The Curious Case of Cognitive Health

By Alan Richman , Contributing Writer | August 21, 2012

There are plenty of clues on how to deal with ADHD, Alzheimer’s and autism, but solutions remain elusive.

America’s current mental health report card is marked—and marred—by the presence of four “As” and one “D.” The As are for ADD/ADHD, Alzheimer’s disease, Anxiety and Autism, and the D is for Depression.
There are numerous factors that will make this situation worse before it gets better. For one, the U.S. population—like that of most developed nations—is aging rapidly. Sam Wright IV, CEO of The Wright Group, Crowley, LA, says that beginning this year and continuing for as much as 20 years into the future, “a U.S. Baby Boomer will turn 65 every eight seconds.” 
In that vein, Mr. Wright said, “Fear of developing Alzheimer’s disease and the many other forms of age-related dementia exceed fear of cancer for most older people. The Alzheimer’s Disease Association reports that 5.4 million Americans have this condition, 5.2 million of whom are over 65. Alzheimer’s affects 13% of all those over 65 and 45% of those over 85. This does not include other dementia-related disorders.”
On a related note, Mr. Wright pointed out that the number of Americans over 85 will quadruple by 2050 to 21 million people (most of whom will be driving!). “It is estimated that the current cost of caring for these patients is $200 billion annually and will approach $1 trillion by 2050,” he said.
In previous times, Mr. Wright observed, “People used to die before these conditions could affect them in such great numbers.”
Meanwhile, seniors aren’t the only ones dealing with cognitive health issues. At the other end of the age scale, increasing numbers of children are displaying symptoms severe enough to require treatment. It is now generally agreed that almost 3 million children in U.S. schools have specific learning disabilities. About one in every 88 children is identified with an autism spectrum disorder (it was one in 110 in 2006). These are characterized by poor social interaction communication skills, repetitive and ritual patterns, and aversion to noise. Meltdowns are not uncommon. In addition, attention deficit hyperactivity disorder (ADHD) affects 5-7% of the nation’s youngsters, which translates to about 4 million kids or more. About 50% of these are expected to carry their symptoms into adulthood.
Nor do the adults between youth and old age get a bye. According to Medline Plus, a publication of the National Library of Medicine, “A 2004 study showed that 8% of American adults (which was about 17.1 million at the time) had experienced at least one major depressive episode during the last year. An estimated 10-15% of women experience postpartum depression after giving birth.”
And the National Institute of Mental Health (NIMH) reports, “Anxiety disorders affect about 40 million American adults age 18 years and older (about 18%) in a given year, causing them to be filled with fearfulness and uncertainty.” 
Philosophies Differ
None of this has gone unnoticed by either Big Pharma or the nutraceuticals industry. Both have leaped into the breach with products that may benefit those with cognitive woes. Members of the nutritional products industry emphasize that there are distinctive differences between prescription meds and nutritional supplements. 
Chief among these differences, says Kathy Lund, vice president of business development for AIDP, Inc., City of Industry, CA, is that the drugs are aimed at “stimulating the brain neurons,” whereas substances like AIDP’s Magtein are intended to help rebuild the brain neuron density. “This is a more healthful and potentially better, longer-term solution to managing cognitive decline,” she commented. “In addition, because Magtein is magnesium-based it is a more natural solution.” 
Others express a similar view. According to Puya Yazdi, MD, medical director for Irvine, CA-based Cyvex Nutrition, Inc., “Our ingredients—including Cognisetin, OmegaActiv, Euro Black Currant, vinpocetine and Solathin—are geared toward maintaining a healthy cognitive function, while the majority of pharmaceutical agents and drugs aim to treat precise medical conditions and ailments after the inciting agents have already damaged those biochemical pathways. In addition to diet, exercise and maintaining a healthy lifestyle, such natural nutraceutical ingredients as OmegaActiv and vinpocetine can help fight off the normal cognitive decline associated with the aging process.”
Anurag Pande, PhD, vice president of scientific affairs for Sabinsa Corporation, added, “Pharmaceutical drugs are primarily focused on the diseases,” while “the supplement industry focuses on preventive care and cognitive function enhancement.” 
