Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Relationship among Plasma Homocysteine, Folate, Vitamin $B_{12}$ and Nutrient Intake and Neurocognitive Function in the Elderly

노인의 혈중 호모시스테인, 엽산, 비타민 $B_{12}$ 수준 및 영양소 섭취 상태와 신경인지기능과의 관련성

  • Kim, Hee-Jung (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Hye-Sook (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Ki-Nam (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Ggot-Pin (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Son, Jung-In (Department of Psychiatry, Seoul Asan Medical Center) ;
  • Kim, Seong-Yoon (Department of Psychiatry, Seoul Asan Medical Center) ;
  • Chang, Nam-Soo (Department of Nutritional Science and Food Management, Ewha Womans University)
  • 김희정 (이화여자대학교 식품영양학과) ;
  • 김혜숙 (이화여자대학교 식품영양학과) ;
  • 김기남 (이화여자대학교 식품영양학과) ;
  • 김꽃핀 (이화여자대학교 식품영양학과) ;
  • 손정인 (서울아산병원 정신과) ;
  • 김성윤 (서울아산병원 정신과) ;
  • 장남수 (이화여자대학교 식품영양학과)
  • Received : 2011.09.01
  • Accepted : 2011.10.25
  • Published : 2011.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

This study examined the relationship among plasma homocysteine, folate, and vitamin $B_{12}$ levels and neurocognitive function in 118 community-dwelling elderly subjects (mean age, $75.1{\pm}6.7$ years). The Mini-Mental State Examination (MMSE-KC) was used to screen and assess neurocognitive function in the participants. Dietary intake data including the use of dietary supplements were obtained using the 24-hour recall method by well-trained interviewers. Plasma folate and vitamin $B_{12}$ concentrations were analyzed by radioimmunoassay, and homocysteine was assessed by a high performance liquid chromatography-fluorescence method. The proportions of participants with suboptimal levels of plasma folate (< 3 ng/mL), vitamin $B_{12}$ (< 221 pmol/mL), and homocysteine (> $15{\mu}mol/L$) were 16.1%, 5.9%, and 21.2%, respectively. A multiple regression analysis showed that plasma homocysteine was negatively associated with plasma folate and vitamin $B_{12}$ levels. The MMSE-KC test scores were significantly associated with plasma homocysteine and folate, but not with vitamin $B_{12}$, after adjusting for age, gender, body mass index, living with spouse, education, current smoking, energy intake, and chronic diseases such as hypertension, diabetes, thyroid disease, dyslipidemia, stroke, and cardiovascular disease. A general linear model adjusted for covariates revealed that MMSE-KC test scores increased from the lowest to the highest quartiles of vitamin $B_1$, vitamin $B_2$, vitamin $B_6$, vitamin $B_{12}$, and vitamin C intake (p for trend = 0.012, 0.039, 0.014, 0.046, 0.026, respectively). These results indicate that the problem of folate inadequacy and hyperhomocysteinemia are highly prevalent among community-dwelling elderly people and that dietary intake of the B vitamins and vitamin C is positively associated with cognitive function scores.

