Galantamine Boosts Brain Acetylcholine

Galantamine Improves Both
Alzheimer's and Vascular Dementia

Dual mode of action of this natural supplement accounts for its
exceptional ability to restore and maintain acetylcholine function
By Will Block

rose by any other name would smell as sweet," said Shakespeare, whose way with words was surely touched by angels. With apologies to the Bard, consider this snappy line: "An acetylcholinesterase inhibitor that's also a nicotinic receptor modulator would be more effective." (Apology not accepted. - W.S.) But you knew that, right? Oh . . . well, then, we'll explain it - it's easy, once you get past the big words.

The words pertain to the treatment of dementias, of which Alzheimer's disease is the most prevalent type. It is widely acknowledged that the most effective treatment for this dread disease is through the use of compounds called acetylcholinesterase inhibitors, whose effect is to boost one's brain levels of the neurotransmitter acetylcholine. Several such agents are currently being sold as prescription drugs in the United States - notably donepezil, rivastigmine, and galantamine (another one, tacrine, is rarely used any more, owing to its dangerous side effects).

Galantamine Is the Most Effective

There is much clinical evidence showing that the natural compound galantamine is the most effective of these agents, for reasons that we have written about in previous issues of Life Enhancement. In a nutshell, galantamine's special advantages are:

  • Long-term efficacy - Galantamine works as well as or better than donepezil and rivastigmine as an acetylcholinesterase inhibitor (AChEI), in part because, unlike those drugs, it does not induce drug tolerance. That means that the body does not become increasingly tolerant of it (which is to say, resistant to it), thereby causing it to become less and less effective. A major part of the reason for this virtue of galantamine has to do with its other principal virtue:
  • Modulation of nicotinic receptors - Galantamine does something the other AChEIs do not do: it modulates certain key receptors on our brain cells, called nicotinic receptors, in such a way as to preserve both their numbers and their functional integrity (this is important because nicotinic receptors are the primary receptors for acetylcholine). Absent this protective action, the nicotinic receptors in Alzheimer's disease tend to deteriorate over time, and that contributes to drug tolerance with the other AChEIs. The symptoms of Alzheimer's disease thus gradually become worse.

Considering that galantamine (which is derived from certain flowers) is the most effective available anti-Alzheimer's agent, it is all the more remarkable - and fortunate for the general public - that it can be obtained not just as a prescription drug but also without prescription as a nutritional supplement, because that is exactly what it is. How many prescription drugs can you think of that are also available in this way as the same chemical compound with the same biological activity, and, not incidentally, at much lower cost?

Galantamine Improves Cognitive Functions and More

Galantamine is not a cure for Alzheimer's disease - tragically, there is no cure, and the cause is not known either. Galantamine has, however, shown long-term benefits in combating the disease by halting its progression and even bringing about improvements in several important areas: cognitive function (including memory), behavior, and activities of daily living (the ability to perform ordinary and necessary tasks, such as eating, washing, and dressing).1,2,3 Although numerous studies have demonstrated galantamine's effectiveness in Alzheimer's disease, there has been less research done on its effectiveness against the second most common form of dementia, vascular dementia.

Vascular Disease Affects the Brain and the Heart (and More)

The cause of vascular dementia is well known: it is cerebrovascular disease, which is the brain's equivalent of cardiovascular disease - a disease of clogged arteries that impair blood flow to vital organs, contribute to high blood pressure, and act as time bombs, waiting to unleash a crippling or fatal event, such as a heart attack or stroke. The disease is relatively easy to prevent through diet and exercise, and it's even reversible to some degree.


Galantamine has shown long-term
benefits in combating Alzheimer's
by halting its progression and
even bringing about improvements
in several important areas.

Since our cerebrovascular and cardiovascular systems are just two parts of one vast, interconnected system of blood vessels,* it should not be surprising that disease in one part of the system is often accompanied by disease in other parts as well. This is not always true, however, because different parts of the vascular system are, well, different in various ways and do not necessarily respond equally to the things we do and the stuff we eat. Still, it's a useful generalization that if you have cardiovascular disease, you probably have cerebrovascular disease too, and vice versa. Thus, if you're at risk for a heart attack, you're probably also at risk for a stroke, and vice versa. (You would do well to take this warning to heart - and mind.)


*How vast is it, you say? Well, if you added up all the arteries, arterioles, capillaries, venules, and veins in one human vascular system, it would come to about 60,000 miles of blood vessels. Almost all of that is capillaries - they're very short, but there are about 40 billion of them (it took days to count them).


Vascular Dementia Often Accompanies Alzheimer's Disease

Vascular dementia is often caused by stroke - a major one or, more often, a series of minor ones called mini-strokes, which can cause damage to one or more regions of the brain when the neurons (brain cells) are deprived of oxygen. The damage tends to be cumulative, as are its effects on cognitive function. The cognitive decline caused by vascular dementia does not progress steadily, as it does in Alzheimer's disease, but often in an irregular, stepwise fashion at long intervals. These different patterns reflect the different ways in which damage to the brain occurs and accumulates in the two diseases.

Ultimately, the damage becomes manifest through the symptoms of dementia - chiefly cognitive impairments, including loss of memory. But which dementia, Alzheimer's or vascular? It's not always easy to tell, especially when, as often occurs in older people with dementia, these two major types coexist. They share several vascular risk factors, such as cerebrovascular disease and high blood pressure, and both produce various kinds of pathological changes in the brain that are related to the symptoms of dementia.