Dr. Pande, whose company has offices in East Windsor, NJ, and Payson, UT, says Sabinsa’s Bacopa and Centella products “have been studied in Ayurveda for their cognitive enhancing effects as well as preventive care for old-age cognitive loss. Mucuna has been studied for its alleviating effect on cognitive decline in Parkinson’s disease. Curcumin has been part of some studies to slow down cognitive decline in Alzheimer’s, by its effect on beta amyloid deposition in the brain.”
Research Is Key
Numerous research efforts support ingredients like those mentioned previously. AIDP’s Ms. Lund, for example, cites two published studies showing that enhancement of plasticity in certain brain regions, such as the prefrontal cortex (PFC) and/or hippocampus, might enhance the efficacy of cognitive therapy. Magtein, its novel magnesium compound, was previously shown to increase brain synaptic density in the hippocampus and facilitate short- and long-term memory.
Enzymotec Ltd., Migdal HaEmeq, Israel, offers two major compounds for cognitive health—phosphatidylserine (PS) and alpha-GPC. Dr. Rami Hayun, senior scientist, R&D, in the BioActive Ingredients Division, and Dr. Sigalit Zchut, director of research and development, say the company conducted a series of clinical and pre-clinical trials to learn more about the efficacy, safety and mechanism of action of PS/omega3. Findings showed PS/omega3 elevates the absorption of DHA into the brain, has cognitive benefits in elderly people with memory complaints, and improves several memory and learning abilities, especially in participants with relatively good cognitive performance at baseline. This last study was a 15-week, double-blind, placebo-controlled clinical trial conducted with 157 non-demented elderly individuals with memory complaints.
In addition, Enzymotec conducted two clinical trials with children, and both showed that PS/omega3 reduced the negative symptoms of children diagnosed with ADHD.
In April, Lonza, a Swiss company with U.S. offices in Allendale, NJ, announced new ingredients associated with cognitive health: DHAid, a “next generation” vegetarian docosahexaenoic acid (DHA), in two new oil versions—DHAid FNO-350 and DHAid CL-400. These join the company’s powdered product, DHAid Dry. The Lonza lineup also includes Memree and Memree Plus, patented combinations of soy-derived PS and phosphatidic acid.
According to Kevin Owen PhD, the firm’s NAFTA head of technical marketing and scientific affairs, “Research has shown that DHA may be important for optimal brain health across the age spectrum. For infants and children, it is well established that DHA is required during fetal and child brain growth. In adolescents, supplementation with DHA was found to prevent aggression enhancement during times of mental stress, such as exam periods. In adults and elderly populations, DHA helps maintain normal brain function. Scientific evidence links reduced DHA levels to several mental disorders including depression, dementia, schizophrenia and Alzheimer’s disease.”
Eric Anderson, vice president of sales and marketing for Issaquah, WA-based Aker BioMarine Antarctic US, also touts the value of DHA contained in his firm’s Superba Krill Oil. “Omega 3 has been shown to improve brain function and memory due to its unique composition of phospholipids. Simply said, DHA is necessary for brain cells to communicate. It is especially important for the proper development of the brain in the fetus and in young children,” he said. “Moreover, DHA increases the production of two hormones, serotonin and dopamine. Increasing the level of these two hormones might improve the quality of life—in a natural way.”
Citing a study that appeared in the International Dairy Journal, Mr. Anderson says that researchers looked at several markers showing the impact of omega 3s from krill oil and fish oil in Zucker rats. They found that both fish oil and krill oil were able to influence long chain polyunsaturated fatty acid (PUFA) profiles in the brain. “However,” he added, “only krill oil was able to significantly increase DHA levels in brain phospholipids, suggesting that krill phospholipid omega 3s may have superior activity.”
DHA also is featured in the broad portfolio of cognitive health choices from DSM Nutritional Products, Inc., in Parsippany, NJ. According to Aparna Parikh, MBA, RD, senior marketing manager, “Newborn babies need DHA, ARA (arachidonic acid) and lutein (an antioxidant carotenoid) for brain and eye development. Our algal-based life’sDHA omega 3 fatty acid and FloraGLO lutein are included in leading infant formulas for that specific reason.”
