More support for zinc-antiatherogenic link
reduced athlerosclerosis in rabbit models have used a different
method to lend support to their hypothesis that the effect may be
due to a reduction in iron-catalyzed free radical reactions.
Researchers from the National University of Singapore reported in the journal Free Radical Biology and Medicine last year that supplementation of a high cholesterol diet with zinc reduced the formation of lesions in the arteries of rabbits, but said that the effects were not linked to changes in cholesterol levels.
Rather, the decrease in atherosclerotic lesions was linked to a decrease in iron concentrations in the tissue, which has previously been reported to catalytically promote damaging free-radical reactions and the development of atherosclerosis.
The findings of their latest research in this area are reported in the same journal this month. Atherosclerosis, whereby fatty substances such as cholesterol and calcium form plaque on the inner lining of an artery, is a risk factor for cardiovascular disease. If they can be translated to humans they could contribute to understanding of nutritional measures to preserve heart health.
The new study involved two groups of New Zealand white rabbits that were both fed a high cholesterol diet over an eight-week period. One of the groups also received zinc supplements at levels of 1g per kg of body weight. A control group was fed a normal diet.
The aim of the researchers, led by Barry Halliwell from the National University of Singapore, was to examine the role of zinc on lipid peroxidation in relation to atherosclerosis. They used isotope dilution gas chromatography-mass spectrometry techniques to measure biomarkers of oxidative lipid damage in atherosclerotic rabbit aorta.
In the past the research team used F(2)-isoprostane measurement. But since analysis of different biomarkers often requires different protocols, it adapted this technique to include the quantitation of cholesterol oxidation products in the same sample.
Halliwell's team found that zinc supplementation did not have a significant impact on the increase in total blood cholesterol levels in animals fed high cholesterol, but it did seem to significantly reduce the accumulation of total cholesterol levels on arterial walls.
In the cholesterol diet group cholesterol concentration levels were seen to be around 11.5 mg/g tissue, compared to around 4.5 mg/g tissue in the cholesterol diet plus zinc group.
Average aortic lesion cross-sectional areas were around 3mm2 in the cholesterol diet group, but only around 1.5mm2 in the cholesterol diet plus zinc group.
They also observed that elevated levels of cholesterol oxidation products (5,6-alpha and beta cholesterol epoxides, 7beta-hydroxycholesterol, 7-ketocholesterol) in aorta.
Total F(2)-isoprostanes in plasma of the rabbits that were fed a cholesterol diet were around 1.7 mg/ml in the cholesterol plus zinc group - on a par with the control group - compared to around 5.3 ng/ml in the cholesterol diet only group.
Likewise with total F(2)-isoprostane content in tissue, the cholesterol plus zinc group and control group had around 3.3ng/ml, compared to around 5ng/ml in the control group.
"Our data indicate that zinc has an anti-atherogenic effect, possibly due to a reduction in iron-catalyzed free radical reactions," wrote the researchers.
"Since some groups of the population have deficient dietary intake or lower tissue levels of zinc reasonable supplementation of zinc in the diet of humans at risk of atherosclerosis should be considered as a strong candidate for further clinical investigation."
However they said that the mechanism of action is still unclear, despite several studies demonstrating that zinc supplementation can reduce oxidative damage. Since zinc is not redox active, it probably does not act directly as an antioxidant.
Atherosclerosis occurs naturally in humans as part of the aging process, but certain factors including high blood cholesterol, smoking, high blood pressure, obesity and diabetes increase the risk.
Zinc deficiency is known to lead to growth impairment, neuropathy, diarrhea, dermatitis, hypotension and hyperthermia.
Source: Free Radical Biology and Medicine Volume 42, (2007) Pages 559-566 "Zinc supplementation inhibits lipid peroxidation and the development of atherosclerosis in rabbits fed a high cholesterol diet" Authors: Andrew Jenner, Minqin Ren, Reshmi Rajendran, Pan Ning, Beny Tan Kwong Huat, Frank Wattt, Barry Halliwell.