title: Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer's disease: a prospective, open-label pilot study.
abstract: OBJECTIVE
  This is the first clinical trial of this type in Japan, designed to analyze two important aspects of Alzheimer's disease (AD) management using medium-chain triglycerides. Axona was administered for 3 months (40 g of powder containing 20 g of caprylic triglycerides). We used an indurating, four-step dose-titration method (from 10 to 40 g per day) for 7 days before the trial, and examined the tolerance and adverse effects of this intervention. We also investigated its effect on cognitive function in mild-to-moderate AD patients.
  
  
  METHODS
  This was a clinical intervention in 22 Japanese patients with sporadic AD at a mild-to-moderate stage (ten females, 12 males), mean age (± standard deviation) 63.9 (±8.5) years, Mini-Mental State Examination (MMSE) score, 10-25, seven patients were ApoE4-positive. During Axona administration, we examined changes in cognitive function by obtaining MMSE and AD assessment-scale scores. Intolerance and serum ketone concentrations were also examined.
  
  
  RESULTS
  The tolerance of Axona was good, without severe gastrointestinal adverse effects. Axona did not improve cognitive function in our sample of AD patients, even in those patients without the ApoE4 allele. However, some ApoE4-negative patients with baseline MMSE score ≥14 showed improvement in their cognitive functions.
  
  
  CONCLUSIONS
  The modified dose-titration method, starting with a low dose of Axona, decreased gastrointestinal adverse effects in Japanese patients. Axona might be effective for some relatively mildly affected patients with AD (with cognitive function MMSE score of ≥14 and lacking the ApoE4 allele).
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohnuma
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Toda
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kimoto
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Takebayashi
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Higashiyama
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tagata
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Tsuneyoshi
authors.initials: T
authors.lastname: Ota
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Nobuto
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Department of Psychiatry, Juntendo University Alzheimer's Disease Project, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005526:Food, Formulated; D006801:Humans; D007564:Japan; D007657:Ketone Bodies / Q000097:blood; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010865:Pilot Projects; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014280:Triglycerides / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D007657:Ketone Bodies; D014280:Triglycerides
keywords: Alzheimer’s disease; apolipoprotein E epsilon 4; cognitive function; ketone; medium-chain triglycerides
references.citation: Lancet. 1991 May 11;337(8750):1158-9
references.pmid: 1674030
references.citation: Ann Neurol. 1996 Jan;39(1):62-70
references.pmid: 8572669
references.citation: Nat Rev Neurol. 2011 Mar;7(3):137-52
references.pmid: 21304480
references.citation: Neurotherapeutics. 2008 Jul;5(3):470-80
references.pmid: 18625458
references.citation: Psychopharmacol Bull. 1983;19(3):448-50
references.pmid: 6635122
references.citation: Expert Opin Investig Drugs. 2007 Dec;16(12):1921-31
references.pmid: 18042001
references.citation: Neurochem Res. 2008 Dec;33(12):2390-400
references.pmid: 18415677
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2011 Mar 30;35(2):348-55
references.pmid: 20736041
references.citation: Nutr Metab (Lond). 2009 Aug 10;6:31
references.pmid: 19664276
references.citation: Am J Psychiatry. 1995 Dec;152(12):1757-64
references.pmid: 8526242
references.citation: Alzheimers Dement. 2010 Jan;6(1):1-10.e1
references.pmid: 20129316
references.citation: Circulation. 2008 Dec 16;118(25):2672-8
references.pmid: 19106389
references.citation: Neurobiol Aging. 2005 Dec;26 Suppl 1:133-6
references.pmid: 16266772
references.citation: Arch Gen Psychiatry. 1989 Jun;46(6):527-32
references.pmid: 2730277
references.citation: J Am Coll Nutr. 2008 Oct;27(5):547-52
references.pmid: 18845704
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Nutrition. 2011 Jan;27(1):3-20
references.pmid: 21035308
references.citation: Neurobiol Aging. 2004 Mar;25(3):311-4
references.pmid: 15123336
references.citation: JAMA. 1995 Mar 22-29;273(12):942-7
references.pmid: 7884953
references.citation: Clin Pract (Lond). 2012 Mar;9(2):199-209
references.pmid: 23362453
references.citation: Mutat Res. 2009 Feb 10;661(1-2):25-34
references.pmid: 19027755
references.citation: BMC Med Genet. 2011;12:137
references.pmid: 21992747
references.citation: J Alzheimers Dis. 2010;21(2):373-83
references.pmid: 20555132
references.citation: J Clin Invest. 1967 Oct;46(10):1589-95
references.pmid: 6061736
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: PLoS One. 2013;8(2):e54483
references.pmid: 23405083
references.citation: Scand J Gastroenterol. 1997 Sep;32(9):920-4
references.pmid: 9299672
references.citation: Issues Ment Health Nurs. 2010 Jun;31(6):435-6
references.pmid: 20450347
references.citation: Am J Physiol. 1996 May;270(5 Pt 1):E746-51
references.pmid: 8967461