Dietary fat and atherosclerosis.
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Journal Article↗
Biomedical subjects
D Kritchevsky
Publications and source records attributed to D Kritchevsky.
Inulin and oligofructose as dietary fiber: a review of the evidence.
This critical review article examines the composition and source of inulin and oligofructose, the physiological effects of their consumption, and how these materials relate to the concept of dietary fiber. Inulin and oligofructose are fructans extracted on a commercial basis from the chicory root. Inulin has been defined as a polydisperse carbohydrate material consisting mainly, if not exclusively, of beta (2-1) fructosyl-fructose links ranging from 2 to 60 units long. Native chicory inulin has an average degree of polymerization (DP) of 10 to 20, whereas oligofructose contains chains of DP 2 to 10, with an average DP of 4. While a universally accepted definition for dietary fiber does not exist, it is generally agreed that this term includes saccharides (+ lignin) that are not hydrolyzed or absorbed in the upper part of the gastrointestinal tract. These materials reach the colon, where they may be totally fermented, partially fermented, or remain unfermented. In addition, fibers contribute to fecal bulking. Inulin and oligofructose are not digested in the upper part of the gastrointestinal tract or are they absorbed and metabolized in the glycolytic pathway, or directly stored as glycogen like 'sugars' or starches. None of the molecules of fructose and glucose that form inulin and oligofructose appear in the portal blood. These materials are quantitatively fermented by the microflora of the colon; further, it has been demonstrated that this fermentation leads to the selective stimulation of the growth of the bifidobacteria population. After reviewing their chemistry, origin, and physiological effects, it is the opinion of the authors that inulin and oligofructose are dietary fiber. They share the basic common characteristics of dietary fibers, that is, saccharides of plant origin, resistance to digestion and absorption in the small intestine, and fermentation in the colon to produce short-chain fatty acids that are absorbed and metabolized in various parts of the body. Moreover, this fermentation induces a bulking effect.
Animals↗
Caloric restriction and cancer.
In 1909 Moreschi observed that tumors transplanted into underfed mice did not grow as well as those transplanted into mice fed ad libitum. His finding stimulated a decade of research which showed that caloric restriction also affected negatively the growth of spontaneous tumors. Between 1920 and 1940 little work was done in this area, possibly because of limiting methodology. In the 1940s the laboratories of Tannenbaum (Chicago) and Baumann (Wisconsin) were able to design studies using defined diets and showed that the observed effect was due to caloric content of the diet independently of the source of calories. After another active decade research activity in the calorie-cancer area declined until it was reborn in the 1980s. By the 1980s knowledge of physiology and molecular biology had advanced enough to allow investigators to probe mechanisms underlying the calorie-cancer phenomenon. We now know that caloric expenditure (as work or exercise) will lead to reduced risk. Energy restriction enhances DNA repair and moderates oxidative damage to DNA. Energy restriction reduces oncogene expression as well. Over a half century ago, Boutwell noted that energy restriction in female rats resulted in adrenal hypertrophy and reduced weight of ovaries and uterus. He suggested that energy restriction resulted in "pseudohypophysectomy." We now know that adrenalectomy can negate the effects of caloric restriction. Caloric restriction also affects insulin metabolism and may influence gene expression. These recent observations should help us understand some of the basic mechanisms involved in establishment and proliferation of tumors.
Animals↗
Diet and atherosclerosis.
Everything in the diet can affect cholesterolemia and experimental atherosclerosis. Dietary cholesterol has relatively little effect on blood cholesterol. Saturated fat is a major factor in cholesterolemia. In rabbits, triglyceride structure affects atherosclerosis but not blood cholesterol. Protein and carbohydrate effects are secondary to those of fat. Soluble fiber lowers blood lipid levels. In the United States the mortality from heart disease (age adjusted cases per 100,000) has been falling since 1968. The "French Paradox" is attributed variably to red wine, exercise or other factors but no generally accepted explanation is available. One area of nutrition research that is almost untouched is that of interaction of nutrients which may explain some of the dichotomies. A new trend to study dietary patterns rather than specific dietary components may help to elucidate observed effects. For healthy people the most reasonable dietary advice is moderation, balance and variety.
Animals↗
Cholesterol vehicle in experimental atherosclerosis. 23. Effects of specific synthetic triglycerides.
