October 19, 2011
The growing senior population has brought more attention to brain health and cognitive performance. Frankly, whether they are in their sunset years or still a decade out, people are afraid of losing their minds. Research America reported surveyed adults are more than twice as likely to fear losing their mental capacity (62 percent) as their physical abilities (29 percent). The Centers for Disease Control and Prevention (CDC) noted in its Healthy Brain Initiative, Alzheimers disease (AD) has been in the top 10 leading causes of death since the start of the 20th century. CDC added while mortality rates for heart disease and cancer have declined, rates for AD are on the rise.
According to the Alzheimers Association, 5.4 million Americans have AD, with as many as 200,000 of them under the age of 65. Two-thirds of those with AD are women. By 2050, as many as 16 million Americans are expected to suffer AD. Without touching the emotional costs of the disease, the Alzheimers Association placed 2011 monetary costs at an estimated $183 billion, an increase of $11 billion over last year. At this rate, projections place potential 2050 costs at $1.1 trillion.
Of course, AD is not the only brain health worry. Reduced cognitive function and memory loss/dementia round out most peoples brain health fears. Mild cognitive impairment or cognitive impairment no dementia may be a problem for 16 to 25 percent of the elderly population (65 and older). However, the notion that neurological degeneration is an inevitable consequence of aging is misguided. The Alzheimers Association pointed out a health aging brain forms new synapses and regenerates nerve cells.
The American Society for Aging (ASA) and Met Life Foundation conducted surveys that revealed Americans awareness and attitudes on the brain and aging have taken some positive turns. Nearly nine of 10 people surveyed said they thought it is possible to improve cognitive fitness, and six of 10 felt they should have their cognitive health checked regularly. About 84 percent of respondents reported engaging in some kind of daily activities associated with improving brain health, including art or creative projects, reading, keeping physically active, playing games or doing puzzles, working, or spending time with family and friends. More than half of those surveyed were optimistic a major medical breakthrough on an AD cure would occur in the next 20 years.
Scientific investigation and research studies have propelled numerous nutritional, specialty and botanical ingredients to cognitive notability. Some of the ingredients are intrinsic to the brain. According to Bruce Holub, Ph.D., professor emeritus in the Department of Human Health & Nutritional Sciences at the University of Guelph, Ontario, docosahexaenoic acid (DHA) levels in the brain increase about 30-fold from about 24 weeks gestation to about 2 years of age. While sufficient DHA early in life is crucial for infant brain development, this essential fatty acid (EFA) is important throughout life.
DHA highly concentrates in the phospholipid-rich brain and retina, making it essential for both cognitive and visual health. About half of the fatty acids in the brain are DHA molecules, and neuronal cell membranes are more fluid when they have a higher percentage of DHA; this improves communication between synapses and protects against apoptosis.1 Some studies have connected fluidity changes in neuronal membranes and synaptic to memory loss in Alzheimers; theyve suggested DHA is a potential neuroprotective agent and may prevent declines in cognitive learning and memory.2,3
Scientists from the Louisiana State University (LSU) Health Sciences Center, New Orleans, confirmed in their 2011 research report how DHA plays a key role in vision, neuroprotection, successful aging, memory and other vital functions.4 Their study of DHA signalipidomics highlighted DHA uptake and distribution in cells and tissues, as well as the function of membrane-rich, DHA-derived bioactive lipids, including neuroprotectin D1 (NPD1)NPD1 triggers powerful anti-inflammatory actions and prohomeostatic bioactivity, is anti-angiogenic, promotes corneal nerve regeneration and induces cell survival, according to their report. Earlier, the same LSU team found both DHA and NPD1 are effective in treating human brain cells and reducing inflammation and toxicity from beta amyloid, the protein involved in the plaques that are central to AD progression.5 In their research, they also looked at areas of the human brain important to memory formation and cognition, finding 20- to 25-fold decreases in NPD1 in people with AD. Further, their in vitro work showed DHA added to aging brain cells reduced beta amyloid and increased NPD1.
