Achieving and maintaining optimal brain health, as well as preventing and supporting debilitating diseases, such as Alzheimer's and Parkinson's, has become one of the most prevalent health issues in today's society. Although the issue of maintaining healthy brain function is generally associated with old age, there exists today an ever-expanding brain-support market targeting everyone from infants to the elderly. Science continues to emerge, which supports the benefits of supplementing the diet with nutrients for the brain over the course of an entire lifespan.

As of 2000, one baby boomer turned 50 every nine seconds, according to James Gormley, director of trade communications, Nutrition 21, Purchase, NY, and author of DHA, A Good Fat. "The U.S. Census reported that 50+ households control 41% of all discretionary income, totaling over $169 billion, and people over 50 comprise 68.2 million (one-third) of the adult population. In the next 20 years, that number will increase to 115 million," he said. "Since the quality of the mind is at the core of quality of life, the natural products industry is attempting to anticipate and meet the self-care needs of a rapidly aging population."

Stressing the importance of brain health throughout the human lifespan was Scott Hagerman, president, Chemi Nutraceuticals, White Bear Lake, MN. "Perhaps the most important asset that we possess and wish to possess in our advancing years is our cognitive ability, since it is so extremely important both now and later in life," he said. "People should begin to view the topic of brain health very critically, since beginning as early as age 35, signs of diminishment in mental performance can be present."

Trends In The Brain Health Market
The market for brain health products is being driven forward by various health conditions. According to Parris Kidd, Ph.D., scientific consultant, Science & Ingredients, Inc., Carlsbad, CA, children's products are being fueled by an epidemic of autistic disorders, ADHD-ADD and other learning and attention conditions. Among adults, depression has reached epidemic proportions and working people report being stressed out most of their waking hours. As for the elderly, severe cognitive decline with diseases such as Alzheimer's continues to become an increasing threat to that segment of the population.

Commenting on the evolution of the brain health market was Nutrition 21's Mr. Gormley. "There is less of a magic bullet approach and more of a comprehensive, whole-body approach to brain health today, which involves dieting, exercising and customized supplementation regimens," he said. "In addition, the bar is being raised on the level of science that is needed with which to introduce new products, ingredients and ingredient formulations and with which to go forward with appropriate structure/function and marketing claims. Many companies are beginning to recognize these things."

Katie Ferren, director of botanical products, BI Nutraceuticals, Long Beach, CA, offered her opinion on the evolution of the brain health market. "The brain health category has evolved similarly to other categories," she said. "A few years ago there was a lot of science and mass market media attention. There were dozens of different brain nutrient options a consumer could purchase off a health food store shelf. Additionally, several large companies were promoting their products heavily through television and radio for mass market consumption. However, when the media started downplaying the effectiveness of supplements, the diversity of products decreased." Today, she said, brain nutrients remain solid components of product lines because they have solid science behind their claims. Growth in the category will most likely come from more highly publicized published studies or from new ingredients.

At this time, research is showing that brain or central nervous system (CNS) health products have overlapping functions, according to Alex Moffett, president, Renaissance Herbs, Chatsworth, CA. "We can expect to see one product being useful in several categories," he said. "Cognitive health (memory and learning ability), protection against the effects of stress, anti-anxiety (anxiolytic) and mood balance, which involves a number of neurotransmitters, are the basic categories. Neuroprotection as a category of CNS health products is a relatively untapped market. We expect it will grow as consumers become aware of products that have CNS-antioxidant activity, for example, and as consumers gain a greater general awareness of the effects of aging and stress on the brain."

Targeting Consumers
The natural, and perhaps most obvious, target market for brain health products in general are the elderly. However, as previously mentioned, other segments of the population will likely become important future targets as well. Discussing the former category was Dr. Ariel Katz, CEO, Enzymotec, Migdal HaEmeq, Israel. "The elderly suffer from many age-related symptoms, which negatively influence their cognitive day-to-day functions, such as memory, mood and concentration, in addition to more severe conditions, including Alzheimer's Disease and other related syndromes," he said. "Science has shown that brain health supplements can definitely assist in alleviating these conditions and improve the quality of life of the elderly."