Keywords

References

  1. Smith AD, Earles JL. Memory changes in normal aging. In: Blanchard-Fields F, Hess TM, editors. Perspectives on Cogni tive Change in Adulthood and Aging. New York: McGraw-Hill; 1996. p.192-220
  2. Statistics for elderly population. Daejeon: Statistics Korea; 2010
  3. Oh YH. Living and behavioral differentials of the elderly. Seoul: Korea Institute for Health and Social Affairs (KIHASA); 2010
  4. Irizarry MC, Gurol ME, Raju S, Diaz-Arrastia R, Locascio JJ, Tennis M, Hyman BT, Growdon JH, Greenberg SM, Bottiglieri T. Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology 2005; 65 (9): 1402-1408 https://doi.org/10.1212/01.wnl.0000183063.99107.5c
  5. Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, Haughey N, Lee J, Evans M, Mattson MP. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci 2002; 22(5): 1752-1762
  6. Garcia A, Zanibbi K. Homocysteine and cognitive function in elderly people. CMAJ 2004; 171(8): 897-904 https://doi.org/10.1503/cmaj.1031586
  7. Duthie SJ, Whalley LJ, Collins AR, Leaper S, Berger K, Deary IJ. Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr 2002; 75(5): 908-913
  8. Tucker KL, Qiao N, Scott T, Rosenberg I, Spiro A 3rd. High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study. Am J Clin Nutr 2005; 82(3): 627-635
  9. Nelson C, Wengreen HJ, Munger RG, Corcoran CD. Dietary folate, vitamin B-12, vitamin B-6 and incident Alzheimer's disease: the cache county memory, health and aging study. J Nutr Health Aging 2009; 13(10): 899-905 https://doi.org/10.1007/s12603-009-0249-9
  10. Kim JM, Stewart R, Kim SW, Shin IS, Yang SJ, Shin HY, Yoon JS. Changes in folate, vitamin B12 and homocysteine associated with incident dementia. J Neurol Neurosurg Psychiatry 2008; 79 (8): 864-868 https://doi.org/10.1136/jnnp.2007.131482
  11. Koike T, Kuzuya M, Kanda S, Okada K, Izawa S, Enoki H, Iguchi A. Raised homocysteine and low folate and vitamin B-12 concentrations predict cognitive decline in community-dwelling older Japanese adults. Clin Nutr 2008; 27(6): 865-871 https://doi.org/10.1016/j.clnu.2008.08.006
  12. Stewart R, Asonganyi B, Sherwood R. Plasma homocysteine and cognitive impairment in an older British African-Caribbean population. J Am Geriatr Soc 2002; 50(7): 1227-1232 https://doi.org/10.1046/j.1532-5415.2002.50309.x
  13. Kado DM, Karlamangla AS, Huang MH, Troen A, Rowe JW, Selhub J, Seeman TE. Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. Am J Med 2005; 118(2): 161-167 https://doi.org/10.1016/j.amjmed.2004.08.019
  14. Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L. Vitamin B(12) and folate in relation to the development of Alzheimer's disease. Neurology 2001; 56(9): 1188-1194
  15. Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol 2007; 64(1): 86-92 https://doi.org/10.1001/archneur.64.1.86
  16. Morris MC, Evans DA, Bienias JL, Tangney CC, Hebert LE, Scherr PA, Schneider JA. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol 2005; 62(4): 641-645 https://doi.org/10.1001/archneur.62.4.641
  17. Dangour AD, Whitehouse PJ, Rafferty K, Mitchell SA, Smith L, Hawkesworth S, Vellas B. B-vitamins and fatty acids in the prevention and treatment of Alzheimer's disease and dementia: a systematic review. J Alzheimers Dis 2010; 22(1): 205-224
  18. Balk EM, Raman G, Tatsioni A, Chung M, Lau J, Rosenberg IH. Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch Intern Med 2007; 167(1): 21-30 https://doi.org/10.1001/archinte.167.1.21
  19. Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, Verhoef P. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007; 369(9557): 208-216 https://doi.org/10.1016/S0140-6736(07)60109-3
  20. Lee L, Kang SA, Lee HO, Lee BH, Park JS, Kim JH, Jung IK, Park YJ, Lee JE. Relationships between dietary intake and cognitive function level in Korean elderly people. Public Health 2001; 115(2): 133-138
  21. Kim JH, Kang SA, Ahn HS, Jung IK, Lee L. Relationship between cognitive function and dietary patterns in Korean elderly women. Korean J Nutr 1998; 31(9): 1457-1467
  22. Jung K, Lee YA, Kim SY, Chang N. Associations of cognitive function and dietary factors in elderly patients with Alzheimer's disease. Korean J Nutr 2008; 41(8): 718-732
  23. Han C, Jo SA, Kim NH, Jo I, Park MH. Study design and methods of the Ansan Geriatric Study (AGE study). BMC Neurol 2009; 9: 10 https://doi.org/10.1186/1471-2377-9-10
  24. Hoey L, McNulty H, Askin N, Dunne A, Ward M, Pentieva K, Strain J, Molloy AM, Flynn CA, Scott JM. Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults. Am J Clin Nutr 2007; 86(5): 1405-1413
  25. Lee JH, Lee KU, Lee DY, Kim KW, Jhoo JH, Kim JH, Lee KH, Kim SY, Han SH, Woo JI. Development of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K): clinical and neuropsychological assessment batteries. J Gerontol B Psychol Sci Soc Sci 2002; 57(1): P47-P53 https://doi.org/10.1093/geronb/57.1.P47
