Pancytopenia during ingestion of alfalfa seeds.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M R Malinow.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We determine the effects of alfalfa top saponins on cholesterol and bile acid balance in eight cynomolgus macaques (Macaca fascicularis). The monkeys ate semipurified food containing cholesterol with or without added saponins. The saponins decreased cholesterolemia without changing the levels of high density lipoprotein-cholesterol; hence, they reduced the total cholesterol/high density lipoprotein-cholesterol ratio. Furthermore, they decreased intestinal absorption of cholesterol, increased fecal excretion of endogenous and exogenous neutral steroids and bile acids, and decreased the percent distribution of fecal deoxycholic and lithocholic acids. The fecal excretion of fat was also slightly increased, but steatorrhea did not occur. We saw no signs of toxicity in the monkeys after 6 or 8 wk of saponin ingestion. The data suggest that alfalfa top saponins may be of use in the treatment of patients with hypercholesterolemia, but long-term studies on possible toxicity are needed before this therapy can be recommended for humans.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Changes of arterial wall lipid and connective tissue components were studied under various regression regimes on experimental high fat-cholesterol diet induced atherosclerosis in non-human primates. Levels of plasma lipids and aorta tissue lipids were closely related, while an inverse relationship between plasma cholesterol levels was noted with the ratio of aorta tissue free/ester cholesterol. Although the total content of glycosaminoglycan increased slightly with increasing disease, changes of individual glycosaminoglycans were most closely related to the severity of aorta atherosclerosis associated with both induction and regression of disease. With increasing atherosclerosis hyaluronic acid tended to decrease, while chondroitin sulfates decreased. Heparan sulfate decreased considerably with increasing severity of atherosclerosis. Consequently, regression regimens reducing the severity reversed the glycosominoglycan changes. Withdrawal of the dietary stimulus and cholestryamine produced the greatest reversal of atherosclerosis. In contrast, D-thyroxine treatment resulted in severe aorta atherosclerosis comparable to controls receiving no treatment. The effectiveness of regression depends on favorably altering plasma lipids but without adversely affecting the arterial wall structural elements.
Plasma cholesterol concentrations were reduced in 3 human volunteers during ingestion of diets containing alfalfa seeds (AS) for 3 weeks. No signs of toxicity were detected through serum determinations of multiple parameters. The ingestion of AS in rats decreased the concentration of plasma cholesterol, reduced intestinal absorption of exogenous and endogenous cholesterol, and increased fecal biliary excretion.
The long-term dropout rate was examined in a physical exercise rehabilitation program in which 203 cardiac patients were followed for 40 months. The dropout curve was found to be downward-sloping and negatively accelerated with most of the dropouts occurring during the first 3 months. This dropout rate appeared to resemble the group release curve previously found in the treatment of addictive behaviors. Implications of the present findings are discussed in terms of the development of strategies to facilitate long-term compliance.
plasma and aortic tissue lipid changes in atherosclerotic Macaca fascicularis monkeys were studied following various regression regimens for 18 months. Atherosclerosis was induced in groups of 18 Macaca fascicularis monkeys by feeding a semipurified diet containing 43% of the calories as fat and 1.2 mg/kcal cholesterol for 6 months. Five groups of animals were continued on the same diet containing 0.34 mg/kcal cholesterol during the regression period, and were given the following hypocholesterolemic regimens: none (positive controls); D-thyroxine; pyrimidine derivative; cholestyramine; and alfalfa. Another group of animals was maintained on regular monkey chow alone during the regression period (negative control). Among the hypocholesterolemic agents, cholestyramine very effectively reduced the plasma cholesterol, and aorta free- and esterified cholesterol and phospholipids. D-Thyroxine significantly lowered the plasma cholesterol levels but, surprisingly, tissue lipid levels were the highest among the groups studied. Alfalfa, although not as effective as cholestyramine, tended to reduce the plasma and tissue lipids more than other drugs. Pyrimidine derivative actually increased the mean levels of plasma and tissue cholesterol. Plasma cholesterol correlated positively with aortic tissue cholesterol, free and esterified cholesterol. Both the plasma percentage distribution of alpha-lipoprotein and the phospholipid/cholesterol ratio were inversely related to all tissues lipids. Plasma cholesterol accounted for 43% and 30% respectively of the variability in tissue total and esterified cholesterol. Thus the effectiveness of any hypocholesterolemic regimen is probably dependent on achieving a favorable lipoprotein distribution in plasma without any adverse effect on the arterial wall metabolism.
Since alfalfa meal prevents hypercholesterolemia and atherosclerosis in rabbits and alfalfa saponins prevent the expected rise in cholesterolemia induced by dietary cholesterol in monkeys, the experiments being reported here were performed to determine whether alfalfa saponins affect atherogenesis in rabbits. In addition, the effects of alfalfa seeds were studied. Cholesterol-feb rabbits were randomly assigned to 3 groups: (a) control animals (N = 18); (b) animals maintained on a diet containing 1.0 to 1.2% alfalfa saponins (N = 18); and (c) animals maintained on a diet containing 40% alfalfa seeds (N = 17). Results after a 4-month observation period demonstrated that alfalfa saponins and alfalfa seeds reduce hypercholesterolemia, aortic sudanophilia, and the concentration of cholesterol in aortic intima-plus-media and in the liver, but do not induce changes in the hematocrit.
