October 16, 2009
Aristotle referred to the mind, or nous, as, the part of the soul by which it knows and understands. Stanfords Encyclopedia of Philosophy described Aristotles school of thought, according to his writings in Metaphysics and De Anima, stating, It is plain that humans can know and understand things; indeed, Aristotle supposes that it is our very nature to desire knowledge and understanding. In this way, just as the having of sensory faculties is essential to being an animal, so the having of a mind is essential to being a human. In line with Aristotles philosophy, we are almost nothing without our mind. It becomes a center, or possibly, the center, of our existence, in the same way that its the center of the central nervous system. And, with our desire for knowledge and quest for understanding, the mind becomes absolutely essential to our existence.
The brain is extremely complex. It is the source of vision, hearing, balance, taste and smell. It houses our memories, moods and behavior; in essenceit defines us, and without it, our lives begin to deteriorate and we become unable to participate in the simple, everyday tasks and the thoughtful moments that make up our lives.
There are many diseases that can take a toll on brain health. Alzheimers disease (AD) is a neurodegenerative disease that destroys brain cells, resulting in memory loss and problems with thinking, behavior, lifelong hobbies and social life. It is a progressive and fatal disease without a current cure. It affects both men and women usually 65 years and older, but an early-onset form also exists. Alzheimers is the seventh leading cause of death in the United States; as many as 5 million Americans are living with AD, according to the National Alzheimers Association (Alz.org). One of its characteristics is the deposition of senile plaques containing amyloid-beta, a protein that promotes inflammation and oxidation. Natural supplementation is becoming a popular preventive method for addressing AD and other neurodegenerative diseases, by enhancing memory and cognitive functions.
New research is revealing the cognitive and neuroprotective effects of everyday foods such as strawberries and colorful antioxidants, aka carotenoids, like astaxanthin. The 2009 Berry Health Symposium unveiled several studies consistently showing strawberry consumption is a simple way to improve cognitive function. For example, one unpublished study presented by researchers from the Chicago Healthy Aging Project (CHAP) showed older adults who consume strawberries at least once per month have less cognitive decline. Specifically, women who consumed more than one serving of strawberries per month had a 16.2-percent slower rate of cognitive decline versus those who consumed less. Research from James Joseph, Ph.D., and Barbara Shukitt-Hale, Ph.D., Tufts University, Boston, demonstrated aging results in deficits in learning, memory and motor function, such as balance and walking speed; and found strawberries and other berries improved both memory and motor function in rats.
Japanese researchers strongly suggested treatment with astaxanthin may be effective for oxidative stress-associated neurodegeneration and a potential candidate for natural brain food.1 The neuroprotective effect of astaxanthin was studied by using an oxidative stress-induced neuronal cell damage system. The treatment with DHA hydroperoxide (DHA-OOH) or 6-hydroxydopamine (6-OHDA), led to a significant decrease in viable dopaminergic SH-SY5Y cells by the MTT assay, whereas a significant protection was shown when the cells were pretreated with astaxanthin. Moreover, 100 nM astaxanthin pretreatment significantly inhibited intracellular ROS generation that occurred in either DHA-OOH- or 6-OHDA-treated cells. The neuroprotective effect of astaxanthin is suggested to be dependent upon its antioxidant potential and mitochondria protection.
Whether in Thailand, India or England, sampling cognitive-boosting dishes rife with curcumin, the principal curcuminoid in the Indian curry spice turmeric, is a necessity. This spicy-laden ingredient not only jumpstarts metabolism, but it boasts an array of benefits for brain health. University of California, Los Angeles (UCLA), researchers found a form of vitamin D with curcumin may help stimulate the immune system to clear the brain of amyloid beta.2 Using blood samples from nine Alzheimer's patients, one patient with mild cognitive impairment and three healthy control subjects, scientists isolated monocyte cells, which transform into macrophages. The macrophages were incubated with amyloid beta, vitamin D3, and natural or synthetic curcumin. Curcuminoids enhanced the surface binding of amyloid beta to macrophages, and vitamin D strongly stimulated the uptake and absorption of amyloid beta in macrophages in a majority of patients.
In a 2009 study out of Florida, curcumin was suggested as a possible therapy for learning and memory disturbances.3 The study investigated the effects of curcumin on restraint stress-induced spatial learning and memory dysfunction. The results showed memory deficits were reversed with curcumin in a dose-dependent manner, as were stress-induced increases in serum corticosterone levels (similar to the effects of antidepressant Imipramine). Curcumin also prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus. In primary hippocampal neurons, curcumin or Imipramine protected hippocampal neurons against corticosterone-induced toxicity. The portion of calcium/calmodulin kinase II (CaMKII) that is activated (phosphorylated CaMKII, pCaMKII), and the glutamate receptor sub-type expressions were increased in the presence of corticosterone. These effects were also blocked by curcumin or Imipramine treatment. Curcumins neuroprotective effect was mediated in part by normalizing the corticosterone response, resulting in down-regulating of the pCaMKII and glutamate receptor levels.
