The Prevention of Alzheimer’s Disease by Vitamin E and Selenium trial randomized more than 7,500 older men to take vitamin E, selenium, both, or neither (just placebos) for five years.
Friday Favorites: Can Vitamin and Mineral Supplements Prevent Alzheimer’s?
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Oxidative stress from free radicals is the one of the pathways implicated in the development and deterioration of Alzheimer’s brains, given the evidence of excess of oxidative DNA damage on autopsy. So, what about trying an antioxidant? Vitamin E levels tend to be lower in the bloodstreams of those with cognitive impairment or dementia, but which came first? Maybe Alzheimer’s disease led to poor eating, rather than poor eating leading to Alzheimer’s disease. Greater vitamin E intake from foods is clearly associated with lower risk of developing Alzheimer’s, but greater vitamin E intake from supplements is not. But that didn’t stop researchers from including a vitamin E arm in the largest primary prevention study of Alzheimer’s disease to date.
The Prevention of Alzheimer’s Disease by Vitamin E and Selenium trial randomized more than 7,500 older men to take vitamin E, selenium, both, or neither—just placebos—for five years. To quote from the conclusion: “Neither supplement prevented dementia.” A separate long-term vitamin E supplementation trial of older women similarly found no protection against cognitive decline. Neither did vitamin E appear to benefit those with mild cognitive impairment. But the trials on Alzheimer’s patients themselves started to get more interesting.
The first trial, published in the New England Journal of Medicine, randomized more than 150 Alzheimer’s patients to vitamin E or placebo to see if vitamin E could slow the progression of the disease. The primary outcome was the number of days until of one of any of the following happened: death, institutionalization, loss of the ability to perform basic activities of daily living, or sliding into severe dementia, where you suffer a complete loss of sense of time or place. On first analysis, vitamin E flopped: no significant slowing of progression. Digging deeper, the researchers realized that despite the random allotment, the placebo group just by chance ended up with patients with milder disease. After taking that into account, the difference in outcomes between the vitamin E and placebo groups widened substantially. Now, this kind of unplanned post-hoc analysis is heavily frowned upon, but the effect seemed so sizable they went ahead and published it. In the placebo group, the adjusted time to death or loss of independence was 440 days. But in the vitamin E group, after the baseline cognition was normalized, it was 670 days––more than seven months later. However, given the unorthodox analysis, the scientific world waited for the study to be replicated.
And here we go: more than 600 patients with mild to moderate Alzheimer’s disease were subsequently randomized to vitamin E supplements, the drug memantine, both, or neither (just placebos) for two years. Although there was no slowing of cognitive decline after adjusting for multiple comparisons, there was a slowing of functional decline, in terms of managing daily activities like bathing and dressing. The vitamin E group appeared to only suffer about 1.5 years of functional deterioration in the two years’ time, resulting in approximately two hours less caregiver time required each day compared to the drug group.
If those were the only two clinical vitamin E trials, I would give vitamin E serious consideration for those with Alzheimer’s disease. But, there’s a third, a six-month trial, that suggested vitamin E may be detrimental to cognition in some Alzheimer’s patients. Obviously, more research needs to be done.
In my next video, I’ll cover other antioxidants that have been put to the test, including vitamin C, beta carotene, Centrum multivitamin, and the minerals zinc and calcium.
Alzheimer’s patients have significantly lower blood levels of eight out of 10 antioxidants investigated––though, of course, this could just be a consequence of demented individuals eating diets poor in fruits and vegetables. When put to the test, the PREADViSE study found no benefit for vitamin E or selenium in terms of preventing dementia. What about other antioxidants? In the Harvard Physician’s Health Study, nearly 6,000 older men were randomized to beta carotene or placebo. No difference was found after three years. But after 15 years, those unknowingly taking the equivalent of 3/4 cup (150 g) of sweet potato worth of beta carotene a day had slightly yet significantly better overall cognitive performance. A similar study of older women found no cognitive benefit over a period of nine years. Maybe they just didn’t wait long enough?
Vitamin E and C were also tested. Vitamin E similarly flopped throughout, and so did vitamin C, up until the last cognitive assessment at around year nine where the vitamin C group appeared to pull ahead. However, two trials of a combination of vitamin C, E, and beta carotene together versus placebo—one randomizing 1,500 older patients for seven years and another truly massive one randomizing more than 20,000 adults for five years—both failed to show any cognitive benefit for the antioxidant cocktail.
