Therapeutics

Multivitamin-mineral Supplement

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Overview

Name: Multivitamin-mineral Supplement
Synonyms: Centrum Silver
Therapy Type: Supplement, Dietary (timeline)
Target Type: Other (timeline)
Condition(s): Mild Cognitive Impairment
U.S. FDA Status: Mild Cognitive Impairment (Not Regulated)
Company: Pfizer

Background

Multivitamin deficiencies in older adults may increase risk for cognitive decline and dementia (Littlejohns et al., 2014; Mohajeri et al., 2015). In the only large, randomized trial completed to date, a daily multivitamin produced no cognitive benefit in nearly 6,000 male physicians followed for 12 years (Grodstein et al., 2013). A smaller study suggested older people and those at risk of nutritional deficiencies might gain from supplementation (McNeill et al., 2007).

Multivitamin use in the U.S. increased in the 1980s to 2000s, but since then has declined, both in the general population and in older adults (Sandoval, 2023; Cowan et al., 2023). Current studies find approximately 40 percent of older people in the U.S. take multivitamin supplements, with use skewed toward women with higher education levels, frailty, and taking prescription medications (Fravel et al., 2023).

Findings

In September 2016, the Cocoa Supplement and Multivitamin Outcomes Study of Cognition (COSMOS-Mind) began enrolling 2,262 people 65 or older without dementia to evaluate the effect of three years of daily supplementation on global cognition. The four-arm study compared a patented, defined cocoa extract plus a Centrum Silver brand multivitamin to the extract plus placebo, the multivitamin plus placebo, or placebo only. The cocoa extract contains 500 mg of flavanols with 80 mg of epicatechin. Participants were recruited by mail across the United States. They took cognitive assessments via telephone at baseline and annually. The primary outcome was a cognitive composite comprising the Telephone Interview for Cognitive Status-modified (TICSm), and telephone versions of delayed recall, oral trail-making test, category and verbal fluency, digit span, and digit ordering. Other outcomes were scores for executive function and memory, and incident MCI and AD-related dementia. The study design is published (Baker et al., 2019). This is an ancillary study of the COSMOS trial, which examined the effect of cocoa extract and a multivitamin on cardiovascular and cancer endpoints in more than 21,000 older adults (Rautiainen et al., 2018; Sesso et al., 2022).

COSMOS-Mind finished in February 2021; results were shown in November at CTAD. Multivitamin supplementation was presented to have improved global cognition, memory, and executive function compared to placebo over three years. In a prespecified subgroup analysis, people with a history of cardiovascular disease started with a lower baseline cognitive composite score but benefitted more from the vitamins. Outcomes modeling suggests the daily multivitamin slowed cognitive aging by 60 percent, or 1.8 years. Cocoa extract had no effect on global cognitive function. Seventy-seven percent of participants completed the trial. Most were white, and had at least some college or higher education. The results were published after peer review (Baker et al., 2023). The study found no difference in the incidence of MCI or dementia with either supplement compared to placebo (Sachs et al., 2023). However, when people taking the multivitamin developed MCI, their scores for global cognition and executive function were higher, and had declined less relative to the previous year, compared to placebo.

In August 2016, another substudy, COSMOS Web, began to measure changes in cognition via an online test battery in 3,947 COSMOS participants randomized to the multivitamin, cocoa extract, both, or placebo, for three years. The primary outcome was change in episodic memory after one year, measured by the ModRey Assessment of Immediate Recall and Learning and Episodic Memory (Hale et al., 2019). The study included additional cognitive tests and MRI measures of brain structure and blood flow as secondary endpoints. It finished in December 2020; results are published (Yeung et al., 2023). People taking the vitamin did better than the placebo group on the ModRey assessment at one and three years. The difference was claimed to represent 3.1 years of age-related memory change. Secondary outcomes did not differ.

For details on these trials, see clinicaltrials.gov.

