Improved working memory but no effect on striatal vesicular monoamine transporter type 2 after omega-3 polyunsaturated fatty acid supplementation.
Studies in rodents indicate that diets deficient in omega-3 polyunsaturated fatty acids (n-3 PUFA) lower dopamine neurotransmission as measured by striatal vesicular monoamine transporter type 2 (VMAT2) density and amphetamine-induced dopamine release. This suggests that dietary supplementation with fish oil might increase VMAT2 availability, enhance dopamine storage and release, and improve dopamine-dependent cognitive functions such as working memory. To investigate this mechanism in humans, positron emission tomography (PET) was used to measure VMAT2 availability pre- and post-supplementation of n-3 PUFA in healthy individuals. Healthy young adult subjects were scanned with PET using [(11)C]-(+)-α-dihydrotetrabenzine (DTBZ) before and after six months of n-3 PUFA supplementation (Lovaza, 2 g/day containing docosahexaenonic acid, DHA 750 mg/d and eicosapentaenoic acid, EPA 930 mg/d). In addition, subjects underwent a working memory task (n-back) and red blood cell membrane (RBC) fatty acid composition analysis pre- and post-supplementation. RBC analysis showed a significant increase in both DHA and EPA post-supplementation. In contrast, no significant change in [(11)C]DTBZ binding potential (BP(ND)) in striatum and its subdivisions were observed after supplementation with n-3 PUFA. No correlation was evident between n-3 PUFA induced change in RBC DHA or EPA levels and change in [(11)C]DTBZ BP(ND) in striatal subdivisions. However, pre-supplementation RBC DHA levels was predictive of baseline performance (i.e., adjusted hit rate, AHR on 3-back) on the n-back task (y = 0.19+0.07, r(2) = 0.55, p = 0.009). In addition, subjects AHR performance improved on 3-back post-supplementation (pre 0.65±0.27, post 0.80±0.15, p = 0.04). The correlation between n-back performance, and DHA levels are consistent with reports in which higher DHA levels is related to improved cognitive performance. However, the lack of change in [(11)C]DBTZ BP(ND) indicates that striatal VMAT2 regulation is not the mechanism of action by which n-3 PUFA improves cognitive performance.
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America. narendranr@upmc.edu
Rajesh
R
Narendran
William G
WG
Frankle
Neale S
NS
Mason
Matthew F
MF
Muldoon
Bita
B
Moghaddam
D019587:Dietary Supplements; D004298:Dopamine / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D013747:Tetrabenazine / Q000031:analogs & derivatives; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*; D055815:Young Adult
C575320:(11C)-(+)-alpha-dihydrotetrabenazine; D015525:Fatty Acids, Omega-3; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; D004298:Dopamine; D013747:Tetrabenazine