Life Extension Magazine March 2013
Nutritional Strategies to Combat Alzheimer's
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