Efecto de la suplementación con vitaminas del complejo B sobre el declive cognitivo en pacientes con enfermedad de Alzheimer. Revisión sistemática y metanálisis

Autores/as

  • Gustavo Alfonso Díaz Muñoz Universidad El Bosque. Facultad de Medicina
  • Luis García Rairán
  • Valentina Corredor
  • María Angélica Cruz
  • Diana Useche
  • Fernanda Wilches
  • Laura Wilches

DOI:

https://doi.org/10.14306/renhyd.27.1.1826

Palabras clave:

Enfermedad de Alzheimer, declive cognitivo, vitaminas del complejo B, metanálisis

Resumen

Introducción: el declive cognitivo es un marcador de la aparición y avance de la enfermedad de Alzheimer (EA). Actualmente, la modificación de factores de riesgo, como la nutrición, son promisorios para el tratamiento de la EA. El objetivo fue Identificar el efecto de la suplementación de vitaminas del complejo B sobre el declive cognitivo en pacientes con daño cognitivo o EA.

Materiales y métodos: Revisión sistemática y metaanálisis de la literatura en cinco buscadores (PROSPERO CRD42021247743). Se incluyeron experimentos controlados, en adultos de 60 o más años, con medición del estado cognitivo (ADAS-Cog, Clinical dementia ratin-CDR y/o Mini Mental State Examination-MMSE) y uso de suplementos de vitaminas del complejo B de manera individual o combinada con otras vitaminas o fármacos. La evaluación de la calidad se hizo con la herramienta RoB-2. La selección, extracción y evaluación se hizo por tres investigadores de manera independiente. El metaanálisis empleo la diferencia media y modelos de efectos aleatorios.

Resultados: la búsqueda arrojo 247 referencias y finalmente se incluyeron 12 para el metaanálisis. No se encontraron sesgos de publicación. La calidad de los estudios es adecuada. El suplemento de vitamina B no mostró efecto sobre el declive cognitivo medido por ADAS-Cog (DM 0.01 IC95% -0.7 a 0.72), CDR (DM –0.06 IC95% -0.48 a 0.36) y MMSE (DM 0.3 IC95% -0.01 a 0.61).

Conclusiones: el declive cognitivo es invariable ante la suplementación de vitaminas del complejo B en adultos con daño cognitivo o Enfermedad de Alzheimer. Futuras investigaciones deben enfocarse hacia estrategias multi intervención.

Palabras claves: Enfermedad de Alzheimer; declive cognitivo; vitaminas del complejo B; metaanálisis.

Financiación: Los autores/as declaran que no ha existido financiación para realizar este estudio.

Registro: PROSPERO CRD42021247743

Biografía del autor/a

Gustavo Alfonso Díaz Muñoz, Universidad El Bosque. Facultad de Medicina

Docente e investigador.

Grupo de investigación en nutrición, genética y metabolismo

Citas

(1) 2021 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia. 2021;17(3):327-406, doi: 10.1002/ALZ.12328.

(2) Grabher BJ Effects of Alzheimer disease on patients and their family. J Nucl Med Technol. 2018;46(4):335-40, doi: 10.2967/jnmt.118.218057.

(3) Van Oostveen WM, de Lange ECM Imaging techniques in alzheimer’s disease: A review of applications in early diagnosis and longitudinal monitoring. Int J Mol Sci. 2021;22(4):1-34, doi: 10.3390/ijms22042110.

(4) Zetterberg H, Bendlin BB Biomarkers for Alzheimer’s disease – preparing for a new era of disease-modifying therapies. Mol Psychiatry. 2021;26(1):296, doi: 10.1038/S41380-020-0721-9.

(5) Ashrafian H, Zadeh EH, Khan RH Review on Alzheimer’s disease: Inhibition of amyloid beta and tau tangle formation. Int J Biol Macromol. 2021;167:382-94, doi: 10.1016/j.ijbiomac.2020.11.192.

(6) Malafaia D, Albuquerque HMT, Silva AMS Amyloid-β and tau aggregation dual-inhibitors: A synthetic and structure-activity relationship focused review. Eur J Med Chem. 2021;214:113209, doi: 10.1016/j.ejmech.2021.113209.

(7) Stoiljkovic M, Horvath TL, Hajós M Therapy for Alzheimer’s disease: Missing targets and functional markers? Ageing Res Rev. 2021;68, doi: 10.1016/J.ARR.2021.101318.

