The journal of nutrition, health & aging

, Volume 14, Issue 3, pp 224–230 | Cite as

A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia

  • A. Chan
  • R. Remington
  • E. Kotyla
  • A. Lepore
  • J. Zemianek
  • T. B. Shea


Adults of both genders without dementia consumed a nutriceutical formulation (“NF,” consisting of folic acid, B12, Vitamin E, S-adenosylmethionine, N-acetyl cysteine and Acetyl-L-carnitine), previously shown to improve cognitive performance in Alzheimer’s disease, or placebo. Participants receiving NF but not placebo improved statistically and clinically in the California Verbal Learning Test II and the Trail-Making Test. Both groups improved further during a 3-month open-label extension. Additional individuals displayed identical improvement during a separate 6-month open-label trial. Performance declined to baseline following withdrawal of NF, and statistically improved when participants resumed taking NF. Additional participants receiving NF but not placebo demonstrated improvement within 2 weeks in Trail-making and Digit-Memory tests; both groups improved in a 2-week open-label extension. An increased percentage of participants ≥ 74 years of age did not show improvement with NF, which may relate to age-related difficulties in adsorption and/or basal nutritional deficiencies, or age-related cognitive decline during the course of this study. These findings support the benefit of nutritional supplements for cognitive performance and suggest that additional supplementation may be required for the elderly.


