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Vitamin E

physician assistant

Introduction:

Vitamin E is an antioxidant and fat-soluble nutrient which requires the presence of fat in the digestive system in order for it to be absorbed. Vitamin E may assist the immune system in combating bacteria and viruses. It is beneficial for blood vessel health and may reduce the ability of blood to clot. Vitamin E may be harmful in supplement form, and is not recommended except possibly only within a few specific cases. Therefore, vitamin E is best from food sources such as tree nuts and from vegetables such as tomatoes and spinach.

The negative findings in various research has shown vitamin E supplements to be harmful in several ways. Vitamin E supplements have been shown to increase mortality in risk trials (2,3), have yielded a negative result when used for retinitis pigmentosa (8), and may increase the risk of bleeding (5,6). It may be beneficial for eye health in age-related macular degeneration (9) and may reduce colonic adenomas (13) but it is difficult to separate out whether the benefit was due to the vitamin E, one of the other antioxidants, or the combination of antioxidants. Vitamin E supplements may reduce the rate of preterm birth but showed increased rates of threatened preterm delivery and threatened abortion (12), and other possible harmful effects (15). Vitamin E may also help infants avoid asthma when the mother consumes more vitamin E during gestation (10).

Vitamin E and the U.S. Preventive Services Task Force (USPSTF): According to the USPSTF, there is insufficient evidence to recommend for or against the use of vitamin E supplements or multivitamins with folic acid or antioxidant combinations for the prevention of cancer or cardiovascular disease. (1)

 

Vitamin E and mortality:

A meta-analysis that included 78 randomized clinical trials was conducted to determine the relationship of oral antioxidant supplementation (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) and mortality. Mean duration of supplementation was 3 years. When all of the trials were combined, and the analysis that is typically used when similarity is present was conducted (fixed-effect model), antioxidant use did slightly increase mortality. When the trials with low risks of bias were considered, the patients consuming the antioxidants had a 4% higher risk of death compared to those taking placebo or no intervention (relative risk [RR]=1.04). The increased risk of mortality was significantly associated with use of beta-carotene (death rate: 13.8% on supplement vs 11.1% on placebo; RR=1.05) and vitamin E (12.0% vs 10.3%; RR=1.03) and possibly vitamin A, though the relationship was not significant with a 14.0% death rate among those taking vitamin A compared to a 13.6% death rate among placebo subjects. The current evidence does not support the use of these antioxidant supplements in the general population or in patients with various diseases. (2)

Bjelakovic G. et al (the same author as the previous study) used a meta-regression method on 47 low bias risk trials with 180, 938 subjects to evaluate antioxidant effect upon mortality. Mortality was increased in those subjects taking vitamin A, beta-carotene or vitamin E supplements. (3)

 

Vitamin E adverse reactions and interactions:

Vitamin E and clotting parameters:

Vitamin E and warfarin can safely be taken together according to results from a study on 21 individuals on long-term warfarin therapy who were randomized to receive either vitamin E or placebo. The study reports no significant change in the international normalized ratio (INR), used to report the results of blood clotting tests, in participants taking vitamin E. (4)

Vitamin E was found to enhance aspirin’s ability to prevent blood clots. This study reports that vitamin E (50 and 100 μM) inhibited aggregation of platelets, one of many cell types present within blood. In addition, vitamin E was associated with an 80% reduction in platelet adhesion to collagen (a protein). Platelet adhesion to collagen is fundamental during blood clotting. (5)

Researchers conducted a study to determine if vitamin E supplementation affects vitamin K status or blood clotting time in patients not treated with warfarin. Their study involved 38 men and women with rheumatoid arthritis and 32 healthy men participating in two independent 12-week randomized clinical trials of vitamin E supplementation. All trial participants were given 1000 IU/day of natural vitamin-E. The researchers used plasma concentration of proteins induced by vitamin K absence-factor II, or PIVKA-II for short, as a sensitive measure of vitamin K status. A normal value for PIVKA-II is 2.4 ng/mL or less and values higher than this indicate poorer vitamin-K status. At the end of the 12-week supplementation period PIVKA-II had increased from 1.7 to 11.9 ng/mL in the rheumatoid arthritis group and from 1.8 to 5.3 ng/mL in the healthy men. Thus, it would appear that supplementation with a high dose of vitamin E does indeed reduce body stores of vitamin K. The researchers concluded that high-dose vitamin E supplementation does reduce vitamin K status, but are uncertain whether this interaction is immaterial, beneficial (reduced stroke risk) or harmful (loss of bone density). (6)

