Food and Nutrition for Older Adults

FNOA: Antioxidants (2011-2012)

• Assessment
  What is the relationship between antioxidants and cognition in older adults with diagnosed cognitive impairment or Alzheimer's Disease?

  • Conclusion

    Compared to healthy older adults, intakes of all nutrients may be lower in older adults with diagnosed cognitive impairment or Alzheimer's Disease, however it is unclear whether low levels of nutrients precede or are the consequence of cognitive impairment. In addition, antioxidant intake at supplemental levels demonstrated no difference in the delay of cognitive decline. Additional research is needed in this area.
     

  • Grade: II
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the relationship between antioxidants and cognition in older adults with diagnosed cognitive impairment or Alzheimer's Disease?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Baldeiras I, Santana I, Proenca MT, Garrucho MH, Pascoal R, Rodrigues A, Duro D, Oliveira CR.  Peripheral oxidative damage in mild cognitive impairment and mild Alzheimer's disease. J Alzheimers Dis. 2008; 15 (1): 117-128.
      • Dong J, Robertson JD, Markesbery WR, Lovell MA. Serum zinc in the progression of Alzheimer's disease. J Alzheimers Dis. 2008;15 (3): 443-450.
      • Dunn JE, Weintraub S, Stoddard AM, Banks S. Serum alpha-tocopherol, concurrent and past vitamin E intake, and mild cognitive impairment. Neurology. 2007 Feb 27; 68(9): 670-676. 
      • Fillenbaum GG, Kuchibhatla MN, Hanlon JT, Artz MB, Pieper CF, Schmader KE, Dysken MW, Gray SL. Dementia and Alzheimer's disease in community-dwelling elders taking vitamin C and/or vitamin E. Ann Pharmacother 2005; 39: 2,009-2,014.
      • Gerhardsson L, Lundh T, Minthon L, Londos E. Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer's Disease. Dement Geriatr Cogn Disord. 2008; 25: 508-515.
      • Gray SL, Anderson ML, Crane PK, Breitner JC, McCormick W, Bowen JD, Teri L, Larson E. Antioxidant vitamin supplement use and risk of dementia or Alzheimer's disease in older adults. J Am Geriatr Soc. 2008 Feb; 56(2): 291-295.
      • Isaac MG, Quinn R, Tabet N. Vitamin E for Alzheimer's disease and mild cognitive impairment.  Cochrane Database Syst Rev 2008; (3): CD002854.
      • Kessler H, Bayer TA, Bach D, Schneider-Axmann T, Supprian T, Herrmann W, Haber M, Multhaup G, Falkai P, Pajonk FG. Intake of copper has no effect on cognition in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial. J Neural Transm. 2008; 115 (8): 1,181-1,187.
      • Kessler H, Pajonk FG, Meisser P, Schneider-Axmann T, Hoffmann KH, Supprian T, Herrmann W, Obeid R, Multhaup G, Falkai P, Bayer TA. Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and ceruloplasmin in patients with Alzheimer's disease. J Neural Transm 2006; 113 (11): 1,763-1,769.
      • Shatenstein B, Kergoat MJ, Reid I. Poor nutrient intakes during one-year follow-up with community-dwelling older adults with early-stage Alzheimer dementia compared to cognitively intact matched controls. J Am Diet Assoc. 2007; 107(12): 2,091-2,099.
      • Squitti R, Bressi F, Pasqualetti P, Bonomini C, Ghidoni R, Binetti G, Cassetta E, Moffa F, Ventriglia M, Vernieri F, Rossini PM. Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease. Neurology, 2009; 72 (1): 50-55. 
  • Search Plan and Results: FNOA: Antioxidants and Cognition 2009
     
  What is the relationship between antioxidants and cognition in older adults without cognitive impairment?

  • Conclusion

    While studies on healthy older adults consuming recommended levels of antioxidants generally reported no association with impaired cognitive function, studies regarding antioxidant intakes below recommended levels reported an association with cognitive decline. Research on antioxidant intakes at supplemental levels are inconclusive; conflicting results may be due to genetic factors and prior nutrient deficiencies. Further research is needed in this area.
    

