The most elegant of human organs, the brain also is the most essential. Unlike the heart, liver and kidneys, it cannot yet be replaced with either a transplant or an artificial unit. When the brain goes, we go.
 
Although it is protected from external shock to some extent by the hard, bony cranium, it is at least as vulnerable, and possibly more so, to insidious, systemic disease and deterioration.
 
The Enemies
Alzheimer’s disease (AD), other dementia, stroke, anxiety, depression, mood swings, stress, sleep issues, ADHD and PTSD are 10 of the most serious threats to brain health. Any one of these alone could cause havoc not only for individuals themselves, but also for their families, co-workers and the nation as a whole.
 
More than five million Americans are now living with Alzheimer’s; one in three seniors dies with Alzheimer’s, the sixth leading cause of death in the U.S. Every 66 seconds a new case is detected. It kills more than breast cancer and prostate cancer combined, according to the Alzheimer’s Association.
 
Family caregivers spend more than $5,000 per year caring for someone with Alzheimer’s. Along with other dementias, AD will also cost the U.S. an estimated $236 billion per year.
 
“Alzheimer’s already is the world’s most costly disease per patient, and among the most feared,” said Mark Thurston, president of AIDP, Inc., City of Industry, CA.
 
Mr. Thurston also cited these statistics from the National Institute of Mental Health: 18.1% of U.S. adults have an anxiety disorder, and of these, 22.8% are classified as severe.
 
In addition, the National Institutes of Health (NIH) reported that 50-70 million Americans are affected by sleep problems. The Nielsen Company estimated U.S. sales of sleep aids at about $427 million in 2015, with expectations of growth as Baby Boomers advance in age, obesity rates climb, and stress from the economy and longer workdays persist.
 
Evan DeMarco, director of market development at Bexbach, Germany-based KD Pharma, suggested that the annual pharmaceutical bill for ADHD is $11 billion a year, while drugs for Alzheimer’s and depression, taken together, reach nearly $29 billion.
 
However, the U.S. isn’t the only place where brain health is at risk. Euromonitor International estimated the global brain health supplement market totaled $1.53 billion in 2016.
 
Fields of Battle
Unlike some other natural products sectors that have a single focus, like weight control, the cognitive health category is concerned with a number of different target benefits, all of which interact and support one another. Among these are attention, memory, learning, language, problem solving, mood, sleep and more, said Barbara Davis, PhD, RD, vice president of medical and scientific affairs for PLT Health Solutions, Morristown, NJ.
 
“American culture has a problem; we tend to be overworked and under-rested,” said Jackson Zapp, vice president of innovation at Applied Food Sciences, Inc., Austin, Texas. “We get the fewest number of workdays off in the developed world, according to the Center for Economic and Policy Research, and during those waking hours we are chasing one stimulant after another to make the most of them. It is no wonder, then, that American people are left wired and are increasingly reporting the inability to unwind, relax and go to sleep.”
 
This is particularly noticeable among senior citizens. As AIDP’s Mr. Thurston pointed out, “The brain naturally undergoes gradual structural and functional changes as we age.” That’s the bad news.
 
“The good news,” he continued, “is that the adult brain is capable of a greater degree of plasticity than scientists had previously believed. Research in animals has shown that old neurons can be restored, leading to an increase in synaptic density, and improvements in attention, working memory, short- and long-term memory.”
 
Stephen Ashmead, senior fellow, Balchem Corporation, New Hampton, NY, concurred. “Cognitive decline is a natural part of aging, and is inevitable and unavoidable as neuronal and brain tissue reaches the end of the lifecycle,” he explained. But, he added, “Consuming adequate nutrition, including supplements, may help delay this cognitive decline.”
 
“The old adage, ‘if you don’t use it, you lose it,’ is incredibly accurate in brain health,” said KD Pharma’s Mr. DeMarco.
 