(8) Breijyeh Z, Karaman R, Muñoz-Torrero D, Dembinski R Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules 2020, Vol 25, Page 5789. 2020;25(24):5789, doi: 10.3390/molecules25245789.

(9) Srivastava S, Ahmad R, Khare SK Alzheimer’s disease and its treatment by different approaches: A review. Eur J Med Chem. 2021:113320, doi: 10.1016/j.ejmech.2021.113320.

(10) Qu Y, Ma YH, Huang YY, Ou YN, Shen XN, Chen SD, et al. Blood biomarkers for the diagnosis of amnestic mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2021:479-86, doi: 10.1016/j.neubiorev.2021.07.007.

(11) Lu L, Zheng X, Wang S, Tang C, Zhang Y, Yao G, et al. Anti-Aβ agents for mild to moderate Alzheimer’s disease: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2020;91(12):1316-24, doi: 10.1136/JNNP-2020-323497.

(12) Wang Q, Zhao J, Chang H, Liu X, Zhu R Homocysteine and Folic Acid: Risk Factors for Alzheimer’s Disease—An Updated Meta-Analysis. Front Aging Neurosci. 2021;13, doi: 10.3389/fnagi.2021.665114.

(13) Smith AD, Refsum H, Bottiglieri T, Fenech M, Hooshmand B, McCaddon A, et al. Homocysteine and Dementia: An International Consensus Statement. Journal of Alzheimer’s Disease. 2018;62:561-70, doi: 10.3233/JAD-171042.

(14) Swarbrick S, Wragg N, Ghosh S, Stolzing A Systematic Review of miRNA as Biomarkers in Alzheimer’s Disease. Mol Neurobiol. 2019;56(9):6156-67, doi: 10.1007/S12035-019-1500-Y.

(15) Sun J, Wen S, Zhou J, Ding S Association between malnutrition and hyperhomocysteine in Alzheimer’s disease patients and diet intervention of betaine. J Clin Lab Anal. 2017;31(5), doi: 10.1002/jcla.22090.

(16) Sade Yazdi D, Laor Bar-Yosef D, Adsi H, Kreiser T, Sigal S, Bera S, et al. Homocysteine fibrillar assemblies display cross-talk with Alzheimer’s disease β-amyloid polypeptide. Proceedings of the National Academy of Sciences. 2021;118(24):e2017575118, doi: 10.1073/pnas.2017575118.

(17) Ma F, Lv X, Du Y, Chen H, Liu S, Zhao J, et al. Association of Leukocyte Telomere Length with Mild Cognitive Impairment and Alzheimer’s Disease: Role of Folate and Homocysteine. Dement Geriatr Cogn Disord. 2019;48(1-2):56-67, doi: 10.1159/000501958.

(18) Nieraad H, de Bruin N, Arne O, Hofmann MCJ, Gurke R, Schmidt D, et al. Effects of Alzheimer-like pathology on homocysteine and homocysteic acid levels-an exploratory in vivo kinetic study. Int J Mol Sci. 2021;22(2):1-18, doi: 10.3390/ijms22020927.

(19) Li S, Guo Y, Men J, Fu H, Xu T The preventive efficacy of vitamin B supplements on the cognitive decline of elderly adults: a systematic review and meta-analysis. BMC Geriatr. 2021;21(1):1-14, doi: 10.1186/S12877-021-02253-3/FIGURES/7.

(20) Xu W, Tan L, Wang H-F, Jiang T, Tan M-S, Tan L, et al. Meta-analysis of modifiable risk factors for Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2015;86(12):1299-306, doi: 10.1136/jnnp-2015-310548.

(21) McCleery J, Abraham RP, Denton DA, Rutjes AW, Chong L-Y, Al-Assaf AS, et al. Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment. Cochrane Database Syst Rev. 2018;11(11):CD011905, doi: 10.1002/14651858.CD011905.pub2.

(22) Chen H, Liu S, Ge B, Zhou D, Li M, Li W, et al. Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer’s Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial. Journal of Prevention of Alzheimer’s Disease. 2021, doi: 10.14283/jpad.2021.22.

(23) Gibson GE, Luchsinger JA, Cirio R, Chen H, Franchino-Elder J, Hirsch JA, et al. Benfotiamine and Cognitive Decline in Alzheimer’s Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial. J Alzheimers Dis. 2020;78(3):989-1010, doi: 10.3233/JAD-200896.