Despite the promising early discoveries, DHA has not conclusively improved brain health in all AD patients. A 2006 Swedish trial found 12 months of supplementation with DHA and eicosapentaenoic acid (EPA) did not affect cognitive function in patients with mild to moderate AD, but did arrest cognitive decline in patients with very mild AD.6 However, a subsequent study by this team did show DHA supplementation decreases inflammation in AD patients.7
Beyond AD, randomized trials have discovered short-term supplementation with DHA and EPA positively affects various aspects of cognitive function in both healthy older adults and those with mild cognitive impairment.8 Further evidence of DHAs neuroprotective properties came from a November 2010 study report, which detailed how 24 weeks of supplementation with 900 mg/d DHA (as lifesDHA, from DSM/Martek Biosciences) improved learning and memory function in older adults with age-related cognitive decline.9 DHA has proven beneficial for all ages, as research suggests adults at mid-life with higher serum levels of DHA have greater mental flexibility, reasoning and memory, indicating sufficient DHA intake throughout life is crucial to both current and future brain health.10
DHA is found in brain phospholipids, major components of cell membranes. One such phospholipid is phosphatidylserine (PS), which makes up about 7 percent to 10 percent of the cell membranes of neurons. Maintaining proper PS levels appears to benefit brain performance. In a 2010 pilot study out of Israel, elderly volunteers with subjective memory complaints who took PS containing DHA (as SharpThoughts, containing Sharp-PS® GOLD from Enzymotec) for six weeks had a 42-percent increase in the ability to recall words in the delayed condition.11 A related research team published results of a larger-scale trial in 2011 involving 157 participants were randomized to receive either PS-DHA or placebo for 15 weeks and were run through a battery of cognitive performance tests.12 The researchers found the PS-DHA formula can improve cognitive performance in non-demented elderly with memory complaints. Further, their post-hoc analysis of subgroups indicated subjects with higher baseline cognitive status were most likely to respond to PS-DHA.
A review confirmed PS is effective in age-related memory impairment and cognitive decline, which can be successfully addressed with PS supplementation.13 And a Japanese trial found cognitive enhancements from 300 mg/d of soy PS supplementation in elderly adults with memory problems, improving their delayed memory recall, which is often otherwise decreased in early stages of dementia.14
More recently, a 2010 study showed PS derived from krill directed significant neuroprotective activity against the neuronal and cognitive impairments that occur with normal aging in rats.15 The research focused on changes in the brains cholinergic system, including acetylcholinesterase immunoreactivity in the hippocampus. Acetylcholine (ACL) is a neurotransmitter involved in learning and memory. Impairments in acetylcholine receptor function have been linked to onset and progression of AD.16
Choline is a precursor to acetylcholine, and sufficient intake and membrane levels of choline are important to brain mitochondrial and cognitive function.17,18 The phospholipid phosphatidylcholine (PC) is a source of choline and a key nutrient for cell membranes. Alpha-glycerylphosphorylcholine (aGPC) is a form of choline found in the brain. A multicenter, double blind, randomized trial found patients with mild to moderate dementia who took 400-mg capsules of alpha-GPC three times daily for 90 and 180 days showed statistically significant improvements in cognitive and behavior scores.19
In the middle of the conversion of choline to PC is cytidine diphosphate-choline (CDP-choline), a major constituent of the brains gray matter. Its role in brain metabolism and restoring brain phospholipids may contribute to findings of improved learning, memory and cognitive function in neurodegenerative diseases. A month-long study on the effects of 1,000 mg/d of oral CDP-choline (as Cognizin®, from Kyowa Hakko) on cognitive function in patients with early- or late-onset AD resulted in significantly improved cognitive function in the early-onset group with a trend toward increasing cognitive function in the overall cohort.20
Further, a study presented at the 2009 International Society of Sports Nutrition annual conference investigated Cognizins effect on brain activity in healthy middle-aged adults, finding six weeks of daily supplementation with Cognizin increased energy levels in the brain and the ability to focus and concentrate. As in the case of PS, citicoline may affect cognition by supporting the cholinergic system and promoting the repair of neuronal membranes.21
At SupplySide West 2010, University of Utah researchers presented details on a six-week study conducted at Harvard Medical School-affiliated McLean Hospital and designed to measure and visualize the functional effects of Cognizin on various brain function parameters. Researchers used neuroimaging during specialized tasks to measure attention and reaction time, as well as spatial memory. Subjects then took either 500 mg/d or 2,000 mg/d of Cognizin for six weeks before a second round of imaging. Cognizin supplementation appeared to improve spatial memory, brain metabolism and accuracy of responses. The results were nearly identical for both 500 mg and 2,000 mg doses of Cognizin. The same team also presented research at the 2011 NCDEU (New Clinical Drug Evaluation Unit) Annual Meeting, showing subjects taking either 250 mg or 500 mg of citicoline had fewer errors during performance testing, compared to the placebo group.
