Nutritional Strategies to Combat Alzheimer'sMarch 2013
By Liam Hawkins
Someone in America develops Alzheimer’s every 68 seconds. This rate is projected to more than double by 2050, to one every 33 seconds.1
Alzheimer’s research is accelerating, but there is still no cure.
A vast array of published data, however, shows that making healthy dietary choices, along with proper use of nutrients, hormones, and drugs may dramatically reduce one’s risk of developing this mind-destroying killer.
Most recently, an innovative brain scan was unveiled that for the first time can accurately diagnose the brain plaques that are characteristic of Alzheimer’s. More than 300 hospitals and imaging centers have the ability to perform this scan.2
The dilemma we face today is that the five drugs approved for Alzheimer’s only partially treat some of the symptoms. None of them can slow or stop the progression of the disease itself—let alone reverse it.3
Just because mainstream medicine has no solutions doesn’t mean you’re powerless against Alzheimer’s.
Dozens of compounds have ample research behind them demonstrating their ability to take aim at multiple degenerative steps in the development of Alzheimer’s.4,5 This may not only prevent the disease from developing, but it can also modify the course of the disease itself—reversing cognitive deficits, restoring memory, delaying the progression of disease, and more.
The Complexity of Alzheimer’s
Symptoms of Alzheimer’s disease, the most common form of dementia, begin with insidious loss of memory which progresses to involve all aspects of cognition, including confusion and mood swings.6,7 After a painful and lingering illness, Alzheimer’s causes death; it’s the 6th leading cause of death in Americans overall, and the 5th among those over 64.2
Doctors are in a scientific and therapeutic quandary with Alzheimer’s. We know a great deal about the disease’s risk factors, about the pathological changes that occur in the brain, and about the biochemistry underlying them. We can predict with accuracy the natural course of the disease, once its symptoms become evident.
But to date, conventional medicine can do almost nothing to slow or stop the disease’s progression, let alone prevent or reverse it.3,7
Part of the problem is the tremendous complexity of Alzheimer’s. Rather than having a single or a few clear-cut causes that can be targeted with individual medicines, a complex presentation of interrelated abnormalities contribute to Alzheimer’s disease.4 These develop slowly, and most are already in place by the time the first symptom arises.6 Ultimately, loss of brain cells and their billions of connections leads to atrophy, or shrinkage, of the brain itself, especially in the hippocampus and cortex, brain areas responsible for memory, cognition, and personality.6
No single-targeted synthetic drug can yet address these multiple factors. Nutraceuticals offer an entirely different approach. Rather than a single target, these natural products take aim at multiple steps in the development of Alzheimer’s.5
The list of researched nutraceuticals that offer hope for modifying the course of Alzheimer’s disease is long, and growing. Many of these nutrients attack Alzheimer’s at multiple target points.8-10
The list is so long, in fact, that it’s easy to become overwhelmed and to wonder which nutrients are right for any one individual to choose. That answer, of course, is highly individualized.
What we have done is meticulously compile a listing of supplements grouped by the kind of evidence available to support their use. The first group includes nutrients with good support from strong human studies. The second group includes those with extensive evidence from epidemiological studies relating intake (or blood levels) to the risk of Alzheimer’s disease. The third group is comprised of nutrients for which we have strong laboratory evidence, but for which human studies are still incomplete. The science behind nutritional strategies for preventing Alzheimer’s continues to evolve. Here’s what we know as of today…
Nutrients with Strong Evidence from Human Studies
Acetyl-L-Carnitine is a natural amino acid-derived molecule that contributes to movement of fatty acids and other vital fuels from the cell into mitochondria.11-13 As such, it contributes to brain mitochondrial health and efficiency.12-15
Animal studies show that acetyl-l-carnitine supplementation decreases buildup of amyloid beta and tau proteins, and speeds degradation of amyloid beta, contributing to its rapid clearance from brain cells.15-17 At the same time, acetyl-l-carnitine boosts natural cellular antioxidant levels.15 These changes are accompanied by improved memory, cognition, and behavior, including slowing the rate of deterioration.13,18
Compared to control patients, Alzheimer’s patients supplemented with acetyl-l-carnitine at doses of 2 to 3 grams/day for three to six months show slower decline in multiple cognitive functions, reduced attention deficits, and increased energy available to cells as ATP, the universal energy-storage molecule.19-23 Acetyl-l-carnitine research provides the first demonstration that a nutrient therapy may modify the clinical and central nervous system neurochemical parameters of the disease, unlike any existing drugs, which only influence symptoms.3,20
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.21,22 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%.11
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.24-27 Animal studies show that ginseng treatment reverses many of the memory and behavioral abnormalities found in models of Alzheimer’s.28
Human clinical trials show good efficacy of ginseng extracts in terms of improving scores on the standard Alzheimer’s rating scales.29 One study of ginseng, 4.5 grams/day showed improvements that continued until treatment was stopped, after which scores declined to those of the control group.30
Huperzine A 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.31,32 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.33 Finally, huperzine protects mitochondria from the destructive effects of amyloid beta, and triggers enzymes that degrade the toxic protein.34,35
Human studies of Huperzine at doses of 200 to 400 mcg twice daily have shown significant improvement,31,36-39 with some studies demonstrating improvements of 61% to 348% compared with placebo in scores measuring Alzheimer’s disease severity and activities of daily living.31,37 Minor side effects such as ankle swelling and insomnia have been reported in 3% of patients taking huperzine.37
Lipoic acid is a small molecule that’s essential for proper mitochondrial energy production.40 It boosts natural cellular antioxidant systems.40,41 Lipoic acid protects brain cells from death induced by amyloid beta and other oxidizing substances.42 It also binds tightly to toxic metal ions, preventing them from inducing oxidant stress.43 Lipoic acid boosts production of acetylcholine in the brain, making more of the neurotransmitter available.40 In animal models of aging brains, alpha-lipoic acid slows development of cognitive dysfunction and memory loss, and prevents degeneration of brain cells.44-46
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.47,48 As with most supplements, the effects are more pronounced in patients with early stages of the disease.48
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.49