Responding to rising consumer interest, DSM also launched two new brain-oriented formulas in May. “Energize your mind” and “Relax your mind,” both part of the company’s existing “Empower your mind” platform, contain Ginkgo biloba extract, which has been shown to boost mood and alertness, and Coenzyme Q10 (CoQ10), which supports cellular energy production to compensate for the toll aging takes on natural levels. Other active ingredients include lemon balm and chamomile, which have been found to have a positive effect on mood and to help reduce symptoms of nervous tension.
In addition to all these inputs from individual ingredient formulators are the efforts of the Global Organization for EPA and DHA Omega 3s (GOED), located in Salt Lake City, UT. GOED describes itself as a “proactive and accountable association of the finest manufacturers, marketers, and supporters of EPA and DHA omega 3 fatty acids, working to educate consumers and work with government groups, the healthcare community and the industry, while setting high ethical and quality standards for our business sector.” Besides initiating and supporting research on omega 3s, GOED monitors others’ projects and reports on them. 
Harry Rice, PhD, GOED’s vice president of regulatory and scientific affairs, commented on the extensive research behind omega 3s. “Of all the substances reported to affect cognition, the long-chain omega 3s have the largest scientific body of literature to support their use. Research in this area is exploding, and the more that is published, the more compelling the story becomes.”
Mr. Rice cites one study, released in May, in which scientists found that higher long-chain omega 3 intake was associated with lower plasma levels of the peptide amyloid beta 42, suggesting a reduced risk of Alzheimer’s disease.
He also notes increasing evidence that “there are relative deficiencies in the long-chain omega 3 fatty acids in children with ADHD and related behavioral and learning difficulties, including dyslexia, dyspraxia and autism.” (For more information on recent controversial omega 3 research, see the side bar on page 56).
Beyond Omega 3s
Zembrin is P.L. Thomas’ trade name for a standardized plant extract from kanna (Sceletium tortuosum), a functional food source utilized by South African nomads, the descendants of original hunters and gatherers known as the San people (or “Bushmen”). Vladimir Badmaev, MD, PhD, medical and scientific affairs adviser for the Morristown, NJ-based company, summarized its benefits. “The evidence indicates that traditional benefits of Zembrin may be owed to one of the most sought-after mechanisms in neuropharmacology, i.e. enhancing intracellular signaling and communication between and among neural cells,” he said. “This becomes possible with inhibition of the phosphodiesterase subtype-4 enzyme (PDE-4), which helps preserve the intracellular communication messenger, cAMP (cyclic adenosine monophosphate).”
Dr. Badmaev cites studies showing that inhibition of PDE-4 prevents premature destruction of cAMP and preserves the signaling molecules that enhance cognitive, memory and affective processes. What is special about Zembrin, he adds, is that it does not produce nausea in healthy humans, as many other PDE-4 inhibitors do.
In one double-blind, placebo-controlled crossover 3 week study, says Dr. Badmaev, normal subjects showed signs of significant change in cognitive flexibility and executive function. The improvement in mood with Zembrin coincided with the observation that patients who were “hyper” as well as “hypo” normalized on Zembrin. In addition, sleep quality improved in the active receiving group. The P.L. Thomas executive believes this is related to the perception that Zembrin is an adaptogen and modulates the central nervous system (CNS) functions.
Mr. Wright of the Wright Group suggests that in the end “those ingredients with the most proven scientific evidence will be the most successful. Among these are citicoline, phosphatidylserine, caffeine and DHA omega 3.”
“We see the cognitive health space as a broad set of needs and benefits, which span energy, mood, stress, memory and mild-to-moderate depressive states. Since this area is so broad, many ingredients can be found in products targeted at this population. The major ones we see are citicoline, caffeine, taurine, HMB (beta-hydroxy methyl butyrate), DMAE (dimethylaminoethanol), vinpocetine, DHA omega 3s, phospholipids such as phosphatidylcholine and phosphatidylserine, and a wide range of herbal products—especially Ginkgo biloba, St. John’s Wort, huperzine and kava—as well as B vitamins, carotenoids, flavonoids and minerals such as iron and magnesium.
Because many of these ingredients are “inherently unstable, reactive and problematic from a flavor and odor perspective,” Mr. Wright sees “tremendous opportunities” for his company’s SuperCoat microencapsulation technology.
