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Biomedical subjects

W S Harris

Publications and source records attributed to W S Harris.

At least 55 records · Page 3Linked to original sources
PubMed1992

The prevention of atherosclerosis with antioxidants.

Recent research findings have suggested a role for pharmacologic as well as nutritional antioxidants in the prevention of atherosclerosis. Data from animal studies as well as cell culture experiments have shown that the drug probucol, which has hypocholesterolemic and antioxidant properties, is able to prevent oxidative modification of low density lipoproteins (LDL). Such modification is now believed to play a major part in the initiation and progression of arterial lesions. Nutrients with antioxidant properties such as vitamins C and E, beta-carotene, and mono-unsaturated fatty acids (when they replace polyunsaturated fatty acids) can reduce the susceptibility of LDL to oxidation. Antioxidant therapy, if proven useful, should be considered an adjunct to lipid-lowering therapy in order to have the greatest impact on coronary heart disease.

Animals↗
PubMed1991

Effects of four doses of n-3 fatty acids given to hyperlipidemic patients for six months.

The long-term effects of practical amounts of fish oil on plasma lipids and lipoprotein cholesterol levels, bleeding times, erythrocyte deformabilities, and plasma phospholipid fatty acid (FA) composition were investigated in this trial. Twenty-eight hyperlipidemic patients with elevated cholesterol and triglyceride (TG) levels were randomly assigned to take 3, 6, 9, or 12 capsules of fish oil daily for 6 months, providing 1.25-5 g of n-3 FAs per day. Baseline parameters were compared to values after 1 and 6 months of treatment, and after 1 month of washout. There were no statistically significant changes in total cholesterol levels at any dose. Both low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels tended to rise, resulting in an unchanged ratio of LDL-C to HDL-C. The TG and very-low-density-lipoprotein cholesterol (VLDL-C) levels decreased significantly with all but the lowest dose. Bleeding times were unaffected despite a nonsignificant 34% increase detected at the highest dose. Red blood cell deformability tended to increase with the two middle doses only. The EPA level in plasma phospholipids was strongly correlated with n-3 FA (FA) consumption. We conclude that long-term treatment of hyperlipidemic patients with practical intakes of n-3 FAs produced persistent reductions in TG levels and no change in the LDL-C/HDL-C ratio.

Arachidonic Acid↗
PubMed1990

The combined effects of N-3 fatty acids and aspirin on hemostatic parameters in man.

Both fish oils and aspirin are readily available to the consumer as over-the-counter preparations. Since both of these products have been shown to prolong bleeding times, it is possible that hemostasis might be adversely affected in subjects taking them in combination. This study was undertaken to examine the effects of n-3 fatty acids and aspirin on platelet function. Eight healthy men took a total of 485 mg of aspirin over 3 days before beginning two weeks of fish oil supplementation (4.5 g of n-3 fatty acids/day). Subjects continued with fish oil while resuming aspirin treatment for 3 days. Aspirin alone prolonged bleeding times by 34% (p less than 0.05). Fish oil alone raised bleeding times only slightly (9%; N.S.), but aspirin plus fish oil raised them by 78% (p less than 0.01). The increase in bleeding times with the combination (78%) was not significantly different than the sum of the individual increases (43%). The effects of fish oil and aspirin on platelet aggregation were investigated using single and dual agonists. Although fish oil alone did not significantly raise aggregation thresholds for collagen, arachidonic acid, or PAF, it did reduce the extent of aggregation with collagen. When challenged by single or dual agonists, the combination of fish oil and aspirin did not make platelets less sensitive than did aspirin alone. Since fish oil and aspirin had synergistic effects on bleeding times, but not on platelet aggregation, these two substances appear to affect hemostasis by different mechanisms.

Adult↗
PubMed1990

LCAT inhibitors interfere with the enzymatic determination of cholesterol and triglycerides.