Earlier work has shown that increasing concentration of palmitic acid at the sn-2 position of a fat enhances the atherogenic properties of that fat. This effect has been observed with lard, tallow, cottonseed oil, and palm oil. In the experiment reported here, we have studied the atherogenic effects of four synthetic fats fed to rabbits as 58% (w/w) of the total fat (15%) (w/w) of a semipurified diet containing 0.05% cholesterol. The fats being tested were: 1,3-stearoyl-2-oleoylglycerol (SOS); 1,2-stearoyl-3-oleoylglycerol (SSO); 1,3-palmitoyl-2-oleoylglycerol (POP); and 1,2-palmitoyl-3-oleoylglycerol (PPO). After 20 wk on diet there were no differences among the groups in weight gain, liver weight, serum, or liver lipids. These data are consistent with our previous findings. There were significant differences in atherosclerosis. The most severe atherosclerosis was observed in group PPO and the least in groups SSO and POP. Severity of atherosclerosis was graded visually on a 0-4 scale. The average atherosclerosis [(aortic arch and thoracic aorta) divided by 2] was: SOS--1.35; SSO--0.97; POP--0.83; and PPO--1.80. Fecal fat excretion (an indicator of fat absorption) was higher in the two groups fed the stearic acid-rich fats and lower in groups fed the palmitic acid-rich fats. There were no differences in low density lipoprotein particle size. The results confirm previous findings concerning the increased atherogenicity of fats bearing palmitic acid at the sn-2 position. The mechanism underlying these observations is moot but may, in part, reflect greater absorption of the atherogenic fat.
Animals↗
Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits.
OBJECTIVE: To determine effects of conjugated linoleic acid (CLA) on establishment and progression of experimentally-induced atherosclerosis in rabbits. METHODS: For establishment of atherosclerosis, New Zealand White rabbits were fed a semipurified diet containing 0.1% to 0.2% cholesterol for 90 days. Some groups were fed diet and CLA. For effects on progression of atherosclerosis, rabbits with established atherosclerosis were fed a semipurified diet +/- CLA for 90 days. RESULTS: At dietary levels as low as 0.1%, CLA inhibited atherogenesis. At dietary levels of 1%, CLA caused substantial (30%) regression of established atherosclerosis. This is the first example of substantial regression of atherosclerosis being caused by diet alone. CONCLUSION: Dietary CLA is an effective inhibitor of atherogenesis and also causes regression of established atherosclerosis.
Animals↗
Egg consumption and coronary heart disease: an epidemiologic overview.
Serum cholesterol has been established as a modifiable risk factor for coronary heart disease. Experimental feeding studies show that saturated fat and cholesterol increase serum cholesterol levels; thus, dietary recommendations for lowering the risk of heart disease proscribe the intake of both substances. Recommendations have also included limits on the intake of eggs because of their high cholesterol content. In free-living populations, diet reflects a pattern of associated choices. Increases in one food may lead to changes in the consumption of other foods that may modulate disease risk. Epidemiologic data are helpful in assessing the importance of foods and nutrients in the context in which they are actually consumed. We review epidemiologic data relating dietary cholesterol and eggs to coronary disease risk. Cholesterol intake was associated with a modest increase in the risk of coronary events. The true magnitude of the association is difficult to estimate because most studies fail to account for potential confounding by other features of the diet. When a full-range of confounding factors was considered, the association between cholesterol intake and heart disease risk was small (6% increase in risk for 200mg/1,000kcal/day difference in cholesterol intake). Several studies have examined egg intake and its relationship with coronary outcomes. All but one failed to consider the role of other potentially confounding dietary factors. When dietary confounders were considered, no association was seen between egg consumption at levels up to 1 + egg per day and the risk of coronary heart disease in non-diabetic men and women.
Cholesterol, Dietary↗
Kenneth K. Carroll (1923-1998)
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Journal Article↗
Antimutagenic and some other effects of conjugated linoleic acid.
Conjugated linoleic acid (CLA) is a collective term for positional and geometric isomers of octadecadienoic acid in which the double bonds are conjugated, i.e. contiguous. CLA was identified as a component of milk and dairy products over 20 years ago. It is formed as an intermediate in the course of the conversion of linoleic acid to oleic acid in the rumen. The predominant naturally occurring isomer is the cis-9, trans-11 modification. Treatment of linoleic acid-rich oils such as safflower oil, soybean oil, or maize oil with base and heat will result in the formation of CLA. Two isomers predominate in the synthetic preparation, c9,t11 and t10,c12. CLA has been shown to inhibit chemically-induced skin, stomach, mammary or colon tumours in mice and rats. The inhibition of mammary tumours in rats is effective regardless of type of carcinogen or type or amount of dietary fat. CLA has also been shown to inhibit cholesterol-induced atherosclerosis in rabbits. When young animals (mice, pigs) are placed on CLA-containing diets after weaning they accumulate more body protein and less fat. Since CLA is derived from the milk of ruminant animals and is found primarily in their meat and in products derived from their milk there is a concerted world-wide effort to increase CLA content of milk by dietary means. Its effect on growth (less fat, more protein) is also a subject of active research. The mechanisms underlying the effects of CLA are still moot.