Galantamine Tested on Both Types of Dementia

These problems confronted the designers of a large clinical trial of the efficacy of galantamine in patients with a diagnosis of Alzheimer's disease with cerebrovascular disease (i.e., the two conditions together) and probable vascular dementia (which implies having cerebrovascular disease, because that is the cause of this form of dementia).4 This was a 6-month, randomized, placebo-controlled, double-blind trial undertaken in ten countries and coordinated by the authors of the paper, who are from Finland, Germany, Canada, the United Kingdom, and the United States.

The subjects of the study were 592 patients (men and women, average age 75) who were chosen using the best available diagnostic techniques for determining dementia status. In the galantamine group (396 individuals), 48% had Alzheimer's disease with cerebrovascular disease, 43% had probable vascular dementia, and 9% had an intermediate diagnosis (dementia, but unspecified). In the control group (196 individuals), these percentages were almost identical. In both groups, about two-thirds had concomitant cardiovascular disorders, which, as we have seen, is pretty much to be expected.


The patients taking galantamine
showed significant improvements in
both types of dementia, relative to
baseline, i.e., they gained ground.

Galantamine or placebo was administered orally, twice daily, following a dose-escalation schedule (see the sidebar, "Take Galantamine Slow and Easy," for details) that culminated in a daily dose of 24 mg after the first 6 weeks of the trial. The patients were evaluated several times, using a number of internationally accepted, standardized test protocols, on measures of cognition, global functioning (a clinician's interview-based impressions of change, plus input from the patient's caregiver), behavioral symptoms, and activities of daily living.

Take Galantamine Slow and Easy

For some people, galantamine takes awhile to get used to, so a gradual increase in dosage is the best approach. Doctors call this dose escalation. In the study described in the accompanying article, the initial dose was 4 mg/day, and it was increased by an additional 4 mg/day at 1-week intervals until, after 6 weeks, it was 24 mg/day. That dose was maintained for the remainder of the 6-month study.

Nonetheless, the galantamine treatment produced some side effects, primarily gastrointestinal upsets, such as nausea. Although most of the side effects were only mild to moderate and of short duration, they occurred more often in the galantamine group than in the control group.

Significantly, however, these effects occurred more often during the dose-escalation period of the trial than during the ensuing maintenance-dose period. For example, the weekly proportion of galantamine-treated patients having nausea during the dose-escalation period was 3.2%, on average, whereas subsequently it was only 0.5%.

Clearly, the dose escalation was too fast. The authors suggested that a better scheme may be to start with 8 mg/day and increase the amount by an additional 8 mg/day at 4-week intervals until the desired level is reached.1 Thus, one would be taking 16 mg/day (generally regarded as an effective dose) after 4 weeks. That's actually the same as in the study discussed here, but the increase to 24 mg/day - if desired or if recommended by a doctor - would not occur for another 4 weeks instead of another 2 weeks. This somewhat slower dose-escalation scheme has been well accepted in all countries where galantamine has been introduced.

  1. Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C. A 5-month, randomized, placebo-controlled trial of galantamine in Alzheimer's disease. Neurology 2000;54:2269-76.

Galantamine Enabled Patients to Gain Ground

After 6 months, the results were in: galantamine showed a positive therapeutic effect in all key areas of cognitive and noncognitive abilities in the demented patients. The improvements noted were of similar size to those seen previously in galantamine studies on patients with Alzheimer's disease.1,2,3

In the present study, the patients taking placebo showed a disease progression typical of what would be expected in their respective types of dementia: those with combined Alzheimer's disease and cerebrovascular disease experienced a steady deterioration of function, whereas those with probable vascular dementia did not, because that disease tends to proceed (as mentioned above) in irregular steps at long intervals - particularly in this group, which was selected in part on the basis of having a relatively stable form of the disease with a low risk of further stroke.

By contrast, the patients taking galantamine showed significant improvements in both types of dementia, relative to the baseline values measured at the outset of the study, i.e., they gained ground. This kind of improvement in the Alzheimer's group is particularly gratifying, because with other anti-Alzheimer's drugs, the best one can usually hope for is to stop losing ground, i.e., to hold steady, for about 6 months (after which the drugs start to lose their effectiveness).

Galantamine - Available to All

Thus, galantamine has demonstrated yet again that it is effective (and safe) in the treatment of dementia. In the authors' words,

Galantamine has shown broad, sustained efficacy in patients with mild to moderate Alzheimer's disease, and this efficacy is not compromised by concomitant cerebrovascular disease. The subgroup of patients with probable vascular dementia who were treated with galantamine in this study showed significant improvement in cognition . . . . the results observed with galantamine in our study represent an important finding for this subgroup of patients and provide evidence of efficacy further to those in previous trials with other cholinergic agents. The broad benefits of galantamine may reflect its novel mechanism of action.

For those whose lives have been touched, one way or another, by the scourge of dementia, it should be reassuring to know that galantamine, a natural nutritional supplement with a history of use going back several thousand years, is readily available to anyone who wants it. That is as it should be.

References

  1. Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C. A 5-month, randomized, placebo-controlled trial of galantamine in Alzheimer's disease. Neurology 2000;54:2269-76.
  2. Raskind MA, Peskind ER, Wessel T, Yuan W, and the Galantamine USA-1 Study Group. Galantamine in AD: a 6-month, randomized, placebo-controlled trial with a 6-month extension. Neurology 2000;54:2261-8.
  3. Wilcock GK, Lilienfeld S, Gaens E, on behalf of the Galantamine International-1 Study Group. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: a multicentre randomised controlled trial. Brit Med J 2000;321:1445-8.
  4. Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial. Lancet 2002 Apr 13;359:1283-90.


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


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