5,5-Dithiobis-(2-nitrobenzoic acid) (DTNB) and p-chloro-mercuriphenylsulfonic acid (PCMPS) are well-known sulfhydryl inhibitors that are used to inhibit lecithin: cholesterol acyltransferase (LCAT). They were each found to interfere with the enzymatic assays of cholesterol and triglycerides. DTNB falsely reduced the measured plasma cholesterol content, and falsely increased triglyceride readings. The interference with the triglyceride assay could be largely prevented by blanking for glycerol. PCMPS had only a slight effect on the cholesterol assay, but falsely lowered the triglyceride readings to a great extent, even with glycerol-blanking. Thus, these inhibitors should be avoided when plasma samples are to be enzymatically analyzed for cholesterol or triglycerides.

4-Chloromercuribenzenesulfonate↗
PubMed1990

Changes in lipoprotein composition in hypertriglyceridemic patients taking cholesterol-free fish oil supplements.

Fish oils rich in n - 3 fatty acids (FAs) have been shown to markedly lower levels of very low density lipoproteins (VLDL), but not the low density lipoproteins (LDL) which are derived from VLDL. Changes in the size and chemical composition of lipoproteins may affect their metabolism. In order to examine the effects of n - 3 FAs on lipoprotein metabolism, 6 patients with hypertriglyceridemia were given 6 g n - 3 FAs/day. Plasma lipid and apoprotein (apo A-I, A-II, B, E, C-II, C-III) levels (mg/dl) were measured before and after 4 weeks of treatment. Changes in lipoprotein size were assessed by gel chromatography. n - 3 FAs lowered VLDL cholesterol (58 +/- 35 to 40 +/- 30, P less than 0.01) and total triglyceride (410 +/- 170 to 236 +/- 114, P less than 0.01). In spite of this, LDL cholesterol levels did not decrease, and apo B levels increased (98 +/- 28 to 111 +/- 27, P less than 0.05). HDL cholesterol rose (31 +/- 5 to 34 +/- 7, P less than 0.05). The lipid content of smaller VLDL particles was reduced by over 40%, but the protein content was largely unchanged. Large triglyceride-rich lipoprotein particles were reduced to a greater extent than were small particles. These changes in VLDL particle size and composition may enhance the synthesis of LDL in hypertriglyceridemic patients taking n - 3 FA supplements.

Blood Proteins↗
PubMed1990

Effects of the ACAT inhibitor CL 277,082 on cholesterol metabolism in humans.

A common pharmacologic approach to lowering elevated serum cholesterol levels has been to interfere with intestinal sterol absorption. Inhibitors of acyl coenzyme A: cholesterol acyltransferase (ACAT) should produce this effect. In this study, we examined the effects of CL 277,082, N-(2,4-difluorophenyl)-N-(4-neopentylbenzyl)-N-(n-heptyl)urea, an ACAT inhibitor, on cholesterol metabolism in humans. Eight healthy male volunteers were given a placebo for 14 days, followed by 750 mg/day CL 277,082 for 20 days in a single-blind, crossover design. Subjects were studied in a hospital research unit and were fed strictly controlled diets. Cholesterol absorption was measured by the dual isotope method during the final week of both the placebo and the drug phases. Sterol balance was also assessed during these two periods by measuring cholesterol intake, and fecal neutral and acidic sterol excretion rates. Plasma lipids and lipoproteins were measured at the end of each period. The drug was well tolerated and produced no detectable clinical or laboratory side effects. Cholesterol absorption, sterol excretion rates, and plasma lipoprotein levels were all unaffected by treatment. We conclude that CL 277,082 may not interfere with ACAT activity or cholesterol absorption in humans at the doses given under the conditions tested in this study.

Adult↗
PubMed1990

Fish oils in hypertriglyceridemia: a dose-response study.

The effects of three supplemental doses of fish oil on plasma lipids, lipoproteins, and bleeding times were studied in ten hypertriglyceridemic patients. After a 3-wk baseline period each patient was given 15, 25, or 40 mL fish oil/d (containing 4.5, 7.5, and 12 g n-3 fatty acids) for three successive 6-wk periods, each separated by a 4-wk period of no supplementation. Plasma cholesterol concentrations decreased from 7.40 mmol/L to 6.35, 6.55, and 6.40 mmol/L with increasing doses of fish oil (p less than 0.01 vs baseline for each). Plasma triglyceride concentrations decreased from 6.10 mmol/L to 2.90, 2.80, and 2.35 mmol/L (p less than 0.01 vs baseline for each). Low-density-lipoprotein cholesterol concentrations increased significantly (by 23% and 28%) with the two higher doses, respectively. Bleeding times increased only with the largest dose. The lowest dose was the most hypolipidemic per gram n-3 fatty acids.

