Chapter 43. Vitamin E, Curse or Blessing?

Chapter 43. Vitamin E, Curse or Blessing?

Years ago, when the kids were little, my family went on a rafting trip on the Snake River in Idaho.  Everyone enjoyed the river adventure, and we later took a side trip through Coeur D'Alene where we found a dusty second hand book store called the "Book Worm".  Inside the store, I found a 1964 copy of "Vitamin E, Your Key to a Healthy Heart" by Herbert Bailey.(49)   This was one of the first books that stimulated interest in Vitamin E and sold a million copies.

The History of Vitamin E - Discovered in 1922

About 90 years ago, an obscure researcher named Herbert Evans, was hot on the trail of an unknown dietary ingredient in wheat germ required for fertility in his laboratory rats. This was Vitamin E. The chemical structure was determined in 1938, and Evans named it "tocopherol", a word meaning "to bear young" in ancient Greek.   Early work also found Vitamin E prevented muscular dystrophy in young rats fed a vitamin E deficient diet. (46-48).  In the 1930's and 1940's, two Canadian cardiologists, Wilfred and Evan Shute treated 30,000 patients with natural vitamin E and reported considerable success in reversing heart disease.(45)

A Medical Conference on Vitamin E

In 2008, I attended the ACAM Medical Meeting in Orlando where Kenny Jialal, MD was awarded the Linus Pauling Medal in recognition of his Vitamin E research.(3-4)  Dr. Jialal then took the podium and spoke on Vitamin E, summarizing hundreds of research studies over decades.  Some studies were favorable, some were unfavorable, some used one type of vitamin E, and some used another type of vitamin E, some he had no idea which type was used.  I think you get the gist.  At the end of the hour, Dr Jialal had completely confused my remaining understanding of Vitamin E, transforming the topic into a giant enigma wrapped in a mystery.  I left the room with a headache.  In this article, we will hopefully remedy the headache, and clear up any confusion about Vitamin E with new insights.  First, let's look at some recent doubts about Vitamin E.

New Doubts About Vitamin E, Vitamin E is Deadly !!

You may have seen news reports that Vitamin E is dangerous, deadly and increases mortality.  These media stories were based on an article by Edgar Miller in the Jan 2005 Annals of Internal Medicine, a meta-analysis of 19 studies on Vitamin E, concluding that Vitamin E increases mortality. (13-14)  Here are a few of the news reports:

The Solution: Use Natural Vitamin E and Avoid Synthetic E

The effect of Miller's Vitamin E article was that many people stopped taking Vitamin E.  An excellent rebuttal to Dr Miller by Dr Mark Houston pointed out the type of Vitamin E used in Miller's meta-Analysis was synthetic DL alpha tocopherol. "None of the 19 studies in Miller's review article included any of the other seven forms of vitamin E, and, in fact, most of them used the synthetic DL alpha tocopherol form."(15)   It is important to distinguish natural vitamin E from the synthetic Vitamin E which is to be avoided.  In addition, Houston recommends a mixture of the 8 types of Vitamin E found in nature.

The Fox Guarding the Henhouse?

Amazingly, another negative Vitamin E study published by Sesso in JAMA Nov 9, 2008 again used the synthetic form of Vitamin E.(9)  You would think that doctors are highly intelligent, and would know to use the natural form of vitamin E, when designing such a study.  A skeptic might suggest that perhaps the synthetic form was intentionally used to insure failure and discredit vitamin E.  Another disturbing fact is that Sesso's negative Vitamin study was sponsored by Wyeth, a drug company with a long history of animosity to natural treatments. The paper also disclosed that the authors were in bed with the drug companies. They received funding from Wyeth, Merck, Bristol Meyer Squibb, Astra Zeneca, Pfizer and Bayer. Dr. Gaziano, the chair of the project, even served as expert witness for Merck, defending the drug company in court. (9)  I would say this is another example of “the Fox Guarding the Henhouse”.(10)

The Different Types of Vitamin E, Synthetic vs. Natural

Natural vitamin E is in the "D" form (D is for Dextro which is Latin for Right-Handed). Synthetic Vitamin E is a combination of D and L form (i.e. DL).  The synthetic form is cheaper, but is not recommended.  There are the 8 types of Vitamin E - tocopherols in natures including, alpha, delta, gamma forms.  Dr. Jialal says the gamma form is more beneficial than the alpha form.

