Dietary supplements that support cognitive health
Our health is influenced by numerous factors. Shoppers may not immediately associate cognitive health with their overall wellbeing, but cognitive, physical and even emotional health are very much entwined. This is demonstrated in the way that various nutritional deficiencies may cause declines in cognitive function (e.g., B12 and magnesium).
It is also evident as we age. The older we get, the fewer nutrients the body can absorb from food, which may result in deficiencies. It is easy to dismiss forgetfulness and lack of focus as symptoms of age, which they are, but they are also symptomatic of the overall condition of our bodies as a result of aging. Supplementation, by making up for deficits in nutrients, can in turn improve cognitive function. Here are some specific nutrients associated with cognitive health.
Omega-3 Fatty Acids
One-third of the brain is composed of polyunsaturated fatty acids (PUFA), accounting for 15–30% of the brain’s dry weight, with docosahexaenoic acid (DHA) making up about one-third of that (1).
DHA is an omega-3 fatty acid that plays a crucial role in the brain, concentrating in parts of the brain that require the highest degree of electrical activity, including synaptosomes where nerve endings meet and communicate with one another, mitochondria, which generate energy for nerve cells, and the cerebral cortex, which is the outer layer of the brain (2). It is well established that DHA is an important component for infant and child brain development and it is critical throughout life for maintaining proper cognitive health. The importance of DHA as we age becomes evident when looking at those affected by age-related decline, such as Alzheimer’s disease (a form of dementia that causes progressive memory, cognitive and behavioral decline).
According to a review by Thomas et al., “In patients diagnosed with Alzheimer’s disease, significantly lower DHA levels were detected in blood plasma and brain. This not only could be due to lower dietary intake of omega-3 fatty acids, but it could also be attributed to increased oxidation of PUFAs”(3).
In Alzheimer’s patients, cognitive decline is thought to be caused by the protein beta-amyloid, which is toxic to nerve cells. When levels of this protein become excessive, they destroy large tracts of brain cells, leaving behind the amyloid plaques that are associated with the disease (2).
Various studies have shown that DHA can have a neuroprotective effect by reducing beta-amyloid toxicity and by providing an anti-inflammatory effect that can reduce amyloid plaque-caused oxidative stress and decrease levels of oxidized proteins by 57% (2). While a DHA deficiency in Alzheimer’s sufferers may have some implications for how supplementation can benefit them, it should be noted that supplements cannot cure this or any disease and studies addressing that topic have had mixed results.
Supplements are not medicine, and the fact is Alzheimer’s patients advanced in age are going to benefit the least from DHA or other nutraceuticals for cognitive support because by the time they are diagnosed, the physical damage has already been done to the brain.
Nonetheless, some researchers are investigating whether DHA supplementation can slow the progression of cognitive decline. Itay Shafat Ph.D., senior scientist for the nutrition division at Enzymotec, Ltd., with U.S. office in Morristown, NJ, cites a study by Yourko-Mauro et al. that found, “Supplementation of 900 mg/day DHA for 24 weeks, to subjects aged >55 with moderate cognitive decline, improved their memory and learning skills” (4).
While some consumers may not think about cognitive health until problems arise, it is key for retailers to remind them of the importance of DHA for the brain throughout life. In fact, DHA can support the cognitive health of young adults who are healthy and have no obvious nutrient deficiencies. A recent randomized controlled trial by Stonehouse et al., studying 176 healthy adults ages 18 to 45, found, “DHA supplementation significantly improved the reaction time of episodic memory, whereas the accuracy of episodic memory was improved in women, and the reaction time of working memory was improved in men” (5). This improvement at a relatively young age can translate into a body and mind better prepared for the challenges of advanced age.
Alpha-linolenic acid (ALA) is an omega-3, typically sourced from plants like chia and flaxseed as an alternative to marine oils. ALA is a precursor to DHA, but the multi-step conversion from ALA to DHA is inefficient in many people, thereby making dietary DHA crucial for cognitive support. ALA does, however, have other important functions in its own right. Herb Joiner-Bey, medical science consultant for Barlean’s, Ferndale, WA, says that ALA is also, “used by brain cells to make local hormones, including ‘neuroprotectins,’ critical to brain function.” He says that neuroprotectins are also found to be low in Alzheimer’s patients and in laboratory experiments, ALA has been deemed essential to brain development.
