Which might actually make cognition worse: Centrum multivitamin, vitamin C, beta carotene, Souvenaid, zinc, or calcium supplements?
Centrum Multivitamin, Vitamin C, Beta Carotene, Souvenaid, Zinc, or Calcium Supplements for Preventing Alzheimer’s?
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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.
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.
- 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.
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.
- 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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Centrum Multivitamin, Vitamin C, Beta Carotene, Souvenaid, Zinc, or Calcium Supplements for Preventing Alzheimer’s?
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
Check out my previous video, Can Vitamin E or Selenium Supplements Prevent or Treat Alzheimer’s?.
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 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.)
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