Marian Zboraj06.01.07
According to the National Institute of Aging, which is part of the National Institutes of Health (NIH), approximately 4.5 million Americans suffer from Alzheimer's disease (AD), the most common form of dementia. The disease usually begins after age 60, with risk increasing further as people enter their "golden years." About 5% of men and women ages 65 to 74 already have AD, while nearly half of those age 85 and older are likely to have the disease.
Parkinson's disease (PD) is the second most common neurodegenerative disorder after AD. It affects at least one million people in the U.S. typically over age 50.
Acknowledging these shocking statistics, pharmaceutical and dietary supplement companies alike have been searching for solutions over the last several years, especially in the context of a rapidly aging population. Most recently, however, there is a lot of attention being paid to supplement ingredients, especially within the research community. The next several years will involve research exploring the merits of these ingredients in preventing, delaying or stalling these debilitating diseases. In the end, WH Leong, vice president, Carotech Inc., Edison, NJ, hopes these nutraceutical compounds can alleviate some of the economic burden associated with neurodegenerative diseases.
It's no shock to discover that as people age the risk of being afflicted with some form of neurodegenerative disease increases, so it should also come as no surprise to learn that today's consumers are taking steps to proactively secure proper cognitive function in the future.
Charlene Lee, executive vice president and general manager, Cyvex Nutrition, Inc., Irvine, CA, explains that cognitive function includes perception and perceptual acuity, which encompasses how much visual information one can integrate in a given period of time. She also discussed the different elements of cognitive function. "Once the visual information is perceived and encoded it is then consolidated and filed away in a process of learning and memory, which are two elements of cognitive function," she said. Other elements include attention, focus and concentration, as well as executive cognitive function, which includes planning, thought-based processes, decision-making and problem solving.
As mentioned previously, the primary reason for cognitive decline is aging. "As we age there are many changes within the brain as there are with all of our organs," said Karen Todd, RD, director of marketing, Kyowa Hakko U.S.A., Inc., Ann Arbor, MI. "Most of us begin losing neurons in our early 20's. And evidence of brain vascular changes can be seen in individuals as young as 40. Certain neurotransmitters decline along with certain functions of the brain as people age, sowe need to prevent the onset or delay this 'aging effect' as long as possible."
Tina Sampalis, MD, PhD, vice president-R&D and Business Development, Neptune Technologies & Bioressources Inc., Laval, Quebec, says it has been suggested that if the onset of AD could be delayed by as little as six months in the next generation, there is a good chance the incidence of dementia could be reduced by as many as a million cases. Further, she said, "If we could delay it by five years, we could actually reduce the number of cases by 50%."
Several factors contribute to cognitive decline, according to Dr. Parris Kidd, a technical consultant for Science and Ingredients, Inc., Carlsbad, CA. One factor is chronic stress, which has been proven to kill brain cells. Toxic agents in poorly cooked or processed foods are also likely to be a factor in premature cognitive decline.
Another contributor is environmental toxins. Dr. Kidd claims that indoor exposure to insecticides is linked to Parkinson's causation. In addition, he said, mercury and solvents, ever-present in the modern environment, are linked to poor fetal brain development, multiple sclerosis and PD.
Genetic influences may also be factor. And deficiencies in nutrients essential to brain vitality-such as B vitamins and omega 3's-also play a role in cognitive decline.
"On the positive side, it is implied that lifestyle and dietary reform and mental and physical exercise can substantially slow cognitive decline,'" said Dr. Kidd.
Thanks to the increasing number of mainstream articles pointing to the benefit of supplementation for cognitive health, the market is experiencing a boost in sales. Evelyn Scalora, product manager, InterHealth Nutraceuticals, Inc. Benicia, CA, supports this point by highlighting data from Nutrition Business Journal, San Diego, CA, which reported that sales in the "mental acuity" supplement market rose dramatically from 1999 to 2005, with ginkgo biloba being one of the top selling herbs in 2005.
Substantial evidence indicates that elderly patients with low levels of omega 3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in the blood have a greater decline in cognitive functions. "DHA is the structural fat in the brain and nervous system; 20% of our brain by dry weight is DHA," said Robert Orr, president, Ocean Nutrition Canada (ONC), Dartmouth, Nova Scotia, Canada, "EPA is an anti-inflammatory nutrient that promotes hormones in the brain responsible for regulating normal brain function. Together these essential nutrients lead to better concentration."