Factors to consider when taking DHA supplements are dosage and bioavailability. Many individuals do not get enough DHA in their diet and would benefit from taking highly concentrated or higher dosages. The importance of dosage was recently brought to light in a five-year study by Chew et al. that found no significant difference in cognitive function during omega-3 supplementation in elderly subjects (mean age: 72) with age-related macular degeneration. Many nutrition experts were skeptical of the study design. For instance, Jay Levy, director of sales for Wakunaga of America Co., Ltd., Mission Viejo, CA, stated, “The DHA component was only 350 mg while recent meta-analysis found that daily DHA doses over 580 mg were needed to confer cognitive function benefits” (6).
Douglas Bibus, Ph.D., a scientific advisory board member for Coromega, Vista, CA, cited an article by the Global Organization for EPA and DHA Omega-3s (GOED) titled “Omega-3s and Cognition: Dosage Matters.” The group found, after “examining 20 cognitive-based studies conducted within the past 10 years, only studies supplying 700 mg of DHA or more per day reported positive outcomes” (7).
Certain delivery forms may make marine oils more absorbable. For example, Andrew Aussie, executive vice president and chief operating officer at Coromega, says his company specializes in, “emulsified omega-3 supplements that offer 300% better absorption.” According to the study by Raatz et al. that Aussie cites, lipid emulsification in the stomach is an important step in fat digestion “through the generation of a lipid-water interface essential for the interaction between water-soluble lipases and insoluble lipids” (8). Thus, by emulsifying the fish oil, this process is bypassed, enhancing its absorbability (8).
Another factor affecting bioavailability is the molecular form of omega-3. Chris Oswald, DC, CNS, a member of the advisory board at Nordic Naturals, Watsonville, CA, believes that the triglyceride form of omega-3s is more effective at raising blood serum levels than synthetic versions. Compared with the synthetic ethyl ester-bound molecules, the natural triglyceride form is much less resistant to enzymatic digestion, making it up to 300% more absorbable (2). Because of its molecular structure of three fatty acids attached to a glycerol backbone, when fish oils are digested, their lipid content is converted into single-strand fatty acids. After being absorbed through the epithelial cells, they are reconverted back into triglycerides. This is made possible by the available glycerol backbone, which an ethyl ester would not have (2).
Other companies believe phospholipid-bound omega-3s will improve absorption. Cheryl Meyers, chief of education and scientific affairs at EuroPharma, Inc., Greenbay, WI, says this structure “not only acts as the transport mechanism for the omega-3s, but also provides strong brain support on their own.”
Myers describes one supplement from her company that provides phospholipid-bound omega-3s extracted from salmon heads (Vectomega). The supplement also contains peptides that she believes “can protect delicate blood vessels in the brain by fighting oxidative damage.”
For similar reasons, some companies choose to formulate with krill oil, another source of phospholipid-bound omega-3s that offer good bioavailability because of their water solubility. Lena Burri, director scientific writing at Aker Biomarine Antarctic AS, Oslo, Norway, provides an additional explanation for why this form of DHA is so important: one “DHA transporter (Mfsd2a, major facilitator super family domain containing 2a)…accepts DHA only if it is bound to phospholipids—to be exact to lysoPC” (9).
One randomized, double-blind, parallel-group comparative study measured the effects of krill oil, sardine oil (triglyceride form) and placebo on working memory and calculation tasks in 45 older males ages from 61–72 for 12 weeks. By measuring the changes of oxyhemoglobin concentrations during tasks, results showed greater changes in concentration in a particular channel after 12 weeks than placebo, suggesting that long term supplementation of both krill and sardine oil “promotes working memory function by activating the dorsolateral prefrontal cortex in elderly people, and thus prevents deterioration in cognitive activity”(10).
However, with regard to the calculation tasks, krill oil “showed significantly greater changes in oxyhemoglobin concentrations in the left frontal area,” compared to placebo and sardine oil, which did not demonstrate any activation effects during the calculation tasks (10).
Other than aiding in the absorption of omega-3s, phospholipids play an important role in cognitive health in their own right. According to Burri, phospholipids make up about 60% of the brain by weight, particularly enriched in dendrites and synapses. In addition to this, she says that in vitro, nerve growth creates an increased demand for phospholipids and nerve growth factor stimulates phospholipid generation. Supplementation with phospholipids is highly utilized and effective in aiding cognitive function because their structure is similar to those in nerve membranes.
