A HEAD FOR SUPPLEMENTS
08/Aug/2005
Ingredients, branded and otherwise, can boost cognitive function and memory.
July/August Issue of the Nutrition Industry Executive
By Paul Bubny
A recent U.S. News & World Report cover story told readers that human beings are only consciously aware of about 5 percent of their own cognitive systemâs daily operations. However, just as scientists are making new discoveries about the other 95 percent, so consumers are learning more about how valuable nutrition is in maintaining and preserving cognitive function and memory.
"Almost every week there are articles that address new research findings on various ingredients that help maintain and improve memory, learning, focus, and concentration," said Scott Hagerman, president and CEO of Chemi Nutra (White Bear Lake, MN), which markets SerinAid PS.
"Most consumers," Hagerman said, "would agree that mental abilities are perhaps the most important abilities that we possess, and therefore, any natural approach to maintaining and improving these core abilities is worth investing in. Obviously, it has been shown that proper diet, exercise, and sleep can all help contribute to overall mental performance. But without doubt, there are a number of scientifically proven natural ingredients, like [phosphatidylserine, or PS] and alpha-glyceryl phosphoryl choline [A-GPC, a/k/a GPC]that can dramatically assist in cognitive enhancement, stress reduction, and mood improvement."
It's a far cry from, say, 10 years ago, when ginkgo biloba, which Hagerman credited with originating the brain-health category, was pretty much all most consumers recognized. Today, said researcher and author Parris M. Kidd, Ph.D., a consultant to Science & Ingredients, Inc. (Carlsbad, CA), "We see considerable awareness of PS. This is seen as the premier nutrient for memory and cognition. There is still less awareness of GPC, but this nutrient also has a great deal of credibility and strong science behind it, so that its awareness is rapidly on the increase."
"Both these nutrients are orthomolecules, occurring naturally in all our cells and integral to life since its very beginnings," he continued. "This helps explain why they are as safe and effective as the clinical research has shown them to be. Some consumers still associate ginkgo with memory function, but the number of users has declined sharply in the last years, while the demand for PS and GPC has sharply increased."
Certainly, as people reach middle age and beyond, the tendency is to interpret every instance of forgetfulness as an early sign of Alzheimerâs disease (AD). Age-related cognitive decline is a fact of life, making consumers in this age group a natural customer base for supplements that address cognitive health. However, as Peter Rohde, CEO of Science & Ingredients, pointed out, "Brain related products cover a wide field of applications. Among these," said Rohde, are the following:
- "About 10 percent of all children (and most likely also adults) have attention problems."
- "People of all ages, but particularly students, want to improve learning and memory."
- "Fighting stress is a serious challenge for younger and middle age people."
- "When people grow older, they become concerned about age related memory impairment."
- "When people are old, they have increasing concern about dementia. PS and GPC [a/k/a A-GPC] provide opportunities for all these age groups and conditions."
"Obviously, cognitive enhancing supplements cost more than traditional vitamins and minerals because they are often complex, science-substantiated, and costly to manufacture," added Hagerman. "For this reason, brain-related supplements are likely more often purchased by individuals, for example baby-boomers, who have higher levels of disposable income, and generally also higher education levels."
"There is a strong and growing consumer awareness generated by media about cognitive function, especially related to neurodegenerative diseases," said Neil Sullivan, director of marketing for New York City-based Kyowa Hakko USA, suppliers of the citocoline-derived ingredient Cognizin. "With many new and innovative ingredients such as Cognizin available in the U.S. market, the potential for manufacturers to provide optimum, efficacious products to the widening range of consumers is increasing. The innovative applications for brain health products will cause a revolution in the development of more effective and disease specific supplements."
Kenn Israel, director of communications for Soft Gel Technologies, Inc. (Los Angeles), offered a similar take. "The market for cognitive support will continue to grow as nutritional products consumers continue to gray," he said. "The awareness that cognitive function can be maintained throughout life coupled with the increased stress and competitive nature of modern life translates into demand for this class of products. Providing effective materials and formulations is the task of suppliers and manufacturers."
"The popularity of ginkgo was just the beginning of the cognitive support category; research demonstrating the efficacy of other ingredients will support increased sales," Israel continued. "Currently there are untapped potential sales, and effective ingredients and formulas will capitalize on these opportunities."
New Findings
In recent weeks, studies have been disseminated showing cognitive-function benefits for a number of supplement ingredients. Writing in the Journal of Nutrition, researchers at the Julius Center for Health Sciences and Primary Care in Utrecht, the Netherlands, reported that consuming lignans could help preserve cognitive function in postmenopausal women and lower their risk of developing AD.
The study involved 394 healthy postmenopausal women who had an intact uterus and at least one intact ovary, and who had not used hormonal replacement therapy since their last menstrual period. One group had experienced a natural menopause between 1969 and 1979, and the others between 1987 and 1989.
