Skip to main content

Advertisement

SpringerLink
Log in

Effect of antioxidant intake patterns on risks of dementia and cognitive decline

  • Review
  • Published:
European Geriatric Medicine Aims and scope Submit manuscript

Key summary points

AbstractSection Aim

This systematic review and meta-analysis aims to quantitatively investigate the relationships between the pattern of antioxidant intakes and risks of dementia and cognitive decline.

AbstractSection Findings

For the risk of all-cause dementia, it is supplemental, not dietary, use of vitamin E or vitamin C that can significantly reduce the risk. For AD risk, dietary plus supplemental, not supplemental alone, intakes of vitamin E or vitamin C decrease markedly the risk. Furthermore, linear dose-response analyses further verified the positive effect of dietary plus supplemental intake of vitamin C on a reduced incidence of Alzheimer’s dementia, with an association of every 20 mg/day increase in vitamin C and a 2% decrease in AD risk by diet plus supplement intake.

AbstractSection Message

The findings support dietary guidelines that recommend increased intake of vitamin-C-rich foods accompanied by supplemental use of vitamin C which may be more beneficial to reduce the risk of Alzheimer-type dementia.

Abstract

Background

Previous studies have suggested that increased antioxidant intakes might reduce risk of cognitive disorders including Alzheimer’s disease (AD). Which avenue of antioxidant intake (vitamin E/C) is more effective for decreasing risk, however, is largely unknown.

Objectives

To quantitatively investigate the relationships between the pattern of antioxidant intakes and risks of dementia and cognitive decline.

Methods

We searched all related prospective cohort studies reporting antioxidant intakes (diet and/or supplement) from patients with cognitive disorders. We conducted dose–response meta-analyses to assess potential linear and non-linear dose–response relationships. Summary RRs and 95% CIs were calculated using a random- or fixed-effects model.

Results

73 eligible cohort studies totaling > 28,257 participants were included in the meta-analysis; the pooled relative risks of AD were 0.75 (95% CI 0.57–0.99; I2 = 59.9%) for the dietary only intake of vitamin E, 0.73 (95% CI 0.54–1.00; I2 = 0%) for the dietary plus supplemental intake of vitamin E, and 0.70 (95% CI 0.51–0.95; I2 = 0%) for the dietary plus supplemental intake of vitamin C. Moreover, pooled RRs of AD and vitamin C intake per 20 mg/day increase were 0.98 (95% CI 0.97–0.99) via dietary plus supplemental intake, 0.98 (95% CI 0.96–1.00) in the dietary only intake and 0.98 (95% CI 0.98–0.99) in the overall intake. There were no significant associations of all-cause dementia or cognitive impairment no dementia with the antioxidant intake.

Conclusions

The risk of incident AD is significantly reduced by higher consumption of vitamin C by the intake avenue of diet plus supplement.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Gunther VK, Schafer P, Holzner BJ, Kemmler GW (2003) Long-term improvements in cognitive performance through computer-assisted cognitive training: a pilot study in a residential home for older people. Aging Ment Health 7(3):200–206

    Article  CAS  Google Scholar 

  2. Wald DS, Kasturiratne A, Simmonds M (2011) Serum homocysteine and dementia: meta-analysis of eight cohort studies including 8669 participants. Alzheimers Dement 7(4):412–417

    Article  CAS  Google Scholar 

  3. Zhou F, Shuangrong C, Qu L (2015) Reactive oxygen species mediate abnormal tau phosphorylation in a zinc-induced model. J Neurol Sci (Turkish) 32(1):115–121

    Google Scholar 

  4. Zhou F, Chen S (2018) Effects of gender and other confounding factors on leptin concentrations in Alzheimer’s disease: evidence from the combined analysis of 27 case-control studies. J Alzheimers Dis 62(1):477–486

    Article  CAS  Google Scholar 

  5. Zhou F (2017) The bridging integrator 1 Gene rs7561528 polymorphism contributes to Alzheimer’s disease susceptibility in East Asian and Caucasian populations. Clin Chim Acta 469:13–21

    Article  CAS  Google Scholar 

  6. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–2012

    Article  CAS  Google Scholar 

  7. Xu C, Zeng XT, Liu TZ, Zhang C, Yang ZH, Li S, Chen XY (2015) Fruits and vegetables intake and risk of bladder cancer: a PRISMA-compliant systematic review and dose-response meta-analysis of prospective cohort studies. Medicine (Baltimore) 94(17):e759

    Article  CAS  Google Scholar 

  8. Zhang J, Yu KF (1998) What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280(19):1690–1691

    Article  CAS  Google Scholar 

  9. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC (2004) Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache county study. Arch Neurol 61(1):82–88

    Article  Google Scholar 

  10. Bekkering GE, Harris RJ, Thomas S, Mayer AM, Beynon R, Ness AR, Harbord RM, Bain C, Smith GD, Sterne JA (2008) How much of the data published in observational studies of the association between diet and prostate or bladder cancer is usable for meta-analysis? Am J Epidemiol 167(9):1017–1026