N-acetylcysteine (NAC) is an amino acid precursor of the cellular antioxidant glutathione.50 As such, it can boost intracellular protection against the ravages of oxidant stress. NAC has been used in the laboratory successfully to clean up reactive oxygen species and ameliorate the behavioral changes seen in older animals and those with features of Alzheimer’s.41,51
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.52
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.53
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.54-57
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.57-60 Once the disease has reached the mild to moderate stage, no beneficial effects are seen.61
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.62,63 Vitamin D is now considered a neurohormone, with multiple beneficial effects in the brain.64
Older adults, and especially people with Alzheimer’s have abnormally low vitamin D levels compared with the healthy population.64-66 Those with the lowest levels have as much as a 25-fold risk of having the Alzheimer’s predecessor, mild cognitive impairment when compared to those with highest vitamin D levels.67
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.62,68-71 Vitamin D also stimulates clearance of amyloid beta, an effect that is boosted by curcumin.63,64,72,73
Studies show an improvement in cognition associated with an improvement in vitamin D status.64 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.70,74
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.75 Ginkgo reduces brain cell death and may enhance clearance of the precursor to amyloid beta proteins.76,77
Clinical trials in the US and Europe demonstrate that ginkgo extracts improve cognitive function,78-80 but the findings have not been consistent.81,82 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.79
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.83,84
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,85-87 but not all human studies show benefit.81,82
Nutrients with Strong Evidence from Epidemiological Studies
Many large epidemiological studies show that moderate coffee consumption (3-5 cups of caffeinated coffee/day) is associated with reduced risk for Alzheimer’s.88-91
People who drank coffee at that level in mid-life had a 65% decrease in Alzheimer’s risk later in life.91,92 And high blood caffeine levels appear to prevent the progression of minimal cognitive impairment to fully-developed Alzheimer’s.93
Studies show that caffeine can reduce brain levels of toxic amyloid beta proteins in animals, while not only slowing but in fact reversing the amyloid beta-associated cognitive impairment.89,94,95 Just 1 to 2 months of caffeine treatment restored memory and lowered brain amyloid beta levels in mice.89
Coffee’s other components, including chlorogenic acid, also have major protective effects on brain cells.90,96-99 It is likely, however, that coffee’s primary benefit to brain health is related largely to its caffeine content.
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.100
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.101,102 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.103
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.104-106
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.107,108 The difference is that most supplements are comprised almost solely of the alpha tocopherol form of vitamin E,107,109 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.110,111
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.107-109,112
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.113
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.113
Laboratory findings reveal that ashwagandha extract inhibits acetylcholinesterase, an enzyme responsible for breaking down acetylcholine, one of the brain’s key chemical messengers.114 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.115
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.116-118
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.119,120
Blueberries are extremely rich in the beneficial plant molecules called polyphenols, which are powerful antioxidants.121 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.122
Blueberry extracts’ antioxidant actions help protect neurons against the damage done by amyloid beta proteins.121,123 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.124-126
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.127-130
Laboratory studies show that CoQ10 supplementation reduces the amount of amyloid beta plaque formation in brain cells, resulting in improved behavior.131,132 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.133
Curcumin is a yellow biomolecule derived from the spice turmeric.134 Like other antioxidants, curcumin protects brain cells and their mitochondria against amyloid beta-induced toxicity and inhibits formation of abnormal proteins.134-136
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.”141 Studies of diabetic animals reveal that curcumin enhances actions of insulin receptors in brain tissue.142,143
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.144-147 When the animals’ brains are examined at the end of such experiments, they demonstrate significantly less brain cell death in memory-processing brain areas.145
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.148 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.149 And they readily cross the blood-brain barrier to be deposited in brain tissue.150
These effects result in reduction of Amyloid beta formation by several different mechanisms, as well as enhanced amyloid beta clearance.151-153 Grape seed extracts also reduce inflammation in animal models of Alzheimer’s disease.154
EGCG physically blocks the assembly of amyloid beta proteins, preventing them from clumping together to form plaques.156 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.157
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.158,159
Resveratrol is a multi-functional polyphenol that plants use as an antifungal compound; it is found abundantly in red grapes.8,160-162 Resveratrol has antioxidant characteristics, but scientists are especially excited about its ability to change how genes are expressed.163 This so-called epigenetic capability allows resveratrol to affect multiple points in the complex series of events that ultimately produces Alzheimer’s symptoms.164
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.160,165-168
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.169
Vinpocetine is an alkaloid derived from the periwinkle (Vinca) plant.170 It increases brain blood flow and decreases platelet aggregation through its inhibition of the enzyme PDE1.170,171 Vinpocetine also produces higher brain levels of the neurotransmitter acetylcholine that is deficient in Alzheimer’s disease.171
By separate mechanisms, vinpocetine provides antioxidant protection to brain cells, and markedly reduces mitochondrial dysfunction.170-172 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.171
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.173
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.174
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.175 Even in institutionalized patients with later-stage disease, this formulation produced an improvement of about 30% on the standard neuropsychiatric inventory.176 This formulation has also been shown to improve cognitive performance in people without dementia, demonstrating the power of combined supplementation.177
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.178
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.