Their intake of phytoestrogens (lignans as well as isoflavones) during the year before enrolling in the study was estimated by a validated food frequency questionnaire. Cognitive function was assessed by a mini-mental state examination (MMSE), entailing questions and tasks associated with orientation, registration, attention, calculation, recall and language. The researchers found that those who consumed higher levels of lignans performed better in the MMSE, particularly the women who experienced menopause between 1969 and 1979. One possible explanation, the researchers wrote, was the cumulative effect of consuming lignans.
The lignans study did not look for evidence of AD or other forms of dementia in its subjects, but another Dutch study, presented at an Alzheimerâs Association convention held in Washington, DC, focused on dementia prevention through high doses of folic acid supplements. Participants in the study were men and women ages 50 to 70 with elevated levels of homocysteine. Those who took 800 mcg of folic acid daily over three years performed significantly better in cognitive tests than those who took a placebo. Their memory was comparable to that of people two to five years younger, according to researchers from Wageningen University in the Netherlands.
The researchers claimed that theirs was the first study to zero in on the cognition-preserving effects of folic acid, rather than B vitamins in general. A trial is underway at the National Institutes of Health to determine whether very high doses of folic acid and vitamins B-6 and B-12 can slow the rate of mental decline in AD patients. Results are expected next year.
Unigen Pharmaceuticals (Lacey, WA) recently issued the results of a randomized, double blind placebo controlled human clinical study of its ingredient Lasoperin, which is derived from two traditional plants: the roots of Scutellaria baicalensis and the heartwood of Acacia catechu. According to Unigen, the study showed improvement of cognitive function in healthy people ages 35 to 65 over a four-week trial period; recruitment, qualification, and examination of the subjects were all completed via the Internet.
"Lasoperin produced significant improvements in processing speed, and in processing efficiency reflecting significantly improved attention, or focus over the 4 week trial (vs. baseline measure)," according to Unigen. "It is interesting to note that the benefits observed in this study are primarily related to performance speed (e.g., reaction time) and improved consistency (e.g., reduced standard deviation). Performance relative to the number of items correct in the memory tasks improved slightly but ceiling effects may prevent detection of statistically significant findings with this index of cognitive function."
"In healthy adults who are already functioning at near optimal levels, many of the standard 'pencil and paper' tests are not sensitive to subtle changes," the company stated. "The use of computerized tests offers an advantage of adding a temporal measure, which may be more sensitive to subtle benefits or deficits. This is the case with respect to the cognitive benefits demonstrated by Lasoperin examined in this study, a high baseline level of performance for correct choices limits the sensitivity of that particular measure, but the speed of processing demonstrates a significant improvement in response to the treatment."
Numerous Studies
Kyowa Hakko's Sullivan said "numerous scientific studies" have been conducted on his company's Cognizin, indicating "its effectiveness in treating the symptoms of Alzheimer's and Parkinson's disease, improved stroke recuperation, and ocular health including glaucoma." Research conducted by the company has shown that Cognizin provides "a targeted action for increasing brain phospholipid synthesis," said Sullivan. "Cognizin is broken down and absorbed as uridine and choline within the brain; neuron cells convert uridine into cytidine, which reacts with choline to reconstitute Cognizin. Cognizin then moves into the metabolic pathway of phosphatidylcholine production in the brain."
In a study that helped the company win the NutrAward for product innovation at Natural Products Supply Expo in Anaheim, CA last year, Kyowa Hakko conducted a Cognizin study using a Morris water maze (cylindrical water-filled pool) platform to research the memory capacity of mice. The study involving 40 eight-week-old male mice focused on the tendency of mice to memorize the platform location and to mount it from the water. The device measured the subject's memorization and learning capacities.
"At the start of training, mice exhibited a tendency to swim around the pool structure. During a four-week period, half the mice were fed a diet containing 2 percent Cognizin. Mice who ingested Cognizin remembered how to reach the submerged platform better, thus exhibiting enhanced memory-related abilities," Sullivan said. "The study also showed that because both groups of mice were swimming at the same speed during the test, Cognizin did not appear to affect mobility."
In an article available for download at the Cognizin Website, Toshi Kamiya, Ph.D., researcher with Kyowa's parent company, discussed a 1996 human study of citocoline conducted at the Massachusetts Institute Technology. In all, 95 men and women ages 50 to 85 participated; there was a second, crossover study involving a subgroup of 32 subjects "whose members had relatively inefficient memories," Kamiya wrote. "The [95] subjects either took a placebo or citicoline, 1,000 mg daily, for three months in the initial study. In the crossover study, subjects took both placebo and citicoline, 2,000 mg daily, each for two months."
