ONE IN THREE SENIORS DIE FROM ALZHEIMER’S
500,000 people die each year from Alzheimer’s
Alzheimer’s is the 5th leading cause of death in the United States for American’s 65 and older.
More than 5 million Americans have Alzheimer’s.
Alzheimer’s kills more than Breast & Prostate Cancer combined.
The facts above are from the Alzheimer’s Association web site, there is a lot more there if you want to check, www.alz.org.
"One of my worst fears is to see strangers around me, who I suddenly recognize as my family, only to have them taken away again and go back into a state of nothingness. My sister, Carol, is in that state right now and that is why I decided to find out what we all can do, now, to make sure we don’t end our life that way."
HERE IS WHAT I FOUND OUT:
NUTRIENTS WITH STRONG EVIDENCE FROM HUMAN STUDIES
Compared to control patients, Alzheimer’s patients supplemented with Acetyl-l-carnitine supplements, like most nutraceuticals, work in the earliest stages of Alzheimer's disease, emphasizing the importance of starting the supplement well before the onset of detectable symptoms. Studies also show that adding acetyl-l-carnitine to the prescription drugs donepezil or rivastigmine in mild Alzheimer’s can improve the response rate to these drugs from 38% to 50%.
Panax ginseng and its extracts are used in traditional Chinese medicine to enhance memory and cognition. This natural plant product has multiple mechanisms of action, including reducing amyloid beta plaque formation, enhancing amyloid beta clearance, and reducing brain cell death. Animal studies show that ginseng treatment reverses many of the memory and behavioral abnormalities found in models of Alzheimer’s. Human clinical trials show good efficacy of ginseng extracts in terms of improving scores on the standard Alzheimer’s rating scales.
Huperzine is a biochemical component of the Chinese club moss Huperzia serrata. It binds reversibly to the enzyme that destroys the neurotransmitter acetylcholine, helping to maintain the signaling molecule’s presence in the synapses, where nerve cells communicate. This mechanism is similar to that of most common Alzheimer’s drugs available today, but Huperzine also blocks the excitatory NMDA channels that overstimulate brain cells, offering a path not only to symptom relief but also to slowing the disease itself. Finally, huperzine protects mitochondria from the destructive effects of amyloid beta, and triggers enzymes that degrade the toxic protein.
Human studies of Huperzine at doses of 200 to 400 mcg twice daily have shown significant improvement, with some studies demonstrating improvements of 61% to 348% compared with placebo in scores measuring Alzheimer’s disease severity and activities of daily living. Minor side effects such as ankle swelling and insomnia have been reported in 3% of patients taking huperzine.
Lipoic acid is a small molecule that’s essential for proper mitochondrial energy production. It boosts natural cellular antioxidant systems. Lipoic acid protects brain cells from death induced by amyloid beta and other oxidizing substances. It also binds tightly to toxic metal ions, preventing them from inducing oxidant stress. Lipoic acid boosts production of acetylcholine in the brain, making more of the neurotransmitter available. In animal models of aging brains, alpha-lipoic acid slows development of cognitive dysfunction and memory loss, and prevents degeneration of brain cells.
In human studies, alpha-lipoic acid supplementation at 600 mg/day led to stabilization or slowing of cognitive decline, with Alzheimer’s disease scores remaining constant for 1 year and progressing extremely slowly over 4 years. As with most supplements, the effects are more pronounced in patients with early stages of the disease.
Editor’s Note: Alpha-lipoic acid is a 50/50 mixture of two different chemical forms of lipoic acid, an “ R” form and an “S” form. Studies show that the “ R” form is more biologically active and more bioavailable than the “ S” form—as such, a lower dose of pure R-lipoic acid can be considered.
Social isolation is known to increase the risk of Alzheimer’s disease, resulting in increased oxidant stress levels and higher levels of amyloid beta. An intriguing study in mice showed that NAC supplementation could mitigate isolation-induced oxidant stress and amyloid beta formation.
Human studies, though limited in number, have demonstrated slowing of deterioration in those with Alzheimer’s supplemented with n-acetylcysteine (NAC), particularly for cognitive tasks.
Omega-3 Fatty Acids
People with high intakes of fish oil, rich in omega-3 fatty acids, have lower levels of all kinds of dementia, including Alzheimer’s disease. People with lower levels of omega-3 intake have greater Alzheimer’s risk. Omega-3 fatty acids, especially DHA and EPA, reduce inflammation and form important components of brain cell membranes.