What about a multivitamin? The Physician’s Health Study also tested taking the daily multivitamin/multimineral supplement Centrum Silver for 12 years. Compared to those instead randomized to a placebo, the Centrum group experienced no cognitive benefit.
Souvenaid is a nutritional drink containing a patented formulation of nutrients, branded as Fortasyn Connect, specifically designed to help in Alzheimer’s disease. Unfortunately, it doesn’t work. There have been three randomized controlled trials enrolling more than a thousand people, and those taking Souvenaid were no less likely to develop dementia in the first place, and probably it has little or no effect on measures of memory or other thinking skills in both those with mild cognitive impairment or Alzheimer’s disease.
In terms of specific minerals other than the failed selenium, zinc has similarly flopped to improve overall cognition over months or years of supplementation, and it’s possible calcium supplements could make things worse.
Cross-sectionally, those taking calcium have more “hyperintensity” brain lesions on MRI (shown here in red, denoting evidence of mini-strokes) and longitudinally over time, women taking calcium supplements appear to have twice the odds of developing dementia. The Women’s Health Initiative should have been able to settle the question once and for all. Thousands of older women were randomized to calcium supplements (plus vitamin D) or placebo for about eight years. Thankfully, there was no difference in the risk of developing cognitive impairment or dementia. But, that’s what was originally found for heart attack and stroke rates before pre-existing supplement use was taken into account. See, more than half of the women were already taking personal calcium supplements before entering the study and being randomized to calcium or placebo. You can imagine how this could muddy the results. If you just look at the women who weren’t on calcium beforehand, starting calcium resulted in a significant increase in the risk of cardiovascular events, consistent with a meta-analysis of calcium trials showing a 15 percent increase in heart attacks or strokes among those randomized to calcium supplements over placebo. Unfortunately, such a reanalysis has yet to be performed on the dementia data.
The bottom line is that vitamin and mineral supplements probably aren’t going to help prevent dementia or treat it, but there are tons of other things we can do. Preserving your Mind is the largest chapter of my book How Not to Age. Check it out at your local public library or listen to me read it on audiobook. All proceeds I receive from the sales of all my books go to charity.
Please consider volunteering to help out on the site.
- Wang W, Li J, Zhang H, Wang X, Zhang X. Effects of vitamin E supplementation on the risk and progression of AD: a systematic review and meta-analysis. Nutr Neurosci. 2021;24(1):13-22.
- Lin X, Kapoor A, Gu Y, et al. Contributions of DNA damage to Alzheimer’s disease. Int J Mol Sci. 2020;21(5):1666.
- Browne D, McGuinness B, Woodside JV, McKay GJ. Vitamin E and Alzheimer’s disease: what do we know so far? Clin Interv Aging. 2019;14:1303-1317.
- Kryscio RJ, Abner EL, Caban-Holt A, et al. Association of antioxidant supplement use and dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium trial (PREADViSE). JAMA Neurol. 2017;74(5):567-573.
- Kang JH, Cook N, Manson J, Buring JE, Grodstein F. A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med. 2006;166(22):2462-2468.
- Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379-2388.
- Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med. 1997;336(17):1216-1222.
- Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014;311(1):33-44.
- Lloret A, Badía MC, Mora NJ, Pallardó FV, Alonso MD, Viña J. Vitamin E paradox in Alzheimer’s disease: it does not prevent loss of cognition and may even be detrimental. J Alzheimers Dis. 2009;17(1):143-149.
- Mullan K, Cardwell CR, McGuinness B, Woodside JV, McKay GJ. Plasma antioxidant status in patients with alzheimer’s disease and cognitively intact elderly: a meta-analysis of case-control studies. J Alzheimers Dis. 2018;62(1):305-317.
- Kryscio RJ, Abner EL, Caban-Holt A, et al. Association of antioxidant supplement use and dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium trial (PREADViSE). JAMA Neurol. 2017;74(5):567-573.
- Grodstein F, Kang JH, Glynn RJ, Cook NR, Gaziano JM. A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians’ Health Study II. Arch Intern Med. 2007;167(20):2184-2190.