  26. Serving size of food for food intake research. Seoul: Korea Food Industry Association; 1988
  27. Food values. Seoul: The Korean Nutrition Society; 2009
  28. Kwak CS, Hwang JY, Watanabe F, Park SC. Vitamin B12 contents in some Korean fermented foods and edible seaweeds. Korean J Nutr 2008; 41(5): 439-447
  29. Ravaglia G, Forti P, Maioli F, Muscari A, Sacchetti L, Arnone G, Nativio V, Talerico T, Mariani E. Homocysteine and cognitive function in healthy elderly community dwellers in Italy. Am J Clin Nutr 2003; 77(3): 668-673
  30. McCaddon A, Hudson P, Davies G, Hughes A, Williams JH, Wilkinson C. Homocysteine and cognitive decline in healthy elderly. Dement Geriatr Cogn Disord 2001; 12(5): 309-313 https://doi.org/10.1159/000051275
  31. Kalmijn S, Launer LJ, Lindemans J, Bots ML, Hofman A, Breteler MM. Total homocysteine and cognitive decline in a community-based sample of elderly subjects: the Rotterdam Study. Am J Epidemiol 1999; 150(3): 283-289 https://doi.org/10.1093/oxfordjournals.aje.a010000
  32. Ravaglia G, Forti P, Maioli F, Zanardi V, Dalmonte E, Grossi G, Cucinotta D, Macini P, Caldarera M. Blood homocysteine and vitamin B levels are not associated with cognitive skills in healthy normally ageing subjects. J Nutr Health Aging 2000; 4(4): 218- 222
  33. Religa D, Styczynska M, Peplonska B, Gabryelewicz T, Pfeffer A, Chodakowska M, Luczywek E, Wasiak B, Stepien K, Golebiowski M, Winblad B, Barcikowska M. Homocysteine, apolipoproteine E and methylenetetrahydrofolate reductase in Alzheimer's disease and mild cognitive impairment. Dement Geriatr Cogn Disord 2003; 16(2): 64-70 https://doi.org/10.1159/000070677
  34. Kim J, Park MH, Kim E, Han C, Jo SA, Jo I. Plasma homocysteine is associated with the risk of mild cognitive impairment in an elderly Korean population. J Nutr 2007; 137(9): 2093-2097
  35. Görtz P, Hoinkes A, Fleischer W, Otto F, Schwahn B, Wendel U, Siebler M. Implications for hyperhomocysteinemia: not homocysteine but its oxidized forms strongly inhibit neuronal network activity. J Neurol Sci 2004; 218(1-2): 109-114 https://doi.org/10.1016/j.jns.2003.11.009
  36. Ganji V, Kafai MR. Frequent consumption of milk, yogurt, cold breakfast cereals, peppers, and cruciferous vegetables and intakes of dietary folate and riboflavin but not vitamins B-12 and B-6 are inversely associated with serum total homocysteine concentrations in the US population. Am J Clin Nutr 2004; 80(6): 1500-1507
  37. Brussaard JH, Lowik MR, van den Berg H, Brants HA, Goldbohm RA. Folate intake and status among adults in the Netherlands. Eur J Clin Nutr 1997; 51 Suppl 3: S46-S50
  38. Planells E, Sánchez C, Montellano MA, Mataix J, Llopis J. Vitamins B6 and B12 and folate status in an adult Mediterranean population. Eur J Clin Nutr 2003; 57(6): 777-785 https://doi.org/10.1038/sj.ejcn.1601610
  39. Hatzis CM, Bertsias GK, Linardakis M, Scott JM, Kafatos AG. Dietary and other lifestyle correlates of serum folate concentrations in a healthy adult population in Crete, Greece: a cross-sectional study. Nutr J 2006; 5: 5 https://doi.org/10.1186/1475-2891-5-5
  40. Shim YJ, Paik HY. Reanalysis of 2007 Korean National Health and Nutrition Examination Survey (2007 KNHANES) results by CAN-Pro 3.0 Nutrient Database. Korean J Nutr 2009; 42(6): 577-595 https://doi.org/10.4163/kjn.2009.42.6.577
  41. Salerno-Kennedy R, Cashman KD. Relationship between dementia and nutrition-related factors and disorders: an overview. Int J Vitam Nutr Res 2005; 75(2): 83-95 https://doi.org/10.1024/0300-9831.75.2.83
  42. Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 2003; 26(3): 137-146 https://doi.org/10.1016/S0166-2236(03)00032-8
  43. Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, Bottiglieri T, Jin S, Stokes KT, Thomas RG, Thal LJ; Alzheimer Disease Cooperative Study. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 2008; 300(15): 1774-1783 https://doi.org/10.1001/jama.300.15.1774
  44. Requejo AM, Ortega RM, Robles F, Navia B, Faci M, Aparicio A. Influence of nutrition on cognitive function in a group of elderly, independently living people. Eur J Clin Nutr 2003; 57 Suppl 1: S54-S57
  45. Pepersack T, Garbusinski J, Robberecht J, Beyer I, Willems D, Fuss M. Clinical relevance of thiamine status amongst hospitalized elderly patients. Gerontology 1999; 45(2): 96-101 https://doi.org/10.1159/000022070
  46. Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000; 54(6): 1265-1272 https://doi.org/10.1212/WNL.54.6.1265
  47. Drew KL, Toien O, Rivera PM, Smith MA, Perry G, Rice ME. Role of the antioxidant ascorbate in hibernation and warming from hibernation. Comp Biochem Physiol C Toxicol Pharmacol 2002; 133(4): 483-492 https://doi.org/10.1016/S1532-0456(02)00118-7
  48. Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, Breteler MM. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002; 287(24): 3223- 3229 https://doi.org/10.1001/jama.287.24.3223