(24) Chen H, Liu S, Ji L, Wu T, Ji Y, Zhou Y, et al. Folic Acid Supplementation Mitigates Alzheimer’s Disease by Reducing Inflammation: A Randomized Controlled Trial. Mediators Inflamm. 2016;2016:5912146, doi: 10.1155/2016/5912146.

(25) Remington R, Bechtel C, Larsen D, Samar A, Doshanjh L, Fishman P, et al. A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer’s Disease. J Alzheimers Dis. 2015;45(2):395-405, doi: 10.3233/JAD-142499.

(26) De Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012;27(6):592-600, doi: 10.1002/GPS.2758.

(27) Ford AH, Flicker L, Alfonso H, Thomas J, Clarnette R, Martins R, et al. Vitamins B12, B6, and folic acid for cognition in older men. Neurology. 2010;75(17):1540-7, doi: 10.1212/WNL.0b013e3181f962c4.

(28) Scheltens P, Kamphuis PJGH, Verhey FRJ, Olde Rikkert MGM, Wurtman RJ, Wilkinson D, et al. Efficacy of a medical food in mild Alzheimer’s disease: A randomized, controlled trial. Alzheimer’s and Dementia. 2010;6(1), doi: 10.1016/j.jalz.2009.10.003.

(29) van Dyck CH, Lyness JM, Rohrbaugh RM, Siegal AP Cognitive and psychiatric effects of vitamin B12 replacement in dementia with low serum B12 levels: a nursing home study. Int Psychogeriatr. 2009;21(1):138-47.

(30) Manders M, De Groot LCPGM, Hoefnagels WHL, Dhonukshe-Rutten RAM, Wouters-Wesseling W, Mulders AJMJ, et al. The effect of a nutrient dense drink on mental and physical function in institutionalized elderly people. Journal of Nutrition, Health and Aging. 2009;13(9):760-7, doi: 10.1007/s12603-009-0211-x.

(31) Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300(15):1774-83, doi: 10.1001/jama.300.15.1774.

(32) Connelly PJ, Prentice NP, Cousland G, Bonham J A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer’s disease. Int J Geriatr Psychiatry. 2008;23(2):155-60, doi: 10.1002/gps.1856.

(33) Sun Y, Lu CJ, Chien KL, Chen ST, Chen RC Efficacy of Multivitamin Supplementation Containing Vitamins B6 and B12 and Folic Acid as Adjunctive Treatment with a Cholinesterase Inhibitor in Alzheimer’s Disease: A 26-Week, Randomized, Double-Blind, Placebo-Controlled Study in Taiwanese Patients. Clin Ther. 2007;29(10):2204-14, doi: 10.1016/j.clinthera.2007.10.012.

(34) Zhang C, Luo J, Yuan C, Ding D Vitamin B12, B6, or Folate and Cognitive Function in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis. Journal of Alzheimer’s Disease. 2020:781-94, doi: 10.3233/JAD-200534.

(35) Bai D, Fan J, Li M, Dong C, Gao Y, Fu M, et al. Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial. J Alzheimers Dis. 2021;81(1):155-67, doi: 10.3233/JAD-200997.

(36) Rainey-Smith SR, Gu Y, Gardener SL, Doecke JD, Villemagne VL, Brown BM, et al. Mediterranean diet adherence and rate of cerebral Aβ-amyloid accumulation: Data from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing. Transl Psychiatry. 2018;8(1):238, doi: 10.1038/s41398-018-0293-5.

(37) Díaz G, Lengele L, Sourdet S, Soriano G, de Souto Barreto P Nutrients and amyloid β status in the brain: a narrative review. Ageing Res Rev. 2022;81:101728, doi: https://doi.org/10.1016/j.arr.2022.101728.

(38) Li M-M, Yu J-T, Wang H-F, Jiang T, Wang J, Meng X-F, et al. Efficacy of vitamins B supplementation on mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis. Curr Alzheimer Res. 2014;11(9):844-52, doi: 10.2174/1567205011666141001114140.

(39) Munoz Fernandez SS, Ivanauskas T, Lima Ribeiro SM Nutritional Strategies in the Management of Alzheimer Disease: Systematic Review With Network Meta-Analysis. J Am Med Dir Assoc. 2017;18(10), doi: 10.1016/j.jamda.2017.06.015.

(40) Wang Z, Zhu W, Xing Y, Jia J, Tang Y B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev. 2022;80(4):931-49, doi: 10.1093/nutrit/nuab057.

(41) Ford AH, Almeida OP Effect of Vitamin B Supplementation on Cognitive Function in the Elderly: A Systematic Review and Meta-Analysis. Drugs Aging. 2019;36(5):419-34, doi: 10.1007/s40266-019-00649-w.

