Monday March 16, 2009
International Scientists Find Harmful Effects From Wireless Technologies Urge New Safety Rules for Cell Phones
(CSRwire) NEW YORK, NY -- (MARKET WIRE) -- 03/16/09 -- Public health concerns and scientific evidence for risks from cell phones and other wireless devices are published today in the journal Pathophysiology. Research professor and Editor Martin Blank, PhD (Associate Professor, Columbia University College of Physicians and Surgeons) says, "This special issue of Pathophysiology is about the human body's sensitivity to EMF signals in the environment, e.g., EMF effects on DNA, effects on the brain from cell phone radiation, and how EMFs in the environment may lead to Alzheimer's disease, dementia and breast cancer. The scientific evidence tells us that our safety standards are inadequate, and that we must protect ourselves from exposure to EMF due to power lines, cell phones and the like."
International researchers have urged quick precautionary action to address a possible epidemic of brain tumors and many other health risks (www.bioinitiative.org/report/docs/section_17.pdf). Over four billion people around the world now use cell phones. They are rapidly eliminating the use of traditional land-line phones throughout the world. Health researchers from six countries give findings in fifteen (15) chapters covering health risks to humans and wildlife from electromagnetic fields and radiofrequency radiation. A summary of findings and quotes from authors are available at www.bioinitiative.org/press_release/index.htm
Wildlife biologist Alfonso Balmoro, PhD of Valladolid, Spain, reports that, "Electromagnetic radiation is a form of environmental pollution which may hurt wildlife. Phone masts located in their living areas are irradiating continuously some species that could suffer long-term effects, like reduction of their natural defenses, deterioration of their health, problems in reproduction and reduction of their useful territory through habitat deterioration. Therefore microwave and radiofrequency pollution constitutes a potential cause for the decline of animal populations and deterioration of health of plants living near phone masts."
Articles
On-Line:
http://www.sciencedirect.com/
For more information please contact:
Professor Martin Blank, PhD
(212) 305-3644
_________________________________
Fighting Cancer Metastasis and Heavy Metal Toxicities With Modified Citrus Pectin
Life Extension Magazine March 2009
Despite billions of research dollars spent every year, cancer remains the second leading killer of Americans. One reason cancer is so lethal is its tendency to metastasize to essential organs throughout the body.
Certain malignancies (like brain tumors) kill by infiltrating into healthy tissues, but the vast majority of cancer deaths occur when tumor cells enter the blood and lymphatic systems and travel to the liver, lungs, bones, and other distant parts of the body.
Unfortunately, there have been few effective approaches to preventing cancer metastasis. The encouraging news is that a specialized fruit polysaccharide called modified citrus pectin has demonstrated unique properties in blocking cancer cell aggregation, adhesion, and metastasis.1
Clinical research shows that modified citrus pectin helps limit disease progression in men with advanced prostate cancer.2 In addition to its cancer-inhibiting effects, modified citrus pectin shows promise in chelating toxic heavy metals that can be so damaging to overall health.3
Here, we’ll explore how this novel compound offers such distinctive and protective effects.
What is Modified Citrus Pectin?
The American Cancer Society recommends that adults eat five servings of fruits and vegetables each day in order to help reduce cancer risk.4 One way to get some of the benefits of citrus fruits such as oranges and grapefruits is with modified citrus pectin.
Pectin is a naturally occurring substance found in the cell walls of most plants and especially concentrated in the peel and pulp of citrus fruits (lemons, limes, oranges, and grapefruits), plums, and apples. It was first identified in 1825, but home cooks had long used fruits with high levels of pectin in jams and marmalades because of their gelling properties. While pectin provides little nutritional content, this carbohydrate acts as a beneficial type of soluble dietary fiber.
Researchers attempted to find a process to alter pectin to create a food supplement that would allow the body to benefit from its various health-promoting properties. Recently, scientists have been able to use pH and temperature modifications to break down pectin’s long, branched chains of polysaccharides into shorter, unbranched lengths of soluble fiber molecules that dissolve easily in water. The result, modified citrus pectin (MCP), is a substance that is rich in galactose residues, which are easily processed by the digestive system and absorbed into the bloodstream.5 Scientists continue to refine MCP in their quest for a more active and effective agent.
Preventing Cancer Metastasis
Modified citrus pectin is thought to be useful in the prevention and treatment of metastatic cancer, especially in solid tumors like melanoma and cancers of the prostate, colon, and breast. Scientists believe that MCP works by inhibiting two key processes involved in cancer progression: angiogenesis and metastasis.6,7
Angiogenesis is the process in which cancer cells establish their own blood supply to fuel their growth. Metastasis occurs when cancer cells break away from the original tumor, enter the bloodstream or lymphatic system, and form a new tumor in a different organ or other parts of the body.8 Secondary or metastatic cancers often pose more life-threatening circumstances than the original tumor.
As scientists begin to decipher the process of how cells receive, interpret, and relay the signals that recruit them to form new tumors,9 they are focusing their attention on molecules called galactose-binding lectins, or galectins. Galectins are overexpressed adhesion and blood vessel-attracting surface molecules that are thought to be involved in the spread of cancer.6 A growing number of small studies in humans and animals have reported that MCP interferes with the cancer cell’s interactions with other cancer cells by acting as a galectin-3 antagonist—that is, an agent that blocks the normal activity of galectins.
Via the mechanism of galectin-3 antagonism, MCP appears to disrupt the processes that allow cancer cells to communicate with one another. When the MCP molecules bind to receptors on the surface of cancer cells, they block galectin-3 and other molecules from penetrating into nearby healthy tissue to create a new tumor and establish the tumor’s blood supply (angiogenesis). In this way, MCP seems to play a role in preventing cancerous tumors from metastasizing and spreading to other organs—one of the main causes of death from cancer.
When MCP interferes with cancer cells trying to form a new tumor, the cancer cells circulate in the bloodstream until they die. By working to inhibit the spread of cancer, MCP keeps the body’s immune system from becoming overwhelmed by an increasing cancer cell load.10
Modified Citrus Pectin’s Effects in Prostate Cancer
Prostate cancer is the most common cancer diagnosed in men in the United States. One in six American men will be diagnosed with prostate cancer during his lifetime. The American Cancer Society (ACS) estimates that 28,660 men die of prostate cancer annually, with only lung cancer more lethal to men.11 The ACS estimates a five-year survival rate of nearly 100% for men whose prostate cancer is diagnosed and treated at an early stage. But for those men with late stage, metastatic prostate cancer, the treatment options are very limited.
One of the first promising studies to show the potential of MCP to inhibit prostate cancer metastasis was published in the Journal of the National Cancer Institute in 1995. Laboratory rats were injected with human prostate cancer cells and divided into four groups. The control group received plain water and the other groups received water with varying concentrations of MCP. After 30 days, only 50% of the rats that drank water with MCP (0.1% weight/volume) had any metastases, while 94% of the rats that drank regular water had cancer metastasize to their lungs. The researchers called for further study to determine both “the role of galectin-3 in normal and cancerous prostate tissues” and “the ability of modified citrus pectin to inhibit human prostate metastasis in nude mice.”12
In 1999, Dr. Stephen Strum, an oncologist specializing in prostate cancer and a respected member of Life Extension’s Scientific Advisory Board, and his colleagues were the first to show the positive effects of MCP on humans with advanced prostate cancer. In a paper presented at an International Conference on Diet and Prevention of Cancer, they reported that five of seven men with advanced prostate cancer and unable to benefit from conventional treatment had a positive response after taking MCP every day for three months or longer. The response was measured by an increase in prostate-specific antigen doubling time (PSADT), which measures the rate at which blood levels of prostate-specific antigen (PSA) rise. Since PSA is a marker of prostate cancer progression or recurrence, longer PSA doubling time is associated with slower disease progression and is thus desirable. One of the five patients had no increase to his PSA level at all.13
A more recent study led by Brad Guess and Drs. Mark Scholz and Stephen Strum also found that MCP increases the PSA doubling time. In this phase II pilot study of 10 men whose prostate cancer had returned after an initial treatment with surgery or radiation, PSADT increased in eight (80%) of the 10 men after taking MCP for 12 months.14
Dr. Strum told Life Extension, “My clinical experience using MCP in prostate cancer has been that it slows PSA doubling time in the majority of patients taking the standard dose of 5 grams three times per day. Because this treatment is well tolerated, I use MCP in situations where sustained increases in PSA may occur.” In a study published in 2007, 49 patients with advanced prostate cancer and few treatment options were given oral doses of MCP powder diluted in water and juice three times a day at eight-hour intervals for a four-week cycle. After two cycles of treatment with MCP, 21% of the patients had a clinical benefit of disease stabilization or improved quality of life; 12% had stable disease for more than 24 weeks. One patient with stage IV metastatic prostate cancer showed a 50% decrease in serum PSA level after 16 weeks of treatment, improving his quality of life and also decreasing pain. “MCP seems to have positive impacts especially regarding clinical benefit and life quality for patients with far advanced solid tumors,” the researchers
Modified Citrus Pectin and Chelation
Beyond its benefits in fighting cancer metastasis, MCP may have applications in mitigating the health dangers posed by toxic heavy metals. Chelation therapy is a chemical process in which a substance is used to bind molecules, such as heavy metals or minerals, and hold them tightly so that they can be removed from a system, such as the body. Chelation can help rid the body of excess or toxic metals, but it is not known if this reduces artery disease risk. Chelation is used to treat lead and mercury poisoning.15,16
In most instances, chelation therapy involves the infusion of compounds via a catheter placed in an arm vein. This procedure must be done in a clinical setting over a specified course of treatments. In contrast, chelation therapy using MCP is done via the oral route and can be administered to the patient in almost any clinical setting, since the supplement can be ingested anywhere. A pilot trial evaluating MCP’s chelating effects provided evidence that orally administered MCP significantly increases urinary excretion of toxic metals. In a study published in 2006, eight healthy individuals were given 15 grams of MCP daily for five days and 20 grams of MCP on day six. Twenty-four hour urine samples were collected on days one and six and analyzed for toxic and essential elements. The investigators reported that significant urinary excretion of arsenic, mercury, cadmium, and lead increased within one to six days of MCP treatment. There was a 150% increase in the excretion of cadmium and a 560% increase in lead excretion on day six.3 Essential minerals such as calcium, zinc, and magnesium were not seen to increase in the urine analysis, indicating that MCP treatment did not deplete these nutrients.
