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D Kritchevsky

Publications and source records attributed to D Kritchevsky.

At least 19 recordsLinked to original sources
PubMed1992

Herman Award Lecture, 1992: lipid nutrition--a personal perspective.

In the 1950s excess dietary fat was thought to be a risk factor for development of atherosclerosis. Over the ensuing years we have examined and given advice concerning first, saturation and unsaturation, and later, specific fatty acids such as oleic and stearic acids. Current work is further refining the delineation of fatty acids that might be harmful. Eventually, we will probably again cite excess fat as the problem.

Awards and Prizes↗
PubMed1992

Serum cholesterol and cancer risk: an epidemiologic perspective.

This review has examined the evidence surrounding two questions: (a) Is having low serum cholesterol associated with increased risk of cancer? (b) Does reducing serum cholesterol increase the occurrence of cancer? Some elevated risk of cancer for males with low serum cholesterol levels has been noted: the median of the studies examined is consistent with a 30% increased risk. The answer for females is less clear. The median of the studies examined suggests no more than a 5-10% increased risk associated with having low serum cholesterol. However, the risk seems to depend strongly on whether females have a central or peripheral body fat pattern (54). The cancers most consistently associated with low serum cholesterol levels are those of the colon and lung in males, the cervix and breast (but only for females under 50 years of age) in females, and leukemia in both sexes. In contrast, high cholesterol levels have been linked with an increase in brain cancer. While immunologic, genetic, and dietary explanations have been offered to explain the association, it is difficult to support the idea that low serum cholesterol causes cancer in any direct manner. First, the findings themselves tend to be generally weak and somewhat inconsistent. Second, the strong influence of fat distribution in women suggests that a metabolic/hormonal basis underlies the association. One would not expect the results to differ by body fat pattern if the relationship were a causal one. Finally, if there were a direct causal role, one would expect populations with low serum cholesterol levels to have higher cancer rates. In China, counties with the lowest average plasma cholesterol levels have the lowest cancer rates (78). While this observation is open to a number of interpretations, it does not support the idea that low serum cholesterol is a tumor initiator. In aggregate, the trials of lipid-lowering interventions reviewed here show an increase in cancer occurrence (primarily mortality) of approximately 24% in the cholesterol-lowered groups. However, the post-trial experience has shown a comparative deficit of cancer occurrence in the experimental groups. Recent evidence indicates that products in the cholesterol biosynthetic pathway affect DNA replication and cell proliferation. These findings suggests a mechanism by which cholesterol lowering might accelerate the development of tumors already initiated. The data that have been reviewed in no way suggest that treatment of hypercholesterolemia should not be pursued. They do suggest the presence of a relatively small subpopulation in whom reduction of plasma cholesterol may lead to increased occurrence of cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Cholesterol↗
PubMed1991

Effects of glycerol tripalmitate and glycerol trioleate on intestinal absorption of glycerol tristearate.

The goal of the present study was to determine 1) whether the poor digestion and absorption of glycerol tristearate (TS) that we observed previously is due to amount fed and 2) whether the digestion, absorption, and lymphatic transport of TS is affected by the presence of either a saturated fat [glycerol tripalmitate (TP)] or a monounsaturated fat [glycerol trioleate (TO)]. Three groups of intestinal lymph fistula rats were used. Group A was fed a lipid emulsion containing 12.5 mumol of TS (labeled as [glyceryl-1,3-14C]tristerate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline per hour for 8 h. Group B rats were fed the same emulsion as group A, but with 12.5 mumols of TO added. Group C rats had 12.5 mumols of TP instead of TO added to the group A emulsion. The lymphatic radioactivity and triglyceride outputs were significantly lower in group A, with group C next and group B having the highest outputs. Significantly more TS remained in the lumen of the group A rats compared with groups B and C. The majority of the radioactivity in the lumen was still in the TS form in all three groups, indicating poor lipolysis. However, once the fatty acid and monoglyceride were absorbed, the reesterification process was similar in all three groups. When we studied the ability of the three groups of animals to transport the absorbed lipid into lymph (lymph transport index), both groups B and C were significantly better than group A rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Reduction of enhanced mammary carcinogenesis in LA/N-cp (corpulent) rats by energy restriction.

