Cognitive Health Update


Benjamin Franklin once warned Americans to "beware of the young doctor and the old barber." However, demographic trends suggest that in the not-so-distant future, the country may have far more old barbers than young doctors. By 2050, nearly 87 million people, about 21% of the estimated total U.S. population, will be over the age of 65; only 12% were that old in 2006, according to the U.S. Census Bureau (Suitland, MD). The Bureau also projects a 147% increase in the 65-and-older population between 2000 and 2050, compared with only a 49% increase for the population as a whole.

As the population ages, cognitive health is likely to remain a key concern. So-called mood foods frequently rank high in market research trends reports. And they aren't just for older consumers: more and more, younger shoppers are reaching for products that contain phospholipids, omega-3s, botanical extracts, and other natural ingredients.


In 2003, FDA approved two qualified health claims for the phospholipid phosphatidylserine (PS), linking its consumption to a reduced risk of cognitive decline and dementia in the elderly. Even though it found the evidence "very limited and preliminary," the agency decided to permit the claims, provided manufacturers also include a disclaimer reflecting the state of the evidence.

To meet the rising demand for products that address cognitive health, raw-material suppliers have been busy developing novel PS-related ingredients. For instance, Chemi Nutra (White Bear Lake, MN) launched a new, water-dispersible PS last October that can be used in functional beverages. Chemi developed the ingredient, called SerinAid Disperse 1.5F, in collaboration with Ingredient Innovations International (3i; Wooster, OH). The two companies began working together 10 years ago, said Chemi Nutra president Scott Hagerman.

"With 3i's demonstrated capabilities and our combined applications work in functional drinks, we are excited that PS can now be easily and effectively added to functional beverages, a rapidly evolving segment in the functional foods arena," Hagerman said.

While much of the earlier research involving PS revolved around cognitive decline, some newer studies have explored other mental health concerns, most notably, stress.

At this year's Natural Products Expo West show, held in March in Anaheim, CA, Lipogen Ltd. (Haifa, Israel) announced that it had received a patent from the office of the EU Patent Examiner for its PAS ingredient, a complex of PS and phosphatidic acid derived from soy lecithin. The company already holds the same patent, which covers mental and psychological stress control, in Israel and the United States. According to Lipogen CEO David Rutenberg, PAS helps provide resilience to stress by modulating cortisol levels.

PS may also have a possible application in the field of sports-related stress relief. In the December 4, 2007, issue of the Journal of the International Society of Sports Nutrition, a team of German researchers reported that golfers who ate nutrition bars containing 200 mg of PS for six weeks every day as part of a double-blind, placebo-controlled trial experienced significantly improved ball flight accuracy compared with golfers in a placebo group. The researchers also noted, however, that improvements in stress levels during tee-off were not statistically significant.

"The primary finding of this investigation was that oral supplementation with 200 mg of PS for six weeks in the form of a functional bar significantly improved the number of good ball flights in a group of male golfers with a handicap of 15–40," wrote the authors. "Furthermore, PS intake resulted in a trend of improved perceived stress levels during tee-off. These results suggest that the effective dose of PS supplementation to combat distress might be lower than previously described."


Another phospholipid, citicoline (also known as CDP-choline), may also play a role in cognitive health. Citicoline is a precursor of phosphatidylcholine (PC), which stabilizes neuronal cell membranes. The human body also converts citicoline into the neurotransmitter acetylcholine.

According to Kyowa Hakko USA (New York City), which supplies a citicoline ingredient called Cognizin, citicoline has been used "extensively for the promotion of optimal neural and cognitive function." Moreover, in a review of citicoline studies published in the Cochrane Library in April 2005, the authors concluded that there is "some evidence that CDP-choline has a positive effect on memory and behavior in at least the short- to medium-term in elderly people with cognitive deficits associated with chronic cerebral disorders of the brain."

More recently, researchers led by Perry Renshaw, MD, at McLean Hospital (Belmont, MA), have studied the effects of citicoline on the cognitive function of healthy, middle-aged subjects. In one study, Renshaw's team measured the effects of citicoline on brain energy supply by using mag­netic resonance imaging (MRI) at baseline and then again six weeks after daily supplementation with 500 mg of the nutrient. The team found that the supplement yielded improvements in several brain regions, according to an April 9, 2008, report by CBS News.



For the past few decades, scientists have lavished great attention on the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA and EPA appear to play important roles in a variety of processes related to cognitive health and neural development, making them a key area of interest.

One of the most recent studies involving DHA examined how the nutrient might affect the risk of developing late-onset Alzheimer's disease (AD). In that preclinical study, which was published in the December 26, 2007, issue of the Journal of Neuroscience, UCLA researchers found that DHA stimulates the production of LR11, a protein that may inhibit the production of amyloid plaques linked to AD. The study tested LR11's effects on mouse and rat models as well as cultured human cells.

The researchers used Martek Biosciences Corp.'s (Columbia, MD) life'sDHA for part of the research. NIH scientists are also using Martek's DHA as part of a large clinical study to determine whether DHA slows the progression of AD. That study's results are expected in 2010.

"This study adds to the evidence supporting the important brain health benefits provided by an enhanced DHA status, and there are a number of on­going studies investigating the role of DHA in reducing the risk for neurological diseases like Alzheimer's," said Edward Nelson, MD, vice president of medical research for Martek.