Animals↗
Protective role of wheat bran fiber: preclinical data.
Although animal data relating to the effects of dietary fiber on experimentally induced colon tumors are not easily summarized, it appears that wheat bran fiber protects against colon cancer. In a recent direct comparison, an ad libitum diet containing wheat bran fiber led to a 40% lower incidence of colon tumors, compared with a cellulose-containing diet. In addition, the greater protective effect of wheat bran fiber as compared with the cellulose was shown in rats fed 10% or 20% energy-restricted diets containing wheat bran or cellulose.
Animals↗
Effect of peanut oil and randomized peanut oil on cholesterol and oleic acid absorption, transport, and distribution in the lymph of the rat.
Peanut oil was shown to be atherogenic in cholesterol-fed rats, rabbits, and monkeys. However, after randomization, a process in which the fatty acids in peanut oil are randomly rearranged, its atherogenicity was significantly reduced in cholesterol-fed rabbits and monkeys. The mechanism for this effect remains unknown. This study was designed to investigate whether the absorption, transport and distribution of dietary cholesterol and oleic acid in the lymph were altered in the presence of peanut oil or randomized peanut oil. Previous investigators collected lymph through the mesenteric duct for 6 h and analyzed lymph for cholesterol. In the present study, lymph fluids were collected at timed intervals for up to 8 h and then at 24 h via the thoracic duct. Cholesterol and oleic acid (fatty acid) were estimated not only in the whole lymph but also in lymph lipoprotein fractions and in major lipid fractions. A 24-h lymph collection will enhance accuracy as short-term fluctuations in lipid absorption will not affect the results. Thoracic duct lymph collection is quantitative compared to mesenteric duct lymph collection, which provides only a fraction of the total lymph. Rats were given a lipid emulsion containing either peanut oil or randomized peanut oil. The emulsion also contained cholesterol, oleic acid, and sodium taurocholate in saline and was given through a duodenal catheter. Results show that absorption, transport, and distribution of cholesterol and oleic acid in the lymph fluids were similar in both dietary groups. These results suggest that the atherogenicity of peanut oil may be due to other events taking place subsequent to the release of cholesterol-containing chylomicrons and very low density lipoprotein by the small intestinal epithelial cells into the blood or may be due to the triglyceride structure itself.
Animals↗
Caloric restriction and experimental carcinogenesis.
Investigation into the influence of energy restriction in cancer has gone through 3 distinct periods. After the initial observation by Moreschi in 1909, there was about a decade of active research in this area. Then interest waned, possibly because the field had gone as far as it could, considering the knowledge and methodology available at the time. Interest was rekindled in 1940 due, principally, to the work coming from the laboratories of Tannenbaum at the Michael Reese Hospital in Chicago and Baumann at the University of Wisconsin. Another decade of active research followed. In this period, we learned how to design experimental diets and interest was expressed in dietary constituents. By 1950, publications on this type of research had dwindled and the field lay virtually dormant for 30 years. Since the early 1980's, research on this topic has blossomed and we now know enough about physiology and molecular biology to probe the mechanisms underlying the phenomenon. Energy flux, as in exercise, also inhibits carcinogenesis. Energy restriction modulates oxidative DNA damage and enhances DNA repair. It is now apparent that energy restriction affects adrenal metabolism (as hypothesized by Boutwell in 1949), insulin metabolism, and various aspects of gene expression. Understanding the basic mechanisms should provide important insights into control of tumor proliferation.
Animals↗
The lymphatic absorption of dihydrolanosterol and cholesterol in the rat.