Results of a 4-week study of the effect of vitamin E (800 IU of dl-alpha-tocopherol acetate) on platelet aggregation, blood clotting, and simulated bleeding time in 40 healthy individuals suggests that vitamin E does not affect anticoagulation. Vitamin E supplementation was not associated with any significant change in any of the above mentioned study parameters. (7)

 

Vitamin E and eye health:

Researchers conducted a randomized, controlled, double-blind trial to determine whether vitamin A or vitamin E, alone or in combination, would stop or slow the progression of retinitis pigmentosa, an eye disease in which there is damage to the retina. A total of 601 patients aged 18-49 years old over where assigned to either 15,000 IU/d of vitamin A, 15,000 IU/d of vitamin A plus 400 IU/d of vitamin E, trace amounts of both vitamins, or 400 IU/d of vitamin E. Findings show that those receiving 15,000 IU/d of vitamin A had on average a slower rate of decline of retinal function than the two groups not receiving this dosage.  However, 400 IU/d of vitamin E had a negative impact on the progression of retinitis pigmentosa. (8)

 

Age-related macular degeneration (AMD) and vitamin E

Age-related macular degeneration (AMD) is an aging change in the back of the eye that may lead to loss of the central vision. A study reported that the beneficial effect of antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; beta carotene, 15 mg; and zinc, 80 mg as zinc oxide with 2 mg of cupric oxide) on the risk of AMD progression among Age-Related Eye Disease Study (AREDS) participants.  Investigators also examined the relationship between AMD, cataract and mortality. During a median follow-up of 6.5 years, 11% or 534 participants had died. This marked an increased mortality risk among participants with advanced AMD. However, participants randomly assigned to receive 80 mg zinc with 2 mg cupric oxide, whether alone or combined with antioxidants, had lower mortality than those not taking the mineral. They report a 27% lower relative risk of mortality for zinc alone, and a 12% lower relative risk for those who took zinc combined with beta-carotene, vitamin C and vitamin E. The beneficial effect of zinc on mortality was associated with less death from respiratory causes. (9)

 

Vitamin E and pregnancy:

Yong, SB et al expressed that diets during pregnancy which include greater amounts of vitamin E, vitamin D, and/or probiotics have been found to result in less rates of childhod asthma and that modifying the diet to include vitamin E and other nutrients may prevent asthma. (10)

Clark J found that a dietary intervention by counseling resulted in the improvement of vitamin E intake from foods which may result in less rates of childhood asthma if it can be sustained during the entire pregnancy. (11)

Bártfai L et al found that if pregnant women were treated with about 450 mg of vitamin E, preterm births were reduced by 30%. This conclusion was drawn as a result of the treatment group being compared to a large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. In addition, the duration of gestation was found to be 0.2 weeks longer. Despite this positive finding, threatened abortion and threatened preterm delivery occurred much more frequently in the vitamin E group. (12)

 

Vitamin E and colonic adenomas:

Antioxidant vitamins A, C, and E were found to lower the recurrence rate of cancers of the colon. Individuals (n=255) with a history of colonic adenoma were randomized to receive treatment with either (1) vitamin A (30,000 IU per day), vitamin C (1 gram per day), and vitamin E (70 mg per day); (2) lactulose; or (3) placebo for an average of 18 months. At the end of the treatment period, adenoma recurrence had occurred in 5.7% of the antioxidant vitamin group compared to 14.7% in the lactulose group and 35.9% in the placebo group. (13)

 

Common Highest Vitamin E Containing Foods (14):

GENERAL MILLS, TOTAL Raisin Bran, 1 cup 21 IU
KELLOGG, KELLOGG’S PRODUCT, 1 cup 20 IU
GENERAL MILLS, Whole Grain TOTAL, 3/4 cup 20 IU
KELLOGG’S ALL-BRAN COMPLETE Wheat Flakes, 3/4 cup 20 IU
Tomato products, canned, paste, without salt added, 1 cup 17 IU
Cereals ready-to-eat, KELLOGG, KELLOGG’S RICE KRISPIES, 1-1/4 cup 13 IU
Seeds, sunflower seed kernels, dry roasted, with salt added, 1/4 cup 12 IU
Nuts, almonds,1 oz (24 nuts) 11 IU
Seeds, sunflower seed kernels, dry roasted, with salt added, 1 oz 11 IU
Spinach, frozen, chopped or leaf, cooked, boiled, drained, without salt, 1 cup 10 IU
Sauce, pasta, spaghetti/marinara, ready-to-serve, 1 cup 9 IU
Oil, sunflower, linoleic, (approx. 65%), 1 tbsp 8 IU
Pie crust, cookie-type, prepared from recipe, graham cracker, Baked, 1 pie shell 8 IU
Tomato products, canned, puree, without salt added, 1 cup 7 IU
Cereals ready-to-eat, KELLOGG, KELLOGG’S SPECIAL K, 1 cup 7 IU
Oil, safflower, salad or cooking, high oleic, 1 tbsp 7 IU
Turnip greens, frozen, cooked, boiled, drained, without salt, 1 cup 7 IU
Nuts, hazelnuts or filberts, 1 oz 6 IU
Spinach, canned, regular pack, drained solids, 1 cup 6 IU
Fast foods, shrimp, breaded and fried, 6-8 shrimp 6 IU
Fast foods, onion rings, breaded and fried, 8-9 rings 6 IU
Spinach, cooked, boiled, drained, without salt, 1 cup 6 IU
Tomato products, canned, sauce, 1 cup 5 IU

