As brain health has a sizable influence on quality of life, it’s no wonder that supplement manufacturers have taken up the mantle of expanding the category. It’s also no surprise that consumers, for their part, are flocking to these brain boosters like they do their multivitamins and heart health supplements.

But before we get ahead of ourselves with a foray into the contemporary brain supplements scene, it is important to keep in mind the foundations of healthy cognition on a long-term basis. “Good, solid, basic nutrition has to be the starting point. What good will it do if someone begins a supplement routine for the brain if the basic nutrition needs are not met?” says Mark J. Kaylor, vice president of education and research at Mushroom Wisdom, East Rutherford, NJ. Diet and lifestyle factors, he emphasizes, are keys to a healthy brain; these include the benefits of a whole food, plant-based diet and getting plenty of exercise.

Indeed, the benefits that supplementation can bestow on our brains, both long- and short-term, can often be achieved through other means. “For example, studies have shown that following a Mediterranean diet may lower dementia risk over our lifetime,” says Cynthia Green, Ph.D., author and president of Memory Arts, LLC, Upper Montclair, NJ. This is a diet loaded with fruits and vegetables (and is therefore rich in antioxidants), along with a focus on lean protein and healthy fatty acids from olive oil.

Recent research has also steered some focus toward what people weigh, and how that weight is carried, when it comes to predicting brain health, according to Green. She says, “In these studies, participants who were obese or even just overweight were significantly more likely to develop a serious memory disorder later in life. This risk increased when that additional body fat was carried in the visceral, or belly area.”

These elements must be attended to if consumers of all ages don’t want to fight an uphill battle for their brain’s health. That said, it will certainly help you inform your customers, as they navigate a complex category, if you can tell your alpha-glyceryl phosphoryl choline from your acetyl-L-carnitine.

Staying Sharp: Preventing Decline
Whether diagnosed and classified as Alzheimer’s disease or not, individual cases of cognitive decline can range from bothersome to devastating in their effects on quality of life. This goes for the patients themselves, the people who care for them and, when the problem grows large enough, the society in which they live. Not to mention that, when it takes the form of disease, cases of cognitive decline can be fatal. “The financial and physical implications are enormous, both on the patients and on society at large,” says Nagabhushanam Kalyanam, Ph.D., president of R&D at Sabinsa Corp., East Windsor, NJ.

Kalyanam says that Alzheimer’s and Parkinson’s disease, the nervous system condition that has relevance in any discussion of brain health, can be attributed in part to the deposition of protein aggregates in the neuronal cells of the brain. Often termed amyloid plaque in the case of Alzheimer’s, these protein aggregates have a strong, studied link to the symptoms of cognitive decline when the patients’ brains are examined postmortem. Kalyanam says that curcuminoids, biologically active constituents of the turmeric plant that possess antioxidant qualities, have shown definite promise in the research when applied to both of these conditions.

Macrophage cells, according to Kalyanam, are not necessarily effective on their own in the removal of these amyloid tangles from brain cells. But there is evidence that curcumin can aid macrophages in the removal of the deposits, and one curcuminoid, bis-demethoxycurcumin, may be even more effective.

Turmeric and its derivation curcumin, according to David Winston, RH (AHG), president of Herbalist and Alchemist, Inc., Washington, NJ, may be the most studied of the herbal applications for brain health. Herbs that may benefit the brain through neurochemical changes can be placed under the heading of nootropics. Turmeric is not to be classed this way, Winston says, since its effects are of the anti-inflammatory kind. This reduction in inflammation can help inhibit the formation of amyloid plaque in the brain.

For an introduction to two more central figures in the brain health arena, we turn to Chase Hagerman, business development and marketing manager for Chemi Nutra, White Bear Lake, MN. “One of the best ingredients on the market for reducing cognitive dysfunction is alpha-glyceryl phosphoryl choline (A-GPC),” he says. In some cases developed and sold as a pharmaceutical in foreign markets, A-GPC has been studied for its potential benefits in Alzheimer’s disease, dementia, stroke, brain injury and other aspects of brain wellness. It has, therefore, found its way into many supplement formulations in recent years, as well as functional foods and beverages.