  • Grade: II
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the relationship between antioxidants and cognition in older adults without cognitive impairment?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Akbaraly NT, Faure H, Gourlet V, Favier A, Berr C. Plasma carotenoid levels and cognitive performance in an elderly population: Results of the EVA study. J Gerontol A Biol Sci Med Sci. 2007 Mar; 62(3): 308-316. 
      • Akbaraly TN, Hininger-Favier I, Carriere I, Arnaud J, Gourlet V, Roussel AM, Berr C. Plasma selenium over time and cognitive decline in the elderly. Epidemiology. 2007; 18(1): 52-58.
      • Chin AV, Robinson DJ, O'Connell H, Hamilton F, Bruce I, Coen R, Walsh B, Coakley D, Molloy A, Scott J, Lawlor BA, Cunningham CJ. Vascular biomarkers of cognitive performance in a community-based elderly population: The Dublin Healthy Aging study. Aging. 2008 Sep; 37(5): 559-564.  
      • Crews WD Jr, Harrison DW, Wright JW. A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health:  Clinical findings from a sample of healthy, cognitively intact older adults. Am J Clin Nutr. 2008; 87(4): 872-880.
      • Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB. Fruit and vegetable juices and Alzheimer's disease: The Kame Project. Am J Med. 2006 Sep; 119 (9): 751-759.
      • Fotuhi M, Zandi PP, Hayden KM, Khachaturian AS, Szekely CA, Wengreen H, Munger RG, Norton MC, Tschanz JT, Lyketsos CG, Breitner JCS, Welsh-Bohmer KA. Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with NSAIDs: The Cache County Study. Alzheimers Dement. 2008; 4 (3): 223-227.
      • Fournier LR, Ryan-Borchers TA, Robison LM, Wiediger M, Park J-S, Chew BP, McGuire MK, Sclar DA, Skaer TL, Beerman KA. The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women. J Nutr Health Aging 2007; 11 (2): 155-164.
      • Gao S, Jin Y, Hall KS, Liang C, Unverzagt FW, Ji R, Murrell JR, Cao J, Shen J, Ma F, Matesan J, Ying B, Cheng Y, Bian J, Li P, Hendrie HC. Selenium level and cognitive function in rural elderly chinese. Am J Epidemiol. 2007 Apr 15; 165 (8): 955-965. Epub 2007 Jan 31.
      • Gao S, Jin Y, Unverzagt FW, Ma F, Hall KS, Murrell JR, Cheng Y, Shen J, Ying B, Ji R, Matesan J, Liang C, Hendrie HC. Trace element levels and cognitive function in rural elderly chinese. J Gerontol A Biol Sci Med Sci. 2008 Jun; 63 (6): 635-641.
      • Gleason CE, Carlsson CM, Barnet JH, Meade SA, Setchell KDR, Atwood CS, Johnson SC, Ries ML, Asthana S. A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women. Age and Aging 2009; 38: 86-93.
      • Grodstein F, Kang JH, Glynn RJ, Cook NR, Gaziano M. A randomized trial of beta carotene supplementation and cognitive function in men: The Physicians' Health Study II. Arch Intern Med. 2007; 167 (20): 2,184-2,190.
      • Ho SC, Chan AS, Ho YP, So EKF, Sham A, Zee B, Woo JLF. Effects of soy isoflavone supplementation on cognitive function in Chinese postmenopausal women: A double-blind, randomized, controlled trial. Menopause. 2007 May-Jun; 14(3 Pt 1): 489-499.
      • Hogervorst E, Sadjimim T, Yesufu A, Kreager P, Rahardjo TB. High tofu intake is associated with worse memory in elderly Indonesian men and women. Dement Geriatr Cogn Disord. 2008; 26(1): 50-57. 
      • Hu P, Bretsky P, Crimmins EM, Guralnik JM, Reuben DB, Seeman TE. Association between serum beta-carotene levels and decline of cognitive function in high-functioning older persons with or without apolipoprotein E4 alleles: MacArthur studies of successful aging. J Gerontol A Biol Sci. 2006 Jan; 61(6): 616-620.   
      • Johnson EJ, McDonald K, Caldarella SM, Chung HY, Troen AM, Snodderly DM.  Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women.   Nutr Neurosci. 2008 Apr;11(2):75-83.
      • Kang JH, Cook N, Manson J, Buring JE, Grodstein F. A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med. 2006; 166(22): 2,462-2,468.
      • Kang JH, Grodstein F. Plasma carotenoids and tocopherols and cognitive function: A prospective study. Neurobiol Aging. 2008; 29(9): 1,394-1,403.
      • Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, van der Schouw YT. Dietary phytoestrogen intake and cognitive function in older women. J Gerontol A Biol Sci Med Sci. 2007; 62(5): 556-562.