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  1. 1.
    Bourre JM, Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging, 2006. 10(5): p. 377–385.PubMedGoogle Scholar
  2. 2.
    Dye L, Lluch A, and Blundell JE, Macronutrients and mental performance. Nutrition, 2000. 16(10): p. 1021–1034.CrossRefPubMedGoogle Scholar
  3. 3.
    Rogers PJ, A healthy body, a healthy mind: long-term impact of diet on mood and cognitive function. Proc Nutr Soc, 2001. 60(1): p. 135–143.CrossRefPubMedGoogle Scholar
  4. 4.
    Whalley LJ, Fox HC, Wahle KW, Starr JM, and Deary IJ, Cognitive aging, childhood intelligence, and the use of food supplements: possible involvement of n-3 fatty acids. Am J Clin Nutr, 2004. 80(6): p. 1650–1657.PubMedGoogle Scholar
  5. 5.
    Balk EM, Raman G, Tatsioni A, Chung M, Lau J, and Rosenberg IH, Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch Intern Med, 2007. 167(1): p. 21–30.CrossRefPubMedGoogle Scholar
  6. 6.
    Bryan J, Calvaresi E, and Hughes D, Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr, 2002. 132(6): p. 1345–1356.PubMedGoogle Scholar
  7. 7.
    Malouf R and Grimley Evans J, Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev, 2008(4): p. CD004514.Google Scholar
  8. 8.
    Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, and White LR, Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology, 2000. 54(6): p. 1265–1272.PubMedGoogle Scholar
  9. 9.
    Bourre JM, Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing. J Nutr Health Aging, 2004. 8(3): p. 163–174.PubMedGoogle Scholar
  10. 10.
    Kalmijn S, van Boxtel MP, Ocke M, Verschuren WM, Kromhout D, and Launer LJ, Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology, 2004. 62(2): p. 275–280.PubMedGoogle Scholar
  11. 11.
    van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Hoefnagels WH, Beekman AT, and de Groot LC, Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr, 2008. 88(3): p. 706–713.PubMedGoogle Scholar
  12. 12.
    Woodside JV, McCall D, McGartland C, and Young IS, Micronutrients: dietary intake v. supplement use. Proc Nutr Soc, 2005. 64(4): p. 543–553.PubMedGoogle Scholar
  13. 13.
    Birks J and Grimley Evans J, Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev, 2009(1): p. CD003120.Google Scholar
  14. 14.
    Kleijnen J and Knipschild P, Ginkgo biloba for cerebral insufficiency. Br J Clin Pharmacol, 1992. 34(4): p. 352–358.PubMedGoogle Scholar
  15. 15.
    Huang HY, Caballero B, Chang S, Alberg A, Semba R, Schneyer C, Wilson RF, Cheng TY, Prokopowicz G, Barnes GJ, 2nd, Vassy J, and Bass EB, Multivitamin/mineral supplements and prevention of chronic disease. Evid Rep Technol Assess (Full Rep), 2006(139): p. 1–117.Google Scholar
  16. 16.
    McDaniel MA, Maier SF, and Einstein GO, “Brain-specific” nutrients: a memory cure? Nutrition, 2003. 19(11–12): p. 957–975.CrossRefPubMedGoogle Scholar
  17. 17.
    Chan A, Tchantchou F, Graves V, Rozen R, and Shea TB, Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: critical role of S-adenosyl methionine. J Nutr Health Aging, 2008. 12(4): p. 252–261.CrossRefPubMedGoogle Scholar
  18. 18.
    Choi J, Conrad CC, Dai R, Malakowsky CA, Talent JM, Carroll CA, Weintraub ST, and Gracy RW, Vitamin E prevents oxidation of antiapoptotic proteins in neuronal cells. Proteomics, 2003. 3(1): p. 73–77.CrossRefPubMedGoogle Scholar
  19. 19.
    Joseph JA, Denisova NA, Bielinski D, Fisher DR, and Shukitt-Hale B, Oxidative stress protection and vulnerability in aging: putative nutritional implications for intervention. Mech Ageing Dev, 2000. 116(2–3): p. 141–153.CrossRefPubMedGoogle Scholar
  20. 20.
    Rogers EJ, Milhalik S, Orthiz D, and Shea TB, Apple juice prevents oxidative stress and impaired cognitive performance caused by genetic and dietary deficiencies in mice. J Nutr Health Aging, 2004. 8(2): p. 92–97.PubMedGoogle Scholar
  21. 21.
    Tchantchou F, Graves M, Falcone D, and Shea TB, S-adenosylmethionine mediates glutathione efficacy by increasing glutathione S-transferase activity: implications for S-adenosyl methionine as a neuroprotective dietary supplement. J Alzheimers Dis, 2008. 14(3): p. 323–328.PubMedGoogle Scholar
  22. 22.
    Willis LM, Shukitt-Hale B, and Joseph JA, Recent advances in berry supplementation and age-related cognitive decline. Curr Opin Clin Nutr Metab Care, 2009. 12(1): p. 91–94.CrossRefPubMedGoogle Scholar
  23. 23.
    Fotuhi M, Zandi PP, Hayden KM, Khachaturian AS, Szekely CA, Wengreen H, Munger RG, Norton MC, Tschanz JT, Lyketsos CG, Breitner JC, and Welsh-Bohmer K, Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study. Alzheimers Dement, 2008. 4(3): p. 223–227.CrossRefPubMedGoogle Scholar
  24. 24.
    Haskell CF, Scholey AB, Jackson PA, Elliott JM, Defeyter MA, Greer J, Robertson BC, Buchanan T, Tiplady B, and Kennedy DO, Cognitive and mood effects in healthy children during 12 weeks’ supplementation with multi-vitamin/minerals. Br J Nutr, 2008. 100(5): p. 1086–1096.CrossRefPubMedGoogle Scholar
