Abstract:  A large body of 25 research studies now shows with  high consistency and significance that the intake of 200 IU per day or more of Vitamin E over periods of at least 5-7 years - and preferably for at least 10-15 or more years - can reduce substantially the risk of all or nearly all types of cancer by about one third.  An exception is that pre-menopausal women may not obtain reduced risk of breast cancer.  Reduction in risk will require use of Vitamin E as supplements because amounts in food are too small to be useful.  With accompanying confirmed reductions in risk of coronary disease, research to date now shows that continued use of Vitamin E supplements can add 3 to 6 years of Well-Days to the life of an average middle-age US man or woman.

 

The Results of Actual Research:  Table E following provides the results of key studies of the effect of Vitamin E on cancer.  The 25 comparisons include results for the vitamin for all cancer and for cancer at individual sites including the breast, prostate, lung, colon, rectum, ovaries, cervix, and bladder.  All but one of the 25 observation studies that probably considered use of vitamin for periods of 7 years or longer showed that Vitamin E produced a benefit.  Two clinical studies also showed a benefit.  Nearly all of the Vitamin E used in these studies were from Vitamin E supplements of mostly alpha tocopherol.  The values noted in Table E in the column labeled 'Amt Diff"  refer to difference in amount of vitamin used in IU per day.  Although these are not all of the population studies published on Vitamin E and cancer, these results appear representative of the results from a few other published studies found.

 

The average risk ratio of all 25 research comparisons of Vitamin E use is 0.67, a reduction in cancer of about 1/3rd.  Yet none of the studies included the amount and probable kind of Vitamin E that produces maximum benefit.  Further, most of the studies involved use of the Vitamin for periods much shorter than that needed to obtain maximum benefit.  Use of 400 IU of most effective Vitamin E over periods of 15 years or more probably will reduce the risk of cancer at least in half.  An exception discussed following is that pre-menopausal women may not obtain a useful reduction in cancer risk for use of antioxidants during these years.

 

Vitamin E use appears to reduce risk of all types of cancer.  The research results for use of Vitamin E are summarized and averaged following:                                   

 

Cancer Type	Number of Comparisons	Average Risk Ratio
All Cancer	2	0.55
Breast Cancer	4	0.82
Prostate Cancer	3	0.67
Lung Cancer	2	0.53
Colorectal Cancer	9	0.70
Ovarian Cancer	3	0.73
Cervical Cancer	2	0.51
Bladder Cancer	2	0.86

 

 

The above results are not adequate to identify statistically differing benefits for vitamin E in reducing cancer risk at different sites.  The  'All Cancer' comparisons showed benefits similar to those for other research.  Thus the hypothesis that all types of cancer are benefited similarly appears to be a most reasonable assumption from research obtained to date, and this assumption is now used in Life Ahead with the exception on breast cancer that follows.  Nearly all other studies are statistically consistent with the average risk ratio of 0.67, and thus establish this usual value of benefit for middle age and older men and women with very high significance.

 

Risks for Breast Cancer May Differ:  The lower risk for breast cancer is due to the small benefit found in the important Nurse's study of Hunter. Similar smaller than usual cancer benefits from this study were found herein for the benefit of Vitamin E on ovarian cancer by Fairfield, for cancer benefits from antioxidant Vitamins A and C, for cancer benefits from the antioxidant selenium.  Many women in the Nurse's study were pre-menopausal at start and during much of the term of the study, whereas most women in other studies were older and post-menopausal.  A possible reason for the lower benefit found in this study is that the the strong estrogen environment during the pre-menopausal years that increases cancer risk by about 3% for each year of estrogen exposure was not offset by antioxidants during these years.  A sub-comparison in the Hunter study did confirm a possible 10% lower risk benefit for pre-menopausal women than for post-menopausal women.  Other research listed in Table E indicated similar benefits for women and men. 

 

A number of other studies identified effects of various antioxidants on risk of breast cancer either from diet or from amounts measured in blood or body tissues.  Results were highly mixed, a probable problem of statistical confusion.  First, the small above indicated benefit of Vitamin E on breast cancer is less than the margin of error of most studies.  Thus their results cannot pass the usual 95% statistical significance test for this level of benefit and study error. Second, foods and most multivitamin supplements contain various combination amounts of Vitamins A, B, C, and E and statistical methods cannot separate out accurately their separate effects. Thus although most studies report benefits for some of these antioxidants in reducing cancer risk, different studies tend to pick differing antioxidants as the contributors that could be statistical happen-chance. 

