Study analysis · Annals of Internal Medicine · 2013
A 12-year randomized trial of 5,947 older men found daily multivitamins did nothing to slow cognitive decline.
Taking a daily multivitamin for more than a decade did not protect memory or thinking in older men.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
In simple terms
This study gave some men a multivitamin every day and others a fake pill, then checked their memory and thinking skills for over 10 years. It found no difference between the two groups, so we can say the multivitamin didn't help their brains in this group.
What’s the bottom line?
Researchers tested whether a daily multivitamin could protect thinking and memory in older men. They followed nearly 6,000 male doctors for more than a decade.
How strong is this study?
This was a super well-done study because they randomly picked who got the real pill, nobody knew who got what, and they followed thousands of people for a very long time. That means we can trust the results — if the multivitamin had helped, we’d have seen it.
40 / 100
- COI disclosure+40/40
- Data availabilitydata not shared
- Code availabilitycode not shared
100 / 100
- Randomization+20/20
- Blinding+15/15
- Control group+15/15
- Sample size (n=5947)+20/20
- Follow-up+10/10
100 / 100
100 / 100
- P-values+15/15
- Effect size+20/20
- Confidence intervals+15/15
- Pre-registration+15/15
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 588 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
This design can establish causation. This study is a randomized controlled trial with double-blinding and a large sample size, which allows for causal inference by minimizing confounding and bias. However, the population is limited to male physicians who may be well-nourished, so causation is established within this specific group but may not generalize to others.
No Conflicts
No conflicts of interest identified
No conflicts of interest were disclosed, and the study was funded by public sources with no evidence of industry influence on design, analysis, or publication.
Funders
Conflict Details
National Institutes of Health: Funded the Physicians’ Health Study II, including the cognitive substudy.
National Institute on Aging: Provided funding support for the cognitive substudy.
Pfizer (formerly Wyeth): Supplied the multivitamin (Centrum Silver) and placebo pills as part of the study intervention.
BASF Corporation: Supplied beta-carotene, vitamin E, and ascorbic acid supplements and placebos.
Independent Analysis Safeguards
- Randomized, double-blind, placebo-controlled design
- Pre-specified outcomes and statistical methods
- Analysis conducted using SAS by study team with unstructured covariance models
- Cognitive assessments conducted via validated telephone interviews
Although industry supplied the supplements, they had no role in study design, data analysis, or interpretation. The study was investigator-initiated and funded by public agencies. No authors are disclosed as employees or shareholders of the supplement manufacturers.
Key takeaways
- 01
There was no meaningful difference between the multivitamin and placebo groups.
- 02
On a global thinking score, the difference in change over follow-up was -0.01 standard units (95% CI -0.04 to 0.02).
- 03
On verbal memory, the difference was -0.005 standard units (95% CI -0.04 to 0.03).
- 04
For comparison, the men declined by about -0.045 standard units per year as they aged.
- 05
The absolute difference was tiny and much smaller than one year of normal age-related decline.
- 06
In plain terms, taking a daily multivitamin did not measurably slow thinking or memory decline in this group.
- 07
The study did not report extra dementia cases prevented because it measured cognitive test scores, not dementia diagnoses.
- 08
It also has corrections/errata, so check those notices.
Surprising findings
- No cognitive benefit despite strong biological plausibility and some observational hintsVitamins C, E, beta-carotene, B vitamins, and vitamin A have plausible mechanisms for protecting the brain, and some observational studies suggested slower decline. This large RCT found nothing.
- A small pure-placebo subgroup suggested multivitamins might worsen declineIt contradicts the idea that multivitamins are at worst harmless. But the authors call it unreliable due to small sample size and baseline imbalance.
- Beta-carotene in the same trial previously showed cognitive benefits after 18 years, but multivitamin did notSame cohort, same overall trial infrastructure, different supplement—and opposite results. This suggests specific nutrients or timing may matter, or that the beta-carotene finding was a chance result.
Practical takeaways
Do not take a daily multivitamin solely to protect your memory or thinking.
