Vitamin E and Mortality in Male Smokers of the ATBC Study: Implications for Nutritional Recommendations

Abstract Objectives Vitamin E is an essential micronutrient and critical human antioxidant that has been tested for cancer and cardiovascular preventative effects for decades with conflicting results. For example, prostate cancer incidence was reduced by a low-dose vitamin E supplement in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, but the findings were not replicated by high-dose vitamin E trials such as the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The present investigation examined the serum metabolomic responses to low- and high-dose vitamin E supplementation in order to gain biological insight into the divergent trial outcomes. Methods We examined baseline and on-study serum samples for 154 men randomly assigned to receive 400 IU vitamin E (as alpha-tocopheryl acetate; ATA) or placebo daily in the Vitamin E Atherosclerosis Prevention Study (VEAPS), and 100 men administered 50 IU ATA or placebo daily in the ATBC Study. Over 970 known metabolites were identified using an ultrahigh-performance LC-MS/MS platform. Linear regression models estimated the change in serum metabolites of men supplemented with vitamin E to those assigned to placebo in VEAPS compared with ATBC. Results Serum alpha-carboxyethyl hydrochroman (CEHC) sulfate, alpha-tocopherol, and beta-/gamma-tocopherol were significantly altered by supplementation with ATA in both the VEAPS and ATBC trials (all P-values ≤ 5.1 × 10−5, the Bonferroni multiple-comparisons corrected statistical threshold). Serum C22 lactone sulfate was also significantly decreased in response to the high-dose vitamin E supplement in VEAPS (β = −0.70, P-value = 8.1 × 10−6), but not altered in the low-dose ATBC trial (β = −0.17, P-value = 0.4). Additionally, changes in several androgenic steroid metabolites were strongly related to the vitamin E supplement-associated change in C22 lactone sulfate only in the high-dose VEAPS trial. Conclusions We found evidence of a dose-dependent vitamin E supplementation effect on a novel C22 lactone sulfate compound as well as several androgenic steroids that may have relevance to previous controlled trial findings for prostate cancer. Funding Sources This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, U.S. Public Health Service, Department of Health and Human Services.

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Vitamin E and the risk of pneumonia: using the I2 statistic to quantify heterogeneity within a controlled trial

British Journal Of Nutrition ◽

10.1017/s0007114516003408 ◽

2016 ◽

Vol 116 (9) ◽

pp. 1530-1536 ◽

Cited By ~ 6

Author(s):

Harri Hemilä

Keyword(s):

Vitamin E ◽

Cancer Prevention ◽

Treatment Effect ◽

Leisure Time ◽

Controlled Trial ◽

Beta Carotene ◽

Alpha Tocopherol ◽

Nutritional Epidemiology ◽

Atbc Study ◽

Vitamin E Supplementation

AbstractAnalyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50–69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I2 statistic. The I2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89 % (95 % CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92 % (95 % CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69 % among participants who had the least exposure to smoking and exercised during leisure time (7·6 % of the ATBC participants), and vitamin E increased pneumonia risk by 68 % among those who had the highest exposure to smoking and did not exercise (22 % of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.

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Serum Metabolomic Response to Long-Term Supplementation withall-rac-α-Tocopheryl Acetate in a Randomized Controlled Trial

Journal of Nutrition and Metabolism ◽

10.1155/2016/6158436 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Alison M. Mondul ◽

Steven C. Moore ◽

Stephanie J. Weinstein ◽

Anne M. Evans ◽

Edward D. Karoly ◽

...

Keyword(s):

Prostate Cancer ◽

Vitamin E ◽

Cancer Prevention ◽

Controlled Trial ◽

Prostate Cancer Risk ◽

Alpha Tocopherol ◽

Tocopheryl Acetate ◽

Metabolite Level ◽

Randomized Controlled ◽

Atbc Study

Background. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however.Objective. We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all-rac-α-tocopheryl acetate (ATA), 20 mg/dayβ-carotene, both, placebo).Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.).Results. After correction for multiple comparisons, five metabolites were statistically significantly altered (βis the change in metabolite level expressed as number of standard deviations on the log scale):α-CEHC sulfate (β=1.51,p=1.45×10-38),α-CEHC glucuronide (β=1.41,p=1.02×10-31),α-tocopherol (β=0.97,p=2.22×10-13),γ-tocopherol (β=-0.90,p=1.76×10-11), andβ-tocopherol (β=-0.73,p=9.40×10-8). Glutarylcarnitine, beta-alanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation (βrange 0.40 to −0.36), but not statistically significantly.Conclusions. Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings.