When ingested, Hagerman says, A-GPC is eventually converted to phosphorylcholine, the metabolically active form of choline. “Phosphorylcholine migrates to the synaptic nerve endings found throughout the entire central nervous system, and in turn increases the synthesis and release of acetylcholine (AC),” he says. The neurotransmitter AC is a crucial presence in the brain, being instrumental in a range of cognitive functions.

There is a mound of research supporting citicoline as an ingredient able to benefit cognition, including an ability to improve some symptoms of dementia. For instance, one study on a branded citicoline ingredient (Cognizin from Kyowa Hakko U.S.A.) found a benefit to the memory of elderly individuals. These improvements were seen in tests of word recall, immediate object recall and delayed object recall. Those researchers described citicoline as “a choline donor involved in the biosynthesis of brain phospholipids and acetylcholine,” (1).

Phosphatidylserine (PS) also enjoys a well-deserved popularity in the brain health market. “In fact, PS has two FDA health claims related to cognitive dysfunction and dementia in the elderly,” Hagerman says. Those U.S. Food and Drug Administration (FDA)-approved product claims read, “Consumption of phosphatidylserine may reduce the risk of dementia in the elderly. Very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of dementia in the elderly. FDA concludes that there is little scientific evidence supporting this claim,” with an identical claim allowed when swapping out the term dementia for “cognitive dysfunction.” This is a strong allowance from the agency, relatively speaking, based upon a review of PS’s safety and efficacy data, and speaks to the volume of evidence for the benefit of PS in human beings.

To illustrate, there is evidence that PS, when attached at the molecular level to omega-3 fatty acids, has cognitive benefits in elderly people presenting memory complaints, according to a recent study cited by Rami Hayun, senior scientist, R&D, BioActive Ingredients division of Israel-based Enzymotec Ltd., U.S. headquarters in Morristown, NJ (2). Hayun explains that PS “is found to improve several cognitive aspects such as learning, memory and concentration, and in addition, when the PS is attached to DHA, it elevates the DHA absorption into the brain more effectively than fish oil does.”

“Omega-3 fatty acids have repeatedly been shown to reduce cognitive decline and improve acute cognitive function in older individuals, Alzheimer’s patients and animals,” says Xingwu Liu, founder, SeabuckWonders, Chicago, IL. Sea buckthorn, high in omega-3s, is also high in vitamin E, known for its antioxidant capacities. A study Liu points us to reveals a combination of omega-3 fatty acids and low-dose B vitamins could help enhance brain function in the wake of a stroke (3).

It is, however, in the preventive role that omega-3s and brain health are often linked. They are generally known, DHA in particular, for an ability to prevent cognitive decline, according to Hayun. Their benefits for cardiovascular health may also mean a reduced risk of Ischemic stroke, which is due to blocked blood vessels feeding the brain. But in the context of brain health supplements, we are more concerned with the topic of cognition. Referring to specific studies, Kevin Owen, Ph.D., NAFTA head of technical marketing and scientific affairs for Lonza Inc., Allendale, NJ, states, “Among various other factors such as family history, gender and age, DHA levels seem to be important in affecting the risk of dementia. Increased DHA intake was found to be protective against cognitive decline, and the risk of developing Alzheimer’s in various studies.”

Owen goes on to say that generally speaking, among omega-3s, only DHA was found to be protective in these studies (4). Patients with Alzheimer’s-related dementia were reported to have 30% less DHA in their brain tissue than those with normal cognition of the same age. The neuroprotective effects of DHA, Owen explains, may be the result of DHA-derived molecules like neuroprotectin D1. These neuroprotectins promote neuronal cell survival and reduce cell death in the human brain (5).

To further underscore the importance of DHA in the brain, there is a new study linking low blood plasma levels of DHA conjugated to phospholipids (of which PS is one) with higher incidences of Alzheimer’s and cognitive impairment (6). Much of the body of research on omega-3s points to the anti-inflammatory effects these substances impart on the brain, which can also positively impact many other facets of human health, Hayun explains.