Unfortunately, according to Cecilia McCollum, executive vice president, Blue California, Rancho Santa Margarita, CA, most consumers have diets that are deficient in natural sources of essential fatty acids necessary for proper brain function. "The recommended daily intake of DHA and EPA is about 400 mg per day, however the average intake of DHA in the U.S. is only 80 mg per day, which is alarmingly inadequate," she said. "Eating cold-water fish, such as salmon, twice a week would reduce the need for supplementation. But even for those with healthy diets, DHA supplementation is recommended to maintain proper brain function and help prevent depression, dementia, memory loss and poor vision."
Previous research indicates that Alzheimer's patients tend to have low concentrations of DHA in the brain. To further test the role DHA might play, a placebo-controlled, double-blind clinical study was conducted on patients with early stage AD. Two hundred and four patients were randomly assigned to receive EPAX AS (Lysaker, Norway) 050 TG, providing a daily dose of 1.7 grams of DHA or matching placebo for 6 months. After the 6-month period, the placebo patients were switched to active treatment and all patients were followed for another half year. All patients were receiving acetylcholinesterase inhibitor treatment. The main parameter was Mini-Mental State Examination (MMSE).
One hundred seventy-four patients fulfilled the trial. At 6 months, the decline in cognitive functions did not differ between the two groups. However, in a subgroup with very mild cognitive dysfunction (MMSE >27 points), a statistically significant reduction in MMSE decline rate was observed in the DHA-treated group compared to the placebo group. A similar arrest in decline rate was observed between 6 and 12 months in the placebo group when it started DHA supplementation.
Additional evidence supporting DHA's role in AD was discussed in the April 18, 2007 issue of the Journal of Neuroscience. The article suggested that diets rich in DHA could help prevent the development of AD later in life. Researchers at the University of California, Irvine, found that DHA may help slow the growth of two kinds of brain lesions associated with AD. While previous studies have shown that DHA may have therapeutic value for Alzheimer's patients, this research is among the first to show that it may delay the onset of the disease.
Of the four classes of phospholipids-phosphatidylcholine (PC), phosphatidylserine (PS), glycerophosphocholine (GPC) and omegaphospholipids (OPL)-PS is currently hogging the spotlight for its positive role in mental performance. "PS occurs naturally in all our cells, and is most concentrated in the brain," said Dr. Kidd. The good news is in healthy people over 50, PS may restore some of the age-related decline in memory, learning and other higher cognitive functions. In elderly people with severe cognitive decline, PS can improve activities of daily living, along with sociability and other quality of life functions.
According to Scott Hagerman, president and CEO, Chemi Nutra, White Bear Lake, MN, PS was first marketed in the 1980s as a drug to benefit aging adults, and was targeted to slow down memory loss and improve cognitive function in general. It was only recently, in February 2003, that FDA granted two significant health claims for PS. The first claim reads: "Phosphatidylserine (PS) may reduce the risk of cognitive dysfunction in the elderly." The second claim reads: "Phosphatidylserine (PS) may reduce the risk of dementia in the elderly." Although there is no Reference Daily Intake (RDI) for PS and the health claim does not identify specific intake quantities, studies have shown that PS supplementation offers health benefits at dosages between 75 mg and 500 mg per day.
"The establishment of health claims for PS is very significant, since approximately 7 million Americans, including a large percentage of the elderly, have some form of cognitive dysfunction or dementia," said. Mr. Hagerman. "This development underscores the health benefits of PS, and now allows the addition of PS to many more products geared toward consumers and their mental performance."
One such product launched last year by Country Life, Hauppauge, NY, is Sharp Thought, a cognitive brand based on Enzymotec Ltd's (Migdal HaEmeq, Israel) patented Sharp-PS Gold nutrient. Exhibiting the current trend of phospholipids rich in omega 3 fatty acids, Sharp Thought is marketed in the natural food industry with Enzymotec's PS-DHA conjugate to improve memory, learning and concentration.
Elzaphan Hotam, BSc, MBA, vice president, Business Development, Enzymotec, is optimistic about the resurfacing of the PS-DHA conjugate concept. "Currently, PS is extracted from soy and used to help adults slow down age-related decline in cognitive capabilities," said Mr. Hotam. "In the past, PS was extracted from bovine brains and actually contained significant amounts of DHA, conjugated to its backbone, forming PS-DHA. This form is rare yet naturally occurring and is found in the brain and in breast milk. It is also a functional form of PS on which the majority of scientifically valid clinical trials, the only which established PS's unique value proposition, were based upon."
Currently Chemi Nutra is preparing for a second quarter 2007 launch of products that are rich in omega 3's (EPA and DHA) and utilize Chemi's PS production patents. Chemi plans to invest in research studies to flesh out how this new PS variant will perform in improving memory, reducing stress, and improving attention deficit issues.
