Omega-3 Fatty Acid Supplementation Effects on Weight and Appetite in Patients with Alzheimer’s Disease: The Omega-3 Alzheimer’s Disease Study Gerd Faxe ´n Irving, PhD, à Ãà Yvonne Freund-Levi, MD, w Ãà Maria Eriksdotter-Jo ¨ nhagen, MD, PhD, w Hans Basun, MD, PhD, z Kerstin Brismar, MD, PhD, § Erik Hjorth, MSc, w Jan Palmblad, MD, PhD, k Bengt Vessby, MD, PhD, # Inger Vedin, Msc, k Lars-Olof Wahlund, MD, PhD, w and Tommy Cederholm, MD, PhD # OBJECTIVES: To study the effects of omega (O)-3 fatty acid (FA) supplements on weight and appetite in patients with mild to moderate Alzheimer’s disease (AD) in rela- tion to inflammatory biomarkers and apolipoprotein E e4 (APOEe4). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Specialist memory clinics in the Stockholm catchment area. PARTICIPANTS: Two hundred four patients (aged 73  9, 52% women) with mild to moderate AD. INTERVENTION: Patients with AD received 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) (O-3/O-3 group; n 5 89, aged 73  9, 57% women) or placebo 0.6 g of linoleic acid per day (placebo/ O-3 group; n 5 85, aged 73  9, 46% women) for 6 months. After 6 months, all patients received DHA and EPA for another 6 months. MEASUREMENTS: Anthropometry, biochemical nutri- tional and inflammatory markers, and appetite assessed by caregiver. RESULTS: Mean weight and body mass index (kg/m 2 ) at baseline were 70.0  11.8 kg and 24.3  3.0 kg/m 2 , respec- tively. At 6- and 12-month follow-up, weight had increased 0.7  2.5 kg (P 5.02) and 1.4  2.9 kg (Po.001) in the O-3/ O-3 group. In the placebo group, weight was unchanged at 6 months but had increased (P 5.01) at 12 months follow- up after O-3 supplementation was initiated. Appetite im- proved in the O-3/O-3 group over the treatment period (P 5.01). In logistic regression analyses, not carrying the APOEe4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow-up. CONCLUSION: A DHA-enriched O-3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD. Not carrying the APOEe4 allele and high DHA were independently associated with weight gain. J Am Geriatr Soc 57:11–17, 2009. Key words: O-3 fatty acids; weight gain; Alzheimer’s disease; dementia; appetite; nutrition; APOE C ross-sectional studies show that patients with dementia weigh less and have lower body mass index than cog- nitively intact elderly. 1 Weight loss might precede the diag- nosis of Alzheimer’s disease (AD). 2,3 Even though weight loss is present in the early stages of the disease, it increases with the severity and progression of AD. 4 The etiology of the weight loss is probably multifactorial. Potential con- tributing factors are inflammatory components of the dis- ease; impaired olfaction and taste; 5 and behavior problems like agitation, restlessness, 6 and wandering, which lead to increased energy expenditure. 7 Although it has been suggested that inflammatory pro- cesses in the brain are of etiologic importance in AD, 8 only a few studies have reported high levels of proinflammatory cytokines in the plasma or cerebrospinal fluid of patients with AD. 9,10 Tumor necrosis factor alpha (TNF-a) derived from the local central nervous system (CNS) inflammatory reaction in AD may account for the AD-related anorexia and weight loss. 11 It has been reported that antiinflammatory Address correspondence to Gerd Faxen-Irving, Karolinska University Hos- pital Huddinge, SE-141 86 Stockholm, Sweden. E-mail: gerd.faxen.irving@ ki.se DOI: 10.1111/j.1532-5415.2008.02055.x From the Sections of à Clinical Nutrition and w Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, § Department of Molecular Medicine and Surgery, k Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm; and Divisions of z Geriatrics and # Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden; Ãà Shared equal authorship. JAGS 57:11–17, 2009 r 2008, Copyright the Authors Journal compilation r 2008, The American Geriatrics Society 0002-8614/09/$15.00