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Abstract:  The average benefit found from 29 observation study measurements of the risk of cardiovascular disease was a reduction in risk of 34%.   All but 2 or 93% of the research measurements noted an advantage for use of Vitamin E.   But because its benefits accrue from a duration related process this level of benefit may accrue only after 20 years of its continued use. Benefit after 5 years of use will be a reduction in risk of a lesser 15% and little benefit will accrue during a 1st year or two of use.   As the most effective of the usual antioxidants, Vitamin E acts in combination with other antioxidants present, and there is a probable limit to benefits that either vitamin E per se or a sum total of all antioxidants others can produce.  A level of 200 to 400 IU of vitamin E may produces its maximum potential benefit.

The average risk from 9 measurements in 4 randomized clinical studies of presumably health persons developed an average risk of 0.83. The results of each of these studies were consistent within their accuracy limits with benefits expected from the amounts of vitamin used and durations of exposure.  Results of 9 comparisons of 7 randomized clinical studies of patients of disease develop only a 0.98 risk vs the 0.90 values expected for their duration.   This nutrient thu may provide no useful benefits for heart disease patients or patients of some other diseases for reasons discussed following.  The amount of Vitamin E in foods usually is small.  Most potential benefits accrue from supplements .  

Recognizing that Vitamin E also appears to reduce the risk of cancer and death from all causes, health-interested non-coronary persons should consider taking a daily supplement of at least 200 of natural mixed forms of Vitamin E.     \See more about Vitamin E in the analyses of its effect on cancer, on dementia, on antioxidants , on all causes of death and in the Global Analysis of Antioxidants. 

Few subjects on health have been a subject of more and longer controversy than that of Vitamin E, and its usual constituent alpha-tocopherol.  Proposed enthusiastically as a way to reduce risk both of coronary disease and the disease recurrence in the 1940's by Dr. Evan Shute of Canada, this was  subject of a book "Vitamin E, Your Key to a Healthy Heart" published in 1964   This suggestion was treated with derision for decades by much of the Health Establishment. Yet during the last 15 years the use of Vitamin E as a preventative of heart attacks and cancer has become subject of enormous interest. More than 20,000 scientific papers are referenced to the vitamin or its chemical constituents in Medline, with 5,500 references using Vitamin E as a titled subject. A large majority of these suggest that Vitamin E either is or should be beneficial to a wide variety of health problems including heart disease and cancer.  The failure to find benefits for use of Vitamin E for coronary and other patients has troubled many observers.  Other confusion also has been caused by use of the so-called RDA or nutritional values of Vitamin E in the range of 15 IU per day that infers that these are proper and sufficient amounts of consumption. These small values that may be adequate to halt diseases of insufficiency are too low to provide useful antioxidant benefit. 

A recent large study and two recent statistical meta analyses that are discussed following have claimed "No effect" for Vitamin E on cardiovascular diseases and cancer.  One study even claimed it could harmful. These conclusions as will follow here and elsewhere were seriously faulty and misleading.  Far more and more extensive research including our largest and most important ones have found benefits that in total are very highly significant. A common and simplistic view is that there is or is not an effect, and the correct best study will determine this yes or no answer. A more likely scenario is that we are dealing with very complex biochemical processes that are not adequately understood.  Depending on biochemical environment, there will be or might not be a measureable benefit for use of an added increment of Vitamin E.  We need to look at all studies and all research to obtain a proper answer.  No single study can provide this. We need to achieve an understanding of WHY different studies obtained apparently differing answers.

Many in the scientific community including some health writers have had a heavy bias against all supplements for decades, then finally grudgingly acknowledged that some including Vitamin E and antioxidants could be beneficial, and then moved back and forth pro and con on this depending on just some recent  results from one or two recent studies published. Yet no serious scientifically and objectively oriented review of all of the research obtained on either Vitamin E or of all antioxidants has been found published elsewhere..   Little global analysis of the existing research appears to have been done to understand this WHY.  Life Ahead analysis that follow does provide a serious global scientific analysis of useful population research found published on Vitamin E and other key antioxidant supplements, and this paper on Vitamin E together with hyperlinked supplements provides useful answers to this problem.

