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FILLERS: Vitamin E isn't helpful and may be harmful BMJ 2005; 330: 0-f [Full text]

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Ignoring data isn't helpful and may be harmful

P. David Mitchell   (4 March 2005)

The truth about Vitamin E - Vitamin E is safer than implied

Neil E. Levin   (4 March 2005)

"Comparing vitamin E users" proves nothing.

Barry Savage   (11 March 2005)

Ignoring data isn't helpful and may be harmful 4 March 2005
P. David Mitchell, Professor Emeritus Concordia University, Montreal, H3G1M8 Send response to journal: Re: Ignoring data isn't helpful and may be harmful	The 'Bottom Line' (that Vitamin E "does not decrease all causes mortality in patients with or without pre-existing heart disease") is NOT supported by the study cited. Amongst other design errors, the authors analyzed results from 19 studies (of 31 that met their criteria), most of which used E with high risk patients (e.g. cancer, heart disease, dialysis) and the average age in nearly all was over 60 (range 47 to 84 years). How can one generalize to healthy people of all ages and regardless of natural or synthetic E (no distinction was made)? Moreover a few high dosage trials had much higher death rates than the majority; was this linked to age or disease? Importantly the authors actually screened out 12 of the 31 studies because they had a LOW death rate, keeping only those that had at least 10 deaths! What might we conclude if we examined those 12 missing studies with zero or no deaths? Did vitamin E in high doses produce those low death rates? Competing interests: None declared
The truth about Vitamin E - Vitamin E is safer than implied 4 March 2005
Neil E. Levin, Nutrition Educator, Clinical Nutritionist NOW Foods, 395 S Glen Ellyn Road, Bloomingdale, IL 60108 Send response to journal: Re: The truth about Vitamin E - Vitamin E is safer than implied	An article published in January in the medical journal Annals of Internal Medicine claimed that Vitamin E may have increased the number of deaths in some studies. Researchers at Johns Hopkins subjected only a small number of Vitamin E studies to a meta-analysis, which is where previously published studies are re-examined and compared in order to try to mine more information out of them. These meta-analyses may be highly speculative because the protocol for each study is different enough that it often becomes a stretch to link the results and imply a common thread runs through them, despite possibly increasing the number of variables. For example, the supplement tested may be given in different forms or doses, the patient group may have significant differences in age, health or even compliance, the length of time people were taking the supplement may vary considerably (or may even include previous users and new users), etc. There are also differences between natural and synthetic Vitamin E, with most studies using only the synthetic forms, which are composed of different-shaped molecules only half as effective as natural Vitamin E. Natural Vitamin E is called d-alpha tocopherol and synthetic Vitamin E is called dl-alpha tocopherol. The main study in this analysis apparently used the synthetic form, making it unclear whether the results could be duplicated if testing the natural form. It is also known that alpha tocopherol can block absorption of gamma tocopherol, an important antioxidant. Vitamin E complexes with several forms of natural tocopherols are far better than just one kind of Vitamin E. Official U.S. dietary guidelines set an upper tolerable intake limit of 1,500 IU per day for natural Vitamin E versus only 1,000 IU for the synthetic form, based on the total scientific record. The national Institute of Medicine (the same body that sets our RDAs and Daily Values for vitamins) looked at hundreds of Vitamin E studies, including ones that were reviewed by the Johns Hopkins team. Eighteen of the studies reviewed in this meta-analysis have insignificant death rate variations and the nineteenth had patients taking more than one potency of Vitamin E, so it is impossible to accurately determine a relationship between dose and death. Additionally, 10 of the 19 studies did not isolate Vitamin E use; participants also used other dietary supplements. In my opinion, that team skewed the results by excluding other, perhaps more valid studies, because they used only studies where at least ten people died during the course of the studies from all causes (not necessarily from Vitamin E). These studies were not even originally designed to look at deaths, but the length of the studies and the poor health of the participants made some deaths inevitable. Even so, they only got about a half percent increase in the death rate projected over