Skip to main content
American Journal of Alzheimer's Disease and Other Dementias logoLink to American Journal of Alzheimer's Disease and Other Dementias
. 2009 Feb-Mar;24(1):27–33. doi: 10.1177/1533317508325094

Efficacy of a Vitamin/Nutriceutical Formulation for Moderate-stage to Later-stage Alzheimer's disease: A Placebo-controlled Pilot Study

Ruth Remington 1, Amy Chan 2, James Paskavitz 3, Thomas B Shea 4
PMCID: PMC10846219  PMID: 19056706

Abstract

Recent studies demonstrated efficacy of a vitamin/ nutriceutical formulation (folate, vitamin B12, alpha-tocopherol, S-adenosyl methionine, N-acetyl cysteine, and acetyl-L-carnitine) for mild to moderate Alzheimer's disease. Herein, we tested the efficacy of this formulation in a small cohort of 12 institutionalized patients diagnosed with moderate-stage to later-stage Alzheimer's disease. Participants were randomly separated into treatment of placebo groups. Participants receiving the formulation demonstrated a clinically significant delay in decline in the Dementia Rating Scale and clock-drawing test as compared to those receiving placebo. Institutional caregivers reported approximately 30% improvement in the Neuropyschiatric Inventory and maintenance of performance in the Alzheimer's Disease Cooperative Study—Activities of Daily Living for more than 9 months. This formulation holds promise for delaying the decline in cognition, mood, and daily function that accompanies the progression of Alzheimer's disease, and may be particularly useful as a supplement for pharmacological approaches during later stages of this disorder. A larger trial is warranted.

Keywords: cognition, behavioral response, vitamin, nutriceutical, supplement

Full Text

The Full Text of this article is available as a PDF (236.4 KB).

Contributor Information

Ruth Remington, Department of Nursing, University of Massachusetts Lowell, Lowell, Massachusetts, Center for Cell Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, Lowell, Massachusetts.

Amy Chan, Center for Cell Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, Lowell, Massachusetts.

James Paskavitz, Perceptive Informatics, Inc. Waltham, Massachusetts.

Thomas B. Shea, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, Thomas_Shea@uml.edu, Center for Cell Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, Lowell, Massachusetts.