Two common phospholipids are phosphatidylserine (PS) and phosphatidylcholine (PC). Shafat says that PS has qualified health claims approved by the U.S. Food and Drug Administration (FDA). The claims include: “Consumption of PS may reduce risk of dementia in the elderly,”“Consumption of PS may reduce risk of cognitive dysfunction in the elderly,” and qualified with, “Very limited and preliminary scientific research suggests that PS may reduce risk of dementia/reduce the risk of cognitive dysfunction in the elderly. FDA concludes that there is little scientific evidence supporting this claim.”
Shafat explains that on its own, PS “is effective already at a dose of 100 mg/day,” a smaller amount than some other cognitive-support ingredients.
As far as its function, Chase Hagerman, brand director at ChemiNutra, White Bear Lake, MN, says PS “helps proteins that manage membrane functions involved in the transmission of molecular messages from cell to cell, helps nutrients enter into the cells, and helps harmful stress-related waste products to exit the cell.”
PC, on the other hand, such as that formed from alpha-glyceryl phosphoryl choline (A-GPC), Hagerman says, “migrates to the synaptic nerve endings found throughout the entire central nervous system, and in turn increases the synthesis and release of acetylcholine (AC),” which is an important neurotransmitter “present in both brain and muscle tissue,” playing a key role in “basically every cognitive function while in muscle it is vitally involved in muscle contraction.”
A variety of substances work to this end. Dallas Clouatre, Ph.D., R&D consultant at Jarrow Formulas, Inc., Los Angeles, CA, describes them as “an extended family of one particular substrate,” which include uridine, choline, CDP-choline (Citocoline) and PC as part of a brain cycle sometimes referred to as the Kennedy Cycle. All of these substances play a role in creating PC in the brain and thus synthesizing AC.
AC production is yet another thing that decreases as we age. However, in general, because neurons cannot produce their own choline and must receive it from the blood, choline-deficient diets create an inadequate supply of AC (2). A lack of available choline plays a role in the development of diseases such as Alzheimer’s and age-related cognitive decline. The work of researcher Richard Wurtman, M.D., from Massachusetts Institute of Technology has suggested that because of inadequate choline, the brain might actually cannibalize PC from its own neural membrane to make AC (2).
Neil E. Levin, CCN, DANLA, nutritional education manager at NOW Foods, Bloomingdale, IL describes a formulation “that supports mental alertness and learning by promoting proper AC production and activity,” by combining A-GPC, “the bioavailable form of choline,” with Huperzine A to maintain AC levels (RememBRAIN from NOW Foods). Huperzine A maintains AC by functioning as a selective inhibitor of acetylcholinesterase, which is an enzyme that causes the breakdown of AC (11).
According to Levy, citicoline is one of the newer ingredients for supporting cognition, targeting the frontal lobe, which is the area responsible for problem solving, attention and concentration. He says that supplementation with citicoline in older adults has shown to “improve verbal memory, memory performance and cognition, attention span, blood flow to the brain and bioelectrical activity.” He cites several studies that have shown positive results, including a double-blind, randomized, placebo-controlled trial of 30 Alzheimer’s patients that showed improved cognitive function compared to placebo after taking citicoline daily, especially among those with mild dementia (12).
Elyse Lovett, marketing manager at Kyowa U.S.A., Inc., New York, NY, says her company has the “only clinically studied form of citicoline in healthy adults and adolescents,” and that it is “the only form of citicoline with GRAS [generally recognized as safe] status in the United States” (Cognizin).
Another related supplement, according to Dan Lifton, president of Maypro’s Proprietary Branded Ingredients Group, Purchase, NY, is INM-176 derived from the root Angelica gigas Nakai, which has also been shown to support cognitive health by increasing brain levels of AC.
Vitamins and Minerals
Vitamin deficiencies often present themselves through decline in cognitive function. Vitamin B12 deficiency, for example, can include symptoms such as confusion, memory loss, personality changes, paranoia, depression and other behaviors that resemble dementia. Not only that, but 15% of seniors and as much as 40% of symptomatic people over 60 years of age have low or borderline B12 levels (13).
According to Mohajeri et al., B12 plays an important role in transforming homocysteine (Hcy) into the amino acid methionine, but other B vitamins folate (B9) and B6 are necessary cofactors for the metabolization to occur, without which, Hcy accumulates. Hcy is an amino acid produced in the body from dietary methionine and is essential for normal cellular function, but high concentrations of it undermine said functioning (14). “High blood levels of homocysteine have been shown to compromise memory and several other aspects of cognitive function,” says Michael Mooney, director of science and education at SuperNutrition, Oakland, CA.
