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Biomedical subjects

C K Clifford

Publications and source records attributed to C K Clifford.

At least 19 recordsLinked to original sources

Diet and cancer prevention.

Research from several sources provides strong evidence that vegetables, fruits, and whole grains, dietary fibre, certain micronutrients, some fatty acids and physical activity protect against some cancers. In contrast, other factors, such as obesity, alcohol, some fatty acids and food preparation methods may increase risks. Unravelling the multitude of plausible mechanisms for the effects of dietary factors on cancer risk will likely necessitate that nutrition research moves beyond traditional epidemiological and metabolic studies. Nutritional sciences must build on recent advances in molecular biology and genetics to move the discipline from being largely 'observational' to focusing on 'cause and effect'. Such basic research is fundamental to cancer prevention strategies that incorporate effective dietary interventions for target populations.

Alcohol Drinking↗

Creating a new paradigm in nutrition research within the National Cancer Institute.

Almost two decades after Doll and Peto (1981) provided evidence that one third of cancer deaths are related to diet, it remains unclear which dietary components may be key in cancer prevention. Although the complexity of the diet can become overwhelming, the National Cancer Institute (NCI) of the National Institutes of Health (NIH) has remained steadfast in its commitment to defining the roles that diet and nutrition have in the development of cancer and has provided increased research and training support to assist in unraveling this interrelationship. Evidence for this sustained commitment is highlighted by a fourfold increase in NCI expenditures for nutrition research and training from 1983 to 1998; this substantial increase reflects a trend that is occurring in some universities and the private sector. More than one third of the nutrition-related NCI research is funded by the Division of Cancer Prevention. Supported investigations cover the gamut from basic mechanisms of action of dietary constituents, methodology development, human metabolic studies, clinical trials of dietary modification and the chemopreventive potential of individual nutrients to population-based studies.

Antioxidants↗

The Women's Health Trial Feasibility Study in Minority Populations: changes in dietary intakes.

This randomized clinical trial examined the feasibility of low-fat dietary interventions among postmenopausal women of diverse backgrounds. During 1992-1994, 2,208 women aged 50-79 years, 28% of whom were black and 16% Hispanic, enrolled at clinics in Atlanta, Georgia, Birmingham, Alabama, and Miami, Florida. Intervention/support groups met periodically with a nutritionist to reduce fat intake to 20% of energy and to make other diet modifications. At 6 months postrandomization, the intervention group reduced fat intake from 39.7% of energy at baseline to 26.4%, a reduction of 13.3% of energy, compared with 2.3% among controls. Saturated fatty acid and cholesterol intakes were reduced, but intakes of fruits and vegetables, but not grain products, increased. Similar effects were observed at 12 and 18 months. Black and non-Hispanic white women had similar levels of reduction in fat, but the decrease in Hispanic women was less. Changes did not vary significantly by education. While bias in self-reported intakes may have resulted in somewhat overestimated changes in fat intake, the reported reduction was similar to the approximately 10% of energy decrease found in most trials and suggests that large changes in fat consumption can be attained in diverse study populations and in many subgroups.

Aged↗

Effect of different types and amounts of fat on the development of mammary tumors in rodents: a review.

We performed a meta-analysis on data extracted from 97 reports of experiments, involving a total of 12,803 mice or rats, studying the effect on mammary tumor incidence of different types of dietary fatty acids. Fatty acids were categorized into saturated, monounsaturated, n-6 polyunsaturated, and n-3 polyunsaturated. We modeled the relation between tumor incidence and percentage of total calories from these fatty acids using conditional logistic regression and allowing for varying effects between experiments, and for each fatty acid we estimated the effect of substituting the fatty acid calories for nonfat calories. Our results show that n-6 polyunsaturated fatty acids (PUFAs) have a strong tumor-enhancing effect and that saturated fats have a weaker tumor-enhancing effect. The n-3 PUFAs have a small protective effect that is not statistically significant. There is no significant effect of monounsaturated fats. n-6 PUFAs have a stronger tumor-enhancing effect at levels under 4% of total calories, but an effect is still present at intake levels greater than 4% of calories. In addition, when the intake of n-6 PUFAs is at least 4% of calories, the n-6 PUFA effect remains stronger than the saturated fat effect.