Peter Rohde, CEO, Science & Ingredients, Inc., predicts continuous product developments on phospholipids. "Omega 3 essential fatty acids will play an increasingly bigger role bonded with phospholipids," he said. "New clinical trials will be proving that DHA and EPA are more effective and available when they are bound to a phospholipid molecule."
Neptune Technologies & Bioressources's proprietary marine phospholipids found in Neptune Krill Oil (NKO) provides phospholipids rich in DHA. It also provides potent antioxidants in the form of carotenoids like esterified astaxanthin and flavonoids. Neptune recently elucidated NKO's role in cognition when it released the results of a study investigating the effect NKO on adult Attention Deficit Hyperactivity Disorder (ADHD).
The objective of the non-randomized Phase I open label clinical study was to evaluate the effect of NKO on adult ADHD as measured by Barkley's Executive Function score of behavior inhibition, daily functional capacity and social behavior. Thirty otherwise healthy adults with a confirmed diagnosis of ADHD taking a 500 mg daily dose of NKO were originally enrolled in the study of whom 25 (83%) completed 6 months of treatment. After 6 months of treatment the 25 patients who completed the study showed a statistically significant improvement in all Barkley's Executive Function scores. In particular, patients improved their ability to concentrate and their working capacity by over 60%, their ability to focus by 39% and their planning skills by 50%.
"Based on these encouraging results we will now proceed to the initiation of a pivotal Phase II/III clinical program on cognitive function," said Dr. Sampalis. Neptune is also forming a complete OTC and drug development program to develop validated marine phospholipids for the prevention and treatment of cognitive decline.
While omega 3's and phospholipids continue to steal the spotlight, there are other ingredients worth mentioning in the realm of cognitive function.
Robin Ward, vice president, Commercial Operations, Linnea SA, Riazzino (Locarno), Switzerland, highlighted vinpocetine for its ability to increase blood flow in the brain. He also says it has been found to be effective in improving memory, maintaining cognitive function, and enhancing overall attention and concentration.
Vinpocetine is derived from vincamine, a constituent found in the leaves of common periwinkle (Vinca minor L.), as well as the seeds of various African plants. In addition to aiding memory and promoting healthy brain function, vinpocetine has also shown promise in the treatment of AD.
But Josh Reynolds, a Cyvex partner who has formulated a line of brain health supplements featuring BioVinca vinpocetine, and author of 20/20 Brain Power, warns that purity is a priority when it comes to vinpocetine. "An imported vinpocetine compound that is less than 100% pharmaceutical grade pure must beg the question: what exactly is the remaining percentage?" he said. "That mystery composition may be an impurity that is either unfriendly/ antagonistic or non-proactive in the brain. Since vinpocetine significantly increases blood flow in the brain, if there is some impurity, such as aluminum dioxide, an excipient or binder that is not brain friendly, the vinpocetine will carry it aggressively. This is a clear concern because of the power of the vinpocetine to take any 'passengers' with it into the brain."
According to Lonza Inc., Allendale, NJ, acetyl L-carnitine (ALC), the acetyl derivative of L-carnitine, is found throughout the central nervous system (CNS). ALC plays a broad role in CNS metabolism as a source of acetyl groups both for the synthesis of acetylcholine (a neurotransmitter which is vital to proper brain function) and for energy-producing reactions. ALC has somewhat different applications compared to "regular" L-carnitine in that ALC is capable of crossing the blood-brain barrier. Thus, ALC has found a suitable niche in "brain food" products. ALC has restorative or even protective actions against aging processes and neurodegeneration-providing a vital role in maintaining brain function as the population ages.
Evidence of oxidative stress such as oxidized lipids, DNA, and proteins have been found in patients with AD, Huntington's disease and PD. CoQ10 is thought to play a beneficial role in neurodegenerative diseases due to both its antioxidant effects and its beneficial role in maintaining healthy mitochondria, according to the Knowledge Center on Zymes LLC's (Hasbrouck Heights, NJ) website, www.zymesllc.com.
CoQ10 levels have been found to be decreased in blood and in platelet mitochondria of individuals with PD. As a result, high doses of CoQ10 have been shown to be a beneficial therapy for PD. Although the knowledge of CoQ10's role in patients with AD is not as broad as it is for PD, advances are being made with in vitro experiments and animal models of this disease. Proteins fold in specific ways to enable them to perform their biochemical functions in the body. In AD some proteins fold improperly, forming deposits of non-functional proteins in the brain known beta-amyloid fibrils. Decreasing the formation of beta-amyloid fibrils or disrupting already formed beta-amyloid fibrils would be a potential way to treat patients with AD. In vitro experiments have already shown that CoQ10 has the ability to decrease the formation of beta-amyloid fibrils and disrupt already formed beta-amyloid fibrils.