Mohajeri et al. bolsters this statement: “The severity of cognitive impairment has been associated with increased concentrations of plasma Hcy. Moreover, a significantly higher risk of Alzheimer’s disease was reported when both folate and B12 levels were low” (15).
Niacin is another B vitamin that supports memory and cognitive function. According to Mooney, niacin, the more active form of vitamin B3, is often prescribed by doctors at 1,000 mg or more per day to support normal cholesterol levels, but a placebo-controlled study found that a nutritional dose of 425 mg per day improved memory test scores by as much as 40% as well as improving sensory registry by as much as 40%. At higher potencies, niacin is also shown to improve cerebral blood flow, “which increases the circulation of nutrients and oxygen in the brain,” he adds (16).
In addition to niacin, Mooney describes niacinamide, which is another form of vitamin B3. At 3,000 mg/day, niacinamide is being studied by UC Irvine as a potential treatment for Alzheimer’s and memory loss associated with it after positive outcomes in a mouse study. Both forms, he explains, convert in the body into NAD+, a molecule that has been shown to reverse aging in mitochondria, the critically important cellular energy producer. “This is likely a significant contributor to vitamin B3’s memory boosting and other anti-aging effects,” he states.
Another supplement to recommend customers is PQQ. Clouatre says that it is considered by some to be the only new vitamin discovered in the past several decades, showing positive results in areas such as neuroprotection. “PQQ suppresses the excessive generation of a number of radicals, including the extremely harmful peroxynitrite radical,” he says, and in PQQ has shown positive effects in learning and memory in both animal and human studies. One clinical trial found that a combination of 20 mg of PQQ and CoQ10 yielded substantial benefits in human subjects in memory, attention and cognition (17).
Lifton says like niacin, PQQ and CoQ10 support mitochondrial function. He says that CoQ10 does so by protecting “mitochondria specifically from damage due to ongoing free-radical onslaughts,” as well as increasing “cellular energy production, which may result in more energy being available for cognitive processes.” This is important because “exciting new research suggests that one of the main causes of mild memory problems associated with aging is damage to our mitochondria, “says Lifton.
Magnesium is an important mineral for maintaining good cognitive function, or for that matter, body function as a whole. According to Carolyn Dean, M.D., N.D., a medical advisory board member of the Nutritional Magnesium Association, “Magnesium alone is required in 700–800 different enzyme systems” and “ATP (adenosine triphosphate) production in the Krebs cycle depends on magnesium for six of its eight steps.”
On the cognitive front, Dean says that magnesium blocks neuro-inflammation caused by deposits of calcium and other heavy metals in brain cells as well as guarding ion channels and blocking heavy metals from entering. She explains that when magnesium is low, calcium rushes in and causes cell death.
Levin adds, “Recent research has demonstrated that it is also critical for normal brain health and normal cognitive function by maintaining the density and stability of neuronal synapses.”
In her book The Magnesium Miracle, Dean explains that deficiencies in magnesium alone can create symptoms of dementia. This is especially true as we age, since the body’s ability to absorb magnesium from our diet decreases and can also be hindered by medications common in elderly people (18). So, magnesium levels in the blood can decrease because the body lacks the ability to absorb the mineral, poor diet and medications, creating an excess of calcium and glutamate (especially if eating a diet high in MSG), both of which have role to play in chronic neural degeneration and the development of dementia (19).
While nutrients are crucial for maintaining healthy cognitive function, herbal aids can also provide extra support in a variety of capacities. Age-related cognitive decline and dementia can be created in a variety of ways, with reduced cerebral blood flow being one of the most distinct mechanisms. Several herbs function to confront this factor. It should be noted that herbs that improve blood circulation could be dangerous to customers who are already taking a blood-thinning medication such as warfarin.
A main role of Gingko biloba is increasing cerebral blood flow, which plays a large role in the development of dementia whether onset by Alzheimer’s or cerebrovascular disease. It is also said to restore impaired mitochondrial function to improve neuronal energy supply, increase choline uptake in the hippocampus, inhibit aggregation and toxicity of b-amyloid protein and have antioxidant effects (20, 21).