In a case study report, five patients with different illnesses were given MCP (PectaSol®) alone or as an MCP/alginate combination (PectaSol® Chelation Complex™) for up to seven months. Each one had a gradual decrease of total heavy metal burden, which is believed to have played an important role in the patients’ recovery and health maintenance. The patients had a 74% average decrease in toxic heavy metals after treatment. The authors report this is the “first known documentation of evidence” of a possible correlation of positive clinical outcomes and a reduction of toxic heavy metal load using MCP alone or as an MCP/alginate complex. They recommend “further studies be performed to confirm the effectiveness of this gentle non-toxic chelating system as an alternative to harsher chelators in the treatment of patients with a heavy metal body burden.”17
Lead toxicity is an ongoing concern worldwide, and the long-lasting effects of lead exposure in children are especially troubling. A 2008 pilot study at the Children’s Hospital of Zhejiang University, Hangzhou, China looked at whether MCP® could mitigate lead toxicity in children with high blood levels of lead. Seven children hospitalized with toxic lead levels, aged five to 12, were given 15 grams of MCP (PectaSol®) per day in three divided dosages. Blood serum and 24-hour urine excretion analysis were performed on days 0, 14, 21, and 28. Two patients were released after two weeks, three patients were released after three weeks, and two patients were released after four weeks when their blood lead levels had dropped below the criterion. All of the children had a significant increase in urinary excretion of lead. The authors recommend further studies to confirm the effectiveness and safety of MCP as a lead chelator.18
Scientists believe that the ability of MCP (PectaSol®) to chelate toxic metals arises from a low molecular weight pectin that contains 10% rhamnogalacturonan II molecular side groups, which are known to selectively bind heavy metals with a strong affinity. Subsequently, these metal–pectin complexes are eliminated in the urine.
http://www.lef.org/magazine/mag2009/mar2009_Modified-Citrus-Pectin-Fighting
-Cancer-Metastasis-Heavy-Metal-Toxicities_01.htm
Preserving Cognitive Function with Aging
Life Extension Magazine March 2009
One of the most frightening tragedies in life is witnessing dementia rob a loved one of their memory, personality, and dignity. While there are not yet cures for these mind-destroying diseases, scientists are discovering that cognitive deterioration need not be an “inevitable” result of aging. In fact, increasing evidence suggests that cognitive decline and even dementia are preventable, and to some extent perhaps even reversible.1
According to a report from the Alliance for Health and the Future, “individuals can take steps to maintain cognitive health throughout life.”1 In this article, we will explore targeted strategies to help readers take those steps and provide updates from new studies that corroborate these findings.
The Aging Brain—The Molecular View
A remarkable review article by the Human Nutrition Research Center on Aging at Tufts University in Boston provides a comprehensive summary of what we know about brain aging and the special significance of nutrients in slowing down or preventing this process.2 According to scientists, many factors at the cellular and molecular levels account for the behavioral deficits so long assumed to be part of “normal” aging, especially changes in the way cells handle neurotransmitters (the molecules that nerve cells use to communicate with one another).3-6 The resulting loss of neuron function is manifested as changes in both cognitive and motor behaviors that we associate with the aging brain.7,8
Critically, the scientists observe, “substantial research indicates that factors such as oxidative stress and inflammation may be major contributors to the behavioral decrements seen in aging.”2,9-11 According to growing research, there is just no question that oxidative stress is one of the most important deleterious factors for aging brain cells, resulting in decreased availability of natural antioxidants such as glutathione and increased oxidative destruction of vital lipid molecules in cell membranes12—all of which impair cells’ ability to communicate effectively. Not only is the central nervous system especially vulnerable to oxidative stress in general, but it becomes progressively more so with advancing age,13,14 as structural changes in cells accumulate.
Inflammation adds insult to oxidative injury in the central nervous system.2 Even by middle age, there is an increase in the production of inflammatory proteins;15 by the time “old age” has set in, it no longer even requires a true inflammatory stimulus to launch the process.16 Still worse, when a genuine inflammatory stimulus arises (say, a minor infection or further oxidant stress), older brains react by producing still more inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) than younger brains.17,18 In fact, scientists have noted that, “up-regulation of C-reactive protein [a ubiquitous marker of inflammation] may represent one factor in biological aging.”2
The interactions of inflammation and free oxygen radicals perpetuate a cycle of cell damage and dysfunction.2 Animal models of the central nervous system demonstrate that inflammation produces changes that mimic aging in the ways they influence cellular interactions, and in the ways they influence actual behavior. The Tufts review recounts a stunning series of experiments, for example, showing that injection of a potent bacterial toxin into brain tissue “can reproduce many of the behavioral, inflammatory, neurochemical, and neuropathologic changes seen in the brains of patients with Alzheimer disease… as well as producing changes in spatial learning and memory behavior.”
The ability of many plant food components to reduce or block the effects of the oxidation-inflammation-oxidation cycle has captured the attention of researchers. The benefical way these plant compounds affect behavioral and neuronal aspects of aging has stimulated intense research into this area of dementia prevention.2
Let’s take a systematic tour of the world of cognition-enhancing nutritional ingredients that show promise in protecting against some of the long-term effects of age-related oxidant/inflammatory damage on the human brain.
Berries and Grapes: Plant Polyphenols Preserve Memory
Polyphenols are plant molecules with a remarkable array of characteristics, notably their potent antioxidant capabilities;19 people with a high consumption of these molecules have lower rates of neurodegenerative disorders including Alzheimer’s disease.20 Grape skins and seeds are especially rich in a group of polyphenols known as proanthocyanidins, which are proving to have astonishing anti-aging effects in the brain. Interestingly, grape seed extracts were first studied for their beneficial effects on cardiovascular function;21 cardiovascular disease is an important risk factor in the development of dementia.22
Grape seed extracts have subsequently been shown to have anti-stress and neuroprotective capabilities, preserving rats’ cognitive function in the face of stressors—clearly a highly valuable benefit.23 Interestingly, the reduction in oxidant injury to brain cells increases concentrations of the vital neurotransmitter acetylcholine in animals fed grape seed extract.24 We have recently learned that grape seed extract induces actual neuroprotective changes in brain protein composition, suggesting in the words of one researcher that “grape seed extract may have impact on the actions of psychoactive drugs by maintaining an overall viability of the nervous system.”25
The most exciting and dramatic research on grape seed extract and cognition is in Alzheimer’s disease, where it has long been known that moderate red wine consumption is protective.26 Researchers in psychiatry at Mt. Sinai in New York demonstrated why: in mice fed a concentrated grape seed extract, there was significant reduction in deposits of the damaging amyloid-beta proteins associated with Alzheimer’s disease, and a concomitant reduction in cognitive deterioration.27 The observation that grape seed extract not only blocks amyloid formation but also prevents the resulting brain cell injury suggested to UCLA researchers that “[grape seed extract] is worthy of consideration as a therapeutic agent for Alzheimer’s disease.”26
Tufts University researchers led by Dr. James Joseph have long pursued other sources of antioxidant polyphenols as a means of preventing changes associated with the aging brain.28,29 In 1999, Dr. Joseph’s group demonstrated that blueberries are potent sources of these neuroprotective polyphenols, improving rats’ performance on a host of cognitive tasks, as well as enhancing the release of vital neurotransmitters from aged brain cells.30
Groundbreaking work in 2003 demonstrated that in a mouse model of Alzheimer’s disease, blueberry supplementation prevented cognitive deficits even while brain levels of amyloid-beta remained high.31 Since these mice have actual human genes that predispose them to this disease, scientists concluded “for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.”