Statistical Confusion:  A major problem with research on life and health has been Statistical Confusion. A dogma holds that if a change found in research does not pass a test of 95% certainty it called "Not 'Statistically Significant"  It then then can be said  "There is no effect of this factor"   In the real world the resolution power of most studies on people is usually only plus or minus 30% or higher.. The effects being measured are less than this. . Thus perhaps 20% to 50% of all studies attempting to measure an effect will inevitably  fail to find a factor that passes what is the very severe test of 95% significance.  The inevitable results is that a parade of studies of a single factor will successively show some as significant (showing an effect) and others that show a similar result but that are not significant,  It is common for researchers to claim  "There is "No effect" of something when a more proper conclusion usually is "We did not find an effect that was statistically significant." 

This is neither science or proper use of the statistical method.  Proper reporting should identify the actual effect found plus the probabity that the measurement is true.  Health-interested persons should realize that any statement in health research that "there is no effect of a factor) in a health research paper can be meaningless and probably is not true.  Table VE of Vitamin E and cardiovascular disease shows actual effects and the 5% to 95% limits of most results.  Nearly all show a benefit for the vitamin. Many of these did not pass that severe test of 95% significance that reall f no effect exists, an equal or near equal number of results would be positive and negative. If all or nearly all results show a results less than 1.00  you can be reasonably certain that the effect is real and beneficial.  If results are mostly greater than 1.00, the effect is harmful.  Research results in this and all other Life Ahead papers are quoted as high nutrient risk divided by low benefit risk unless specificed otherwise.

More Statistical Confusion is caused by the improper adjustments for other factors beyond the usually needed ones  for age and gender. Most "Multivariable adjusted" results appearing in heath research papers may not be valid.  More on this is suggested elsewhere.    

See other papers of antioxidants and CV disease for Vitamin A;  Vitamin C; and Selenium and papers of antioxidants and cancer for Vitamin E;  Vitamin A;  Vitamin C; Selenium, and Antioxidants and All Cause Death..

The Observation Studies of Vitamin E:  Results of studies A1 through A19 in Table VE following comprise the key observation study research found that relate risk of coronary heart disease directly to use of Vitamin E for healthy individuals   I have not seen a similar easy-to understand compilation of this important research published elsewhere. This research shows a remarkable confirmation of the benefits for taking Vitamin E  Nearly every one of 32 useful study comparisons of Vitamin E per se found and included in this Table shows likely reductions in the risk of some form of cardiovascular disease for the taking of various amounts of Vitamin E.  Such a consistent directional confirmation of benefits is virtually unknown for any other health risk factor.  I have shown the error range of each study, but not included any comments on "95% statically significant"  that as noted above is an arbitrary device that has no scientific usefulness in an analysis of multiple individual study results.  The average benefit found from the direct observation studies of Vitamin E was a reduction in risk of 34% that has enormously high statistical significance. Please view the consistent results in the column titled "RR" or risk ratio in this table for all observation studies listed as "A" numbers.  

A common criticism of observation studies is that some now unknown factor might always be associated with a factor such as Vitamin E that could be a true cause of results found. The chance that this could be true for the available and useful research Vitamin E that involves populations from different  world countries and multiple research done over long time periods simply is not credible.   Seven of the observation studies in the Table VE show the relationship between risk of cardiovascular disease and measured level of Vitamin E n blood.  These results that are briefly summarized following are important because they confirm more directly a likely causative factor.  The risk ratios are the cardiovascular disease of those having a higher level of Vitamin E as a fraction of those having a lower level in blood.

                     Study No     Risk Ratio               Limits                            Observation

                         A1              0.46                   p = < 0.009               quintiles in blood at constant cholesterol

                         A2              0.37                   0.05-0.93                  p = 0.02

                         A3            various                 p < 0.0002                Correlation of risk with amount of blood in 16 European populations

                         A8             0.40                    0.12-0.70

                         A11           0.53                    0.12-0.70

                         A12           0.16                    0.04-0.55

                         A18           0.81                    0.75-0.88                  p < 0.001  For 8.5 to 16+ mg.l in blood in a large population

Each of these seven study values had very high significance, and the difference in risk of disease is for higher amounts of Vitamin E is substantial.  The figure at left is one of several included in the reference of study A3.  This shows how risk of heart disease in different countries related to differences on levels of Vitamin E in blood  

The amounts of Vitamin E in most of these studies were those related to diet.  But although use of supplements was small overall, the highest quintile of blood values probably did include amounts from supplements.  Risk values were developed from the risk of highest vs. lowest value of nutrient.