The evidence behind tocotrienols' role in benefiting neurodegenerative disorders is constantly growing. To further support their importance, Carotech collaborated with Prof. Chandan Sen and the Ohio State University Medical Center. The research collaboration was funded by a research grant in excess of $1.2 million from the NIH's National Institute of Neurological Disorders and Stroke. In an article published last year in the Journal of Neurochemistry, Prof. Sen's team determined that tocotrienols protect against stroke-induced neurodegeneration by acting as an antioxidant at higher concentrations, and imparting non-antioxidant protection at lower levels.
Prof. Sen also demonstrated that tocotrienol is efficiently delivered to the bloodstream despite the fact that the transfer protein has a lower affinity for tocotrienol than it has for tocopherol. "Since tocotrienols cross the blood-brain barrier, it is prudent to continue taking tocotrienols throughout one's life to ensure that the brain continues to have significant levels for the purpose of protection," said Mr. Leong. "And being an antioxidant, it does protect the brain from free-radical damage, which may lead to other neurodiseases such as Alzheimer's."
Citicoline is the name for CDP choline, which is a naturally occurring compound present in all of the cells of the body. Numerous citicoline studies have indicated its effectiveness in AD, PD and stroke recuperation. "We know that in both older and younger healthy adults Citicoline will increase the synthesis of brain membranes…and in older adults the increase in the synthesis of brain membranes is associated with improvements in verbal learning capacity," said Ms. Todd. Kyowa Hakko markets Citicoline under the brand name Cognizin, which itself has been shown in clinical studies to have multiple benefits for the brain, including improved performance and memory.
Kyowa Hakko recently completed a clinical trial out of Harvard Medical Schools' McLean Hospital Neuroimaging Laboratory in Boston, MA. The study demonstrates the effectiveness of Cognizin on concentration, memory and focus. This study will be presented and published later this year.
There are many marketing opportunities within the cognitive health market. But instead of marketing to the aging population in general, Linnea's Mr. Ward suggested narrowing the focus to more specific groups like peri- or postmenopausal women.
When women go through menopause, their natural estrogen levels gradually decline. The presence of estrogen receptors in the central nervous system indicates its role in cognitive function, but since side effects have been found in the use of estrogen replacement therapy (ERT), many women are turning to the phytoestrogens obtained through diet.
Lignans, in particular, have been shown to help preserve cognitive function in postmenopausal women, according to Mr. Ward. For example, a study conducted by researchers at the Julius Center for Health Sciences and Primary Care in Utrecht, The Netherlands, examined how dietary intake of two phytoestrogens, lignans and isoflavones, in the typical Western diet may affect cognitive function in 394 healthy postmenopausal women. Cognitive function was assessed by a MMSE, which involved questions and tasks associated with orientation, registration, attention, calculation, recall and language. After adjustment for confounders, women who consumed higher levels of lignans performed better in the MMSE.
Although consumer awareness surrounding the health benefits of lignans is low, Mr. Ward expects the population to catch on in a few years, hopefully making lignans leaders in the market.
InterHealth's Ms. Scalora notices that younger individuals are becoming interested in brain health supplementation. She says while seniors and Baby Boomers are concerned about maintaining mental clarity, college-aged consumers are interested in keeping their minds as sharp as possible.
Infant care is another prospect. "An infant's brain requires DHA for proper development," said Blue California's Ms. McCollum. "Children who have no access to this essential nutrient suffer from cognitive problems." Importantly, she noted, the lowest levels of DHA in breast milk are found in the U.S.
ONC's Mr. Orr discussed the importance of EPA in children after the age of two. "This has been described in numerous papers recently," he said. "Notably the Oxford Durham Study where kids ages 7 to 11 with a condition similar to ADHD were given high dose concentrated EPA fish oil versus placebo and learning metric's improved dramatically demonstrating the value of EPA and cognitive function."
As with many nutraceutical products, Mr. Ward says dose is a major issue. "One of the challenges in the brain health market in particular is ensuring that ingredients used in products on the market are supplied in the same dose proven to be most bioavailable in clinical research," he said. "There are some companies that disregard the science and short-change the efficacy of the product."
Ms. Todd agreed, adding that some companies only include 50% of the proper dose to justify the cost.
Of course, education of the public and healthcare professionals on the nutritional needs of the brain is key. Mr. Hagerman advises companies to first strive to fully understand the science behind their ingredients, so that they can effectively create accurate and convincing promotional materials, ultimately targeted to consumers that rightfully demand the highest degree of supportive information.
On the horizon, Cyvex's Ms. Lee sees a cognitive health market full of possibilities. "The intimate relationship between mental and cognitive function and emotional and personal well-being and development is intriguing for the future of dietary supplements that fortify the brain, and perhaps the mind as well," she said.