References

  1. Swerdlow RH Pathogenesis of Alzheimer's disease. Clin Interv Aging. 2007;2:347-359. [PMC free article] [PubMed] [Google Scholar]
  2. Shah S., Reichman WE Treatment of Alzheimer's disease across the spectrum of severity. Clin Interv Aging. 2006;1:131-142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burns A., Gauthier S., Perdomo C. Efficacy and safety of donepezil over 3 years: an open-label, multicentre study in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 2007;22:806-812. [DOI] [PubMed] [Google Scholar]
  4. Feldman HH, Schmitt FA, Olin JT Memantine MEM-MD-02 Study Group. Activities of daily living in moderate-to-severe Alzheimer disease: an analysis of the treatment effects of memantine in patients receiving stable donepezil treatment . Alzheimer Dis Assoc Disord. 2006;20:263-268. [DOI] [PubMed] [Google Scholar]
  5. Johannsen P. Medical treatment of Alzheimer's disease. Ugeskr Laeger. 2006;168:3424-3429. [PubMed] [Google Scholar]
  6. Reisberg B., Doody R., Stoffler A., Schmitt F., Ferris S., Mobius HJ A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease. Arch Neurol. 2006;63:49-54. [DOI] [PubMed] [Google Scholar]
  7. Seow D., Gauthier S. Pharmacotherapy of Alzheimer disease. Can J Psychiatry. 2007;52:620-629. [DOI] [PubMed] [Google Scholar]
  8. Beier MT Treatment strategies for the behavioral symptoms of Alzheimer's disease: focus on early pharmacologic intervention. Pharmacotherapy. 2007;27: 399-411. [DOI] [PubMed] [Google Scholar]
  9. Park KW, Pavlik VN, Rountree SD, Darby EJ, Doody RS Is functional decline necessary for a diagnosis of Alzheimer's disease? Dement Geriatr Cogn Disord. 2007;24: 375-379. [DOI] [PubMed] [Google Scholar]
  10. Touchon J., Portet F., Gauthier S. Prevention trials in Alzheimer disease: one step forward? Neurology. 2006;67(9 suppl 3):S21-S22. [DOI] [PubMed] [Google Scholar]
  11. Fusco D., Colloca G., Lo Monaco MR, Cesari M. Effects of antioxidant supplementation on the aging process. Clin Interv Aging. 2007;2:377-387. [PMC free article] [PubMed] [Google Scholar]
  12. Mattson MM, Shea TB Folate and homocysteine in neural plasticity and neurodegenerative disorders . Trends Neurosci. 2002;26:137-146. [DOI] [PubMed] [Google Scholar]
  13. Burgener SC , Buettner L., Coen Buckwlater K., et al. Evidence supporting nutritional interventions for persons in early-stage Alzheimer's disease. J Nutr Health Aging. 2008;12:18-21. [DOI] [PubMed] [Google Scholar]
  14. Panza F., Solfrizzi V., Colacicco AM, et al. Mediterranean diet and cognitive decline. Pub Health Nutri. 2004;7: 959-963. [DOI] [PubMed] [Google Scholar]
  15. Chan A., Paskavitz J., Remington R., Shea TB Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer's disease: a one-year open-label pilot study with an 11-month extension. Am J Alzheimers Dis Other Demen. [IN PRESS]. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dhitavat S. , Rivera E., Shea TB Differential efficacy of lipophilic and cytosolic antioxidants on generation of reactive oxygen species by amyloid-beta. J Alzheimers Dis. 2001;3:525-529. [PubMed] [Google Scholar]
  17. Fuso A., Seminara L., Cavallaro RA, D'Anselmi F., Scarpa S. S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production . Mol Cell Neurosci. 2005;28:195-204. [DOI] [PubMed] [Google Scholar]
  18. Scarpa S., Fuso A., D'Anselmi F., Cavallaro RA Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease? FEBS Lett. 2003;541:145-148. [DOI] [PubMed] [Google Scholar]
  19. Barnes CA, Markowska AL, Ingram DK, et al. Acetyl-1-carnitine. 2. Effects on learning and memory performance of aged rats in simple and complex mazes. Neurobiol Aging. 1990;11:499-506. [DOI] [PubMed] [Google Scholar]
  20. Chan A., Shea TB Dietary and genetically-induced oxidative stress alter tau phosphorylation: influence of folate and apolipoprotein E deficiency. J Alzheimers Dis. 2006;9:399-405. [DOI] [PubMed] [Google Scholar]
  21. Chan A., Shea TB Folate deprivation increases presenilin expression, gamma-secretase activity and Abeta levels in murine brain: potentiation by Apoe deficiency and alleviation by dietary S-adenosyl methionine. J Neurochem. 2007;102:753-760. [DOI] [PubMed] [Google Scholar]
  22. Chan A., Tchantchou F., Graves V., Rozen R., Shea TB Dietary and genetic compromise in folate availability reduces acetylcholine and cognitive performance: critical role of S-adenosylmethionine. J Health Nutr Aging. 2008;12:252-261. [DOI] [PubMed] [Google Scholar]
  23. De La Cruz JP, Pavia J., Gonzalez-Correa JA, Ortiz P., Sanchez de la Cuesta F. Effects of chronic administration of S-adenosyl-L-methionine on brain oxidative stress in rats. Naunyn Schmiedebergs Arch Pharmacol. 2000;361:47-52. [DOI] [PubMed] [Google Scholar]