In Singapore, authors investigated the association between usual curry consumption level and cognitive function.4 In a population-based cohort of 1,010 non-demented elderly Asian subjects, aged 60 to 93 years, Mini-Mental State Examination (MMSE) scores were compared for three categories of regular curry consumption, taking into account known sociodemographic, health and behavioral correlates of MMSE performance. Those who consumed curry "occasionally" and "often or very often" had significantly better MMSE scores than did subjects who "never or rarely" consumed curry.
Another study from UCLA treated macrophages from six Alzheimers patients and three controls with curcuminoids in vitro (as Curcumin C3 Complex, from Sabinsa), and measured amyloid beta uptake.5 After treating the macrophages with curcuminoids, amyloid beta uptake by macrophages of three of the six Alzheimers patients was significantly increased (P<0.001 to 0.081).
A sweeter spice, cinnamon, has also demonstrated its ability to fight against neurodegenerative diseases. An aqueous extract of Ceylon cinnamon (C. zeylanicum) was found to inhibit tau aggregation and filament formation.6 The extract can promote complete disassembly of recombinant tau filaments and cause substantial alteration of the morphology of paired-helical filaments isolated from AD brain. Cinnamon extract was not deleterious to the normal cellular function of tau, namely the assembly of free tubulin into microtubules. An A-linked proanthocyanidin trimer molecule was purified from a cinnamon extract and shown to contain a significant proportion of the inhibitory activity. The study concluded compounds endogenous to cinnamon may be beneficial to AD or may guide the discovery of other potential therapeutics if their mechanisms of action can be discerned.
Green Tea Extract
The favorable effects of green tea, namely epigallocatechin-3-gallate (EGCG), the main polyphenol constituent of green tea, seem to be endless, and there is no shortage on research when it comes to green tea and brain health. According to a 2009 Chinese study, moderate green tea polyphenols (GTPs) modulation could improve impaired cognitive performance caused by psychological stress.7 The study randomly assigned Wistar rats to five groups: control group; stress group; and three stress groups with low, medium and high-doses of GTPs modulation, respectively. Serum levels of cortisol were all increased in the four stress groups, which resulted in cognitive performance changes. These changes were improved in stress medium and high-doses of GTPs modulation groups. In addition, plasma levels of IL-6 and IL-2 were increased in four stress groups, and serum norepinephrine and dopamine were decreased dramatically in stress group and stress low-dose GTPs modulation group. The serum norepinephrine and dopamine levels in stress medium and high-doses of GTPs modulation groups were increased in contrast to that of the stress group. Furthermore, the changes of antioxidative capacity in brain tissue were also measured. Except superoxide dismutase (SOD), the changes of malondialdehyde, reactive oxidative species and total antioxidative capacity of the stress group were significantly different from that of the control group. These changes in stress medium and high-doses of GTPs modulation groups were improved.
In another study published in the American Journal of Respiratory and Critical Care Medicine, researchers measured levels and expression of malondialdehyde (MDA), prostaglandin E(2), p47(phox) subunit of NADPH oxidase, receptor for advanced glycation end products (RAGE), and glial fibrillary acidic protein expression in rodent brain tissue.8 GTP treatment prevented intermittent hypoxia (IH)-induced decreases in spatial bias as well as IH-induced increases in p47phox expression within the hippocampal CA1 region. In untreated animals, IH exposure was associated with doubling of cortical MDA levels in comparison to room air control animals, and GTP-treated animals exposed to IH showed a 40-percent reduction in MDA levels. Increases in brain RAGE and glial fibrillary acidic protein expression were observed in IH-exposed animals, and these increases were attenuated in animals treated with GTP. Researchers concluded, Oral GTP attenuates IH-induced spatial learning deficits and mitigates IH-induced oxidative stress through multiple beneficial effects on oxidant pathways. Because oxidative processes underlie neurocognitive deficits associated with IH, the potential therapeutic role of GTP in sleep-disordered breathing deserves further exploration.
