Scant Data, Benefit of Omega-3 Fatty Acids in Alzheimer Disease

Developers of the proprietary drink, Souvenaid, claim its ingredients work synergistically to restore neuronal synapses in diseases like Alzheimer disease (for necessary background on Souvenaid clinical development, see yesterday's post). However, many of the individual components in the formula have been shown to be ineffective, or only marginally effective, in AD. Among these ingredients are omega-3 fatty acids—specifically docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). One rationale for using DHA and EPA supplementation in AD is based on their potential to reduce disease-associated inflammation.

A directed PubMed search reveals exactly 1 randomized, double-blind, placebo-controlled study of DHA and EPA in AD. The 6-month study, with a 6-month open-label extension, was performed at the Karolinska Institute between 2001 and 2004 in 174 patients with mild-to-moderate disease who were receiving acetylcholinesterase-inhibitor therapy (eg, Aricept). Data were collected on cognitive decline, neuropsychiatric symptoms, weight gain, and plasma markers of inflammation and were parsed into 4 articles, published from 2006 to 2009.

Daily DHA (1.6 g) and EPA (0.6 g) supplementation did not affect cognitive decline (measured with the MMSE and ADAS-cog scales) at 6 months; however, in the subgroup with very mild AD (n = 32), supplementation was associated with a statistically significant reduction in the decline of the MMSE score. (This observation likely informed the enrollment of patients with very mild AD in the Souvenaid trial.)

Nor did DHA/EPA supplementation affect neuropsychiatric symptoms, the ability to perform activities of daily living (ADL), or caregiver burden at 6 months. In detailed subgroup analyses, however, supplementation reduced agitation in APOE ε4 carriers* (n = 125) and depression in APOE ε4 noncarriers (n = 49). Make of that what you can; I don't make much of it.

On the other hand, weight increased significantly with supplementation at 6 months and continued to increase for both treatment groups in the open-label extension phase. APOE ε4 noncarriers and high DHA plasma levels were independently associated with weight gain, reported the authors.

As expected, plasma levels of DHA and EPA increased with supplementation (n = 23). In addition, they were associated with reduced levels of some inflammatory cytokines (eg, interleukin-6).

* A genetic risk factor for late-onset AD.

ADAS-cog = Alzheimer's Disease Assessment Scale, cognitive subscale; APOE = apolipoprotein E; MMSE = Mini-Mental State Examination.

Image of cod liver oil capsules from Wikipedia.