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Biomedical subjects

W S Harris

Publications and source records attributed to W S Harris.

At least 37 records · Page 2Linked to original sources
PubMed1997

Influence of n-3 fatty acid supplementation on the endogenous activities of plasma lipases.

The aim of these studies was to explore the possibility that enhanced triacylglycerol clearance may contribute to the hypotriacylglycerolemic effect of n-3 fatty acids in humans. Healthy subjects (n = 20) and hypertriacylglycerolemic patients (n = 6) were given a placebo (olive oil, OO) or a fish-oil concentrate (FOC; 41% eicosapentaenoic acid and 23% docosahexaenoic acid) in two, independent, randomized, blind trials. For the healthy subjects, the FOC treatment period was 3 wk long and FOC intakes were 5 g/d. For the patients, treatment periods were 4 wk long and dosages were 5 g.70 kg body wt-1.d-1. Washout periods were 2-4 wk for both groups. Blood samples were drawn at the end of each phase and analyzed for plasma lipids, lipoproteins, and endogenous (nonheparin-stimulated) activities of lipoprotein lipase (LPL) and hepatic lipase (HL). In the healthy subjects the FOC decreased plasma triacylglycerol concentrations by 18% (P < 0.01), whereas in the patients concentrations were reduced by 35% (P < 0.05). Low-density-lipoprotein-cholesterol concentrations increased by 25% in the latter group (P = 0.06). FOC increased the endogenous activities of LPL and HL by 62% and 68%, respectively (P < 0.0001), in the healthy subjects, but only LPL in the patients (65%, P < 0.005). These data suggest that endogenous lipase activities may be altered by nutritional interventions, and further, that accelerated lipolysis could contribute, at least in part, to the observed effects of n-3 fatty acids on human lipoprotein metabolism.

Fatty Acids, Omega-3↗
PubMed1997

Inhibiting cholesterol absorption with CP-88,818 (beta-tigogenin cellobioside; tiqueside): studies in normal and hyperlipidemic subjects.

CP-88,818 (beta-tigogenin cellobioside; tiqueside) is a synthetic saponin developed to treat hypercholesterolemia by inhibiting the absorption of biliary and dietary cholesterol. Two studies are reported here: one in patients to assess safety and efficacy, and one in normal volunteers to explore the mechanism of action. The former included 15 hypercholesterolemic outpatients [low-density lipoprotein cholesterol (LDL-C) > or = 160 mg/dl] treated with 1, 2, and 3 g of tiqueside daily (b.i.d.) in a crossover design for three 2-week treatment periods, each separated by a 3-week placebo period. The mechanistic study was conducted with 24 healthy male subjects who were randomized in a parallel group design to either placebo (n = 6) or tiqueside (2 or 4 g/day; n = 9 each) once daily for 3 weeks. All subjects in this study were fed a low-fat, low-cholesterol diet [National Cholesterol Education Program (NCEP) Step 1]. Fecal steroid excretion rates and plasma lipid levels were determined at baseline and after 3 weeks of treatment. Fractional cholesterol absorption was measured before and after treatment by the continuous feeding, dual-isotope method. Tiqueside produced a dose-dependent reduction in plasma LDL cholesterol levels in the hypercholesterolemic patients. In the mechanistic study, it decreased fractional cholesterol absorption rates and increased fecal neutral sterol excretion rates, changes associated with trends toward lower LDL cholesterol levels. Other lipoprotein levels were unaffected, as were fecal fat and bile acid excretion and fat-soluble vitamin absorption. Thus tiqueside dose-dependently inhibits cholesterol absorption in humans, resulting in a reduction in serum LDL cholesterol levels.

Adolescent↗
PubMed1997

Exercise training, postprandial hypertriglyceridemia, and LDL subfraction distribution.

The purpose of this study was to examine differences in postprandial hypertriglyceridemia (PP-HTG) and low density lipoprotein (LDL) subfraction distribution among groups of men and women with different fitness levels. Fifty-four men and women (ages 30-53 yr) were recruited based on their previous two-year activity level: sedentary (S), recreational exercisers (R), and endurance trained (T). After a 24-h dietary preparation, blood was collected, and LDL subfractions were separated and analyzed for cholesterol (C) and apoprotein B100. Plasma triglyceride (TG) concentration was assessed before and at 2, 4, 6, and 8 h after fat meal. PP-HTG was significantly higher for the S group compared with the two activity groups. LDL3-C and LDL3-apoprotein B100 were significantly higher for the S group compared with the T group and for men compared with women. These findings suggest that both recreational and competitive aerobic training are associated with a lower TG response after a fatty meal. However, higher volume aerobic training may be necessary to reduce the number of dense LDL molecules and their cholesterol content.

