Newly released preclinical studies suggest that supplementation with magnesium L-threonate may bolster the body's ability to slow and perhaps reverse synaptic changes in the brain which pave the way to Alzheimer's disease. In the following article Life Extension Foundation® Technical Director William Faloon explains this fast-progressing research and its implications.
The article was first published in the Jan 2012 issue of Life Extension Magazine* and is reproduced here with kind permission.
(As We See It) Reversing Brain Decay
By William Faloon*
Some facts are so terrifying that people pretend they are not real. A recent survey found Alzheimer's is the second most feared disease... cancer ranked number one.(1) Yet most cancers are curable, while Alzheimer's insidiously kills every one of its victims.
Alzheimer's incidence increases exponentially as humans age. If we make it to 80-85 years, Alzheimer's prevalence rises to a startling 25% to 30%.(2,3)
It is unsettling to think that our odds of developing Alzheimer's are so high, but there is reason for optimism. Scientists have identified factors that increase Alzheimer's risk. This enables enlightened individuals to neutralize underlying causes of Alzheimer's and spare themselves the frightening statistical probabilities faced by the general population.
Life Extension® members do a lot to reduce senility risk, such as suppressing destructive inflammatory reactions in the brain (with nutrients like curcumin),(4-7) while ingesting structural components required by brain cell membranes (such as DHA from fish oil).(8-11)
In a remarkable discovery, the loss of synapses has been shown to occur early in the process of Alzheimer's and may trigger onset of the disease.(12)
Fortunately, a highly absorbable form of magnesium not only protects the integrity of delicate brain synapses, but also increases synaptic density, thus helping to reverse the structural loss of this critical brain component.(13)
What Is a "Synapse?"
Our brain consists of about 100 billion cells called neurons. In order for neurons to communicate in a way that enables you to exist, they must connect to one another.
A synapse is the connection that allows information to pass from one neuron to the next. Your synapses control electrical impulses and the release of neurotransmitters between neurons. Brain synapses serve as a junction that enables neurons to pass signals in a synchronized/organized pattern.
Synapses, as you might imagine, are essential to neuronal function. Not only are synapses crucial to short-term memory in the young, but their structural integrity is imperative in aging individuals seeking to stave off cognitive impairment and senility.
What Happens When Our Synapses Degrade?
Alzheimer's disease is characterized by the pathological accumulation of non-functioning plaque in neurons and loss of normal neurotransmitter flow between neurons.
Before neurons encounter this severe damage, scientists have found a marked decline in synaptic density. This loss of synaptic density causes a decline in neuronal connectivity that strongly correlates to the cognitive impairment observed in Alzheimer's disease.(14-17)
In fact, a consistent finding in the brains of Alzheimer's victims is a significant loss of synaptic contacts. This led one group of researchers to conclude:
"...synapse loss is an early event in the disease process and suggests that mild cognitive impairment may be a transitional stage between early Alzheimer's disease and no cognitive impairment, with synaptic loss a structural correlate involved in cognitive decline."(18)
Another group of scientists looked at synaptic decay and concluded that it "may represent an early and subtle alteration able to trigger the development of senile plaques and neurodegenerative events."(19)
There are about 5 million Americans suffering from Alzheimer's today. That number will spike upward to 8.6 million by the year 2030 and to an astounding 16 million by 2050.(20) America does not have the economic or human resources to care for this many Alzheimer's victims.
A compelling need exists for an intervention that prevents the downward cascade of neuro-degeneration that will manifest as Alzheimer's in 25% to 30% of aged individuals.(21)
Magnesium Protects and Restores Synaptic Density
In a series of unprecedented laboratory experiments, a highly absorbable form of magnesium was shown to not only increase magnesium blood levels, but it also substantially increases magnesium brain concentrations.(13)
In response to this elevation in cerebral magnesium, there were significant increases in synaptic density and corresponding improvements in synaptic functioning and neuronal signaling.(13)
These improvements in synaptic structure and function translated into improvements in measurements of cognitive function.
Restoration of Short- and Long-term Memory
Using this highly absorbable magnesium (magnesium-L-threonate), scientists were able to obtain remarkably high brain magnesium concentrations compared to other forms tested.
In one study, just 24 days' oral supplementation with magnesium-L-threonate produced an increase in cerebrospinal magnesium sufficient to boost short- and long-term memory scores. Other forms of magnesium (such as magnesium chloride, magnesium citrate, magnesium glycinate, and magnesium gluconate) did not significantly elevate brain magnesium compared to the control group.(13,22)
Another test on aging animals (rats) that had suffered memory decline showed that magnesium-L-threonate could reverse the kind of cognitive dysfunction that occurs in normal aging humans. The animals had magnesium-L-threonate added to their drinking water for one month. The findings showed improvements of 18% in short-term memory in animals treated with magnesium-L-threonate. In a validated test for long-term memory, these same animals supplemented with magnesium- L-threonate exhibited 100% enhanced performance.(13)
Enhancement of Spatial Short-term Memory
Spatial memory relates to how an organism functions in a particular space. In this study, groups of animals were reward-trained in a maze. At the end of training, some groups received magnesium-L-threonate while the others served as controls.