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Vitamin E supplementation may transiently increase tuberculosis risk in males who smoke heavily and have high dietary vitamin C intake

British Journal Of Nutrition ◽

10.1017/s0007114508923709 ◽

2008 ◽

Vol 100 (4) ◽

pp. 896-902 ◽

Cited By ~ 24

Author(s):

Harri Hemilä ◽

Jaakko Kaprio

Keyword(s):

Vitamin E ◽

Vitamin C ◽

Alpha Tocopherol ◽

Dietary Vitamin ◽

Study Cohort ◽

Adjusted Risk ◽

Atbc Study ◽

Β Carotene ◽

Tuberculosis Risk ◽

Vitamin E Supplementation

Vitamin E and β-carotene affect the immune function and might influence the predisposition of man to infections. To examine whether vitamin E or β-carotene supplementation affects tuberculosis risk, we analysed data of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study, a randomised controlled trial which examined the effects of vitamin E (50 mg/d) and β-carotene (20 mg/d) on lung cancer. The trial was conducted in the general community in Finland in 1985–93; the intervention lasted for 6·1 years (median). The ATBC Study cohort consists of 29 023 males aged 50–69 years, smoking at baseline, with no tuberculosis diagnosis prior to randomisation. Vitamin E supplementation had no overall effect on the incidence of tuberculosis (risk ratio (RR) = 1·18; 95 % CI 0·87, 1·59) nor had β-carotene (RR = 1·07; 95 % CI 0·80, 1·45). Nevertheless, dietary vitamin C intake significantly modified the vitamin E effect. Among participants who obtained 90 mg/d or more of vitamin C in foods (n13 502), vitamin E supplementation increased tuberculosis risk by 72 (95 % CI 4, 185)%. This effect was restricted to participants who smoked heavily. Finally, in participants not supplemented with vitamin E, dietary vitamin C had a negative association with tuberculosis risk so that the adjusted risk was 60 (95 % CI 16, 81) % lower in the highest intake quartile compared with the lowest. Our finding that vitamin E seemed to transiently increase the risk of tuberculosis in those who smoked heavily and had high dietary vitamin C intake should increase caution towards vitamin E supplementation for improving the immune system.

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Vitamin E: Recommended Intake

10.5772/intechopen.97381 ◽

2021 ◽

Author(s):

Marianna Schwarzova ◽

Katarina Fatrcova-Sramkova ◽

Eva Tvrda ◽

Miroslava Kacaniova

Keyword(s):

Fatty Acids ◽

Biological Activity ◽

Vitamin E ◽

Dietary Factors ◽

Compelling Evidence ◽

Older Individuals ◽

Nutritional Factors ◽

Nutritional Recommendations ◽

Dietary Consumption ◽

Vitamin E Homologs

Data of vitamin E intake and status are controversial. Vitamin E is an essential micronutrient for humans and achieving an optimal status is assumed to produce beneficial health outcomes. Dietary intake recommendations for vitamin E vary considerably by different countries and organizations. It appears to be still a challenge to define these despite the wealth of data published. Vitamin E requirements have been proposed to depend on other nutritional factors, such as the intake of polyunsaturated fatty acids (PUFA). Although several foods contain naturally occurring sources of vitamin E, it is frequently the case that the intake recommendations are not achieved. Several other dietary factors affect the need for vitamin E. In this regard, significant challenges to be considered include the efficiency of other tocopherol variants and their properties that could affect the revision of the nutritional recommendations for vitamin E. Particularly, an ever-increasing evidence indicates that other vitamin E homologs may potentially present with a higher biological activity. Low dietary consumption of vitamin E, coupled with compelling evidence that increased intake of vitamin E above current recommendations for the general population may benefit older individuals.

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