This applies to well-nourished older men in this trial; it does not mean multivitamins are harmful, and they may still be indicated for diagnosed deficiencies.
high confidenceIf you have a diagnosed vitamin deficiency, continue to follow your doctor's advice about supplementation.
This trial did not study people with deficiencies, so results may not apply.
high confidenceFor brain health, prioritize evidence-based strategies like blood pressure control, physical activity, and a balanced diet rather than relying on multivitamins.
These strategies were not directly tested in this trial; the recommendation comes from broader medical consensus.
medium confidenceIf you take a multivitamin for other reasons, such as cancer risk reduction seen in PHS II, discuss the trade-offs with your doctor.
The cancer benefit was modest and in the same population; this cognitive substudy found no brain benefit.
medium confidenceWhy this study matters
The 12-year null result
In a double-blind RCT, 5,947 male physicians aged 65+ took a daily multivitamin (Centrum Silver) or placebo for up to 12 years. The absolute difference in global cognitive change was -0.01 standard units (95% CI -0.04 to 0.02), and verbal memory change was -0.005 SD (95% CI -0.04 to 0.03). Both confidence intervals cross zero, meaning no detectable benefit.
Most people assume multivitamins support brain health, but this is the longest and largest randomized test of that idea in older men.
The effect is smaller than one year of aging
The population declined by about -0.045 standard units per year on the global cognitive score. The entire multivitamin-versus-placebo difference over the whole follow-up was only -0.01 SD. In other words, any possible effect was smaller than the decline expected from a single year of normal aging.
It puts the tiny effect size in human terms: even if there were a benefit, it would be too small to notice in daily life.
High adherence rules out the 'people forgot to take them' excuse
83.5% of the multivitamin group and 84.2% of the placebo group took at least two-thirds of their pills over more than a decade. Follow-up rates were also high: 90-96% of contacted participants completed each cognitive assessment.
A common criticism of null trials is that participants didn't actually take the supplement. Here, they did—and it still didn't work.
No subgroup was helped
The study tested whether age, smoking, alcohol use, BMI, diabetes, hypertension, high cholesterol, folate intake, fruit and vegetable intake, or depression history changed the result. None did. The null finding held across all measured risk factors.
People often hope their personal risk profile means they'll be the exception. This trial found no evidence of any such exception.
A tiny subgroup hinted at harm—but don't panic
In a secondary analysis of 372 men who took no other active study supplements, those randomized to multivitamin showed greater decline than those on pure placebo: global cognition -0.08 SD (95% CI -0.14 to -0.01), verbal memory -0.10 SD (95% CI -0.17 to -0.02). The authors caution this is unreliable because the pure placebo group was small and the multivitamin group likely had a random baseline advantage.
It's the kind of finding that could become a scary headline, but the authors explicitly say not to trust it.
Want the whole report?
Detailed mode opens the full scientific breakdown — every score component, the methodology, conflicts of interest, the evidence analysis behind each claim, and the raw study data.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Researchers tested whether a daily multivitamin could protect thinking and memory in older men. They followed nearly 6,000 male doctors for more than a decade.
Research results
There was no meaningful difference between the multivitamin and placebo groups. On a global thinking score, the difference in change over follow-up was -0.01 standard units (95% CI -0.04 to 0.02). On verbal memory, the difference was -0.005 standard units (95% CI -0.04 to 0.03). For comparison, the men declined by about -0.045 standard units per year as they aged.
What this means - more context
The absolute difference was tiny and much smaller than one year of normal age-related decline. In plain terms, taking a daily multivitamin did not measurably slow thinking or memory decline in this group. The study did not report extra dementia cases prevented because it measured cognitive test scores, not dementia diagnoses. It also has corrections/errata, so check those notices.
To evaluate whether long-term daily multivitamin supplementation affects cognitive health in later life.
In a randomized, double-blind, placebo-controlled substudy of the Physicians' Health Study II, 5,947 male physicians aged 65 or older took a daily multivitamin or placebo for up to 12 years. No difference was found in cognitive change over time or cognitive level at any assessment. NOTE: This study has published corrections/errata; readers should check the correction notices for updated information.
