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.

Application of fatty acid and lipid measurements in neuropsychiatry

“…Senile plaques are also one of the characteristics of AD and their main component is β-amyloid [112]. To counteract some of the AD symptoms, such as cognitive impairment, supplementing with omega-3 fatty acids showed a positive outcome both in mice models [114,115] and AD patients [116].…”

Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease

“…Finally, the most recent trial was carried out on a small group of patients with mild-tomoderate AD who were administered fish oil containing DHA and EPA. In this pilot study, significant recovery of cognitive capacity was evident in the patients treated with fish oil (with or without lipoic acid supplementation) [150] (clinicaltrials.gov ID: #NCT00090402). Together, these studies indicate that DHA supplementation may represent a plausible therapeutic approach for the treatment of the physiological age-related cognitive decline, although it is unclear what type of ω-3 PUFAs could be used to treat AD.…”

“…Some of these discrepancies in the different randomized studies may reflect the source of the ω-3 PUFAs administered to the patients. As yet there is no consensus with regards the defined sources of ω-3 PUFAs or a standard ratio or dose of DHA and EPA: Quinn et al [80] evaluated 2 g/day DHA, FreundLevi et al [149] evaluated the effect of fish oil administration with a DHA and EPA content of 1.7 and 0.6 g/day, respectively (EPAX 1500 TG; Pronova Biocare, Norway), and Shinto et al [150] evaluated a fish oil daily dose containing 675 mg DHA and 975 mg EPA, the latter trial being the only efficacious treatment against AD in humans and having a different DHA:EPA ratio with respect to the former.…”

Curative role of lactulose, L-carnitine, alpha-lipoic acid and combination of L-carnitine and alpha-lipoic acid in a rat model of acute hepatic encephalopathy: Biochemical observations

“…ALA Possesses a unique antioxidant ALA/DHLA system. Thus, DHLA is able to reduce not only reactive oxygen species (ROS) but also oxidize forms of other antioxidants [7]. Due to thiol groups and free thiols, ALA is essential in GSH synthesis, thereby maintaining maximum levels of other antioxidants such as vitamins C and E, SOD and catalase (CAT) [8].…”