Galantamine May Help You Remain a Smart Cookie

Galantamine Keeps on Working and Working . . .

Galantamine May Help You
Remain a Smart Cookie

3-Year study confirms its efficacy—and early intervention
for long-term prevention makes sense
By Will Block

here’s a birthday card that says, “You’re not really getting old until you start having trouble making sense of simple things . . . [and inside] . . . isn’t it?” We laugh, but perhaps with a twinge of apprehension. Getting old isn’t all that funny, especially if the body outlasts the mind. No one wants to contemplate the gradual erosion of memory and other cognitive functions that are such a characteristic (but largely unnecessary) part of the aging process. When you’ve seen it happen in others—perhaps a friend or a loved one—it makes you all the more determined to hang on to your own mental faculties for dear life.

But how do you do that? The mind is an abstraction, a will-o’-the-wisp, not something you can lasso and put in a box for safekeeping (besides, we’re always being admonished to “think outside the box”). You must use the very faculties you wish to protect to figure out what to do. Your thinking might go something like this: There are no certainties when it comes to protecting the mind. However, there are probabilities, based on current scientific knowledge, that I could act upon to maximize my chances of success. But where can I find that knowledge? . . . Hey, I’m reading this article, aren’t I? That’s a good start.

Supplementation Can Help Your Brain

So we’ve established that you’re a smart cookie, and you want to stay that way. Your mission is to take decisive action on your own behalf so as to preserve and protect the cognitive functions that are allowing you to read and understand these words, and that will allow you to remember, if not the words, then the central idea they convey, namely:

It is possible, through intelligent nutritional supplementation, to augment the benefits to your brain of a good diet and regular exercise, so as to enhance the probability that your brain will remain healthy and sharp for the rest of your life.

You Have a Cornucopia of Choices

If you could take but one supplement for your overall well-being, it should be the best multivitamin, multimineral, multiantioxidant formulation you can find. Those are the supplement building blocks not only for a healthy body, but also for a lucid mind. There is abundant scientific evidence of the beneficial effects on brain function (and, of course, heart function and other functions) of many of these vitally important compounds—especially vitamins E and C—and it’s hard to fathom why anyone would willingly forego the myriad health advantages they offer. (For more on this subject, see the article on page 21 of this issue.)

Thus, taking a “multi-VMA” to lay the groundwork for a healthy brain is a no-brainer, so to speak. But then what? Suddenly the options are varied, and the choices bewildering. Many different supplements have been shown to enhance memory or other aspects of cognitive function in one way or another, and all have something to recommend them.


The patients’ decline was delayed
by one full year compared with
the controls. By the end of the
36-month period, they had
gained about 18 months worth of
preservation of cognitive function
relative to the prediction.


There are, e.g., the natural amine choline and its derivative CDP-choline; the amino acids phenylalanine, arginine, acetyl-L-carnitine, and creatine; the lipids phosphatidylserine and phosphatidylcholine; the omega-3 fatty acids DHA and EPA; the phytonutrients vinpocetine, huperzine A, and resveratrol; and herbal extracts of Ginkgo biloba, Bacopa monniera, and Melissa officinalis (lemon balm).

Galantamine—a Supplement—Stands Apart

All these supplements have been discussed in past issues of Life Enhancement (the omega-3 fatty acids are discussed again in this issue—see page 29), and all are worthy of your serious consideration. This article, however, is about one supplement for cognitive enhancement—galantamine—that stands apart from the rest, for one compelling reason: it has been clinically proven to be a safe and effective treatment in mild to moderate cases of Alzheimer’s disease. Galantamine is, in fact, the active ingredient in an FDA-approved prescription medication (Reminyl®) for that purpose.

I know what you’re thinking: how can a supplement be a prescription drug? Aren’t they mutually exclusive? Actually, no. Before being declared a “drug” in 2001, galantamine had been sold as a nutritional supplement for many years, and its use as a folk remedy is believed to go back several thousand years. Because of its documented history of use as a supplement, it is still a supplement, and it can be obtained as such without prescription (at far lower cost than as a prescription drug) by anyone.