The antioxidant capacities of cocoa extract are also garnering attention. This benefit derives from the phytochemicals that are found in dark chocolate and which, when extracted from the cocoa bean, can be concentrated to provide an effective dose for brain health. “The polyphenols found in the cocoa bean, the source of the rich, delicious flavor in chocolate, work as powerful antioxidants that can reduce oxidative stress, which left unchecked can accelerate aging and poor cellular function,” says Joseph Maroon, M.D., FACS, senior vice president of the American Academy of Anti-Aging Medicine.

“In a recent study involving the preservation of telomeres and DNA integrity, dark chocolate consumption was shown to slow the shortening of telomeres. Telomeres are structures that protect the ends of our chromosomes, or strains of DNA found in the cell nucleus, and protect normal cell division,” Maroon writes in an article on brain health supplements. Damage to and instability within DNA as we age is likely a factor in many diseases of aging, including those related to cognitive decline. Therefore, the polyphenols found in dark chocolate may be able to preserve cognitive function, according to this research on telomeres (7).

Beyond the aforementioned turmeric and cocoa, an abundance of plant-based supplements or herbs are linked to brain health benefits (see sidebar on page 38 for a simplified list and more information). According to Winston, these benefits overlap significantly; nootropics may, for instance, help preserve cognitive function while also enhancing mood, focus and memory, often through improved cerebral blood circulation. “Bacopa is a nootropic. In addition to being a nootropic, it’s a neuroprotective agent, and it also has anti-anxiety, or anxiolytic activity,” Winston says. He has referred individuals to bacopa for help in recovering from head trauma, reducing anxiety or improving impaired memory and general cognitive function.

Winston also suggests the use of solid extracts from potent fruits like blueberries and goji berries. These herbal supplements are highly concentrated at low-heat, producing a thick, paste-like substance that appeals to the taste much like a jam, sans the sugar and pectin. The antioxidizing role that these flavonoid-rich fruits can play provides protection for the brain, according to Winston.

Nutrients such as turmeric and acetyl-L-carnitine, a form of L-carnitine able to cross the blood–brain barrier and protect the brain, are time-tested as brain-support basics, Kaylor explains. “But there is a ‘new kid on the block’: the Lion’s Mane mushroom that initial research suggests may hold much promise for maintaining a healthy brain and helping in bringing balance to an aging brain as well,” he says.

In detailing the benefits of this supplement, Kaylor notes a parallel with our developing understanding of cognitive decline. “The research and product progression of the Lion’s Mane mushroom is an excellent example of how good product development can evolve along with the science,” he says. Research into Alzheimer’s has often focused on amyloid beta plaque buildup on neural networks as a cause. The active compounds in Lion’s Mane, meanwhile, have been researched for their ability to stimulate nerve growth factor (NGF), an essential protein for the health of the brain’s billions of neurons. As later research implicated inflammation and free radical damage in the Alzheimer’s picture, it was also discovered that a compound called amyloban in Lion’s Mane can serve to shield healthy brain cells from these very damages.

Getting Sharper: Boosting Cognition
It’s easy to forget amidst the concern about cognitive decline, and all the effort to prevent the brain from sustaining damage, that the reason we want to protect the brain is so it can perform its higher functions effectively, thus allowing us to live happy lives and fulfill our responsibilities. This is where cognitive-enhancement supplements designed for everyone, including and often especially younger people, enter the frame, to help with functions such as memory, focus, task performance and even mood.

There is promise held in the concept of improving cognition through a multi-faceted nutritional approach. A patent-pending blend of vitamins, minerals, antioxidants and other nutrients thought to support the brain, FOCUSfactor from Factor Nutrition Labs, was studied on a group of 96 subjects between the ages of 18 and 65. It was found that this blend improved scores in this group on the Rey Auditory Verbal Learning Test (RAVLT), a standardized, common neuropsychological test of traits including memory, focus and concentration.

A form of magnesium called magnesium L-threonate may have significant cognitive benefits, according to Kathy Lund, director of business development and marketing for AIDP, Inc., City of Industry, CA. She says it was discovered by a group from MIT along with others at Tsinghua University in Beijing, China, and subsequent studies using a patented ingredient (Magtein from AIDP) have made it into top journals like Neuron and The Journal of Neuroscience. By increasing magnesium levels in the brain, “animal studies have shown it to improve short-term and long-term memory, improve the management of anxiety and increase brain synapse density, one of the keys to overall brain health,” Lund says. Spatial recognition in animals was also tested and found to improve.