Indian researchers also reported on green teas ability to enhance learning and memory in aged rats.9 Rats were orally administered 0.5 percent green tea extract for a period of eight weeks. Young and old rats treated with the extract showed no significant difference in performance on the rota rod treadmill test/righting reflex time. However, the extract significantly improved learning and memory in older rats, with increased retention latency to enter difference in passive avoidance test. In the elevated maze test, green tea treatment resulted in significantly more number of entries in the enclosed arm by the young and old rats. Decline in acetylcholinesterase activity was observed in the cerebrum of green tea treated old rats in comparison to the green tea treated young rats.
Omega-3 essential fatty acids (EFAs) and omega-3-enriched diets have a vast benefit on the brain. A study published in Nutrition Research demonstrated dietary supplementation with the omega-3 docosahexaenoic acid (DHA) plus alpha-lipoic acid (ALA), acetyl-L-carnitine (ALCAR), glycerophosphocholine (GPC) and phosphatidylserine (PS) reduced reactive oxygen species in normal mice by 57 percent and prevented the increase in reactive oxygen species normally observed in mice lacking murine ApoE when maintained on a vitamin-free, iron-enriched, oxidative-challenge diet.10 Supplementation with these agents also prevented the marked cognitive decline otherwise observed in normal mice maintained on this challenge diet.
A 2006 placebo-controlled intervention, conducted by the Karolinska Institute in Sweden, demonstrated patients given an omega-3 concentrate high in DHA (as EPAX 1050 TG, from EPAX AS) halted further memory decline while patients on the placebo continued to deteriorate.11 A total of 204 patients in an early stage of AD were randomized to received 1.7 g/d of DHA and 0.6 g/d of eicosapentaenoic acid (EPA), or a placebo, for six months, after which all received omega-3 supplementation for six more months. After six months, the decline in cognitive functions did not differ between the groups. However, in a subgroup (n = 32) with very mild cognitive dysfunction, a significant (P<0.05) reduction in MMSE decline rate was observed in the DHA/EPAtreated group compared with the placebo group. A similar arrest in decline rate was observed between six and 12 months in this placebo subgroup when receiving omega-3 fatty acids.
In another trial, UCLA researchers placed aged animals (17 to 19 months old) in one of three groups until 22.5 months of age: control (0.09 percent DHA), low-DHA (0 percent) or high-DHA (0.6 percent) chow.12 Beta-amyloid ELISA of the detergent-insoluble extract of cortical homogenates showed DHA-enriched diets significantly reduced total beta-amyloidby more than 70 percentcompared with low-DHA or control chow diets. Dietary DHA also decreased beta-amyloid 42 levels below those seen with control chow. Image analysis of brain sections with an antibody against beta-amyloid revealed overall plaque burden was significantly reduced by 40.3 percent, with the largest reductions (40 to 50 percent) in the hippocampus and parietal cortex. DHA modulated amyloid precursor protein (APP) processing by decreasing both alpha- and beta-APP C-terminal fragment products and full-length APP. BACE1 (beta-secretase activity of the beta-site APP-cleaving enzyme), ApoE (apolipoprotein E) and transthyretin gene expression were unchanged with the high-DHA diet.
PS, GPC and Citicoline
PS, a phospholipid essential for the normal functioning of neuronal cell membranes mainly found in fish, green leafy vegetables, soybeans and rice, has been shown to improve cognition and behavior. In 2008, 16 healthy subjects completed cognitive tasks after induced stress in a test-re-test design (T1 and T2).13 Directly after T1, subjects were assigned double blind to either PS or placebo groups followed by T2 after 42 days. Chronic supplementation of PS significantly decreased beta-1 power in the right hemispheric frontal brain regions (F8; P<0.05) before and after induced stress. The results for Beta-1 power in the PS group were connected to a more relaxed state compared to the controls.
A separated study examined the neuroprotective effects of a nutraceutical supplement containing PS, Ginkgo biloba, vitamin E and pyridoxine.14 Nine aged beagles were tested on performance on a delayed-non-matching-to-position task, which is a neuropsychological test of short-term visuospatial memory. All subjects were tested on five baseline sessions; then, in a crossover design, one group received the supplement and the other a control substance in the first phase, with treatment conditions being reversed in the second phase. Performance accuracy was significantly improved in supplemented dogs compared with control dogs and the effect was long lasting.
A double blind Italian study orally treated 494 elderly patients with moderate to severe cognitive decline 300 mg/d of bovine cortex-derived PS (BC-PS) for six months.15 Within the six-month trial period, 69 patients dropped out. Compared to the placebo group, statistically significant improvements in behavioral and cognitive parameters in the PS-treated group were observed. In addition, clinical evaluation and laboratory tests demonstrated that the BC-PS was well tolerated.
