Tapping into Brain Power

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The more consumers learn and remember about brain and memory support supplements, the more likely they are to turn to them for a mental boost.


The more consumers learn and remember about brain and memory support supplements, the more likely they are to turn to them for a mental boost.

That’s the consensus of industry experts, who predict a bright future for the category as long as sound science supports supplements’ role in improving mental acuity.

“Based on research Kyowa Hakko commissioned from the Gallup Organization, we have found that use of vitamins and minerals or herbal supplements exceeds the use of prescription medication to treat or prevent memory loss,” says Karen Todd, senior marketing manager for Kyowa Hakko (New York City). “We are seeing that typical vitamin users are now taking formulations specifically for memory over those taking herbal supplements. And over half of those using vitamin and mineral supplements to treat memory loss believe that nutrients have benefits for memory or concentration.”

Scott Hagerman, president of Chemi Nutra (White Bear Lake, MN), agrees that cognitive-enhancing nutraceuticals have nowhere to go but up, as the number of consumers affected by problems with memory and mental acuity continues to grow. In particular, he cites recent research by Matthew Muldoon, MD, at the University of Pittsburgh that suggests statins, used by an estimated 20 million Americans to lower cholesterol, may impair cognitive functioning. The study results, published in the American Journal of Medicine last December, showed minor negative changes in attention and memory in patients who used simvastatin (Zocor), similar to results from a 2000 study involving lovastatin (Mevacor).

Hagerman also points to new research looking at an association between hormone replacement therapy in women and impaired mental performance. Coupled with projections from the Alzheimer’s Association (Chicago) that the disease will strike more than 14 million people by 2050-up from 4 million today-he foresees an increasing number of consumers looking for ways to improve mental acuity without drugs.


Omega-3 fatty acids are the highest-profile brain support ingredient today, thanks to a solid foundation of research. In fact, the Alzheimer’s Foundation of America (New York City) recommends that consumers eat a diet with an “abundant supply of omega-3 fatty acids” for brain health, while the Alzheimer’s Association advocates consuming “cold water fish that may contain beneficial omega-3 fatty acids.”

“Omega-3 fatty acids are generally becoming more popular,” says Todd. “As the research continues, they are finding that omega-3 fatty acids may possess mood-stabilizing action and could be of benefit for brain support.” Docosahexaenoic acid (DHA) is the most important omega-3 fatty acid for brain health, according to studies, and it is significantly enriched in tissues such as the brain, but it can become depleted if a consumer’s diet is low in DHA.

Unfortunately, most Americans eat very little of the organ meats and fish that contain the greatest amounts of DHA. To help remedy that, the updated Dietary Guidelines for Americans, released in January by the United States Department of Health and Human Services (Washington, DC) and the United States Department of Agriculture (Washington, DC), for the first time include a mention of DHA. The guidelines state that “limited evidence suggests an association between consumption of fatty acids in fish and reduced risks of mortality from cardiovascular disease for the general population.”

“DHA is an important structural component of the brain and supports brain function. Every day, we lose about 1% of DHA from our brain, so it’s important to get preformed DHA from our diet every day to replace these losses,” says Lorie Ellis, principal clinical research scientist with Martek Biosciences (Columbia, MD), which markets DHA created by a process that extracts DHA from algae. “Americans consume the lowest levels of preformed DHA from our diet. What scientists are now beginning to understand is that inadequate consumption of dietary DHA over a period of 20 or more years may lead to drastically reduced levels of DHA in tissues such as the brain. Most importantly, we need to educate people that maintaining adequate DHA throughout life may not only be important for supporting optimal development and function of the brain, but it may also be important for prevention of chronic disease.”

One of the newest studies, using Martek DHA and aged mice, suggests that DHA may protect against the accumulation of a protein believed to be linked to Alzheimer’s disease, according to results published in the March 30, 2005, issue of The Journal of Neuroscience.

“The study is significant because it shows that DHA added to the diet altered the processing of the amyloid precursor protein and the accumulation of its toxic amyloid protein metabolite that is widely believed to cause Alzheimer’s,” says Greg Cole, PhD, lead investigator for the study, associate director for geriatric research at the Veterans Administration Greater Los Angeles Healthcare System, and professor of medicine and neurology at the University of California at Los Angeles. “These and other beneficial results were observed even when the diets were changed late in life.

“While there are powerful new experimental drugs that may also work, we were doubly excited to get this result with a treatment that has already been proved so safe in humans that it is added to infant formula. Because of this proven safety and epidemiological evidence associating low DHA intake with increased risk of Alzheimer’s disease, we are now hopeful that clinical trials will show that DHA can prevent or help treat this terrible disease,” says Cole.

And in September, results will be released from the OmegAD controlled clinical study in Stockholm, Sweden, a six-month research project involving patients with an early stage of Alzheimer’s dementia. In the placebo-controlled study at Karolinska Hospital in Stockholm, patients were randomly assigned to treatment with either a Pronova Biocare (Lysaker, Norway) EPAX omega-3 supplement containing DHA and eicosapentaenoic acid (EPA), or a placebo, to see if a high intake of a DHA-enriched concentrate would help cognitive development in an early stage of Alzheimer’s disease. At the other end of the life spectrum, a study published in the April 2005 issue of The Journal of Pediatrics suggests that infant formula supplemented with DHA and arachidonic acid (ARA) results in enhanced growth and higher mental and psychomotor development in preterm infants.