Adult↗
PubMed1997

N-3 fatty acids and chylomicron metabolism in the rat.

Dietary n-3 fatty acids (FAs) reduce postprandial triacylglycerol concentrations in humans by unknown mechanisms. Our goals were to reproduce this phenomenon in the rat, and then to determine the mechanism. In an oral fat tolerance study two groups of rats were fed diets containing 2.1% ethyl esters of n-3 FA or olive oil for 2 weeks. After gavaging with emulsified soybean oil, the postprandial chylomicron triacylglycerol levels in the n-3 FA group were reduced by 40% (P < 0.05). The hypothesis that n-3 FA feeding reduced chylomicron production/secretion from the gut was tested by blocking chylomicron removal with Triton WR1339 before gavaging the rats with the fat load. This completely eliminated the hypochylomicronemic effect suggesting that chylomicron input was not inhibited by n-3 FAs. Chylomicron clearance was studied by injecting chylomicrons containing radioactive retinyl esters and triacylglycerol into rats from both groups. Pre-feeding with n-3 FAs accelerated the removal of chylomicron triacylglycerol and retinyl esters from the plasma with significantly lower fractions of dose remaining at 2, 4, and 8 min post-injection for both tracers. These findings suggest than n-3 FAs reduce postprandial chylomicronemia in the rat by accelerating chylomicron lipid clearance.

Animals↗
PubMed1996

n-3 fatty acids and lipoproteins: comparison of results from human and animal studies.

The impact of n-3 fatty acids (FA) on blood lipoprotein levels has been examined in many studies over the last 15 yr in both animals and humans. Studies in humans first demonstrated the potent triglyceride-lowering effect of n-3 FA, and these were followed up with animal studies to unravel the mechanism of action. This paper reviews the reported effects of n-3 FA on blood lipoproteins in 72 placebo-controlled human trials, at least 2 wk in length and providing 7 or less g of n-3 FA/day. Trials in normolipidemic subjects (triglycerides < 2.0 mM; 177 mg/dL) were compared to those in hypertriglyceridemic patients (triglycerides > or = 2.0 mM). In the healthy subjects, mean triglyceride levels decreased by 25% (P < 0.0001), and total cholesterol (C) levels increased by 2% (P < 0.009) due to the combined increases in low density lipoprotein (LDL)-C (4%, P < 0.02) and high density lipoprotein (HDL)-C (3%, P < 0.008). In the patients, triglyceride levels decreased by 28% (P < 0.0001), LDL-C rose by 7% (P < 0.0001), but neither total C nor HDL-C changed significantly. Although the effect on triglyceride levels is also observed in rats and swine, it is rarely seen in mice, rabbits, monkeys, dogs, and hamsters. Whereas n-3 FA have only a minor impact on lipoprotein C levels in humans, they often markedly lower both total C and HDL-C levels in animals, especially monkeys. These differences are not widely appreciated and must be taken into account when studying the effects of n-3 FA on lipoprotein metabolism.

Animals↗
PubMed1996

Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans.

The aim of this study was to determine whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), or both, were responsible for the triglyceride (TG)-lowering effects of fish oil. EPA (91% pure) and DHA (83% pure), a fish oil concentrate (FOC; 41% EPA and 23% DHA) and an olive oil (OO) placebo (all ethyl esters) were tested. A total of 49 normolipidemic subjects participated. Each subject was given placebo for 2-3 wk and one of the n-3 supplements for 3 wk in randomized, blinded trials. The target n-3 fatty acid (FA) intake was 3 g/day in all studies. Blood samples were drawn twice at the end of each supplementation phase and analyzed for lipids, lipoproteins, and phospholipid FA composition. In all groups, the phospholipid FA composition changed to reflect the n-3 FA given. On DHA supplementation, EPA levels increased to a small but significant extent, suggesting that some retroconversion may have occurred. EPA supplementation did not raise DHA levels, however. FOC and EPA produced significant decreases in both TG and very low density lipoprotein (VLDL) cholesterol (C) levels (P < 0.01) and increases in low density lipoprotein (LDL) cholesterol levels (P < 0.05). DHA supplementation did not affect cholesterol, triglyceride, VLDL, LDL, or high density lipoprotein (HDL) levels, but it did cause a significant increase in the HDL2/HDL3 cholesterol ratio. We conclude that EPA appears to be primarily responsible for TG-lowering (and LDL-C raising) effects of fish oil.

