance and ovarian follicle development prior to the first ovulation postpartum in dairy cows receiving three levels of dietary fat.

The objectives of this study were to characterize early postpartum (PP) follicular development in dairy cows and to evaluate the influence of energy balance (EB) and the level of dietary fat on dominant follicle development and function. Forty-five multiparous Holstein cows were fed either low (LF, 3.3%), moderate (MF, 5.2%), or high (HF, 7.1%) total dietary fat beginning at parturition, and daily EB was determined for all cows. Follicular development was monitored by ultrasonography, and blood plasma was analyzed for metabolites, metabolic hormones, progesterone, estradiol, and FSH. After an increase (p < 0.01) in mean plasma FSH during Days 1-5, all cows experienced a wave of follicular development during the second week PP regardless of diet or EB. Feeding the MF (p < 0.05) or HF (p < 0.06) diet resulted in a greater number of class IV (> 15 mm) follicles on Day 14 PP as compared to the LF diet. Cows fed the MF diet had higher (p < 0.05) peak plasma estradiol during the first follicular wave and a shorter (p < 0.05) interval to first ovulation than both LF and HF cows. Follicular development prior to first ovulation was characterized by either ovulation of the first dominant follicle (OV, n = 19), one or more waves of nonovulatory dominant follicles (NOV, n = 18), or the formation of a follicular cyst (CYST, n = 8). Ovulation failure during the first follicular wave PP was accompanied by lower (p < 0.001) peak plasma estradiol (0.96 +/- 0.36 vs. 5.0 +/- 0.35 pg/ml), a smaller (p < 0.01) maximum follicle diameter (16.0 +/- 0.9 vs. 20.0 +/- 1.0 mm), lower (p < 0.09) levels of plasma insulin-like growth factor-I (IGF-I; 73.5 +/- 10.1 vs. 102.9 +/- 9.9 ng/ml), and a longer (p < 0.02) interval to the EB nadir (14.6 +/- 1.9 vs. 6.4 +/- 1.9 days). The number of days to first ovulation was positively correlated with days to the EB nadir (r = 0.55), with dominant follicles that emerged after the EB nadir exhibiting enhanced (p < 0.01) production of estradiol and greater (p < 0.01) ovulatory success. The development of large (> 10 mm) dominant follicles was not a limiting factor in PP reproductive recovery, and moderate dietary fat shortened the interval to first ovulation. Follicular competence early PP was associated with higher plasma IGF-I and a shorter interval to the EB nadir.

Animals↗

Effects of quantity and unsaturation of dietary fat on serum components in normal and diabetic Macaca nigra.

Dietary fat affects serum lipids independently of dietary cholesterol. Normal and diabetic monkeys (Macaca nigra) were fed cereal-based, specially formulated diets with either a low fat (LF = 2.5%) or a higher fat (13.2%) content; the latter had varying concentrations of safflower and coconut oil to attain greater polyunsaturation (SFO) or saturation (CCO) in the diets. Dietary cholesterol was less than 0.01%. Serum triglyceride concentrations were greatest when monkeys consumed the LF (higher carbohydrate) diet and lowest when they consumed the SFO diet. Concentrations were greater in diabetic than in normal monkeys fed the LF and SFO diets, but both groups had similar concentrations when fed the CCO diet. Cholesterol levels in diabetic monkeys were only slightly higher than in normals regardless of diet; in both groups, levels were lowest when the LF diet was fed and highest when the CCO diet was fed. The quantity of fat had a greater effect on serum cholesterol than did the degree of polyunsaturation. In both groups, triglyceride concentrations correlated significantly with VLDL protein, and cholesterol levels correlated with LDL protein. Thus the responses of Macaca nigra to dietary fat manipulation depend upon both the diet fat content and composition as well as the normal or diabetic metabolic state of each monkey.

Animals↗

Influence of dietary fat source, alpha-tocopherol, and ascorbic acid supplementation on sensory quality of dark chicken meat.

We studied the influence of dietary fat source and dl-alpha-tocopheryl acetate and ascorbic acid supplementation on the sensory quality of cooked dark chicken meat stored at -20 C for different periods. Results showed that dietary fat source and alpha-tocopheryl acetate supplementation influenced sensory scores (rancid flavor and aroma and acceptability). Ascorbic acid had no influence on these scores. Thiobarbituric acid values showed a high correlation with sensory scores. In addition, the low levels of alpha-tocopheryl acetate contained in the trace mineral-vitamin mix (20 IU/kg of feed) were enough to prevent rancidity development in cooked dark chicken meat when broilers were fed a saturated fat diet and samples were vacuum-packed and stored at -20 C for 13 mo.