Lund says that a human study testing this form of magnesium’s effect on memory and cognitive function is underway at the University of Southern California’s psychology department. The double-blind, placebo-controlled study involves 40 individuals, and preliminary results are slated to be available by the middle of 2012.

Several previously introduced supplements will now make a comeback in the context of bolstering cognition in healthy brains. “GPC improves cognitive performance including memory and attention. It was shown to significantly benefit attention, mental focus, recall and other higher mental functions, including in young healthy subjects,” says Hayun.

Though the positive research has focused on the aging brain, Kaylor reports anecdotally that Lion’s Mane, specifically the amyloban extract, can act as “a significant and fast-acting boost to the brain, sharpening and quickening the mind and memory.” Similarly, though the fruit extracts known for their antioxidant properties can exert protective effects, Winston notes that blueberries, for example, have also been studied in animals and humans for enhancing cognitive function and memory. He points out that it is the high levels of oligomeric proanthocyanidins (OPCs) in these supplements that consumers can thank for their myriad benefits.

Herbs such as bacopa can also serve to enhance memory, according to Kalyanam, whose company offers an extract of the Bacopa monniera plant, standardized for a minimum of 20% bacosides A and B. Bacopa is one of two herbs referred to in Ayurvedic medicine as “Brahmi” (the other being Centella asiatica), and used traditionally for their cognition enhancement effects, according to a review cited by Winston (8).

In addition to the research behind the herb perhaps most recognized for enhancing cognition, ginkgo biloba, there is evidence for the mind-boosting claims made by traditional medicine for other herbs as well. For instance, a recent paper reports the finding that American ginseng extract can better the working memory of young adults (9). Specifically, scores on a working memory test called the Corsi block task were improved at all doses of the extract, with no change registered in blood glucose levels.

Not in any mood. A person’s mood state at a given time, or their typical cycle of moods, is arguably a function of their circumstances, outlook and brain physiology all at once, but with supplements, we focus on the physical aspect. Many supplements can help to balance and even improve moods as well as perform the often related function of mediating stress. PS, according to Hagerman, is a blocker of the stress hormone cortisol, making it an ideal supplement ingredient for reducing stress and thereby improving mood. Long-term, Hagerman notes, “Elevated cortisol levels can ravage brain cells and impair cellular activity.”

A proprietary blend of PS with phosphatic acid has been studied in the contexts of stress reduction, general cognitive health and exercise recovery, according to Owen. In one double-blind and placebo-controlled trial, participants took this blend (MemreePlus from Lonza) or a placebo for three weeks. “After three weeks of supplementation, participants completed the Trier Social Stress Test. Salivary and serum cortisol were measured, as was perceived stress,” Owen says. The results: those receiving  400 mg showed statistically significant decreases in cortisol and reported distress.

Medicinal mushroom extracts can help modify mood for the better, and Lion’s Mane in particular can count lifting the mood as well as addressing sleep apnea among its brain health benefits, according to Kaylor. He says the research regarding these benefits is new and the mechanisms behind them aren’t understood, but he speculates that the support for neurons coming from up-regulated NGF has something to do with them.

Crossing the Threshold: Delivery Forms
The challenges inherent to formulating effective brain supplements probably eclipse those of other products. This is due to the brain’s unique position within the body, and the special security with which nature has provided it. “Some brain health ingredients struggle to cross the blood–brain barrier. The blood–brain barrier is essentially a defense mechanism that keeps harmful objects like bacteria from entering into the brain. Unfortunately, this also inhibits many ingredients from properly targeting the brain,” says Hagerman.

Finding substances, as well as supplement delivery methods, that can traverse this barrier successfully is difficult, but it’s necessary if a supplement is to do its job, Kaylor explains how, stating, “It may be for this reason that the fat-soluble active constituents in the Lion’s Mane mushroom, the hericenones and amyloban, are the most effective compounds in the fruiting body of the mushroom for supporting the aging brain.”