Further, a late-2010 review report from Universidad Autonoma de Madrid highlighted citicolines beneficial effect on several cognitive function parameters, but found the methodological heterogeneity of most citicoline-cognitive studies inconclusive on the mechanism of action.22 However, they noted citicoline could help repair the brain after acute cerebral ischaemia, as evidenced in experimental models.
Choline is often grouped with the B vitamins, which themselves hold promise of better brain health. Of this group, vitamins B6, B9 (folic acid) and B12 have stood out in cognitive studies. B vitamins help decrease high levels of the amino acid homocysteine, which have been associated with increased risk of both cardiovascular disease (CVD) and AD.23
The Oxford Project to Investigate Memory and Aging (OPTIMA), coordinated out of the University of Oxford, noted elevated total plasma homocysteine levels in patients with mild cognitive impairment (MCI), including AD, are associated with faster brain atrophy and decline, and they investigated the ability of B vitamin supplementation to slow this decline in MCI subjects.24 The double blind, controlled design involved 271 subjects older than 70 years old with MCI who were randomized to receive either placebo or a combination of folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d as cyanocobalamin) and vitamin B6 (20 mg/d as pyridoxine HcL) for two years. A subset of 187 individuals volunteered to have cranial MRI scans at the start and finish of the study. In those taking active supplementation, mean plasma folate levels increased by nearly 270 percent and plasma vitamin B12 doubled, compared to 3 percent and 10 percent, respectively, in the placebo group. Further, Plasma homocysteine decreased by 22.5 percent in the active group, but increased by 7.7 percent in the placebo group. In the end, the mean rate of brain atrophy per year was 0.76 percent in the B vitamin group and 1.08 percent in the placebo group, with treatment response related to baseline homocysteine levels. The researchers concluded vitamin B intervention can slow the rate of brain atrophy in MCI patients.
For years, scientists and public health officials have urged pregnant women to take folic acid supplements to limit the chances of brain and spinal birth defects. Researchers from the Johns Hopkins Bloomberg School of Public Health reported supplementation with folic acid and iron during pregnancy positively impacted working memory, inhibitory control and fine motor functioning in the school-aged children.25
Other micronutrients important to brain health include magnesium, vitamins D and E. Magnesium plays a role in the myelin sheaths that protect and insulate nerve fibers and is a co-factor for many enzymatic reactions in the body related to cognitive function and cerebral metabolism.26 Research has shown magnesium deficiency has a negative effect on cognitive performance, and post-brain jury administration of magnesium can boost recovery of cognitive function.27,28
In other micronutrient deficiency research, a French trial showed women with inadequate vitamin D had impaired cognitive function compared to those who met the recommended daily allowance (RDA).29 Similarly, the inCHIANTI (invecchiare in Chianti, aging in the Chianti region) population-based study of 850 older adults found low serum levels of vitamin D were associated with substantial cognitive decline over a six-year period.30 Then in late-2010, Tehran University of Medical Sciences, Iran, researchers reported rats with AD had a lower performance on a Morris water maze task than did control rats, and AD rats with vitamin D-deficient diet generally exhibited poorer spatial learning than either the AD rats with a normal diet or those supplemented with vitamin D.31
The story of vitamin E in brain health is a bit more complicated. Of vitamin Es various components, the tocotrienols have an unsaturated side tail that allows them to penetrate the brain and other membranes layered with saturated fat. In 2005, the American Heart Associations journal Stroke published study results demonstrating palm tocotrienols (as Tocomin SupraBio®, from Carotech), but not tocopherols, act on key molecular checkpoints to protect against glutamate- and stroke-induced neurodegeneration.32
Since 2000, Carotech has teamed up with the Ohio State University (OSU) Medical Center on research into the effect of Tocomin SupraBio® in reducing stroke-induced neurodegeneraton; the research has been funded by the National Institutes of Health (NIH). Among the results generated by this work, tocotrienols from Tocamin were found to cross the blood-brain barrier, where they protect neurons from glutamate-induced neurodegenerationglutamate-induced oxidative stress and toxicity are major factors in stroke, Lou Gehrigs disease (ALS) and other neurodegenerative disorders.33 In fact, Chandan Sen, Ph.D., and his OSU team found numerous times nanomolar amounts of tocotrienol, but not alpha-tocopherolor other antioxidant testedprotected brain cells and neurons from glutamate-induced toxicity and death.34,35 Other OSU research showed pregnant rats orally supplemented with Tocomin had increased tocotrienol levels, and fetal brains increased by 5-fold in one study and 20-fold in another study.36,37
In 2006, they published another paper in Stroke, describing how Tocomin full-spectrum palm tocotrienol complex administered to spontaneously hypertensive rats not only increased tocotrienol levels, but also conveyed more stroke protection, compared to controls.38 Another OSU study in 2006 clarified tocotrienol at low concentrations protects neurons from homocysteic acid toxicity, and in higher concentrations inhibits free-radical-induced neurotoxicity caused by the fatty acid linoleic acid.39 Tocotrienol did not exhibit antioxidant protection until it reached a concentration 10- to 20-times stronger than the low concentration that protected against homocysteic acid cell death.