That’s the good news. The bad news is . . . uh . . . correction, there is no bad news about galantamine—but there is more good news! There is now clinical evidence that galantamine’s efficacy in preserving and protecting cognitive function against the ravages of Alzheimer’s disease extends for a much longer period (at least 3 years) than had previously been demonstrated.1 This is important, because a major problem with most of the other anti-Alzheimer’s agents is that they tend to lose their efficacy within 6 to 12 months.

Galantamine Slows Rate of Cognitive Decline

Obviously, the longer a therapeutic agent can remain effective in use, the better it is for the patient. Most of the clinical trials with galantamine conducted thus far have lasted one year or less, but even within that limited interval, galantamine’s superior efficacy has been evident.2 While other agents tend only to slow the patients’ rate of decline, galantamine typically halts it completely for several months, and in some cases even reverses it for a few months. Ultimately, however, the decline is inevitable, as is the patient’s end—there is no cure for this terrible disease.* The objective, therefore, is to retard its progress as strongly as possible for as long as possible.


*A recent study indicates that life expectancy in people suffering from dementia is much shorter than had previously been believed: 3.3 years after onset of the disease, rather than the previous estimate of 5 to 9.3 years.3


That’s where galantamine shines. This remarkable compound (which is extracted from certain flowers, such as the snowdrop, daffodil, and spider lily) has a unique, dual mode of action in the brain, the net effect of which is to maintain cholinergic function (those aspects of brain activity, including memory and other cognitive functions, that depend on acetylcholine as the neurotransmitter). Galantamine does this more effectively than any other anti-Alzheimer’s agent.

Galantamine Is Tested for 36 Months

Dramatic new evidence of galantamine’s ability is found in a 36-month study published by researchers from the University of Washington, Johnson & Johnson, and the J & J subsidiary Janssen Pharmaceutica Products (which markets Reminyl).1 They investigated the long-term safety and efficacy of galantamine in 194 patients (average age 76) with mild to moderate Alzheimer’s disease (AD).

The patients in the new study, who had been enrolled in either of two randomized, double-blind, placebo-controlled trials of galantamine for a 12-month period, subsequently received an additional 24 months of treatment (24 mg/day) on an “open label” basis, i.e., the trial was not blinded—they were all receiving galantamine during this extension phase, and they all knew it. (With serious diseases, ethical considerations preclude the long-term use of placebo—it’s not fair to the patients.)

Making Dumb Bunnies Smarter

Bunnies (OK, rabbits, if you must be technical) sure are cute, but let’s face it, they’re not exactly known for their high IQs. Heck, when you’re that endearing, you don’t have to be smart. Nonetheless, a tiny infusion of brains wouldn’t hurt. That is what two teams of researchers at American universities tried recently, in the form of galantamine.1,2 Using both young and old rabbits in similar studies, they administered galantamine by injection, at dosages roughly 10 times greater than those typically used by humans.

The purpose was to see whether the rabbits’ capacity for attention and learning could be improved through the biochemical actions of galantamine on their brains (these actions are the same in rabbits as in humans). The experiments involved the use of an eyeblink technique for Pavlovian conditioned responses to certain stimuli. The results: the galantamine-treated animals did indeed show significantly improved performance compared with age-matched controls.

So in effect, those dumb bunnies—whether old or young!—got a little smarter, thanks to galantamine. And if galantamine can do that for them, perhaps it could do the same for somewhat higher organisms as well.

  1. Simon BB, Knuckley B, Powell DA. Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits. Learn Mem 2004;11:116-22.
  2. Weible AP, Oh MM, Lee G, Disterhoft JF. Galantamine facilitates acquisition of hippocampus-dependent trace eyeblink conditioning in aged rabbits. Learn Mem 2004;11:108-15.

The researchers measured the patients’ performance on standardized tests of cognitive function and compared them with: (1) the test scores of a clinically and demographically similar control group of AD patients who had received placebo for 12 months in a previous clinical trial, and (2) the mathematically predicted rate of cognitive decline in untreated AD patients over a 36-month period, based on voluminous existing data.