Explore the source record for details and available documents.
The activity of prolyl hydroxylase and the rate of collagen synthesis were examined in two anatomically different arterial segments of cholesterol-fold cynomolgus monkeys. In the aortic arch vessels the activity of prolyl hydroxylase was increased after six months on a high fat and high cholesterol diet. In this tissue the enzyme activity showed positive correlation with the levels of plasma and tissue cholesterol content. By contrast in the abdominal aortas of the same animals no significant increase of arterial tissue cholesterol or prolyl hydroxylase activity was seen. Despite the elevation of prolyl hydroxylase activity in the arch vessels of hyper cholesterolemic animals, no concomitant increase of collagen synthesis was seen. Neither cholesterolemia nor arterial cholesterol showed a positive correlation with the rate of arterial collagen synthesis. No significant changes of the rate of collagen metabolism were detected at the end of an 18 months intervention phase when the cholesterol content both in plasma and in the arterial tissue was substantially reduced.
Fundus color photographs and retinal fluorescein angiograms were obtained from 48 nonhuman primates of three macaque species. Yellow pigmentation of the macula was present in monkeys fed a standard laboratory diet containing xanthophylls but was absent in animals maintained on semipurified or liquid formula diets with no xanthophyll content. Plasma levels of xanthophylls ranged from 0.5 to 2.4 microliters/ml in monkeys receiving the standard diet but were undetectable in animals raised on semipurified or liquid formula diets. Fluorescein angiograms revealed foveal areas of hyperfluorescence in almost all monkeys; however, the degree of hyperfluorescence was significantly greater in monkeys maintained on the semipurified or liquid formula diets.
Intestinal absorption of cholesterol was measured in control rats fed semipurified diets and in rats fed alfalfa meal, in which saponins had been previously extracted, or this extracted material plus alfalfa saponins. A dose of 2 mg radioactive cholesterol was administered intragastrically, and fecal excretion of labeled neutral steroids measured. Absorption of cholesterol was about 76% in control animals, and about 47% in alfalfa-red rats. Extraction of saponins from alfalfa eliminated the cholesterol absorption-lowering effect, while addition of 0.26% alfalfa saponins to the extracted alfalfa restored its activity. The results demonstrate that alfalfa saponins are responsible for the effect of alfalfa meal in reducing cholesterol absorption, and that alfalfa fiber is not involved in this activity.
A semipurified diet containing 1.2 mg of cholesterol/Cal was fed to cynomolgus monkeys (Macaca fascicularis). At the end of 6 months, a group of 18 animals was killed for evaluation of atherosclerosis in the aorta and the coronary arteries. The remaining monkeys were assigned to three groups of 18 animals each and fed, during the following 18 months, semipurified diets containing 0.34 mg of cholesterol/Cal with or without alfalfa meal, or a diet consisting entirely of Monkey Chow. a decrease in cholesterolemia and plasma phospholipid levels, normalization in the distribution of plasma lipoproteins, and reduction in the extent of aortic and coronary atherosclerosis were observed in monkeys fed the semipurified diet containing alfalfa, although the intake of cholesterol remained as high as in the usual American diet. These changes, also observed in monkeys fed a chow diet almost devoid of cholesterol, suggest that alfalfa counteracts the atherogenic effect of dietary cholesterol.
A semipurified diet containing 43% of the calories as fat and 1.2 mg of cholesterol/cal was fed to cynomolgus monkeys (Macaca fascicularis) for 6 months; the cholesterol content was reduced to 0.34 mg/cal for the next 18 months. During the latter period, the monkeys were assigned to 4 groups of 18 animals each and received the following dietary additions: A, none (controls); B, cholestyramine (5%, w/w); C, dextrothyroxine (0.003%); and D, Wy-14,643 (0.45%). Cholestyramine normalized plasma lipid levels and reduced the size of aortic and coronary atherosclerotic lesions in spite of the high-fat, high-cholesterol intake. Dextrothyroxine reduced cholesterolemia but did not modify the extent of arterial lesions. Wy-14,643 changed neither plasma cholesterol levels nor the extent of atherosclerosis.
Digitonin mixed in the diet was well tolerated by rats and cynomolgus monkeys (Macaca fascicularis), and prevented the expected rise in plasma cholesterol in monkeys fed a diet containing butter and cholesterol. Both digitonin and mildly hydrolyzed digitonin precipitated cholesterol dispersed in micellar suspensions and decreased intestinal absorption of cholesterol in rats, but only digitonin bound cholesterol in vitro. The hypocholesterolemic effect of digitonin may be secondary to decreased intestinal absorption of cholesterol associated with a disturbance in the micellar suspension of cholesterol in the intestinal content. Modification of other mechanisms that may be involved in membrane transport of cholesterol through the intestinal epithelium is not ruled out by the present findings.