A 2011 report in Stroke confirmed in damaged brain tissue tocotrienol targets multidrug resistance-associated protein 1 (MRP1), a key mediator of intracellular oxidized glutathione efflux from neural cells, as well as microRNAs involved in stroke pathogenesis.40 While much of the research on Tocomin has been in vitro or animal, the largest human clinical trial on Tocomin, including 400 patients, is underway and will use imaging (MRI) of white legions in the brain to gauge the neuroprotective effects of tocotrienols (supplied by Carotech).
Antioxidant protection has become a hot brain health research area. Scientists have reported protein oxidation byproducts are accumulated in AD and may contribute to formation of beta-amyloid protein and plaques, while Parkinsons disease (PD) is associated with oxidative stress that damages and degenerates dopaminergic neurons.41 They further noted antioxidantsincluding glutathione, vitamin C, vitamin E, lipoic acid, flavonoids and curcuminmay help fight oxidative stress in the brain induced by high levels of certain metals, possibly reducing onset or progression of neurodegenerative conditions.
Curcumin not only reduces oxidative damage and inflammation, but it also reduces beta-amyloid accumulation and synaptic marker loss, resulting in improved cognitive health.42 According to research presented at the International Conference on Alzheimer's Disease in July, 2011, late intervention of curcumin treatment (as Longvida®, from Verdure Sciences) in wild-type human tau transgenic micewhich have insoluble tau and neurofibrillary tangles associated with ADreduced elevated soluble tau oligomers, tau partner fyn, glutamate receptor dysregulation and cognitive deficits.
Alpha-lipoic acid (ALA) scavenges free radicals and chelates metals, and help address various neuropathies.43 One review noted ALA may interfere with the onset or progression of AD by increasing acetylcholine production, inhibiting hydroxyl radical formation and reducing the expression of pro-inflammatory proteins.44 In a clinical study, patients with moderate dementia who took ALA experienced decreased disease.45 Researchers at the University of Massachusetts, Lowell, studied a combination of ALA, ALC, alpha-GPC, DHA and PS in mice, finding supplementation reduced reactive oxygen species (ROS) in normal mice by 57 percent and prevented the increase in ROS normally observed in mice lacking murine ApoE when on an oxidative-challenge diet. Further, antioxidant supplementation inhibited the cognitive decline normally seen in mice on the challenge diet.
In another animal study, superoxide dismutase (SOD, as GliSODin®, from PL Thomas) limited stress-induced impairment of cognitive function and maintained neurogenesis in the hippocampus via antioxidant mechanisms.46
Polyphenols are also important in hippocampus health. USDA Human Nutrition Research Center on Aging, Tufts University, Boston, researchers discovered among the stilbenes (including resveratrol) found in fruits and vegetables, pterostilbene was most effective in reversing oxidative stress-related aging effects.47 They also noted pterostilbene reversed cognitive behavioral deficits and dopamine release, and working memory was correlated with pterostilbene levels in the hippocampus.