Levy cites a four-week pilot study in Neuroradiology that “revealed a four to seven percent increase in cerebral blood flow at a moderate dose of 120 mg per day” of gingko (22). A separate randomized, placebo-controlled, double-blind study determining the efficacy and safety of gingko biloba on patients with mild cognitive impairment and neuropsychiatric symptoms (NPS) by Gavrilova et al., found that “during the 24-week course of treatment, improvements in NPS and cognitive abilities were significant and consistently more pronounced in patients taking 240 mg per day of G. biloba extract EGb 761 than in patients taking placebo” (23).
The efficacy of gingko biloba is even being tested on other conditions such as attention deficit hyperactive disorder (ADHD) in children. One limited but promising study by Sandersleben et al. reported that after supplementation with gingko, ”significant improvements were found for the parents’ assessment of their children’s attentiveness…hyperactivity, impulsivity, and the total score of symptom severity were decreased significantly,” and, “significant improvement regarding Prosocial Behavior” (24). Because of the study’s limitations, such as not having a control or bigger sample, no solid conclusion can be drawn on its efficacy, but hopefully it will encourage more detailed randomized, control trials.
Another herb that functions similarly is Bacopa monniera which, according to Levy, a recent animal study in Phytotherapy Research showed a “25% increase in blood flow to the brain among animals taking 60 mg of bacopa monniera daily compared to no increase in those given donepezil” (25).
It is also said to have antioxidant properties. According to Shaheen Majeed, marketing director of Sabinsa Corp., East Windsor, NJ, bacopa “inhibits lipid peroxidation and thereby prevents damage to cortical neurons.” Lipid peroxidation occurs during oxidative stress associated with a DHA deficiency, which, again, is symptomatic of Alzheimer’s.
Mary Rove, N.D., medical educator at Gaia Herb, Brevard, NC, also mentions supplementing their Gingko supplements with herbs such as peppermint and rosemary. According to her, peppermint supports alertness and “research has honed in on rosmaranic acid, an active constituent with antioxidant properties.” Turns out, she adds, “there’s a lot of modern data to hold up that little slogan ‘rosemary for remembrance.’”
Huperzine A, mentioned previously for its function as an acetylcholinesterase inhibitor, is derived from the Chinese herb Huperzia serrata. Its ability to prevent the breakdown of acetylcholine is similar to that of FDA-approved drugs approved to treat symptoms of Alzheimer’s disease including donepezil, galantamine and rivastigmine, which are cholinesterase inhibitors (11).
A meta-analysis conducted by Yang et al. concluded, “Huperzine A seems to have some beneficial effects on improvement of cognitive function, daily living activity and global clinical assessment in participants with Alzheimer’s disease.” They warned, however, that findings should be interpreted cautiously due to the poor methodological quality of the included trials, and called for additional more rigorous trials (11).
Antioxidants. Many of the discussed supplements have antioxidant capacities, which help make them effective against cognitive impairments, which oxidative stresses often contribute to. According to Meyers, “In virtually all diseases in the brain, inflammation is a significant factor—it changes the nature of how cells interact with each other.” That is why there has been such a surge in popularity and research into curcumin, which is a compound obtained from turmeric, shown to reduce inflammatory and oxidative damage in the brain and support proper firing of neurons, says Meyers.
In the case of conditions such as Alzheimer’s, curcumin may have the potential to disrupt the buildup of beta-amyloid. One study by Zhang et al., which tested curcumin on cell cultures and mouse primary cortical neurons, found that the herb decreased beta-amyloid levels by slowing the maturation of amyloid-beta precursor protein (APP). It attenuated APP maturation by simultaneously increasing the stability of immature APP and reducing stability of mature APP (26).
More research is required to fully understand the kind of effects curcumin can have on cognition and how it can improve cognitive impairments. Currently, the McCusker Alzheimer’s Research Foundation is supporting research being conducted at Edith Cowan University in Perth, Australia, to test the efficacy of curcumin on patients with mild cognitive impairment. The 12-month study will evaluate whether the herb will preserve the patients’ cognitive function.
Another powerful antioxidant that supports cognitive function is Pycnogenol (distributed by Horphag Research). Besides being a considerable force against oxidative damage, the herb, which is derived from French maritime pine bark, has also been shown to improve blood circulation, including microcirculation in the brain as well as increase the production of nitric oxide, which acts as a neurotransmitter, possibly contributing to memory and learning ability (25). In one eight-week study, researchers gave 53 students ranging in age from 18 to 27 Pycnogenol and evaluated their performance on actual tests. Results showed that the experimental group failed fewer tests than the control (seven vs. nine) and performed 7.6% better than control (27). WF
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Published in WholeFoods Magazine January 2016