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Vitamin E in cardiovascular disease: has the die been cast?
1Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia. dkfper@mail.hukm.ukm.my
Insights
Antioxidants, particularly vitamin E, show promise in reducing cardiovascular disease (CVD) by combating inflammation in atherosclerotic plaques. However, large trials have yielded inconclusive results, necessitating further research into specific forms like alpha-tocotrienol for effective CAD treatment.
Area of Science:
- Cardiovascular Medicine
- Nutritional Science
- Biochemistry
Background:
- Coronary artery disease (CAD) is a leading cause of mortality, driven by atherosclerotic plaque formation and rupture.
- Oxidative stress and inflammation are key contributors to plaque development and instability.
- Oxidized low-density lipoproteins (LDL) play a crucial role in the transformation of macrophages into foam cells, initiating plaque formation.
Purpose of the Study:
- To investigate the role of antioxidants, specifically vitamin E, in the prevention and treatment of coronary artery disease (CAD).
- To evaluate the impact of vitamin E supplementation on atherosclerotic plaque formation, rupture, and related cardiovascular events.
- To explore the potential of alpha-tocotrienol, a potent form of vitamin E, in addressing inflammation during plaque rupture.
Main Methods:
- Review of existing literature on oxidative stress, inflammation, and CAD pathogenesis.
- Analysis of observational studies linking antioxidant intake to CAD incidence.
- Examination of results from large-scale, placebo-controlled clinical trials on vitamin E supplementation.
- Critical appraisal of study limitations and identification of areas for future research.
Main Results:
- Animal studies and human observational data suggest antioxidants, including vitamin E, may reduce plaque formation and cardiovascular events.
- Vitamin E supplementation has been associated with reduced risks of myocardial infarction and recurrent cardiovascular events in some studies.
- Large clinical trials have failed to demonstrate significant benefits of vitamin E supplementation in treating CAD, leading to inconclusive results.
Conclusions:
- While observational data suggests a beneficial role for antioxidants in CAD, large clinical trials have not confirmed these findings.
- Limitations in existing studies, including the specific forms of vitamin E used, render current conclusions inconclusive.
- Further research focusing on potent antioxidants like alpha-tocotrienol is needed to clarify the role of vitamin E in CAD prevention and treatment.
Abstract:
Cardiovascular disease, in particular coronary artery disease (CAD), remains the most important cause of morbidity and mortality in developed countries and, in the near future, more so in the developing world. Atherosclerotic plaque formation is the underlying basis for CAD. Growth of the plaque leads to coronary stenosis, causing a progressive decrease in blood flow that results in angina pectoris. Acute myocardial infarction and unstable angina were recently recognised as related to plaque rupture, not progressive coronary stenosis. Acute thrombus formation causes an abrupt coronary occlusion. The characteristics of the fibrin cap, contents of the plaque, rheological factors and active inflammation within the plaque contribute to plaque rupture. Oxidative processes are important in plaque formation. Oxidized low density lipoproteins (LDL) but not unoxidized LDL is engulfed by resident intimal macrophages, transforming them into foam cells which develop into fatty streaks, the precursors of the atherosclerotic plaque. Inflammation is important both in plaque formation and rupture. Animal studies have shown that antioxidants reduce plaque formation and lead to plaque stabilisation. In humans, high intakes of antioxidants are associated with lower incidence of CAD, despite high serum cholesterol levels. This observation suggests a role for inflammation in CAD and that reducing inflammation using antioxidants may ameliorate these processes. Men and women with high intakes of vitamin E were found to have less CAD. Vitamin E supplementation was associated with a significant reduction in myocardial infarction and cardiovascular events in the incidence of recurrent myocardial infarction. In the hierarchy of evidence in evidence-based medicine, data from large placebo-controlled clinical trials is considered necessary. Results from various mega-trials have not shown benefits (nor adverse effects) conferred by vitamin E supplementation, suggesting that vitamin E has no role in the treatment of CAD. These results do not seem to confirm, at the clinical level, the effect of antioxidants against active inflammation during plaque rupture. However, a closer examination of these studies showed a number of limitations, rendering them inconclusive in addressing the role of vitamin E in CAD prevention and treatment. Further studies that specifically address the issue of vitamin E in the pathogenesis of atherosclerosis and in the treatment of CAD need be performed. These studies should use the more potent antioxidant property of alpha-tocotrienol vitamin E.