Adult↗
PubMed1990

Effects of fish oil on VLDL triglyceride kinetics in humans.

Dietary n-3 fatty acids (FAs) found in fish oils markedly lower plasma triglyceride (TG) and very low density lipoprotein (VLDL) levels in both normal and hypertriglyceridemic subjects. The present study examined the mechanism of this effect. Ten subjects with widely different plasma triglyceride levels (82 to 1002 mg/dl) were fed metabolically controlled diets containing 20% fat. The control diet contained a blend of cocoa butter and peanut oil (P/S = 0.8). The test diet contained fish oil (P/S = 1.1) and provided 10-17 g of n-3 FAs per day (depending on calorie intake). After 3 to 5 weeks of each diet, the kinetics of VLDL-TG were determined over a 48-h period after the injection of [3H]glycerol. The fish oil diet reduced the VLDL-TG synthetic rate from 23 +/- 14.3 (mean +/- SD) to 12.6 +/- 7.5 mg/h per kg ideal weight (P less than 0.005) and increased the fractional catabolic rate (FCR) for VLDL-TG from 0.23 +/- 0.12 to 0.38 +/- 0.16 h -1 (P less than 0.005). At the same time, there was a 66% reduction of plasma triglyceride levels, resulting largely from a 78% decrease in VLDL-TG levels (398 +/- 317 to 87 +/- 77 mg/dl; P less than 0.005). There was a strong correlation (r = 0.83; P less than 0.01) between the change in synthetic rates and pool sizes, but there was no correlation (r = 0.24; NS) between changes in FCRs and pool sizes. The VLDL cholesterol: triglyceride ratio increased during the n-3 diet suggesting that smaller VLDL particles were present. These particles would be expected to leave the VLDL fraction more rapidly than larger particles producing a higher FCR. We conclude that the hypotriglyceridemic effect of fish oil appears to be caused primarily by an inhibition of very low density lipoprotein-triglyceride synthesis, but an additional, independent effect upon VLDL catabolism cannot be ruled out.

Dietary Fats, Unsaturated↗
PubMed1989

Short-term effects of omega-3 fatty acids on exercise stress test parameters, angina and lipoproteins.

The short-term effects of omega-3 fatty acids on exercise test parameters in patients with known coronary artery disease are poorly defined. Therefore, we administered a preparation containing 5.4 g of eicosapentaenoic acid and 3.6 g docosahexaenoic acid to 8 patients in a random order, double-blind, crossover design. The patients were given either fish oil or a vegetable oil control for 6 wk and then crossed over to the other treatment for a second 6-wk period, after a 2-wk wash-out interval. Exercise test parameters, angina frequency, and lipoprotein composition were measured at baseline and at the end of each trial phase. No significant changes were found in resting or peak exercise heart rate or double product, exercise duration or ischemic electrocardiographic changes at peak exercise. Angina frequency and sublingual nitroglycerin usage did not change during either the fish oil or the control oil phase. Plasma triglyceride levels decreased significantly with fish oil treatment and HDL cholesterol levels rose slightly. Total and LDL cholesterol levels were unchanged. We conclude that relatively high dose, short-term administration of omega-3 fatty acids does not alter exercise test parameters.

Adult↗
PubMed1989

Hypolipidaemic effects of n-3 fatty acids in primary hyperlipoproteinaemia.

The influence of fish oils rich in n-3 fatty acids on plasma lipid and lipoprotein concentrations in patients with primary hyperlipoproteinaemia is reviewed. When used as a dietary supplement, n-3 fatty acids exert their greatest effect on the concentrations of triglyceride-rich lipoproteins and these effects are dose dependent. Low doses of n-3 fatty acids reduce plasma triglyceride concentrations in patients with phenotypic type IV, type V and type IIB hyperlipoproteinaemia, but concurrently result in modest increases in the plasma concentrations of low density lipoprotein (LDL). With very high doses plasma concentrations of LDL cholesterol decrease in patients with the type IIB phenotype. At low doses n-3 fatty acids do not significantly lower concentrations of LDL cholesterol in patients with primary hypercholesterolaemia whereas at higher doses a modest LDL lowering effect is achieved. The results indicate that the therapeutic potential of n-3 fatty acids as hypolipidaemic agents is greatest in patients with hypertriglyceridaemia.