"Verbal memory was tested at the beginning of each study using a logical memory passage," Kamiya wrote. "Memory scores were analyzed using repeated measures analysis of variance and covariance, followed by planned comparisons when appropriate. In the initial study, citicoline therapy improved delayed recall on logical memory only for the subjects with relatively inefficient memories. In the crossover study, the higher dosage of citicoline was clearly associated with improved immediate and delayed logical memory. The [MIT] study concluded that citicoline therapy improved verbal memory functioning in older individuals with relatively inefficient memories. The study also suggested that citicoline might prove to be helpful for elderly who are more intellectual than the participating subjects. As a result, citicoline may prove effective in treating age-related cognitive decline that may be the precursor of dementia."
Sullivan said his company has created "an aggressive advertising, publicity, and marketing campaign" for Cognizin, using broadcast, print, and Internet media to educate consumers. Furthermore, he said, "The Cognizin Website (www.cognizin.com) includes numerous studies, references, and articles that can be downloaded by retailers. Kyowa Hakko also sponsors educational seminars at industry trade shows to provide [retailers and manufacturers] with current research and development."
At this year's SupplySide East trade show, for example, the company presented Perry Renshaw, M.D., Ph.D., professor of psychiatry at Harvard Medical School, in a seminar titled "The Role of Citicoline and Pyrimidines in Brain Health." Kyowa Hakko will offer a seminar discussing Cognizinâs particular benefits for brain health at the upcoming SupplySide West.
The PS Claim
At present, the only dietary supplement ingredient with a health claim linked to cognitive function is PS, which Hagerman noted is "part of every cell membrane in the human body. In the brain, PS is found in particularly high amounts due to its association with the neuronal structure and brain chemistry. Numerous human and animal studies indicate that PS aids in the release and utilization of the brain chemicals acetylcholine, dopamine, epinephrine, norepinephrine, serotonin, GABA, and endorphins. Age, stress, and a poor diet can contribute to a decline in the functions of the brain, and therefore a diminishment in cognitive ability. Even when we are young, the effects of stress and questionable diet can deplete our ability to reason, recall, memorize, and generally think effectively."
"Unfortunately, getting adequate PS in the diet is difficult if not impossible," he continued. "Few foods, with the exception of animal brain and soybeans, contain any significant amount of PS. However, it is unlikely that these foods would normally be included in our diet."
The Food and Drug Administration (FDA) authorized two health claims for PS in February 2003. The first claim, "Phosphatidylserine (PS) may reduce the risk of cognitive dysfunction in the elderly," and the second claim, "Phosphatidylserine (PS) may reduce the risk of dementia in the elderly," both carry FDA's required disclaimer language.
Some observers have opined that the claims allowed by FDA are less forceful than they could be, but Hagerman would not concur. ãThe qualification language is simply FDA's standard current practice to the granting of health claims, and should not be viewed as diminishing the claims. Rather, the qualification is FDA's most accurate manner to address the known level of science supporting the claims, and is likely 'standard practice' now.
"In the filing, the petitioner, Dr. Kyle Smith, stated, 'Phosphatidylserine is both a food and a food ingredient and is safe and lawful at the levels necessary to justify the proposed health claim,' thus meeting FDA's regulations. The establishment of health claims for PS was very significant, since approximately five million Americans, including a large percentage of the elderly, have some form of cognitive dysfunction or dementia. This development underscores the health benefits of PS, and now allows the addition of PS to many more products targeted to consumers and their mental performance."
Added Rohde, "It is good for consumers that FDA agreed to allow these qualified health claims for PS. Certainly the health claims should have been stronger. We do not look to FDA for understanding and leadership in this area. The strong clinical and basic science behind these nutrients speaks louder than any political agency. We continue to investigate the diverse health benefits of both PS and GPC for the middle aged, the elderly, and children. GPC, in particular, has demonstrated superiority over several medical drugs in direct clinical comparisons. Finally, it will remain our task anyway to promote the benefits of our products to the public."
Nothing Fishy About It
Another supplement category with a lengthy catalogue of research tying to it to cognitive function is essential fatty acids (EFAs) from fish oils. The body of research was recently expanded with a study published in the American Journal of Clinical Nutrition, showing that people who consume oily fish or take fish oil supplements throughout their lives show better cognitive function and fewer early signs of AD at age 64.
A team from the University of Aberdeen and the University of Edinburgh, both in Scotland, gathered data from about 300 people who had participated in a national IQ survey in 1947 at age 11, and tested the subjects again in 2000-01. The researchers used a questionnaire to find out about the subjectsâ intake of omega-3s from their diet and use of supplements, and also tested their plasma levels of omega-3s. They found that cognitive function in the 64-year-olds was higher if they supplemented with omega-3s. In particular, mental speed was greater among supplement users. [Whalley LJ, Fox HC, Wahle KW, Starr JM, Deary IJ. Cognitive aging, childhood intelligence, and the use of food supplements: possible involvement of no3 fatty acids. Am J Clin Nutr 2004 80: 1650-1657.]