Human studies of omega-3 supplementation are encouraging, but it appears that benefits arise mainly in people with very early Alzheimer’s, or mild cognitive impairment, the stage that precedes Alzheimer’s itself. Once the disease has reached the mild to moderate stage, no beneficial effects are seen.
Vitamin D is best known for its role in calcium metabolism and bone health, but the past decade has revealed multiple other crucial effects of the vitamin, which has receptor molecules throughout the body, especially in brain cells. Vitamin D is now considered a neurohormone, with multiple beneficial effects in the brain. Older adults, and especially people with Alzheimer’s have abnormally low vitamin D levels compared with the healthy population. Those with the lowest levels have as much as a 25-fold risk of having the Alzheimer’s predecessor, compared with mild cognitive impairment when compared to those with highest vitamin D levels.
The specific cause and effect relationship remains murky, but it is clear that vitamin D has many different means of protecting brain cells. These include regulation of brain cell calcium channels, nerve growth factor, and nitric oxide synthesis, as well as antioxidant and anti-inflammatory mechanisms. Vitamin D also stimulates clearance of amyloid beta, an effect that is boosted by curcumin.
Studies show an improvement in cognition associated with an improvement in vitamin D status. Vitamin D has some overlap in mechanisms with the Alzheimer’s drug memantine, and a recent study showed that using both the drug and supplement together gave superior results to using either alone.
Extracts of Ginkgo biloba have been in use in Europe for more than a decade as a prescription drug to treat degenerative dementias including Alzheimer’s disease. Ginkgo reduces brain cell death and may enhance clearance of the precursor to amyloid beta proteins.
Clinical trials in the US and Europe demonstrate that ginkgo extracts improve cognitive function, but the findings have not been consistent. One study showed ginkgo extracts can slow progression of early Alzheimer’s by up to 25 months, while also delaying the need for dependence on caregivers.
Several studies compared ginkgo with donepezil, one of the standard drugs for Alzheimer’s treatment. Both showed no detectable differences between donepezil 5-10 mg and ginkgo 160-240 mg in terms of cognitive improvement, and one showed that the combination of donepezil and ginkgo, while not improving outcomes, did reduce the donepezil-related side effects.
Ginkgo extracts at the higher dose of 240 mg/day seem to show still more impressive benefits in randomized, placebo-controlled trials, again in patients with mild to moderate Alzheimer’s, but not all human studies show benefit.
Magnesium is a mineral that is essential for myriad human biological functions. It is especially important in the brain. Increasing brain magnesium using a special compound called magnesium-L-threonate restores degraded neuronal connections by increasing synaptic density, a process that underlies learning and memory.
Lab studies show that magnesium modulates enzymes involved in amyloid beta production; at low levels, magnesium favors amyloid beta buildup, while at higher levels it favors amyloid beta breakdown. There’s also evidence that magnesium opposes the effects of excitotoxic neurotransmitters; this would have the effect of reducing inflammation and perhaps amyloid beta deposition.
Magnesium levels are markedly lower in people with Alzheimer’s disease than in healthy controls, and the degree of magnesium deficiency correlates with the severity of the disease.
People who have high intakes of vitamin E from food are at lower risk of Alzheimer’s than those who don’t, but studies of typical vitamin E supplements don’t find that effect. The difference is that most supplements are comprised almost solely of the alpha tocopherol form of vitamin E, whereas the major form of vitamin E from food is gamma tocopherol . More current studies show that the gamma forms of vitamin E provide needed brain benefits. Specifically, higher intakes and levels of gamma tocopherol and gamma tocotrienol are associated with lower risks for both Alzheimer’s and its predecessor, mild cognitive impairment.
Nutrients with Strong Laboratory and Theoretical Evidence
The Ayurvedic plant, Ashwagandha, has widely-demonstrated beneficial effects, many of which are attributed to several of its antioxidant components, which are more powerful than most commercial antioxidants.
Extracts from Ashwagandha’s fruit and root protect brain cells in culture from the oxidant effects of amyloid beta; in one study they negated the cell death caused by amyloid beta.
Laboratory findings reveal that ashwagandha extract inhibits acetylcholinesterase, an enzyme responsible for breaking down acetylcholine, one of the brain’s key chemical messengers. Drugs such as Aricept®, which is currently used in the treatment of Alzheimer’s disease, act in this very manner to slow the progression of this mind-robbing disease as well as improve cognition and behavior.