      • Lam PK, Kritz-Silverstein D, Barrett-Connor E, Milne D, Nielsen F, Gamst A, Morton D, Wingard D. Plasma trace elements and cognitive function in older men and women: The Rancho Bernardo study. J Nutr Health Aging 2008; 12 (1): 22-27. 
      • Lee Y, Kim J, Back JH. The influence of multiple lifestyle behaviors on cognitive function in older persons living in the community. Prev Med 2009; 48 (1): 86-90.
      • Letenneur L, Proust-Lima C, Le Gouge A, Dartiques JF, Barberger-Gateau P. Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol 2007; 165 (12): 1,364-1,371.
      • Marcellini F, Giuli C, Papa R, Gagliardi C, Dedoussis H, Herbein G, Fulop T, Monti D, Rink L, Jajte J, Mocchegiani E. Zinc status, psychological and nutritional assessment in old people recruited in five European countries: Zincage study. Biogerontology 2006; 7 (5-6): 339-345.
      • Maylor EA, Simpson EEA, Secker DL, Meunier N, Andriollo-Sanchez M, Polito A, Stewart-Knox B, McConville C, O'Connor JM, Coudray C. Effects of zinc supplementation on cognitive function in healthy middle-aged and older adults: The ZENITH study. Br J Nutr.  2006 Oct; 96(4): 752-760. 
      • 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 and over: A randomized controlled trial. Nutr J. 2007; 6: 10. 
      • Morris MC, Evans DA, Tangney CC, Bienias JL, Schneider JA, Wilson RS, Scherr PA. Dietary copper and high saturated and trans fat intakes associated with cognitive decline. Arch Neurol. 2006; 63(8): 1,085-1,088.
      • Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Associations of vegetable and fruit consumption with age-related cognitive change. Neurology. 2006; 67(8): 1,370-1,376.
      • Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderly. Am J Epidemiol. 2006; 164(9): 898-906.
      • Nurk E, Refsum H, Drevon CA, Tell GS, Nygaard HA, Engedal K, Smith AD. Intake of flavonoid-rich wine, tea and chocolate by elderly men and women is associated with better cognitive test performance. J Nutr 2009; 139 (1): 120-127.
      • Pipingas A, Silberstein RB, Vitetta L, Rooy CV, Harris EV, Young JM, Frampton CM, Sali A, Nastasi J. Improved cognitive performance after dietary supplementation with a Pinus radiata bark extract formulation. Phytother Res. 2008; 22(9): 1168-1,174. 
      • Rahman A, Sawyer Baker P, Allman RM, Zamrini E. Dietary factors and cognitive impairment in community-dwelling elderly. J Nutr Health Aging 2007;11 (1): 49-54.
      • Ravaglia G, Forti P, Lucicesare A, Pisacane N, Rietti E, Mangialasche F, Cecchetti R, Patterson C, Mecocci P. Plasma tocopherols and risk of cognitive impairment in an elderly Italian cohort. Am J Clin Nutr 2008; 87 (5): 1,306-1,313.
      • Ryan J, Croft K, Mori T, Wesnes K, Spong J, Downey L, Kure C, Lloyd J, Stough C. An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population. J Psychopharmacol 2008; 22 (5): 553-562.
      • Samieri C, Jutand MA, Feart C, Capuron L, Letenneur L, Barberger-Gateau P.  Dietary patterns derived by hybrid clustering method in older people: Association with cognition, mood and self-rated health. J Am Diet Assoc 2008; 108 (9): 1,461-1,471.
      • Sato R, Helzlsouer KJ, Comstock GW, Hoffman SC, Norkus EP, Fried LP. A cross-sectional study of vitamin C and cognitive function in older adults: The differential effects of gender. J Nutr Health Aging 2006; 10 (1): 37-44.
      • Simpson EE, Maylor EA, Rae G, Meunier N, Andriollo-Sanchez M, Catasta G, McConville C, Ferry M, Polito A, Stewart-Knox BJ, Secker DL, Coudray C. Cognitive function in healthy older European adults: The ZENITH study. Eur J Clin Nutr 2005; 59 Suppl 2: S26-S30.
      • Wengreen HJ, Munger RG, Corcoran CD, Zandi P, Hayden KM, Fotuhi M, Skoog I, Norton MC, Tschanz J, Breitner JC, Welsh-Bohmer KA. Antioxidant intake and cognitive function of elderly men and women: The Cache County Study. J Nutr Health Aging 2007; 11 (3): 230-237.
      • Woo J, Lynn H, Lau WY, Leung J, Lau E, Wong SY, Kwok T. Nutrient intake and psychological health in an elderly Chinese population. Int J Geriatr Psychiatry 2006; 21 (11): 1,036-1,043.
  • Search Plan and Results: FNOA: Antioxidants and Cognition 2009
     