An unpublished open-label clinical trial treated eight patients (mean age of 69 years) with subjective memory complaints with 300 mg/d of SharpPS®GOLD (a proprietary PS-DHA conjugation; from Enzymotec) for six weeks. According to the company, the study findings indicated SharpPS may have a favorable effect on memory abilities, specifically on the ability to store, hold and retrieve information of an episodic nature. Additionally, in a separate unpublished, single-center, open label study, 30 male and female subjects with memory impairment, aged 60 to 90, took three capsules/d of a combination of proprietary PS-DHA conjugation and alpha-GPC (as Cognitex, from Enzymotec) for 12 weeks. Cognitex supplementation was shown to improve cognitive abilities related to attention, learning, memory and complex activities of daily living following only two weeks of supplementation, and were maintained or amplified by the end of the 12 weeks, according to the company.
Alpha-GPC is a precursor for the synthesis of phosphatidylcholine (PC), which may help stimulate human growth hormone (HGH) release. In a study published in the International Journal of Clinical Pharmacology, 12 normal volunteers were studied on three randomized occasions: in a control day without drug administration, after 1,000 mg of intramuscular (IM) alpha GPC (as AlphaSize, from Chemi Nutra), and after 1,000 mg of IM citicoline, a form of the B vitamin choline, which supports phospholipid production in the brain.16 Alpha GPC was associated with a rapid risen plasma choline. Thereafter, the concentration of choline declined gradually and returned to near baseline values at the end of the observation period. After the administration of citicoline, plasma choline levels showed a similar time course, but were considerably lower than those observed after alpha-GPC. Pharmacokinetic parameters indicated exogenously derived choline declined in plasma with a half-life of 0.5 to 6.2 hour, without any significant difference between alpha-GPC and citicoline. Choline AUC values after alpha-GPC were significantly higher than those observed after citicoline, but the difference was no longer significant when AUCs were corrected for the different choline content of the two preparations. Researchers concluded alpha-GPC provided an effective means of increasing plasma choline levels.
Citicoline has been studied separately for its ability to improve neurodegenerative disorders. According to a study presented at the International Society of Sports Nutrition Annual Conference 2009 in New Orleans, Cognizin® (from Kyowa Hakko) increased energy (ATP) levels in the brain. Researchers observed increases in brain activity among healthy middle-aged adults who had taken Cognizin for six weeks, particularly when individuals performed tasks that required sustained attention or memory.
In a separate double blind, placebo-controlled, randomized clinical trial, 30 patients with mild to moderate senile dementia of the Alzheimer type were treated with 1,000 mg/d of citicoline (as Cognizin) (n=13) or a placebo (n=17) for 12 weeks.17 Compared to the placebo, citicoline improved cognitive performance in Alzheimers patients with ApoE; this improvement was more pronounced in patients with mild dementia. Citicoline also increased cerebral blood flow velocities in comparison with the placebo (P<0.05), as well as diastolic velocity in the left middle cerebral artery (P<0.05). Patients treated with citicoline showed an increase in the percentage of brain bioelectrical activity of alpha (occipital electrodes) and theta type (left-side electrodes), accompanied by a decrease in relative delta activity particularly marked in the left temporal lobe. Significant differences with respect to the placebo (P<0.05) were observed for theta activity in several fronto-parieto-temporal electrodes of the left hemisphere. Treatment with citicoline tended to reduce serum IL-1 beta levels, mainly after four weeks of administration, with no modified blood histamine content. In addition, neither adverse side effects nor alterations in biological and hematological parameters were induced by citicoline.
A study at Northwestern University, Chicago, involved 11 subjects (8 males, 3 females), who received nightly total parenteral nutrition (TPN) for more than 80 percent of their nutritional needs for at least 12 weeks before entry in the study.18 Patients were randomly assigned to receive their usual TPN regimen over a 12-hour nightly infusion or their usual TPN regimen plus 2 g of choline chloride. Significant improvements were found in the delayed visual recall of the Weschler Memory Scale-Revised and borderline improvements in the List B subset of the California Verbal Learning Test and the Trails A test. No other statistically significant changes were seen, indicating both verbal and visual memory may be impaired in patients who require long-term TPN and both may be improved with choline supplementation.
Chromium is an essential nutrient vital to insulin receptor signaling and may possibly improved mood in depressed individuals. In an unpublished, placebo-controlled, double blind trial presented at the American College of Nurse Practitioners (ACNP) Conference 2007, researchers randomly assigned 21 older adults with early memory changes, but not dementia, to receive either chromium picolinate (CrPic; as Chromax® chromium picolinate, from Nutrition 21) containing 1,000 mcg/d of elemental chromium (n=11) or a placebo (n=10) for 12 weeks. At treatment termination, Cr to creatinine ratios were significantly elevated in the supplemented group. In preliminary, repeated measures analyses, researchers observed trends for reduced semantic interference on the memory task and enhanced motor speed. Effect sizes were in the moderate range. These trends were corroborated by differences in activation patterns on pre- and post-intervention fMRI scans for individual subjects from the CrPic and placebo groups. Scans for the CrPic treated subject showed increasing activation in left frontal and left parietal cortices in association with increasing working memory load and reduced nonspecific right hemisphere activation. Scans for the placebo-treated subject showed relatively constant activation in both left and right hemispheres across increasing task loads.
