The Effects of Vitamin E on Oxidative Stress and Cardiovascular Disease

Melanie Beale, Adriana Jakupi, Jonathan Jeffrey, Kody SpringsteenDepartment 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.jpg11. 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.gif16. Image 2: http://atvb.ahajournals.org/content/25/5/904/F2.large.jpg17. Image 3: https://www.cnsforum.com/educationalresources/imagebank/drugs_other/moa_vite18. 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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