  What is the relationship between antioxidants and progression of age-related macular degeneration in older adults?

  • Conclusion

    Studies have found a beneficial effect of beta-carotene, vitamin C, vitamin E, lutein, zeaxanthin, zinc and copper from diet or supplementation on delaying progression of advanced age-related macular degeneration. However, other studies have reported inconclusive findings. Further research is needed, given the risks of over supplementation.

  • Grade: II
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the relationship between antioxidants and progression of age-related macular degeneration in older adults?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol. 2007 Sep; 125 (9): 1,225-1,232.
      • Cangemi FE. TOZAL study: An open case control study of an oral antioxidant and omega-3 supplement for dry AMD. BMC Ophthalmology 2007, 7: 3.
      • Evans JR. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev 2006; (2): CD000254.
      • Klein ML, Francis PJ, Rosner B, Reynolds R, Hamon SC, Schultz DW, Ott J, Seddon JM.   CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration. Ophthalmology. 2008 Jun; 115 (6): 1,019-1,025. 
      • Montgomery MP, Kamel F, Pericak-Vance MA, Haines JL, Postel EA, Agarwal A, Richards M, Scott WK, Schmidt S. Overall diet quality and age-related macular degeneration. Ophthalmic Epidemiol 2010; 17 (1): 58-65.
      • Newsome DA. A randomized, prospective, placebo-controlled clinical trial of a novel zinc-monocysteine compound in age-related macular degeneration. Curr Eye Res. 2008 Jul; 33 (7): 591-598. 
      • Obana A, Hiramitsu T, Gohto Y, Ohira A, Mizuno S, Hirano T, Bernstein PS, Fujii H, Iseki K, Tanito M, Hotta Y.  Macular carotenoid levels of normal subjects and age-related maculopathy patients in a Japanese population. Ophthalmology. 2008 Jan; 115 (1): 147-157.
      • Owsley C, McGwin G, Jackson GR, Heimburger DC, Piyathilake CJ, Klein R, White MF, Kallies K. Effect of short-term, high-dose retinol on dark adaptation in aging and early age-related maculopathy. Invest Ophthalmol Vis Sci. 2006 Apr; 47 (4): 1,310-1,318. 
      • Parisi V, Tedeschi M, Gallinaro G, Varano M, Saviano S, Piermarocchi S, CARMIS Study Group. Carotenoids and antioxidants in age-related maculopathy Italian study: Multifocal electroretinogram modifications after one year.  Ophthalmology. 2008 Feb; 115(2): 324-333.e2. 
      • Richer S, Devenport J, Lang JC. LAST II: Differential temporal responses of macular pigment optical density in patients with atrophic age-related macular degeneration to dietary supplementation with xanthophylls. Optometry.  2007 May; 78(5): 213-219.
      • Robman L, Vu H, Hodge A, Tikellis G, Dimitrov P, McCarty C, Guymer R. Dietary lutein, zeaxanthin, and fats and the progression of age-related macular degeneration. Can J Opththalmol 2007; 42: 720-726.
      • Rosenthal JM, Kim J, de Monastario F, Thompson DJS, Bone RA, Landrum JT, de Moura FF, Khachik F, Chen H, Schleicher RL, Ferris FL, Chew EY. Dose-ranging study of lutein supplementation in persons aged 60 years or older. Invest Opthalmol Vis Sci. 2006; 47: 5,227-5,233.
  • Search Plan and Results: FNOA: Antioxidants and Macular Degeneration 2011
     