Table VE also includes 29 risk ratio measurements from 12 observation studies that mostly involve the effect of vitamin E supplements in reducing risk of heart or cardiovascular disease. 28 show Vitamin E to be beneficial.  Only 1 shows a contrary effect. The table also includes 9 measurements taken in random clinical trials on healthy people.  8 of those 9 measurements show Vitamin E supplements to reduce  risk of cardiovascular disease. If we add in the 7 positive results for higher vitamin E in blood, we have a total of 43 beneficial findings to 2 not confirming.  If we eliiminate the confusion of statistics on individual studies that have no relevance to this remarkable overall result, the overall statistic on this health benefit of Vitamin E must rank in the muliti-millions to one in favor Vitamin E.  Yet today we have supposedly knowledgable experts telling people not to take advantage of this most simple and inexpensive of all known methods for living a longer and more healthful  life.  Some simple averages are:

                                                       For Amounts in              For Other Observation                    For Prmary

                                                            Blood(7)                           Studies(29)                           Clinical Trials((9)

    Average reduction in Risk                        55                                    30                                             16

As will follow, the clinical trial measures only a part of the true benefit of an antioxidant.  But even recognizing this, the average computed benefit for the simple taking vitamin E based on these 45 differing measurements is a 31% reduction in the risk of the most important cause of death in industrialized countries of the world. More on the above cllinical trials follows later.

Risk of Vitamin E Depends on its Duration of Use:  Biochemical studies show that antioxidants develop their benefit by reducing the oxidative state of LDL cholesterol.  Because cholesterol develops the atherosclerosis that clogs arteries gradually over a lifetime, this means that the benefit of antioxidants should develop only gradually with their time of use.  Study A16 in the appended Table VE was a survey of the Heart Disease suffered by 17,900 users of Vitamin E.   This survey showed that the percentages of the 3,725 men and women that suffered disease were related to time of vitamin use for each individual ten year age group from age 50-59 through 80-89.  The survey  risk ratio of 0.53 was obtained for longer term use of about 200 IU per day of Vitamin E for all age groups is consistent with the risk ratios from the larger peer reviewed studies. The important study A4 of more than 40,000 health professionals showed only a 0.95 risk ratio for use of one year, 0.78 risk ratio for 7 years of use, and a 0.65 risk ratio for 15 years of Vitamin E use.  Study A5 - the large study of women nurses - also found only a small effect for short term use of the Vitamin but a highly significant risk ratio of 0.59 for average user duration of use that probably was from at least 7 to 15  years.  Unfortunately, most researchers did not report time of use.

Studies A5 and A16 comprise the best direct evidence found quantifying the all-important risk factor of the duration of use of Vitamin E.  A comparison of the statistically smoothed risk ratios vs. duration found for use of Vitamin E supplements in these two studies are:

                                                                  Study A4                     Study A16

                1 Year                                           0.97                             0.975                     

                2 Years                                         0.94                             0.95

                3 Years                                         0.91                             0.925

                5 Years                                         0.86                             0.87     

                7 Years                                         0.81                             0.78

               10 Years                                        0.74                             0.72

               15 Years                                        0.64                             0.58 

The results of the two data sets are quite similar.  These show a benefit of  the average amount of Vitamin E use of from 2.5 to 3.5% per year, or an annual  risk factor of 0.965 to 0.975.  A Global Statistical analysis of all useful research results found on healthy people in Table VE discussed following develops confirming probable risk values for use of Vitamin E varying from 0.98 per year for 30 IU increasing to 0.96 per year at 400 IU of Vitamin E.

Most researchers and analysts have been unaware of this important effect of duration of exposure for antioxidants. A typical error margin of studies in Table VE is a 5%-95% range in risk of 0.5 to 0.6.  The accuracy range on values from the largest studies of 40,000 or more individuals still range from 0.3 to 0.5.  Thus unless a study is carried out for at least 10 years, it will be incapable of identifying the risk of an antioxidant. Much of the controversy about antioxidants has been due to this statistical confusion of inadequate study resolution power.