In addition to the type of solid fruit extract previously described, herbal supplement makers like Winston’s company primarily rely on tinctures to get the job done, in general, and this goes for the nootropics already discussed. Tinctures have the benefit of being easily ingested liquids, they are more concentrated than other forms, and the alcohol in them can enhance absorption by about 30%, according to Winston. There are also encapsulated herb supplements that have proven effective. But, the real distinction to be made in the herbal supplement arena concerns what’s inside of these delivery forms.

Standardized extracts, designed to provide specific bioactive compounds, can contrast with whole herb formulations in terms of effectiveness, safety and history of use. Curcumin, for example, is often delivered in the form of a standardized extract. It has a reputation in some circles for being poorly absorbed. “It doesn’t matter how good the product you’re taking is. If you can’t absorb it, it’s not going to do you any good,” Winston says.

But, Winston says that curcumin is actually very well absorbed, and that it is just excreted too quickly to make it into the bloodstream. Whole turmeric, he says, is better absorbed and stays in the bloodstream for longer periods than isolated curcumin. His company’s whole turmeric, for example, is presented as a tincture and contains the dozens of other active compounds naturally found in turmeric.

Another consideration is the form in which an individual herb has been scientifically tested most often for benefits, or which form has the longest and most traditional history of use, such as in Traditional Chinese Medicine. Ginkgo biloba, Winston says for example, has been shown to slow cognitive decline. But importantly, he recommends the standardized extract, the form in which the herb’s benefits have usually been on display.

For brain supplements in general, encapsulated products seem to be the most popular, Hagerman claims, both due to their ease of production and the flexibility they afford manufacturers. Softgel capsules, he adds, are a good alternative due to the smoothness of their delivery. “But there is a huge population of consumers who have ‘pill fatigue’ and have difficulty swallowing pills. For this type of consumer, alternatives such as liquids, foods, and other edible or drinkable forms are invaluable,” Hagerman says. Fortified brain-boosting beverages are on the rise for this reason, as well as for their convenience.

“The entire cognitive category is growing rapidly through a variety of delivery forms,” says Lund. She goes on to note, “Brain health focused beverage products tend to provide focus and alertness benefits,” adding that this type of product often crosses over into the energy segment. While these products may provide a real and safe brain boost, Lund argues, they may not do much in the way of proper dosing of ingredients, and may not approach the problem of long-term brain health, for which traditional supplements remain the answer. WF

References
1. X.A. Alvarez, et al., “Citicoline Improves Memory Performance in Elderly Subjects,” Methods & Findings in Experimental & Clinical Pharmacology. 19(3), 201-10 (1997).
2.Y. Richter, et al., “The effect of phosphatidylserine-containing omega-3 fatty acids on memory abilities in subjects with subjective memory complaints: a pilot study,” Clin Interv Aging. 5, 313-6 (2010).
3. V.A. Andreeva, et al., “Cognitive function after supplementation with B vitamins and long-chain omega-3 fatty acids: ancillary findings from the SU.FOL.OM3 randomized trial,” Am J Clin Nutr. 94(1), 278-86 (2011).
4. M.C. Morris, et al., “Consumption of Fish and n-3 Fatty Acids and Risk of Incident Alzheimer Disease,” Arch Neurol. 60, 940-946 (2003).
5. N.G. Bazan, “Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection,” Curr Opin Clin Nutr Metab Care. 10(2), 136-41 (2007).
6. S.C. Cunnane, et al., “Plasma and brain Fatty Acid profiles in mild cognitive impairment and Alzheimer's disease,” J Alzheimers Dis. 29(3), 691-7 (2012).
7. A. Spadafranca, et al., “Effect of dark chocolate on plasma epicatechin levels, DNA resistance to oxidative stress and total antioxidant activity in healthy subjects,” Br J Nutr. 103(7), 1008-14 (2010).
8. G.K. Shinomol, et al., “Exploring the role of “Brahmi” (Bacopa monnieri and Centella asiatica) in brain function and therapy,” Recent Pat Endocr Metab Immune Drug Discov. 5(1), 33-49 (2011).
9. A. Scholey, et al., “Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomized, double-blind, placebo-controlled, crossover study,” Psychopharmacology (Berl). 212(3), 345-56 (2010).  

Published in WholeFoods Magazine, June 2012