Methods Used
Randomized, double-blind, placebo-controlled trial within the Physicians' Health Study II. Participants were 5,947 male physicians aged 65 years or older. Intervention was daily multivitamin (Centrum Silver) or placebo. Up to four telephone cognitive assessments were completed over 12 years, with a primary global composite score and a secondary verbal memory composite score.
Main Finding
Long-term daily multivitamin supplementation did not slow cognitive decline. For the global composite score, the mean difference in cognitive change over follow-up was -0.01 standard units (95% CI -0.04 to 0.02) comparing multivitamin with placebo. For verbal memory, the mean difference was -0.005 standard units (95% CI -0.04 to 0.03). The absolute difference was smaller than the approximately -0.045 standard units per year decline expected from one year of aging.
Confidence Level
High confidence due to the large randomized double-blind design, long follow-up, high adherence (83.5% of the multivitamin group took at least two-thirds of pills) and high follow-up rates. Limitations include a well-nourished, highly educated male physician population, possible low vitamin doses, and published corrections/errata that readers should check.
Study Flags
Red Flags
- •Corrections/errata have been issued; readers should check correction notices.
- •Population was well-nourished, highly educated male physicians, limiting generalizability to women or nutrient-deficient groups.
- •Vitamin doses may be too low to affect cognition; cognitive testing began on average 2.5 years after randomization.
Surprising Findings
No cognitive benefit despite strong biological plausibility and some observational hints
Vitamins C, E, beta-carotene, B vitamins, and vitamin A have plausible mechanisms for protecting the brain, and some observational studies suggested slower decline. This large RCT found nothing.
Practical Takeaways
Do not take a daily multivitamin solely to protect your memory or thinking.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 588 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
Human RCT
Subject
High probability
on the GRADE evidence scale
This study gave some men a multivitamin every day and others a fake pill, then checked their memory and thinking skills for over 10 years. It found no difference between the two groups, so we can say the multivitamin didn't help their brains in this group.
The study has a COI section but no disclosure was found. A small penalty has been applied.
Strengths
- Randomized, double-blind, placebo-controlled design
- Large sample size (n=5,947)
- Long follow-up duration (over 12 years)
Weaknesses
- Population limited to male physicians, reducing diversity
- Cognitive testing began 2.5 years after randomization, missing early effects
- Multivitamin formulation changed slightly over time (though consistent during trial)
Methodology
Evidence Keywords
Statistical Reporting
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Researchers tested whether a daily multivitamin could protect thinking and memory in older men. They followed nearly 6,000 male doctors for more than a decade.
Research results
There was no meaningful difference between the multivitamin and placebo groups. On a global thinking score, the difference in change over follow-up was -0.01 standard units (95% CI -0.04 to 0.02). On verbal memory, the difference was -0.005 standard units (95% CI -0.04 to 0.03). For comparison, the men declined by about -0.045 standard units per year as they aged.
What this means - more context
The absolute difference was tiny and much smaller than one year of normal age-related decline. In plain terms, taking a daily multivitamin did not measurably slow thinking or memory decline in this group. The study did not report extra dementia cases prevented because it measured cognitive test scores, not dementia diagnoses. It also has corrections/errata, so check those notices.
To evaluate whether long-term daily multivitamin supplementation affects cognitive health in later life.
In a randomized, double-blind, placebo-controlled substudy of the Physicians' Health Study II, 5,947 male physicians aged 65 or older took a daily multivitamin or placebo for up to 12 years. No difference was found in cognitive change over time or cognitive level at any assessment. NOTE: This study has published corrections/errata; readers should check the correction notices for updated information.
Methods Used
Randomized, double-blind, placebo-controlled trial within the Physicians' Health Study II. Participants were 5,947 male physicians aged 65 years or older. Intervention was daily multivitamin (Centrum Silver) or placebo. Up to four telephone cognitive assessments were completed over 12 years, with a primary global composite score and a secondary verbal memory composite score.