Evidence that the Natural Form of Vitamin E is Beneficial

Two landmark Vitamin E studies were published in 1993 in the New England Journal of Medicine.  Eric Rimm's study showed a 36% reduction in heart disease in men taking the relatively modest 60 IU vitamin E daily in the diet.(41)  Meir Stamfer's study showed a 33% reduction in heart attacks in women with the highest dietary vitamin E consumption.(43)

More Studies Showing Benefits of Natural Vitamin E

In 1992, Verlangieri published a study in which natural vitamin E reversed atherosclerosis in a primate model.(27)  A 1995 study published in JAMA by Hodis showed Vitamin E caused regression of atherosclerosis on serial coronary angiography. (28)  Dr. Hodis concluded with this statement: "These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression."  In 1996, Stephens published his study in Lancet which showed that tocopherol (vitamin E ) given to patients with advanced coronary artery disease reduced the risk of non-fatal Myocardial Infarction (MI) by 77%, (but did not decrease total mortality in this study).(37)  In 2000, Boaz published a study in Lancet showing that 800 IU/daily of natural Vitamin E reduced heart attacks by 70% over 1.4 years in Hemodialysis patients. (44)

Reversing Carotid Stenosis with Natural Vitamin E

In 1997 Bierenbaum presented data on reversal of atherosclerosis in carotid stenosis with mixed tocopherols and tocotrienols at a meeting in Montreal.(2)   The Bierenbaum study was done at the Kenneth Jordan Heart Research Foundation in New Jersey. The five-year study evaluated 50 patients who had stenosis of the carotid artery. One group of 25 patients received 650 mgs of tocotrienols plus tocopherols. The other group of 25 received a placebo. All patients had serial carotid sonography every six months. In the Placebo group, fifteen patients showed worsening of the stenosis, eight remained stable and two showed some improvement.  In the Vitamin E Group using Tocotrienol plus tocopherol, three patients showed minor worsening, and 12 remained stable.  Ten patients showed regression of stenosis with improvement.(29-32)

Not only is there a difference between synthetic and natural vitamin E, there is also a new form of vitamin E called Tocotrienol which new research suggests is the more biologically useful form. (22)  Let's take a look at the Tocotrienol form of Vitamin E:

The 21st Century Form of Vitamin E - Tocotrienol

The Difference Between the Tocopherol and Tocotrienol Forms

Tocotrienol is IDENTICAL to Tocopherol except for the three double bonds in the tail. These three double bonds create a kinked configuration of the "tail" which allows the molecule more mobility through lipid membranes.  The double bond also indicates a state of electron desaturation, meaning it can accept electrons readily as an antioxidant. The three double bonds represent an "unsaturated" side chain which allows the molecule to penetrate into saturated lipid membrane layers in various target organs.  Thus, the tocotrienol form is superior to tocopherol as an antioxidant, serving to reverse lipid peroxidation.  About 99% of medical research since the discovery of Vitamin E has been devoted to the tocopherol form, and 1% on the tocotrienol form.  This seems to be changing. There are no synthetic forms of tocotrienols available, only natural ones.(5-8)(16-19)(22-25)

Processed Trans-Fats vs. Natural  Oils

Remember the difference between Processed Trans-Fats and Natural Oils such as cold pressed olive oil?  The unhealthy Trans-Fats have a straight carbon tail because they have been processed, so the Carbons are located on the opposite sides of the double bonds (trans).  The healthy natural oils have a curved configuration of the carbon tail because the Carbons are on the same side of the double bond (cis). This difference is called cis-trans isomerism.

