Skip to main content
SpringerLink
Log in

Fruit Intake and Alzheimer’s Disease: Results from Mendelian Randomization

  • Brief Communication
  • Published:
The Journal of Prevention of Alzheimer's Disease Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia in old age, recognized as a global health priority. To explore causal effects of fresh fruit intake and dried fruit intake on AD liability, this study utilized GWAS from the UK Biobank and FinnGen to conduct Mendelian randomization (MR) analysis, and used inverse variance weighted (IVW), MR-Egger, and weighted median approaches for MR estimates, and visual inspections judged result stability. Results suggested little evidence of a potential causal relationship between fresh fruit intake and AD (OR=0.97, 95%CI=0.50–1.91, P=0.939), while significant, robust causality was indicated between dried fruit intake and AD (OR=4.09, 95%CI=2.07–8.10, P<0.001). Stability evaluations showed no heterogeneity or pleiotropy affecting interpretability and credibility of primary analyses. In conclusion, we strengthened evidence for positive causality from dried fruit intake to AD liability, with causality from fresh fruit intake on AD risk was not demonstrated.

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

Figure 1
Figure 2

Data Share Statement: Data described in the manuscript, code book, and analytic code will be made available upon request pending application.

References

  1. Zhang XX, Tian Y, Wang ZT, Ma YH, Tan L, Yu JT. The Epidemiology of Alzheimer’s Disease Modifiable Risk Factors and Prevention. J Prev Alzheimers Dis. 2021;8(3):313–321. doi:https://doi.org/10.14283/jpad.2021.15

    PubMed  Google Scholar 

  2. Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol. 2018;25(1):59–70. doi:https://doi.org/10.1111/ene.13439

    Article  PubMed  CAS  Google Scholar 

  3. Silva MVF, Loures CMG, Alves LCV, de Souza LC, Borges KBG, Carvalho MDG. Alzheimer’s disease: risk factors and potentially protective measures. J Biomed Sci. 2019;26(1):33. Published 2019 May 9. doi:https://doi.org/10.1186/s12929-019-0524-y

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mayeux R, Stern Y. Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(8):a006239. Published 2012 Aug 1. doi:https://doi.org/10.1101/cshperspect.a006239

    Article  PubMed  PubMed Central  Google Scholar 

  5. Smith PJ, Blumenthal JA. Diet and neurocognition: review of evidence and methodological considerations. Curr Aging Sci. 2010;3(1):57–66. doi:https://doi.org/10.2174/1874609811003010057

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Solfrizzi V, Panza F, Frisardi V, et al. Diet and Alzheimer’s disease risk factors or prevention: the current evidence. Expert Rev Neurother. 2011;11(5):677–708. doi:https://doi.org/10.1586/ern.11.56

    Article  PubMed  CAS  Google Scholar 

  7. Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004;61(1):82–88. doi:https://doi.org/10.1001/archneur.61.1.82

    Article  PubMed  Google Scholar 

  8. Devore EE, Grodstein F, van Rooij FJ, et al. Dietary antioxidants and long-term risk of dementia. Arch Neurol. 2010;67(7):819–825. doi:https://doi.org/10.1001/archneurol.2010.144

    Article  PubMed  PubMed Central  Google Scholar 

  9. Li H, Chen K, Yang L, Wang Q, Zhang J, He J. The role of plasma cortisol in dementia, epilepsy, and multiple sclerosis: A Mendelian randomization study. Front Endocrinol (Lausanne). 2023;14:1107780. Published 2023 Mar 15. doi:https://doi.org/10.3389/fendo.2023.1107780

    Article  PubMed  Google Scholar 

  10. Qian XH, Liu XL, Zhang B, et al. Investigating the causal association between branched-chain amino acids and Alzheimer’s disease: A bidirectional Mendelian randomized study. Front Nutr. 2023;10:1103303. Published 2023 Mar 31. doi:https://doi.org/10.3389/fnut.2023.1103303