Not content to stop there, scientists explored the mechanisms by which blueberries enhance learning and memory in a study of the hippocampus—the brain region where memories are processed, and which loses neurons with age.32 When they supplemented aging animals with blueberries, the researchers identified improvements in the rate at which hippocampal cells form and develop receptors for neurotransmitters. They found that these structural changes correlated well with actual improvements in spatial memory. The research team also showed that blueberry polyphenol molecules can cross the vital blood-brain barrier, and hence that they exert their potent neuroprotection directly within the brain.33
Finally, in late 2008, neuroscientists at the University of South Florida discovered that blueberry extracts actually prevent the final steps in formation of the dangerous amyloid-beta proteins in Alzheimer’s disease.34 They concluded that these findings could explain the recovery seen in supplemented animals and that supplementation could tip the scales away from formation of these destructive proteins in those at risk for Alzheimer’s disease.34
Vinpocetine Manages Brain Blood Flow
To support its many vital functions, the brain receives a huge proportion of total blood flow, and has a powerful and exquisitely sensitive mechanism for regulating that flow through control of blood vessel tone.35 One cause of cognitive decline with age is the gradual diminution of blood flow to vital areas, along with a decreased responsiveness to moment-by-moment needs, much of which results from oxidant damage to vessels.36,37
A little-known compound called vinpocetine, derived from the common periwinkle plant, has shown great promise in improving cerebral blood flow and restoring lost cognitive abilities. Vinpocetine appears to work by inhibiting the action of an enzyme called phosphodiesterase 1 (PDE1), resulting in relaxation of cerebral blood vessel walls and increased cerebral blood flow. This mechanism is similar to that of much better-known drugs such as sildenafil (Viagra®),38,39 which helps restore vital blood flow by inhibiting phosphodiesterase 5 (PDE5). Additionally, vinpocetine helps support cerebral glucose metabolism by enhancing glucose supply to brain tissue.40,41
As early as 1987, geriatricians showed that vinpocetine could produce a significant improvement in elderly patients with chronic cerebral dysfunction.42 The researchers gave vinpocetine supplements to 42 sufferers for 90 days, while control patients received placebo. Supplemented patients scored better on all effectiveness scales, which included measures of cognition and overall mental status. No side effects were reported.
A much larger, controlled, randomized trial followed in 1991, when another group of Britons studied 203 patients with mild-to-moderate forms of cognitive impairment, giving them vinpocetine or placebo for 16 weeks.43 Again, no side effects were noted, and there were significant improvements in the supplemented group’s performance on cognitive performance scales.
In 2003, a Bulgarian research group summarized evidence that vinpocetine can actually protect brain tissue from the effects of asymptomatic cerebrovascular disease, the silent blood vessel damage that precedes a stroke.44 Their landmark paper cited the supplement’s ability to interfere at various stages in the cascade of events leading to stroke, including its antioxidant powers, its inhibition of damage caused by overstimulation of nerve cells, and prevention of free radical release. They showed that vinpocetine passes rapidly across the blood-brain barrier, and that it is selectively accumulated in parts of the brain most closely related to cognitive function. Finally, the review cited the known beneficial effects of vinpocetine on cerebral blood flow. The paper concluded, “vinpocetine may also become a new therapeutic approach to prophylactic neuroprotection in patients at high risk of ischemic stroke.”
A 2005 clinical study in Hungary clinched the effects of vinpocetine on brain blood flow.45 In this elegant study, patients with multiple past strokes underwent ultrasound scans of brain blood vessels to examine flow, and three months later performed a battery of cognitive tests. Supplemented patients’ brain blood flow was significantly improved compared with placebo recipients—and on cognitive tests, placebo patients deteriorated significantly while supplement recipients had no change at three months. This study dramatically demonstrated both the cause and the effect of neuroprotection by vinpocetine!
Most of the groundbreaking work on vinpocetine has been done in European countries, and experts there recently wrote that the supplement “improves the blood flow and the metabolism of the affected brain areas. There is increasing evidence that vinpocetine improves the quality of life in chronic cerebrovascular patients.”46 Such findings are leading more researchers to recommend the use of vinpocetine for the treatment of patients with mild cognitive impairment.47
Phosphatidylserine Maintains Cellular Integrity in the Brain
Brain cells’ electrical activity and hence overall function depends critically on the status of their membranes, which are composed of a complex mix of proteins and specialized fat molecules called phospholipids, the most predominant being phosphatidylserine.48,49 Since 1990, evidence has been growing that phosphatidylserine therapy is beneficial for preserving and even restoring brain function.50
In 1992, memory experts in Bethesda studied 51 people who met criteria for probable Alzheimer’s disease, treating them with phosphatidylserine (300 mg/day) or placebo.51 Phosphatidylserine recipients showed improvement on several cognitive measures compared with placebo recipients; benefits were most prominent among those who began with less severe impairment. The researchers noted that “phosphatidylserine may be a promising candidate for study in the early stages of Alzheimer’s disease.”As scientists’ interest grew in preventing the inflammation produced by amyloid-beta in the brain cells of patients with Alzheimer’s disease, many researchers naturally turned to phosphatidylserine as a potential inhibitor of inflammation. Japanese neuropsychiatrists discovered that they could inhibit production of free oxygen radicals, and of the inflammatory cytokine TNF-alpha, if they pretreated amyloid-infested brain cells with phosphatidylserine,52 demonstrating powerful neuroprotective properties. Those properties were demonstrated in live animals by Canadian scientists who supplemented aged beagles with phosphatidylserine along with ginkgo biloba, vitamin E, and vitamin B6.53 The aged dogs, previously impaired on tests of visuo-spatial memory, improved their accuracy significantly after supplementation—and the improvement was long-lived.
In mid-2008, German sports physiologists demonstrated positive effects of phosphatidylserine supplements on brain activity and cognition following mental stress (stress tends to worsen any given degree of cognitive impairment).54 They tested 16 healthy subjects on a cognitive test battery while they were connected to a brainwave scanner (EEG), enabling them to monitor actual brain activity along with cognitive performance. After baseline testing, the subjects were given phosphatidylserine or placebo for 42 days, and were then re-tested and re-scanned. Supplemented patients demonstrated brainwave activity strongly associated with a greater state of relaxation than was experienced by the placebo group. This exciting work suggests that, in addition to objective improvement in cognitive tasks, phosphatidylserine can also cut down on stress that interferes with performance of those tasks.
Evidence for phosphatidylserine has finally managed to convince the ever-skeptical FDA. In 2003, the agency gave “qualified health claim” status to phosphatidylserine, noting that “consumption of phosphatidylserine may reduce the risk of dementia in the elderly” and “consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly.”55
GPC Reverses Cognitive Impairment
Studies suggest that GPC (glycerophosphocholine), a compound related to phosphatidylcholine, may help prevent, halt, or even partially reverse cognitive impairment in the early stages of senile dementia.56,57
GPC helps boost brain function via several mechanisms. GPC helps stimulate the manufacture of new acetylcholine, a neurotransmitter involved in memory and cognition. It also stimulates release of the neurotransmitter GABA (gamma-aminobutyric acid), making more GABA available to brain cells. Dwindling levels of GABA in the elderly may partly account for early cognitive impairment, contributing to the dementia, mood disorders, and confusion seen in degenerative brain conditions such as Alzheimer’s disease.58
The cognitive benefits of GPC have been demonstrated in numerous human studies. A multicenter study of patients with probable Alzheimer’s disease showed that GPC improved cognition and was well tolerated.59 In a review of 13 published clinical trials involving 4,054 patients with age-related memory loss or vascular dementia caused by stroke or mini-stroke (transient ischemic attack), scientists found that GPC helped improve memory and attention, and significantly improved patients’ clinical conditions.56
A controlled, multicenter study showed that GPC improved cognitive function in 261 patients with mild-to-moderate Alzheimer’s disease. Each day for six months, the patients received either GPC or placebo. At the study’s end, patients who received GPC performed better on several standardized psychological tests of cognitive function. In contrast, a measure of cognitive function worsened in the placebo group. Individuals who received GPC also demonstrated behavioral improvements and improvements in physician ratings. The study findings support GPC’s efficacy in treating the cognitive symptoms of dementia disorders such as Alzheimer’s.60
UMP’s Role in Cognition Enhancement
Another approach to cognition and memory enhancement is the use of a substance known as uridine-5’-monophosphate (UMP), which helps comprise RNA, the DNA-like structure that cells use to create proteins from blueprints in genes. UMP supplementation in animals dramatically increases the production of vital brain cell membrane structural molecules, such as CDP-choline.61 Such structural molecules are vital for cell growth and repair, and even more importantly, for proper function of the synapses, the relay points at which brain and nerve cells communicate with each other.62
UMP supplementation in animals not only increases the synthesis of those vital proteins and phospholipids, but it actually helps stimulate production of neurotransmitters and of the tiny but critical cell outgrowths called neurites63 that are themselves formed and then remodeled in the process of learning64-66 and of cell repair.67
Brain scientists at MIT took those observations to a higher level when they supplemented nutritionally impoverished rats with UMP and studied the effects on memory.68 The animals were given either a control or a UMP-supplemented diet, and assessed for learning and memory skills. As expected, the impoverished animals fed a control diet did poorly on memory-dependent learning tasks, but those deficits were dramatically prevented in the UMP-supplemented group. One result of studies such as this one is the now-routine addition of UMP to infant formulas to promote healthy brain development.69
Declining ability to produce or respond to the neurotransmitter acetylcholine is one of the hallmarks of Alzheimer’s disease and other disorders of memory. In 2007, the MIT research group found that they could increase acetylcholine concentrations in aged rats with UMP supplementation.70 This is a stunning finding, since drugs like Aricept® that are used to treat Alzheimer’s disease work by inhibiting the enzyme that breaks down acetylcholine—an approach that has had mixed success and may cause serious side effects.71
The same MIT researchers, partnering with Turkish neuroscientists, have recently shown that UMP, together with the omega-3 fatty acid docosahexaenoic acid (DHA), can restore function in an animal model of Parkinson’s disease as well.72 And the same team demonstrated in late 2008 that they could actually enhance the learning and memory improvements caused by DHA in gerbils by adding UMP to the supplementation.73 They concluded, “these findings demonstrate that [UMP/DHA supplements] can enhance cognitive functions in normal animals” (emphasis added).74 In other words, one needn’t already have cognitive impairment to enjoy the potential benefits of UMP supplementation on learning and memory—and who wouldn’t want better memory even at baseline?