Toxic Trans Fats Have Straight Tails - Tocotrienols Have Curved Tails

Similar to the beneficial natural oils, Tocotrienols have a curved carbon tail, giving them more biological activity than the tocopherol counterpart.  The Tocotrienol tail is not stationary, but actually vibrates back and forth in space like a pendulum, absorbing energy within the membrane bi-layer. (8)

Health Benefits of Tocotrienol Form of Vitamin E

1) Tocotrienols are protective in stroke-induced injuries. Natural palm tocotrienol complex fed to hypertensive rats led to increased tocotrienols level in the brain, and more protection against stroke-induced injury compared to controls. (50)

2) Tocotrienol reversed atherosclerosis in carotid artery stenosis in a human study by Bierenbaum. (51)

3) Tocotrienols and cholesterol reduction: Gamma tocotrienol inhibit hepatic cholesterol synthesis without interfering with CoQ10 production, thus reducing LDL cholesterol levels safely. (5-7)

Apo-E Mouse Studies Show Tocotrienol Protects, Tocopherol Does NOT

The Apo-E Mouse Model is a genetically modified mouse that develops atherosclerosis of the aorta. Two separate studies, by Qureshi and another by Black showed that feeding Tocotrienols to the Apo-E mice virtually eliminates atherosclerotic plaque. (38,39)  Tocotrienols reduced the atherosclerosis plaque by 98%, an amazing result. On the other hand, Tocopherols had no such beneficial effect in Apo-E mice in the study by Shaish (1999) who found no change in plaque size with Tocopherols.(40)

Reversing Coronary Artery Disease

My previous article discussed the use of high dose Vitamin C, and the amino acid, Lysine, (the Linus Pauling Protocol) for reversing heart disease.  Steve Hickey and Hilary Roberts come right out on page 167 of their book, and make the statement, "Vitamin C and Tocotrienols can reverse coronary artery disease". (52)  They would improve the Linus Pauling Protocol by adding the Tocotrienol form of Vitamin E.  Regarding heart disease and atherosclerotic vascular disease, the authors state that "on the available evidence, the combination of Vitamin C and Tocotrienols could be curative with no known harmful effects." (52)

Future Research for the NIH, the Guinea Pig Model:

Tocotrienols clearly prevent atherosclerosis in the Apo-E mouse model.  Further research in the guinea pig model should be done.  C. G. Willis showed that Vitamin C deprived guinea pigs develop atherosclerotic vascular disease. (see references in Chapter 37)   Experiments should be done giving tocotrienols to Vitamin C deprived guinea pigs, and I would predict Tocotrienols would be beneficial, reducing or preventing atherosclerotic plaque formation.  In addition, there is a GLO deficient mouse model used to study atherosclerosis.  Experiments giving tocotrienols to GLO deficient mice should also be done.

For references and links, see my web site: www.bioidenticalhormones101.com

References for Chapter 43. Vitamin E, Curse or Blessing?

(1) http://news.bbc.co.uk/1/hi/health/3998847.stm
High dose vitamin E death warning , November 11, 2004, BBC News.

(2) http://www.usatoday.com/news/health/2004-11-10-vitamin-e-risks_x.htm
Study: High dose of Vitamin E increases death risk. By Steve Sternberg, USA TODAY 11/10/2004

(3) http://www.ucdmc.ucdavis.edu/ucdavismedicine/issues/fall2008/
departments/honors_and_awards.html
American College for Advancement in Medicine presented Ishwarlal Jialal with the Linus Pauling Award.

