Randomised controlled trialcited by the Tayebat archivefull text checked★ key study A-SUP-23 in-depth review

SELECT: vitamin E and prostate cancer

Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Overview

Klein EA et al.. JAMA 2011 · PMID 21990298 · DOI 10.1001/jama.2011.1437

Vitamin E pills raised prostate cancer by 17% (1.6 extra cases per 1,000 men per year).

Does the study support the specific claim? Yes · Methodological quality: high

Original publication

Plain-language summary

Study explained simply

What did the researchers want to find out?: Prostate cancer prevention.
How was the study done?: RCT.
How many people, animals or samples were studied?: 35,533 men.
What was actually found?: More prostate cancer with vitamin E.
How large was the observed effect?: HR 1.17; +1.6/1,000 py.
What do the results mean in everyday life?: Avoid vitamin E pills.
What are the study's limitations?: Modest effect.
What does it say about Elawady's specific claim?: Supports.
Do the results apply to Germany and Europe?: Applicable.
What can explicitly not be concluded from this study?: Mortality effects.

Scientific in-depth review

1. Full reference

Authors: Klein EA, Thompson IM, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL, Baker LH
Journal: JAMA
Year: 2011
Identifier: PMID 21990298 DOI 10.1001/jama.2011.1437 · PMC4169010
Verification: verified – PubMed E-utilities efetch, 2026-10-25
Retracted: no
Corrections: none
Extent checked: full text
Conflicts of interest and funding: NCI cooperative agreement CA37429 and NCCAM (NIH), which participated in design, oversight and reporting; study agents donated by Perrigo, Sabinsa, Tishcon and DSM Nutritional Products. Several authors report industry relationships (Wyeth/Pfizer pill supply, Janssen, Amgen, Novartis, AstraZeneca, Merck board, Cancer Prevention Pharmaceuticals co-founder).

2. Research question

Long-term effect of vitamin E and selenium on prostate cancer

3. Study design and population

Study design: Randomised controlled trial – Randomised, double-blind, placebo-controlled four-arm trial (SELECT; NCT00006392); extended follow-up including an unblinded phase after supplements were stopped in October 2008
Population: Relatively healthy men aged >=50 (African American) or >=55 (others) with PSA <=4.0 ng/mL and non-suspicious DRE; median age 62-63; 79% white, 12-13% African American
Country: USA, Canada, Puerto Rico (427 sites)
Period: Randomisation 22 Aug 2001 - 24 Jun 2004; blinded supplementation until 23 Oct 2008; unblinded follow-up to 5 Jul 2011
Sample size: 35,533 randomised; 34,887 analysed (selenium 8752, vitamin E 8737, both 8702, placebo 8696)
Inclusion and exclusion criteria: Age and PSA/DRE criteria as above

4. Methods and endpoints

Exposure / intervention: Vitamin E 400 IU/day all-rac-alpha-tocopheryl acetate; selenium 200 ug/day L-selenomethionine; or both
Comparator: Matched placebos
Endpoints: Prostate cancer incidence (community diagnosis, 82-86% centrally confirmed); secondary: Gleason >=7, lung, colorectal and other cancers, deaths, grade >=4 cardiovascular events, diabetes
Statistical methods: Proportional hazards models with 99% CIs (prespecified one-sided 0.005 for prevention; two-sided P reported); interaction model for vitamin E x selenium; competing-risk cumulative incidence

5. Actual results

Results: Prostate cancers: placebo 529, vitamin E 620 (HR 1.17, 99% CI 1.004-1.36, P=0.008), selenium 575 (1.09, 0.93-1.27), combination 555 (1.05, 0.89-1.22); significant vitamin E x selenium interaction (P=0.021). Gleason >=7: vitamin E HR 1.16 (0.86-1.58), NS. Almost all cancers non-metastatic. No difference in all-cause deaths (vitamin E HR 1.01, 0.86-1.17), other cancers, cardiovascular events or diabetes. Testing intensity (PSA, DRE, biopsy) similar across arms.
Absolute risks: Prostate cancer 10.9 vs 9.3 per 1000 person-years (vitamin E vs placebo; +1.6 per 1000 person-years); selenium +0.9, combination +0.4
Authors' conclusion: Vitamin E significantly increased prostate cancer risk among healthy men.