    Article  Google Scholar 

  11. Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135(11):1301–1309

    Article  CAS  Google Scholar 

  12. Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D (2012) Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software. Am J Epidemiol 175(1):66–73

    Article  Google Scholar 

  13. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L (2008) Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol 61(10):991–996

    Article  Google Scholar 

  14. Basambombo LL, Carmichael PH, Cote S, Laurin D (2017) Use of vitamin e and c supplements for the prevention of cognitive decline. Ann Pharmacother 51(2):118–124

    Article  CAS  Google Scholar 

  15. Corrada MM, Kawas CH, Hallfrisch J, Muller D, Brookmeyer R (2005) Reduced risk of Alzheimer’s disease with high folate intake: the Baltimore longitudinal study of aging. Alzheimers Dement 1(1):11–18

    Article  CAS  Google Scholar 

  16. Devore EE, Grodstein F, van Rooij FJ, Hofman A, Stampfer MJ, Witteman JC, Breteler MM (2010) Dietary antioxidants and long-term risk of dementia. Arch Neurol 67(7):819–825

    Article  Google Scholar 

  17. Gray SL, Anderson ML, Crane PK, Breitner JCS, McCormick W, Bowen JD, Teri L, Larson E (2008) Antioxidant vitamin supplement use and risk of dementia or Alzheimer’s disease in older adults. J Am Geriatr Soc 56(2):291–295

    Article  Google Scholar 

  18. Laurin D, Masaki KH, Foley DJ, White LR, Launer LJ (2004) Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia aging study. Am J Epidemiol 159(10):959–967

    Article  Google Scholar 

  19. Luchsinger JA, Tang MX, Shea S, Mayeux R (2003) Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol 60(2):203–208

    Article  Google Scholar 

  20. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, Scherr PA (2002) Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 287(24):3230–3237

    Article  CAS  Google Scholar 

  21. Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS, Aggarwal NT, Scherr PA (2005) Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr 81(2):508–514

    Article  CAS  Google Scholar 

  22. Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR (2000) Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 54(6):1265–1272

    Article  CAS  Google Scholar 

  23. Fillenbaum GG, Kuchibhatla MN, Hanlon JT, Artz MB, Pieper CF, Schmader KE, Dysken MW, Gray SL (2005) Dementia and Alzheimer’s disease in community-dwelling elders taking vitamin C and/or vitamin E. Ann Pharmacother 39(12):2009–2014

    Article  CAS  Google Scholar 

  24. Maxwell CJ, Hicks MS, Hogan DB, Basran J, Ebly EM (2005) Supplemental use of antioxidant vitamins and subsequent risk of cognitive decline and dementia. Dement Geriatr Cogn Disord 20(1):45–51

    Article  CAS  Google Scholar 

  25. Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, Breteler MM (2002) Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 287(24):3223–3229

    Article  CAS  Google Scholar 

  26. Kryscio RJ, Abner EL, Caban-Holt A, Lovell M, Goodman P, Darke AK, Yee M, Crowley J, Schmitt FA (2017) Association of antioxidant supplement use and dementia in the prevention of alzheimer’s disease by vitamin e and selenium trial (PREADViSE). Jama Neurol 74(5):567–573

    Article  Google Scholar 

  27. Paganini-Hill A, Kawas CH, Corrada MM (2016) Lifestyle factors and dementia in the oldest-old: the 90+ study. Alzheimer Dis Assoc Disord 30(1):21–26

    Article  Google Scholar 

  28. Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues JF (2000) Intake of flavonoids and risk of dementia. Eur J Epidemiol 16(4):357–363

    Article  CAS  Google Scholar 

  29. Kalmijn S, Feskens EJ, Launer LJ, Kromhout D (1997) Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. Am J Epidemiol 145(1):33–41

    Article  CAS  Google Scholar 

  30. Grodstein F, Chen J, Willett WC (2003) High-dose antioxidant supplements and cognitive function in community-dwelling elderly women. Am J Clin Nutr 77(4):975–984

    Article  CAS  Google Scholar 

  31. Paleologos M, Cumming RG, Lazarus R (1998) Cohort study of vitamin C intake and cognitive impairment. Am J Epidemiol 148(1):45–50

    Article  CAS  Google Scholar 

  32. Rafnsson SB, Dilis V, Trichopoulou A (2013) Antioxidant nutrients and age-related cognitive decline: a systematic review of population-based cohort studies. Eur J Nutr 52(6):1553–1567

    Article  CAS  Google Scholar 

  33. Cao L, Tan L, Wang HF, Jiang T, Zhu XC, Lu H, Tan MS, Yu JT (2016) Dietary patterns and risk of dementia: a systematic review and Meta-Analysis of cohort studies. Mol Neurobiol 53(9):6144–6154

    Article  CAS  Google Scholar 

  34. Li FJ, Shen L, Ji HF (2012) Dietary intakes of vitamin E, vitamin C, and beta-carotene and risk of Alzheimer’s disease: a meta-analysis. J Alzheimers Dis 31(2):253–258