THE ROLE OF ANTI-INFLAMMATORY DRUGS AND METFORMIN
Given the impact of inflammation in the Alzheimer’s disease brain, it is natural that scientists would look with hope to the group of drugs known as non-steroidal antiinflammatory drugs (NSAIDs). The NSAIDs include common, over-the-counter drugs like ibuprofen and naproxen, certain prescription drugs, such as celecoxib, and aspirin, the oldest NSAID in existence.
All of the NSAIDs work by inhibiting activities of enzymes, cyclooxegenases (or simply COX), which are involved in production of inflammatory signaling molecules called prostaglandins. By inhibiting COX activity, the hope is that one might reduce inflammatory changes in brain tissues of people with Alzheimer’s disease.
Epidemiological studies are encouraging, consistently showing lower incidence of Alzheimer’s disease among people who use NSAIDs regularly, with greater protection among those who use them over long time periods. The rate of protection varies somewhat, but in general NSAID users develop Alzheimer’s at rates in the range of 40 to 65% of those in people not using NSAIDs.
Animal studies also show improvement both in physical changes in the brain on NSAIDs and also in behavior, memory, and cognition. Unfortunately, human studies have been less convincing, until quite recently. Earlier studies showed little improvement in Alzheimer’s patients taking NSAIDs, but more recent, and more carefully-designed studies now suggest that certain NSAIDs (naproxen and ibuprofen) may slow disease progression in patients with very early, mild disease. And at least one study showed that a regimen of both ibuprofen 400 mg/day and aspirin 500 mg/day for one year resulted in modest increases in performance on cognitive testing in middle-aged women with normal cognition.
But these beneficial results seem to occur only in patients with very early Alzheimer’s, or in those who as yet show no symptoms. In fact, there’s some evidence that taking NSAIDs in more advanced Alzheimer’s disease can worsen certain aspects of the disease.
Some studies focus specifically on aspirin, the prototypical NSAID derived originally from willow bark. In addition to its ability to block the inflammation-inducing COX enzymes, aspirin has additional benefits of importance in Alzheimer’s disease. For example, it reduces the number of activated platelets; people with Alzheimer’s often have excessive amounts of activated platelets, which may contribute to poor blood flow in the disease. An exciting synergistic effect has been suggested between aspirin and the omega-3 fatty acid DHA: aspirin appears to promote conversion of DHA into anti-inflammatory molecules that may help to blunt the effects of inflammation on development of Alzheimer’s disease.
Metformin, like aspirin, is a well-established modern-day drug with natural origins (it’s derived from a French lilac bush). Most applications for metformin today have to do with diabetes and insulin resistance, which are increasingly relevant topics for Alzheimer’s researchers. In fact, the brain impact of diabetes and insulin resistance is so great that some scientists term Alzheimer’s “Type III diabetes.” Studies show that metformin helps the body break down and deactivate proteins that contribute to the neurofibrillary tangles characteristic of neurons affected by Alzheimer’s disease; obese mice with experimental Alzheimer’s show fewer biochemical brain changes when treated with metformin.
The B vitamins folate (B9), pyridoxine (B6), and cobalamin (B12) are essential for recycling of the molecules that make up DNA; without sufficient B vitamins there is a buildup of the amino acid homocysteine, which is toxic to many tissues. Elevated homocysteine levels are a known risk factor for Alzheimer’s disease, though it is still unclear if homocysteine is actually a cause of the condition.
Laboratory and human studies show that B vitamin supplements lower homocysteine, slow buildup of abnormal proteins amyloid beta and tau, and reverse the cognitive and memory deficits induced by artificially elevated homocysteine levels.
Blueberries are extremely rich in the beneficial plant molecules called polyphenols, which are powerful antioxidants. Polyphenols can also affect the way genes are expressed, switching on those that offer protection against neuronal damage, and switching off those that signal increased inflammation or other deleterious effects.
Blueberry extracts’ antioxidant actions help protect neurons against the damage done by amyloid beta proteins. They have also been shown to protect neurons and improve animal behavior even when amyloid beta levels are unchanged, meaning that they provide protection “downstream” from amyloid beta’s oxidant and inflammatory effects.
CoQ10 and PQQ
Coenzyme Q10 (CoQ10) and pyrroloquinoline quinone (PQQ) are essential nutrients that help keep mitochondria healthy by improving their efficiency at burning foods to produce energy.
