Marvin L. Bierenbaum

Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis

Antioxidants may have a role in the prevention of atherosclerosis. In the present trial, we investigated the antioxidant properties of Palm Vitee, a γ-tocotrienol-, and α-tocopherol enriched fraction of palm oil, in patients with carotid atherosclerosis. Serum lipids, fatty acid peroxides, platelet aggregation, and carotid artery stenosis were measured over an 18-month period in fifty patients with cerebrovascular disease. Change in stenosis was measured with duplex ultrasonography. Ultrasound scans were done at six months, twelve months, and yearly thereafter. Bilateral duplex ultrasonography revealed apparent carotid atherosclerotic regression in seven and progression in two of the 25 tocotrienol patients, while none of the control group exhibited regression and ten of 25 showed progression (P<0.002). Serum thiobarbituric acid reactive substances, anex vivo indicator of maximal platelet peroxidation, decreased in the treatment group from 1.08±0.70 to 0.80±0.55 μM/L (P<0.05) after 12 mon, and in the placebo group, they increased nonsignificantly from 0.99±0.80 to 1.26±0.54 μM/L. Both tocotrienol and placebo groups displayed significantly attenuated collagen-induced platelet aggregation responses (P<0.05) as compared with entry values. Serum total cholesterol, low density lipoprotein cholesterol, and triglyceride values remained unchanged in both groups, as did the plasma high density lipoprotein cholesterol values. These findings suggest that antioxidants, such as tocotrienols, may influence the course of carotid atherosclerosis.

γ-tocotrienol as a hypocholesterolemic and antioxidant agent in rats fed atherogenic diets

This study was designed to determine whether incorporation of γ-tocotrienol or α-tocopherol in an atherogenic diet would reduce the concentration of plasma cholesterol, triglycerides and fatty acid peroxides, and attenuate platelet aggregability in rats. For six weeks, male Wistar rats (n=90) were fed AIN76A semisynthetic test diets containing cholesterol (2% by weight), providing fat as partially hydrogenated soybean oil (20% by weight), menhaden oil (20%) or corn oil (2%). Feeding the ration with menhaden oil resulted in the highest concentrations of plasma cholesterol, low and very low density lipoprotein cholesterol, triglycerides, thiobarbituric acid reactive substances and fatty acid hydroperoxides. Consumption of the ration containing γ-tocotrienol (50 μ/kg) and α-tocopherol (500 mg/kg) for six weeks led to decreased plasma lipid concentrations. Plasma cholesterol, low and very low density lipoprotein cholesterol, and triglycerides each decreased significantly (P<0.001). Plasma thiobarbituric acid reactive substances decreased significantly (P<0.01), as did the fatty acid hydroperoxides (P<0.05), when the diet contained both chromanols. Supplementation with γ-tocotrienol resulted in similar, though quantitatively smaller, decrements in these plasma values. Plasma α-tocopherol concentrations were lowest in rats fed menhaden oil without either chromanol. Though plasma α-tocopherol did not rise with γ-tocotrienol supplementation at 50 mg/kg, γ-tocotrienol at 100 mg/kg of ration spared plasma α-tocopherol, which rose from 0.60±0.2 to 1.34±0.4 mg/dL (P<0.05). The highest concentration of α-tocopherol was measured in plasma of animals fed a ration supplemented with α-tocopherol at 500 mg/kg. In response to added collagen, the partially hydrogenated soybean oil diet without supplementary cholesterol led to reduced platelet aggregation as compared with the cholesterol-supplemented diet. However, γ-tocotrienol at a level of 50 mg/kg in the cholesterol-supplemented diet did not significantly reduce platelet aggregation. Platelets from animals fed the menhaden oil diet released less adenosine triphosphate than the ones from any other diet group. The data suggest that the combination of γ-tocotrienol and α-tocopherol, as present in palm oil distillates, deserves further evaluation as a potential hypolipemic agent in hyperlipemic humans at atherogenic risk.

Long term human studies on the lipid effects of oral calcium

Ingestion of 2 g of supplemental dietary calcium carbonate daily over a period of one year by eight hyperlipemic men and two hyperlipemic women caused a significant 25% decrease in serum cholesterol, after these subjects had shown stable levels for the previous year, and when compared to a group without therapy. Body weights for both groups remained stable throughout the period of observation. The experimental group also showed a reversal in the cholesterol-phospholipid ratio from a preexperimental ratio of 1.04 to a ratio of 0.92. In addition there was a 113 mg per 100 ml decrease in serum triglycerides and a 48 mg per 100 ml decrease in serum phospholipids, but these were not statistically significant due to the large between individual variations and the limited sample size. Calcium carbonate should be considered as a potential agent for usage in long term studies designed to produce hypolipemia, since it appears to be effective and without significant side effects.

Effect of red and white wine on serum lipids, platelet aggregation, oxidation products and antioxidants: A preliminary report

Abstract Recent studies suggest a protective effect of moderate alcohol consumption upon the incidence of coronary heart disease (CHD). Since red wine was proposed to be most beneficial, a three-month crossover design comparing the effects of red versus white wine upon serum lipids, clotting factors, oxidation products and antioxidant levels in twenty adult hypercholesterolemics was undertaken. Combining data from both wines showed a reduced thrombin-initiated platelet aggregation (THROM) from 0.91±0.06 to 0.75±0.04 U/ml, p

In vivo platelet function in acute myocardial infarction, acute cerbrovascular accidents and following surgery

Abstract In vivo platelet aggregation time is significantly decreased and platelet disaggregation time is significantly increased in patients suffering an acute myocardial infarction or acute cerebrovascular accident. Postsurgical patients exhibited a similar effect.