- Kang JH, Cook NR, Manson JE, Buring JE, Albert CM, Grodstein F. Vitamin E, vitamin C, beta carotene, and cognitive function among women with or at risk of cardiovascular disease: The Women’s Antioxidant and Cardiovascular Study. Circulation. 2009;119(21):2772-2780.
- Yaffe K, Clemons TE, McBee WL, Lindblad AS, Age-Related Eye Disease Study Research Group. Impact of antioxidants, zinc, and copper on cognition in the elderly: a randomized, controlled trial. Neurology. 2004;63(9):1705-1707.
- Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):23-33.
- Burckhardt M, Watzke S, Wienke A, Langer G, Fink A. Souvenaid for Alzheimer’s disease. Cochrane Database Syst Rev. 2020;12(12):CD011679.
- Maylor EA, Simpson EEA, Secker DL, et al. Effects of zinc supplementation on cognitive function in healthy middle-aged and older adults: the ZENITH study. Br J Nutr. 2006;96(4):752-760.
- Payne ME, McQuoid DR, Steffens DC, Anderson JJB. Elevated brain lesion volumes in older adults who use calcium supplements: a cross-sectional clinical observational study. Br J Nutr. 2014;112(2):220-227.
- Kern J, Kern S, Blennow K, et al. Calcium supplementation and risk of dementia in women with cerebrovascular disease. Neurology. 2016;87(16):1674-1680.
- Rossom RC, Espeland MA, Manson JE, et al. Calcium and vitamin D supplementation and cognitive impairment in the women’s health initiative. J Am Geriatr Soc. 2012;60(12):2197-2205.
- Hsia J, Heiss G, Ren H, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115(7):846-854.
- Grodstein F, O'Brien J, Kang JH, et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann Intern Med. 2013;159(12):806-814.
- Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ. 2011;342:d2040.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Oxidative stress from free radicals is the one of the pathways implicated in the development and deterioration of Alzheimer’s brains, given the evidence of excess of oxidative DNA damage on autopsy. So, what about trying an antioxidant? Vitamin E levels tend to be lower in the bloodstreams of those with cognitive impairment or dementia, but which came first? Maybe Alzheimer’s disease led to poor eating, rather than poor eating leading to Alzheimer’s disease. Greater vitamin E intake from foods is clearly associated with lower risk of developing Alzheimer’s, but greater vitamin E intake from supplements is not. But that didn’t stop researchers from including a vitamin E arm in the largest primary prevention study of Alzheimer’s disease to date.
The Prevention of Alzheimer’s Disease by Vitamin E and Selenium trial randomized more than 7,500 older men to take vitamin E, selenium, both, or neither—just placebos—for five years. To quote from the conclusion: “Neither supplement prevented dementia.” A separate long-term vitamin E supplementation trial of older women similarly found no protection against cognitive decline. Neither did vitamin E appear to benefit those with mild cognitive impairment. But the trials on Alzheimer’s patients themselves started to get more interesting.
The first trial, published in the New England Journal of Medicine, randomized more than 150 Alzheimer’s patients to vitamin E or placebo to see if vitamin E could slow the progression of the disease. The primary outcome was the number of days until of one of any of the following happened: death, institutionalization, loss of the ability to perform basic activities of daily living, or sliding into severe dementia, where you suffer a complete loss of sense of time or place. On first analysis, vitamin E flopped: no significant slowing of progression. Digging deeper, the researchers realized that despite the random allotment, the placebo group just by chance ended up with patients with milder disease. After taking that into account, the difference in outcomes between the vitamin E and placebo groups widened substantially. Now, this kind of unplanned post-hoc analysis is heavily frowned upon, but the effect seemed so sizable they went ahead and published it. In the placebo group, the adjusted time to death or loss of independence was 440 days. But in the vitamin E group, after the baseline cognition was normalized, it was 670 days––more than seven months later. However, given the unorthodox analysis, the scientific world waited for the study to be replicated.