(4) http://www.ucdmc.ucdavis.edu/search/faculty/biodetail.asp?bioid=860
Ishwarlal Jialal, M.D., Ph.D. UC Davis  Professor Robert E. Stowell Endowed Chair in Experimental Pathology Director of Laboratory for Atherosclerosis and Metabolic Research  Specialty: Pathology and Laboratory Medicine, Biological Chemistry 

(5) http://www.drpasswater.com/nutrition_library/tan_1.html Doctor Tocotrienol Barrie Tan Part One

(6) http://www.drpasswater.com/nutrition_library/tan_2.html  Doctor Tocotrienol Barrie Tan Part Two

(7) http://www.acgrace.com/images/stories/acgrace/healthbenefitsbeyondvitamineactivity.pdf
Health Benefits Beyond Vitamin E Activity, Solving the Tocotrienol Riddle.  Dr. Barrie Tan

(8) http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17507086
Mol Aspects Med. 2007; 28(5-6): 692–728.  Tocotrienols in health and disease: the other half of the natural vitamin E family. Chandan K. Sen, Savita Khanna, and Sashwati Roy

(9) http://jama.ama-assn.org/cgi/content/full/300/18/2123 Vitamins E and C in the Prevention of Cardiovascular Disease in Men. The Physicians' Health Study II Randomized Controlled Trial. Howard D. Sesso et al JAMA. 2008;300(18):2123-2133. November 9, 2008

(10) http://aahf.nonprofitsoapbox.com/index.php?option=com_content&task=view&id=601&Itemid=
Unfair Attacks on Supplements. The following is an analysis of a recent study on vitamins C and E by the scientific team of the Alliance for Natural Health, our international affiliate. Designed To Fail: A Trial Without Meaning. Contributed by Steve Hickey, Ph.D.; Damien Downing, M.B.B.S.; and Robert Verkerk, Ph.D., Alliance for Natural Health.

(11) http://www.ncbi.nlm.nih.gov/pubmed/16190316
Nutr Rev. 2005 Aug;63(8):290-3.  Failure of vitamin E in clinical trials: is gamma-tocopherol the answer? Devaraj S, Jialal I.

(12) http://www.annals.org/cgi/content/full/142/1/75
 Vitamin E Supplements: Good in Theory, but Is the Theory Good?  E. Robert Greenberg, MD  Annals of Internal Medicine 4 January 2005, Vol 142, Issue 1, Pages 75-76

(13) http://www.annals.org/cgi/content/full/142/1/37
 High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality Edgar R. Miller et al. Annals of Internal Medicine  4 January 2005 | Volume 142 Issue 1 | Pages 37-46

(14) http://www.annals.org/cgi/content/full/142/1/I-40
SUMMARIES FOR PATIENTS Vitamin E Supplements May Be Harmful. Annals of Internal Medicine 4 January 2005 | Volume 142 Issue 1 | Page I-40

(15) http://ana-jana.org/reprints/VitaminEEditorialbyMarkHouston,_MD.pdf
JANA Vol. 8 No. 1, 2005, “Meta-Analysis, Metaphysics and Mythology”Scientific and Clinical Perspective on the Controversies Regarding Vitamin E for the Prevention and Treatment of Disease in Humans  by Mark Houston, MD

(16) Nesaretnam K, Ambra R, Selvaduray KR, et al. (2004). Tocotrienol-rich fraction from palm oil and gene expression in human breast cancer cells. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1031: 143-157. 

(17) Conte C, Floridi A, Aisa C, et al. (2004). Gamma-Tocotrienol metabolism and antiproliferative effect in prostate cancer cells. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1031: 391-394. 

(18) Hasselwander O, Kramer K, Hoppe PP, et al. (2002). Effects of feeding various tocotrienol sources on plasma lipids and aortic atherosclerotic lesions in cholesterol-fed rabbits. FOOD RESEARCH INTERNATIONAL 35 (2-3): 245-251
 
(19) http://www.acgrace.com/index.php?option=com_virtuemart&Itemid=5
UNIQUE E® Tocotrienols - 60 Softgels $39.50 , AC Grace Co.

(20) Kappus H, Diplock AT. Tolerance and safety of vitamin E: a toxicological position report. Free Radic Biol Med 1992;13:55–’D074.

