Main Menu Health Library Antioxidant Model
VITAMIN E and CARDIOVASCULAR DISEASE
Abstract: Vitamin E taken regularly in amounts of 200 IU per day eventually should reduce the risk of heart disease and other cardiovascular disease by 40-50%. But because its benefits accrue from a slowing of atherosclerosis of about 2-4% per year, this maximum benefit may accrue only after 15-20 years of its continued use. Benefit after 5 years of use will be a reduction in risk of a lesser 15-20% and little benefit will accrue during a first year or two of use. Benefits should accrue a bit faster for use of a daily 400 IU. 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 a sum total of all antioxidants can produce. Also, its benefits for heart disease patients have not been verified. The amount of Vitamin E in foods is much too small to be considered useful. Recognizing that it also reduces risks of cancer, health interested non-coronary persons should consider taking daily supplement of at least 200 and preferably 400 IU of natural mixed forms of Vitamin E. This action taken alone can provide an average benefit of from 3 to 6 years of additional Well-Days of healthy life.
Background: Few subjects about Health have been a subject of more and longer controversy than that of Vitamin E, and its key constituent alpha-tocopherol. Proposed enthusiastically as a way to reduce risk of both initial coronary disease and the disease recurrence in the 1940's by Dr. Evan Shute of Canada, this was a subject of a book "Vitamin E, Your Key to a Healthy Heart" first published in 1964. The idea 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 a 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 health. Yet determined opposition from long dedicated opponents of both this and most other diet supplements may have kept much of the public from benefiting from these massive research findings.
Vitamin E has been shown to be a strong antioxidant in biochemical research. Life Ahead recognizes cardiovascular diseases and cancer as chemical processes that develop gradually throughout life. As noted elsewhere herein, an antioxidant should slow the progress of atherosclerosis mediated by LDL cholesterol, and thus operate as chemical rate modifier. This mechanism would be expected to reduce risk of heart and other cardiovascular diseases as a direct function of its duration of use. The vitamin also has been suggested to slow blood clotting - and any benefits via this mechanism would be expected to develop fairly promptly in response to its use. Thus an important objective in valuing the potential benefit of Vitamin E and other antioxidants is the identifying of both its duration related effect and its non-duration related effect on risk of disease.
The Observation Studies: Results of studies V1 through V8 in Table VE1 following comprise the key research that relates risk of coronary heart disease directly to the use of Vitamin E supplements. All of the studies that included its use for a probably duration of 7 years or more show that Vitamin E reduced risks of disease. An average risk ratio of 0.53 was obtained from these 12 available comparisons. This was for an average use of about 200 IU of Vitamin E per day, and benefits were related to the amount of vitamin used. Most research was for natural vitamin E that is more active than the synthetic variety.
An important observation for the research in Table VE is that the effect of the vitamin is strongly related to its duration of use. The smoothed curve of data included in important study V1 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, and a 0.65 risk ratio for 15 years of use. Study V2, the large study of women nurses, also found no effect for short term use of Vitamin E, but a highly significant risk ratio of 0.59 for average user duration of use that probably was about 7 years. Unfortunately, most researchers did not report time of use, and thus this average estimate of 7 years use is noted for results lacking a duration measurement or estimate. It seems possible from some of the information reported that this average time of use may have been as long as 10-12 years rather than the 7 years noted. Thus this research shows that Vitamin E operates mostly via a duration related effect.
Study V9 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 age group from age 50-59 through ages 80-89. Although not conducted with the usual rigor of the other papers, the survey risk ratio of 0.53 was obtained for longer term use of about 200 Vitamin E per day for all age groups is consistent with the risk ratios obtained in the peer reviewed studies. Study V9 also showed only a small benefit for use of Vitamin E for only 1.5 years, and that the duration related effect applied similarly to individuals of all ages above age 50. This further supports the mechanism that the vitamin benefits as a direct function of duration of use.
Studies V1 and V9 comprise the best evidence found for quantifying the all-important risk factor of duration of use of Vitamin E. Most researchers appear to have been unaware of this key factor. A comparison of the statistically smoothed risk ratios vs. duration found from these two studies follows:
Duration of Use Risk, Study V1 Risk, Study V9
1 year 0.97 0.97
2 years 0.95 0.94
3 years 0.91 0.91
5 years 0.86 0.85
7 years 0.81 0.78
10 years 0.74 0.72
15 years 0.64 0.58
The results of the two sets are both quite significant and similar. The average of all observation studies suggests a risk ratio of about 0.67 for perhaps about 10 years of average use vs. the risk ratio of 0.73 measured above. A surprising and consistent result is that the short term effect of Vitamin E is essentially nil. This suggests that its benefits via anti-clotting must be minimal, and that the vitamin operates primarily as an antioxidant that reduces the rate of atherosclerosis or other chemical processes that produce risk. In contrast, aspirin produces its benefits near immediately.
Thus the proper risk ratio for Vitamin E - and this applies similarly for other antioxidants - is its annual risk ratio per year of exposure. From the research to date this value is about 0.96 per year of use of about 200 IU of Vitamin E. This risk ratio also is amount of vitamin related. But Life Ahead now assumes no benefit for Vitamin E beyond a value of 400 IU per day in accord with a policy of not accepting benefits beyond those actually measured by research data. Also the program now assumes a maximum duration of use of 20 years. And as will be discussed following, a risk is not computed for Vitamin E alone, but for its presence in a group of vitamins that is assumed to have a further limit in potential of benefits. These limits thus produce very conservative valuations of the potential benefits of the vitamin over the long term.