“Parents can make sure infants receive an adequate amount of these nutrients by selecting an infant formula with a sufficient level of DHA and ARA,” says Henry Linsert Jr., chairman and CEO of Martek. “In addition, women who are breastfeeding can take a DHA dietary supplement to ensure adequate levels of DHA in their breast milk. This is particularly important because pregnant and nursing women in the United States do not typically receive enough DHA through their diets to pass on the necessary amount to their developing infants.”


With more than 550 peer-reviewed published articles about its use and efficacy as a drug worldwide-and as a dietary supplement in the United States-citicoline has been recognized for its role in cognitive function and memory retention. Citicoline is involved in the synthesis of phospholipids, which make up the membranes of cells, especially the pathway involving phosphatidylcholine, says Kyowa Hakko’s Todd. “When taken orally, citicoline is metabolized to yield the free nucleotides uridine and choline,” says Todd. “Both elements cross the blood-brain barrier, become incorporated into brain membrane phospholipids, and increase the production of neurotransmitters in the central nervous system, including the synthesis of acetylcholine, noradrenaline, and dopamine.”

And recent studies have shown that citicoline has a targeted action for increasing brain phospholipids synthesis. “Kyowa Hakko conducted a Cognizin citicoline study using a Morris water maze, a cylindrical water-filled pool with a hidden platform,” says Todd, adding that mice normally learn the location of the platform after repeated training. However, the mice in the study were fed a diet containing 2% Cognizin for four weeks without training. “Mice that ingested Cognizin citicoline remembered how to reach the submerged platform better than control mice,” says Todd, “thus exhibiting enhanced memory-related abilities.”

Citicoline was also the subject of two recent studies under the direction of Perry Renshaw, MD, PhD, director of the Brain Imaging Center at McLean Hospital (Belmont, MA) and a psychiatry professor at Harvard Medical School (Boston). Both studies showed highly beneficial effects in maintaining cognitive function, and one of the studies provided the first in vivo data demonstrating that oral citicoline intake may be useful in reversing age-related cognitive changes.


Phosphatidylserine (PS), a naturally occurring phospholipid that is essential to brain cell structure, has been researched in more than 60 human clinical studies over more than 20 years in both North America and Europe. It has also been studied in 17 double-blind, placebo-controlled clinical trials that have consistently proved its value as a dietary supplement. In fact, two years ago, the Food and Drug Administration (Rockville, MD) approved two health claims for PS: “Phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly,” and “Phosphatidylserine may reduce the risk of dementia in the elderly.”

“The establishment of health claims for PS [was] very significant, since approximately 5 million Americans, including a large percentage of the elderly, have some form of cognitive dysfunction or dementia,” says Hagerman of Chemi Nutra, which markets soybean-derived phospholipid compounds in the United States under the SerinAid label. “This development underscores the health benefits of PS.”

Today, researchers continue to study PS, including a one-year project at the University of Guadalajara in Mexico that was scheduled to conclude in May, examining the incidence of memory loss that accompanies hormone replacement therapy in women.

Hagerman also recommends combining PS with alpha-glyceryl phosphoryl choline (A-GPC), an important building block of acetylcholine, the brain’s most prominent neurotransmitter. A-GPC has long been prescribed as a pharma-ceutical in Europe, and Chemi Nutra introduced AlphaSize A-GPC in the United States several years ago, backed up by research suggesting that it may play a role in improving conditions associated with mild to moderate Alzheimer’s dementia. Both PS and A-GPC have great application in mental acuity formulations, says Hagerman, and would make an ideal brain support nutritional supplement when used together.


In April, scientists at the Oregon Health & Science University School of Medicine’s (OHSU; Portland, OR) Department of Neurology and the OHSU MS Center of Oregon reported the results of a study that found that ginkgo, which is derived from the fan-shaped leaves of the Ginkgo biloba tree, may help improve attention in multiple sclerosis patients with cognitive impairment. The 20 patients in the study who received Ginkgo biloba “performed better on a test that measures a person’s ability to pay attention and to sort conflicting information,” according to Jesus Lovera, MD, the study’s lead author. Lovera says the differences in test results among those who received ginkgo and those who received a placebo were comparable to the differences in test scores between healthy people ages 30 to 39 and those ages 50 to 59.

“[Ginkgo] has been shown to be of benefit in Alzheimer’s, but we did not know if it would work for MS,” he adds. “The study suggests that for cognitive problems, it may only help a certain group of [MS] patients. We need to study this further.”


Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata, used in Chinese traditional medicine for swelling, fever, and blood disorders. But it has recently generated interest as an Alzheimer’s treatment to improve cognitive function, and studies suggest that huperzine A may also have chemical properties that help protect nerve cells.

“Huperzine A helps to prevent the breakdown of acetylcholine, which is used by the central nervous system in signal transmission,” explains Corey McNeely, national sales manager for Creative Compounds LLC (Scott City, MO). “Studies testing the efficacy of huperzine A have shown improvements in memory and comprehension that suggest huperzine A’s benefits could extend beyond Alzheimer’s applications to healthy adults.”

The first controlled clinical trials to assess toxicity and efficacy outside of China started in April 2004, funded by the National Institutes of Health’s (Bethesda, MD) National Institute on Aging. The multicenter, double-blind, placebo-controlled trial of huperzine as a treatment for mild to moderate Alzheimer’s disease is expected to be completed in December 2005, with a planned enrollment of 150 patients.