Pterostilbene is found in blueberries and grapes, both of which have demonstrated antioxidant-related neuroprotection. USDA researchers reported berries and grape juice are rich in antioxidants that may enhance cognitive function in aging.48 Research has shown blueberry polyphenols can inhibit acetylcholinesterase activity and improve antioxidant capacity, in addition to fighting toxin-induced learning impairments and exerting an anti-inflammatory effect.49,50 Similarly, grapeseed extract has exhibited an ability to inhibit the aggregation of Abeta into high-weight oligomers and to counteract acetylcholinesterase activity.51,52
The carotenoid astaxanthin has also proven useful in preventing age- and oxidative stress- related cognitive decline. Pre-treating brain cells with astaxanthin protected against oxidative stress-induced neuronal cell damage and inhibited the formation of reactive oxygen species (ROS).53 Taiwanese researchers reported astaxanthin protected brain cells from beta amyloid25-35 via several mechanisms, including suppressing ROS.54 A University of Pittsburgh study also found astaxanthin was neuroprotective via inhibition of oxidative stress damage.55 Taking the research one step further, Chinese scientists found pre-treating coritical neurons with astaxanthin inhibited hydrogen peroxide-induced apoptosis, and administration in rats prior to ischemia protected against cerebral ischemic injury, diminished infarct volume and improved neurological deficit in a dose-dependent manner. And in another Taiwanese study, nerve system cells treated with either astaxanthin or canxanthin were protected from cell death that normally results from exposure to hydrogen peroxide;56 the carotenoid treatments also inhibited ROS formation and several inflammatory compounds.
Animal research revealed five weeks of continuous astaxanthin supplementation delayed the incidence of stroke, an effect attributed to nitric oxide suppression.57 In the same study, rodents fed astaxanthin one hour before ischemia performed better in a maze; astaxanthin prevented the ischemia-induced impairment of spatial memory in the rodents.
In a human study, taking 12 mg/d astaxanthin extract for 12 weeks helped 10 subjects with age-related forgetfulness curb age-related decline in cognitive and improve psychomotor function.58 In another Japanese human trial, subjects taking either 6 mg or 12 mg daily of astaxanthin for 12 weeks had decreased levels of phospholipid hydroperoxides, which accumulate in dementia, and improved erythrocyte antioxidant status.59
French maritime pine bark extract (as Pycnogenol®, from Horphag) is another potent antioxidant and chelating agent that also stimulates the activities of other antioxidants such as SOD. In brain health, Pycnogenol has been researched for improvements in children with attention deficient hyperactivity disorder (ADHD). In a 2006 randomized, double blind, placebo-controlled study out of Slovakia, children taking 1 mg/kg body weight/day of Pycnogenol for one month had significantly decreased oxidized glutathione (GSSG) and significantly increased reduced glutathione (GSH) levels, as well as an improved GSH:GSSG ratio, compared to children taking a placebo over the same period.60 The same researchers also reported on another study in which one month of Pycnogenol administration (1 mg/kg/day)in children with ADHD significantly reduced hyperactivity and improved attention and visual-motoric coordination and concentration, compared to those taking placebo.61 They noted a relapse of symptoms occurred one month after Pycnogenol treatment was stopped.
Bacopa monniera, also known as Brahmi, has also conveyed benefits to ADHD in recent research. In a 2010 randomized, double blind, placebo-controlled out of Israeli, 120 children recently diagnosed with ADHD took either a compound herbal preparation containing bacopa or a placebo supplement for four months.62 Attention, cognition and impulse control were all improved in the intervention group, compared to placebo. The formula also contains lemon balm white peony, spirulina and ashwagandha.
In a study of ischemia-induced injury in rats, Bacopa monniera improved cognitive performance and memory, in addition to reducing infarct size in the ischemic brain and decreasing nitrate and lipid peroxidation.63 In an open label, prospective, uncontrolled, non-randomized trial conducted in India and published in 2011, newly diagnosed patients (60 to 65 years of age) with AD took 300 mg of bacopa (as Bacognize®, from Verdure Sciences) orally twice a day for six months and underwent a mental examination both at baseline and post-intervention period.64 The researchers reported several statistically significant improvements including orientation of time, place and person; attention; reading, writing and comprehension; quality of life; irritability; and insomnia.
