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High Dose

Vitamin E

Written by: Shahdad Azmoon, MD and Sedigheh Omidi

Date of  Publication:  September 11th, 2005

“High dose Vitamin E in the 21^st century”

           Vitamin E is found among many of the different food group including vegetables, nuts, legumes, and oil.  Vitamin E can also be obtained through the use of multivitamins and supplements.  In comparing multivitamins with supplements, usually multivitamins contain about 30 international units (IU) of vitamin E, where as 200,400, 1000 IU or more Vitamin E maybe found in supplements.  The current tolerable upper limits of Vitamin E intake are designated at 1500 IU of natural vitamin E per day an amount approximately equivalent to 1100 IU of synthetic vitamin E per day (1) 

            Although in the past some research has suggested that Vitamin E may help treat or prevent some diseases, there is concern for the amount of use of Vitamin E because of several recent reports which suggested that high intake of Vitamin E (400 IU or more daily) for long periods in patients with vascular disease or diabetes mellitus maybe associated with an increase risk of heart failure (2) and death (3).  More specifically the risk of death progressively rose with increased dosage of Vitamin E use above 150 IU. (3)  This is an important notion as Balluz and colleagues pointed out the regular consumption of Vitamins in the United States (4).  Ford and colleagues reported Vitamin E supplementation of 400 IU or greater in a significant amount of the adult US population with which daily dose appeared to have a positive correlation with increasing patient age. (13)  There was particular reference to Vitamin E use noted to patients with established cardiovascular diseases and cancer by Satia-Abouta and colleagues. (5) 

            Vitamin E, a fat-soluble vitamin was considered safe (6) compared to its counterpart fat-soluble vitamins including Vitamins A, D, & K.  However it could still be associated with adverse effects (7), including pro-oxidant effects at high doses (8, 9) which may work against the plausible benefits of anti-oxidants.  This effect maybe augmented even more as other fat soluble antioxidants maybe displaced by patients taking the high dosages of Vitamin E. (10)  Vitamin E is also noted to have anticoagulant properties (11) where Heinonen and colleagues reported a slightly increased risk of hemorrhagic stroke among patients with lung and other cancers who were also on Vitamin E equivalent supplementation compared to patients with similar cancers who were not on concurrent Vitamin E supplementation during this trial. (12)

            Withdrawal effects have been well established for a variety of drugs in which the human body has become dependant on after its chronic use.  Such withdrawal symptoms maybe augmented by irregular use of such drugs as well.  Anderson and colleagues noted in a small study of 15 patients that when patients with angina discontinued their chronic Vitamin E use abruptly, a significant increase in their anginal or anginal equivalent symptoms were noted compared to patients with similar history of angina pectoris who continued with their Vitamin E usage.  In fact 3 patients in the placebo group had to discontinue the trial prematurely because of their worsening anginal symptoms. (13)

            To date there has not been enough trials noted concerning the use of Vitamin E in a detailed dose–response analysis of cause-specific end points.  As well, inconsistent reporting of events across trials and small trial size was noted by Miller and colleagues in their meta-analysis of high dose Vitamin E supplementation. (3)  Many studies on Vitamin E have not been performed on patients completely free of other chronic diseases which may have had influence on its use and adverse outcomes as well as the use of other medications including other vitamins.  Given current suggestions of increased mortality it would be un-ethical to organize trials of Vitamin E for long term dose response with end point for mortality in any class of patients.  It is apparent that publicity of such results may have confounded the general public’s knowledge and use of all vitamins, including those of Vitamin E.  More so, such over whelming news may have put burden on the benefits of Vitamin E.  However as noted in Anderson and colleagues’ small, non-replicated trial published in 1974 (14), one can’t stop to take notice of the possible outcomes given abrupt discontinuation of high dose Vitamin E supplementation.  Since the climax of high dose Vitamin E trials, little has been mentioned regarding the proper methods of discontinuation for those patients who have been on long term Vitamin E therapy.  Given long-term vitamin E supplementation does not prevent cancer (12) or major cardiovascular events and may increase the risk for heart failure and death (2,3), physicians need to inquire more about their patient’s use of Vitamin E supplementation and possibly suggest a slow taper to daily recommended values. 

 References:

1. Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. A report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Food Nutrition Board. Washington, DC: National Academies Pr; 2000.

2. Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, et al. Effects of long-term vitamin  E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293:1338-47 [Abstract/Free Full Text]

3. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46. [Abstract/Free Full Text]

4. Balluz LS, Kieszak SM, Philen RM, Mulinare J. Vitamin and mineral supplement use in the United States. Results from the third National Health and Nutrition Examination Survey. Arch Fam Med. 2000;9:258-62. [Abstract/Free Full Text]

5. Satia-Abouta J, Kristal AR, Patterson RE, Littman AJ, Stratton KL, White E. Dietary supplement use and medical conditions: the VITAL study. Am J Prev Med. 2003;24:43-51.

6. Bendich A, Machlin LJ. Safety of oral intake of vitamin E. Am J Clin Nutr. 1988;48:612-9. [Abstract]

7. Roberts HJ. Perspective on vitamin E as therapy. JAMA. 1981;246:129-31.

8. Bowry VW, Stocker R. Tocopherol-mediated peroxidation. The prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein. Journal of the American Chemical Society. 1993;115:6029-44.

9. Abudu N, Miller JJ, Attaelmannan M, Levinson SS. Vitamins in human arteriosclerosis with emphasis on vitamin C and vitamin E. Clin Chim Acta. 2004;339:11-25.

10. Huang HY, Appel LJ. Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr. 2003;133:3137-40. [Abstract/Free Full Text]

11. Dowd P, Zheng ZB. On the mechanism of the anticlotting action of vitamin E quinone. Proc Natl Acad Sci U S A. 1995;92:8171-5. [Abstract/Free Full Text]

12. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994;330:1029-35. [Abstract/Free Full Text]

13. Earl S. Ford, Umed A. Ajani, and Ali H. Mokdad, Brief Communication: The Prevalence of High Intake of Vitamin E from the Use of Supplements among U.S. Adults, Annals 2005 143: 116-120. [Abstract] [Summary] [Full Text]  

14. Anderson TW, Reid DB. A double-blind trial of vitamin E in angina pectoris. Am J Clin Nutr. 1974;27:1174-8.

Remember:

1)  Please follow up with your physician on a routine basis as needed.

2)  Please follow directions when taking medications.

3)  Please do not hesitate to see a physician when concerns arise regarding your health.

4)  Your health should be your most important investment, take good care of it!

Sincerely,

Dr. Azmoon

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