Adult↗

A prospective study of dietary fat and risk of prostate cancer.

BACKGROUND: The strong correlation between national consumption of fat and national rate of mortality from prostate cancer has raised the hypothesis that dietary fat increases the risk of this malignancy. Case-control and cohort studies have not consistently supported this hypothesis. PURPOSE: We examined prospectively the relationship between prostate cancer and dietary fat, including specific fatty acids and dietary sources of fat. We examined the relationship of fat consumption to the incidence of advanced prostate cancer (stages C, D, or fatal cases) and to the total incidence of prostate cancer. METHODS: We used data from the Health Professionals Follow-up Study, which is a prospective cohort of 51529 U.S. men, aged 40 through 75, who completed a validated food-frequency questionnaire in 1986. We sent follow-up questionnaires to the entire cohort in 1988 and 1990 to document new cases of a variety of diseases and to update exposure information. As of January 31, 1990, 300 new cases of prostate cancer, including 126 advanced cases, were documented in 47855 participants initially free of diagnosed cancer. The Mantel-Haenszel summary estimator was used to adjust for age and other potentially confounding variables. Multiple logistic regression was used to estimate relative risks (RRs) when controlling simultaneously for more than two covariates. RESULTS: Total fat consumption was directly related to risk of advanced prostate cancer (age- and energy-adjusted RR = 1.79, with 95% confidence interval [CI] = 1.04-3.07, for high versus low quintile of intake; P [trend] = .06). This association was due primarily to animal fat (RR = 1.63; 95% CI = 0.95-2.78; P [trend] = .08), but not vegetable fat. Red meat represented the food group with the strongest positive association with advanced cancer (RR = 2.64; 95% CI = 1.21-5.77; P = .02). Fat from dairy products (with the exception of butter) or fish was unrelated to risk. Saturated fat, monounsaturated fat, and alpha-linolenic acid, but not linoleic acid, were associated with advanced prostate cancer risk; only the association with alpha-linolenic acid persisted when saturated fat, monounsaturated fat, linoleic acid, and alpha-linolenic acid were modeled simultaneously (multivariate RR = 3.43; 95% CI = 1.67-7.04; P [trend] = .002). CONCLUSION: The results support the hypothesis that animal fat, especially fat from red meat, is associated with an elevated risk of advanced prostate cancer. IMPLICATIONS: These findings support recommendations to lower intake of meat to reduce the risk of prostate cancer. The potential roles of carcinogens formed in cooking animal fat and of alpha-linolenic acid in the progression of prostate cancer need to be explored.

Adult↗

Regulation of new fat cell formation in rats: the role of dietary fats.

Factors that stimulate formation of new adipocytes during development of obesity are yet to be identified. We examined whether diet acts directly on preadipocytes to stimulate replication and differentiation or indirectly by interacting with adipocytes to release or modify local growth factors. Male Sprague-Dawley rats were fed chow or diets high in starch (HST), saturated (HFS) or polyunsaturated (HFP) fats until 5-7 months of age. We found that, compared to other diets, HFS induced acceleration of replication of preadipocytes in primary culture (doubling time of retroperitoneal-derived preadipocytes: HFS 17 +/- 1 versus chow 32 +/- 6 and HFP 29 +/- 3 h, P < 0.05). HFS stimulated greater expansion of retroperitoneal fat than HFP even when caloric intake was equal and increased adipocyte number threefold. Preadipocyte pool size in inguinal and retroperitoneal fat pads changed relative to fat pad weight in rats fed all diets compared to chow, suggesting that the balance between the number of cells capable of replicating and those terminally differentiated was perturbed. Differentiation of preadipocytes and release of adipocyte growth factors in vitro were unaffected by diet. We concluded that dietary saturated fats induced expansion of adipose tissue mass more effectively than polyunsaturated fats and that this may, in part, be achieved by acceleration of preadipocyte replication.

Adipocytes↗

Dietary fat consumption, readiness to change, and ethnocultural association in midlife African American women.

Cardiovascular disease (CVD) is the number 1 killer of American women, with African American women disproportionately represented. Dietary fat consumption is a major risk factor for the development of CVD. This study examined the average daily diet of urban midlife African American women, specifically the relation between dietary fat, readiness to change, ethnocultural association, and selected sociodemographic variables. Three hundred days of dietary data were collected. Sixty five percent of the participants reported currently avoiding high fat food with another 25% planning to avoid high fat food. Although 90% of the participants were avoiding or planning to avoid high fat foods, 77% were consuming diets with over 30% of their calories from fat. Of 11 variables considered, ethnocultural association was the only variable found to be consistently positively related to dietary fat intake. Community dietary education for midlife African American women needs to target all, especially those with stronger cultural bonds.