And here we go: more than 600 patients with mild to moderate Alzheimer’s disease were subsequently randomized to vitamin E supplements, the drug memantine, both, or neither (just placebos) for two years. Although there was no slowing of cognitive decline after adjusting for multiple comparisons, there was a slowing of functional decline, in terms of managing daily activities like bathing and dressing. The vitamin E group appeared to only suffer about 1.5 years of functional deterioration in the two years’ time, resulting in approximately two hours less caregiver time required each day compared to the drug group.
If those were the only two clinical vitamin E trials, I would give vitamin E serious consideration for those with Alzheimer’s disease. But, there’s a third, a six-month trial, that suggested vitamin E may be detrimental to cognition in some Alzheimer’s patients. Obviously, more research needs to be done.
In my next video, I’ll cover other antioxidants that have been put to the test, including vitamin C, beta carotene, Centrum multivitamin, and the minerals zinc and calcium.
Alzheimer’s patients have significantly lower blood levels of eight out of 10 antioxidants investigated––though, of course, this could just be a consequence of demented individuals eating diets poor in fruits and vegetables. When put to the test, the PREADViSE study found no benefit for vitamin E or selenium in terms of preventing dementia. What about other antioxidants? In the Harvard Physician’s Health Study, nearly 6,000 older men were randomized to beta carotene or placebo. No difference was found after three years. But after 15 years, those unknowingly taking the equivalent of 3/4 cup (150 g) of sweet potato worth of beta carotene a day had slightly yet significantly better overall cognitive performance. A similar study of older women found no cognitive benefit over a period of nine years. Maybe they just didn’t wait long enough?
Vitamin E and C were also tested. Vitamin E similarly flopped throughout, and so did vitamin C, up until the last cognitive assessment at around year nine where the vitamin C group appeared to pull ahead. However, two trials of a combination of vitamin C, E, and beta carotene together versus placebo—one randomizing 1,500 older patients for seven years and another truly massive one randomizing more than 20,000 adults for five years—both failed to show any cognitive benefit for the antioxidant cocktail.
What about a multivitamin? The Physician’s Health Study also tested taking the daily multivitamin/multimineral supplement Centrum Silver for 12 years. Compared to those instead randomized to a placebo, the Centrum group experienced no cognitive benefit.
Souvenaid is a nutritional drink containing a patented formulation of nutrients, branded as Fortasyn Connect, specifically designed to help in Alzheimer’s disease. Unfortunately, it doesn’t work. There have been three randomized controlled trials enrolling more than a thousand people, and those taking Souvenaid were no less likely to develop dementia in the first place, and probably it has little or no effect on measures of memory or other thinking skills in both those with mild cognitive impairment or Alzheimer’s disease.
In terms of specific minerals other than the failed selenium, zinc has similarly flopped to improve overall cognition over months or years of supplementation, and it’s possible calcium supplements could make things worse.
Cross-sectionally, those taking calcium have more “hyperintensity” brain lesions on MRI (shown here in red, denoting evidence of mini-strokes) and longitudinally over time, women taking calcium supplements appear to have twice the odds of developing dementia. The Women’s Health Initiative should have been able to settle the question once and for all. Thousands of older women were randomized to calcium supplements (plus vitamin D) or placebo for about eight years. Thankfully, there was no difference in the risk of developing cognitive impairment or dementia. But, that’s what was originally found for heart attack and stroke rates before pre-existing supplement use was taken into account. See, more than half of the women were already taking personal calcium supplements before entering the study and being randomized to calcium or placebo. You can imagine how this could muddy the results. If you just look at the women who weren’t on calcium beforehand, starting calcium resulted in a significant increase in the risk of cardiovascular events, consistent with a meta-analysis of calcium trials showing a 15 percent increase in heart attacks or strokes among those randomized to calcium supplements over placebo. Unfortunately, such a reanalysis has yet to be performed on the dementia data.
The bottom line is that vitamin and mineral supplements probably aren’t going to help prevent dementia or treat it, but there are tons of other things we can do. Preserving your Mind is the largest chapter of my book How Not to Age. Check it out at your local public library or listen to me read it on audiobook. All proceeds I receive from the sales of all my books go to charity.
Please consider volunteering to help out on the site.
- Wang W, Li J, Zhang H, Wang X, Zhang X. Effects of vitamin E supplementation on the risk and progression of AD: a systematic review and meta-analysis. Nutr Neurosci. 2021;24(1):13-22.