Launched just last May, ReQollect is a branded vinpocetine marketed by Minnetonka, MN-based Alchem USA Inc. Manufactured in India by Alchem’s parent company, the product is derived from periwinkle and Voacanga africana plants. 
According to Laurent Leduc, the firm’s chief operating officer, “Vinpocetine is often called the ‘smart nutrient’ for its studied ability to help improve cognitive function and memory by increasing blood circulation through the brain.” Noting that there have been published clinical studies involving more than 30,000 individuals, Mr. Leduc says vinpocetine is approved for use by both the European and British Pharmacopeias.
The Alchem executive cites three multi-center, double-blind, placebo-controlled and randomized trials involving 583 patients aged 58 years and older who were administered 15-60 mg vinpocetine. Clinical Global Impression Scale and Syndrome Kurtz Test scores showed significant improvement over placebo among the subjects receiving vinpocetine.
Earlier this year, naturopath Michael Murray, a well-known author and lecturer, called pyrroloquinoline quinone (PQQ) one of “tomorrow’s best sellers.” The ingredient, available from Purchase, NY-based Maypro Industries, is not unlike CoQ10 in that it functions as an oxidoreductase coenzyme. In one placebo-controlled, double-blind human study, Japanese subjects between 50 and 70 years old were found to improve not only in immediate memory, but also in higher brain functions such as spatial awareness. Participants in the research were either self-identified as being forgetful, or a family member attested to their forgetfulness. All subjects were given PQQ alone, or PQQ together with CoQ10, or placebo for a period of 24 weeks. The combination of the PQQ and CoQ10 worked better than the PQQ alone.
Today, says P.L. Thomas’ Dr. Badmaev, cognitive health compounds are being delivered to consumers in virtually every imaginable format, including hard-shell capsules, tablets, softgels, drinks and sublingual strips. In clinical studies, he reports, Zembrin has been administered in the form of two-piece hard gel capsules and also as sublingual strips.
In Mr. Wright’s view, “Beverages, in particular, are more suitable for older consumers who may have problems swallowing tablets or capsules. It is also easier to mask unpleasant organoleptic characteristics in liquid systems where sweeteners, thickeners and flavors are utilized.”
“The form of a product is often based on its efficacy and acceptance by the population. The palatability of certain ingredients will determine whether they are delivered as a supplement or in a food matrix,” said Keith Garleb, PhD, director of global discovery research and development for Abbott Nutrition, Columbus, OH. 
‘Thinking’ About the Future
Despite the variety of natural approaches, not to mention the pharmaceutical options, we still can’t corral the mental health mustang. As noted at the beginning of this article, statistics suggest that the incidence of conditions like ADHD and Alzheimer’s continues to soar. According to Mr. Garleb, Abbott wants to change this. Together with the University of Illinois Urbana-Champaign (UIUC), the company has created the Center for Nutrition, Learning and Memory. Current efforts are underway to address many cognitive health issues, such as so-called “baby brain” and “chemo-brain.”
In May, the Center announced its plan to provide $10 million in funding for 13 research projects to be conducted in the next one to three years. Recipients were selected as part of a “Grand Challenge” research competition aimed at identifying potential active ingredients and determining which populations could benefit most from intervention with food products. 
The current Abbott product lineup features such science-based pediatric and adult nutritional formulas as Similac, Gain, PediaSure, Ensure and Glucerna. Mr. Garleb explained, “Similac Advance was designed with breast milk in mind and offers a new lutein and DHA blend, which support a baby’s brain and eyes during this critical time of development.”
Overall, the cognitive health market seems assured going forward. Forecasting a “tsunami of demand,” Mr. Wright said, “This will become a much more visible and credible category during the next two to three years because of demographics and emerging science.”
Cyvex Nutrition’s Dr. Yazdi says, “With each passing year, cognitive health will become a bigger, pressing need. The most likely scenario will be one in which more people will be looking for one or two cognitive function ingredients to add to an existing supplement regime that has some cognitive healthy benefits but isn’t specific.” In other words, consumers will attempt to deal with cardiovascular health or weight management and cognitive function at the same time. Cynics might say that ought to be a snap for a population that is increasingly attracted to multitasking.                

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