Age related cognitive decline (ARCD) is a clinically accepted condition of which the medical arena is well aware. For this reason, individuals in their 50's and beyond were traditionally targeted for brain health supplements, according to Chemi Nutraceuticals' Mr. Hagerman. However, he said, in response to science that has emerged, the brain health market has cast a wider net hoping to pull in younger segments of the population. "Younger individuals may benefit from mental performance supplements because age is not the sole factor that affects cognitive ability," he said. "Therefore, the market has targeted individuals of all adult ages, even children who are experiencing diminished mental performance for a variety of reasons."

Shogo Hirayama, sales manager, Covex, S.A., Madrid, Spain, also said brain health is not just for the elderly. "The brain health umbrella covers everyone including children, students, people in the their 30's, baby boomers and seniors. All of these people may be the target of brain health products," he said "The target, however, depends on the marketing approach of each company."

Mr. Katz discussed some of the benefits of brain health products for younger population segments. "In the last few years scientific work has demonstrated the health benefits of brain health products in younger populations, including stressed career workers, students and even developing youth," he said. "These studies show that these populations benefit by improving their cognitive functions and memory. In addition they showed enhanced levels of concentration and reduction in stress levels. In all cases, brain health supplements contributed to a higher quality of life and improved functioning of the individual in his or her environment."

Delivering Brain Nutrients
In terms of delivering brain health ingredients, the industry is moving toward blends and functional foods, although it doesn't appear that single ingredient supplements are going away any time soon. "For the future, we will see more finished product combination complexes, including cognition cocktails, than ever before," offered Nutrition 21's Mr. Gormley. "In line with that, there is more nutrient crossover than ever before, so we will see more minerals, vitamins and herbs being blended together in formulations that, in the past, were either all-herb or all-vitamin. The single-ingredient formulations that remain will be those which have the very highest degree of science behind them."

The most popular and convenient form of delivery for brain nutrients is in capsules, according to Renaissance Herbs' Mr. Moffett. He also touted the superiority of blended products stating, "Blends have the potential of providing greater results because they may target a broader range of body systems."

Enzymotec's Dr. Katz agreed that the most popular form of delivery for brain health ingredients is in capsules. However, with regard to blends, he feels the future lies in unique blends serving as health packages to deliver a range of health benefits. "Consumers will appreciate such products that will make nutraceuticals easier to consume and may offer synergistic effects, which are not found in single ingredient products," he said. However, he feels the future also lies with novel and friendlier delivery systems, such as in foods and drinks. "We are very likely to see more ingredients for CNS health in beverages and snacks and in effective amounts," he offered. "The marketplace has been limited to a few ingredients, but with more to choose from I think we'll see this become a more active growth category. This, of course, demands further improvement of the current formulation and development of novel formulations and products that will be compatible with these new delivery systems."

Expressing some skepticism toward the inclusion of brain health nutrients in functional foods was Science & Ingredients' Dr. Kidd. "Specific brain health products have seen some involvement in functional foods," he said. "However, a major challenge for functional foods, one which undoubtedly is limiting their growth in North America, is the ability to deliver clinically meaningful intakes of the active ingredient(s). Until this challenge can be overcome functional foods are unlikely to be replacing dietary supplements."

Mr. Gormley concurred. "Despite numerous entries into the functional arena, the ability of formulators to include therapeutic levels of cognition-boosting nutrients in these products will continue to pose a long term challenge. Supplements will stay central to this category, although functional food applications will rise to a certain level and stay there."

Brain Builders
Phosphatidylserine (PS). Phosphatidylserine (PS) is a phospholipid that is crucial for proper brain structure and function. Explaining phospholipids, which are complex molecules that are the major building blocks for cell membranes, was Peter Rohde, president, Science & Ingredients. "Phospholipids belong to the safest products on the market. As orthomolecules, phospholipids are substances that are already part of our body's natural formula, that is, how our body is built and functions," he said.