    Article  PubMed  PubMed Central  Google Scholar 

  11. Davey Smith G, Holmes MV, Davies NM, Ebrahim S. Mendel’s laws, Mendelian randomization and causal inference in observational data: substantive and nomenclatural issues. Eur J Epidemiol. 2020;35(2):99–111. doi:https://doi.org/10.1007/s10654-020-00622-7

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017;3:17038. Published 2017 Jun 22. doi:https://doi.org/10.1038/nrdp.2017.38

    Article  PubMed  Google Scholar 

  13. Yarmolinsky J, Wade KH, Richmond RC, et al. Causal Inference in Cancer Epidemiology: What Is the Role of Mendelian Randomization?. Cancer Epidemiol Biomarkers Prev. 2018;27(9):995–1010. doi:https://doi.org/10.1158/1055-9965.EPI-17-1177

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases [published correction appears in Nat Genet. 2018 Aug;50(8):1196]. Nat Genet. 2018;50(5):693–698. doi:https://doi.org/10.1038/s41588-018-0099-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Burgess S, Scott RA, Timpson NJ, Davey Smith G, Thompson SG; EPIC-InterAct Consortium. Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors. Eur J Epidemiol. 2015;30(7):543–552. doi:https://doi.org/10.1007/s10654-015-0011-z

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–525. doi:https://doi.org/10.1093/ije/dyv080

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016;40(4):304–314. doi:https://doi.org/10.1002/gepi.21965

    Article  PubMed  PubMed Central  Google Scholar 

  18. A.C. Nooyens, H.B. Bueno-de-Mesquita, M.P. van Boxtel, B.M. van Gelder, H. Verhagen, and W.M. Verschuren, Fruit and vegetable intake and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study. The British journal of nutrition 106 (2011) 752–61.

    Article  PubMed  CAS  Google Scholar 

  19. Hughes TF, Andel R, Small BJ, et al. Midlife fruit and vegetable consumption and risk of dementia in later life in Swedish twins. Am J Geriatr Psychiatry. 2010;18(5):413–420. doi:https://doi.org/10.1097/JGP.0b013e3181c65250

    Article  PubMed  PubMed Central  Google Scholar 

  20. Choi DY, Lee YJ, Hong JT, Lee HJ. Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer’s disease. Brain Res Bull. 2012;87(2–3):144–153. doi:https://doi.org/10.1016/j.brainresbull.2011.11.014

    Article  PubMed  CAS  Google Scholar 

  21. Rababah TM, Ereifej KI, Howard L. Effect of ascorbic acid and dehydration on concentrations of total phenolics, antioxidant capacity, anthocyanins, and color in fruits. J Agric Food Chem. 2005;53(11):4444–4447. doi:https://doi.org/10.1021/jf0502810

    Article  PubMed  CAS  Google Scholar 

  22. Magiera A, Kołodziejczyk-Czepas J, Skrobacz K, et al. Valorisation of the Inhibitory Potential of Fresh and Dried Fruit Extracts of Prunus spinosa L. towards Carbohydrate Hydrolysing Enzymes, Protein Glycation, Multiple Oxidants and Oxidative Stress-Induced Changes in Human Plasma Constituents. Pharmaceuticals (Basel). 2022;15(10):1300. Published 2022 Oct 21. doi:https://doi.org/10.3390/ph15101300

    Article  PubMed  CAS  Google Scholar 

  23. Langston FMA, Nash GR, Bows JR. The retention and bioavailability of phytochemicals in the manufacturing of baked snacks. Crit Rev Food Sci Nutr. 2023;63(14):2141–2177. doi:https://doi.org/10.1080/10408398.2021.1971944

    Article  PubMed  CAS  Google Scholar 

  24. Moniruzzaman M, Asaduzzaman M, Hossain MS, et al. In vitro antioxidant and cholinesterase inhibitory activities of methanolic fruit extract of Phyllanthus acidus. BMC Complement Altern Med. 2015;15:403. Published 2015 Nov 9. doi:https://doi.org/10.1186/s12906-015-0930-y