Another fact revealed by the above results is that Vitamin E probably does not develop its key benefits via reducing blood clotting. A benefit from this mechanism would seem likely from some biochemical research that shows that vitamin E  does reduce platelet aggregation.   Aspirin that does reduce clotting  reduces risk of heart disease in immediate time.  There is no such short term benefit for Vitamin E or other antioxidants.   More on this is important observation is discussed later.

The atherosclerosis of arteries may progress through eight different states.  Early stages during first three decades of life involves gradual deposits of plaque on artery surface.  Later stages involve an entering of the artery walls and more drastic modifications of artery structure. Antioxidants probably are most effective the early states of this process, and other factors as inflammation and clotting become involved as the progress of atherosclerosis becomes advanced.

A Global Analysis of the Benefit of Vitamin E in Preventing Cardiovascular Disease on Healthy People.  The observation and clinical research results in Table VE were organized for scientific analysis via stepwise and other regression to understand better the likely causative factors involved.. A problem was that duration of supplement exposure was not identified in many of the studies involved. Some studies have suggested that a typical Vitamin E user probably had been taking ia supplement for a time of from 7 to 10 years.  Even in 1975 many people reported use of 10 years, and thus many people have been using it for  20 or even 30 years. Results from the case control studies suggested a duration of use of at least 10 to 15 or more years was needed to generate the difference in risks measured.  Some direct tests suggested that the high Vitamin E users probably had been using supplements for 10 years prior to study initiation. Thus the likely durations of exposure in prospective studies were increased by 10 years past the actual follow-up times in studies where duration was not specifically identified.

It seemed obvious that benefit was not directly proportional to amount of Vitamin E used. Rather, the amount in blood that would be a more likely casual factor moved up only gradually in response to increases in amount in supplement. As example, study C1 blood values moved from 34.3 to 51.1 mg/l with 400 IU of Vitamin E, and to 64.5 with 800 IU.  It was at about 16 mg/l at 30 IU of Vitamin E. The best fit of results in Table VE was obtained assuming risk developed at about the 0.50 power of vitamin  E level. A value of 0.50 power was selected for the final model. 

No statistically useful effect could be identified for differences between men and women or for differences in population age from this data set. Similar results were obtained from 25 observation study results  per se and from the total of 32 observation studies that include random clinical trial results on healthy people. The primary factor responsible for results from all studies either for 25 comparisons of 'A' or 32 comparisons of  'A plus B' studies in Table VE was duration of exposure.  A first order relationship of duration of exposure to risk had a very high 't' value of 8.9 vs. a value of only 2 needed for 95% significance. The relation between amount of vitamin E and risk had a similarly high first order 't' value of 6.5.  These two key factors thus had very high significance. The effect of study duration derived from all research was similar to that derived from the more specific results of studies A4 and A16 noted above.   The final model selected was:

Risk Ratio of Vitamin E, Cardiovascular diseases, =  Exp ( -0.0021 *  yrs of exposure * Vitamin E amount ^ ^0.5)

                                                                                           correlation coefficient = 0.82

This simple model meets the requirement that risk is unity either for zero exposure or zero Vitamin E.  This requirement is not developed

from usual statistical regression models. Some values from this model are:

The Randomized Clinical Studies on Healthy People:  Statistical theory suggests that selecting two groups of similar populations - with one group taking the vitamin and another taking a placebo - will eliminate the likelihood that some unknown confounding factor is associated differently with the normal use and non-use of the vitamin.  But a fact poorly understood is that a clinical type study measures a quite different value for risk than does a case control or other observation study.  First, the observation study measures the full difference in risk across 4 or 5 usual segments of a population for lowest to highest amounts of a nutrient.  Even if supplement use is only 20%,  the highest value of the quintile of nutrient that is the usual basis of measurement will include the effect of the nutrient supplements involved.  In contrast, a clinical study of an antioxidant uses as a base not the lowest amount of a nutrient but an average value present in the population. If the value of a supplement measured is similar to that of the highest amount in the observation study and the effect of the nutrient is linear with amount, a clinical study might measure only half of the risk potential from an observation study.