Dihydrolanosterol (DHL) and its analogs have been studied extensively as cholesterol biosynthesis inhibitors. They inhibit specific steps in cholesterol synthesis by inhibiting lanosterol demethylase and by suppressing HMG-CoA reductase. The present study was designed to estimate the lymphatic absorption of DHL. For comparison, a cholesterol group was included. The left thoracic duct of male Wistar rats weighing between 210 and 230 g was cannulated. A lipid emulsion containing 0.75microCi of either [3H]-DHL or [3H]-cholesterol was given intragastrically. After the lipid meal, lymph was collected at 3 h intervals up to 9 h and then at 24 h. Radioactivity of DHL and cholesterol in the lymph was estimated. Lipid extracts of lymph specimens were also subjected to thin layer chromatography and fractions of DHL, cholesterol and their esters were isolated and the masses were estimated. There were no differences in lymph volumes between the two groups. However, absorption and esterification of DHL in lymph were significantly reduced compared with the cholesterol group. The marked decrease in the esterification of DHL is likely due to its poor absorption into the mucosal cell and subsequently into the lymphatic system. The amount of DHL available in the mucosal cell for esterification may be a limiting factor.
Animals↗
Lectin may contribute to the atherogenicity of peanut oil.
Peanut oil is unexpectedly atherogenic for rats, rabbits, and primates. The lesions it produces are more fibrous than fatty. The mechanism underlying the atherogenicity of peanut oil has been elusive. Randomization of peanut oil reduces significantly its atherogenic properties, but native and randomized peanut oils have similar rates of lipolysis, and rats fed the two oils absorb and transport lipids in a similar fashion. Peanut oil differs from other oils in having a relatively high lectin content, and the randomization process markedly reduces the lectin content as well. The biologically active lectin of peanut oil has an affinity for glycoproteins found specifically on arterial smooth muscle cells. Peanut lectin has been shown to stimulate growth of smooth muscle and pulmonary arterial cells. Vigorous washing of peanut oil reduces its lectin content by 46%. Compared to rabbits fed cholesterol and peanut oil, rabbits fed cholesterol and washed peanut oil exhibited less severe atherosclerosis in the aortic arch (by 9%) and in the thoracic aorta (by 31%). The data suggest that peanut oils' endogenous lectin may contribute significantly to its atherogenic properties.
Animals↗
Atherosclerosis: aortic lipid changes induced by diets suggest diffuse disease with focal severity in primates that model human atheromas.
Atherosclerosis in Vervet or African Green monkeys (Cercopithecus aethiops) models the morphology and cytology of the disease of humans, and it is well established that the rate of atherogenesis in Vervets is influenced by diet. Aortic intimal concentrations of lipids and phospholipids known to be major components of atheromas were determined in female Vervets fed for 4 years on either an atherogenic (AD) or a prudent Western diet (PD). Lipid concentrations detectable microscopically as cholesterol crystals and foam cells were confirmed biochemically. In addition, the AD was associated with diffuse, invisible accumulation of lipids throughout aortic tissue to the extent that tissue with no fatty streaks or plaque (AD) contained the same or more lipids than visible fatty streaks (PD). Correlations between lipid concentrations and atherosclerosis were highly positive, which supports known correlations between aortic, plasma, and dietary lipids during atherogenesis, and validates the aortic lipid analysis. These aortic lipid concentration results imply that atherosclerosis is not confined to focal pathologic anatomy, but in terms of lipid components of the disease, it develops throughout the arterial system of Old World omnivorous primates. If the results are applicable to people, they provide new insight and emphasize the need to minimize dietary sources of atherogenic lipids.
Animals↗
History of recommendations to the public about dietary fat.
Recommendations to Americans concerning dietary fat and heart disease began to appear in the late 1950s. This followed the publications of Gofman et al. (1950) and Keys (1953) relating to techniques for separating plasma lipoprotein fractions and the epidemiologic correlations between dietary fat, serum cholesterol and heart disease, respectively. Advice to the public after 40 years is similar to that given originally, namely, to reduce total fat, saturated fat and cholesterol intake, although cholesterol intake per se is not correlated strongly with cholesterolemia. Newer players on the heart disease stage are homocysteinemia, chlamydia infection and cytomegalovirus. These findings, when amplified, may alter the thrust of medical and dietary advice. In the meantime, since 1950, deaths from all causes in the U.S. (per 100,000, age-adjusted) have fallen by 40% and deaths from heart disease and stroke have fallen by 53 and 70%, respectively.
Arteriosclerosis↗
Cereal fibres and colorectal cancer: a search for mechanisms.
The relationship between fibre intake and risk of colorectal cancer has occupied the attention of scientists and physicians for more than two decades. No satisfying, generalized mechanism for the observed effects has yet been formulated, which is not surprising, since fibre is only one component of a varied diet. Currently, the effects of the short-chain fatty acids offer the most interesting and plausible leads.
Colorectal Neoplasms↗