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wang HM, Wang LW, Liu XM, Li CL, Xu SP, Farooq AD. Neuroprotective effects of forsythiaside on learning and memory deficits in senescence-accelerated mouse prone (SAMP8) mice. Pharmacol Biochem Behav. 2013;105:134–141. doi:https://doi.org/10.1016/j.pbb.2012.12.016

    Article  PubMed  CAS  Google Scholar 

  26. Flanagan E, Cameron D, Sobhan R, et al. Chronic Consumption of Cranberries (Vaccinium macrocarpon) for 12 Weeks Improves Episodic Memory and Regional Brain Perfusion in Healthy Older Adults: A Randomised, Placebo-Controlled, Parallel-Groups Feasibility Study. Front Nutr. 2022;9:849902. Published 2022 May 19. doi:https://doi.org/10.3389/fnut.2022.849902

    Article  PubMed  PubMed Central  Google Scholar 

  27. Parrott MD, Winocur G, Bazinet RP, Ma DW, Greenwood CE. Whole-food diet worsened cognitive dysfunction in an Alzheimer’s disease mouse model. Neurobiol Aging. 2015;36(1):90–99. doi:https://doi.org/10.1016/j.neurobiolaging.2014.08.013

    Article  PubMed  Google Scholar 

  28. Dafnis I, Mountaki C, Fanarioti E, et al. Temporal Pattern of Neuroinflammation Associated with a Low Glycemic Index Diet in the 5xFAD Mouse Model of Alzheimer’s Disease. Mol Neurobiol. 2022;59(12):7303–7322. doi:https://doi.org/10.1007/s12035-022-03047-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Makhlouf MMM. Histological and ultrastructural study of AflatoxinB1 induced neurotoxicity in Sciatic nerve of adult male Albino rats. Ultrastruct Pathol. 2020;44(1):52–60. doi:https://doi.org/10.1080/01913123.2019.1709933

    Article  PubMed  CAS  Google Scholar 

  30. Burgess S, Thompson SG; CRP CHD Genetics Collaboration. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 2011;40(3):755–764. doi:https://doi.org/10.1093/ije/dyr036

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We appreciate the time and effort given by participants and investigators of the UK Biobank, the MRC-IEU consortium, and FinnGen database. We are grateful for instructions from Prof. Xiong Chen and Prof. Jia-Hao Cai on methodologies and the details of the study design.

Funding

Funding: The study did not receive any funding.

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China

    Wan-Zhe Liao, X.-F. Zhu, Q. Xin, Y.-T. Mo, L.-L. Wang, X.-P. He & Xu-Guang Guo

  2. Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, King Med School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 510000, China

    Wan-Zhe Liao, X.-F. Zhu, Q. Xin, Y.-T. Mo, L.-L. Wang, X.-P. He & Xu-Guang Guo

  3. The Nanshan College of Guangzhou Medical University, Guangzhou, 511436, China

    Wan-Zhe Liao, X.-F. Zhu & Xu-Guang Guo

  4. Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 511436, China

    Q. Xin, Y.-T. Mo, L.-L. Wang & X.-P. He

Authors
  1. Wan-Zhe Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X.-F. Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Q. Xin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y.-T. Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L.-L. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. X.-P. He
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xu-Guang Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Author contribution: LWZ contributed to data enrollment, statistical analysis, study design, manuscript writing, and proofreading, ZXF, XQ, MYT, and WLL contributed to the statistical analysis and composing of the manuscript, HXP contributed to the writing of the manuscript, and GXG contributed to the project design and administration. All authors have granted their approval for the manuscript.

Corresponding authors

Correspondence to Wan-Zhe Liao or Xu-Guang Guo.

Ethics declarations

Ethical approval: No additional ethics approval was needed because all data in the study was previously collected, analyzed, and published.

Declaration of competing interest: The authors declare no conflicts of interest.

Consent for publication: Not applicable.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liao, WZ., Zhu, XF., Xin, Q. et al. Fruit Intake and Alzheimer’s Disease: Results from Mendelian Randomization. J Prev Alzheimers Dis 11, 445–452 (2024). https://doi.org/10.14283/jpad.2024.31

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.14283/jpad.2024.31

Key words

Search

Navigation