(42) Liu KY, Schneider LS, Howard R The need to show minimum clinically important differences in Alzheimer’s disease trials. Lancet Psychiatry. 2021;8(11):1013-6, doi: 10.1016/S2215-0366(21)00197-8.

(43) McGrattan A, van Aller C, Narytnyk A, Reidpath D, Keage H, Mohan D, et al. Nutritional interventions for the prevention of cognitive impairment and dementia in developing economies in East-Asia: a systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2022;62(7):1838-55, doi: 10.1080/10408398.2020.1848785.

(44) Li Y, Xiong C, Aschenbrenner AJ, Chang C-H, Weiner MW, Nosheny RL, et al. Item response theory analysis of the Clinical Dementia Rating. Alzheimers Dement. 2021;17(3):534-42, doi: 10.1002/alz.12210.

(45) Arevalo-Rodriguez I, Smailagic N, Roqué-Figuls M, Ciapponi A, Sanchez-Perez E, Giannakou A, et al. Mini-Mental State Examination (MMSE) for the early detection of dementia in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2021;7(7):CD010783, doi: 10.1002/14651858.CD010783.pub3.

(46) Wessels AM, Dowsett SA, Sims JR Detecting Treatment Group Differences in Alzheimer’s Disease Clinical Trials: A Comparison of Alzheimer’s Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) and the Clinical Dementia Rating - Sum of Boxes (CDR-SB). J Prev Alzheimers Dis. 2018;5(1):15-20, doi: 10.14283/jpad.2018.2.

(47) Jiang Y, Yang H, Zhao J, Wu Y, Zhou X, Cheng Z Reliability and concurrent validity of Alzheimer’s disease assessment scale - Cognitive subscale, Chinese version (ADAS-Cog-C) among Chinese community-dwelling older people population. Clin Neuropsychol. 2020;34(sup1):43-53, doi: 10.1080/13854046.2020.1750704.

(48) Kwok T, Lee J, Ma RC, Wong SY, Kung K, Lam A, et al. A randomized placebo controlled trial of vitamin B(12) supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B(12). Clin Nutr. 2017;36(6):1509-15, doi: 10.1016/j.clnu.2016.10.018.

(49) Szczechowiak K, Diniz BS, Leszek J Diet and Alzheimer’s dementia – Nutritional approach to modulate inflammation. Pharmacol Biochem Behav. 2019, doi: 10.1016/j.pbb.2019.172743.

(50) Calfio C, Gonzalez A, Singh SK, Rojo LE, MacCioni RB The Emerging Role of Nutraceuticals and Phytochemicals in the Prevention and Treatment of Alzheimer’s Disease. Journal of Alzheimer’s Disease. 2020;77(1):33-51, doi: 10.3233/JAD-200443.

(51) Jin-Tai Y, Xu W, Chen-Chen T, Andrieu S, Suckling J, Evangelou E, et al. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020;91(11):1201-9, doi: http://dx.doi.org/10.1136/jnnp-2019-321913.

(52) Serrano-Pozo A, Growdon JH Is Alzheimer’s Disease Risk Modifiable? JOURNAL OF ALZHEIMERS DISEASE. 2019;67(3):795-819, doi: 10.3233/JAD181028.

(53) Lauer AA, Grimm HS, Apel B, Golobrodska N, Kruse L, Ratanski E, et al. Mechanistic Link between Vitamin B12 and Alzheimer’s Disease. Biomolecules. 2022;12(1), doi: 10.3390/BIOM12010129.

(54) Solfrizzi V, Agosti P, Lozupone M, Custodero C, Schilardi A, Valiani V, et al. Nutritional interventions and cognitive-related outcomes in patients with late-life cognitive disorders: A systematic review. Neurosci Biobehav Rev. 2018;95:480-98, doi: 10.1016/j.neubiorev.2018.10.022.

Archivos adicionales

Publicado

2023-02-03

Cómo citar

Díaz Muñoz, G. A., García Rairán, L., Corredor, V., Cruz, M. A., Useche , D., Wilches, F., & Wilches , L. (2023). Efecto de la suplementación con vitaminas del complejo B sobre el declive cognitivo en pacientes con enfermedad de Alzheimer. Revisión sistemática y metanálisis. Revista Española De Nutrición Humana Y Dietética, 27(1), 72–83. https://doi.org/10.14306/renhyd.27.1.1826