Heavy Weapons
In the struggle to preserve and improve brain health, consumers can deploy a wide-ranging arsenal of weapons. Macro-elements—the artillery, so to speak—consist of what Annie Eng, CEO of HP Ingredients, Bradenton, FL, called “all the obvious habits: eating a healthy, nutrient-dense diet; exercise; alcohol in moderation; ensuring six to eight hours of sleep per night; and healthy stress management.” To these she added “sound supplementation,” which is always narrower in scope and more target-specific than the big guns mentioned earlier.
 
Ms. Eng also believes in “brain training,” including cognitive and memory games. She cited an as yet unpublished study in which researchers used a computer-based game to reduce people’s risk for dementia. The training nearly halved the incidence of Alzheimer’s disease and other devastating forms of cognitive and memory loss in older adults a decade after they completed it, the scientists reported.
 
These results, presented at the Alzheimer’s Association International Conference in Toronto, came from the U.S. government-funded ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) study. The research effort conducted by the National Institute on Aging and the National Institute of Nursing Research (two components of the NIH) began in 1998 with 2,832 healthy participants who were an average age of 74 at the start.
 
“If the surprising finding holds up, the intervention would be the first of any kind—including drugs, diet and exercise—to do that,” said Ms. Eng.
 
Rifle Shots
As exciting as the brain training experience may be, it does not negate the need for more customary options, such as dietary supplements. NeuroActin, a patent-pending and proprietary extract of Andrographis paniculata, is HP Ingredients’ leading product for brain health, Ms. Eng said.
 
Noting that the product is supported by two research studies (Biochemical Journal, 2014; Molecular Neurodegeneration, 2014), she said it has five mechanisms of action: activates both canonical and non-canonical Wnt signaling (Wnt signaling transduction pathways are made of proteins that pass signals into a cell through cell surface receptors); inhibits GSK-3β (a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues); reduces tau hyperphosphorylation (a hallmark of several neurodegenerative disorders); induces postsynaptic proteins and synaptic function (LTP); and stimulates neurogenesis. “These actions correlate to increased cognitive function and memory creation and retrieval,” said Ms. Eng.
 
“We offer several herbs that may help support cognitive health,” said Steve Siegel, vice president, Ecuadorian Rainforest LLC, Belleville, NJ. In one study observing more than 3,600 non-demented elderly subjects, he reported, those taking ginkgo biloba extract showed lower cognitive declines than those who did not (PLOS ONE, 2013).
 
In another study, Mr. Siegel said, 33 subjects given gotu kola (Centella asiatica) twice daily after meals experienced reduced anxiety levels when tested at intervals of 30 days and 60 days (Nepal Medical College Journal, 2010).
 
He also cited studies in which use of wild blueberry juice showed a lot of promise in strengthening the memory of the elderly, and vitamin C played an important role in the overall health in the brain (Journal of Agricultural and Food Chemistry, 2010).
 
AIDP’s flagship brain health product is Magtein, a patented ingredient discovered by MIT scientists, which contains L-threonic acid magnesium salt (L-TAMS) as its key component. “Magtein has been shown in animal studies and human clinicals to restore aging neurons to their youthful conditions,” said Mr. Thurston, noting that a three-month regimen was associated with a nine-year reversal in brain age (Journal of Alzheimer’s Disease, 2016).
 
Lactium, a patented hydrolysate of milk proteins that contain a bioactive peptide with relaxing properties, leads the brain product roster at Pharmachem Laboratories, Kearny, NJ. Discussing a double-blind crossover study of 63 female volunteers, Mitch Skop, senior director of new product development, said, “Those receiving Lactium (150 mg/day) reported a significantly greater improvement in stress symptoms (vs. placebo) in the following areas: digestive, intellectual, social, cardiovascular, and emotional.” (European Journal of Clinical Nutrition, 2006.)
 