Adult↗
PubMed1996

Dietary fish oil and blood lipids.

Triglyceride lowering is the most consistent effect of fish oils, having been observed in Greenland Eskimos and subsequently in controlled clinical trials. Although total cholesterol levels are not altered, LDL levels may rise, especially in hypertriglyceridemic patients. The persistence of the hypotriglyceridemic effect has been documented in two recent trials following large numbers of patients from 6-9 months. These studies also provided evidence that the LDL raising effect may not persist. The safety of fish oils was also supported in these studies because problems with excessive bleeding and worsening glycemic control did not materialize. However, in one of these studies fish oils proved ineffective in slowing the rate of restenosis after coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1996

Lifestyle change for coronary artery disease. What to tell patients.

Heart-healthy living is a wise choice for anyone, but it assumes even greater importance in persons who have or are at risk for coronary artery disease. Such patients need to know which measures have proved most effective in the prevention and treatment of the disease. This article reviews the data regarding risk factor reduction and offers recommendations for effective lifestyle modifications.

Alcohol Drinking↗
PubMed1995

Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia.

This study was designed to evaluate the therapeutic effectiveness of 3 different pharmacologic lipid-lowering regimens in the treatment of patients with clustered lipid risk factors. Sixty-five patients with low high-density lipoprotein (HDL) levels and hypertriglyceridemia were randomized to 1 of 3 treatment arms: pravastatin/niacin, pravastatin/magnesium, or pravastatin/placebo. After 18 weeks, patients in the pravastatin/niacin group had a -41% change in the total cholesterol/HDL ratio compared with -13% in the pravastatin/magnesium arm and -16% in the pravastatin/placebo group. The HDL2 and HDL3 subfractions, as well as the apolipoprotein A-I levels, were increased significantly only in the pravastatin/niacin arm. The levels of small dense low-density lipoprotein (LDL) cholesterol (LDL3) were decreased to a greater extent in the pravastatin/niacin arm (-43%) than in either the pravastatin/magnesium (-13%) or the pravastatin/placebo (-20%) arm. Only the pravastatin/niacin regimen significantly diminished postprandial lipemia (-32% change in the remnant particle triglyceride concentration and decreased very-low-density lipoprotein remnant levels). Thus, in this group of patients with clustered risk factors, the combination of pravastatin and niacin resulted in significant improvements in HDL and triglyceride levels, total cholesterol to HDL ratio, small dense LDL levels, and postprandial lipemia. Pravastatin alone or in combination with magnesium resulted in less significant changes that were largely limited to LDL cholesterol reduction.

Adult↗
PubMed1995

Comparison of two scoring systems used to monitor diets in outpatient clinical trials.