The problem of measurement becomes even more difficult for a clinical study because "all other factors" are not equal.  First, the effect of Vitamin E is not linear with amount.. The risk associated with half of a an amount is much higher than half of the average risk.  Second and even more important, an observation study of the subject initiates with populations that have been using different amounts of an active nutrient for perhaps 10 or more years of duration. The clinical study starts with groups having the same risks. Thus the expected result from a clinical study of practical duration can be only a small fraction of that developed from an observation study. Another factor reducing the potential risk measurement of a clinical study is the compliance of users in taking the supplemenrts provided.  A usual compliance of about 75% reduces the resulting risk measurement even further.  These problems lead to serious problems of measurement because the error margin of practical clinical studies on people can be much larger than amount they were attempting to measure.

Results from the clinical type studies found of Vitamin E done on otherwise healthy people are summarized following as nine risk comparisons from four different studies as B1-B4 in Table VE.  I include an expected value for each study from the above model of all useful research of Vitamin E assuming a usual study compliance of 75% for the supplement taking group.

      Study     Duration      Amt Vit E/Day  Risk Ratio  Statistical Limits   Expected Value    Comparison

        B1             6.1                  75 IU                 0.96             0.90-1.03                 0.90             Finland, smokers

        B2             4.7                  75 IU                 0.91             0.83-0.99                 0.92             Finland, smokers

        B3             3.0                 300 IU                 1.0                  n/a                        0.93             Italy, no diabetes 

        B3             3.6                 300 IU                0.91                 n/a                        0.91             Italy, with diabetes

        B4             10                  300 IU                0.93              0.82-1.05                0.84             US women, all CVD events            

        B4             10                  300 IU                0.76              0.59-0.95                0.84             Fatal CVD, same study

        B4             10                  300 IU                0.74              0.59-0.93                0.84             Women age 65+  all events

        B4             10                  300 IU                0.51              0.33-0.77                0.84             Women age 65+ of CVD death

        B4             10                  300 IU                0.88              0.75-1.03                0.84             No multivitamin use

Studies B1 and B2 are different results reported for the same large study in Finland.  These together with results for B3 are quite consistent with what is expected from the results of all studies on healthy people for vitamin amount an study duration.  But the difference in risk both expected and confirmed is far too small for results to called "statistically significant"  Thus considered individually these studies provide no useful evidence about the benefit of Vitamin E.  But they do confirm the likely order of magnitude of the effect for short durations, and they do illustrate the problem of obtaining useful results for clinical type studies.    

The results from more important study B4 done for a duration of 10 years should provide results that are useful.  The actual study results are not consistent with the researcher's conclusion that inferred incorrectly to the public that there was "No benefit for Vitamin E." .  The usual quoted risk value for all cardiovascular events of 0.93 from this study really identifies a likely statistical range from 0.82 to 1.05.  And this  was accompanied by an equally important close to expected target risk of 0.76 for CVD death that was statistically significant.  The values for risk of death for the older women that also were statistically significant were close to expected target for all CVD events, and below target for CVD death.  Because most women live much past age 65, and risks of heart disease are far higher at older ages, this study actually did confirm the important expected benefit for using Vitamin E during life.  On balance, this study did confirm a risk benefit on cardiovascular disease for Vitamin E that was close the value expected from the study of all observation study research.  These  results of available results on clinical studies of healthy people thus suggest the same probable benefits  for conditions involved as do observation study results. And they highlight the difficulty of obtaining useful significant results on antioxidants from clinical studies

Study B4 had other problems that were not reflected in the identified statistical limits. First, 39 % of all inviduals were taking vitamin supplements both before the during the trial. This would have reduced the risk of the placebo group and done little to improve that of the user group that was taking the near maximum useful 300 mg per day. Thus adjusting for this would replace a 0.70 expected value for 300 iu of Vitamin E with a 0.70 value divided by 0.89 for the equivalent vitamin E in the placebo group.  This adjusted 0.79 value becomes 0.84 when we further include the effect of com;liance.   Note the above overall risk value of 0.88 of the group not taking multivitams that is within the limits of the expected value. The value of the group taking supplements was close to unity, suggesting the the benefit from the supplements provided most of the potential from the larger amount tested.  Second, the population had a much lower risk of heart disease than that of average US women of the same age. This suggests that they had observed better overall lifestyle habits than average that would have reduced their potential for gaining benefit from any further measured risk factor. Third, the potential risk improvement from a clinical study as discussed above  is inherently lower than that from a observation study.. Each of these factors strengthens further the indicated benefits for the taking of Vitamin E.   