6. Strengths

Very large double-blind placebo-controlled RCT
Pathology centrally confirmed in most cases
Testing intensity balanced between arms
Prespecified comparisons and 99% CIs

7. Weaknesses

Absolute effect small (1.6 per 1000 person-years)
About 16-21% of cancers diagnosed during unblinded follow-up after supplements stopped
Significant only for vitamin E alone, not combined with selenium; no significant increase in high-grade disease; no effect on mortality
Result emerged with extended follow-up after the primary report (multiple looks)
Not replicated in PHS II (HR 0.97); ATBC (50 mg/day, smokers) found fewer prostate cancers

8. Risk of bias

Orienting tool: RoB 2
Type of assessment: structured assessment based on the full text by a single reviewer (no formal double review)
Full formal assessment: no
Overall risk of bias: some concerns
Rationale: Single-reviewer structured RoB 2 judgement from full text; not formal (needs two independent reviewers and protocol). Downgraded from low to some concerns because part of follow-up was unblinded and the finding emerged on extended analysis; the result remains credible given balanced testing.

8. Risk of bias
Domain	Judgement	Rationale
D1 Randomisation process	low	Large randomised trial with balanced baseline characteristics.
D2 Deviations from intended interventions	low	Double-blind until October 2008; ITT analysis; supplements stopped for all arms simultaneously.
D3 Missing outcome data	low	34,887 of 35,533 analysed; balanced follow-up.
D4 Measurement of the outcome	some concerns	Community-based diagnosis; part of follow-up unblinded, but PSA/DRE/biopsy rates were similar across arms after unblinding.
D5 Selection of the reported result	some concerns	Prespecified outcome, but significant result arose after additional analyses of extended follow-up (multiple looks).

Full-text review (25 October 2026): Added absolute rates (10.9 vs 9.3/1000 py), vitamin E x selenium interaction, non-significant Gleason >=7 and mortality (HR 1.01) results, unblinded follow-up phase, balanced testing intensity, funding/agent donors and COI; RoB 2 domains with overall changed from low to some concerns.

9. Assessment of the statistical interpretation

Relative increase of 17% with a 99% CI lower bound just above 1 (1.004); small absolute increase (1.6 per 1000 person-years) mostly in low-grade, localised cancers; no effect on mortality in SELECT.

10. Relevance to the specific claim

C-SUP-03.

11. Independent contrary findings

ATBC (A-SUP-05): fewer prostate cancers with 50 mg alpha-tocopherol.

12. Transferability to Germany and Europe

High: biology and trial populations comparable to European adults.

13. Overall methodological judgement

Strong RCT evidence of modest harm.

Multidimensional assessment
Multidimensional assessment
Authenticity of the source	verified
Methodological quality	high
Risk of bias	some concerns
Precision of results	moderate
Directness	direct
Reproducibility	not replicated
Consistency with the overall evidence	mixed
Regional transferability	high
Adequacy of the interpretation (by the archive)	essentially correct but incomplete

14. Open questions

Mechanism of the vitamin E-selenium interaction; long-term effect on aggressive disease.

15. Linked fact checks

High-dose vitamin E (400 IU/day) increases prostate cancer (SELECT, +17%) and may increase all-cause mortality (Miller 2005: +39 per 10,000). – Studies supporting the claim

Use by the Tayebat archive

Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.

What the archive says about the study: SELECT found vitamin E 400 IU/day significantly increased prostate cancer risk (620 vs 529; HR 1.17).
A. What was actually studied?: Vitamin E/selenium vs placebo.
B. What did the authors find?: HR 1.17 vitamin E.
C. What conclusions do the authors themselves draw?: Vitamin E increased risk.
D. What does the archive derive from it?: Used as evidence of harm.
E. Is this derivation scientifically justified?: Essentially correct for prostate cancer incidence; the archive omits the small absolute increase (1.6/1000 person-years), the lack of a significant effect on high-grade cancer and the absence of any mortality difference in SELECT (HR 1.01).
Adequacy of the interpretation (by the archive): essentially correct but incomplete