Animals↗

Register of dietary assessment calibration-validation studies: a status report.

A register of dietary assessment calibration-validation studies was created to improve communication between investigators, avoid duplication of effort, and identify gaps in knowledge. Calibration-validation studies were defined as investigations in which the participants completed at least two different dietary measurements. A questionnaire soliciting descriptive information about such studies was widely distributed. Completed questionnaires were received from October 1993 through September 1994 and the data from them were entered into a computer database. Preliminary individual reports were mailed to all contributors in September 1994 for revision or updating. Responses received by the end of October 1994 were incorporated into the database. A status report was published in December 1994. The report includes descriptions of 84 studies, 15 summary tables, and 6 reference indexes. Of the 84 studies included, 44 (52%) were conducted in North America, 35 (42%) in Europe, 2 (2%) in South America, 2 (2%) in Asia, and 1 (1%) in Australia. Sixty-three of the 84 studies (75%) used food-frequency questionnaires, 52 (62%) used food records, 35 (42%) used one or more dietary recalls, 11 (13%) used biological measures, and 8 (10%) used diet histories. Plans for maintaining and updating the register are being developed.

Biomarkers↗

The Women's Health Trial Feasibility Study in Minority Populations: design and baseline descriptions.

The Women's Health Trial: Feasibility Study in Minority Populations (WHT:FSMP), a randomized trial of 2208 women, was conducted to investigate three questions. First, can women from minority and low-socioeconomic-status populations be recruited in numbers sufficient to evaluate a dietary intervention designed to lower fat intake. Second, the efficacy of a low fat, increased fruit/vegetable/ grain product intervention for reducing fat consumption. Third, will participation in the intervention lower plasma cholesterol and estradiol levels relative to the controls. The baseline results showed that an adequate number of minority and low SES women could be recruited to test the study hypotheses. A diverse study population of postmenopausal women consuming a high fat diet was recruited: 28% of participants were Black, 16% were Hispanic, 11% had less than a high school level of education, and 15.5% had household incomes of < $15,000.

Aged↗

Feasibility of a randomized trial of a low-fat diet for the prevention of breast cancer: dietary compliance in the Women's Health Trial Vanguard Study.

The Women's Health Trial Vanguard Study was conducted to examine the feasibility of a nationwide, randomized multicenter intervention trial to test the hypothesis that a low-fat diet followed for a period of 10 years will reduce breast cancer risk. Women ages 45-69 years at increased risk of breast cancer were randomized into intervention (low-fat diet, n = 184) and control (usual diet, n = 119) groups. On the basis of 4-day food records, baseline fat intakes were comparable in the two groups, averaging 1,718 kcal with 39% of energy as fat. Intervention women reported substantially lower fat intake at 6 (20.9% kcal), 12 (21.6%), and 24 months (22.6% kcal). In contrast, control women reported only slight reductions in fat intake (37.3% kcal at 12 months and 36.8% kcal at 24 months). Evidence that these women were indeed complying with the low-fat dietary intervention comes from (a) the reasonable nature of reported nutrient changes within food groups in the intervention women and (b) agreement between observed and expected differences in plasma total cholesterol between the control and the intervention groups. At 12 months, the observed control - intervention plasma cholesterol difference was 13.1 +/- 4.6 mg/dl while the expected difference based on the Keys equation was 15.1 +/- 1.1 mg/dl; at 24 months, the observed difference was 15.5 +/- 4.3 mg/dl and the expected difference was 12.0 +/- 1.2 mg/dl. These analyses indicate that the intervention women made substantial dietary changes and have successfully maintained these changes over a 2-year period. This study thus demonstrates the feasibility of a randomized trial with an intensive low-fat dietary intervention.

Aged↗

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↗

NCI dietary guidelines: rationale.

The National Cancer Institute (NCI) believes that the potential for dietary changes to reduce the risk of cancer is considerable and that the existing scientific data provide evidence that is sufficiently consistent to warrant prudent interim dietary guidelines that will promote good health and reduce the risk of some types of cancer. Six interim dietary guidelines and their scientific rationale are discussed herein. The evidence presented for the scientific rationale is based on the 1982 National Academy of Sciences Committee report Diet, Nutrition and Cancer and NCI's own scientific reviews that link long-term dietary patterns with cancer risk. These guidelines to the American public are consistent with other dietary recommendations from the US departments of Agriculture and Health and Human Services, the American Cancer Society, and the American Heart Association.