Laboratory studies show that CoQ10 supplementation reduces the amount of amyloid beta plaque formation in brain cells, resulting in improved behavior. PQQ acts after amyloid beta has already accumulated, helping cells recover from amyloid beta-induced oxidant stress, preventing neuronal cell death, and decreasing further production of reactive oxygen species.
“Read more about both in the “Analysis of Supplements” section.
Check them carefully because from everything I have read they seem to be important.”
BALANCING HORMONES, ESPECIALLY DHEA, IN ALZHEIMER’S
Although its effects are not fully understood, it’s clear that stress of all kinds takes a toll on the brain. Eventually, mainly under the influence of excessive levels of the stress-response hormone cortisol, structural and functional changes occur, especially in the hippocampus, the brain’s most concentrated region of memory-processing neurons.
Normally, the effects of cortisol are balanced by high brain concentrations of the neurosteroid dehydroepiandrosterone (DHEA). DHEA, and its “sulfate” form, DHEAS, are the most abundant hormones produced by the adrenal glands, the body’s stress-controlling organs. These hormones serve to protect hippocampus and other brain cells from oxidative stress and the deleterious immune system disruptions induced by cortisol, which left unchecked can drive inflammatory processes that further damage memory and cognition.
With advancing age comes a drop in DHEA production, however, while cortisol production is relatively unchanged (in fact, some studies suggest that cortisol increases with age). The sharp decline in DHEA levels is often referred to as “adrenopause,” and is thought to contribute to age-related increases in atherosclerosis, cancer, and dementia.
The resulting imbalance in the DHEA/cortisol ratio is a direct measure of risk for Alzheimer’s disease: people (especially women) with Alzheimer’s have much lower DHEA/cortisol ratios than do healthy age-matched controls, who in turn have lower ratios than younger adults.
Laboratory and animal studies demonstrate that DHEA supplementation has substantial anti-inflammatory effects in the brain, including inhibition of nitric acid production, an early inflammatory signaling molecule. DHEA also stimulates production of new neurons in tissue-culture experiments. DHEA produces a restoration of youthful cognition and memory when older animals, or those with Alzheimer’s disease, are supplemented with the neurohormone.
Indian Turmeric Abstract
Curcumin is a yellow biomolecule derived from the spice turmeric. Like other antioxidants, curcumin protects brain cells and their mitochondria against amyloid beta-induced toxicity and inhibits formation of abnormal proteins.
But curcumin also possesses some unique features with regard to Alzheimer’s disease. Sophisticated molecular studies reveal that curcumin can prevent amyloid beta molecules from assembling, and can also destabilize amyloid beta plaques after they have formed. 137,138 This permits the body’s natural cleanup cells, macrophages, to rapidly clear amyloid beta fragments before they can re-form and damage brain cells. And curcumin stimulates macrophages to make that cleanup process still more rapid and efficient.
Another beneficial mechanism of curcumin is to enhance the health of mitochondria, the tiny cellular power plants that provide energy to all of our cells. Aging mitochondria are thought to be responsible for much of the brain cell death and dysfunction that occurs in Alzheimer’s disease. 139 Curcumin, through its antioxidant actions, scavenges dangerous oxygen free radicals produced by ailing mitochondria, preventing their death and enhancing their action. 140
Finally, curcumin has favorable effects on brain insulin receptors. The balance between glucose levels and insulin in the brain is capturing scientists attention, with some even referring to Alzheimer’s disease as “type III diabetes.” Studies of diabetic animals reveal that curcumin enhances actions of insulin receptors in brain tissue.
Studies in animal models of Alzheimer’s disease demonstrate the value of these multiple mechanisms on learning and memory. Curcumin supplements given even after the onset of Alzheimer’s-like symptoms result in fewer mistakes on memory-dependent tasks, and improved performance on mazes that test both reasoning and memory. When the animals’ brains are examined at the end of such experiments, they demonstrate significantly less brain cell death in memory-processing brain areas.
In one of the most dramatic experiments to date, curcumin supplements were found to protect against brain aging in general among mice treated with an age-accelerating compound. These remarkable findings were accompanied by improved performance on cognitive tasks and enhanced locomotion; in these animals’ brains improved oxidant defenses and restored mitochondrial enzyme activities were observed as well.
This kind of reversal of Alzheimer’s damage is something no existing drug can do.