According to Enzymotec's Dr. Katz, "Membranes are the working surfaces of every cell, carrying out the essential functions of cellular communication and hormonal signal transduction. Nerve cells, in particular, depend on healthy membrane function for normal neurotransmitter metabolism and nerve signal transmission. PS occupies a crucial role in many of these membrane-associated nerve cell processes. The fundamental function of PS is to help maintain proper membrane fluidity, which has major implications on most membrane functions."

Going into more detail about PS from a physiological standpoint was Chemi's Mr. Hagerman. "PS becomes a cell membrane constituent and is concentrated in organ tissues, especially in the brain matter," he explained. "With advancing age, poor nutritional and lifestyle choices, toxins and stress, the level of PS diminishes markedly and an insufficient amount is gained from the diet. Supplemental PS plays a pivotal role in maintaining the fluidity of the brain matter, regulating hormones and enzymes that are involved in dendritic repair and regulating transmission of electrical impulses, which constitute the thought process, including memory, learning and focus."

Discussing some of the health benefits of PS for people of all ages was Science & Ingredients' Dr. Kidd. "PS benefits people of all ages. In the middle-aged and elderly PS restores fading memory, brightens mood and helps lift anxiety. It also helps people cope with stress, even young and healthy individuals who have trouble adapting to stressful situations. Preliminary research indicates PS may also benefit children with attention, learning or behavioral problems."

Discussing pricing and education issues, Mr. Rohde commented, "After significant competitive changes in the composition of raw material suppliers in the phospholipid category three years ago, the raw material suppliers now refrain from investing in new clinical trials due to sharply decreased profitability and/or lack of interest in further development. The raw material cost for PS has come down by as much as 35% since 2000, but the prices in the health food stores are still widely the same. At the same time, there are no signs that the promotion and education for this category is increasing."

What may help consumer education, however, are the new qualified health claims for PS. In February, FDA granted two limited health claims for PS, both related to its benefits for memory and other higher brain functions, which should further open the door for PS's inclusion in functional foods, as well as establish it more in nutritional supplements. The new claims, coupled with extensive research touting the benefits of PS, paint a bright picture for its future role in the brain health category.

Acetyl-L-Carnitine (ALCAR). Acetyl-L-carnitine (ALCAR) is an ester of L-carnitine and is naturally found throughout the human body. In a report titled, "Acetyl-L-Carnitine Slows Brain Aging," (International Journal of Integrative Medicine, May 2000) Robert Crayhon, Ph.D., discussed ALCAR in the context of brain aging. "Certain nutrients have been examined for their potential in promoting brain health in older adults. One of the most extensively researched nutrients is acetyl-L-carnitine," he said. "ALCAR has demonstrated the ability to slow and even reverse many of the signs of brain aging in controlled human trials, suggesting that it may have the ability to slow the very process of aging."

Discussing ALCAR's function was Paula Gaynor, associate director, nutrition, Lonza, Inc., Fair Lawn, NJ. "ALCAR plays an important role in nerve cell metabolism by acting as a source of acetyl groups both for the synthesis of the key neurotransmitter acetylcholine and for energy-producing reactions," she explained. "Acetyl-L-carnitine plays a vital role in maintaining brain function as we age. This nutrient has been well studied in clinical trials, including trials involving Alzheimer's patients. In this population, clinical evidence indicates that ALCAR supplementation helps to slow down the rate of progression of the disease and in particular has beneficial effects on memory and attention span. This beneficial effect of ALCAR has been partly ascribed to its cholinergic effects, as well as its ability to support cellular functioning at the mitochondrial level."

Going into further detail about ALCAR's composition and function was Ken Hassen, vice president-Fine Chemicals Division, sigma-tau HealthScience, Gaithersburg, MD. "Acetyl-L-carnitine is an acetyl derivative of L-carnitine (gamma-trimethyl-beta-acetylbutyrobetaine) and over recent years, has been the subject of particular attention due to its biochemical, pharmacological and nutritional properties," he said. "Acetyl-L-carnitine is a naturally occurring substance that acts as a carrier of fatty acids from the cytosol into the mitochondrial matrix where they can be subjected to oxidation and it is freely exchanged across membranes and can provide acetyl groups, from which to regenerate acetyl-CoA, therefore facilitating the transport of metabolic energy. In animal studies, ALCAR has been reported to protect central and peripheral nervous system synapses in neurodegenerative and aging models to elevate nerve growth factor levels."