BACKGROUND: Dietary stability and compliance are crucial to the proper interpretation of the results of clinical trials evaluating the efficacy of lipid-lowering drugs since dietary variations can obscure the true effects of the drugs being tested. Documentation of compliance to National Cholesterol Education Program (NCEP) dietary guidelines can be difficult to obtain, however, especially since many diets may meet one or two but not all the criteria for a Step 1 or 2 classification. The purpose of this study was to compare the ability of two diet scoring systems (the Food Record Rating [FRR] and the Ratio of Ingested Saturated fat and Cholesterol to Calories [RISCC]) to classify these ambiguous diets. METHODS: Three-day diet diaries (n = 622) were obtained from patients participating in a multicenter, clinical trial testing the lipid-lowering effects of a fiber supplement. The FRR score of each diary was calculated; the diary was then computer analyzed for nutrient composition, and the RISCC score was calculated. Based upon the NCEP dietary criteria for total fat, saturated fat, and cholesterol each diet was classified as either Step 1 or Step 2. Diets exceeding Step 1 criteria were classified as typical American (Step 0). Diets not meeting all 3 criteria for any given Step were considered 'NCEP unclassifiable'. Using the FRR and RISCC scores of only the NCEP-classifiable diets, the optimal RISCC and FRR cutoff points to distinguish between Step 0 and 1 diets and Step 1 and 2 diets were determined. RESULTS: Only 50% of the diets were NCEP-classifiable. Using these diets, a RISCC of 20 best distinguished a Step 0 from a Step 1 diet, and 13 segregated Step 1 from 2 diets. The FRR cutoff points were 14 and 8, respectively. Using these values, the RISCC was able correctly to classify 92-97% of the diets, whereas the FRR correctly classified only 73-80%. Variability of scores within each Step was twice as high for the FRR as for the RISCC. The FRR was more biased by total kilocalories than was the RISCC. CONCLUSION: We conclude that the RISCC scoring system was more accurate and precise than the FRR system for diet classification, and was a superior tool for classifying the ambiguous diets. Since the RISCC also requires (and therefore provides) quantitative nutrient data and the FRR does not, the former is a better dietary monitoring tool for clinical trials.

Diet Records↗
PubMed1994

Comparison of effects of probucol versus vitamin E on ex vivo oxidation susceptibility of lipoproteins in hyperlipoproteinemia.

Oxidative modification of low-density lipoprotein (LDL) cholesterol appears to contribute to atherogenesis. Probucol reduces LDL cholesterol oxidation susceptibility, but the consistency, dose, and time course are not well described. Twelve hyperlipidemic patients were given probucol for 4 weeks at the usual dose for cholesterol reduction (1,000 mg/day), or one half (500 mg/day) or one quarter (250 mg/day) the usual dose. Lipoprotein oxidation susceptibility of apolipoprotein B-containing lipoproteins was assessed using a rapid test in which LDL cholesterol and very-low-density lipoprotein are precipitated with dextran sulfate and magnesium ions, redissolved, incubated with copper ions for 3 hours, and tested for thiobarbituric acid-reactive substances. Results are expressed as nmoles of malonyldialdehyde (MDA) generated per mg (nmol MDA/mg) non-high-density lipoprotein cholesterol. Lipoproteins from probucol-treated patients become resistant to oxidation with a predrug value of 85 +/- 19, and decreasing to 3 +/- 1 nmol MDA/mg after drug administration (p < 0.001). Both "half" and "full" doses were effective in lowering lipoprotein oxidation susceptibility by 95%. The "quarter" dose was less effective. Oxidation inhibition was maximized within 2 weeks, returning to baseline 4 to 6 weeks after discontinuing probucol. Four patients were subsequently crossed over to vitamin E (1,200 IU/day). Vitamin E had a milder, less predictable antioxidant effect, lowering lipoprotein oxidation susceptibility by a mean of 24%. In conclusion, probucol treatment effectively and predictably reduces plasma lipoprotein susceptibility to ex vivo, copper-induced oxidation. This clinically applicable test may provide quantitation of antioxidant effects of probucol or other antioxidants and thus facilitate dose adjustments and correlation with antiatherosclerotic effects.

Antioxidants↗
PubMed1993

Comparative effects of atenolol versus celiprolol on serum lipids and blood pressure in hyperlipidemic and hypertensive subjects.

Antihypertensive drugs may affect serum lipoprotein levels in mixed populations but data in hyperlipidemic patients are scanty. Atenolol versus celiprolol effects on serum lipoproteins were compared in 159 hyperlipoproteinemic hypertensive patients. This was a randomized, double-blind, parallel-group, positive-controlled multicenter trial with centralized lipoprotein laboratory and diet constancy monitoring. Blood pressure reduction and serum lipoprotein and apoprotein levels were monitored for 3 months. Both drugs reduced systolic and diastolic blood pressures. Atenolol had greater effects than celiprolol on diastolic pressure, but effects on systolic blood pressure were not different. Patients receiving atenolol had lower serum high-density lipoprotein cholesterol levels and higher low-density lipoprotein/high-density lipoprotein cholesterol ratios, whereas patients treated with celiprolol showed no contrasting changes. These differences in lipoprotein levels between drug treatment groups were statistically significant at weeks 9 and 12. The difference between drug treatments was also significant if the values of the 9- and 12-week visits were averaged. Patients taking atenolol had statistically significantly higher serum levels of total cholesterol, triglycerides and apoprotein B at 9 weeks. These divergent directional changes were consistent throughout and statistically significantly different between drugs.