Diet↗

Effects of dietary triglycerides on serum and liver lipids and sterol excretion of rats.

The effects of several highly purified simple and mixed dietary triglycerides (TGs) on serum and liver cholesterol and on sterol excretion were studied in rats. The TGs contained 4- to 18-carbon fatty acids with melting points of -75 to 63.5 degrees C. Ratios of polyunsaturated to saturated fatty acids ranged from 0.1 to 105. Ratios of total unsaturated to saturated fatty acids ranged from 0.1 to 115. All diets contained 8% TG plus 0.82% safflower oil. Sterols were quantified directly by a new and improved high resolution gas chromatographic method and were identified by mass spectrometry. TG digestibilities correlated negatively with melting points above 30 degrees C (R = -0.9). Serum cholesterol was lower in rats fed tributyrin, tricaproin, tricaprylin, tricaprin, trielaidin, trilinolein or partially hydrogenated soybean oil (43-49 mg/dl) than in those fed trilaurin, trimyristin, tripalmitin, tristearin, triolein or corn oil (54-59 mg/dl). Liver lipid levels correlated (R = 0.65) with the degree of unsaturation of dietary TGs. Liver cholesterol levels correlated negatively with fecal excretion of coprostanol plus cholesterol (R = -0.4). Coprostanol plus cholesterol excreted in feces correlated weakly (R = 0.3) with intake of total sterol and of polyunsaturated TGs (R greater than or equal to 0.4 are at least 80% significant). The results demonstrate that consumption of polyunsaturated TGs was associated with higher hepatic lipid levels. Also, greater fecal excretion of coprostanol plus cholesterol was associated with lower hepatic cholesterol levels.

Animals↗

The Diet and Cancer Branch, NCI: current projects and future research directions.

Diet, perhaps more than any other environmental factor, has a significant potential for reducing the incidence of cancer. It has been projected that as much as 35 percent of all human cancer can be prevented through effective dietary modification strategies. The comprehensive research program of the DCB significantly directs diet and cancer research toward the ultimate cancer prevention goal of modifying dietary habits of the general population for optimal health. The DCB is currently supporting projects along the entire continuum from laboratory research to human intervention trials: basic research projects in food composition, encompassing dietary fiber, vitamin A and carotenoids and development of INFOODS; physiologic studies establishing safe and effective levels of dietary fiber and carotenoids; modification of eating behavior; human intervention trials of low fat diets in prevention of breast cancer; and clinical nutrition research units.

Diet↗

Effects of purine amino groups on the development of Drosophila.

The effect of a variety of 6-substituted purines on development of Drosophila melanogaster, eggs and larva, were studied. Purine and 2,6-diaminopurine both were very toxic to egg development. Adenine and 2,6-diaminopurine were moderately and equally toxic to larva development. Substitution on the 6-position of the purine ring was very effective in regulating metamorphosis of Drosophila.

2-Aminopurine↗

Folate deficiency in rats fed amino acid diets.

Growth rate, hematological changes, serum, erythrocyte and liver folate levels, and urinary excretion of formiminoglutamic acid (FIGLU) were measured in rats fed p-aminobenzoic acid (PABA)-free, sulfonamide-supplemented purified amino acid diets with and without folic acid and fiber, individually and in combination. Fiber had no effect on growth but was necessary to prevent mortality in the absence of folic acid. Folic acid did not affect growth during the first 40 days, but after this period rats failed to gain weight in the absence of folic acid. Although blood hematocrit was lower when the diet was devoid of fiber and folic acid and leucocyte counts were lower when the diets were devoid of folic acid, the hematological values remained within normal physiological limits for healthy rats of comparable age. FIGLU excretion was increased and serum, erythrocyte and liver folate levels were depressed when rats were fed folic acid-free diets for 28 days. Neutrophil hypersegmentation was clearly evident after 28 days of feeding the folic acid-free diets. The use of an amino acid diet without PABA but containing 5% fiber and 1% succinylsulfathiazole is a useful system to study chronic folic acid deficiency in the rat.

Amino Acids↗