Adult↗

An application of the stage model of behavior change to dietary fat reduction.

To assess the applicability of Prochaska and DiClemente's stage model to dietary change, stage of dietary fat reduction was assessed in two samples of adults. Results were consistent across the two samples. Males and females differed in their distribution across five stages of change, with more males than females in a precontemplation stage and more females than males in a maintenance stage. Significant positive correlates with stage for men and women were age, education, body mass index, number of chronic conditions and being told one has a high serum cholesterol. For both genders, stage of dietary fat reduction was significantly associated with percent of calories from fat, even when controlling for demographic and health status covariates.

Adult↗

Effects of dietary fats on the activity of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol synthesis in the liver of fasted-refed rats.

The time course of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity and lipogenesis and cholesterogenesis from 1-14C-acetate and 2-14C-mevalonate was examined in the liver of rats refed diets containing different fats at the 10% level after 48 hr fasting. Fasting caused a profound depression of the reductase activity and sterol and fatty acid synthesis. In rats refed for 30 hr, the activity of HMG-CoA reductase was restored to about one-half of the level observed in prefasting rats, irrespective of the type of dietary fats. When safflower oil and trilaurin were dietary fats, the activity remained this level until 78 hr, then declined, whereas with tristearin, activity progressively increased until 78 hr. On refeeding for 174 to 222hr, the reductase activity was significantly higher in the tristearin than in the trilaurin group. Similar patterns were demonstrated in cholesterogenesis either from acetate or mevalonate, though extents of activation after refeeding were markedly different in these precursors. Dietary fat dependent changes in the content of hepatic cholesterol and in the concentration of plasma cholesterol were also observed.

Animal Nutritional Physiological Phenomena↗

Effect of dietary fat on the development of non-insulin dependent diabetes mellitus in obese Zucker diabetic fatty male and female rats.

The obese Zucker diabetic fatty male rat (ZDF/Gmi¿trade mark omitted¿-fa) has become a widely used animal model of NIDDM, in contrast to the obese ZDF females that rarely develop NIDDM. However, preliminary observations suggest that obese ZDF females may become diabetic on high-fat diets. Therefore, we studied the effect of dietary fat on development of NIDDM, dyslipidemia, and alterations in organ-specific serum panels in obese ZDF males and females. Results indicated different effects of dietary fat-content on development of diabetes in males and females. Males, even on low fat-content diets, developed diabetes but the process was accelerated as a function of dietary fat-content, whereas only the highest fat-content diet induced development of NIDDM in obese ZDF females. Additionally, triglyceride/apolipoprotein B ratios demonstrated gender-specific differences in the nature of circulating lipoprotein particles independent of diabetic state with values for females approximately twice those of males indicating more highly triglyceride-enriched lipoprotein particles in females. We conclude that the obese ZDF female rat has the potential to become an important animal model of NIDDM especially in women where few models currently exist.

Animals↗

CD36 may determine our desire for dietary fats.

There is a strong link between high fat intake and obesity. In addition to its high caloric density, dietary fat has a hyperphagic effect, in part as a result of its high palatability. The recent identification by Laugerette et al. of CD36 as a taste receptor for fatty acids provides insight into the molecular basis of our preference for fat (see the related article beginning on page 3177). As we gain more information regarding the function of this receptor, we may be able to devise better strategies to address the addictive potential of dietary fat.

Animals↗

Cancer mortality and age: relationship with dietary fat.

Highly significant correlations exist between total cancer mortality and age expressed by a log total cancer mortality-log age equation (mean r2 0.991 in men and 0.996 in women) or by a second-order polynomial equation including age and age2 (mean r2 0.999 in men and 0.998 in women). In all countries considered (n = 32), the second-order term of age is negative, indicating a decrease in the rate of rise of log cancer mortality at older age. This could be explained by a lesser accuracy of the diagnosis of cancer at older age, by selective survival of subjects resistant to cancer, by a cohort effect, or by a decrease in the rate of growth of cancer at older age. The decrease in the rate of rise of cancer mortality after 65 years of age occurs in all countries and applies to nearly all cancers except breast cancer in women after 75 years of age. A high cancer mortality in a country is characterized by a low intercept and a steep slope of the log mortality-log age equation. These parameters are influenced by dietary fat intake in men and women, with saturated fat increasing total cancer mortality and the ratio of polyunsaturated to saturated fat and the ratio of unsaturated to saturated fat decreasing it. The data on dietary fat were obtained from the Food and Agriculture Organization of the United Nations (FAO) food balance sheets (n = 32) and from dietary surveys (n = 21). Both vary in the same direction, but only the dietary data from the FAO correlate significantly with cancer mortality. This finding points toward a relationship between the level of dietary fat intake and total cancer mortality at the population level.