(21) Vitamins E and C are safe across a broad range of intakes. Hathcock JN, Azzi A, Blumberg J, Bray T, Dickinson A, Frei B, Jialal I, Johnston CS, Kelly FJ, Kraemer K, Packer L, Parthasarathy S, Sies H, Traber MG. Am J Clin Nutr. 2005 Apr;81(4):736-45.

(22) http://www.ncbi.nlm.nih.gov/pubmed/10480444
Clin Biochem. 1999 Jul;32(5):309-19. Tocotrienol: a review of its therapeutic potential.Theriault A, Chao JT, Wang Q, Gapor A, Adeli K..

(23) http://www.ncbi.nlm.nih.gov/pubmed/15753140
Ann N Y Acad Sci. 2004 Dec;1031:127-42. Tocotrienol: the natural vitamin E to defend the nervous system? Sen CK, Khanna S, Roy S.

(24) http://ajpheart.physiology.org/cgi/content/full/289/1/H361
Am J Physiol Heart Circ Physiol 289: H361-H367, 2005. Cardioprotection with palm tocotrienol: antioxidant activity of tocotrienol is linked with its ability to stabilize proteasomes. Samarjit Das et al.

(25) http://www.drpasswater.com/nutrition_library/bierenbaum.html
Reversing Arteriosclerosis with Tocotrienols: An interview with Marvin Bierenbaum, M.D. and Tom Watkins, Ph.D.  by Richard A. Passwater, Ph.D.

(26) Passwater, R.A. (1992) Reversing atherosclerosis:  An interview with Dr. Anthony Verlangieri. Whole Foods 15(9):27-30.

(27) Verlangieri, A.J. and Bush, M.K. (1992)  Effects of d-alpha-tocopherol supplementation on experimentally induced primate atherosclerosis. J. Amer. Coll. Nutr. 11:131-138.

(28) Hodis, H.N.; Mack, W.J.; LaBree, L.; Cashin-Hemphill, L.; Sevanian, A.; Johnson, R. and Azen, S.P. (1995) Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 273(23):1849-1854.

(29) Kooyenga, D.K.; Geller,M.; Watkins, T.R. and Bierenbaum, M.L. (July 29, 1997)
Antioxidant-induced regression of carotid stenosis over three-years. Proceedings of the 16th International Congress of Nutrition. Montreal.

(30) Watkins, T.; Lenz, P.; Gapor, A.; Struck, M.: Tomeo, A. and Bierenbaum, M. (1993) Gamma- tocotrienol as a hypocholesterolemic and antioxidant agent in rats fed atherogenic diets. Lipids 28(12):1113-1118.

(31) Suzuki, Y.J.; Tsuchiya, M.; Wassall, S.R.; Choo, Y.M.; Govil, G.; Kagan, V.E. and Packer, L. (1993) Structural and dynamic membrane properties of alpha-tocopherol and alpha-tocotrienol: implication to the molecular mechanism of their antioxidant potency. Biochem. 32:10692-10699.

(32). Tomeo, A.C.; Geller, M.; Watkins, T.R.; Gapor, A. and Bierenbaum, M.L. (1995) Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis. Lipids 30(12):1179-1183.

(33) http://www.douglaslabs.com/pdf/nutrinews/Vitamin%20E%20NN%20(01-08).pdf
Vitamin E: A New Perspective. NutriNews  from Douglas Laboratories January/February 2008 . Andreas M. Papas, Ph.D.

(34) http://stroke.ahajournals.org/cgi/content/full/36/10/e144
Stroke. 2005;36:e144. Neuroprotective Properties of the Natural Vitamin E -Tocotrienol Savita Khanna, PhD; Sashwati Roy, et al. T

(35) http://www.jacn.org/cgi/content/abstract/11/2/131
J Am Col of Nut, Vol 11, Issue 2 131-138, 1992. Effects of d-alpha-tocopherol supplementation on experimentally induced primate atherosclerosis. A. J. Verlangieri and M. J. Bush

(37) http://www.ncbi.nlm.nih.gov/pubmed/8622332
Lancet. 1996 Mar 23;347(9004):781-6. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS)Stephens NG, Parsons A et al.

