1. The Effects of Vitamin E on Oxidative
Stress and Cardiovascular Disease
Melanie Beale, Adriana Jakupi, Jonathan Jeffrey, Kody Springsteen
Department of Food Science & Human Nutrition, Colorado State University, Fort Collins, CO
Fall 2015 FSHN492
Cardiovascular disease (CVD) is a serious health problem facing
the world today. Vitamin E is a fat-soluble vitamin that helps to
prevent the oxidation of low density lipoprotein (LDL), which is a
step in atherogenesis. The accumulation of atherosclerotic plaque
is responsible for most types of CVD. Diets such as the American
Heart Association (AHA) diet and the Dietary Approaches to Stop
Hypertension (DASH) are rich in vitamin E and may help reduce the
risk of CVD.
Abstract
• Describe the physiology of cardiovascular disease and its
relationship with oxidative stress
• Describe the functions of vitamin E that relate to cardiovascular
disease
• Provide dietary approaches to consume adequate vitamin E to
reduce the risk of cardiovascular disease
Objectives
Cardiovascular disease (CVD) is the leading cause of death in
the United States and throughout the world, and on average, one
American dies of CVD every 40 seconds.1 CVD is an umbrella term
that describes any malfunction of the cardiovascular system in
humans. This includes coronary heart disease, atherosclerosis,
hypertension, congestive heart failure, and any other congenital or
lifestyle-related disorder related to the cardiovascular system.
Atherosclerotic heart disease is the most common form of CVD.1,2
CVD typically occurs as a result of plaque buildup in the intimal
layer of the endothelium, known as atherosclerosis.3-5,6 This
plaque build-up is exacerbated by oxidized low density
lipoproteins. Reactive oxygen and nitrogen species, also known as
free radicals, are molecules responsible for oxidation of LDL and
many other compounds.7 Despite their detrimental effects on
tissues, ROS and RNS have important roles in cell signaling,
adaptation, and cell homeostasis.7
Antioxidants are a class of molecules responsible for the repair
of oxidative damage. Antioxidants exist as enzymes such as
superoxide dismutase, minerals such as Selenium, and vitamins
such as vitamin E.7 Antioxidants are available from dietary sources
including fresh fruits and vegetables, red wine, and tea.7-9
Supplemental sources include capsules of vitamin E, vitamin C,
vitamin A, selenium, phytochemicals, and various enzymes.
Introduction
CVD typically occurs as a result of plaque buildup in the intimal layer of the
endothelium. This plaque build-up is exacerbated when oxidized LDL migrates into
the intimal layer of the endothelium and becomes oxidized due to ROS or RNS.7
Upon oxidation of LDL, the positive charges on its apoliprotein, Apo B 100, become
masked. This prevents LDL from binding to the LDL receptor. Therefore, LDL cannot
enter cells and must be scavenged by macrophages. Then, monocytes are recruited
from circulation, differentiated into macrophages, and endocytose oxidized LDL.10
These lipid-laden macrophages differentiate into foam cells, and the accumulation of
foam cells constitutes the aforementioned plaque. This process also leads to smooth
muscle cell migration into the intima resulting in narrowing of the arteries. This
process is responsible for atherosclerosis and ultimately leads to CVD.
Vitamin E is the name for eight related tocopherols and tocotrienols that have
different chemical structures, but are fat-soluble vitamins with antioxidant
characteristics.2-7,11 Vitamin E is similar to lipids in the way that it is absorbed into
the body. After ingestion, vitamin E is solubilized by bile acids, absorbed through the
epithelial cells of the small intestine, packaged into chylomicrons, and then
transported throughout the body by the lymphatic system. Once in the circulation,
the liver takes up the chylomicrons and vitamin E is repackaged into VLDL, where it is
recirculated throughout the body, absorbed by various tissues, and stored in adipose
tissue.2
The most bioavailable form of vitamin E is ⍺-tocopherol, which has shown to be
an effective fat-soluble antioxidant.2-3,6-7,11 ⍺-tocopherol protects against CVD by
preventing the oxidation of LDL. 4, 7 ⍺-tocopherol interrupts oxidation of membranes
by reacting with free radicals and disrupting the lipid peroxidation chain reaction.6
Once ⍺-tocopherol has neutralized a radical, its antioxidant capacity is diminished
because it has become oxidized. However, vitamin C can reduce ⍺-tocopherol and
restore its antioxidant ability.7 Although the main function of ⍺-tocopherol is to
maintain cell membrane integrity, research has shown that insufficient intake of ⍺-
tocopherol may be an indicator of CVD risk.2-6, 12-13
Physiology
• CVD is one of the most widespread and costly health problems
facing the U.S. today, and it is also among the most preventable.14
• According to the Center for Disease Control and Prevention, in
2010, heart related medical costs in the US were approximately
444 billion dollars.14
• The American Heart Association recommends consumption of
vitamin E through dietary sources such as fresh fruits and
vegetables.8
• Research efforts have found dietary vitamin E to be more
beneficial than vitamin E in supplemental form. In fact, multiple
studies have found no effects of vitamin E supplementation on
prevention of CVD.4,11,13
CVD is the leading killer of Americans and people across the
globe. Further, it costs billions of dollars per year in health care
costs.1,14 Vitamin E is a powerful antioxidant that can combat
oxidation of LDL and ultimately reduce the risk of CVD. The
most bioavailable form of vitamin E, ⍺-tocopherol, provides the
largest effect of all vitamin E derivatives on preventing the
oxidation of LDL. Vitamin E is the most effective when
consumed in the diet rather than via supplementation. Good
sources of vitamin E include leafy green vegetables, nuts, seeds,
and legumes. These sources are included in both the AHA diet
and the DASH diet.8,9
1. Cardiovascular diseases (CVDs). World Health Organization website.
http://www.who.int/mediacentre/factsheets/fs317/en/. Published February 21, 2010. Updated January 10,
