Inhibition of Atherosclerosis by Cod-Liver Oil in a Hyperlipidemic Swine Model

Weiner, Bonnie H.; Ockene, Ira S.; Levine, Peter H.; Cuénoud, Henri F.; Fisher, Marc; Johnson, Brian F. G.; Daoud, A.S.; Jarmolych, J.; Hosmer, David W.; Johnson, Mark H.

doi:10.1056/nejm198610023151401

Cited by 328 publications

(76 citation statements)

References 43 publications

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“…21 The results of the latter study demonstrated that omega-3 fatty acids not only lowered platelet arachidonic acid and serum thromboxane concentrations, but also had inhibitory effects on both coronary atherosclerosis and intimal hyperplasia after endothelial disruption. It was concluded that the reduction in coronary artery disease was a possible result of altered prostaglandin metabolism.…”

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confidence: 88%

Effect of dietary omega-3 fatty acid on serum lipids, platelet function, and atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

et al. 1989

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Omega-3 fatty acids have been shown to lower plasma cholesterol and triglycerlde concentrations In humans. However, the effects of these fatty acids on the Interactions among llpld concentrations, platelet activity, and atherogenesls have not been characterized In humans or In animals with low density llpoproteln (LDL) receptor deficiencies. To test the hypothesis that omega-3 fatty adds exert a protective effect In LDL receptor-deficient animals by lowering hyperlipldemla, reducing platelet aggregation, and reducing the severity of atherosclerosis, we evaluated young homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits that were fed omega-3 fatty adds. One-month-old male and female WHHL rabbits were placed on either a control diet (standard laboratory rabbit chow) or a diet supplemented with Menhaden fish oil (MFO), which contained elcosapentaenolc acid (EPA). Consumption measurements during the 5 months of the study Indicated that the MFO-fed group received 150 to 200 mg/kg/day of EPA. Six-month-old, MFO-fed, female WHHL rabbits had significantly lower plasma concentrations of total cholesterol (582±20 mg/dl vs. 856±44 mg/dl, control, p<0.05) and triglycertdes (266±21 mg/dl vs. 459±15 mg/dl, control, p<0.05), with lower serum/plasma llpoproteln concentrations [very low density llpoproteln (VLDL), LDL, high density llpoproteln (HDL)] compared to control female WHHL rabbits. Male MFO-fed rabbits had only significantly lower VLDLs (46±9 mg/dl) compared to control male WHHL rabbits (156±9 mg/dl, p<0.05). The platelet fatty acid composition In MFO-fed rabbits had significantly greater amounts of omega-3 fatty adds and lesser amounts of omega-6 fatty acids. Additionally, the threshold concentration of collagen and arachldonate required to aggregate platelets In MFO-fed rabbits was nearly double that of controls. In contrast, the platelet aggregation response to the thromboxane analogue, U-46619, was similar in both groups of animals. Morphometric evaluation of intimal surface of the aortas failed to demonstrate significant differences In llpld accumulation or Intimal or medial thickening between MFO-fed and control WHHL rabbits, even when the potential effects of gender were considered. In conclusion: 1) omega-3 fatty adds exert hypdlpldemlc and antlplatelet effects In LDL receptor-defldent animals, and 2) despite these actions, omega-3 fatty adds do not reduce the severity of atherosclerosis In WHHL rabbits. (Arteriosclerosis 9:529-537, July/August 1989)

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confidence: 88%

Effect of dietary omega-3 fatty acid on serum lipids, platelet function, and atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

et al. 1989

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“…The health implication of an increased n-3 VLCPUFA intake is therefore not unequivocal. The diverging results of trials in which animals were fed n-3 VLCPUFA further underscore this uncertainty (Weiner et al, 1986;Davis et al, 1987;Fincham et al, 1991;Barbeau et al, 1997). Accordingly, it is still a controversial issue whether ®sh protects against CHD.…”

Section: Introductionmentioning

confidence: 99%

Fish consumption and coronary heart disease mortality. A systematic review of prospective cohort studies

Marckmann¹,

1999

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Objectives: To review all prospective cohort studies examining the relationship between ®sh intake and coronary heart disease mortality, and to assess the strength and consistency of their ®ndings. Design: Systematic review of studies based on individual records of ®sh or n-3 polyunsaturated fatty acid consumption and coronary heart disease death. Studies were given scienti®c quality scores and divided into categories of high, intermediate, or insuf®cient quality. Main outcome measure: Coronary heart disease mortality. Results: Eleven studies were identi®ed. The cohorts counted a total of 116 764 individuals. Of four studies judged to be of high quality, the two largest (n 44 895 and 20 051) were performed in populations at low risk of coronary heart disease. They found no protective effect of ®sh consumption. The other two high-quality studies were relatively small (n 852 and 1822) and included individuals at higher risk. They both found an inverse relationship between ®sh consumption and coronary heart disease death, suggesting that 40 ± 60 g ®sh per day is optimal and associated with a risk reduction of 40 ± 60%. Results of four studies of intermediate quality support that ®sh consumption is inversely associated with coronary heart disease mortality in high-risk populations only. Three studies were judged to be of insuf®cient quality to be used for drawing conclusions. Conclusions: Fish consumption is not associated with reduced coronary heart disease mortality in low-risk populations. However, ®sh consumption at 40 ± 60 g daily is associated with markedly reduced coronary heart disease mortality in high-risk populations. The underlying biochemical mechanism is not known and causal inference premature.