It’s never too early to be
concerned about the possibility of
serious cognitive decline, even for
those of middle age.


Galantamine Buys 18 Months of Time

The results were gratifying: whereas the condition of the controls declined steadily from day one, that of the galantamine-treated patients actually improved during the first 3 months and only then began to decline slowly. The patients returned to their cognitive starting point 9 months later (i.e., 12 months from the outset of the trial), and their decline continued unabated—having been delayed, however, by one full year compared with the controls. By the end of the 36-month period, the extent of their cognitive decline was only half that of the mathematically predicted amount, and they had gained about 18 months worth of preservation of cognitive function relative to the prediction. In the authors’ words:

These data support the hypothesis that continuous galantamine treatment slows the rate of cognitive decline in AD patients for up to 3 years. . . . Together with findings from other studies, these results strengthen the argument for early diagnosis and treatment . . . .

It’s Never Too Early to Protect Your Brain

Surely early diagnosis and treatment make sense—but how early is early? One could argue that it’s never too early to be concerned about the possibility of serious cognitive decline somewhere down the road—it could be years in the future, or it could be just around the corner, even for those of middle age. Interpreting the symptoms can be tricky, though. After all, a certain amount of benign forgetfulness is a normal aspect of the aging process. No big deal, right?

Well, maybe, maybe not. Over a period of time, something more sinister can develop: the clinically defined condition called mild cognitive impairment (MCI), which exceeds normal forgetfulness but falls short of being outright dementia. MCI is a kind of “Alzheimer’s lite” that usually (but not always) leads to the real thing.* Just as there is no well-defined boundary between normal, age-related forgetfulness and MCI, there is none between MCI and AD. The transitions, if they occur, are seamless. By the time anyone notices that something is wrong, much damage may already have been done.


*By one estimate, more than 80% of patients with MCI develop AD within 10 years, at a rate of about 10–15% of patients per year.4


Because the symptoms of MCI are so similar to those of AD (just less severe), it seems reasonable to suppose that anything that retarded the progression of AD would do the same for MCI—and probably more effectively, since the cognitive deficits in MCI are smaller to begin with. That argues in favor of using galantamine early, as a kind of insurance policy against what could happen.

How to Be Smart

Well, you’ve read this far, so you must have been interested (thanks!). If you want more information, there’s a lot of it out there, in back issues of Life Enhancement (also available on our Web site) and elsewhere. Whether you’re man or woman, young or not so young, you’ll truly be a smart cookie if you decide to take appropriate action to help preserve and protect your precious cognitive functions from time’s erosion. Think of it as a way to help supplement the quality, and perhaps even the quantity, of your life.

References

  1. Raskind MA, Peskind ER, Truyen L, Kershaw P, Damaraju CRV. The cognitive benefits of galantamine are sustained for at least 36 months. Arch Neurol 2004;61:252-6.
  2. Olin J, Schneider L. Galantamine for Alzheimer’s disease (Cochrane review). In The Cochrane Library, Issue 2, 2001. Oxford: Update Software.
  3. Wolfson C, Wolfson DB, Asgharian M, M’Lan CE, Østbye T, Rockwood K, Hogan DB. A reevaluation of the duration of survival after the onset of dementia. N Engl J Med 2001 Apr 12;344(15):1111-6.
  4. Peripheral and Central Nervous System Drugs Advisory Committee of the U.S. Food and Drug Administration, as reported by Reuters Health, March 14, 2001.

Dual-Action Galantamine

Galantamine provides a heralded dual-mode action for boosting cholinergic function: it inhibits the enzyme acetylcholinesterase, thereby boosting brain levels of acetylcholine, and it modulates the brain's nicotinic receptors so as to maintain their function. The recommended daily serving ranges from a low of 4 to 8 mg of galantamine to begin with to a maximum of 24 mg, depending on the individual's response.

For an added measure of benefit, it is a good idea to take choline, the precursor molecule to acetylcholine, as well as pantothenic acid (vitamin B5), an important cofactor for choline. Thus it is possible to cover all bases in providing the means to enhance the levels and effectiveness of your acetylcholine.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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