Another omega-3 study currently in progress will compare the effects of DHA and EPA against each other and a placebo on depression. Cedars-Sinai Medical Center (Los Angeles) re­search­ers will conduct the NIH-sponsored study, which will involve 300 adults with major depressive disorder, over a five-year period.

"This study is one of several in­vestigations of alternative and com­plementary medicine that our de­partment has pursued over the past de­cade," said lead principal investigator and department chair Mark Rapaport, MD. "Expanding our psychiatry studies to include natural treatments has shown promising benefits to patients suffering from a variety of mental illnesses."

While many omega-3 studies have yielded positive re­sults, a new review published on April 16, 2008, in the Cochrane Library suggests that, for some problems related to cognitive health, the benefits of DHA and EPA are uncertain. One area that needs more data, according to the Cochrane review's authors, is the area of bipolar disorder.

In the review, Oxford University lecturer Paul Montgomery, PhD, and senior research fellow Alex Richardson, PhD, found that of five studies that tested the effects of omega-3 supplements on bipolar disorder, only one had enough data for analysis. That study, which involved 75 patients, found that omega-3 supplements seemed to reduce severe depression but not mania.

"There is currently insufficient evidence on which to base any clear recommendations concerning omega-3 fatty acids for bipolar disorder," wrote Montgomery and Richardson. "However, given the general health benefits and safety of omega-3s, the preliminary evidence from this review provides a strong case for well-powered, high-quality trials in specific index populations."


At the 19th annual meeting of the American Neuropsychiatric Association (Columbus, OH), held in March in Savannah, GA, University of Cincinnati researchers described new research involving chromium picolinate.

Because chromium picolinate is known to regulate blood glucose levels, the researchers decided to test its effects on cognitive performance by randomly administering either 1000 µg of chromium picolinate or a placebo per day for 12 weeks to 13 elderly volunteers in the early stages of memory decline. The researchers then analyzed the brain activity of the volunteers by using functional magnetic resonance imaging (fMRI). The volunteers in the treatment group showed greater activity in several regions of the brain.

The research expanded on findings from a December 2007 study that linked intake of chromium picolinate with improved brain glucose metabolism, memory recall, and motor speed. In both studies, the researchers used chromium picolinate supplied by Nutrition 21 (Purchase, NY).

"The current study showed that older adults taking chro­mium picolinate exhibited greater brain activation while engaged in a cognitively demanding task," said lead investigator Robert Krikorian, PhD, an associate professor at the University of Cincinnati's College of Medicine. "These brain imaging results support findings from the prior study suggesting that chromium picolinate may be beneficial for older adults with early memory decline and metabolic irregularities, factors that substantially increase the risk for dementia. These findings substantiate the need for continued research to determine the nature and extent of this enhancement."


Lastly, several recent studies suggest that some botanical ingredients may also have a positive impact on cognitive health. Although their exact mechanisms of action are still largely unknown, some herbs appear to inhibit the production of enzymes and other compounds that lead to nerve cell damage. Many of these early findings, however, are based on in vitro or pilot clinical trials that require more follow-up.

One in vitro study that appeared in the September 2006 issue of the Journal of Alzheimer's Disease found that turmeric extracts known as curcuminoids may help macrophage cells clear amyloid-beta plaques. In the experiment, the researchers added the curcuminoids to macrophage cells collected from six AD patients and three control patients. The researchers determined that amyloid-beta uptake in three of the six AD macrophage samples increased significantly. Sabinsa Corp. (Piscataway, NJ) supplied its Curcumin 3 complex for use in the study.

Researchers are also taking a closer look at another bo­tanical ingredient, Huperzine A. Derived from the moss Huperzia serrata, Huperzine A may inhibit acetylcholine­sterase, an enzyme that depletes stores of the neurotransmitter acetylcholine. Because its actions appear to be similar to some drugs used to treat AD, researchers have ex­plored the possibility that the extract could one day be useful for people with that condition. However, according to a review of six clinical trials involving 454 people that was recently published in the Cochrane Library, evidence for Huperzine A is mixed. The review's authors wrote that while the ingredient may have some beneficial effects, more clinical studies are needed.

"These findings are based on a small number of trials, but the data indicate that it would be well worth setting up some more high-quality assessments of this interesting drug," said lead author Hongmei Wu, PhD, an associate professor of geriatrics at Sichuan University (Chengu, Sichuan, China).

Another botanical ingredient, pine bark (Pinus pinaster) extract, may have a protective effect via its antioxidant properties. At the 2008 World Congress on Oxidants and Antioxidants in Bio­logy conference, held in March in Santa Barbara, CA, researchers from Swinburne University's Center for Neuro­psychology (Melbourne, Australia) reported that the pine bark extract Pycnogenol had beneficial cognitive effects on older people.

In the double-blind, placebo-controlled study, which will be published in a future issue of the Journal of Psychopharmacology, elderly volunteers who consumed 150 mg of Pycnogenol per day for three months had lower levels of F2-isoprostanes, a by-product of the oxidation of fatty acids in nerve cell membranes, than volunteers in the placebo group. Horphag Research (Geneva) supplied the Pycnogenol used in the study.

"These results support research from a range of disciplines that suggest that antioxidants may have an effect in preserving or enhancing specific mental functions," said the study's lead investigator, Con Stough, PhD, director of Swinburne University's Center for Neuropsychology. "Cognitive research in this area specifically indicates that the putative benefits associated with antioxidant supplementation are associated with memory."

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