decades. This is statistically questionable, and several statisticians have commented on this in the responses to the Annals article. The original studies alone did not generate any increased deaths among Vitamin E users, so this group of studies would not be expected to yield additional deaths unless the protocol somehow magnified insignificant differences. The problematic selection of studies reviewed, the inability to adequately control variables in this analysis and the pooling of studies using different dosages and forms to generate a slightly negative result generates much heat but no light on the truth of Vitamin E safety. Vitamin E prevents cellular damage and does not cause more deaths when all studies are correctly reviewed, as the Institute of Medicine has done. While these meta-analyses may be academically useful to point to potential new problems or solutions, by no means are they necessarily proof of anything, due to the lack of uniform protocols and patient groups. These doctors and researchers may be well-meaning, but results of this kind of preliminary study can be publicized and take on a life of their own, with a new role as “proof” of the dangers of taking vitamins. One thing that many of the patients in this analysis of previous studies had in common was being elderly and sick. So the first caution issued by the report’s own authors is that their speculative findings do not apply to healthy or younger people. That’s one BIG argument against using this analysis to set general restrictions on Vitamin E dosages. We already have some evidence that taking one antioxidant, rather than antioxidant formulas or multiple vitamins, may increase cancer risks for aged smokers. This may be because antioxidants need to recharge and support each other or else (in large doses) some can actually transform into pro-oxidants that can increase cellular damage. I always caution against taking mega-doses of one nutrient without considering potential side effects. Taking only one antioxidant may effectively deplete others because of the way they interact, with one antioxidant chemically supporting the others. A surplus of one nutrient may increase a person's need for one or more other nutrients, creating an apparent functional deficiency. There is a recent example that illustrates my point. Some years ago an antioxidant study in Finland was halted early, with a widely reported increase in cancer rates among male smokers taking beta-carotene. Headlines associated this vitamin with greater cancer risks. Despite objections that the study was flawed, beta-carotene use dropped. Fast-forward to 2004. A new analysis published in July took another look at that same Finnish smokers' study, but now takes into account their total antioxidant intake, and this clears up that whole controversy. Their risk of getting lung cancer was closely associated with total antioxidants in the diet, with more antioxidants meaning less cancer. A composite antioxidant index was generated for each of the 27,000 men over 14 years. The calculated amounts of carotenoids, flavonoids, Vitamin E, selenium and Vitamin C were compared to actual lung cancer rates, with a clear result: a combination of antioxidants lowers lung cancer risk in male smokers. What does this all mean? I think we are in for another round of attacks on vitamins based on this crude analysis of Vitamin E, with some medical advocates calling for sharp restrictions on vitamin potency. That would be a mistake legally, scientifically and from a public health viewpoint. The message should be that people shouldn’t try to take a high dose of one supplement without considering that it may increase our need for other nutrients, and that natural molecules are safer than other forms. Elderly, sick people need a more holistic approach rather than using a single nutrient in high doses, as if it were a drug. Nutrients just don’t work well in isolation from each other. Vitamins are essential to health and life, but the average American gets only 1/3 of the recommended daily intake of Vitamin E, the amount that the Institute of Medicine determined to be needed to prevent serious illnesses. Most people would benefit from taking a multiple vitamin and a Vitamin E supplement, and it would be safer than just the Vitamin E alone. People with serious heart diseases are more likely to take a Vitamin E supplement than the general population, but the supplement may not work very quickly or effectively on these seriously ill people, making them more likely to die during a lengthy study...from their pre-existing disease, not from taking a vitamin! Antioxidant vitamins are useful to prevent aging and chronic diseases, which was actually demonstrated by some of the same studies that these scientists “re-examined” to find