    Article  CAS  Google Scholar 

  35. Brewer GJ (2010) Why vitamin E therapy fails for treatment of Alzheimer’s disease. J Alzheimers Dis 19(1):27–30

    Article  Google Scholar 

  36. Monacelli F, Acquarone E, Giannotti C, Borghi R, Nencioni A, Vitamin C (2017) Aging and Alzheimer’s disease. Nutrients 9(7):670

    Article  Google Scholar 

  37. Dhingra D, Parle M, Kulkarni SK (2006) Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice. J Med Food 9(2):281–283

    Article  CAS  Google Scholar 

  38. Cai P, Ye J, Zhu J, Liu D, Chen D, Wei X, Johnson NR, Wang Z, Zhang H, Cao G et al (2016) Inhibition of endoplasmic reticulum stress is involved in the neuroprotective effect of bFGF in the 6-OHDA-Induced Parkinson’s disease model. Aging Dis 7(4):336

    Article  Google Scholar 

  39. Lam V, Hackett M, Takechi R (2016) Antioxidants and dementia risk: consideration through a cerebrovascular perspective. Nutrients 8(12):828

    Article  Google Scholar 

  40. Tonnies E, Trushina E (2017) Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis 57(4):1105–1121

    Article  Google Scholar 

  41. Huang J, May JM (2006) Ascorbic acid protects SH-SY5Y neuroblastoma cells from apoptosis and death induced by beta-amyloid. Brain Res 1097(1):52–58

    Article  CAS  Google Scholar 

  42. Rosales-Corral S, Tan DX, Reiter RJ, Valdivia-Velazquez M, Martinez-Barboza G, Acosta-Martinez JP, Ortiz GG (2003) Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid-beta peptide in rat brain: a comparative, in vivo study versus vitamin C and E. J Pineal Res 35(2):80–84

    Article  CAS  Google Scholar 

  43. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2012) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 3:D7176

    Google Scholar 

  44. Zlokovic BV (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 12(12):723–738

    Article  CAS  Google Scholar 

  45. van de Haar HJ, Burgmans S, Jansen JF, van Osch MJ, van Buchem MA, Muller M, Hofman PA, Verhey FR, Backes WH (2016) Blood–brain barrier leakage in patients with early Alzheimer disease. Radiology 281(2):527–535

    Article  Google Scholar 

  46. Kook SY, Lee KM, Kim Y, Cha MY, Kang S, Baik SH, Lee H, Park R, Mook-Jung I (2014) High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice. Cell Death Dis 5:e1083

    Article  CAS  Google Scholar 

  47. Riviere S, Birlouez-Aragon I, Nourhashemi F, Vellas B (1998) Low plasma vitamin C in Alzheimer patients despite an adequate diet. Int J Geriatr Psychiatry 13(11):749–754

    Article  CAS  Google Scholar 

  48. Sil S, Ghosh T, Gupta P, Ghosh R, Kabir SN, Roy A (2016) Dual role of vitamin c on the neuroinflammation mediated neurodegeneration and memory impairments in colchicine induced rat model of Alzheimer disease. J Mol Neurosci 60(4):421–435

    Article  CAS  Google Scholar 

  49. Scheffler J, Bork K, Bezold V, Rosenstock P, Gnanapragassam VS, Horstkorte R (2019) Ascorbic acid leads to glycation and interferes with neurite outgrowth. Exp Gerontol 117:25–30

    Article  CAS  Google Scholar 

  50. Sofic E, Sapcanin A, Tahirovic I, Gavrankapetanovic I, Jellinger K, Reynolds GP, Tatschner T, Riederer P (2006) Antioxidant capacity in postmortem brain tissues of Parkinson’s and Alzheimer’s diseases. J Neural Transm Suppl 71:39–43

    CAS  Google Scholar 

Download references

Acknowledgements

ZFT, ZHZ and LT designed research; XXH and LT analyzed data; ZFT and ZHZ wrote the paper; ZFT had primary responsibility for final content. All authors read and approved the final manuscript.

Funding

The work was supported by the National Natural Science Foundation of China (No. 32160212), the Natural Science Foundation of Jiangxi Province (No. 20202BAB206031) and Nature Science Foundation of Gannan Medical University under Grant No. QD201914.

Author information

Authors and Affiliations

  1. School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, 341000, Jiangxi, China

    Futao Zhou & Xinhua Xie

  2. Military Sports Training Center, Beijing, 100072, China

    Haizhong Zhang

  3. Chinese People’s Liberation Army Special Operations College, Guangzhou, 510500, Guangdong, China

    Tao Liu

Authors
  1. Futao Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinhua Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haizhong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Futao Zhou.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

Not applicable.

Informed consent

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 633 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, F., Xie, X., Zhang, H. et al. Effect of antioxidant intake patterns on risks of dementia and cognitive decline. Eur Geriatr Med 14, 9–17 (2023). https://doi.org/10.1007/s41999-022-00720-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41999-022-00720-7

Keywords

Search

Navigation