Parkinson's disease (PD) is the second most common neurodegenerative disorder after AD. It affects at least one million people in the U.S. typically over age 50.
Acknowledging these shocking statistics, pharmaceutical and dietary supplement companies alike have been searching for solutions over the last several years, especially in the context of a rapidly aging population. Most recently, however, there is a lot of attention being paid to supplement ingredients, especially within the research community. The next several years will involve research exploring the merits of these ingredients in preventing, delaying or stalling these debilitating diseases. In the end, WH Leong, vice president, Carotech Inc., Edison, NJ, hopes these nutraceutical compounds can alleviate some of the economic burden associated with neurodegenerative diseases.
The Aging Brain
It's no shock to discover that as people age the risk of being afflicted with some form of neurodegenerative disease increases, so it should also come as no surprise to learn that today's consumers are taking steps to proactively secure proper cognitive function in the future.
Charlene Lee, executive vice president and general manager, Cyvex Nutrition, Inc., Irvine, CA, explains that cognitive function includes perception and perceptual acuity, which encompasses how much visual information one can integrate in a given period of time. She also discussed the different elements of cognitive function. "Once the visual information is perceived and encoded it is then consolidated and filed away in a process of learning and memory, which are two elements of cognitive function," she said. Other elements include attention, focus and concentration, as well as executive cognitive function, which includes planning, thought-based processes, decision-making and problem solving.
As mentioned previously, the primary reason for cognitive decline is aging. "As we age there are many changes within the brain as there are with all of our organs," said Karen Todd, RD, director of marketing, Kyowa Hakko U.S.A., Inc., Ann Arbor, MI. "Most of us begin losing neurons in our early 20's. And evidence of brain vascular changes can be seen in individuals as young as 40. Certain neurotransmitters decline along with certain functions of the brain as people age, sowe need to prevent the onset or delay this 'aging effect' as long as possible."
Tina Sampalis, MD, PhD, vice president-R&D and Business Development, Neptune Technologies & Bioressources Inc., Laval, Quebec, says it has been suggested that if the onset of AD could be delayed by as little as six months in the next generation, there is a good chance the incidence of dementia could be reduced by as many as a million cases. Further, she said, "If we could delay it by five years, we could actually reduce the number of cases by 50%."
Several factors contribute to cognitive decline, according to Dr. Parris Kidd, a technical consultant for Science and Ingredients, Inc., Carlsbad, CA. One factor is chronic stress, which has been proven to kill brain cells. Toxic agents in poorly cooked or processed foods are also likely to be a factor in premature cognitive decline.
Another contributor is environmental toxins. Dr. Kidd claims that indoor exposure to insecticides is linked to Parkinson's causation. In addition, he said, mercury and solvents, ever-present in the modern environment, are linked to poor fetal brain development, multiple sclerosis and PD.
Genetic influences may also be factor. And deficiencies in nutrients essential to brain vitality-such as B vitamins and omega 3's-also play a role in cognitive decline.
"On the positive side, it is implied that lifestyle and dietary reform and mental and physical exercise can substantially slow cognitive decline,'" said Dr. Kidd.
Thanks to the increasing number of mainstream articles pointing to the benefit of supplementation for cognitive health, the market is experiencing a boost in sales. Evelyn Scalora, product manager, InterHealth Nutraceuticals, Inc. Benicia, CA, supports this point by highlighting data from Nutrition Business Journal, San Diego, CA, which reported that sales in the "mental acuity" supplement market rose dramatically from 1999 to 2005, with ginkgo biloba being one of the top selling herbs in 2005.
The Omega 3 Connection
Substantial evidence indicates that elderly patients with low levels of omega 3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in the blood have a greater decline in cognitive functions. "DHA is the structural fat in the brain and nervous system; 20% of our brain by dry weight is DHA," said Robert Orr, president, Ocean Nutrition Canada (ONC), Dartmouth, Nova Scotia, Canada, "EPA is an anti-inflammatory nutrient that promotes hormones in the brain responsible for regulating normal brain function. Together these essential nutrients lead to better concentration."
Unfortunately, according to Cecilia McCollum, executive vice president, Blue California, Rancho Santa Margarita, CA, most consumers have diets that are deficient in natural sources of essential fatty acids necessary for proper brain function. "The recommended daily intake of DHA and EPA is about 400 mg per day, however the average intake of DHA in the U.S. is only 80 mg per day, which is alarmingly inadequate," she said. "Eating cold-water fish, such as salmon, twice a week would reduce the need for supplementation. But even for those with healthy diets, DHA supplementation is recommended to maintain proper brain function and help prevent depression, dementia, memory loss and poor vision."