Ashwagandha Relieves Stress, Enhances Cognition
Numerous herbs from ancient India are reputed to promote physical and mental health, improve defense mechanisms of the body, and enhance longevity. Among the most promising of these for promoting cognitive health is a plant known as ashwagandha.
Indian researchers characterized the powerful antioxidant capabilities of ashwagandha extracts in 1997, showing that they increased concentrations of natural antioxidants in animal brains after supplementation.75 These researchers concluded that their findings explained the anti-stress, immunomodulatory, cognition-facilitating, anti-inflammatory, and anti-aging effects reported by other researchers in animal and clinical studies.
The same group later found that they could reduce the chronic stress effects of a mild, unpredictable foot shock in rats if they first supplemented them with ashwagandha extracts.76 Untreated animals experienced elevated blood sugar, glucose intolerance, increased stress steroid levels, gastric ulcers, male sexual dysfunction, cognitive deficits, and depression—common findings in humans exposed to chronic stress—but administration of ashwagandha extracts an hour before shocks dramatically attenuated all of these outcomes. As we noted with phosphatidylserine above, reduced stress allows increased focus on tasks and therefore better cognitive performance, in addition to simply improving quality of life.
A different Indian scientific group studied ashwagandha in diabetic rats, reasoning that the memory impairment seen in diabetes is in part related to oxidative damage in brain regions that are pivotal in memory and the ability to detect and process new information.77 They found a significant increase in production of oxidation end products in those brain regions, and a decrease in cognitive function, after the rats became diabetic. But following supplementation, the oxidative damage in the relevant brain regions was significantly reduced, as were blood glucose levels. Dramatically, memory impairment and motor dysfunction were also improved in the supplemented animals.
In 2007, further support for the use of ashwagandha extracts in Alzheimer’s disease was provided by the discovery that the extracts are among the most potent inhibitors of acetylcholinesterase, an enzyme that breaks down the vital memory-related neurotransmitter acetylcholine.78 Drugs that block acetylcholine breakdown (such as Aricept®) are utilized in the management of Alzheimer’s disease. The researchers correctly observed that “these results partly substantiate the traditional use of these herbs for improvement of cognition.” Western research into the benefits of ashwagandha is very recent, so stay tuned for additional exciting news on this extract’s memory- and cognition-enhancing properties.
Herbal Extracts Spice up Memory
It is now apparent that many traditional spices, in addition to adding interest to our food, can provide vital anti-inflammatory and antioxidant function that is having an impact on how we think about chronic illness and aging.79 Three of these in particular deserve special mention for their powerful effects on learning and memory.
Ginger is an age-old part of Asian kitchens and pharmacopeias,80 and we focus on it here especially for its ability to regulate platelet aggregation, which contributes not only to cardiovascular disease but also to cerebrovascular disease risk.81-84 Experimental studies demonstrated early in the millennium that ginger extracts could protect cells from the inflammatory action of the Alzheimer’s disease-related protein amyloid-beta.85-87 By its blood pressure-lowering effects, ginger can protect against the chronic brain injury caused by hypertension.82
Rosemary is an herb more familiar in Western kitchens, but has an equally distinguished record as a neuroprotectant through its antioxidant constituent, carnosic acid.88 Rosemary extracts block damaging lipid peroxidation, the destruction of brain cells’ fatty membranes that impairs cognitive performance.89 Rosemary also protects cell nuclei from DNA damage that results from both oxidant stress and ultraviolet light90—such damage is at the root of many cancers, but short of cancer it can impair a cell’s ability to function normally.
Neuroscientists in England recently showed a remarkable capacity of rosemary: humans exposed just to the aroma of its essential oil performed significantly better on overall memory quality compared with controls.91 Subjects also had increased states of alertness compared with controls or those exposed to lavender aroma.
Completing the culinary triad of memory-enhancing herbs is hops, the bitter ingredient of beer. Hops’ value may be primarily in its ability to promote relaxation and sleep—in one study, the combination of hops with valerian compared equally with a Valium®-like, sleep-inducing drug, and had none of the “hangover” effects seen with the drug.92 Similar results were found in another study comparing a Valium®-like drug with a hops/valerian combination: both groups did equally well on sleep, relaxation, and quality of life improvement, but patients experienced withdrawal symptoms when they stopped taking the drug.93
Conclusion
Far from being an “inevitable” consequence of aging, we now understand that cognitive decline and memory deficits are the predictable results of a lifetime of oxidative and inflammatory injury that damages brain cells’ ability to communicate with one another. A vast array of valuable nutrients are available to help block that damage—and in some cases to actually reverse it. Strong evidence abounds that the nutrients described in this review have important roles in improving the quality of life of older adults, keeping their wits sharp and their experiences vivid. These nutrients together, therefore, make up a vital part of any long-term brain health regimen
http://www.lef.org/magazine/mag2009/mar2009_Preserving-Cognitive-Function-with-Aging_01.htm
Preserving Cognitive Function with Aging
Life Extension Magazine March 2009
One of the most frightening tragedies in life is witnessing dementia rob a loved one of their memory, personality, and dignity. While there are not yet cures for these mind-destroying diseases, scientists are discovering that cognitive deterioration need not be an “inevitable” result of aging. In fact, increasing evidence suggests that cognitive decline and even dementia are preventable, and to some extent perhaps even reversible.1
According to a report from the Alliance for Health and the Future, “individuals can take steps to maintain cognitive health throughout life.”1 In this article, we will explore targeted strategies to help readers take those steps and provide updates from new studies that corroborate these findings.
The Aging Brain—The Molecular View
A remarkable review article by the Human Nutrition Research Center on Aging at Tufts University in Boston provides a comprehensive summary of what we know about brain aging and the special significance of nutrients in slowing down or preventing this process.2 According to scientists, many factors at the cellular and molecular levels account for the behavioral deficits so long assumed to be part of “normal” aging, especially changes in the way cells handle neurotransmitters (the molecules that nerve cells use to communicate with one another).3-6 The resulting loss of neuron function is manifested as changes in both cognitive and motor behaviors that we associate with the aging brain.7,8
Critically, the scientists observe, “substantial research indicates that factors such as oxidative stress and inflammation may be major contributors to the behavioral decrements seen in aging.”2,9-11 According to growing research, there is just no question that oxidative stress is one of the most important deleterious factors for aging brain cells, resulting in decreased availability of natural antioxidants such as glutathione and increased oxidative destruction of vital lipid molecules in cell membranes12—all of which impair cells’ ability to communicate effectively. Not only is the central nervous system especially vulnerable to oxidative stress in general, but it becomes progressively more so with advancing age,13,14 as structural changes in cells accumulate.
Inflammation adds insult to oxidative injury in the central nervous system.2 Even by middle age, there is an increase in the production of inflammatory proteins;15 by the time “old age” has set in, it no longer even requires a true inflammatory stimulus to launch the process.16 Still worse, when a genuine inflammatory stimulus arises (say, a minor infection or further oxidant stress), older brains react by producing still more inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) than younger brains.17,18 In fact, scientists have noted that, “up-regulation of C-reactive protein [a ubiquitous marker of inflammation] may represent one factor in biological aging.”2
The interactions of inflammation and free oxygen radicals perpetuate a cycle of cell damage and dysfunction.2 Animal models of the central nervous system demonstrate that inflammation produces changes that mimic aging in the ways they influence cellular interactions, and in the ways they influence actual behavior. The Tufts review recounts a stunning series of experiments, for example, showing that injection of a potent bacterial toxin into brain tissue “can reproduce many of the behavioral, inflammatory, neurochemical, and neuropathologic changes seen in the brains of patients with Alzheimer disease… as well as producing changes in spatial learning and memory behavior.”