In the young animal control group, there was no change in ability to navigate the maze. In young animals supplemented with magnesium-L-threonate, there was better performance (up to 13% improvement). Aged animals supplemented with magnesium-L-threonate performed 18% better than the aged control group (not given magnesium-L-threonate).(13)
The scientists stated that a significant improvement in choice accuracy was apparent 6 days after initiation of magnesium-L-threonate supplementation and this improvement continued for more than 30 days after cessation of magnesium-L-threonate in young animals. This finding helps validate the longer-term benefit of the increase in synaptic density. Strikingly, spatial performance of aged animals was re-enhanced within 12 days of re-initiation of magnesium-L-threonate supplementation.(13)
The scientists concluded that magnesium-L-threonate treatment can enhance the spatial working memory in young and aged rats.(13)
Enhanced Long-Term Spatial Performance
Young and old animals underwent maze training with a delay interval. Animals supplemented with magnesium-L-threonate learned to find the hidden platform in the maze faster than non-supplemented animals. In addition, the degree of learning ability enhancement in the aged animals was greater than in young animals. This makes sense since aged animals suffer from loss of synaptic density that magnesium-L-threonate has been shown to restore.(13)
To test the long-term spatial memory, a second trial test was performed 24 hours later. The unsupplemented "control" group forgot how to perform in the maze, whereas young and aged animals supplemented with magnesium-L-threonate retained their ability to navigate the maze. This might be equivalent to an older human being able to find their car in a crowded parking lot. In statistical terms, supplementation with magnesium-L-threonate resulted in long-term spatial memory improvement of 122% in younger animals - and 100% in older animals.(13)
The researchers concluded, "magnesium-L-threonate significantly enhanced hippocampus-dependent spatial learning and memory in both young and aged rats."(13)
Correlation Between Increased Synaptic Density and Memory
To verify that the mechanism behind these improvements in memory and cognitive performance was due to increased density of the synapses, studies were done to precisely measure the various synaptic structural components in the brain.
The rats supplemented with magnesium-L-threonate showed across-the-board improvements in synaptic protein expression, function, and structure, along with long-term potentiation of synaptic strength.(13)
Aging and Synaptic Decline
Several studies indicate that synaptic connections decline in the portion of the brain essential for memory, and the degree of loss of synapses correlates with the impairment of memory functions.(23-25)
To evaluate the impact of magnesium-L-threonate on old animals, one group received the supplement while an unsupplemented group served as controls. After only 1 month, autopsy findings showed synaptic density was 67% higher in the group supplemented with magnesium-L-threonate. This study showed that even in old animals, magnesium-L-threonate increased the density of synaptic components essential for youthful neurotransmitter release.(13)
Critical Importance of Magnesium
Since 1981, Life Extension has recommended high-potency magnesium supplements. The reason is that magnesium is perhaps the most deficient mineral in the American diet.
With all the research linking low magnesium intake with high cardiovascular risks, this mineral would appear to be a simple way to help counter the heart attack and stroke epidemic plaguing aging Americans.
• A government study shows a staggering 68% of Americans do not consume the recommended daily intake of magnesium.(26)
• Even more frightening are data from this same study showing that 19% of Americans do not consume even half of the government's recommended daily intake of magnesium.(26)
Is it any wonder that disability and death from heart attack and stroke are the nation's leading killers?
In the early 1980s, the Life Extension Foundation® was criticized by mainstream doctors for recommending high doses of magnesium relative to calcium. We even had our magnesium supplements seized by the FDA because we presented evidence that it could help prevent heart attack.
While the FDA refuses to recognize the value of magnesium, the National Institutes of Health (NIH) published the following on its website:
"Magnesium is needed for more than 300 biochemical reactions in the body. It helps maintain normal muscle and nerve function, keeps heart rhythm steady, supports a healthy immune system, and keeps bones strong. Magnesium also helps regulate blood sugar levels, promotes normal blood pressure, and is known to be involved in energy metabolism and protein synthesis. There is an increased interest in the role of magnesium in preventing and managing disorders such as hypertension, cardiovascular disease, and diabetes."(27)
The nation's leading health agency (NIH) acknowledges magnesium's critical role in keeping us alive, yet the FDA has done everything it could to keep this mineral out of Americans' bodies. The death toll from the FDA's censorship of magnesium is beyond comprehension.
Potential to Stave Off Health Care Cost Crisis
The cost of caring for those stricken with Alzheimer's and other neurological disorders is adversely impacting this nation's health care system. The enormous burden placed on families with senile loved ones destroys their productivity during critical working years.
Magnesium supplements are widely available, but many do not provide optimal absorption into the bloodstream and virtually none into the brain to restore critical synaptic density.
Widespread supplementation with magnesium-L-threonate has the potential to slash the incidences of many neurological disorders afflicting the aging population. Clinical trials are now beginning to assess whether magnesium-L-threonate functions as well in aging humans as it does in rodents.
With the wealth of data validating the systemic benefits of magnesium, those who don't want to wait years for the human studies to conclude should consider supplementing with 2,000 mg each day of magnesium-L-threonate. Based on animal data, noticeable improvements might occur within a relatively short time....
- William Faloon, January 2012
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* This article is reproduced here with kind permission from the January 2012 issue of Life Extension Magazine ©1995-2012 Life Extension® All rights reserved. The author, Life Extension Foundation Technical Director William Faloon, has published hundreds of articles on integrative approaches to addressing degenerative diseases of aging, and has been instrumental in publication of LEF's reference book Disease Prevention and Treatment, now in its fifth paper edition with web-based updates.
Note: This information has not been evaluated by the FDA. It is not intended to prevent, diagnose, treat or cure any condition, illness or disease. It is based on the research and opinions of the author unless otherwise indicated, and is not meant to replace the attention or advice of a physician or other healthcare professional. It is very important that you make no change in your healthcare plan or dietary, exercise, medication or other health support regimen without researching, discussing, and seeking clearance and guidance from your professional healthcare team.