  24. De La Cruz JP, Villalobos MA, Cuerda MA, Guerrero A., González-Correa JA, Sánchez D.e La Cuesta F. Effects of S-adenosyl-L-methionine on lipid peroxidation and glutathione levels in rat brain slices exposed to reoxygenation after oxygen-glucose deprivation. Neurosci Lett. 2002;318:103-107. [DOI] [PubMed] [Google Scholar]
  25. Dhitavat S. , Ortiz D., Rogers E., Rivera E., Shea TB Folate, vitamin E and acetyl-L-carnitine provide synergistic protection against oxidative stress resulting from exposure of human neuroblastoma cells to amyloid beta. Brain Res. 2005;1061:114-117. [DOI] [PubMed] [Google Scholar]
  26. Fu AL, Dong ZH, Sun MJ Protective effect of N-acetyl-L-cysteine on amyloid beta-peptide-induced learning and memory deficits in mice. Brain Res. 2006. ;1109:201-206. [DOI] [PubMed] [Google Scholar]
  27. Markowska AL , Olton DS Dietary acetyl-L-carnitine improves spatial behaviour of old rats. Int J Clin Pharmacol Res. 1990;10:65-68. [PubMed] [Google Scholar]
  28. Shea TB, Chan A. S-adenosyl methionine: a natural therapeutic agent effective against multiple hallmarks and risk factors associated with Alzheimer's disease. J Alzheimers Dis. 2008;13:67-70. [DOI] [PubMed] [Google Scholar]
  29. Shea TB, Ortiz D., Rogers E. Differential susceptibity of transgenic mice lacking one or both apolipoprotein alleles to folate and vitamin E deprivation. J Alzheimers Dis. 2004;6:269-273. [DOI] [PubMed] [Google Scholar]
  30. Tchantchou F., Graves M., Rogers E., Ortiz D., Shea TB N-acetyl cysteine alleviates neurodegeneration and increased glutathione expression in normal and ApoEdeficient mice. J Alzheimers Dis. 2005;7:135-138. [DOI] [PubMed] [Google Scholar]
  31. Tchantchou F. , Graves M., Rogers E., Ortiz D., Shea TB Dietary supplementation with 3-deaza adenosine, N-acetyl cysteine and S-adenosyl methionine provide neuroprotection against multiple consequences of vitamin deficiency and oxidative challenge: relevance to age-related neurodegeneration. Neuromol Med. 2005;6: 93-104. [DOI] [PubMed] [Google Scholar]
  32. Villalobos MA , De La Cruz JP, Cuerda MA, Ortiz P., Smith-Agreda JM, Sanchez De La Cuesta F. Effect of S-adenosyl-L-methionine on rat brain oxidative stress damage in a combined model of permanent focal ischemia and global ischemia-reperfusion. Brain Res. 2000;883:31-40. [DOI] [PubMed] [Google Scholar]
  33. Chan A., Shea TB Improved cognitive performance and decreased aggression in normal and ApoE4 mice following dietary supplementation with N-acetyl cysteine, acetyl-L-carnitine and S-adenosyl methionine. Neuromol Med. 2007. ;9:264-269. [DOI] [PubMed] [Google Scholar]
  34. Shea TB, Rogers E. Folate quenches oxidative damage in brains of apolipoprotein E-deficient mice: augmentation by vitamin E. Brain Res Mol Brain Res. 2002;108:1-6. [DOI] [PubMed] [Google Scholar]
  35. Mckhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan EM Clinical diagnosis of Alzheimer's disease report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's disease. Neurology. 1984. ;34:939-944. [DOI] [PubMed] [Google Scholar]
  36. Lucas JA, Ivnik RJ, Smith GE, et al. Normative data for the Mattis Dementia Rating Scale. J Clin Exp Neuropsychol. 1993;20:536-547. [DOI] [PubMed] [Google Scholar]
  37. Monsch AU, Bondi MW, Salmon DP, et al. Clinical validity of the Mattis Dementia Rating Scale in detecting dementia of the Alzheimer type. A double cross-validation and application to a community-dwelling sample. Arch Neurol. 1995;52:899-904. [DOI] [PubMed] [Google Scholar]
  38. Royall DR, Cordes JA, Polk M. CLOX: an executive clock drawing test. J Neurol Neurosurg Psychiatry. 1998;64: 588-594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Paskavitz JF , Gunstad JJ, Samuel JE Clock drawing and frontal lobe behavioral effects of memantine in Alzheimer's disease: a rater-blinded study. Am J Alzheimers Dis Other Demen. 2006;21:454-459. [DOI] [PubMed] [Google Scholar]
  40. Cummings JL The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48:S10-S16. [DOI] [PubMed] [Google Scholar]
  41. Galasko D., Bennett D., Sano M., et al. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11(suppl 2): S33-S39. [PubMed] [Google Scholar]
  42. Potkin SG The ABC of Alzheimer's disease: ADL and improving day-to-day functioning of patients. Int Psycho-geriatr. 2002;14(suppl 1):7-26. [DOI] [PubMed] [Google Scholar]
  43. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ: Lawrence Erlbaum; 1988. [Google Scholar]