Mr. Skop also said that Lactium may play a role in improving sleep quality and easing symptoms of burnout. Quoting from a study published in Behavioural Brain Research (2016), he said the product “induces sleep promotion as shown by an augmented pentobarbital-induced sleep in mice and an increased slow (delta) EEG wave in rats. This sleep-promoting effect...is probably mediated through the GABAergic neurotransmitter system.”
 
Sleep is one of three targets for a line of botanical extracts marketed by Israel-based Frutarom. “Lemon balm, valerian, passionflower, linden flower, hops and chamomile extracts are well documented in literature to support sleep promotion,” said Yannick Capelle, global product manager at the company. “For stress resistance, we can offer extracts from adaptogenic plants such as ginseng or schisandra,” he added. “And Neuravena, a patented extract of green oat, and green tea extract EFLA942, have demonstrated in clinical studies a beneficial effect on concentration and executive memory.” (Nutritional Neuroscience, 2015; Journal of Hypertension, 2013; European Journal of Clinical Nutrition, 2012.)
 
Kavoa, a kava root extract, intended as a relaxation, anti-anxiety and sleep aid, is Applied Food Sciences’ proposed answer to problems with sleep and stress. Mr. Zapp said the active compounds in kava, called kavalactones, have been studied in more than a dozen human clinical papers for their temporary benefits in anti-anxiety, stress and sleep.
 
“Current evidence suggests that stress and other anxiety-related mental illness are influenced by changes in GABA or g-aminobutyric acid,” he said (Psychopharmacology, 2009). “GABA is a substance that calms neurons and, in the case of kava, uses specific plant metabolites to bind to neurotransmitters and have a damping effect on nerve transmission that has become overexcited.” (Phytotherapy Research, 2007; Sleep Medicine Reviews, 2011; Spinella, 2001, Psychopharmacology of Herbal Medicine.)
 
Plant scientists employed by Des Moines, IA-based Kemin Industries have been working for more than five years on two proprietary lines of spearmint. The result is Neumentix Phenolic Complex K110-42, a proprietary, spearmint-based ingredient that, according to the company, has been clinically tested and shown to naturally support working memory in adults.
 
On its website, which calls the new product a “360° working memory solution,” Kemin said, “phenolic molecules in Neumentix may act in the brain to provide antioxidant support, increase neurotransmitter levels, protect neurons and promote neural growth.”
 
Astaxanthin (from Haematococcus pluvialis) is the featured product of AstaReal, Inc., Burlington, NJ. Joe Kuncewitch, national sales manager, reported, “Several randomized, double-blind, placebo-controlled studies have shown that three months of supplementing with natural astaxanthin (12 mg AstaReal/daily) improves mental quickness, multitasking, memory and faster learning in senior subjects who noted age-related forgetfulness and loss of mental acuity. Clinical studies also suggest that astaxanthin reduces oxidative byproducts in red blood cells while promoting collective improvements of the blood lipid profile, blood antioxidant capacity, capillary blood flow and blood pressure—five primary factors that ensure healthy vascular conditioning.”
 
Mr. Kuncewitch called particular attention to two studies from Japan. In one, astaxanthin supplementation reduced oxidative byproducts in red blood cells; attenuated lipid peroxidation of the red blood cells’ membranes; and improved red blood cells antioxidant status. Overall, the study suggested that astaxanthin may contribute to the prevention of vascular dementia by improving the quality of blood and quantity of oxygen and nutrients that reach the brain tissues (British Journal of Nutrition, 2011).
 
In the other, he said, “Findings show that pretreatment with astaxanthin improved subjects’ information-processing, memory and learning. The improvement was assessed by using an internationally recognized cognitive function test called CogHealth. Astaxanthin oral intake significantly improved subjects’ simple reaction, choice reaction, divided attention, short-term memory and delayed recall (Journal of Clinical Biochemistry and Nutrition, 2009).
 