The Randomized Clinical Studies: Some health researchers have been disturbed by the null results from three of four randomized clinical studies of Vitamin E. Results of these are noted as V29-V32 in Table VE1. Statisticians venerate the clinical type study - with one group taking the vitamin and another taking a placebo - as is the standard for drug and much other testing. Although this might eliminate the possibility of some unknown confounding factor, these specific clinical studies had a major flaw: They were conducted for far too short a time to measure usefully the duration related effect of Vitamin E. A five year clinical study really measures results for an average duration of exposure of only 2.5 years, because some events occur in year 1, year 2, etc.
Consider study V29, the only clinical one on presumably healthy non-coronary persons. The risk ratio of 0.96 (error margin 0.90-1.03 was for an average duration of 2.5 years. The expected risk for this time would be about 0.93, well within the accuracy of the study. The other three studies were performed on survivors of coronary disease. The two largest ones showed essentially null risks of 0.98 and 1.05. Study V30 although showing a benefit was a much smaller one. But again, event durations were only 1.8 and 2.2 years, far to short to produce a meaningful benefit from Vitamin E. Thus rather than denying an effect of Vitamin E, the clinical studies really support further the finding from other research that its benefits are duration related.
Another consideration must be recognized for use of Vitamin E on coronary patients. These people usually will be taking a cocktail of medications, some of which could perform much or all of the potential benefit of an antioxidant. A much discussed clinical study not in Table VE1 is that of Rapola, JM; Lancet 349:1715 that studied Vitamin E and Beta-Carotene of smokers in Finland for an average duration of about 2.6 years. The risk ratio for Vitamin E was 0.94, again about that expected for the actual duration of vitamin use. But the higher risks for Beta-Carotene in this study raised questions as to the benefits of antioxidant supplements for coronary survivors that still smoke. Smoking provides a heavily pro-oxidant environment that could cancel any potential benefits from use of antioxidants. Life Ahead now gives no health credit for antioxidant supplements for coronary survivors that still smoke.
The Global Analysis shows that available Research is Consistent: Both the observation studies and clinical studies provide a consistent pattern confirming that Vitamin E, taken over a decade or more of time can contribute very substantial health benefits, and that little benefit will accrue during a first 1-3 years of its use. A clinical study of at least 15-20 years would be required to produce a useful result for a nutrient that produces duration related benefits.
Benefits of Vitamin E in Food: Table VE2 lists research results to date on the possible benefits of Vitamin E in food. Two facts appear evident. First, the amounts of this vitamin in foods are insignificant. The difference in amounts consumed by the 20% of participants eating the least and the 20% eating the most was only 6 IU. Second, attempts to measure the effect of Vitamin E in foods usually have been unsuccessful. Unless some vastly different mechanism and quantification of benefits can be devised for different types of Vitamin E, it simply will be impossible to measure a useful risk for such a low amount of the vitamin via present population type studies. Another problem is that the foods that contain Vitamin E have other nutrients that are highly active and of more likely importance than the accompanying amounts of Vitamin E. For example, nuts are high in Vitamin E, but nuts also have high polyunsaturated acids. Cereals can have useful Vitamin E, but these have fiber and may be fortified with folic acid. Study V8 did include a beneficial risk for Vitamin E in food, but this result does not appear credible or consistent with the results of other research, suggesting that other components of the Vitamin E containing foods may have been active here.
Types of Vitamin E: Vitamin E is a name applied to group of at least 8 different chemicals. Participants in most studies identified only their intake of 'Vitamin E' and thus no measure of the amounts of specific chemicals involved were provided. By far the largest form of Vitamin E is alpha tocopherol, but natural Vitamin E could be a mixture of various tocopherols including mostly alpha with some gamma and delta forms, together with isomers of tocotrienols. Some biochemical type research suggests that the gamma form might be have some advantages over alpha, but no really hard research data on this was found here. Health-interested people should use the natural form of Vitamin E, and Life Ahead values are for this form of the Vitamin.
The Life Ahead Valuation of Antioxidants: Life Ahead considers Vitamin E as one of four key antioxidants that produce in combination a slowing of both atherosclerosis and cancer. Because their must be a limit to the chemical effect of any chemical process, this limit it now set at a value that 1) reduces the risk potential of LDL cholesterol about in half, and 2) is consistent with the larger risk values found from the antioxidants either as single agents or in combinations. Vitamin E is the most potent of these antioxidants, and it alone in an amount of 400 IU per day can provide much of the antioxidant benefit now provided by any amount of all four nutrients. See more about this in an Antioxidant Summary.
Life Ahead now computes an advantage of about 6 years of Well-Days for an average US man or woman on an average diet who starts taking a 200 IU supplement of Vitamin E at age and continues this for life. An additional 0.5 year of Well-Days will accrue for taking 400 IU daily. But this assumes improbably that this is the only health action taken. This advantage for Vitamin E can be proportionately much smaller if this action is taken as a part of a series of health improvement actions because results of multiple actions do not simply add to each other.
The present research strongly endorses the conclusion that most health-interested persons should be taking at least 200 IU of Vitamin E regularly to reduce risk of cardiovascular diseases . And many individuals will obtain as much or more benefit from its ability to reduce risk of cancer. Today about 30% of US adults take vitamin E supplements. Increasing use of Vitamin E and other dietary supplements may have contributed in part to he large decline in population coronary disease during the past two decades. But a very much more extensive population use of Vitamin E than is now usual provides an enormous potential for improving the long range public health at minimal inconvenience and a very low cost.
Table VE
VITAMIN E and RISKS of CARDIOVASCULAR DISEASE