  25. 25.
    Kennedy DO, Haskell CF, Robertson B, Reay J, Brewster-Maund C, Luedemann J, Maggini S, Ruf M, Zangara A, and Scholey AB, Improved cognitive performance and mental fatigue following a multi-vitamin and mineral supplement with added guarana (Paullinia cupana). Appetite, 2008. 50(2–3): p. 506–513.PubMedGoogle Scholar
  26. 26.
    Martin A, Cherubini A, Andres-Lacueva C, Paniagua M, and Joseph J, Effects of fruits and vegetables on levels of vitamins E and C in the brain and their association with cognitive performance. J Nutr Health Aging, 2002. 6(6): p. 392–404.PubMedGoogle Scholar
  27. 27.
    Sharkey JR, Laditka JN, Laditka SB, Hochhalter A, and Robare JF, Older adults’ perceptions about the role of nutrition and diet on brain health. J Nutr Health Aging, 2008. 12(7): p. 420.Google Scholar
  28. 28.
    Chan A, Paskavitz J, Remington R, Rasmussen S, and Shea TB, Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer’s disease: a 1-year, openlabel pilot study with an 16-month caregiver extension. Am J Alzheimers Dis Other Demen, 2008. 23(6): p. 571–585.CrossRefPubMedGoogle Scholar
  29. 29.
    Remington R, Chan A, Paskavitz J, and Shea TB, Efficacy of a Vitamin/Nutriceutical Formulation for Moderate-stage to Later-stage Alzheimer’s disease: A Placebocontrolled Pilot Study. Am J Alzheimers Dis Other Demen, 2009. 24(1): p. 27–33.CrossRefPubMedGoogle Scholar
  30. 30.
    Berg MJ, The importance of folic acid. J Gend Specif Med, 1999. 2(3): p. 24–28.PubMedGoogle Scholar
  31. 31.
    Mattson MP and Shea TB, Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci, 2003. 26(3): p. 137–146.CrossRefPubMedGoogle Scholar
  32. 32.
    Muller DP and Goss-Sampson MA, Neurochemical, neurophysiological, and neuropathological studies in vitamin E deficiency. Crit Rev Neurobiol, 1990. 5(3): p. 239–263.PubMedGoogle Scholar
  33. 33.
    Sokol RJ, Vitamin E and neurologic function in man. Free Radic Biol Med, 1989. 6(2): p. 189–207.CrossRefPubMedGoogle Scholar
  34. 34.
    Kennedy BP, Bottiglieri T, Arning E, Ziegler MG, Hansen LA, and Masliah E, Elevated S-adenosylhomocysteine in Alzheimer brain: influence on methyltransferases and cognitive function. J Neural Transm, 2004. 111(4): p. 547–567.CrossRefPubMedGoogle Scholar
  35. 35.
    Tchantchou F, Graves M, Ortiz D, Chan A, Rogers E, and Shea TB, S-adenosyl methionine: A connection between nutritional and genetic risk factors for neurodegeneration in Alzheimer’s disease. J Nutr Health Aging, 2006. 10(6): p. 541–544.PubMedGoogle Scholar
  36. 36.
    Cotgreave IA, N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv Pharmacol, 1997. 38: p. 205–227.CrossRefPubMedGoogle Scholar
  37. 37.
    Calabrese V, Cornelius C, Mancuso C, Pennisi G, Calafato S, Bellia F, Bates TE, Giuffrida Stella AM, Schapira T, Dinkova Kostova AT, and Rizzarelli E, Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity. Neurochem Res, 2008. 33(12): p. 2444–2471.CrossRefPubMedGoogle Scholar
  38. 38.
    Kidd PM, Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management. Altern Med Rev, 2005. 10(4): p. 268–293.PubMedGoogle Scholar
  39. 39.
    Silva-Adaya D, Perez-De La Cruz V, Herrera-Mundo MN, Mendoza-Macedo K, Villeda-Hernandez J, Binienda Z, Ali SF, and Santamaria A, Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: antioxidant and neuroprotective effects of L-carnitine. J Neurochem, 2008. 105(3): p. 677–689.CrossRefPubMedGoogle Scholar
  40. 40.
    Mischoulon D and Fava M, Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr, 2002. 76(5): p. 1158S–1161S.PubMedGoogle Scholar
  41. 41.
    Gelb S, Shapiro RJ, Hill A, and Thornton WL, Cognitive outcome following kidney transplantation. Nephrol Dial Transplant, 2008. 23(3): p. 1032–1038.CrossRefPubMedGoogle Scholar
  42. 42.
    Arbuthnott K and Frank J, Trail making test, part B as a measure of executive control: validation using a set-switching paradigm. J Clin Exp Neuropsychol, 2000. 22(4): p. 518–528.CrossRefPubMedGoogle Scholar
  43. 43.
    Crowe SF, The differential contribution of mental tracking, cognitive flexibility, visual search, and motor speed to performance on parts A and B of the Trail Making Test. J Clin Psychol, 1998. 54(5): p. 585–591.CrossRefPubMedGoogle Scholar
  44. 44.
    Gaudino EA, Geisler MW, and Squires NK, Construct validity in the Trail Making Test: what makes Part B harder? J Clin Exp Neuropsychol, 1995. 17(4): p. 529–535.CrossRefPubMedGoogle Scholar
  45. 45.
    Kortte KB, Horner MD, and Windham WK, The trail making test, part B: cognitive flexibility or ability to maintain set? Appl Neuropsychol, 2002. 9(2): p. 106–109.CrossRefPubMedGoogle Scholar
  46. 46.
    Tombaugh TN, Trail Making Test A and B: normative data stratified by age and education. Arch Clin Neuropsychol, 2004. 19(2): p. 203–214.CrossRefPubMedGoogle Scholar
  47. 47.
    Benedict RH and Zgaljardic DJ, Practice effects during repeated administrations of memory tests with and without alternate forms. J Clin Exp Neuropsychol, 1998. 20(3): p. 339–352.CrossRefPubMedGoogle Scholar