Previous research indicates that Alzheimer's patients tend to have low concentrations of DHA in the brain. To further test the role DHA might play, a placebo-controlled, double-blind clinical study was conducted on patients with early stage AD. Two hundred and four patients were randomly assigned to receive EPAX AS (Lysaker, Norway) 050 TG, providing a daily dose of 1.7 grams of DHA or matching placebo for 6 months. After the 6-month period, the placebo patients were switched to active treatment and all patients were followed for another half year. All patients were receiving acetylcholinesterase inhibitor treatment. The main parameter was Mini-Mental State Examination (MMSE).
One hundred seventy-four patients fulfilled the trial. At 6 months, the decline in cognitive functions did not differ between the two groups. However, in a subgroup with very mild cognitive dysfunction (MMSE >27 points), a statistically significant reduction in MMSE decline rate was observed in the DHA-treated group compared to the placebo group. A similar arrest in decline rate was observed between 6 and 12 months in the placebo group when it started DHA supplementation.
Additional evidence supporting DHA's role in AD was discussed in the April 18, 2007 issue of the Journal of Neuroscience. The article suggested that diets rich in DHA could help prevent the development of AD later in life. Researchers at the University of California, Irvine, found that DHA may help slow the growth of two kinds of brain lesions associated with AD. While previous studies have shown that DHA may have therapeutic value for Alzheimer's patients, this research is among the first to show that it may delay the onset of the disease.
Focusing on Phospholipds
Of the four classes of phospholipids-phosphatidylcholine (PC), phosphatidylserine (PS), glycerophosphocholine (GPC) and omegaphospholipids (OPL)-PS is currently hogging the spotlight for its positive role in mental performance. "PS occurs naturally in all our cells, and is most concentrated in the brain," said Dr. Kidd. The good news is in healthy people over 50, PS may restore some of the age-related decline in memory, learning and other higher cognitive functions. In elderly people with severe cognitive decline, PS can improve activities of daily living, along with sociability and other quality of life functions.
According to Scott Hagerman, president and CEO, Chemi Nutra, White Bear Lake, MN, PS was first marketed in the 1980s as a drug to benefit aging adults, and was targeted to slow down memory loss and improve cognitive function in general. It was only recently, in February 2003, that FDA granted two significant health claims for PS. The first claim reads: "Phosphatidylserine (PS) may reduce the risk of cognitive dysfunction in the elderly." The second claim reads: "Phosphatidylserine (PS) may reduce the risk of dementia in the elderly." Although there is no Reference Daily Intake (RDI) for PS and the health claim does not identify specific intake quantities, studies have shown that PS supplementation offers health benefits at dosages between 75 mg and 500 mg per day.
"The establishment of health claims for PS is very significant, since approximately 7 million Americans, including a large percentage of the elderly, have some form of cognitive dysfunction or dementia," said. Mr. Hagerman. "This development underscores the health benefits of PS, and now allows the addition of PS to many more products geared toward consumers and their mental performance."
One such product launched last year by Country Life, Hauppauge, NY, is Sharp Thought, a cognitive brand based on Enzymotec Ltd's (Migdal HaEmeq, Israel) patented Sharp-PS Gold nutrient. Exhibiting the current trend of phospholipids rich in omega 3 fatty acids, Sharp Thought is marketed in the natural food industry with Enzymotec's PS-DHA conjugate to improve memory, learning and concentration.
Elzaphan Hotam, BSc, MBA, vice president, Business Development, Enzymotec, is optimistic about the resurfacing of the PS-DHA conjugate concept. "Currently, PS is extracted from soy and used to help adults slow down age-related decline in cognitive capabilities," said Mr. Hotam. "In the past, PS was extracted from bovine brains and actually contained significant amounts of DHA, conjugated to its backbone, forming PS-DHA. This form is rare yet naturally occurring and is found in the brain and in breast milk. It is also a functional form of PS on which the majority of scientifically valid clinical trials, the only which established PS's unique value proposition, were based upon."
Currently Chemi Nutra is preparing for a second quarter 2007 launch of products that are rich in omega 3's (EPA and DHA) and utilize Chemi's PS production patents. Chemi plans to invest in research studies to flesh out how this new PS variant will perform in improving memory, reducing stress, and improving attention deficit issues.
Peter Rohde, CEO, Science & Ingredients, Inc., predicts continuous product developments on phospholipids. "Omega 3 essential fatty acids will play an increasingly bigger role bonded with phospholipids," he said. "New clinical trials will be proving that DHA and EPA are more effective and available when they are bound to a phospholipid molecule."