Adult↗

Modulation of the exercise and retirement effects by dietary fat intake in hamsters.

An experiment was conducted to determine the effects and interactions of exercise-retirement and dietary fat intake on body composition and hepatic lipogenic enzyme activities in hamsters. Forty-eight adult female hamsters were randomly allotted to eight groups of six each for a 40-d experiment. Exercise was in the form of voluntary wheel-running. Four groups served as either exercise or sedentary controls and were fed either a low or a high fat diet for 40 d, in a factorial fashion. Another four groups had access to exercise for 32 d and were then retired for 8 d. Of these four groups, two were fed either the low or high fat diet for the entire 40-d period; the other two were changed to the other diet on d 32. Results showed that compared to sedentary hamsters, exercise hamsters had greater body weight gain but less body fat content and hepatic lipogenic enzyme activities. Under both sedentary and exercise conditions, high fat-fed hamsters had lower hepatic lipogenic enzyme activities and less body fat content than low fat-fed hamsters. Upon retirement, high fat feeding led to a faster increase in body fat especially in previously high fat-fed hamsters. Results of this study suggest that dietary fat intake can significantly modulate the exercise and retirement effects with respect to body weight gain and body fat content.

Adipose Tissue↗

Dietary fat and selenium effects on ex vivo prostaglandin production in rat colon, kidney, and blood.

The effects were determined of dietary fat and selenium (Se) levels on prostaglandin (PG) production in rat blood, kidney, and colon mucosa. For 30 weeks, male Wistar-derived MRC rats were prefed diets containing low (6 g/367 kcal) or high (20 g/367 kcal) levels of fat with one of three Se supplements from sodium selenite: 0.0, 0.1, or 2.0 ppm Se. PG production was stopped by adding aspirin immediately following removal of the blood, kidney, and colon samples. Separate samples were allowed to incubate 10 or 60 minutes before blockage of PG production for determination of ex vivo PG production. Prostaglandin E2 (PGE2), thromboxane B2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay following separation on silicic acid columns. Basal levels of the three PGs were not influenced by diet. PGE2 production in the colon was highest in the group fed the high-fat diet that contained 2.0 ppm Se at 10 and 60 minutes, but PGE2 production in the blood and kidney were not altered by diet. Thromboxane B2 production in the rats' blood was higher in those prefed high-fat diets, but it was not influenced by dietary Se. Production of 6-keto-PGF1 alpha in the blood and thromboxane B2 and 6-keto-PGF1 alpha production by the kidney and colonic mucosa were not influenced by either dietary fat or Se.

6-Ketoprostaglandin F1 alpha↗

Dietary fat intake and body mass index in Spanish children.

Our objectives were to describe the pattern of dietary fat intake and to present data on trends of growth in Spanish children in past decades. In 1984 a nationwide nutritional survey was conducted in Spain. The average nationwide fat intake was 42% of energy. Across different regions, saturated fat intakes ranged from 13% to 15% of energy and monounsaturated fat intakes ranged from 18% to 19% of energy. More recently, some surveys were conducted at a regional or local level. In children aged 6-10 y, total fat intake ranged from 38% to 48% of energy, of which saturated fat intake ranged from 16% to 18% and monounsaturated fat ranged from 19% to 20%. In children aged 11-14 y, total fat intake ranged from 41% to 51% of energy, of which saturated fat intake ranged from 12% to 18% and monounsaturated fat intake accounted for 20%. In our region of Aragón, we observed a significant trend in children's growth, especially when we accounted for body mass index. The results reflect an increasing total fat consumption in Spain, especially of saturated and monounsaturated fat. The following question remains unanswered: what percentage of fat intake should be recommended when monounsaturated fat is the principal source of fat? Trends on body mass index values in children of our region during the past decades could be related to the amount of fat intake in our population. To confirm these findings we must measure dietary fat intake and nutritional status in the same population of children and adolescents.

Adolescent↗