fault with. For example, clinical studies show that supplemental antioxidants and lutein, a plant pigment, are the only tested effective method of preventing and safely reversing macular degeneration, a major cause of blindness. Oxidized cholesterol and oxidized forms of estrogen and testosterone are the most dangerous forms in cardiovascular and hormonal health. And researchers at the Lewin Group estimate that if all seniors were to take vitamins that their health care costs would decline by some $3 billion per year. But the authors of the Annals meta-analysis ignored these positive effects. Vitamin E can reduce symptoms of hay fever, prevents oxidation of LDL (“bad”) cholesterol that leads to blocked arteries, is linked to lower rates of prostate and breast cancer, is associated with less risk of getting cataracts in the eyes, less risk of getting a second heart attack, dramatically lowers the risk of cardiovascular problems in diabetics, helps to lower blood pressure, decreases dementia in older people and supports both the lungs and immune system. This research is stronger for the complete family of 8 natural isomers than for isolated alpha tocopherol. The false message that the public is hearing is that "vitamins are dangerous". That simply has not been proven by this particular analysis because there are too many uncontrolled variables that negate the validity of the authors' conclusions . Neil E. Levin, CCN, DANLA, Clinical nutritionist with Diplomate in Advanced Nutritional Laboratory Assessment, Nutrition Educator for Now Foods, Member of the Scientific Council of the Clinical Nutrition Certification Board REFERENCES: 1. July 2004 American Journal of Epidemiology Development of a Comprehensive Dietary Antioxidant Index and Application to Lung Cancer Risk in a Cohort of Male Smokers Margaret E. Wright , Susan T. Mayne, Rachael Z. Stolzenberg-Solomon, Zhaohai Li, Pirjo Pietinen, Philip R. Taylor, Jarmo Virtamo and Demetrius Albanes http://aje.oupjournals.org/cgi/content/abstract/160/1/68? maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&andorexacttitle=an d&andorexacttitleabs=and&fulltext=beta+carotene&andorexactfu lltext=and&searchid=1100534768534_1530&stored_search=&FIRSTI NDEX=0&sortspec=relevance&fdate=7/1/2004&tdate=7/31/2004&jou rnalcode=amjepid 2. High-dose vitamin E supplementation may increase all-cause mortality, a dose response meta-analysis of randomized trials; To be published in Annals of Internal Medicine: Online: Nov. 10, 2004: http://www.annals.org/cgi/content/full/0000605- 200501040-00110v1 Print: 4 January 2005 | Volume 142 Issue 1 3. Am Journal Preventive Medicine 24:43-51, January 2003, Dietary supplement use and medical conditions Satia-Abouta J, Kristal AR, Patterson RE, Littman AJ, Stratton KL, White E http://www.ajpm- online.net/article/PIIS0749379702005718/fulltext 4. J Nutr. 2003 Oct;133(10):3137-40 Huang HY, Appel LJ Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14519797 5. The Lewin Group, DaVanzo, J. et al, "Improving Public Health, Reducing Health Care Costs: An Evidence-Based Study of Five Dietary Supplements," September 22, 2004. http://www.supplementinfo.org/contentman/anmviewer.asp? a=156&z=14 6. The Lewin Group, Al Dobson, Ph.D., et al, A Study of the Cost Effects of Daily Multivitamins for Older Adults Prepared for: Wyeth Consumer Healthcare http://www.lewin.com/NR/rdonlyres/exul3vts44kvq5kr35iw6vt3sc 6nhtmj3hwope245srdtp3iw7bco4dctska6gilvhewvhivcbujnl/Studyth eCostEffectsDailyMultivitaminsforOlderAdult.pdf 7. Richer S, Stiles W, Statkute L et al. Optometry. 2004;75:216-30. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial) http://www.nutrition4health.org/NOHAnews/Biographies/April% 202004%20Optometry%20LAST%20Study.pdf Competing interests: Nutrition Educator for vitamin manufacturer; however, these are my own professional opinions and not necessarily those of my employer.
"Comparing vitamin E users" proves nothing. 11 March 2005
Barry Savage, Inventor and engineer. Dataman Programmers Ltd., Maiden Newton, DT2 0AE Send response to journal: Re: "Comparing vitamin E users" proves nothing.	1) Those motivated to take Vitamin E are likely to be concerned about their hearts 2) Conversely, those who are not concerned about their hearts are less likely to take Vitamin E. 3) Therefore the study compares those who are concerned with those who are not concerned. 4) The results indicate nothing about Vitamin E consumption: they indicate that those who are concerned have cause for concern. 5) The "bottom line" is that Vitamin E might or might not help those who who are concerned about their hearts. 6) What the study really indicates is the need for more intelligent doctors who will make more effective use of funds available for research. Competing interests: None declared