The ability of many plant food components to reduce or block the effects of the oxidation-inflammation-oxidation cycle has captured the attention of researchers. The benefical way these plant compounds affect behavioral and neuronal aspects of aging has stimulated intense research into this area of dementia prevention.2
Let’s take a systematic tour of the world of cognition-enhancing nutritional ingredients that show promise in protecting against some of the long-term effects of age-related oxidant/inflammatory damage on the human brain.
Berries and Grapes: Plant Polyphenols Preserve Memory
Polyphenols are plant molecules with a remarkable array of characteristics, notably their potent antioxidant capabilities;19 people with a high consumption of these molecules have lower rates of neurodegenerative disorders including Alzheimer’s disease.20 Grape skins and seeds are especially rich in a group of polyphenols known as proanthocyanidins, which are proving to have astonishing anti-aging effects in the brain. Interestingly, grape seed extracts were first studied for their beneficial effects on cardiovascular function;21 cardiovascular disease is an important risk factor in the development of dementia.22
Grape seed extracts have subsequently been shown to have anti-stress and neuroprotective capabilities, preserving rats’ cognitive function in the face of stressors—clearly a highly valuable benefit.23 Interestingly, the reduction in oxidant injury to brain cells increases concentrations of the vital neurotransmitter acetylcholine in animals fed grape seed extract.24 We have recently learned that grape seed extract induces actual neuroprotective changes in brain protein composition, suggesting in the words of one researcher that “grape seed extract may have impact on the actions of psychoactive drugs by maintaining an overall viability of the nervous system.”25
The most exciting and dramatic research on grape seed extract and cognition is in Alzheimer’s disease, where it has long been known that moderate red wine consumption is protective.26 Researchers in psychiatry at Mt. Sinai in New York demonstrated why: in mice fed a concentrated grape seed extract, there was significant reduction in deposits of the damaging amyloid-beta proteins associated with Alzheimer’s disease, and a concomitant reduction in cognitive deterioration.27 The observation that grape seed extract not only blocks amyloid formation but also prevents the resulting brain cell injury suggested to UCLA researchers that “[grape seed extract] is worthy of consideration as a therapeutic agent for Alzheimer’s disease.”26
Tufts University researchers led by Dr. James Joseph have long pursued other sources of antioxidant polyphenols as a means of preventing changes associated with the aging brain.28,29 In 1999, Dr. Joseph’s group demonstrated that blueberries are potent sources of these neuroprotective polyphenols, improving rats’ performance on a host of cognitive tasks, as well as enhancing the release of vital neurotransmitters from aged brain cells.30
Groundbreaking work in 2003 demonstrated that in a mouse model of Alzheimer’s disease, blueberry supplementation prevented cognitive deficits even while brain levels of amyloid-beta remained high.31 Since these mice have actual human genes that predispose them to this disease, scientists concluded “for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.”
Not content to stop there, scientists explored the mechanisms by which blueberries enhance learning and memory in a study of the hippocampus—the brain region where memories are processed, and which loses neurons with age.32 When they supplemented aging animals with blueberries, the researchers identified improvements in the rate at which hippocampal cells form and develop receptors for neurotransmitters. They found that these structural changes correlated well with actual improvements in spatial memory. The research team also showed that blueberry polyphenol molecules can cross the vital blood-brain barrier, and hence that they exert their potent neuroprotection directly within the brain.33
Finally, in late 2008, neuroscientists at the University of South Florida discovered that blueberry extracts actually prevent the final steps in formation of the dangerous amyloid-beta proteins in Alzheimer’s disease.34 They concluded that these findings could explain the recovery seen in supplemented animals and that supplementation could tip the scales away from formation of these destructive proteins in those at risk for Alzheimer’s disease.34
Vinpocetine Manages Brain Blood Flow
To support its many vital functions, the brain receives a huge proportion of total blood flow, and has a powerful and exquisitely sensitive mechanism for regulating that flow through control of blood vessel tone.35 One cause of cognitive decline with age is the gradual diminution of blood flow to vital areas, along with a decreased responsiveness to moment-by-moment needs, much of which results from oxidant damage to vessels.36,37
A little-known compound called vinpocetine, derived from the common periwinkle plant, has shown great promise in improving cerebral blood flow and restoring lost cognitive abilities. Vinpocetine appears to work by inhibiting the action of an enzyme called phosphodiesterase 1 (PDE1), resulting in relaxation of cerebral blood vessel walls and increased cerebral blood flow. This mechanism is similar to that of much better-known drugs such as sildenafil (Viagra®),38,39 which helps restore vital blood flow by inhibiting phosphodiesterase 5 (PDE5). Additionally, vinpocetine helps support cerebral glucose metabolism by enhancing glucose supply to brain tissue.40,41
As early as 1987, geriatricians showed that vinpocetine could produce a significant improvement in elderly patients with chronic cerebral dysfunction.42 The researchers gave vinpocetine supplements to 42 sufferers for 90 days, while control patients received placebo. Supplemented patients scored better on all effectiveness scales, which included measures of cognition and overall mental status. No side effects were reported.
A much larger, controlled, randomized trial followed in 1991, when another group of Britons studied 203 patients with mild-to-moderate forms of cognitive impairment, giving them vinpocetine or placebo for 16 weeks.43 Again, no side effects were noted, and there were significant improvements in the supplemented group’s performance on cognitive performance scales.
In 2003, a Bulgarian research group summarized evidence that vinpocetine can actually protect brain tissue from the effects of asymptomatic cerebrovascular disease, the silent blood vessel damage that precedes a stroke.44 Their landmark paper cited the supplement’s ability to interfere at various stages in the cascade of events leading to stroke, including its antioxidant powers, its inhibition of damage caused by overstimulation of nerve cells, and prevention of free radical release. They showed that vinpocetine passes rapidly across the blood-brain barrier, and that it is selectively accumulated in parts of the brain most closely related to cognitive function. Finally, the review cited the known beneficial effects of vinpocetine on cerebral blood flow. The paper concluded, “vinpocetine may also become a new therapeutic approach to prophylactic neuroprotection in patients at high risk of ischemic stroke.”
A 2005 clinical study in Hungary clinched the effects of vinpocetine on brain blood flow.45 In this elegant study, patients with multiple past strokes underwent ultrasound scans of brain blood vessels to examine flow, and three months later performed a battery of cognitive tests. Supplemented patients’ brain blood flow was significantly improved compared with placebo recipients—and on cognitive tests, placebo patients deteriorated significantly while supplement recipients had no change at three months. This study dramatically demonstrated both the cause and the effect of neuroprotection by vinpocetine!
Most of the groundbreaking work on vinpocetine has been done in European countries, and experts there recently wrote that the supplement “improves the blood flow and the metabolism of the affected brain areas. There is increasing evidence that vinpocetine improves the quality of life in chronic cerebrovascular patients.”46 Such findings are leading more researchers to recommend the use of vinpocetine for the treatment of patients with mild cognitive impairment.47
Phosphatidylserine Maintains Cellular Integrity in the Brain
Brain cells’ electrical activity and hence overall function depends critically on the status of their membranes, which are composed of a complex mix of proteins and specialized fat molecules called phospholipids, the most predominant being phosphatidylserine.48,49 Since 1990, evidence has been growing that phosphatidylserine therapy is beneficial for preserving and even restoring brain function.50
In 1992, memory experts in Bethesda studied 51 people who met criteria for probable Alzheimer’s disease, treating them with phosphatidylserine (300 mg/day) or placebo.51 Phosphatidylserine recipients showed improvement on several cognitive measures compared with placebo recipients; benefits were most prominent among those who began with less severe impairment. The researchers noted that “phosphatidylserine may be a promising candidate for study in the early stages of Alzheimer’s disease.”As scientists’ interest grew in preventing the inflammation produced by amyloid-beta in the brain cells of patients with Alzheimer’s disease, many researchers naturally turned to phosphatidylserine as a potential inhibitor of inflammation. Japanese neuropsychiatrists discovered that they could inhibit production of free oxygen radicals, and of the inflammatory cytokine TNF-alpha, if they pretreated amyloid-infested brain cells with phosphatidylserine,52 demonstrating powerful neuroprotective properties. Those properties were demonstrated in live animals by Canadian scientists who supplemented aged beagles with phosphatidylserine along with ginkgo biloba, vitamin E, and vitamin B6.53 The aged dogs, previously impaired on tests of visuo-spatial memory, improved their accuracy significantly after supplementation—and the improvement was long-lived.
In mid-2008, German sports physiologists demonstrated positive effects of phosphatidylserine supplements on brain activity and cognition following mental stress (stress tends to worsen any given degree of cognitive impairment).54 They tested 16 healthy subjects on a cognitive test battery while they were connected to a brainwave scanner (EEG), enabling them to monitor actual brain activity along with cognitive performance. After baseline testing, the subjects were given phosphatidylserine or placebo for 42 days, and were then re-tested and re-scanned. Supplemented patients demonstrated brainwave activity strongly associated with a greater state of relaxation than was experienced by the placebo group. This exciting work suggests that, in addition to objective improvement in cognitive tasks, phosphatidylserine can also cut down on stress that interferes with performance of those tasks.