Neptune Technologies & Bioressources's proprietary marine phospholipids found in Neptune Krill Oil (NKO) provides phospholipids rich in DHA. It also provides potent antioxidants in the form of carotenoids like esterified astaxanthin and flavonoids. Neptune recently elucidated NKO's role in cognition when it released the results of a study investigating the effect NKO on adult Attention Deficit Hyperactivity Disorder (ADHD).
The objective of the non-randomized Phase I open label clinical study was to evaluate the effect of NKO on adult ADHD as measured by Barkley's Executive Function score of behavior inhibition, daily functional capacity and social behavior. Thirty otherwise healthy adults with a confirmed diagnosis of ADHD taking a 500 mg daily dose of NKO were originally enrolled in the study of whom 25 (83%) completed 6 months of treatment. After 6 months of treatment the 25 patients who completed the study showed a statistically significant improvement in all Barkley's Executive Function scores. In particular, patients improved their ability to concentrate and their working capacity by over 60%, their ability to focus by 39% and their planning skills by 50%.
"Based on these encouraging results we will now proceed to the initiation of a pivotal Phase II/III clinical program on cognitive function," said Dr. Sampalis. Neptune is also forming a complete OTC and drug development program to develop validated marine phospholipids for the prevention and treatment of cognitive decline.
Additional 'Smart' Compounds
While omega 3's and phospholipids continue to steal the spotlight, there are other ingredients worth mentioning in the realm of cognitive function.
Robin Ward, vice president, Commercial Operations, Linnea SA, Riazzino (Locarno), Switzerland, highlighted vinpocetine for its ability to increase blood flow in the brain. He also says it has been found to be effective in improving memory, maintaining cognitive function, and enhancing overall attention and concentration.
Vinpocetine is derived from vincamine, a constituent found in the leaves of common periwinkle (Vinca minor L.), as well as the seeds of various African plants. In addition to aiding memory and promoting healthy brain function, vinpocetine has also shown promise in the treatment of AD.
But Josh Reynolds, a Cyvex partner who has formulated a line of brain health supplements featuring BioVinca vinpocetine, and author of 20/20 Brain Power, warns that purity is a priority when it comes to vinpocetine. "An imported vinpocetine compound that is less than 100% pharmaceutical grade pure must beg the question: what exactly is the remaining percentage?" he said. "That mystery composition may be an impurity that is either unfriendly/ antagonistic or non-proactive in the brain. Since vinpocetine significantly increases blood flow in the brain, if there is some impurity, such as aluminum dioxide, an excipient or binder that is not brain friendly, the vinpocetine will carry it aggressively. This is a clear concern because of the power of the vinpocetine to take any 'passengers' with it into the brain."
According to Lonza Inc., Allendale, NJ, acetyl L-carnitine (ALC), the acetyl derivative of L-carnitine, is found throughout the central nervous system (CNS). ALC plays a broad role in CNS metabolism as a source of acetyl groups both for the synthesis of acetylcholine (a neurotransmitter which is vital to proper brain function) and for energy-producing reactions. ALC has somewhat different applications compared to "regular" L-carnitine in that ALC is capable of crossing the blood-brain barrier. Thus, ALC has found a suitable niche in "brain food" products. ALC has restorative or even protective actions against aging processes and neurodegeneration-providing a vital role in maintaining brain function as the population ages.
Evidence of oxidative stress such as oxidized lipids, DNA, and proteins have been found in patients with AD, Huntington's disease and PD. CoQ10 is thought to play a beneficial role in neurodegenerative diseases due to both its antioxidant effects and its beneficial role in maintaining healthy mitochondria, according to the Knowledge Center on Zymes LLC's (Hasbrouck Heights, NJ) website, www.zymesllc.com.
CoQ10 levels have been found to be decreased in blood and in platelet mitochondria of individuals with PD. As a result, high doses of CoQ10 have been shown to be a beneficial therapy for PD. Although the knowledge of CoQ10's role in patients with AD is not as broad as it is for PD, advances are being made with in vitro experiments and animal models of this disease. Proteins fold in specific ways to enable them to perform their biochemical functions in the body. In AD some proteins fold improperly, forming deposits of non-functional proteins in the brain known beta-amyloid fibrils. Decreasing the formation of beta-amyloid fibrils or disrupting already formed beta-amyloid fibrils would be a potential way to treat patients with AD. In vitro experiments have already shown that CoQ10 has the ability to decrease the formation of beta-amyloid fibrils and disrupt already formed beta-amyloid fibrils.