In 2008, subjects classified with age-related memory decline were randomized to receive either CrPic (as Chromax, from Nutrition 21) containing 1,000 mcg of elemental chromium (n=9) or a placebo (n=4) in a 12-week double blind trial.19 At treatment termination, Cr/creatinine ratios were elevated in the supplemented group. Activation did not increase in post-treatment relative to baseline scans for subjects receiving the placebo. However, treated subjects showed greater activation post treatment relative to baseline (P=0.005) in bilateral thalamic, right temporal, right parietal and bilateral frontal regions. Researchers concluded chromium supplementation increases brain activation during performance of resource intensive tasks.
Our diet is packed with essential and vital ingredients that are not only good for overall health, but more specifically, brain health. Spices such as curcumin and cinnamon, good-for-you beverages such as green tea, and beneficial fats are all valuable to brain health and work to ensure our desire for knowledge and quest for understanding can be satisfied.
References on the next page...
References for "Supplements for Better Brain Power"
1. Liu X, Osawa T Astaxanthin protects neuronal cells against oxidative damage and is a potent candidate for brain food Forum Nutr. 2009;61:129-35
2. Ava Masoumi et al. 1,25-dihydroxyvitamin D3 Interacts with Curcuminoids to Stimulate Amyloid- Clearance by Macrophages of Alzheimers Disease Patients J Alz Dise. 2009;17(3):703-17.
3. Xu Y et al. Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress Neuropharmacology. 2009 Sep;57(4):463-71. Epub 2009 Jun 21
4. Ng TP et al. Curry consumption and cognitive function in the elderly. Am J Epidemiol. 2006 Nov 1;164(9):898-906. Epub 2006 Jul 26
5. Zhang, Laura et al. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients J Alzheimers Dis. 2006;10(1):1-7
6. Dylan W. Peterson et al. Cinnamon Extract Inhibits Tau Aggregation Associated with Alzheimers Disease In Vitro J Alz Dise. 2009;17(3):585-97
7. Chen WQ et al. Protective effects of green tea polyphenols on cognitive impairments induced by psychological stress in rats Behav Brain Res. 2009 Aug 24;202(1):71-6. Epub 2009 Mar 21
8. Burckhardt IC et al. Green tea catechin polyphenols attenuate behavioral and oxidative responses to intermittent hypoxia Am J Respir Crit Care Med. 2008 May 15;177(10):1135-41. Epub 2008 Feb 14
9. Kaur T et al. Effects of green tea extract on learning, memory, behavior and acetylcholinesterase activity in young and old male rats Brain Cogn. 2008 Jun;67(1):25-30. Epub 2007 Dec 19
10. Suchy J, Chan A, Shea TB Dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocoline, docosahexaenoic acid, and phosphatidylserine reduces oxidative damage to murine brain and improves cognitive performance Nutr Res. 2009 Jan;29(1):70-4
11. Yvonne Freund-Levi et al. Omega-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study Arc Neurol.63(10):1360-07
12. Lim GP, et al. A diet rich with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci 2005;25:3032-3040
13. Baumeister J et al. Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress Nutr Neurosci. 2008 Jun;11(3):103-10
14. Araujo JA et al. Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine Can Vet J. 2008 Apr;49(4):379-85
15. Cenacchi T et al. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration Aging Clin Exp Res. 1993;5(2):123-33
16. Gatti G et al. A comparative study of free plasma choline levels following intramuscular administration of L-a-glycerylphosphorylcholine and citicoline in normal volunteers Inter J Clin Pharmacol. 1992;30(9):331-35
17. Alvarez XA et al. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion Methods Find Exp Clin Pharmacol. 1999;21(9):633-44
18. Buchman AL et al. Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study JPEN J Parenter Enteral Nutr. 2001 Jan-Feb;25(1):30-5
19. Robert Krikorian et al. Chromium Supplementation Enhances Cerebral Activation in Older Adults with Early Memory Changes Abstract # 22 in Abstracts Presented at the 19th Annual Meeting of the American Neuropsychiatric Association. J Neuropsych Clin Neurosci 2008; 20:232234
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