Vitamin E May not Benefit Populations that have Suffered Major Diseases:  Studies C1 through C7 show the results of clinical studies of Vitamin E that were done for individuals that already have suffered cardiovascular disease or had exceptionally high risks. There is no effect of any duration or amount of vitamin E associated with these results.  Unlike the very high relationships found for the data on otherwise healthy persons,  the first order effects of either amount or duration of Vitamin E for these groups of individuals were nil.  This confirms that Vitamin E probably will not benefit those that have suffered the disease.

Reasons can be suggested for this result.  First and as mentioned previously, antioxidants probably benefit by slowing the progress of atherosclerosis during the decades of life that produces the disease. Differing mechanisms such as blood clotting and plaque disruption finally cause the disease to happen.  Vitamin E does not benefit much these final causative processes.  Thus once a coronary problem occurs or arteries are seriously fouled,  subsequent occurrences usually derive from different processes than atherosclerosis per se. Another contributing factor to the lack of benefit for Vitamin E for sufferers of disease is that these individuals will be taking a variety of medications that can include duplicating benefits. 

A number of studies have been done in an attempt to confirm that antioxidants slow atherosclerosis.  Some of these results are noted at the end of Table VE.  The studies of Salonen confirm that Vitamin E and combinations of Vitamin E and C can slow atherosclerosis significantly. Results from other studies are inconsistent and suggest lesser or no benefits.  But because atherosclerosis proceeds so slowly it is very difficult from present methods of measurement to detect significant changes artery deposits in the short time periods of these studies. 

Meta Analyses Claiming no Benefit for Vitamin E are Seriously Flawed:  A meta analysis of clinical studies of Vitamin E and all cause death recently caused confusion and concern.  (2004, Miller III ER, Ann Int Med 142:37).  Nearly all studies considered in this analysis were of short term and were done on patients of diseases.  Only three of the studies were for Vitamin E and results of these actually showed the small expected benefit of about 4% per year of duration. Another meta-analysis of 62 studies of antioxidants published in 2007 claimed negative benefits for antioxidants.  ((Bjelakovic, G, JAMA 2007, 267:842)  Again, nearly all of these were very small clinical studies done for short time on populations that already had suffered disease and for which antioxidants do not benefit.  None of the really important research on Vitamin E was included in this study.  A review of this study does confirm as previously found and shown in the accompanying Life Ahead paper that very high amounts of Vitamin A and Beta Carotene not only may not be beneficial but can be harmful.  But this appears to be true only for the very high amounts of A and Beta C, and not for lower amounts useful for healthy people of for either Vitamin A or other antioxidants.. The conclusion on benefits of Vitamin E is not supported by any useful data and is invalid.  More on what the research used in this larger invald meta analysis of clinical studies probably shows is included in Life Ahead Supplement

Global Analysis shows Research Results on Vitamin E are Statistically Consistent:  In conclusion, Vitamin E in amounts of 200 IU taken regularly and continuously for a useful number of years and preferably for life will reduce the risk of coronary disease significantly for persons now healthy and not at high risk or who had actually suffered heart disease.  Studies that involved an adequate duration of the vitamin use confirmed a significant benefit for its use, and the aggregate of all studies confirm this benefit with extremely high probability.  This likely benefit is further confirmed by hundreds of  published studies on probable biochemical benefits of the vitamin.  Most randomized clinical studies performed to date are far too short in duration to provide useful evidence for or against the vitamin, or have other problems. And the most important randomized study B44 did confirm a quite substantial effect of vitamin E on both all cardiovascular disease death and for older women.