Cholesterol↗
PubMed1989

Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review.

Epidemiological studies in Greenland Eskimos led to the hypothesis that marine oils rich in n-3 fatty acids (also referred to as omega (omega)-3 fatty acids) are hypolipidemic and ultimately antiatherogenic. Metabolically controlled trials in which large amounts of fish oil were fed to normal volunteers and hyperlipidemic patients showed that these fatty acids (FAs) are effective at lowering plasma cholesterol and triglyceride levels. Although more recent trials using smaller, more practical doses of fish oil supplements have confirmed the hypotriglyceridemic effect, they have shown little effect on total cholesterol levels; hypertriglyceridemic patients have even experienced increases in low density lipoprotein cholesterol (LDL-C) levels of 10-20% while taking n-3 FA supplements. Discrepancies among fish oil studies regarding the effects of n-3 FAs on LDL-C levels may be understood by noting that, in the majority of studies reporting reductions in LDL-C levels, saturated fat intake was lowered when switching from the control diet to the fish oil diet. When fish oil is fed and saturated fat intake is constant, LDL-C levels either do not change or may increase. Levels of high density lipoprotein cholesterol have been found to increase slightly (about 5-10%) with fish oil intake. Plasma apolipoprotein levels change in concert with their associated lipoprotein cholesterol levels. Although the decrease in triglyceride levels appears to result from an inhibition in hepatic triglyceride synthesis, the mechanisms leading to the increases in LDL and HDL have not been determined. Finally, fatty fish or linolenic acid may serve as alternative sources of long-chain n-3 FAs, but further studies will be needed to document their hypolipidemic and/or antiatherogenic effects.

Animals↗
PubMed1988

Effects of a low saturated fat, low cholesterol fish oil supplement in hypertriglyceridemic patients. A placebo-controlled trial.

STUDY OBJECTIVE: To determine the effects of fish oil supplements low in saturated fat and cholesterol on plasma lipid and lipoprotein levels in hypertriglyceridemic patients. DESIGN: Single-blind, placebo-controlled (safflower oil), crossover trial with 6-week treatment periods. SETTING: Outpatient lipid clinic in a university medical center. PATIENTS: Eleven adult patients had isolated hypertriglyceridemia (type IV) and seven had concomitant hypercholesterolemia (Type IIb). INTERVENTION: Twelve 1-g capsules of either fish oil or placebo (safflower oil) were taken daily during each treatment period. MEASUREMENTS AND MAIN RESULTS: Blood was drawn at the fifth and sixth week of each period and analyzed for total lipids; cholesterol in very low, low (LDL), and high density (HDL) lipoproteins (mmol/L); and apoprotein B (mg/dL). Compared with the placebo, fish oil lowered plasma triglyceride levels (4.0 +/- 1.8 to 2.5 +/- 1.0), and raised LDL cholesterol levels (3.7 +/- 1.75 to 4.25 +/- 0.85), apolipoprotein B levels (122 +/- 29 to 140 +/- 34), and the ratio of LDL cholesterol to HDL cholesterol (4.0 +/- 0.9 to 4.7 +/- 1.4) (P less than 0.05; mean +/- SD). No significant changes were seen in levels of HDL or HDL cholesterol subfractions. Similar responses were seen in patients with both type IIb and IV lipoprotein phenotypes. CONCLUSIONS: Because the fish oil supplement contributed negligible amounts of cholesterol and saturated fat to the diet, the n-3 fatty acids most likely caused the observed effects. These findings indicate that relatively small amounts of fish oil can have beneficial effects on plasma triglyceride levels in hypertriglyceridemic patients, but the increase in LDL cholesterol and apoprotein B levels, and in the LDL cholesterol to HDL cholesterol ratio suggests the need for careful monitoring of plasma lipoprotein changes during fish oil supplementation, and for a careful evaluation of their long-term benefits.