  What is the relationship between antioxidants and prevention of age-related macular degeneration in older adults?

  • Conclusion

    Regarding the development of age-related macular degeneration, findings from studies of antioxidant intake below or above recommended dietary allowance (RDA) levels are inconclusive. Further research is needed, given the risks of over-supplementation.

  • Grade: II
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the relationship between antioxidants and prevention of age-related macular degeneration in older adults?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Chiu CJ, Milton RC, Klein R, Gensler G, Taylor A. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study. Ophthalmology, 2009; 116: 939-946.
      • Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: The Women's Antioxidant and Folic Acid Cardiovascular Study.Arch Intern Med. 2009 Feb 23; 169(4): 335-341.
      • Christen WG, Glynn RJ, Chew EY, Buring JE. Vitamin E and age-related macular degeneration in a randomized trial of women. Ophthalmology, 2010; 117: 1,163-1,168.

      • Christen WG, Manson JE, Glynn RJ, Gaziano JM, Chew EY, Buring JE, Hennekens CH. Beta-carotene and age-related maculopathy in a randomized trial of US physicians. Arch Ophthalmol. 2007 Mar; 125 (3): 333-339.  
        

      • Erie JC, Good JA, Butz JA, Pulido JS. Reduced zinc and copper in the retinal pigment epithelium and choroid in age-related macular degeneration. Am J Ophthalmol. 2009 Feb; 147 (2): 276-282.e1.
      • Evans JR, Henshaw KS.  Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database of Systematic Reviews 2008; (1): CD000253.
      • Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C, Chakravarthy U, deJong PTVM, Rahu M, Seland J, Soubrane G, Tomazzoli L, Topouzis F, Vingerling JR, Vioque J. Sunlight exposure, antioxidants and age-related macular degeneration. Arch Opthalmol. 2008; 125(10): 1,396-1,403.
      • Klein BEK, Knudtson MD, Lee KE, Reinke JO, Danforth LG, Wealti AM, Moore E, Klein R. Supplements and age-related eye conditions: The Beaver Dam Eye Study. Ophthalmology. 2008 Jul; 115 (7): 1,203-1,208. Epub 2007 Nov 12.
      • Moeller SM, Parekh N, Tinker L, Ritenbaugh C, Blodi B, Wallace RB, Mares JA; for the CAREDS Research Study Group. Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the Carotenoids in Age-Related Eye Disease Study (CAREDS): Ancillary study of the Women's Health Initiative. Arch Ophthalmol. 2006 Aug; 124(8): 1,151-1,162.
      • Tan JSL, Wang JJ, Flood V, Rochtchina R, Smith W, Mitchell P. Dietary antioxidants and the long-term incidence of age-related macular degeneration. Opthalmology 2008; 115: 334-341.
  • Search Plan and Results: FNOA: Antioxidants and Macular Degeneration 2011