Restriction of energy intake significantly reduces mammary tumorigenesis in normal rats exposed to carcinogens. Genetically obese LA/N-cp (corpulent) female rats were given 7,12-dimethylbenz[a]anthracene and fed purified diets ad libitum or restricted to 60% of the ad libitum caloric intake. Phenotypically lean littermates were also fed ad libitum. Obese animals developed large mammary tumors more rapidly than genetically normal rats so that 100% of the animals had tumors in less than 16 weeks. Only 21% of the lean animals developed tumors; the energy restricted obese animals had a tumor incidence of 27%. Although obese rats fed the restricted diet weighed significantly less than those fed ad libitum, percent body fat was not reduced, indicating that lean tissue was affected more. Obese animals were markedly hyperinsulinemic (1003 +/- 193 microunits/ml) and energy restriction reduced this to 328 +/- 41; the lean animals had insulin levels of 12 +/- 2. Tumor-bearing rats had higher insulin levels than rats without tumors. These data suggest that body fatness is not directly associated with risk of carcinogenesis. Lean body mass, adipose tissue mass, and their interaction with insulin in its capacity as a growth factor rather than body fatness per se may be determinants of tumor promotion.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Dietary fat and experimental atherosclerosis.

This paper reviews studies relating to the effects of fat unsaturation and fatty acid composition on the development of experimental atherosclerosis in rabbits. The results derived from the feeding of various fats are similar whether one feeds cholesterol or an atherogenic, cholesterol-free semipurified diet. In general, the severity of atherosclerosis is inversely related to the level of fat unsaturation. Two exceptions are cocoa butter which is much less atherogenic than expected, most probably due to its high content of stearic acid, and peanut oil, while relatively unsaturated, is surprisingly atherogenic for rats, rabbits and monkeys. This latter effect is not related to the level (6%) of long-chain saturated fatty acids (arachidic, behenic, lignoceric) present in peanut oil, but rather to its triglyceride structure. Randomization of peanut oil, which modifies its triglyceride structure, significantly reduces its atherogenicity.

Animals↗
PubMed1991

The role of calories and caloric restriction in carcinogenesis.

Studies in mice and rats show that caloric restriction (CR) without malnutrition lowers the incidence of most spontaneous and induced tumors and delays their onsets. The maximum life spans of rodents and other experimental animals (e.g., fish, spiders, water fleas) are extended by CR. The molecular events that underlie these outcomes remain unelucidated. Although epidemiologic studies have not usually examined the relationship between caloric intake and cancer incidence, recent findings suggest a positive association for certain cancers such as colorectal, breast, and stomach. It is apparent that future studies of diet and cancer in humans must seriously assess the role of calories and energy balance as well as their interaction with the effects of specific nutrients.

Animals↗
PubMed1990

Steady-state mRNA expression for growth factors in DMBA-induced rat mammary tumors.

Steady-state mRNA levels were examined for insulin-like growth factors (IGF) I and II, transforming growth factor alpha (TGF alpha) and its receptor and the epidermal growth factor (EGF) receptor in mammary tumors induced by DMBA in rats. An abundant 4.8 kb TGF alpha transcript was identified in all tumors, along with a 7.5-8.0 kb IGF-I transcript. A presumptive 2.9 kb IGF-II transcript was also identified in all tumors. Northern analyses and receptor autophosphorylation studies failed to detect EGF receptors in any mammary tumors. These findings suggest the potential for autocrine or paracrine influences of IGF-I and IGF-II in this tumor model and a possible paracrine influence of TGF alpha in tumor-induced neovascularization.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Nutrition and breast cancer.

International comparisons have provided striking correlations between fat consumption and risk of breast cancer, but these comparisons do not often consider variations in life style. Case-control studies carried out in several countries showed no real association between fat intake and breast cancer. There is some evidence that vitamin A or carotenoid intake may exert a protective effect. Alcohol intake, on the other hand, seems to be positively associated with breast cancer risk. Elevated body weight, body mass, stature, and frame size have been found to be associated as risk factors for breast cancer in women. Animal studies found that caloric restriction inhibits growth of spontaneous and induced mammary tumors, an observation that held up even when the calorie-restricted animals ingest more fat than the ad-libitum-fed controls. College women who exercise have a lower incidence of breast cancer than their more sedentary classmates. Exercise is another means of reducing caloric availability.

Animals↗
PubMed1990

Fiber and cancer.

The role of dietary fiber in colon cancer is still not clear. Ecological studies suggested a protective role for high fiber intake, but more recent analysis shows similar intakes of dietary fiber in populations with high or low incidence of colon cancer. Case-control studies generally do not support a protective role for fiber. The data suggest that the effects of fiber must be considered in the context of the total diet and interactions of dietary components. A role for levels of energy intake is not excluded.