Grape Seed Extract
Grapes, and particularly their seeds, contain very high levels of proanthocyanidins, clusters of polyphenols that have multiple health benefits including anti-inflammatory and antioxidant effects. But they also have remarkable gene modulating activities, directing protein expression away from that seen in Alzheimer’s and towards a more normal state. And they readily cross the blood-brain barrier to be deposited in brain tissue. These effects result in reduction of Amyloid beta formation by several different mechanisms, as well as enhanced amyloid beta clearance. Grape seed extracts also reduce inflammation in animal models of Alzheimer’s disease.
Green tea is rich in a variety of polyphenols, especially one called EGCG, that has multiple beneficial attributes. EGCG interferes with the Alzheimer’s disease process in several important ways.
EGCG physically blocks the assembly of amyloid beta proteins, preventing them from clumping together to form plaques. The compound also generates a unique set of stable proteins from the amyloid beta precursor molecule; these proteins can’t bind together at all, further reducing the burden of plaque.
Intriguingly, EGCG, given before exposure, prevents mitochondrial dysfunction induced by amyloid beta in brain cells, while also normalizing cells’ responses to the excitatory neurotransmitter NMDA.
Resveratrol is a multi-functional polyphenol that plants use as an antifungal compound; it is found abundantly in red grapes.8, Resveratrol has antioxidant characteristics, but scientists are especially excited about its ability to change how genes are expressed. This so-called epigenetic capability allows resveratrol to affect multiple points in the complex series of events that ultimately produces Alzheimer’s symptoms.
Studies show that these properties of resveratrol act both before and after amyloid beta protein is deposited in brain tissue. Resveratrol promotes enzyme actions that slow amyloid beta production, and speed its clearance, while it also promotes expression of enzymes that limit the nitric oxide and inflammatory cytokine production that amyloid beta triggers.
Glucose utilization is impaired in the brains of Alzheimer’s patients, leading to further deterioration of their cells; this is one of the many ways that Alzheimer’s and type II diabetes overlap. Breaking research reports that resveratrol can promote glucose utilization in brain cells, potentially mitigating the destructive effect of elevated sugar.
Vinpocetine is an alkaloid derived from the periwinkle (Vinca) plant. It increases brain blood flow and decreases platelet aggregation through its inhibition of the enzyme PDE1. Vinpocetine also produces higher brain levels of the neurotransmitter acetylcholine that is deficient in Alzheimer’s disease.
By separate mechanisms, vinpocetine provides antioxidant protection to brain cells, and markedly reduces mitochondrial dysfunction. These combined mechanisms, and perhaps others, contribute to vinpocetine’s ability to prevent neuronal damage and improve impaired learning and memory in animal models of Alzheimer’s.
The multifactorial nature of Alzheimer’s disease makes it a natural condition for combinations of nutrients that, together, can target many, if not most, of the underlying molecular damage.
Studies of a mouse model of Alzheimer’s reveal so much improvement in learning in supplemented mice that their performance could not be distinguished from that of healthy mice. The supplement contained curcumin, piperine, epigallocatechin gallate, alpha-lipoic acid, n-acetylcysteine, B vitamins, vitamin C, and folate.
Several human studies have been done with a supplement containing curcumin, piperine, EGCG, alpha-lipoic acid, N-acetylcysteine, B vitamins, vitamin C, and folate in those with mild to moderate Alzheimer’s disease. Patients’ performance on standard neuropsychiatric measures were equivalent to those on donepezil, and exceeded those of galantamine, drugs in current use for Alzheimer’s. Even in institutionalized patients with later-stage disease, this formulation produced an improvement of about 30% on the standard neuropsychiatric inventory. This formulation has also been shown to improve cognitive performance in people without dementia, demonstrating the power of combined supplementation.
One proprietary nutritional product (containing Ashwagandha, blueberry, grape seed extract, ginger, vinpocetine, and phosphatidylserine plus alpha-glyceryl phosphoryl choline and other ingredients) has also now been shown to improve cognition in adults with memory and cognition problems and improve working memory, executive function, and inspection time (a measure of decision-making), in an open clinical trial.
Alzheimer’s is a complex, multifactorial, and progressive disease that steals mind and memory. To date, mainstream medicine remains baffled by the condition, with just 5 drugs on the market, none of which can modify or slow disease progression.
Nutritional supplements, on the other hand, have multiple mechanisms, offering a broader front on which to attack Alzhiemer’s. Many different supplements show great promise by acting on several or many different targets in the disease’s progression. Combining many nutrients together is proven to offer even greater impact.
Using a combination of multitargeted supplements may be the only way to stop or slow Alzheimer’s disease, and prevent it from taking away your personality.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
By Liam Hawkins