Last Updated: 03 Jan 2024

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References

Therapeutics Citations

  1. Cocoa Flavanols

Paper Citations

  1. Baker LD, Rapp SR, Shumaker SA, Manson JE, Sesso HD, Gaussoin SA, Harris D, Caudle B, Pleasants D, Espeland MA, COSMOS-Mind Research Group. Design and baseline characteristics of the cocoa supplement and multivitamin outcomes study for the Mind: COSMOS-Mind. Contemp Clin Trials. 2019 Aug;83:57-63. Epub 2019 Jul 2 PubMed.
  2. Rautiainen S, Sesso HD, Manson JE. Large-scale randomized clinical trials of bioactives and nutrients in relation to human health and disease prevention - Lessons from the VITAL and COSMOS trials. Mol Aspects Med. 2018 Jun;61:12-17. Epub 2017 Dec 29 PubMed.
  3. Sesso HD, Rist PM, Aragaki AK, Rautiainen S, Johnson LG, Friedenberg G, Copeland T, Clar A, Mora S, Moorthy MV, Sarkissian A, Wactawski-Wende J, Tinker LF, Carrick WR, Anderson GL, Manson JE, COSMOS Research Group. Multivitamins in the prevention of cancer and cardiovascular disease: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Am J Clin Nutr. 2022 Jun 7;115(6):1501-1510. PubMed.
  4. Baker LD, Manson JE, Rapp SR, Sesso HD, Gaussoin SA, Shumaker SA, Espeland MA. Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial. Alzheimers Dement. 2023 Apr;19(4):1308-1319. Epub 2022 Sep 14 PubMed.
  5. Sachs BC, Williams BJ, Gaussoin SA, Baker LD, Manson JE, Espeland MA, Sesso HD, Shumaker SA, Rapp SR, COSMOS-Mind Research Group. Impact of multivitamin-mineral and cocoa extract on incidence of mild cognitive impairment and dementia: Results from the COcoa Supplement and Multivitamin Outcomes Study for the Mind (COSMOS-Mind). Alzheimers Dement. 2023 Nov;19(11):4863-4871. Epub 2023 Apr 10 PubMed.
  6. Hale C, Last BS, Meier IB, Yeung LK, Budge M, Sloan RP, Small SA, Brickman AM. The ModRey: An Episodic Memory Test for Nonclinical and Preclinical Populations. Assessment. 2019 Sep;26(6):1154-1161. Epub 2017 Aug 11 PubMed.
  7. Yeung LK, Alschuler DM, Wall M, Luttmann-Gibson H, Copeland T, Hale C, Sloan RP, Sesso HD, Manson JE, Brickman AM. Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial. Am J Clin Nutr. 2023 Jul;118(1):273-282. Epub 2023 May 24 PubMed.
  8. Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, Fried L, Kestenbaum BR, Kuller LH, Langa KM, Lopez OL, Kos K, Soni M, Llewellyn DJ. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014 Sep 2;83(10):920-8. Epub 2014 Aug 6 PubMed.
  9. Mohajeri MH, Troesch B, Weber P. Inadequate supply of vitamins and DHA in the elderly: implications for brain aging and Alzheimer-type dementia. Nutrition. 2015 Feb;31(2):261-75. Epub 2014 Jul 24 PubMed.
  10. Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, Manson JE, Glynn RJ, Buring JE, Gaziano M, Sesso HD. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann Intern Med. 2013 Dec 17;159(12):806-14. PubMed.
  11. McNeill G, Avenell A, Campbell MK, Cook JA, Hannaford PC, Kilonzo MM, Milne AC, Ramsay CR, Seymour DG, Stephen AI, Vale LD. Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over: a randomised controlled trial. Nutr J. 2007;6:10. PubMed.
  12. Sandoval KE. Changes in Reported Dietary Supplement Use in Cognitively Normal National Alzheimer's Coordinating Center Participants Aged 55 and Older From 2015 to 2019. J Nutr. 2023 Jun;153(6):1771-1782. Epub 2023 Apr 11 PubMed.
  13. Cowan AE, Tooze JA, Gahche JJ, Eicher-Miller HA, Guenther PM, Dwyer JT, Potischman N, Bhadra A, Carroll RJ, Bailey RL. Trends in Overall and Micronutrient-Containing Dietary Supplement Use in US Adults and Children, NHANES 2007-2018. J Nutr. 2023 Jan 14;152(12):2789-2801. PubMed.
  14. Fravel MA, Ernst ME, Gilmartin-Thomas J, Woods RL, Orchard SG, Owen AJ, ASPirin in Reducing Events in the Elderly Investigator Group. Dietary supplement and complementary and alternative medicine use among older adults in Australia and the United States. J Am Geriatr Soc. 2023 Jul;71(7):2219-2228. Epub 2023 Feb 28 PubMed.

External Citations

  1. clinicaltrials.gov

Further Reading

Papers

  1. Butler M, Nelson VA, Davila H, Ratner E, Fink HA, Hemmy LS, McCarten JR, Barclay TR, Brasure M, Kane RL. Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2018 Jan 2;168(1):52-62. Epub 2017 Dec 19 PubMed.