  44. Bouchard RW, Rossor M. Typical clinical features. In: Gauthier S , ed. Clinical Diagnosis and Management of Alzheimer's Disease . London: Martin Dunitz Ltd; 1996:35-51. [Google Scholar]
  45. Conn D., Thorpe L. Assessment of behavioural and psychological symptoms associated with dementia . Can J Neurol Sci. 2007;34(suppl 1):S67-S71. [DOI] [PubMed] [Google Scholar]
  46. Craig D., Mirakhur A., Hart DJ, McIlroy SP, Passmore AP A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease. Am J Geriatr Psychiatry. 2005;13:460-468. [DOI] [PubMed] [Google Scholar]
  47. Hinchcliffe AC, Hyman IL, Blizard B., Livingston G. Behavioural complications of dementia-can they be treated? Int Geriatr Psychiatry. 1995. ;10:839-847. [Google Scholar]
  48. Matsumoto N. , Ikeda M., Fukuhara R., et al. Caregiver burden associated with behavioral and psychological symptoms of dementia in elderly people in the local community . Dement Geriatr Cogn Disord. 2007;23:219-224. [DOI] [PubMed] [Google Scholar]
  49. de Vugt ME, Riedijk SR, Aalten P., Tibben A., van Swieten JC, Verhey FR Impact of behavioural problems on spousal caregivers: a comparison between Alzheimer's disease and frontotemporal dementia. Dement Geriatr Cogn Disord. 2006;22:35-41. [DOI] [PubMed] [Google Scholar]
  50. Sachs GS A review of agitation in mental illness: burden of illness and underlying pathology. J Clin Psychiatry. 2006;67(suppl 10):5-12. [PubMed] [Google Scholar]
  51. Shin IS, Carter M., Masterman D., Fairbanks L., Cummings JL Neuropsychiatric symptoms and quality of life in Alzheimer disease. Am J Geriatr Psychiatry. 2005;13:469-474. [DOI] [PubMed] [Google Scholar]
  52. Paton J., Johnston K., Katona C., Livingston G. What causes problems in Alzheimer's disease: attributions by caregivers. A qualitative study. Int J Geriatr Psychiatry. 2004;19:527-532. [DOI] [PubMed] [Google Scholar]
  53. Riello R., Geroldi C., Zanetti O., Frisoni GB Caregiver's distress is associated with delusions in Alzheimer's patients . Behav Med. 2002;28:92-98. [DOI] [PubMed] [Google Scholar]
  54. Buhr GT, White HK Difficult behaviors in long-term care patients with dementia. J Am Med Dir Assoc. 2007;8(3 suppl 2):e101-e113. [DOI] [PubMed] [Google Scholar]
  55. Sourial R., McCusker J., Cole M., Abrahamowicz M. Agitation in demented patients in an acute care hospital: prevalence, disruptiveness, and staff burden. Int Psycho-geriatr. 2001. ;13:183-197. [DOI] [PubMed] [Google Scholar]
  56. Aalten P., Verhey FR, Boziki M., et al. Consistency of neuropsychiatric syndromes across dementias: results from the European Alzheimer Disease Consortium. Part II. Dement Geriatr Cogn Disord. 2008;25:1-8. [DOI] [PubMed] [Google Scholar]
  57. Chan A., Paskvitz J., Shea TB A novel vitamin/nutriceutical formulation that delays cognitive decline and improves mood in early-stage Alzheimer's disease. Alzheimers Dement. 2007;3:S98. [Google Scholar]
  58. Rawls WN Donepezil in more advanced Alzheimer's disease. Consult Pharm . 2005;20:592-600. [DOI] [PubMed] [Google Scholar]
  59. Black SE, Doody R., Li H., et al. Alzheimer disease. Neurology. 2007;69:459-469. [DOI] [PubMed] [Google Scholar]
  60. Feldman HH, Schmitt FA, Olin JT Memantine MEM-MD-02 Study Group. Activities of daily living in moderate-to-severe Alzheimer disease: an analysis of the treatment effects of memantine in patients receiving stable donepezil treatment . Alzheimer Dis Assoc Disord. 2006;20:263-268. [DOI] [PubMed] [Google Scholar]
  61. Schmitt FA, Wichems CH A systematic review of assessment and treatment of moderate to severe Alzheimer's disease. Prim Care Companion J Clin Psychiatry. 2006;8:158-159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S., Gergel I. Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial . JAMA. 2004;291:317-324. [DOI] [PubMed] [Google Scholar]
  63. Burgener SC , Buettner L., Coen Buckwalter K., et al. Evidence supporting nutritional interventions for persons in early stage Alzheimer's disease (AD) . J Nutr Health Aging. 2008;12:18-21. [DOI] [PubMed] [Google Scholar]
  64. Kivipelto M. , Solomon A. Alzheimer's disease-the ways of prevention . J Nutr Health Aging. 2008;12: 89S-94S. [DOI] [PubMed] [Google Scholar]
  65. Patterson C. , Feightner JW, Garcia A., Hsiung GY, MacKnight C., Sadovnick AD Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ. 2008;178: 548-556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Zhu X., Su B., Wang X., Smith MA, Perry G. Causes of oxidative stress in Alzheimer disease. Cell Mol Life Sci. 2007;64:2202-2210. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Alzheimer's Disease and Other Dementias are provided here courtesy of SAGE Publications

RESOURCES