Benefits of Vitamin E in Food:  Table VE lists research results to date on the possible benefits of Vitamin E in food. First, the amounts of this vitamin in foods are very small..  The difference in amounts consumed by the 20% of participants eating the least  and the 20% of those eating the most amounts were only about 6 IU.  These amounts compare with a lowest amount in a usual multi-vitamin supplement of 30 IU and usual amounts of 200 to 400 IU in direct vitamin E supplements. Second, attempts to measure the effect of Vitamin E in foods have usually not been successful.  It probably will be impossible to measure any benefits for vitamin E in foods because the vitamin is present mostly in some dietary fats and a few other specific foods that probably derive far more of their effects on health from their other nutrients than from their small amounts of included Vitamin E.  As example, nuts are high in Vitamin E.  But nuts are known to produce health benefits from polyunsaturated fats that should be more consequential than just their small content of Vitamin E.  Cereals can have useful Vitamin E.  But cereals now can be fortified with folic acid, have fiber, and contribute in other ways. 

Results of the effect of small differing amounts of Vitamin E in blood on risk of disease do suggest that there could be some benefit for the differing amounts of Vitamin E in foods. Note especially study A17. Other evidence suggests that the gamma tocopherol mostly present in foods may be quite beneficial.  Other Life Ahead papers on antioxidants such as Vitamin C, Beta Carotene and Selenium show that amounts of these antioxidants do explain the measured benefits of fruits and vegetables in reducing risks of heart disease

Types of Vitamin E:  Vitamin E is a name applied to a group of at least 8 different chemicals.  Participants in most studies identified only their intake of 'Vitamin E', and thus no measure of the actual amounts of specific chemicals taken is provided in any study.  By far the predominant form of Vitamin E is alpha tocopherol. Synthetic Vitamin E may be entirely alpha tocopherol, but natural vitamin E could be a mixture of various tocopherols including mostly alpha with accompanying gamma, and delta forms, and isomers of tocotrienols.  Some natural Vitamin E can be mostly alpha tocopherol with the other forms extracted out.  Also the potency of natural vitamin E appears to be higher per IU unit than that of synthetic Vitamin E.  The results in Table E are largely derived from Vitamin E supplements of mostly natural and synthetic alpha tocopherol. 

Recent biochemical research has attempted to identify possible benefits of other tocopherols, and particularly gamma tocopherol. The gamma type has been found to inhibit cancer cell proliferation better, and to reduce platelet aggregation better than does the alpha form. Vitamin E in food tends to be more in the gamma than in alpha form.  But alpha tocopherol appears to be selectively absorbed both into the blood and into body tissue where it is needed for health benefit.   This biochemical research does suggests however that health-interested people should use natural vitamin E in the mixed form to obtain the potential benefits of a variety of tocopherols and tocotrienols.

A Summary:  Although it may take 10-15 years of use for a really substantial benefit to accrue, few health actions can accomplish such a benefit from such minimal cost and effort as will the regular taking of 200 to 400 IU per day of Vitamin E.  This simple action over the long term could significantly prolong tens of millions of lives. Analysis of various diets via the Life Ahead computer program reveals that most US people will not develop adequate amounts of Vitamin E or other antioxidants from usual diets. Thus the addition of a supplement can produce a quite significant reduction in the risk of major cardiovascular diseases. The present free Life Ahead program shows the likely benefit for use of Vitamin E or any other antioxidant supplement.

Life Ahead does not value Vitamin E directly.  Rather, the program values vitamin E as one of four antioxidants that produce in combination a slowing of both atherosclerosis and cancer, but with a limit to how much slowing can be achieved by any antioxidant combination.  See the discussion on Antioxidants for more on this.  Life Ahead computes the benefit of Vitamin E and other antioxidants as gradually increasing with years of use as per the research in Table VE and the above tabulation.  But a limit is imposed on a maximum benefit computed for each individual and the total of all antioxidant. The present program version does not credit any potential benefit of antioxidants for coronary survivors.  See the other papers noted above for results on other antioxidants.  Today about 30% of all US adults take vitamin E supplements and this together with their increased use of other dietary supplements probably has contributed in part to producing the large decline in population coronary disease during the past 2 decades.