East Windsor NJ-based Sabinsa offers an extensive list of ingredients, many reflecting Ayurvedic principles, and all having a long history of use for cognitive support. Anurag Pande, PhD, vice president of scientific affairs, said, “Baccosides in Bacopa monnieri are known to increase the protein kinase activity, which helps formation of new synapses, and help in improving the learning and memory function of the brain. Clinical studies have shown the cognitive benefits of taking Bacopa-based extracts in both children and adults. Bacopa has also shown reduction in anxiety levels.” (Evidence-Based Complementary and Alternative Medicine, 2015; International Journal of Pharmaceutical Sciences and Drug Research, 2009.
 
Other major Sabinsa brain health products include: DOPA (also called Levodopa or L-DOPA), a precursor of the neurotransmitter dopamine, which helps support healthy mood and mental alertness, and has even been studied in connection with Parkinson’s disease (Journal of Neurology, Neurosurgery & Psychiatry, 2004); gotu kola, which has been found to modulate dopamine in rat brains and may improve learning and memory processes; and Curcumin C3 Complex, which may help with immune clearance of beta-amyloid protein, thus boosting the body’s capacity to clear up plaque in the brain (Journal of Alzheimer’s Disease, 2006).
 
Krill oil, derived from small crustaceans eaten by whales and other marine life, is also proving to be a whale of an ingredient in the natural brain health category. Superba Krill Oil, Aker BioMarine’s flagship omega-3 product, is attached to phospholipids, allowing better absorption into the cells, according to Becky Wright, director of marketing and communications for the firm’s Issaquah, WA-based U.S. headquarters. “Recent research indicates that phospholipids ferry docosahexaenoic acid (DHA) into the brain more efficiently, where its omega-3 content can help maintain a wide range of functions, such as memory, mood and cognition.”
 
The company also offers two variations on the basic Superba product—Superba 2, which features “improved smell, taste and visual appearance,” and Superba Boost, a new krill oil concentrate, which contains a “significantly higher concentration” of the key actives, including phospholipids, omega-3s and choline.
 
Omega-3 nutrition also figures prominently in KD Pharma’s Alpha and Omega. Mr. DeMarco described the ingredient as a trademarked dual action cognitive support supplement combining high-concentrate omega-3 fatty acids with alpha-GPC, a natural choline compound found in the brain. It is also a parasympathomimetic acetylcholine precursor, which has been discussed in connection with the treatment of Alzheimer’s disease and other dementias.
 
Leading the list of brain health ingredients from Balchem is the company’s VitaCholine line of choline products. Mr. Ashmead cited studies showing choline to be vitally important in the cognitive development of infants in utero and continuing postnatally, as well as possibly helping delay cognitive decline and memory loss associated with aging.
 
Other Balchem brain health products include: Ferrochel, a source of supplemental iron, which is believed to be critical for cognitive development in the early stages of life; Zinc Bisglycinate, a chelated form of zinc, which has been examined in connection with both Alzheimer’s patients and children exhibiting depressive symptoms; and several bioavailable forms of magnesium, since some scientists believe a deficiency of magnesium in the hippocampus may have a pathological effect in the development of Alzheimer’s.
 
All the way from Liège, Belgium comes ATAMg. Marketed by Synapharm, this product is described by Pascale Azzam, the firm’s managing director, as an “innovative magnesium with proven physiological action.”
 
The N acetylated taurine induces a better cellular penetration of magnesium and an increase of its neuromuscular activity, making it a more intra cell taurine and a bioavailable magnesium.”
 
Sibelius Limited, headquartered in Oxford, U.K., has launched Sibelius Sage, which the company described as its “first epigenetically active product available for commercial use.” The firm said the extract of sage, which is intended to enhance cognition, was developed with the aid of its patented Chronoscreen technology.
 
Sibelius CEO Peter Leyland called this an important step forward for the company. “Up to now our clients have known us as a partner for testing their proprietary ingredients and products. This product offers our clients something more, a reliable and effective ingredient with epigenetic resetting capabilities, backed by our expertise in botanicals and the science of epigenetics.”
 