Evidence for phosphatidylserine has finally managed to convince the ever-skeptical FDA. In 2003, the agency gave “qualified health claim” status to phosphatidylserine, noting that “consumption of phosphatidylserine may reduce the risk of dementia in the elderly” and “consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly.”55
GPC Reverses Cognitive Impairment
Studies suggest that GPC (glycerophosphocholine), a compound related to phosphatidylcholine, may help prevent, halt, or even partially reverse cognitive impairment in the early stages of senile dementia.56,57
GPC helps boost brain function via several mechanisms. GPC helps stimulate the manufacture of new acetylcholine, a neurotransmitter involved in memory and cognition. It also stimulates release of the neurotransmitter GABA (gamma-aminobutyric acid), making more GABA available to brain cells. Dwindling levels of GABA in the elderly may partly account for early cognitive impairment, contributing to the dementia, mood disorders, and confusion seen in degenerative brain conditions such as Alzheimer’s disease.58
The cognitive benefits of GPC have been demonstrated in numerous human studies. A multicenter study of patients with probable Alzheimer’s disease showed that GPC improved cognition and was well tolerated.59 In a review of 13 published clinical trials involving 4,054 patients with age-related memory loss or vascular dementia caused by stroke or mini-stroke (transient ischemic attack), scientists found that GPC helped improve memory and attention, and significantly improved patients’ clinical conditions.56
A controlled, multicenter study showed that GPC improved cognitive function in 261 patients with mild-to-moderate Alzheimer’s disease. Each day for six months, the patients received either GPC or placebo. At the study’s end, patients who received GPC performed better on several standardized psychological tests of cognitive function. In contrast, a measure of cognitive function worsened in the placebo group. Individuals who received GPC also demonstrated behavioral improvements and improvements in physician ratings. The study findings support GPC’s efficacy in treating the cognitive symptoms of dementia disorders such as Alzheimer’s.60
UMP’s Role in Cognition Enhancement
Another approach to cognition and memory enhancement is the use of a substance known as uridine-5’-monophosphate (UMP), which helps comprise RNA, the DNA-like structure that cells use to create proteins from blueprints in genes. UMP supplementation in animals dramatically increases the production of vital brain cell membrane structural molecules, such as CDP-choline.61 Such structural molecules are vital for cell growth and repair, and even more importantly, for proper function of the synapses, the relay points at which brain and nerve cells communicate with each other.62
UMP supplementation in animals not only increases the synthesis of those vital proteins and phospholipids, but it actually helps stimulate production of neurotransmitters and of the tiny but critical cell outgrowths called neurites63 that are themselves formed and then remodeled in the process of learning64-66 and of cell repair.67
Brain scientists at MIT took those observations to a higher level when they supplemented nutritionally impoverished rats with UMP and studied the effects on memory.68 The animals were given either a control or a UMP-supplemented diet, and assessed for learning and memory skills. As expected, the impoverished animals fed a control diet did poorly on memory-dependent learning tasks, but those deficits were dramatically prevented in the UMP-supplemented group. One result of studies such as this one is the now-routine addition of UMP to infant formulas to promote healthy brain development.69
Declining ability to produce or respond to the neurotransmitter acetylcholine is one of the hallmarks of Alzheimer’s disease and other disorders of memory. In 2007, the MIT research group found that they could increase acetylcholine concentrations in aged rats with UMP supplementation.70 This is a stunning finding, since drugs like Aricept® that are used to treat Alzheimer’s disease work by inhibiting the enzyme that breaks down acetylcholine—an approach that has had mixed success and may cause serious side effects.71
The same MIT researchers, partnering with Turkish neuroscientists, have recently shown that UMP, together with the omega-3 fatty acid docosahexaenoic acid (DHA), can restore function in an animal model of Parkinson’s disease as well.72 And the same team demonstrated in late 2008 that they could actually enhance the learning and memory improvements caused by DHA in gerbils by adding UMP to the supplementation.73 They concluded, “these findings demonstrate that [UMP/DHA supplements] can enhance cognitive functions in normal animals” (emphasis added).74 In other words, one needn’t already have cognitive impairment to enjoy the potential benefits of UMP supplementation on learning and memory—and who wouldn’t want better memory even at baseline?
Ashwagandha Relieves Stress, Enhances Cognition
Numerous herbs from ancient India are reputed to promote physical and mental health, improve defense mechanisms of the body, and enhance longevity. Among the most promising of these for promoting cognitive health is a plant known as ashwagandha.
Indian researchers characterized the powerful antioxidant capabilities of ashwagandha extracts in 1997, showing that they increased concentrations of natural antioxidants in animal brains after supplementation.75 These researchers concluded that their findings explained the anti-stress, immunomodulatory, cognition-facilitating, anti-inflammatory, and anti-aging effects reported by other researchers in animal and clinical studies.
The same group later found that they could reduce the chronic stress effects of a mild, unpredictable foot shock in rats if they first supplemented them with ashwagandha extracts.76 Untreated animals experienced elevated blood sugar, glucose intolerance, increased stress steroid levels, gastric ulcers, male sexual dysfunction, cognitive deficits, and depression—common findings in humans exposed to chronic stress—but administration of ashwagandha extracts an hour before shocks dramatically attenuated all of these outcomes. As we noted with phosphatidylserine above, reduced stress allows increased focus on tasks and therefore better cognitive performance, in addition to simply improving quality of life.
A different Indian scientific group studied ashwagandha in diabetic rats, reasoning that the memory impairment seen in diabetes is in part related to oxidative damage in brain regions that are pivotal in memory and the ability to detect and process new information.77 They found a significant increase in production of oxidation end products in those brain regions, and a decrease in cognitive function, after the rats became diabetic. But following supplementation, the oxidative damage in the relevant brain regions was significantly reduced, as were blood glucose levels. Dramatically, memory impairment and motor dysfunction were also improved in the supplemented animals.
In 2007, further support for the use of ashwagandha extracts in Alzheimer’s disease was provided by the discovery that the extracts are among the most potent inhibitors of acetylcholinesterase, an enzyme that breaks down the vital memory-related neurotransmitter acetylcholine.78 Drugs that block acetylcholine breakdown (such as Aricept®) are utilized in the management of Alzheimer’s disease. The researchers correctly observed that “these results partly substantiate the traditional use of these herbs for improvement of cognition.” Western research into the benefits of ashwagandha is very recent, so stay tuned for additional exciting news on this extract’s memory- and cognition-enhancing properties.
Herbal Extracts Spice up Memory
It is now apparent that many traditional spices, in addition to adding interest to our food, can provide vital anti-inflammatory and antioxidant function that is having an impact on how we think about chronic illness and aging.79 Three of these in particular deserve special mention for their powerful effects on learning and memory.
Ginger is an age-old part of Asian kitchens and pharmacopeias,80 and we focus on it here especially for its ability to regulate platelet aggregation, which contributes not only to cardiovascular disease but also to cerebrovascular disease risk.81-84 Experimental studies demonstrated early in the millennium that ginger extracts could protect cells from the inflammatory action of the Alzheimer’s disease-related protein amyloid-beta.85-87 By its blood pressure-lowering effects, ginger can protect against the chronic brain injury caused by hypertension.82
Rosemary is an herb more familiar in Western kitchens, but has an equally distinguished record as a neuroprotectant through its antioxidant constituent, carnosic acid.88 Rosemary extracts block damaging lipid peroxidation, the destruction of brain cells’ fatty membranes that impairs cognitive performance.89 Rosemary also protects cell nuclei from DNA damage that results from both oxidant stress and ultraviolet light90—such damage is at the root of many cancers, but short of cancer it can impair a cell’s ability to function normally.
Neuroscientists in England recently showed a remarkable capacity of rosemary: humans exposed just to the aroma of its essential oil performed significantly better on overall memory quality compared with controls.91 Subjects also had increased states of alertness compared with controls or those exposed to lavender aroma.
Completing the culinary triad of memory-enhancing herbs is hops, the bitter ingredient of beer. Hops’ value may be primarily in its ability to promote relaxation and sleep—in one study, the combination of hops with valerian compared equally with a Valium®-like, sleep-inducing drug, and had none of the “hangover” effects seen with the drug.92 Similar results were found in another study comparing a Valium®-like drug with a hops/valerian combination: both groups did equally well on sleep, relaxation, and quality of life improvement, but patients experienced withdrawal symptoms when they stopped taking the drug.93
Conclusion
Far from being an “inevitable” consequence of aging, we now understand that cognitive decline and memory deficits are the predictable results of a lifetime of oxidative and inflammatory injury that damages brain cells’ ability to communicate with one another. A vast array of valuable nutrients are available to help block that damage—and in some cases to actually reverse it. Strong evidence abounds that the nutrients described in this review have important roles in improving the quality of life of older adults, keeping their wits sharp and their experiences vivid. These nutrients together, therefore, make up a vital part of any long-term brain health regimen
http://www.lef.org/magazine/mag2009/mar2009_Preserving-Cognitive-Function-with-Aging_01.htm
Enhancing Growth Hormone Naturally
Life Extension Magazine March 2009
During our youth, abundant levels of growth hormone (GH) promote an energetic physiology essential for healthy metabolism and an optimal ratio of lean muscle tissue to body fat.