The Mythology of the Randomized Clinical Study.   It is a common assumption by most health statisticians that the important and definitive study is the Randomized Clinical Study that directly values use of a specific factor versus a placebo on sets of the same population.  The assumption here is that other studies are suggestive, but definitive proof requires one of the clinical type. This assumption is undoubtedly true for the valuation of a drug or medicine that is new to users and that is expected to produce a result in short time.

But this assumption is not true for a study that values the health benefit of lifestyle factor. For this situation the clinical study does not attempt to value some new agent that uis expected to produce benefit in very short time.  Rather, it attempts to value the use of more of a factor that already is present in the population and that develops over very long time.  The key life terminating diseases are heart disease and cancer, these diseases develop from previous habits of 30 or more years.  For this situation a usual short term clinical study can be virtually useless. It can be shown further that the risk developed from a clinical study will be only a small fraction of that measured by an observation study. 

An evident example if clinical study deficiency  is that of smoking cigarettes.  Its takes about 20 years for first cancers to develop from smoking.  Any practical clinical study of cigarettes would show they are harmless to cancer and probably to cardiovascular disease. The real evidence on their harm and that is monumental comes from observation studies.   Similarly, observation studies - and not clinical studies - will be the best and most definitive basis for developing the risk and benefits of other lifestyle habits. More on this problem is discussed in an accompanying paper on the problems using clinical studies for health valuations. .  

 THE RESEARCH on VITAMIN E  and HEART DISEASE FOUND PUBLISHED

Understanding the Research:  The table following includes most of the important useful research in on risks found published to latest date listed.  Most researchers and health writers base their ideas on just a few most recent studies because it can take much time to produce this type of a more complete review. But these comprehensive listings are an essential need to obtain a most up-to-date and correct answer to a most likely risk.  The important finding of research is the risk ratio, or the risk of disease of those with a better health factor vs. those with a base or usually average or poorest health factor.  A risk ratio of 0.5 means risk of those with better health factor have half the risk of those with the poorer one.  A ratio of 0.25 means they have only 1/4th the risk; a ratio above 1.0 means a negative result from the factor. 

Most risk ratios are followed by an error margin, as limits of 5% to 95% probability.  If a ratio is 0.75, and the limits are 0.5 to 0.9, the study really produces a likely result of a risk lying somewhere between 0.5 and 0.9.  The usually quoted risk simply of 0.75 is quite inaccurate. But because the upper limit is still below the null value of 1.00 this result usually will qualify in the study publicity as "Statistically Significant"  If the error margin is say 0.4 to 1.15, and the upper level is above 1.00, the individual study usually will be "Not significant."  Researchers often say incorrectly that "We found no effect" when a value found is beneficial  but  "Not 95% significant"   This produces Statistical Confusion that can be very misleading. 

Because most health studies have high error margins, it is necessary to have results of multiple studies to obtain a probable truth.  Two studies, each finding a risk of 0.75, and each with say error margins individually of 0.45 to 1.10 can define in combination a quite significant result even though each individually did not include sufficient data and was "Not significant"   A best answer and objective answer thus is revealed by what ALL of the RESEARCH shows in combination.  This is what the tables following attempt to show.  Some 'Experts' are quick to dismiss all studies that do not confirm a fixed previous position.  This type of data selection does not provide objective analysis.

Please look at the risk ratios found noted under the RR column.  If risks from most or all studies show values lower than 1.0 you can be assured that the effect being measured is of extremely high significance. The fact that some individual studies do not reach 95% significance individually can be meaningless when viewing multiple results.   5-95% limits that each are below 1.00 at usually confirm an individual study as significant in its own right. If most studies have risks well below 1.00 and error limits also below 1.0, the truth may be established at levels of millions to one.  Some studies include 3, 4 or 5 results at differing "dose" or amounts of factor levels.  If these show steadily declining ratios with dose, significance becomes even larger.  Some studies show "p" ratios of significance.  A p value of 0.05 denotes 95% probability.  A lower p value of say 0.01 is 99% and a p of 0.001 can define significance at a thousand to one.

                                                                    Table VE

                              Effect of Vitamin E on Risk of Heart or Cardiovascular Disease

Effect of Vitamin E in Food on Risk of Heart Disease

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