A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease

Abstract

Oxidative stress, inflammation, and increased cholesterol levels are all mechanisms that have been associated with Alzheimer's disease (AD) pathology. Several epidemiologic studies have reported a decreased risk of AD with fish consumption. This pilot study was designed to evaluate the effects of supplementation with omega-3 fatty acids alone (ω-3) or omega-3 plus alpha lipoic acid (ω-3 + LA) compared to placebo on oxidative stress biomarkers in AD. The primary outcome measure was peripheral F2-isoprostane levels (oxidative stress measure). Secondary outcome measures included performance on: Mini-Mental State Examination (MMSE), Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL), and Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Thirty-nine AD subjects were randomized to one of three groups: 1) placebo, 2) ω-3, or 3) ω-3 + LA for a treatment duration of 12 months. Eighty seven percent (34/39) of the subjects completed the 12-month intervention. There was no difference between groups at 12 months in peripheral F2-isoprostane levels (p = 0.83). The ω-3 + LA and ω-3 were not significantly different than the placebo group in ADAS-cog (p = 0.98, p = 0.86) and in ADL (p = 0.15, p = 0.82). Compared to placebo, the ω-3 + LA showed less decline in MMSE (p < 0.01) and IADL (p = 0.01) and the ω-3 group showed less decline in IADL (p < 0.01). The combination of ω-3 + LA slowed cognitive and functional decline in AD over 12 months. Because the results were generated from a small sample size, further evaluation of the combination of omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted.

Keywords: Alpha-lipoic acid; Alzheimer's disease; clinical trial; omega-3 fatty acids.

Fig. 1

Study flow.

Fig. 2

F2 isoprostane levels. Standardized urine F2-isoprostane levels by adjusting for creatinine. Comparison between groups measured at baseline (p = 0.03), 6 months (p = 0.78), and 12 months (p = 0.83) by linear regression adjusting for age and body mass index. Error bars indicate standard error of the mean.

Fig. 3

Mini-Mental State Exam. Comparison of change scores for activities of daily living, using linear mixed effects model adjusting for age and education, error bars indicate standard error of the mean. A lower score reflects worsening of MMSE. No difference between placebo and ω-3 was found over 12 months (p = 0.80). A significant difference was found between placebo and ω-3 + LA over 12 months (p < 0.01).

Fig. 4

Instrumental activities of daily living. Comparison of change scores for instrumental activities of daily living, using linear mixed effects model adjusting for age and education. Error bars indicate standard error of the mean. A higher score reflects worsening of IADL. A significant difference was found between placebo and ω-3 and between placebo and ω-3+ LA over 12 months (p< 0.01, p = 0.01).