By the time we reach middle age, however, levels of essential hormones such as testosterone and DHEA decline, while age-associated decreases in muscle mass and increases in body fat become noticeable.
Furthermore, research shows that in aging men, the amplitude of pulsatile GH release (the magnitude of the GH pulse) declines by 50% every seven years after 18-25 years of age.1
Exogenous subcutaneous injection of human recombinant growth hormone is expensive and still controversial. Fortunately, studies have shown that there are strategies that may naturally boost the endogenous production of growth hormone and thus provide a viable alternative to expensive injections. In particular, exciting research suggests that the growth hormone-blocker somatostatin can itself be inhibited with a nutrient called CDP-choline, thus slowing the rate at which growth hormone declines.
Naturally supporting the body’s own endogenous growth hormone production using targeted lifestyle and nutritional strategies may provide a safe method of harnessing the vigor and vitality associated with youthful growth hormone levels.
Growth Hormone Basics
Growth hormone (GH), also known as somatotropin, is a peptide hormone produced by the anterior lobe of the pituitary gland. Growth hormone secretion occurs in a pulsatile fashion following a circadian (daily) rhythm, which is controlled by a central area of the brain known as the hypothalamus. The hypothalamus regulates serum GH levels through the release of two functionally opposing hormones: growth hormone-releasing hormone stimulates GH release, while somatotropin release-inhibiting hormone reduces it.
Endogenous (made within the body) GH exerts its actions by binding directly to specific receptors on target tissues including muscle, connective tissue (tendons, ligaments, bone, and fat), as well as every major organ. Growth hormone also works indirectly by stimulating liver cells to produce and secrete polypeptide molecules known as somatomedins, the best studied of which is insulin-like growth factor-1 (IGF-1). Like GH, IGF-1 boasts receptors throughout the body and serves many functions. Together, GH and IGF-1 play influential roles in virtually every system—from muscle, bone, and connective tissue growth and repair, to the selective regulation of various aspects of metabolism, as well as helping maintain normal brain function and cardiac health.
However, GH secretion falls precipitously with advancing age. Furthermore, research shows that in aging men, the amplitude of pulsatile GH release (the magnitude of the GH pulse) declines by 50% every seven years after 18-25 years of age.1
This decline is also mirrored by diminishing IGF-1 levels. The decrease in the secretory activity of the GH/IGF-1 axis, commonly referred to as somatopause, correlates with a number of undesirable symptoms generally associated with aging. Most notably, diminishing GH/IGF-1 has been shown to reflect disordered sleeping patterns, bone frailty, increases in central adiposity (fat accumulation around the middle of the body including the abdomen), as well as decreases in cognition and muscle mass, strength, and conditioning.2-9
Is Synthetic GH Replacement Therapy Beneficial?
Since the decline of GH correlates with the onset of aging-related symptoms, scientists have investigated whether synthetic GH replacement may prove beneficial.
Some of the most compelling evidence that somatopause may respond favorably to synthetic GH replacement therapy comes from investigations involving patients suffering from total or near total absence of GH secretion as a result of pituitary disease. Without treatment, adults suffering from pituitary disease are both physically and psychologically less healthy than their age-matched peers, demonstrating significantly reduced muscle mass, bone density, exercise performance, thyroid function, and collagen production, with a concurrent escalation of central fat mass (especially fat accumulation in the abdominal organs) and insulin resistance, as well as an increased risk for cerebrovascular accidents (strokes) and cardiac events.10 Psychologically, they tend to experience more emotional lability (abrupt changes in mood in response to everyday events), depression, and social isolation,11-14 and their average life expectancy is measurably reduced.15,16
In the late 1980s and early 1990s, GH replacement studies in adults with poor pituitary function were designed with the goal of restoring normal GH levels. However, the doses used in these chronically GH-deficient individuals produced IGF-1 concentrations that greatly exceeded the expected range, resulting in unacceptably high rates of adverse reactions. In subsequent work, with GH doses adjusted to produce age-appropriate IGF-1 concentrations, negative side effects were largely eliminated or reduced to tolerable levels. Study subjects demonstrated significant and sustained improvements in body composition, physical performance, bone density, and psychological well-being, as well as substantial reductions in biomarkers for cardiac disease.17-24
In light of these results, researchers felt cautiously optimistic that men and women with partial GH deficiency secondary to advancing age might also reap the benefits of GH replacement therapy. However, following a landmark study by Rudman and colleagues in 1990, which provided the first evidence that GH supplementation in the elderly could diminish—and potentially reverse—some of the physical symptoms associated with somatopause,25 exogenous GH therapy has been controversial10,26-37 and associated with high costs.
Fortunately, scientists are discovering that the benefits of youthful GH levels can also be harnessed safely by naturally increasing the body’s own hormone levels with the right nutrients and lifestyle practices.
Nutritional Strategies for Optimizing GH
Nutritional strategies can offer targeted support for individuals seeking to enhance their endogenous production of GH. Such nutrients may work either by directly enhancing GH release from the pituitary gland or by enhancing the efficacy of sleep or exercise, the two activities that best support GH secretion.
CDP-Choline Boosts GH, Supports Brain Health
A growing body of research suggests that the compound cytidine-5’-diphosphate choline (CDP-choline) may boost GH secretion while conferring an array of brain health benefits for aging adults.
As adults grow older, GH secretion from the anterior pituitary gland declines precipitously. Exciting scientific research suggests that decreased GH release results in part from increasing levels of somatostatin with aging. Somatostatin produced by the hypothalamus inhibits the release of GH from the anterior pituitary.
This innovative idea has led researchers to search for agents that inhibit somatostatin and thus potentially increase the release of GH. Experimental research shows that treatment with cholinergic agonists increases GH release by inhibiting somatostatin release from the hypothalamus.38
These findings were soon supported by a human study. This compelling investigation showed that administration of CDP-choline to healthy elderly adults resulted in a dramatic four-fold increase in serum GH levels, compared with baseline values.39 These findings build upon evidence from an earlier study showing that CDP-choline administration in healthy men increased serum GH levels.40
In addition to its effects on GH release, CDP-choline acts through other mechanisms to promote brain cell integrity and health. CDP choline acts as an intermediate in the synthesis of neuronal membranes, promoting healthy brain cell membrane structure and function. CDP-choline counteracts the deposition of amyloid-beta, a pathological protein found in the brains of patients with Alzheimer’s disease. Human research suggests that CDP-choline supports release of the essential neurotransmitter norepinephrine, while animal studies show that CDP-choline increases brain levels of key neurotransmitters including dopamine and serotonin.41
In clinical trials, CDP-choline has shown promise in improving age-associated memory impairment, boosting cognitive performance in the early stages of Alzheimer’s disease, and supporting recovery from both ischemic and hemorrhagic stroke.41
These findings combine to suggest a powerful role for CDP-choline in supporting healthy GH levels and in optimizing brain health with aging.
Protein, Amino Acids Enhance GH Release, Lean Body Mass
Protein (especially protein derived from animal sources) provides important essential and conditionally essential amino acids known to assist endogenous GH secretion.42-44 An added bonus: these same essential amino acids are vital for supporting muscle growth and recovery in active men and women.
The most abundant amino acid in the body is glutamine. Consuming even a relatively small amount of glutamine (2,000 mg) has been shown to increase plasma GH levels.45 Glutamine has also been shown to help preserve muscle mass in individuals vulnerable to losing lean body mass due to inactivity following surgery.46 This suggests that glutamine may provide important benefits in maintaining lean body tissue.
Like glutamine, oral intake of the amino acid arginine increases the release of GH at rest. The combination of arginine intake with exercise produces even greater increases in GH levels.47 In addition to its anabolic (tissue-building) effects,48 ornithine alpha-ketoglutarate has also been reported to increase GH secretion.49
Compelling evidence demonstrates that the combination of arginine and ornithine augments the results of resistance training by helping to increase lean body mass and strength. The investigation also indicated that oral doses as relatively small as 1 gram of ornithine and arginine were effective in enhancing strength and lean tissue mass.50
Glycine Supports Healthy Sleep, GH Release
Since GH secretion occurs primarily at night, ensuring good sleeping habits is essential for individuals seeking to optimize their natural levels of GH. Unfortunately, one-third of adults report at least occasional bouts of insomnia, and about one-third of them suffer from sleeplessness or disturbed sleep on a more chronic basis, to the point that it regularly impairs daytime functioning. For the millions of sleepless among us, there may be good news—in the form of an inexpensive, naturally occurring amino acid known as glycine.