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“…Animal studies with hypercholesterolemia Tables 2-4 list the in vivo studies in rabbits [58][59][60][61][62][63][64][65][66][67][68][69], swine [23,28,[70][71][72][73] and monkeys [74][75][76], respectively, on the effects of fish oil on the prevention of atherosclerosis and provides details such as the dietary regimen, duration of study, etc. Except in the Watanabe hereditary hyperlipidemic rabbit and one study in pigs [73], all atherogenic diets are highcholesterol diets, and in case of the swine model [28,[70][71][72], bile acids were also needed to enhance hypercholesterolemia.…”

Section: Fish Oil and The Prevention Of Atherosclerosismentioning

confidence: 99%

“…Except in the Watanabe hereditary hyperlipidemic rabbit and one study in pigs [73], all atherogenic diets are highcholesterol diets, and in case of the swine model [28,[70][71][72], bile acids were also needed to enhance hypercholesterolemia. In small animals (rabbits) usually only the aorta has been used to evaluate the anti-atherogenic effect of fish oil.…”

Section: Fish Oil and The Prevention Of Atherosclerosismentioning

confidence: 99%

“…After judging the results of the twelve rabbit studies and classifying them very globally one can conclude that an equal number of studies report a favorable [60,64,66,67], unfavorable [58,62,65,68] or no effect [59,61,63,69). For the swine studies four [23,[71][72][73] are favorable and two [28,70] show no effect, while in the non-human primates two [74,75] are beneficial and one study [76] shows no effect at all. It is most likely that some studies yielding negative results have not appeared in the international literature.…”

Section: Fish Oil and The Prevention Of Atherosclerosismentioning

confidence: 99%

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Fish oil and the prevention and regression of atherosclerosis

Sassen

Lamers

Verdouw

1994

Cardiovasc Drug Ther

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Summary. Epidemiological studies in the seventies have put forward that dietary rather than genetic factors are responsible for the lower incidence of ischemic heart disease in Greenland Inuit and have generated a large body of both in vitro and in vivo experimental studies, exploring the putative favorable effects of fish (oil) on atherogenesis and its risk factors. The first part of this report reviews the in vivo animal studies, concentrating on the hypercholesterolemic models and the arterialized vein graft model. In the hypercholesterolemic animal studies, the results are inconclusive as the studies reporting a protective effect are matched by the number of studies showing no effect or an adverse effect. The diversity in species, dose of fish oil, duration of study, type of vessel studied and type of fish oil preparation (content of n-3 fatty acids, unesterified n-3 fatty acids, ethylesters or triglyceridcs) could all contribute. Furthermore, the definitions and criteria used in the literature to evaluate atherogenesis are diverse and it appears that while one parameter is affected, another is not necessarily modified in the same direction, stressing the importance of extending the analysis of the effects on atherogenesis to more than one parameter. We also believe that it is time to reach a consensus as to which animal model mimicks most closely a particular human situation. Only in appropriate models, investigating more than one atherosclerosis variable, can the effects of a putative anti-atherogenic drug or diet be verified. In the veno-arterial autograft model, mimicking the patient after coronary bypass grafting, dietary fish oil has been consistently effective in preventing accelerated graft intima proliferation. It could therefore be of interest to evaluate the effects of fish oil on graft patency in patients after coronary bypass surgery after a period of years.The results from studies on restenosis after percutaneous transluminal angioplasty are also reviewed and it is concluded that the two large scale trials, that are currently underway, might reliably answer the question whether fish oil is effective as a non-pharmacological adjuvants in the prevention of restenosis.Lastly, the studies on the effects of fish oil on the regression of experimental atherosclerosis are reviewed. In view of the small number of studies (i.e., four) investigating the effects of fish oil on the regression of atherosclerosis, it is premature to draw any conclusion, and therefore further experimental work is required.

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Inhibition of Atherosclerosis by Cod-Liver Oil in a Hyperlipidemic Swine Model

Cited by 328 publications

References 43 publications

Effect of dietary omega-3 fatty acid on serum lipids, platelet function, and atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Effect of dietary omega-3 fatty acid on serum lipids, platelet function, and atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Fish consumption and coronary heart disease mortality. A systematic review of prospective cohort studies

Fish oil and the prevention and regression of atherosclerosis

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