2015. Accessed November 2, 2015.
2. Myung SK, Ju W, Cho B, et al. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular
disease: systematic review and meta-analysis of randomized controlled trials. BMJ. 2013;346(7893):12. doi:
http://dx.doi.org/10.1136/bmj.f10
3. Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Effects of random allocation to vitamin E
supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study.
Circulation. 2007;116(13):1497-1503. doi: 10.1161/CIRCULATIONAHA.107.716407
4. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the
risk of coronary disease in women. N Engl J Med. 1993;328(20):1444-1449. doi:
10.1056/NEJM199305203282003
5. Knekt P, Reunanen A, Jarvinen R, Seppanen R, Heliovaara M, Aromaa A. Antioxidant vitamin intake and
coronary mortality in a longitudinal population study. Am J Epidemiol. 1994;139(12):1180-1189. URL:
http://aje.oxfordjournals.org/content/139/12/1180.full.pdf
6. Mathur P, Ding ZF, Saldeen T, Mehta JL. Tocopherols in the Prevention and Treatment of Atherosclerosis and
Related Cardiovascular Disease. J Clin Cardiol. 2015;38(9):570–576. doi:10.1002/clc.22422
7. Vitamin E: Fact Sheet for Health Professionals. National Institutes of Health: Office of Dietary Supplements
website. https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/. Published January 15, 2013.
Updated June 5, 2013. Accessed November 3, 2015.
8. The American Heart Association’s Diet and Lifestyle Recommendations. American Heart Association website.
http://www.heart.org/HEARTORG/GettingHealthy/NutritionCenter/HealthyEating/The-American-Heart-
Associations-Diet-and-Lifestyle-Recommendations_UCM_305855_Article.jsp#.VjugCq6rTR2. Published
September 10, 2014. Updated August 12, 2015. Accessed November 2, 2015.
9. DASH diet: Healthy eating to lower your blood pressure. Mayo Clinic website.
http://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/dash-diet/art-20048456.
Published May 15, 2013. Updated February 6, 2015. Accessed November 2, 2015.
10. Image 2: http://atvb.ahajournals.org/content/25/5/904/F2.large.jpg
11. Blumberg JB, Frei B. Why clinical trials of vitamin E and cardiovascular diseases may be fatally flawed.
Commentary on "The relationship between dose of vitamin E and suppression of oxidative stress in humans."
Free Radic Biol Med. 2007;43(10):1374-1376. doi: 10.1016/j.freeadbiomed.2007.08.017
12. Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and
cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005;294(1):56-65. doi:
10.1001/jama.294.1.56.
13. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomised controlled trial of
vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet.
1996;347(9004):781-786. doi:10.1016/S0140-6736(96)90866-1
14. Heart Disease Facts. Center for Disease Control and Prevention website.
http://www.cdc.gov/heartdisease/facts.htm. Updated August 10, 2015. Accessed November 5, 2015.
15. Image 1: https://www.uic.edu/classes/phar/phar332/Clinical_Cases/vitamin%20cases/vitamin%20E/vit-E.gif
16. Image 2: http://atvb.ahajournals.org/content/25/5/904/F2.large.jpg
17. Image 3: https://www.cnsforum.com/educationalresources/imagebank/drugs_other/moa_vite
18. Image 4: http://www.oasisadvancedwellness.com/
Health Implications
Conclusion
References
Related Nutrients and Applications
• When vitamin E scavenges reactive oxygen species within the
lipid membrane, it becomes oxidized, losing its antioxidant
capabilities. Vitamin C, also known as ascorbic acid, regenerates
vitamin E by reducing it back to its active form. This effect is
known as the “vitamin E recycling system.”7
• The Recommended Dietary Allowance (RDA) of vitamin E is 15 mg
(22.4 IU) per day for males and females over the age of 14. 7
• Upper Limit Intake (UL) of 1000 mg per day.7
• Vitamin E supplements typically provide more than the daily
recommended dose, increasing the risk for vitamin E toxicity.
Therefore, supplementation of vitamin E is contraindicated. 7
• Heart-healthy diet recommendations such as the American Heart
Association (AHA) diet and the Dietary Approaches to Stop
Hypertension (DASH) diet are effective methods in which one can
consume adequate vitamin E.8,9 These dietary guidelines
recommend at least five servings of fruits and vegetables per day,
and four to five servings of nuts, seeds, and legumes per week.
This promotes the consumption of dietary vitamin E, vitamin C,
and other antioxidants.8,9
• Vitamin E can be found in the following dietary sources:
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