Medicinal mushrooms, too, can play a role in supporting cognitive health, and have been studied for this purpose. Lion's mane (Hericium erinaceus), used traditionally in China and Japan for centuries, has been said to provide "the steel nerves and memory of a lion" to those who consume it. It has been studied for possible brain-health benefits that include stimulating the synthesis of nerve growth factor, which may help inhibit brain dysfunction associated with AD as well as other neurological disorders, according to Maitake Products, Inc., based in Ridgefield Park, NJ. "Studies also confirm many of its traditional uses, supporting the digestive system, and acting as a tonic for the nervous system," the company stated.
Maitake Products produces a complex known as Super Lion's Mane, containing both an extract and the fruit body of this mushroom, along with an extract of maitake and the fruit body of reishi. It is part of the manufacturer's Mushroom Wisdom line.
Single nutrients are not the only path toward enhancing cognitive function. Asked what ingrediwents might be combined with SerinAid in brain-health formulas, Hagerman said, "Often, B vitamins, A-GPC, anti-oxidants, taurine, tyrosine, omega-3 fatty acids, and sometimes excitatory compounds like caffeine, are used in combination with PS, depending of course on the targeted health benefits."
A multi-nutrient approach may be the way to go. "We see nutrient combinations emerging as the obvious strategy to combine the best available nutrients for the benefits of the consumer," said Rohde. "Foremost will be the non-herbal orthomolecules PS and GPC in combinations with the long-chain omega-3 essential fatty acids DHA and EPA [eicosapentaenoic acid]. We have provided product for a clinical trial utilizing a combination of PS and DHA. For that we are using highly potent nutrients, our new liquid 40 percent PS. and our new fish-oil concentrate with 50 percent DHA."
To that end, supplement manufacturer Natrol, Inc. has launched brainSpeed, a line of three cognitive health supplements that include a patent-pending formula - the brainSpeed Blend. Targeting the cholinergic system - the key to cognitive speed ö the brainSpeed blend was tested clinically to help promote mental agility, maintain memory, and improve speed. There is also an online test by which consumers can measure their own mental processingspeed before and after using the product.
Natrol CEO Elliott Balbert said the company has been working on the brainSpeed project for two years, which included "significant investment" in research and formula and safety testing. "Not only are vital boomers interested in their mental well-being but so are students, professionals, and executives-even game players and athletes," Balbert added. "The brain is the C.P.U. [central processing unit] of our body. It is time the nutraceutical industry delivered a legitimate brain health product from a company that backs it with science, safety, and sincerity."
And the list of nutrients that support brain function is a lengthy one. In addition to ginkgo, PS, and EFAs, Patrick Holford's book Optimum Nutrition for the Mind (Basic Health, 2004) goes from A (acetyl-l-carnitine) to Z (zinc), with the B vitamins, amino acids, magnesium, s-adenosyl methionine, 5-HTP, gamma-amino-butyric acid, and many others along the way. Food allergens, hypothyroidism, heavy metal toxicity, and a host of other contributing factors can affect mental performance, Holford wrote.
The culinary world may soon yield another cognitive-function ingredient for use in supplements: Human clinical trials will be conducted on the Alzheimer's-preventing potential of curcumin, a dietary staple of India, where AD rates are reportedly among the world's lowest. A new UCLA-Veterans Affairs study involving genetically altered mice suggests that curcumin, the yellow pigment in curry spice, inhibits the accumulation of destructive beta amyloids in the brains of AD patients and also breaks up existing plaques. This has prompted the university to begin recruiting for a human trial.
Supplements for Small Minds
Much of the attention paid to supplements for brain health stems from preserving cognitive function in adults. But there's an important customer base at the other end of the spectrum: children, whose cognitive development can be enhanced through nutrients and, conversely, harmed by lack of them.
To grasp how important nutrition is to the developing brain, consider a Duke University study published last year, which suggested that women who supplement with choline during pregnancy may give birth to babies with better learning and memory abilities.
Similarly, an article in the Indian Journal of Pediatrics earlier this year noted. "Infants of mothers supplemented with EFAs [essential fatty acids] and DHA [docahexaenoic acid] had higher mental processing scores, psychomotor development, eye-hand coordination and stereo acuity at 4 years of age. Intake of EFAs and DHA during preschool years may also have a beneficial role in the prevention of attention deficit hyperactivity disorder (ADHD) and enhancing learning capability and academic performance.ä
A study in the December 2004 Archives of Pediatric and Adolescent Medicine suggested a link between iron deficiency and ADHD. Other research has shown that EFAs from fish oils can help address ADHD."