Adapted from: Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. May be accessed at: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w323.pdf

 

 

 

Assessment and Plan: Vitamin E

 

 

 

 

 

 

 

 

 

 

References:

1.Routine Vitamin Supplementation to Prevent Cancer and Cardiovascular Disease, Topic Page. June 2003. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsvita.htm

 

2.Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev, 2012 Mar 14;3:CD007176. http://www.ncbi.nlm.nih.gov/pubmed/22419320

 

3.Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007 Feb 28;297(8):842-57.  http://www.ncbi.nlm.nih.gov/pubmed/17327526

 

4.Kim JM, White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol. 1996 Mar 1;77(7):545-6. http://www.ncbi.nlm.nih.gov/pubmed/8629604

 

5.Celestini A, Pulcinelli FM, Pignatelli P, Lenti L, Frati G, Gazzaniga PP, Violi F. Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets. Haematologica. 2002 Apr; 87(4): 420-6. http://www.ncbi.nlm.nih.gov/pubmed/11940487

 

6.Booth SL, Golly I, Sacheck JM, Roubenoff R, Dallal GE, Hamada K, Blumberg JB. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004 Jul;80(1):143-8.

http://www.ncbi.nlm.nih.gov/pubmed/15213041

 

7.Dereska NH, McLemore EC, Tessier DJ, Bash DS, Brophy CM. Short-term, moderate dosage vitamin E supplementation may have no effect on platelet aggregation, coagulation profile, and bleeding time in healthy individuals. J Surg Res. 2006 May;132(1):121-9. http://www.ncbi.nlm.nih.gov/pubmed/16337968

 

8.Berson, EL., Rosner, B., Sandberg, MA., Hayes, KC., Nicholson, BW., Weigel-DiFranco, C., Willett, W., A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol. 1993 Jun;111(6):761-72. http://www.ncbi.nlm.nih.gov/pubmed/8512476

 

9.AREDS Research Group. Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study. AREDS Report No. 13. Arch Ophthalmol. 122:716-726, 2004. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1473208/?report=abstract

 

10.Yong SB, Wu CC, Wang L, Yang KD.Influence and mechanisms of maternal and infant diets on the development of childhood asthma. Pediatr Neonatol. 2013 Feb;54(1):5-11. http://www.ncbi.nlm.nih.gov/pubmed/23445737

 

11.Clark J, Craig L, McNeill G, Smith N, Norrie J, Devereux G. A novel dietary intervention to optimize vitamin E intake of pregnant women to 15 mg/day. J Acad Nutr Diet. 2012 Feb;112(2):297-301. http://www.ncbi.nlm.nih.gov/pubmed/22741171

 

12.Bártfai L, Bártfai Z, Nedeczky I, Puho EH, Bánhidy F, Czeizel AE. Rate of preterm birth in pregnant women with vitamin E treatment: a population-based study. J Matern Fetal Neonatal Med. 2012 Jun;25(6):575-80. doi: 10.3109/14767058.2011.587060. Epub 2012 Mar 26. http://www.ncbi.nlm.nih.gov/pubmed/22443476

 

13.Roncucci L, Di Donato P, Carati L, et al. Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas. Colorectal Cancer Study Group of the University of Modena and the Health Care District 16. Dis Colon Rectum. 1993 Mar;36(3):227-34. http://www.ncbi.nlm.nih.gov/pubmed/8449125

 

14.Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. May be accessed at: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w323.pdf

 

15.Hovdenak N, Haram K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):127-32. http://www.ncbi.nlm.nih.gov/pubmed/22771225

 

16.The Food and Nutrition Board at the Institute of Medicine Recommended Intakes for Individuals for vitamin E.

 

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