Essential Fatty Acids. Recently, omega 3 and omega 6 fatty acids have been gaining in popularity, particularly in infant nutrition, for their role in optimizing brain health. There exists an established body of population studies, which have linked deficiencies in essential fatty acids to a number of mental, visual and neurological problems.

Nutrition 21's Mr. Gormley highlighted the importance of essential fatty acids for the brain. "Neurons are known to contain a very high percentage of long-chain polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), an omega 3 fat, and arachidonic acid (ARA), an omega 6 fat," he said. "In the brain, millions of neuronal connections are made between dendrites-signaling that involves the release of chemical messengers from the phospholipids, high in DHA, that make up the outer covering of the dendrites, called the dendritic membrane."

Having the right proportion of omega 3 to omega 6 fats is crucial for proper brain function. "Ideally between a 1:1 to 5:1 ratio of omega 3 to omega 6 fats is desired," said Mr. Gormley. "Since the modern industrialized diet, far removed from the DHA-rich fare of our evolutionary ancestors, is overloaded in omega 6 and trans fats, it's not surprising that cognitive, depressive and neurological conditions have risen dramatically over the last 100 years."

Also making the connection between diet and disease was Dr. Morten Bryhn, director-R&D, Pronova Biocare, Lysaker, Norway. "Two studies (The Rotterdam Study and The Bordeaux Study) have consistently demonstrated that a high intake of fish prevents development of dementia, especially Alzheimer's dementia," he said.

Going into further detail, he explained that the brain tissue contains approximately 60% lipids, which means the brain is the most lipid rich organ next to adipose tissue. "These lipids are predominantly phospholipids containing saturated as well as unsaturated fatty acids and phospholipids are the main constituents of brain cell walls. Of all the unsaturated fatty acids, DHA and ARA are preferred by the brain tissue," he said. "The reason for this is not fully elucidated but these PUFA's, being the most unsaturated of the omega 3 and omega 6 PUFA's, have a three dimensional orientation which provides these phospholipids with a high degree of elasticity." He added, "Brain function is based on the rapid transduction of electrical impulses from one neuron to another. The myelin sheet covering the axons is very rich in DHA and increases conductivity by a factor of 50 compared to unmyelinated neurons. Patients with multiple sclerosis experience a breakdown of myelin rendering them with a range of neurological deficiencies that are mainly motorical. This fact that underlines the importance of conductance. Patients with dementia have significantly less DHA (and to a certain extent ARA) compared to age-matched controls."

In terms of eicosapentaenoic acid (EPA), there is very little in the brain. However, Dr. Bryhn said, EPA has shown interesting effects in the treatment of mental depression, schizophrenia and attention deficit disorders. "EPA is a substrate for the production of eikosanoids, local acting hormones," explained Dr. Bryhn. "We know that these hormones have effects on the synapse. The synapse is the gap between one neuron and the next and where the electrical signal is releasing a neurotransmitter, which will augment the conduction time in the next neuron. EPA may interfere with the effect of neurotransmitters, perhaps mostly with serotonin."

Herbs & Botanicals
Vinpocetine. Vinpocetine has only begun to receive attention in the U.S. within the past few years, although outside the U.S., particularly in Europe, it has been used for several years in connection with brain health. Vinpocetine is derived from vincamine of the lesser periwinkle (Vinca minor L). Since its approval as a dietary supplement by the FDA in July 1999, vinpocetine has been gaining in popularity.

As a vasodilator, vinpocetine is a substance that increases blood flow to the brain. According to Denise Lam, manager, technical services, Cyvex Nutrition, Irvine, CA, vasodilation is achieved by improving the rheological properties of blood through inhibition of platelet aggregation and by increasing the deformability of red blood cells. "Blood viscosity and resistance of blood flow in cerebral vessels are reduced, allowing the circulation of more oxygen to brain cells, thereby promoting lucidity and mental alertness/acuity," she said. "Vinpocetine also inhibits phosphidiesterase, the enzyme that breaks down ATP to ADP and AMP. Since ATP is the energy that fuels biochemical reactions, inhibiting phosphidiesterase increases ATP levels in cells, which means an increase in energy available to neurons. Increased metabolism in neurons is indicated by increased glucose metabolism in the brain brought on by increased blood flow due to vinpocetine."