The 5-year experience of modified fat diets on younger men with coronary heart disease.

This is a study of 100 men, 30 to 50 years old, with documented coronary artery disease and past myocardial infarction who were placed under dietary management with a 28% fat diet. One hundred men whose diets were not managed were matched with regard to age at entry to the study, age at infarction, number of infarctions, blood pressure level, degree of angina, and serum cholesterol level among other factors. Over a period of 5 years the diet-managed group experienced and maintained a significant reduction in serum cholesterol level which the nondiet-managed group did not. Under the diet and experimental conditions employed, with saturated fat content below 9% of calories, and cholesterol intake below 400 mg per day, the degree of unsaturation of the fats in the experimental diets did not appear to influence serum cholesterol value or mortality. The serum triglyceride level was significantly lower in the diet-managed group than in the nondiet-managed group; this was presumably related to weight reduction. In the group under dietary management, fatal and nonfatal myocardial reinfarction rates were lower but were statistically significantly so only for the fatal infarction rates in men under age 45. Serum phospholipids above 220 mg/100 ml were associated with a significantly lower rate of recurrent infarction.

Effect of Stress Due to Anticipated Minor Surgery upon in Vivo Platelet Aggregation in Humans

When measured just prior to hospital admission, platelet aggregation was faster and systolic and diastolic blood pressure were higher compared to measurements just prior to surgery and upon discharge fromthe hospital.

Effect of dietary menhaden, Canola and partially hydrogenated soy oil supplemented with vitamin E upon plasma lipids and platelet aggregation.

Male Fisher rats were fed chow diets for two weeks after which they were divided into seven groups of ten rats each and fed 20% Canola, 20% menhaden, 20% partially hydrogenated soy oil (PHSO) or chow only, with or without 500 mg/Kg dietary vitamin E in chow containing 2% cholesterol for six weeks. Triglycerides were lower in the menhaden group and were essentially the same in the E supplemented groups as in their unsupplemented cohorts. Plasma cholesterol was higher in the Canola, and lower in the menhaden, groups, compared to the PHSO group. Cholesterol was the same in the E supplemented groups as in their unsupplemented cohorts. Plasma thiobarbituric acid reactant substances (TBARS) were higher in the menhaden group, compared to the chow group. Vitamin E supplementation lowered TBARS in the menhaden and PHSO groups, compared to the unsupplemented cohorts. Collagen induced platelet aggregation was lower in both Canola and menhaden groups, compared to the PHSO group. Vitamin E supplementation lowered collagen induced platelet aggregation only in the PHSO group. Thrombin induced platelet aggregation was lower in the Canola group, compared to the PHSO group. Vitamin E supplementation did not affect thrombin induced platelet aggregation compared to unsupplemented cohorts. Plasma vitamin E levels were lowest in the menhaden supplemented group compared to all other groups not receiving E, suggesting a greater requirement for E in this group. Finally, vitamin E supplementation raised the plasma E levels in all groups except the menhaden group when compared to unsupplemented cohorts.

The hypolipidemic effect of calcium-containing compounds and vitamin D2 in the rat

Two per cent dietary calcium carbonate alone (Group 1), in combination with vitamin D2 (Group 2) or oyster shell calcium with vitamin D2 (Group 3), was added to an atherogenic diet containing 20% fat and 2% cholesterol and fed to adult male Holtzman strain rats to evaluate the hypolipidemic effects of these supplements. A control group received the same diet, but the calcium was replaced by sand. After 21 days the serum cholesterol concentrations were lower by 35, 27 and 22%, respectively, in experimental groups 1, 2 and 3, compared to the controls. Serum triglyceride concentrations were lower by 10% in experimental groups 1, 2 and 3, compared to the controls. Serum triglyceride concentrations were lower by 10% in groups 1 and 2, and 17% in group 3. Concomitant with these decreases in serum lipids, there were increases in fecal 3-β-hydroxy-5-ene sterol, total glyceride and free fatty acid excretion. Serum calcium was elevated in the rats fed diets containing calcium when compared with the controls, whereas serum magnesium was depressed in thesy animals. Less calcium was excreted in the feces of rats fed calcium carbonate in combination with vitamin D than in those fed calcium carbonate. The results indicate a possible means of simultaneously treating both calcium deficiency and hyperlipidemia with a single agent.

The effects of two low fat dietary patterns on the blood cholesterol level of young male coronary patients.

Abstract 1. 1. Ninety-nine male patients between the ages of 20 yr and 50 yr with documented myocardial infarctions were randomly divided into two diet therapy groups. The comparability of these two groups was defined with regard to age, age at time of infarction, family history of coronary heart disease, prevalence of hypertension, degree of angina, height, weight, long-term anti-coagulant therapy, electrocardiographic severity and blood cholesterol level. 2. 2. The diet plans for two 30 per cent fat diets, one high in polyunsaturated fatty acid to saturated fatty acid and the second with reciprocal ratio, were outlined. 3. 3. Forty-eight subjects who were in the study for one year and maintained or achieved ideal weight were followed on these diet patterns. In the two groups studied, there was no significant difference in cholesterol response. 4. 4. Weight loss was comparable prior to beginning either assigned diet. 5. 5. The diets utilized in the entire group reduced blood cholesterol levels by 23 mg per 100 ml or 9 per cent over the 12-month period. 6. 6. A 30 per cent fat diet, with or without an unsaturated fat supplement, appears to be a satisfactory and palatable regimen for free-living adult males for as prolonged a period as one year. This fact is corroborated by a less than 5 per cent drop-out rate during this period of study. 7. 7. There appears to be a relationship between weight reduction and cholesterol change in the group studied.