Serum Metabolomic Response to Low and High Dose Vitamin E Supplementation in Two Randomized Controlled Trials

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.

Download Full-text

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.

Download Full-text

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.

Download Full-text

Family history of prostate cancer and prostate cancer risk in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study

International Journal of Cancer ◽

10.1002/ijc.23591 ◽

2008 ◽

Vol 123 (5) ◽

pp. 1154-1159 ◽

Cited By ~ 15

Author(s):

Jiyoung Ahn ◽

Roxana Moslehi ◽

Stephanie J. Weinstein ◽

Kirk Snyder ◽

Jarmo Virtamo ◽

...

Keyword(s):

Prostate Cancer ◽

Family History ◽

Cancer Risk ◽

Cancer Prevention ◽

Prostate Cancer Risk ◽

Beta Carotene ◽

Alpha Tocopherol ◽

History Of ◽

Atbc Study

Download Full-text

Alpha tocopherol in CSF of subjects taking high-dose vitamin E in the DATATOP study

Neurology ◽

10.1212/wnl.50.6.1900 ◽

1998 ◽

Vol 50 (6) ◽

pp. 1900-1902 ◽

Cited By ~ 37

Author(s):

G. T. Vatassery ◽

S. Fahn ◽

M. A. Kuskowski

Keyword(s):

Vitamin E ◽

Alpha Tocopherol ◽

High Dose ◽

High Dose Vitamin

Download Full-text

Effects of Vitamin E Supplementation in Male Rats with Crude Oil-Induced Reproductive Toxicity

Notulae Scientia Biologicae ◽

10.15835/nsb9310119 ◽

2017 ◽

Vol 9 (3) ◽

pp. 332-337

Author(s):

Izuchukwu S. OCHIOGU ◽

Udensi M. IGWEBUIKE ◽

Edmund C. MBEGBU ◽

Ikenna O. EZEH ◽

Paschal F. NNAMANI

Keyword(s):

Vitamin E ◽

Crude Oil ◽

Dose Group ◽

Low Dose ◽

Reproductive Toxicity ◽

Male Rats ◽

High Dose ◽

Serum Total Protein ◽

The Mean ◽

Vitamin E Supplementation

Crude oil intoxication is a major threat among people and animals living around the crude oil producing regions of the world, hence the search for ameliorating agents. Forty-four male Wistar rats assigned into three groups were used to investigate the effects of vitamin E supplementation on crude oil-induced reprotoxicity (reproductive toxicity) in male rats. Group A represented the unexposed control, whereas groups B and C were exposed orally to 0.15 and 0.3 ml of crude oil respectively every other day for 56 days. Both the low dose and high dose oral administration of crude oil caused a significant reduction in the serum testosterone level (STL) and cauda epididymal sperm reserve (CESR) of the exposed rats when compared to the control. Crude oil withdrawal and vitamin E supplementation significantly improved the cauda epididymal sperm reserve (CESR) in all the subgroups. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities of the control and low dose group were significantly lower than those of the high dose group. The high dose crude oil administration significantly decreased the mean serum total protein (STP) and sodium ions (Na+) concentration. The mean serum total cholesterol (STC) value of the low dose group was significantly higher than those of the control and high dose group. However, crude oil withdrawal and vitamin E supplementation did not significantly alter the mean serum total protein (STP) and mean serum total cholesterol (STC) values in all the subgroups. Vitamin E supplementation following low dose crude oil withdrawal enhanced the mean serum Chloride ions (Cl-)concentration. The present findings revealed that Nigerian Qua Iboe Brent crude oil induced serious reprotoxic effects in male rats which vitamin E administration within 28 days did not completely reverse.

Download Full-text

Should high-dose vitamin E supplementation be recommended to diabetic patients?

Diabetes Care ◽

10.2337/diacare.22.8.1242 ◽

1999 ◽

Vol 22 (8) ◽

pp. 1242-1244 ◽

Cited By ~ 8

Author(s):

S. K. Jain

Keyword(s):

Vitamin E ◽

Diabetic Patients ◽

High Dose ◽

High Dose Vitamin ◽

Vitamin E Supplementation

Download Full-text

Effect of vitamin E on stroke-associated pneumonia

Journal of International Medical Research ◽

10.1177/0300060520949657 ◽

2020 ◽

Vol 48 (9) ◽

pp. 030006052094965

Author(s):

Hongwei Shen ◽

Bingyan Zhan

Keyword(s):

Vitamin E ◽

Low Dose ◽

Nutritional Assessment ◽

Mini Nutritional Assessment ◽

High Dose ◽

Duration Of Hospitalization ◽

High Dose Vitamin ◽

Different Doses ◽

Better Than

Objective To study the role of vitamin E in stroke-associated pneumonia. Methods We selected 183 patients with stroke-related pneumonia who were divided into different nutrition groups according to the Mini Nutritional Assessment score. Patients were then administered different doses of vitamin E. Results CD55 and CD47 levels in patients taking vitamin E across different nutrition score groups were better than those in patients who did not use vitamin E. The levels of CD55 and CD47 and the duration of hospitalization were better in the high-dose vitamin E group than in the low-dose vitamin E group. Conclusion Vitamin E may have an auxiliary therapeutic effect in patients with stroke-associated pneumonia.

Download Full-text