  48. 48.
    Woods SP, Delis DC, Scott JC, Kramer JH, and Holdnack JA, The California Verbal Learning Test—second edition: test-retest reliability, practice effects, and reliable change indices for the standard and alternate forms. Arch Clin Neuropsychol, 2006. 21(5): p. 413–420.CrossRefPubMedGoogle Scholar
  49. 49.
    McNeill G, Winter J, and Jia X, Diet and cognitive function in later life: a challenge for nutrition epidemiology. Eur J Clin Nutr, 2009. 63Suppl 1: p. S33–S37.CrossRefPubMedGoogle Scholar
  50. 50.
    Riley MA, Baker AA, and Schmit JM, Inverse relation between postural variability and difficulty of a concurrent short-term memory task. Brain Res Bull, 2003. 62(3): p. 191–195.CrossRefPubMedGoogle Scholar
  51. 51.
    Vickery CD, Berry DT, Inman TH, Harris MJ, and Orey SA, Detection of inadequate effort on neuropsychological testing: a meta-analytic review of selected procedures. Arch Clin Neuropsychol, 2001. 16(1): p. 45–73.PubMedGoogle Scholar
  52. 52.
    Cohen J, Statistical power analysis for the behavioral sciences. 2nd ed. 1988, Hillsdale, N.J.: L. Erlbaum Associates. xxi, 567 p.Google Scholar
  53. 53.
    Zalonis I, Kararizou E, Triantafyllou NI, Kapaki E, Papageorgiou S, Sgouropoulos P, and Vassilopoulos D, A normative study of the trail making test A and B in Greek adults. Clin Neuropsychol, 2008. 22(5): p. 842–850.CrossRefPubMedGoogle Scholar
  54. 54.
    Carlson MC, Xue QL, Zhou J, and Fried LP, Executive Decline and Dysfunction Precedes Declines in Memory: The Women’s Health and Aging Study II. J Gerontol A Biol Sci Med Sci, 2009. 64(1): p. 110–117.PubMedGoogle Scholar
  55. 55.
    Johnson JK, Lui LY, and Yaffe K, Executive function, more than global cognition, predicts functional decline and mortality in elderly women. J Gerontol A Biol Sci Med Sci, 2007. 62(10): p. 1134–1141.PubMedGoogle Scholar
  56. 56.
    Mahieux F, Onen F, Berr C, Volteau M, Habert MO, Legrain S, and Dubois B, Early Detection of Patients in the Pre Demented Stage of Alzheimer’s Disease: The PREAL Study. J Nutr Health Aging, 2009. 13(1): p. 21–26.CrossRefPubMedGoogle Scholar
  57. 57.
    Johnson MA, If high folic acid aggravates vitamin B12 deficiency what should be done about it? Nutr Rev, 2007. 65(10): p. 451–458.PubMedGoogle Scholar
  58. 58.
    Koehler KM, Pareo-Tubbeh SL, Romero LJ, Baumgartner RN, and Garry PJ, Folate nutrition and older adults: challenges and opportunities. J Am Diet Assoc, 1997. 97(2): p. 167–173.CrossRefPubMedGoogle Scholar
  59. 59.
    Navarro M and Wood RJ, Plasma changes in micronutrients following a multivitamin and mineral supplement in healthy adults. J Am Coll Nutr, 2003. 22(2): p. 124–132.PubMedGoogle Scholar
  60. 60.
    Rondanelli M, Trotti R, Opizzi A, and Solerte SB, Relationship among nutritional status, pro/antioxidant balance and cognitive performance in a group of free-living healthy elderly. Minerva Med, 2007. 98(6): p. 639–645.PubMedGoogle Scholar
  61. 61.
    Selhub J, Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J Nutr Health Aging, 2002. 6(1): p. 39–42.PubMedGoogle Scholar
  62. 62.
    Sharkey JR, Diet and health outcomes in vulnerable populations. Ann N Y Acad Sci, 2008. 1136: p. 210–217.CrossRefPubMedGoogle Scholar
  63. 63.
    Wolters M, Strohle A, and Hahn A, [Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences]. Z Gerontol Geriatr, 2004. 37(2): p. 109–135.CrossRefPubMedGoogle Scholar
  64. 64.
    Marra MV and Wellman NS, Multivitamin-mineral supplements in the Older Americans Act Nutrition Program: not a one-size-fits-all quick fix. Am J Public Health, 2008. 98(7): p. 1171–1176.CrossRefPubMedGoogle Scholar
  65. 65.
    Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, and 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): p. 208–216.CrossRefPubMedGoogle Scholar
  66. 66.
    McKay DL, Perrone G, Rasmussen H, Dallal G, Hartman W, Cao G, Prior RL, Roubenoff R, and Blumberg JB, The effects of a multivitamin/mineral supplement on micronutrient status, antioxidant capacity and cytokine production in healthy older adults consuming a fortified diet. J Am Coll Nutr, 2000. 19(5): p. 613–621.PubMedGoogle Scholar

Copyright information

© Serdi and Springer Verlag France 2010

Authors and Affiliations

  • A. Chan
    • 1
    • 3
  • R. Remington
    • 2
  • E. Kotyla
    • 4
  • A. Lepore
    • 4
  • J. Zemianek
    • 1
    • 2
  • T. B. Shea
    • 1
    • 5
  1. 1.Center for Cell Neurobiology and Neurodegeneration ResearchUniversity of Massachusetts•LowellLowellUSA
  2. 2.Department of NursingUniversity of Massachusetts•LowellLowellUSA
  3. 3.Department of Work EnvironmentUniversity of Massachusetts•LowellLowellUSA
  4. 4.Department of Clinical and Health SciencesUniversity of MassachusettsLowellUSA
  5. 5.Department of Biological SciencesUniversity of Massachusetts•LowellLowellUSA

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