The actions of vinpocetine are both preventative and specific, according to Robin Ward, sales and marketing manager, Linnea, Locarno, Switzerland. "Its reported anti-aeschemic activity, enhancement of blood flow and cerebral circulation are positives for maintenance of overall brain health," he said. "An increase in the rate of ATP synthesis and consumption of cerebral glucose would be considered more system specific. In both cases, the actions of vinpocetine may help in the management of Alzheimer's or Parkinson's disease as both have been areas of clinical studies with vinpocetine."

Ginkgo biloba. Ginkgo biloba is also a vasodilator that has a long track record when it comes to stimulating circulation. According to Yousry Naguib, Ph.D., manager of new product development, Soft Gel Technologies, Los Angeles, CA, ginkgo enhances cerebral blood circulation, inhibits the binding of platelet-activating factor to membrane receptors and provides strong antioxidant protection of brain cells (neurons) against lipid peroxidation and free radical damage that destroys certain neurotransmitters. "Poor cerebral blood circulation may result in short term memory loss, depression, headache, tinnitus and early Alzheimer's disease," he said.

On the research front, Linnea's Mr. Ward offered, "A recent study showed that ginkgo biloba extract has the potential to buffer the nervous system from oxidative stress." He added that a further study has shown that ginkgo biloba may help attention characteristics, short term visual memory, operational components and integral operator performance index in patients with asthenic disorders.

Since ginkgo is used as a pharmaceutical product in much of Europe, there are hundreds of studies conducted on the herb, most using the standardized 24% ginkgoflavonglycosides and 6% terpene lactones ginkgo biloba extract, explained BI Nutraceuticals' Ms. Ferren.

In terms of U.S. studies, however, the most recent study found that ginkgo had no effect on the memory and verbal skills in a study population of 200 people older than 60 and in good health. "However, this study was challenged by various groups, including the American Botanical Council, Austin, TX, which presented impressive evidence, based on clinical trials published in medical literature, which supported the benefits of ginkgo for memory and other mental functions," stated Mr. Naguib.

Ayverdic herbs. Brahmi or bacopa (Bacopa monniera) is used in Ayurvedic medicine to promote healthy mental functions, including intellectual capacity and memory. Studies continue to tout its reputation in Ayurvedic medicine as a promoter of intellectual faculties, and the brain health industry has taken notice.

According to Renaissance Herbs' Mr. Moffett, "A well-designed placebo-controlled study in healthy adults found that an extract of brahmi produced significant improvements in learning rate, state of anxiety, memory consolidation and visual information processing speed." He continued, "Another randomized, placebo-controlled, double-blind study in healthy adults aged 40-65 years found that brahmi increased the retention of newly acquired information. An earlier placebo-controlled study in school children with brahmi in syrup form found improvements in visual motor function speed and accuracy, immediate memory recall, perceptual organization and visual motor perception."

Preliminary studies on the anti-anxiety effects of brahmi reveals another area of investigation. Mr. Moffett explained, "In one study, anxiety patients were reported to significantly improve in scores of anxiety, depression, mental fatigue, memory span, nervousness, insomnia, headache, palpitation and systolic blood pressure."

Ashwagandha (Withania somnifera) is another ayverdic herb that has hit the radar screen for its cognitive applications. In Ayurvedic medicine, ashwagandha is used to treat insomnia and senile debility. The potential of this herb can be seen in numerous animal and in vitro studies. "In a placebo-controlled study on its psychomotor effects, improvements were found in choice reaction times, auditory reactions, mental arithmetic, processing and logical deduction," said Mr. Moffett. In addition, the root extract of ashwagandha and a number of its constituents were recently found to stimulate the growth of brain neurons. Clinical results also suggest that ashwagandha may be beneficial in Alzheimer's disease.