Study Title:

DHA Improves Working Memory in Healthy Young Adults

Study Abstract

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 [11C]-(+)-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 [11C]DTBZ binding potential (BPND) 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 [11C]DTBZ BPND 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, r2 = 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 [11C]DBTZ BPND indicates that striatal VMAT2 regulation is not the mechanism of action by which n–3 PUFA improves cognitive performance.

From press release:

While Omega-3 essential fatty acids -- found in foods like wild fish and grass-fed livestock -- are necessary for human body functioning, their effects on the working memory of healthy young adults have not been studied until now.


In the first study of its kind, researchers at the University of Pittsburgh have determined that healthy young adults ages 18-25 can improve their working memory even further by increasing their Omega-3 fatty acid intake. Their findings have been published online in PLOS One.

"Before seeing this data, I would have said it was impossible to move young healthy individuals above their cognitive best," said Bita Moghaddam, project investigator and professor of neuroscience. "We found that members of this population can enhance their working memory performance even further, despite their already being at the top of their cognitive game."

Led by Rajesh Narendarn, project principal investigator and associate professor of radiology, the Pitt research team sought healthy young men and women from all ethnicities to boost their Omega-3 intake with supplements for six months. They were monitored monthly through phone calls and outpatient procedures.

Before they began taking the supplements, all participants underwent positron emission tomography (PET) imaging, and their blood samples were analyzed. They were then asked to perform a working memory test in which they were shown a series of letters and numbers. The young adults had to keep track of what appeared one, two, and three times prior, known as a simple "n-back test."

"What was particularly interesting about the presupplementation n-back test was that it correlated positively with plasma Omega-3," said Moghaddam. "This means that the Omega-3s they were getting from their diet already positively correlated with their working memory."

After six months of taking Lovaza -- an Omega-3 supplement approved by the Federal Drug Administration -- the participants were asked to complete this series of outpatient procedures again. It was during this last stage, during the working memory test and blood sampling, that the improved working memory of this population was revealed.

"So many of the previous studies have been done with the elderly or people with medical conditions, leaving this unique population of young adults unaddressed," said Matthew Muldoon, project coinvestigator and associate professor of medicine at Pitt. "But what about our highest-functioning periods? Can we help the brain achieve its full potential by adapting our healthy behaviors in our young adult life? We found that we absolutely can."

Although the effects of Omega-3s on young people were a focus, the Pitt team was also hoping to determine the brain mechanism associated with Omega-3 regulation. Previous rodent studies suggested that removing Omega-3 from the diet might reduce dopamine storage (the neurotransmitter associated with mood as well as working memory) and decrease density in the striatal vesicular monoamine transporter type 2 (commonly referred to as VMAT2, a protein associated with decision making). Therefore, the Pitt researchers posited that increasing VMAT2 protein was the mechanism of action that boosted cognitive performance. Unfortunately, PET imaging revealed this was not the case.

"It is really interesting that diets enriched with Omega-3 fatty acid can enhance cognition in highly functional young individuals," said Narendarn. "Nevertheless, it was a bit disappointing that our imaging studies were unable to clarify the mechanisms by which it enhances working memory."

Ongoing animal modeling studies in the Moghaddam lab indicate that brain mechanisms that are affected by Omega-3s may be differently influenced in adolescents and young adults than they are in older adults. With this in mind, the Pitt team will continue to evaluate the effect of Omega-3 fatty acids in this younger population to find the mechanism that improves cognition.

Study Information

Rajesh Narendran, William G. Frankle, Neale S. Mason, Matthew F. Muldoon, Bita Moghaddam
Improved Working Memory but No Effect on Striatal Vesicular Monoamine Transporter Type 2 after Omega-3 Polyunsaturated Fatty Acid Supplementation
PLoS ONE
2012 October
University of Pittsburgh

Full Study

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0046832