The study, published in The Journal of Nutritional Biochemistry, suggests that alpha- and gamma- tocopherols – both forms of vitamin E – have contradictory oxidant activities, depending on the lipoprotein being oxidized.
Lipoproteins such as high density lipoprotein (HDL) and low density lipoprotein (LDL) are proteins that transport lipids such as cholesterol and triglycerides through the bloodstream. HDL is associated with being a marker of ‘good cholesterol’ whilst LDL is associated with ‘bad cholesterol’.
Researchers from Queen's University Belfast, UK report that whilst the tocopherols offered protection against oxidation with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) – both seen as ‘bad’ cholesterol, the tocopherols had a pro-oxidation effect when incorporated into high density lipoprotein (HDL).
The researchers, led by Dr. Jane McEneny, said that the pro-oxidant activity of both tocopherols toward HDL “may go some way to explain why supplementation studies with vitamin E have not been able to display cardio-protective effects.”
McEneny and her colleagues noted that the oxidation of plasma lipoproteins is “a pivotal event in the development of atherosclerosis.”
As a result, numerous experimental studies have persuasively suggested a major role for oxygen-derived free radicals in the development of the disease, they added.
“It has been demonstrated that antioxidant vitamins can protect against oxidative injury and are therefore believed to provide protection against a myriad of diseases,” said the authors.
There are eight forms of vitamin E – four forms of tocopherol, and four forms of tocotrienols, all of which are known to be antioxidants. Significantly more research attention has focused on the tocopherol forms, with many clinical trials investigating their role in preventing cardiovascular disease. Evidence to date, however, remains inconclusive, said McEneny and her team.
The Belfast-based scientists report that much of the research has focused on tocopherol's effects during LDL oxidation, with little attention being paid to VLDL and HDL. The team therefore questioned whether alpha- and gamma- tocopherols become incorporated into VLDL, LDL and HDL and influence their oxidation potential.
In an in vitro investigation, the authors reported that both alpha- and gamma- tocopherol became incorporated into VLDL, LDL and HDL. However, they said that the vitamin derivatives showed conflicting effects in the lipoproteins.
The tocopherols were found to protect VLDL and LDL against oxidation, whilst “surprisingly, the incorporation into HDL demonstrated pro-oxidant properties,” said McEneny and her team.
In a similar ex vivo study both tocopherols were again incorporated into all three lipoproteins, protecting VLDL and LDL against oxidation; but enhancing the oxidation of HDL.
McEneny and her colleagues said their results may have physiological implications: “HDL is suggested to be responsible for the majority of reverse cholesterol transport in humans and is considered to be an atheroprotective molecule; however, when it becomes dysfunctional, for example, by oxidation, it loses these protective properties and may instead yield detrimental effects.
These results have helped tease out possible mechanisms whereby tocopherol is ineffective during large-scale supplementation studies in bringing about cardioprotective benefits,” they concluded.
Source: The Journal of Nutritional Biochemistry
Published online ahead of print, doi: 10.1016/j.jnutbio.2011.04.009
“The two faces of α- and γ-tocopherols: an in vitro and ex vivo investigation into VLDL, LDL and HDL oxidation”
Authors: N. Nadeem, J.V. Woodside, S. Kelly, R. Allister, I.S. Young, J. McEneny