Within the central nervous system, glycine functions as an inhibitory neurotransmitter, playing a well-documented and critical role in initiating normal patterns of REM sleep.51 Now, a new study of chronic insomniacs demonstrates that glycine administered orally just prior to bedtime significantly improves sleep quality, shortening the latency between sleep onset and initiation of slow-wave (deep) sleep as measured by polysomnography. Volunteers also reported less daytime sleepiness, a subjective finding that was objectively corroborated by improved performance on cognitive tasks testing memory recognition.52
These findings build on previous work showing that a supplement cocktail containing glycine, glutamine, and niacin (vitamin B3) significantly increases endogenous GH secretion in healthy, middle-aged men and women. Individual test subjects in the study who demonstrated a concomitant increase in IGF-1 also exhibited improved memory and vigor.53
Lifestyle Techniques to Naturally Boost Endogenous GH Secretion
Healthy lifestyle practices are an essential component of a program to enhance endogenous GH production. The most important techniques for optimizing GH levels include:
1. Deflate the spare tire. If you happen to suffer from fat stores concentrated centrally around the organs of the abdominal region, GH secretion will be even more impaired. Fortunately, research indicates that declining GH due to body fat gain is partially reversible with weight loss.54 Unfortunately, visceral adiposity is often an indicator of both insulin and leptin resistance and, as a result, can be very difficult to shed permanently. Fortunately recent work has led to the discovery of effective, natural methods for combating leptin resistance.55-58 For more information, see: “Deflating your spare tire for a longer, leaner life…Understanding the risks of leptin resistance” Life Extension, February 2009,58 and “Vindication” (How correcting a testosterone deficit can reduce abdominal adiposity), Life Extension, December 2008.59
2. Avoid high-glycemic-load carbohydrates. Insulin is a powerful, direct inhibitor of GH secretion.42,60 To prevent the unhealthy surges of insulin or “insulin spikes” that decrease endogenous GH levels and increase your risk for type 2 diabetes, avoid highly processed carbohydrates like refined white bread and sugary cereal, as well as high-glycemic-load foods such as white rice, potato chips, cookies, soda, and commercially processed fruit juices (high in fructose and devoid of fiber). Instead, emphasize nutrient and fiber-rich whole fruits, vegetables, nuts, and legumes (beans).61
3. Insist on a good night’s sleep. The majority of GH secretion occurs at night during slow-wave (deep) sleep. Along with high-intensity exercise, another natural stimulus of endogenous GH secretion is sleep itself. It is well documented that inadequate sleep, irregular sleeping patterns, and poor quality sleep can substantially inhibit GH secretion.1,42 To optimize sleep, maintain good sleep hygiene habits: keep to a regular bedtime and wake up time; do not consume alcohol or caffeine 4-6 hours before bedtime; and keep excess light and noise out of the bedroom.
4. Plan your last meal of the day carefully. Your last meal of the day is the most important for maintaining a robust GH/IGF-1 axis. A high-protein, low-carbohydrate snack before bedtime serves a dual purpose. First, it helps minimize insulin release and allows for maximum endogenous GH secretion. Second, important essential and conditionally essential amino acids found in protein assist endogenous GH secretion.42-44 tay active! Exercise is a significant, natural optimizer of GH secretion.62 The type of exercise you do, as well the intensity and duration of your workouts, all play an important role in determining to what degree your training regimen contributes to GH secretion. A number of studies have suggested that the intensity necessary to trigger exercise-induced GH release corresponds to the lactate threshold—the exercise intensity at which lactic acid accumulates in the blood.63 Exercise training above the lactate threshold appears to amplify the pulsatile release of endogenous GH at rest, increasing total secretion for at least 24 hours.64
Conclusion
The plentiful growth hormone levels of youth are associated with strength, good health, and vitality. However, given the high cost and mixed study results associated with recombinant GH injections, optimizing lifestyle choices to enhance endogenous GH production may represent the most intelligent way to benefit from this youthful hormone. Through weight management, exercise, healthy sleep habits, minimizing intake of high-glycemic-load carbohydrates, and consuming targeted nutrients such as CDP-choline, niacin, glycine, glutamine, arginine, and ornithine, you may safely and cost-effectively capture the many benefits of naturally high GH levels.
http://www.lef.org/magazine/mag2009/mar2009_Enhancing-Growth-Hormone-Naturally_01.htm
Sweet fruit may help chemotherapy patients: The power of the so-called 'miracle fruit' to alter the taste of foods may help chemotherapy patients get rid of the metallic taste they experience during treatment.
The Miami Herald 03-13-09
Mar. 13--Miracle fruit isn't just a party trick. The tropical berries that can turn bitter into sweet could also make food taste better for chemotherapy patients.
An oncologist at Mount Sinai's Comprehensive Cancer Center is conducting the first clinical study of the benefits of miracle fruit for cancer patients whose chemo drugs leave an unpleasant metallic taste in their mouth.
"Taste alteration is one of the most common side effects of chemo," said Dr. Mike Cusnir, a Mount Sinai oncologist. "A metallic taste is very common, as is a complete lack of taste. One patient told me he could order a pizza and eat the box and not know the difference."
His study is examining whether miracle fruit -- Synsepalum dulcificum -- helps cancer patients for whom chemotherapy has changed their sense of taste.
Masking is the secret of the fruit, says Linda Bartoshuk, a researcher at the University of Florida's Center for Smell and Taste. A miracle fruit protein called miraculin stimulates the sweet taste receptor whenever there is acid in the mouth.
The idea of giving miracle fruit to chemo patients sprang from Don Blechman, a cancer patient and a volunteer at Fairchild Tropical Botanic Garden.
Blechman was talking to a tropical fruit expert at Fairchild, hoping for some botanical anecdotes he could tell visitors taking his tram tour of the grounds. The curator of the tropical fruit conservatory introduced Blechman to the miracle fruit. On his next visit with Cusnir for chemo, Blechman showed the oncologist how eating a lemon after the miracle fruit turned the lemon's taste from sour to sweet.
Cusnir met with Mike Maunder, then director at Fairchild, and Richard Campbell, senior curator of tropical fruit, and arranged to take berries -- and lemon slices -- to the protocol committee at the hospital. He got the go-ahead to explore using miracle fruit in a study.
That series of events set in motion what would become a $100,000 experimental study in which Cusnir hopes to reach a minimum of 40 patients, using miracle fruit supplied by Fairchild.
It's not just a matter of bitter vs. sweet on the palate. The taste-changing effects of chemo can often result in a loss of appetite, causing patients to eat less and sometimes lose weight they can't afford to lose.
"Calorie intake is important for a better prognosis," Cusnir said. "If patients become malnourished, they lose their resistance and their organs can suffer."
Cusnir got approval from Food and Drug Administration to conduct an initial clinical trial, with hopes of expanding it if the results are promising. An anonymous donor has underwritten the cost of his study.
Each patient must go through a chemo cycle using the fruit and a cycle without the fruit.
Then, each gets a questionnaire about taste.
Several patients have found the miracle fruit beneficial.
With chemo, "you have a bad taste all the time," said Carlos Novela, a Miami Beach chemo patient. "I tried the fruit Dr. Cusnir recommended to me as a trial. Right after I took that, the taste disappeared. It doesn't mean [a sense of taste] totally comes back to normal, but the flavor is masked; you don't really feel it."
The fruit's magic doesn't work for everyone. Linda Rosa said it did not curb the metallic taste she got from a cocktail of five chemicals she was taking for colon cancer.
http://www.lef.org/news/LefDailyNews.htm?NewsID=8009&Section=Disease
A little less salt could reduce heart risk
United Press International 03-13-09
SAN FRANCISCO, Mar 12, 2009 (UPI via COMTEX) -- A moderate decrease in daily salt intake could benefit the U.S. population and reduce the rates of heart disease and deaths, researchers said.
For every gram of salt that Americans reduce in their diets daily, a quarter of a million fewer new heart disease cases -- and at least 200,000 fewer deaths -- would occur over a decade, study lead author Dr. Kirsten Bibbins-Domingo of the University of California, San Francisco.
"A very modest decrease in the amount of salt -- hardly detectable in the taste of food -- can have dramatic health benefits for the United States," Bibbins-Domingo said in a statement. "It was a surprise to see the magnitude of the impact on the population, given the very small reductions in salt that we were modeling."
A 3-gram-a-day reduction in salt intake -- about 1,200 mg of sodium -- would result in 6 percent fewer cases of new heart disease, 8 percent fewer heart attacks and 3 percent fewer deaths, the report said.
Even larger health benefits are projected for African-Americans, who are more likely to have high blood pressure and whose blood pressure may be more sensitive to salt, Bibbins-Domingo said. Among African-Americans, new heart disease cases would be reduced by 10 percent, heart attacks by 13 percent and deaths by 6 percent, the study said.
The findings were presented at the American Heart Association's 49th annual conference on Cardiovascular Disease Epidemiology and Prevention in Palm Harbor, Fla.
http://www.lef.org/news/LefDailyNews.htm?NewsID=8006&Section=NUTRITION
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