The evidence behind tocotrienols' role in benefiting neurodegenerative disorders is constantly growing. To further support their importance, Carotech collaborated with Prof. Chandan Sen and the Ohio State University Medical Center. The research collaboration was funded by a research grant in excess of $1.2 million from the NIH's National Institute of Neurological Disorders and Stroke. In an article published last year in the Journal of Neurochemistry, Prof. Sen's team determined that tocotrienols protect against stroke-induced neurodegeneration by acting as an antioxidant at higher concentrations, and imparting non-antioxidant protection at lower levels.
Prof. Sen also demonstrated that tocotrienol is efficiently delivered to the bloodstream despite the fact that the transfer protein has a lower affinity for tocotrienol than it has for tocopherol. "Since tocotrienols cross the blood-brain barrier, it is prudent to continue taking tocotrienols throughout one's life to ensure that the brain continues to have significant levels for the purpose of protection," said Mr. Leong. "And being an antioxidant, it does protect the brain from free-radical damage, which may lead to other neurodiseases such as Alzheimer's."
Citicoline is the name for CDP choline, which is a naturally occurring compound present in all of the cells of the body. Numerous citicoline studies have indicated its effectiveness in AD, PD and stroke recuperation. "We know that in both older and younger healthy adults Citicoline will increase the synthesis of brain membranes…and in older adults the increase in the synthesis of brain membranes is associated with improvements in verbal learning capacity," said Ms. Todd. Kyowa Hakko markets Citicoline under the brand name Cognizin, which itself has been shown in clinical studies to have multiple benefits for the brain, including improved performance and memory.
Kyowa Hakko recently completed a clinical trial out of Harvard Medical Schools' McLean Hospital Neuroimaging Laboratory in Boston, MA. The study demonstrates the effectiveness of Cognizin on concentration, memory and focus. This study will be presented and published later this year.
Beyond the Baby Boomers
There are many marketing opportunities within the cognitive health market. But instead of marketing to the aging population in general, Linnea's Mr. Ward suggested narrowing the focus to more specific groups like peri- or postmenopausal women.
When women go through menopause, their natural estrogen levels gradually decline. The presence of estrogen receptors in the central nervous system indicates its role in cognitive function, but since side effects have been found in the use of estrogen replacement therapy (ERT), many women are turning to the phytoestrogens obtained through diet.
Lignans, in particular, have been shown to help preserve cognitive function in postmenopausal women, according to Mr. Ward. For example, a study conducted by researchers at the Julius Center for Health Sciences and Primary Care in Utrecht, The Netherlands, examined how dietary intake of two phytoestrogens, lignans and isoflavones, in the typical Western diet may affect cognitive function in 394 healthy postmenopausal women. Cognitive function was assessed by a MMSE, which involved questions and tasks associated with orientation, registration, attention, calculation, recall and language. After adjustment for confounders, women who consumed higher levels of lignans performed better in the MMSE.
Although consumer awareness surrounding the health benefits of lignans is low, Mr. Ward expects the population to catch on in a few years, hopefully making lignans leaders in the market.
InterHealth's Ms. Scalora notices that younger individuals are becoming interested in brain health supplementation. She says while seniors and Baby Boomers are concerned about maintaining mental clarity, college-aged consumers are interested in keeping their minds as sharp as possible.
Infant care is another prospect. "An infant's brain requires DHA for proper development," said Blue California's Ms. McCollum. "Children who have no access to this essential nutrient suffer from cognitive problems." Importantly, she noted, the lowest levels of DHA in breast milk are found in the U.S.
ONC's Mr. Orr discussed the importance of EPA in children after the age of two. "This has been described in numerous papers recently," he said. "Notably the Oxford Durham Study where kids ages 7 to 11 with a condition similar to ADHD were given high dose concentrated EPA fish oil versus placebo and learning metric's improved dramatically demonstrating the value of EPA and cognitive function."
As with many nutraceutical products, Mr. Ward says dose is a major issue. "One of the challenges in the brain health market in particular is ensuring that ingredients used in products on the market are supplied in the same dose proven to be most bioavailable in clinical research," he said. "There are some companies that disregard the science and short-change the efficacy of the product."
Ms. Todd agreed, adding that some companies only include 50% of the proper dose to justify the cost.
Of course, education of the public and healthcare professionals on the nutritional needs of the brain is key. Mr. Hagerman advises companies to first strive to fully understand the science behind their ingredients, so that they can effectively create accurate and convincing promotional materials, ultimately targeted to consumers that rightfully demand the highest degree of supportive information.
On the horizon, Cyvex's Ms. Lee sees a cognitive health market full of possibilities. "The intimate relationship between mental and cognitive function and emotional and personal well-being and development is intriguing for the future of dietary supplements that fortify the brain, and perhaps the mind as well," she said.