Adult↗
PubMed1993

The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia.

BACKGROUND: A diet low in saturated fat and cholesterol is the standard initial treatment for hypercholesterolemia. However, little quantitative information is available about the efficacy of dietary therapy in clinical practice or about the combined effects of diet and drug therapy. METHODS: One hundred eleven outpatients with moderate hypercholesterolemia were treated at five lipid clinics with the National Cholesterol Education Program Step 2 diet (which is low in fat and cholesterol) and lovastatin (20 mg once daily), both alone and together. A diet high in fat and cholesterol and a placebo identical in appearance to the lovastatin were used as the respective controls. Each of the 97 patients completing the study (58 men and 39 women) underwent four consecutive nine-week periods of treatment according to a randomized, balanced design: a high-fat diet-placebo period, a low-fat diet-placebo period, a high-fat diet-lovastatin period, and a low-fat diet-lovastatin period. RESULTS: The level of low-density lipoprotein (LDL) cholesterol was a mean of 5 percent (95 percent confidence interval, 3 to 7 percent) lower during the low-fat diet than during the high-fat diet (P < 0.001). With lovastatin therapy as compared with placebo, the reduction was 27 percent. Together, the low-fat diet and lovastatin led to a mean reduction of 32 percent in the level of LDL cholesterol. The level of high-density lipoprotein (HDL) cholesterol fell by 6 percent (95 percent confidence interval, 4 to 8 percent) during the low-fat diet (P < 0.001) and rose by 4 percent during treatment with lovastatin (P < 0.001). The ratio of LDL to HDL cholesterol and the level of total triglycerides were reduced by lovastatin (P < 0.001), but not by the low-fat diet. CONCLUSIONS: The effects of the low-fat-low-cholesterol diet and lovastatin on lipoprotein levels were independent and additive. However, the reduction in LDL cholesterol produced by the diet was small, and its benefit was possibly offset by the accompanying reduction in the level of HDL cholesterol.

Apolipoproteins↗
PubMed1993

Garlic supplementation and lipoprotein oxidation susceptibility.

Interventions which make serum lipoproteins less susceptible to oxidation may be antiatherogenic. The antioxidant properties of garlic which have been demonstrated in vitro led us to investigate the effects of garlic supplements on lipoprotein oxidation susceptibility in humans. Ten healthy volunteers were given 600 mg/d of garlic powder (6 tablets of Kwai) for two weeks in a placebo-controlled, randomized, double-blind crossover trial. We found that although serum lipid and lipoprotein levels were not lowered in this short time period, the ex vivo susceptibility of apolipoprotein B-containing lipoproteins to oxidation was significantly decreased (-34%). Because garlic has been reported to beneficially affect serum lipid levels, platelet function, fibrinolysis and blood pressure, this additional effect of retarding lipoprotein oxidation may contribute to the potential antiatherosclerotic effect of garlic.

Adult↗
PubMed1993

Fish oil reduces postprandial triglyceride concentrations without accelerating lipid-emulsion removal rates.

Chronic intake of fish oil (FO) reduces postprandial lipemia. Our aim was to determine whether increased clearance of chylomicrons was the mechanism. Eight normal volunteers were randomly assigned to take 64 mg n-3 fatty acids/kg body wt or an olive oil placebo daily for 4 wk in a double-blind, crossover design. At the end of each phase, an intravenous fat-tolerance test and a four-meal, 24-h oral fat-load test were administered. The latter was designed to mimic normal eating patterns (fat provided 42% of energy). FO lowered chylomicron triglyceride and retinyl palmitate concentrations by 40% (P < 0.01) and very-low-density lipoprotein retinyl palmitate concentrations by 27% (P < 0.01). However, clearance rates of the fat emulsion were not significantly different between treatments. The results suggest that the hypochylomicronemic effect of chronic FO supplementation is not due to increased chylomicron clearance, leaving reduced chylomicron production or secretion as a more likely cause of the reduced postprandial lipemia.

Administration, Oral↗