Beauty Health for Life

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 erred to as VMAT2, a protein associated with decision making). Theore, 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.

Other Pitt researchers involved in the project include William G. Frankle, professor of psychiatry, and Neal S. Mason, research assistant professor of radiology.

The paper, “Improved Working Memory but No Effect on Striatal Vesicular Monoamine Transporter Type 2 after Omega-3 Polyunsaturated Fatty Acid Supplementation” was published online Oct. 3 by PLOS One and supported by grants from the National Institute on Drug Abuse and the American Reinvestment and Recovery Act of 2009.

Although problems with memory become increasingly common as people age, in some persons, memories last long time, even a life time. On the other hand, some people experience milder to substantial memory problems even at an earlier age.

Although there are several risk factors of dementia, abnormal fat metabolism has been known to pose a risk for memory and learning. People with high amounts of abdominal fat in their middle age are 3.6 times as likely to develop memory loss and dementia later in their life.

Neurological scientists at the Rush University Medical Center in collaboration with the National Institutes of Health have discovered that same protein that controls fat metabolism in the liver resides in the memory center of the brain (hippocampus) and controls memory and learning.

Results from the study funded by the Alzheimer’s Association and the National Institutes of Health were recently published in Cell Reports.

“We need to better understand how fat is connected to memory and learning so that we can develop effective approach to protect memory and learning,” said Kalipada Pahan, PhD, the Floyd A. Davis professor of neurology at Rush University Medical Center.

The liver is the body’s major fat metabolizing organ. Peroxisome proliferator-activated receptor alpha (PPARalpha) is known to control fat metabolism in the liver. Accordingly, PPARalpha is highly expressed in the liver.

“We are surprised to find high level of PPARalpha in the hippocampus of animal models,” said Pahan.

“While PPARalpha deficient mice are poor in learning and memory, injection of PPARα to the hippocampus of PPARalpha deficient mice improves learning and memory," said Pahan.

Since PPARalpha directly controls fat metabolism, people with abdominal fat levels have depleted PPARalpha in the liver and abnormal lipid metabolism. At first, these individuals lose PPARalpha from the liver and then eventually from the whole body including the brain. Theore, abdominal fat is an early indication of some kind of dementia later in life, according to Pahan.

By bone marrow chimera technique, researchers were able to create some mice having normal PPARalpha in the liver and depleted PPARalpha in the brain. These mice were poor in memory and learning. On the other hand, mice that have normal PPARalpha in the brain and depleted PPARalpha in the liver showed normal memory.

“Our study indicates that people may suffer from memory-related problems only when they lose PPARalpha in the hippocampus”, said Pahan.

CREB (cyclic AMP response element-binding protein) is called the master regulator of memory as it controls different memory-related proteins. “Our study shows that PPARalpha directly stimulates CREB and thereby increases memory-related proteins”, said Pahan.

“Further research must be conducted to see how we could potentially maintain normal PPARalpha in the brain in order to be resistant to memory loss”, said Pahan.

Other Rush researchers involved in this study include Avik Roy, PhD, research assistant professor; Malabendu Jana, PhD assistant professor; Grant Corbett, neuroscience graduate student; Shilpa Ramaswamy, instructor; and Jeffrey H. Kordower, PhD, the Jean Schweppe Armour professor of neurological sciences.

Alzheimer’s disease is the most common human disorder associated with memory loss. This disease slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks. Nationwide, the total payments for services for people with Alzheimer’s and other forms of dementia will total $203 billion in 2013. By 2050, the total costs are expected to increase 500 percent to a staggering $1.2 trillion.