Fellow botanical ashwagandha (Withania somnifera) also protects against oxidative damage and improves cognitive function. A 2010 animal trial found oral treatment of ashwagandha was protective in the cholinergic system and limits cognitive impairment caused by sub-chronic exposure to toxins.65 In a trial conducted at Vikram University, India, a combination of ashwangandha and Aloe vera reduced oxidative damage in both the cortex and hippocampus regions of the brain, in addition to improving memory impairment and motor dysfunction.66
Taking a different approach is Ginkgo biloba. As a potent vasodilator, ginkgo improves blood flow and circulation, and research shows it may improve memory and cognitive function. While a 2010 systematic review out of Germany found ginkgo was more effective on cognition in AD,67 other major randomized, controlled trials (RCTs) found 120 mg ginkgo twice daily had no significant effect on cognitive decline.68,69 However, a 2007 British research report highlighted the ability of standardized G. biloba extract (GBE) combined with soy-derived phospholipids (as Virtiva, from Indena) to improve secondary memory performance and significantly increase speed of memory task performance.70
More evidence of ginkgos cognitive benefits was published in 2011. In a German trial, 188 healthy subjects (aged 45 to 56 years) were randomized to receive either ginkgo extract EGb 761 (240 mg/d) or placebo for six weeks, and researchers used standardized free recall and recognition exercises to measure memory performance. They found the ginkgo extract improved free recall of appointments, which typically requires high demands on self-initiated retrieval of learned material and is known to be sensitive to normal aging. French researchers reported treatment with EGb 761 following ischemia improved post-ischemic cognitive deficits in gerbils.71 They noted long-term treatment with EGb 761 also protected hippocampal neurons and inhibited decreases in plasma SOD activity. And a multicenter RCT involving 410 outpatients with mild to moderate dementia (AD with or without cerebrovascular disease, vascular dementia) showed 240 mg of EGb 761 or placebo once daily for 24 weeks alleviated behavioral and neuropsychiatric symptoms, including apathy/indifference, sleep/night-time behavior, irritability/lability, depression/dysphoria and aberrant motor behavior.72
Beyond botanicals, a pair of compounds created naturally in the body may work on the tiniest of levels, but have been generating big results. Carnitine works on a mitochondrial level to support energy production, and can also deliver cognitive benefits. A meta-analysis conducted by scientists at the Imperial College University of London, found acetyl-L-carnitine was more effective than placebo in treating mild cognitive impairment and mild (early) AD.73 Chinese researchers reported acetyl-L-carnitine reduced memory deficits and various degenerative characteristics of AD.74 In a University of Texas, San Antonio, animal study, acetyl-L-carnitine and ALA, both mitochondrial antioxidants, improved spatial memory and cognitive performance in a rodent model of AD.75 In 2010, Egyptian researchers confirmed total homocysteine, insulin, IGF-1, IL-1 and TNF- were new biomarkers for AD, which is marked by abnormal inflammation, and reported treatment with vitamin E, acetyl-L-carnitine and ALA restored these new biomarkers to near normal levels.76
Melatonin may also affect brain health on a mitochondrial level. Researchers from Oviedo University and the University of Extremadura, Spain, studied the effects of melatonin in the brains of aged mice, and found the antioxidant curtailed beta-amyloid protein expression and alpha-synuclein deposits in the brain.77 In addition, melatonin suppressed rising oxidative stress and translocation of nfKappB, thereby preventing oxidative injury. A 2011 animal study report out of India detailed results showing 5 mg/kg/d melatonin treatment reduced the degenerative effect of a pesticide that is known to cause oxidative stress and memory problems in situations of prolonged exposure.78 In another 2011 publication, Idian researchers wrote how mitochondrial dysfunction is one of the major causative factors in the aging process and neurodegenerative disorders such as PD, AD, and Huntington's disease (HD).79 They further noted increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity, enhanced NO production and impaired electron transport system are all involved in such mitochondrial dysfunction. They said melatonin can counter these factors. They explained that unlike other antioxidants, melatonin is selectively taken up by mitochondrial membranes where it can help prevent oxidative stress-induced mitochondrial dysfunction.
The research is ongoing, but all these nutraceutical ingredients show great potential to support and boost brain health, including cognitive function and memory. Despite the threat of several neurodegenerative diseases, such as AD and PD, and seemingly inevitable memory lapses and slowing mind of advanced age, dietary supplements offer hope and health, and can help ward off oxidative damage, inflammation and dastardly brain lesions that can dull the mind and spirit in the aging population.
References are on the next page...
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