 

Some Estimates are Needed to Replace Lacking Data:  Useful values for specific amounts of Vitamin E consumed by groups were provided in only a few studies.  Thus amounts shown for the other studies are only rough estimates based on information from these studies and other information on the usual Vitamin use by populations.  The duration of use of the Vitamin also was unavailable in nearly all of the studies.  Thus these estimates also are very approximate.  The estimate of 7-10 years is assumed as an average user time of use in observation type studies, and to this was added one half of the duration of a prospective study.  Average duration is estimated at one half total study term for clinical studies.

 

Cancer Risks Should Depend on Duration of a Factor Use:  From BioChemical Engineering and the Global Analysis of cancer it is likely that cancer develops only slowly over time, with risk compounding with duration of carcinogen use.  This is found directly for cigarettes and cancer. Thus the benefit of antioxidants should accrue stepwise depending on the time during which this agent is present. Little information on the effect of antioxidant duration is provided in the available population research.  A study of Jacobs (Cancer Epidemiol Biomarkers Prev 2001, 10:17)  did find a substantial effect of duration of Vitamin C use on risk of colorectal cancer.  A study of  Giovannucci  (Ann Intern Med 1998, 129:517) found colon cancer risk to be markedly reduced after 15 years of use of multivitamins.  A conservative analysis of results in Table E suggests a most likely average cancer risk benefit value of 0.96 per year of use for 200 mg per day of Vitamin E.  

 

The two clinical studies found showed an average  risk benefit of 0.73 for a rather small amount of vitamin E in reducing cancer.  This is somewhat surprising as most clinical studies either of cancer or atherosclerosis related factors would be expected to find and actually did find little benefit during their usual limited duration.  For the 3 year average time of these studies a Life Ahead computed benefit for these two studies would be for a risk ratio of perhaps 0.90. Actually, this higher value is within the margin of error of these studies individually.  The clinical study of adenomas was for much too short a time to identify an effect of a duration related factor. .

 

Vitamin E in Foods:  No research information considered useful regarding a benefit of Vitamin E in foods in reducing risk of cancer was found. An average amount of Vitamin E in foods is about 9 IU per day, with variation among populations of perhaps 6 to 12 IU/day. This difference of only 6 IU is too small an amount to produce a credible benefit measurable via today's population research study method. As per Table E, multiple research studies are needed to verify a benefit even for a Vitamin E difference of 200 IU per day. See more about the problems of Vitamin E in foods in the discussion of Vitamin E and heart disease. 

 

How Life Ahead Computes Risks of Vitamin E:  Life Ahead does not compute a direct effect of Vitamin E on risk of cancer.  Rather, it develops an estimated total antioxidant value from amounts of Vitamins A, C, E and Selenium in both foods and supplements, and imposes a limit on the total of all antioxidants that can be effective. This is the same method as that used for antioxidants and cardiovascular diseases.  For further conservatism Life Ahead uses a maximum benefit as that from 20 years use of antioxidants. Vitamin E is recognized as the most potent of these antioxidants in this valuation.  The use of 400 IU per day of Vitamin E alone produces an antioxidant level close to the maximum now accepted from any amount of use of these four antioxidants.  But a health-interested person should insure useful intake from each of these antioxidants as they may have complementary benefits.

 

Because of the results of the Nurses study, no benefit for antioxidants in reducing risk of cancer is assigned to women who are below the age of menopause.  Thus computed benefits from antioxidants in reducing risk of cancer for women will not become of much significance until they have been used for about 5-7 years after the age at menopause. But note that pre-menopausal women can obtain a substantial reduction in risk of cardiovascular disease for using adequate amounts of antioxidants.

 

See the accompanying discussion of Vitamin E and heart disease for Types of Vitamin E and of the overall potential benefits of Vitamin E in extending Well-Days of life.  See the Antioxidant models for CVD diseases and Cancer for more on how Vitamin E and other antioxidants participate together in producing benefit.