(38) http://jn.nutrition.org/cgi/content/full/131/10/2606
Journal of Nutrition. 2001;131:2606-2618. Novel Tocotrienols of Rice Bran Inhibit Atherosclerotic Lesions in C57BL/6 ApoE-Deficient Mice. Asaf A. Qureshi et. al.

(39) http://jn.nutrition.org/cgi/content/abstract/130/10/2420
Palm Tocotrienols Protect ApoE +/- Mice from Diet-Induced Atheroma Formation Tracy M. Black et al. J. Nutr. October 1, 2000 vol. 130 no. 10 2420-2426

(40) http://atvb.ahajournals.org/cgi/content/full/19/6/1470
Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1470-1475.) Dietary ß-Carotene and -Tocopherol Combination Does Not Inhibit Atherogenesis in an ApoE–Deficient Mouse Model. Aviv Shaish et al.

(41) http://www.benbest.com/nutrceut/VitaminE.html
Vitamin E (Tocopherols and Tocotrienols) by Ben Best

(42) http://content.nejm.org/cgi/content/short/328/20/1450
NEJM Volume 328:1450-1456  May 20, 1993  Number 20. Vitamin E Consumption and the Risk of Coronary Heart Disease in Men. Eric B. Rimm et al.

(43) http://content.nejm.org/cgi/content/short/328/20/1444
NEJM Volume 328:1444-1449  May 20, 1993  Number 20 Vitamin E Consumption and the Risk of Coronary Disease in Women. Meir J. Stampfer, Charles H. Hennekens, JoAnn E. Manson, Graham A. Colditz, Bernard Rosner, and Walter C. Willett 

(44) http://www.ncbi.nlm.nih.gov/pubmed/11072938
Lancet. 2000 Oct 7;356(9237):1213-8. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, Knecht A, Weissgarten Y, Brunner D, Fainaru M, Green MS.

(45) http://www.doctoryourself.com/biblio_shute.html Wilfrid Shute, M.D and Evan Shute, M.D.Partial Bibliography of Papers and Books, website by Andrew Saul, PhD

(46) http://jn.nutrition.org/content/17/4/371.full.pdf HERBERT MCLEAN EVANS (1882-1971) A Biographical Sketch by I. D. RAACKE. Journal of nutrition 1963;79:l-8. 20.

(47) http://jn.nutrition.org/content/17/4/371.full.pdf THE PREVENTIVE EFFECT OF WHEAT GERM OILS AND OF a-TOCOPHEROL IN NUTRITIONAL MUSCULAR DYSTROPHY OF YOUNG RATS 1 MARIANNE GOETTSCH AND JOHANA EITZMANN. J. Nutrition, 1939 vol. 17, p. 371.

(48) http://jn.nutrition.org/content/22/5/463.full.pdf a-TOCOPHEROL REQUIREMENT OF THE RAT FOR REPRODUCTION IN THE FEMALE AND PREVENTION OF MUSCULAR DYSTROPHY IN THE YOUNG, MARIANNE GOETTSCH AND ALWIN M. PAPPENHEIMER   JOURNAL OF OF NUTRITION 1941 P.463.

(49) VITAMIN E , Your Key To a Healthy Heart by Herbert Bailey. N. Y. Arc Books; 10th Printing edition (1971).

(50) http://www.ncbi.nlm.nih.gov/pubmed/16166580 Stroke. 2005 Oct;36(10):2258-64. Neuroprotective properties of the natural vitamin E alpha-tocotrienol. Khanna S et al.

 (51) Watkins TR, Bierenbaum ML, Giampaolo A. Tocotrienols: Biological and Health Effects. In Antioxidant Status, Diet, Nutrition and Health, Papas AM editor, CRC Press, Boca Raton, 1998;479-96.

(52) Ascorbate: The Science of Vitamin C , Dr. Steve Hickey & Dr. Hilary Roberts , LULU (May 20, 2004)

Author: Jeffrey Dach MD