Main Finding
Long-term daily multivitamin supplementation did not slow cognitive decline. For the global composite score, the mean difference in cognitive change over follow-up was -0.01 standard units (95% CI -0.04 to 0.02) comparing multivitamin with placebo. For verbal memory, the mean difference was -0.005 standard units (95% CI -0.04 to 0.03). The absolute difference was smaller than the approximately -0.045 standard units per year decline expected from one year of aging.
Confidence Level
High confidence due to the large randomized double-blind design, long follow-up, high adherence (83.5% of the multivitamin group took at least two-thirds of pills) and high follow-up rates. Limitations include a well-nourished, highly educated male physician population, possible low vitamin doses, and published corrections/errata that readers should check.
Study Flags
Red Flags
- •Corrections/errata have been issued; readers should check correction notices.
- •Population was well-nourished, highly educated male physicians, limiting generalizability to women or nutrient-deficient groups.
- •Vitamin doses may be too low to affect cognition; cognitive testing began on average 2.5 years after randomization.
Surprising Findings
No cognitive benefit despite strong biological plausibility and some observational hints
Vitamins C, E, beta-carotene, B vitamins, and vitamin A have plausible mechanisms for protecting the brain, and some observational studies suggested slower decline. This large RCT found nothing.
Practical Takeaways
Do not take a daily multivitamin solely to protect your memory or thinking.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 588 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
Human RCT
Subject
High probability
on the GRADE evidence scale
This study gave some men a multivitamin every day and others a fake pill, then checked their memory and thinking skills for over 10 years. It found no difference between the two groups, so we can say the multivitamin didn't help their brains in this group.
The study has a COI section but no disclosure was found. A small penalty has been applied.
Strengths
- Randomized, double-blind, placebo-controlled design
- Large sample size (n=5,947)
- Long follow-up duration (over 12 years)
Weaknesses
- Population limited to male physicians, reducing diversity
- Cognitive testing began 2.5 years after randomization, missing early effects
- Multivitamin formulation changed slightly over time (though consistent during trial)
Methodology
Evidence Keywords
Statistical Reporting
Scoring
How strong is this study?
This was a super well-done study because they randomly picked who got the real pill, nobody knew who got what, and they followed thousands of people for a very long time. That means we can trust the results — if the multivitamin had helped, we’d have seen it.
40 / 100
- COI disclosure+40/40
- Data availabilitydata not shared
- Code availabilitycode not shared
100 / 100
- Randomization+20/20
- Blinding+15/15
- Control group+15/15
- Sample size (n=5947)+20/20
- Follow-up+10/10
100 / 100
100 / 100
- P-values+15/15
- Effect size+20/20
- Confidence intervals+15/15
- Pre-registration+15/15
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 588 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
This design can establish causation. This study is a randomized controlled trial with double-blinding and a large sample size, which allows for causal inference by minimizing confounding and bias. However, the population is limited to male physicians who may be well-nourished, so causation is established within this specific group but may not generalize to others.
No Conflicts
No conflicts of interest identified
No conflicts of interest were disclosed, and the study was funded by public sources with no evidence of industry influence on design, analysis, or publication.
Funders
Conflict Details
National Institutes of Health: Funded the Physicians’ Health Study II, including the cognitive substudy.
National Institute on Aging: Provided funding support for the cognitive substudy.
Pfizer (formerly Wyeth): Supplied the multivitamin (Centrum Silver) and placebo pills as part of the study intervention.
BASF Corporation: Supplied beta-carotene, vitamin E, and ascorbic acid supplements and placebos.
Independent Analysis Safeguards
- Randomized, double-blind, placebo-controlled design
- Pre-specified outcomes and statistical methods
- Analysis conducted using SAS by study team with unstructured covariance models
- Cognitive assessments conducted via validated telephone interviews
Although industry supplied the supplements, they had no role in study design, data analysis, or interpretation. The study was investigator-initiated and funded by public agencies. No authors are disclosed as employees or shareholders of the supplement manufacturers.
Standing
The people behind it
The researchers who wrote the study this analysis is built on.
Authored by
11 researchersIf this is your work, this is how we attribute it on Fit Body Science. Francine Grodstein is listed as the lead author.