Cited by

  1. Change of Quality Characteristics of Commercial and Prepared Kimchi Depending on Fermentation vol.33, pp.2, 2017, https://doi.org/10.9724/kfcs.2017.33.2.162
  2. Total Folate Contents of 15 Edible Plants Consumed in Korea Using Trienzyme Extraction Method vol.43, pp.11, 2014, https://doi.org/10.3746/jkfn.2014.43.11.1796
  3. Folate food source, usual intake, and folate status in Korean adults vol.12, pp.1, 2018, https://doi.org/10.4162/nrp.2018.12.1.47
  4. 남성 성인의 흡연 유무에 따른 건강관심도 및 영양소 섭취 상태에 관한 연구 vol.26, pp.4, 2013, https://doi.org/10.9799/ksfan.2013.26.4.713
  5. Physiological Characteristics and Production of Folic Acid of Lactobacillus plantarum JA71 Isolated from Jeotgal, a Traditional Korean Fermented Seafood vol.34, pp.1, 2014, https://doi.org/10.5851/kosfa.2014.34.1.106
  6. 전라남도 장수지역 및 서울 일부 지역 거주 80대 노인의 맛 선호도, 식품섭취빈도, 영양 섭취 상태 비교 vol.29, pp.1, 2011, https://doi.org/10.9799/ksfan.2016.29.1.115
  7. 노인의 인지기능상태에 따른 식품과 영양소 섭취실태 vol.49, pp.5, 2011, https://doi.org/10.4163/jnh.2016.49.5.313
  8. 한국 노인의 주관적 불안·우울 상태에 따른 식품 및 영양소 섭취 실태 : 2013~ 2015년 국민건강영양조사 자료를 이용하여 vol.52, pp.1, 2011, https://doi.org/10.4163/jnh.2019.52.1.58