- Lin X, Kapoor A, Gu Y, et al. Contributions of DNA damage to Alzheimer’s disease. Int J Mol Sci. 2020;21(5):1666.
- Browne D, McGuinness B, Woodside JV, McKay GJ. Vitamin E and Alzheimer’s disease: what do we know so far? Clin Interv Aging. 2019;14:1303-1317.
- Kryscio RJ, Abner EL, Caban-Holt A, et al. Association of antioxidant supplement use and dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium trial (PREADViSE). JAMA Neurol. 2017;74(5):567-573.
- Kang JH, Cook N, Manson J, Buring JE, Grodstein F. A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med. 2006;166(22):2462-2468.
- Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379-2388.
- Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med. 1997;336(17):1216-1222.
- Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014;311(1):33-44.
- Lloret A, Badía MC, Mora NJ, Pallardó FV, Alonso MD, Viña J. Vitamin E paradox in Alzheimer’s disease: it does not prevent loss of cognition and may even be detrimental. J Alzheimers Dis. 2009;17(1):143-149.
- Mullan K, Cardwell CR, McGuinness B, Woodside JV, McKay GJ. Plasma antioxidant status in patients with alzheimer’s disease and cognitively intact elderly: a meta-analysis of case-control studies. J Alzheimers Dis. 2018;62(1):305-317.
- Kryscio RJ, Abner EL, Caban-Holt A, et al. Association of antioxidant supplement use and dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium trial (PREADViSE). JAMA Neurol. 2017;74(5):567-573.
- Grodstein F, Kang JH, Glynn RJ, Cook NR, Gaziano JM. A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians’ Health Study II. Arch Intern Med. 2007;167(20):2184-2190.
- Kang JH, Cook NR, Manson JE, Buring JE, Albert CM, Grodstein F. Vitamin E, vitamin C, beta carotene, and cognitive function among women with or at risk of cardiovascular disease: The Women’s Antioxidant and Cardiovascular Study. Circulation. 2009;119(21):2772-2780.
- Yaffe K, Clemons TE, McBee WL, Lindblad AS, Age-Related Eye Disease Study Research Group. Impact of antioxidants, zinc, and copper on cognition in the elderly: a randomized, controlled trial. Neurology. 2004;63(9):1705-1707.
- Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):23-33.
- Burckhardt M, Watzke S, Wienke A, Langer G, Fink A. Souvenaid for Alzheimer’s disease. Cochrane Database Syst Rev. 2020;12(12):CD011679.
- Maylor EA, Simpson EEA, Secker DL, et al. Effects of zinc supplementation on cognitive function in healthy middle-aged and older adults: the ZENITH study. Br J Nutr. 2006;96(4):752-760.
- Payne ME, McQuoid DR, Steffens DC, Anderson JJB. Elevated brain lesion volumes in older adults who use calcium supplements: a cross-sectional clinical observational study. Br J Nutr. 2014;112(2):220-227.
- Kern J, Kern S, Blennow K, et al. Calcium supplementation and risk of dementia in women with cerebrovascular disease. Neurology. 2016;87(16):1674-1680.
- Rossom RC, Espeland MA, Manson JE, et al. Calcium and vitamin D supplementation and cognitive impairment in the women’s health initiative. J Am Geriatr Soc. 2012;60(12):2197-2205.
- Hsia J, Heiss G, Ren H, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115(7):846-854.
- Grodstein F, O'Brien J, Kang JH, et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann Intern Med. 2013;159(12):806-814.
- Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ. 2011;342:d2040.
Motion graphics by Avo Media
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Title
Friday Favorites: Can Vitamin and Mineral Supplements Prevent Alzheimer’s?
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
For more on brain health and vitamins, see my video Preventing Brain Loss with B Vitamins?.
Does Lion’s Mane Mushroom Powder Have Benefits for Dementia? Watch the video to find out.
For more on Alzheimer’s, check out How to Prevent Alzheimer’s with Diet and Cholesterol and Alzheimer’s Disease.
“Preserving Your Mind” is the largest chapter of my book How Not to Age. Check it out from your local public library, or listen to me read it on audiobook. (All proceeds I receive from the sales of all my books go to charity.)
The original video aired July 3 & 8, 2024
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