Apolipoproteins B↗
PubMed1988

Effects of dietary fish oil on platelet function and plasma lipids in hyperlipoproteinemic and normal subjects.

We studied the effects of dietary supplementation with an encapsulated fish oil concentrate (Maxepa) on platelet function, fibrinolysis, and plasma lipids and lipoproteins in 9 normal subjects, 10 patients with type IV hyperlipoproteinemia, and 6 with type IIB hyperlipoproteinemia. After a baseline period, the subjects crossed over randomly between treatment periods with Maxepa (providing 3.24 g eicosapentaenoic acid and 2.16 g docosahexaenoic acid per day) and safflower oil (used as a control), given for 6 weeks each. Administration of Maxepa led to a slight prolongation of the bleeding time in all groups and to modest inhibition of platelet aggregation in the type IV hyperlipoproteinemics and normal subjects, with partial (41%) inhibition of thromboxane synthesis from baseline levels noted in the normal group. Plasma total fibrinolytic actively did not change significantly in any group. Maxepa treatment resulted in a marked decrease in triglyceride and VLDL-cholesterol and a slight increase in HDL-cholesterol was noted after Maxepa in the type IV hyperlipoproteinemics (4.11 +/- 0.13 mmol/l vs. 3.10 +/- 0.16 mmol/l, Maxepa vs. safflower oil). We conclude that dietary supplementation with fish oil results in a relatively minor degree of inhibition of platelet function in normal and hyperlipoproteinemic subjects, and a potentially adverse increase in LDL-cholesterol in type IV hyperlipoproteinemics.

Adult↗
PubMed1988

Omega-3 fatty acids in hypertriglyceridemic patients: triglycerides vs methyl esters.

The purpose of this study was to compare the relative effects of omega-3 fatty acids (omega-3 FAs) in the triglyceride (TG) and methly ester (ME) forms in a crossover design in patients with type IV hyperlipidemia. Eight male patients were given 18 vegetable-oil capsules (control); 18 capsules of a TG rich in omega-3 FAs (omega-3 TG); and 11 capsules containing omega-3-FA MEs (omega-3 ME). One supplement was given during each of three 6-wk periods. Equivalent amounts of omega-3 FAs (6.8 g/d) were provided by each of the omega-3 treatments. Plasma cholesterol (C) levels were unchanged during the two omega-3 phases whereas plasma TG levels fell by 44% during both. Low-density-lipoprotein cholesterol (LDL-C) levels rose significantly with both omega-3-FA treatments, as did apolipoprotein B levels. When taken in either the TG or ME forms, omega-3 FAs are equally effective hypotriglyceridemic agents but they may raise LDL-C levels.

Adult↗
PubMed1988

Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids.

Long chain n-3 fatty acids present in fish oils have been shown to reduce fasting plasma triglyceride and very low density lipoprotein levels in normal and hyperlipidemic human subjects. The present studies were designed to examine whether dietary n-3 fatty acids influence chylomicron formation and metabolism in healthy volunteers. In the first study seven subjects were fed either saturated fat, vegetable oil, or fish oil-based diets for 4 weeks each, and test meals containing 50 g of the background fat were administered after the second week of each diet. The postprandial rise in triglyceride levels was significantly lower following the fish oil test meal as compared to the saturated fat or vegetable oil test meals. In the second study, six subjects eating their usual home diets were given two fat tolerance tests. The first contained saturated fat and the second, given 1 week later, contained fish oil. There was no difference in the postprandial triglyceride response between the fish oil and the saturated fat meals. A third study was then conducted with eight volunteers in which saturated fat and fish oil test meals were administered during saturated fat and fish oil background diets in a crossover design. The presence of fish oil in the background diet reduced postprandial lipemia regardless of the type of fat in the test meal. Although there was no effect of the fish oil diet on the lipoprotein lipase and hepatic lipase activity of postheparin plasma measured in vitro, stimulation of in vivo lipolysis was not ruled out. Our results suggest that chronic (but not acute) intake of fish oil may inhibit the synthesis or secretion of chylomicrons from the gut. However, accelerated clearance due to decreased VLDL competition cannot be excluded.

Adult↗