Bile Acids and Salts↗
PubMed1990

A comparison of absorption of glycerol tristearate and glycerol trioleate by rat small intestine.

Generally, fats rich in saturated fatty acids raise serum cholesterol, whereas fats rich in polyunsaturated fatty acids lower it. There appear to be exceptions; e.g., stearic acid (18:0)-rich fats have little or no effect on serum cholesterol concentrations. This apparent lack of cholesterolemic effect of stearic acid-rich fat could be because intestinal absorption of fat is poor or subsequent plasma and/or tissue metabolism of fat is different. To investigate mechanisms involved, we compared intestinal digestion, uptake, and lymphatic transport of glycerol tristearate (TS) and glycerol trioleate (TO, 18:1). Two groups of rats bearing intestinal lymph fistulas were used. TO rats were fed intraduodenally for 8 h at a constant rate a lipid emulsion of 25 mumols/h of TO (labeled with glycerol tri[9,10 (n)-3H]oleate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline. TS rats were fed the same lipid emulsion except that TS replaced TO and the emulsion was labeled with glyceryl [1,3-14C]tristearate. The lymph triglyceride and radioactivity were determined. After infusion, the luminal and mucosal radioactive lipid content was analyzed. The results showed that there was significantly less lipid transported in the lymph of TS rats compared with TO rats. The results also showed a significant decrease in the absorption of TS as compared with TO. This was due in part to poor lipolysis. In addition, the lipid absorbed by the intestine of the TS rats was transported into lymph less efficiently than in TO rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Protein and atherosclerosis.

In general, protein of animal origin is more cholesterolemic and atherogenic than plant protein. The addition of single amino acids to the protein can influence cholesterolemia and atherogenicity, by either increasing or decreasing these conditions. The lysine to arginine ratio, which is higher in animal than in plant proteins, may be a factor in cholesterolemia. The results may be explained in part by the findings that lipid absorption is elevated in rabbits or rats fed animal proteins as is turnover time. Animals fed soy protein excrete more neutral and acidic steroids, and have increased activity of hepatic HMG CoA reductase and cholesterol 7 alpha-hydroxylase. Animal protein may exert its hypercholesterolemic effect by mechanisms which include increased absorption of cholesterol and decreased turnover.

Animals↗
PubMed1990

Influence of caloric restriction and exercise on tumorigenesis in rats.

Underfeeding or caloric restriction have been shown to inhibit the growth of spontaneous, transplanted, or chemically induced tumors in rats and mice. At 40% caloric restriction, growth of 7,12-dimethylbenz(a)anthracene-induced mammary and 1,2-dimethylhydrazine-induced colonic tumors is inhibited significantly even when the restricted diet contains twice as much fat as the control diet. Some inhibitory effects become evident even at 10% caloric restriction. In studies involving high fat diets, we find that rats receiving 20% fat ad libitum exhibit significantly higher 7,12-dimethylbenz(a)anthracene-induced mammary tumor incidence, multiplicity, and weight than rats ingesting the same amount of fat daily, but in a diet containing 25% fewer calories. In a study of intermittent ad libitum and restrictive feedings, chemically induced tumorigenicity varies inversely with feed efficiency. Exercise has also been shown to inhibit tumor growth. Sedentary rats fed ad libitum have a 108% higher incidence of 1,2-dimethylhydrazine-induced colon tumors than rats fed ad libitum but subjected to vigorous treadmill exercise. Caloric flux (either reduced intake or increased outflow) appears to reduce tumorigenicity in rodents.

1,2-Dimethylhydrazine↗
PubMed1990

Influence of acarbose (a glucosidase inhibitor) on experimental atherosclerosis in the rabbit.

Acarbose, a complex oligosaccharide of microbial origin, was added at levels of 100, 200 or 400 mg/kg to an atherogenic diet fed to New Zealand White rabbits. The rabbits consumed 75 g/day of each diet, thus the daily intake of Acarbose was 7.5, 15 and 30 mg. Rabbits fed 30 mg/day of Acarbose showed reduced levels of plasma cholesterol, intermediate density lipoprotein (IDL) and low density lipoprotein (LDL). Aortic sudanophilia was inhibited by 23% in rabbits fed 7.5 mg/day of Acarbose and by 43% in rabbits fed 15 or 30 mg/day. Acarbose had been shown previously to lower serum cholesterol and triglyceride levels in rats and mice. Our studies demonstrate that it also inhibits atherogenesis in rabbits fed 0.2% cholesterol.

Acarbose↗