According to PLT Health Solutions’ Dr. Davis, “most cognitive health ingredients and consumer products are aimed at two ends of the age spectrum—pre-natal/childhood for healthy development, and seniors for anti-aging. At PLT, however, we have been focusing on what we consider to be an underserved demographic—the 18-54 age range. Within this group, we see intense interest in issues such as ‘peak performance,’ ‘well-being’ and ‘quality of life.’”
 
Noting that the market opportunity is massive, Dr. Davis said PLT has developed a range of products for this segment. The two best known of these are Zembrin Sceletium tortuosum and Synapsa Natural Memory Support, a patented, standardized form of Bacopa monnieri.
 
Zembrin, being marketed as the world’s first patented, standardized and clinically studied extract of Sceletium tortuosum is said to “experientially support calmness, enhanced mood and improved cognitive function.”
 
Synapsa Natural Memory Support, when used daily over the long term, is aimed at enhancing “learning and memory.” Taken short-term, it is said to improve mental performance in cognitively demanding situations, such as test-taking.
 
Kyowa Hakko U.S.A., New York, NY, is also convinced that brain health is a concern for people of all ages, not just the very young and very old. “While an aging population looks for products that support memory and mental acuity, younger consumers want support to help them stay sharp and focused,” said Karen Todd, RD, the firm’s senior director of global brand marketing.
 
Ms. Todd identified Cognizin, a branded form of citicoline, as a clinically researched brain health ingredient—“found in every cell of the body”—that’s been shown to support mental energy; promote focus and attention; and support overall cognitive health.
 
According to Ms. Todd, “Citicoline is broken down during intestinal absorption and, after passing through the blood/brain barrier, is reconstituted in the brain as a water-soluble compound that supplies precursors for the synthesis of phospholipids, including phosphatidylcholine, a major constituent of brain tissue.”
 
By helping to maintain normal levels of acetylcholine, a chemical that regulates cognitive function, it promotes communication between neurons, protects neural structures from free radical damage, supports healthy brain activity and metabolism, and helps sustain healthy cellular mitochondria to support cognitive health and energy, she said.
 
Future of the Field
When asked about the direction and strength of the natural brain health sector, experts were not—pardon the pun—of one mind. Although all foresee an upward trajectory, some predicted significant growth over the next two or three years, while others were more tempered in their enthusiasm.
 
“In my opinion, brain health and cognitive decline will be the next big public health concern,” said Balchem’s Mr. Ashmead. “As a result, there will be more attention paid to science-backed nutraceuticals and ingredients that can aid in maintaining normal brain health and cognitive function.”
 
Also hopeful about the market, but a little more cautious, PLT’s Dr. Davis said, “Considering the level of consumer interest in cognitive health, it is a little surprising that this market, while growing, is dwarfed by markets for joint health or heart health. If we are going to meet this clear consumer need, it may well be that the industry as a whole needs to re-examine how we approach the concept of cognitive health—from the ingredients that we supply, to the science that we develop to support claims, the target markets we address and end-use formulations we develop.”
 
Sabinsa’s Dr. Pande said one way in which to stimulate more consumer interest might involve changes in dosing formats. “Water-soluble ingredients which could be delivered as beverages or functional foods may be preferred over nutraceutical tablet and capsule dosage forms,” he explained.
 
Dr. Pande suggested that researchers spend time working to innovate stable ingredients that could be incorporated into diverse dosage forms for maximum benefits.
 
According to Ecuadorian Rainforest’s Mr. Siegel, consumers in the 18-35 age bracket may start to look for more products that support mental relaxation. “This may be especially true of anyone in a creative field where mental fatigue is a regular occurrence.” 
 

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Alan Richman, former editor/associate publisher of Whole Foods Magazine, is now a full-time freelancer focusing on the health and nutrition industry. A frequent contributor to Nutraceuticals World, he can be reached at alanrichman@yahoo.com.