Maintain Your Brain

An Exclusive Interview with Durk Pearson & Sandy Shaw®

Maintain your Brain the Durk Pearson & Sandy Shaw Way

First appeared in the May 2004 issue

ack in 1979, I read an article called “Mind Food” in a popular science and fiction magazine, OMNI, advancing the idea that nutritional supplements could enhance memory. This was a spanking new idea to me—it really caused me to sit up and pay attention. The authors of that article were Durk Pearson & Sandy Shaw, to whom we are grateful for their continued enthusiasm and insight and for what they have taught us over the last two decades.

Now it is 25 years later, and while many of us are still interested in cognitive enhancement or performance enhancement, we are rapidly growing more interested, owing to our age, in another aspect of this endeavor: the preservation of memory. It was with this thought that I stoked up the furnaces of Durk & Sandy’s minds and let the interview rip. I didn’t need to prompt them or keep them on track. Durk & Sandy had obviously prepared for the taping with a crystal-clear outline of what they wanted to say and where they wanted to go—a testimony to their ability to preserve their memories.

— Will Block

It’s Personal

Durk Preservation of memory is something very personal to me, because my mother had Alzheimer’s disease in her 80s and died of it at the age of about 90. We have heart disease under control, and cancer is becoming a more treatable chronic disease rather than a terminal disaster after you’re diagnosed. So we’re getting more concerned about keeping our brains functioning well—brain maintenance—because what’s the point of living to 100, 110, 120, or 130 if you lose your marbles when you’re 90 . . .

Sandy . . . particularly as the main focus of our lives is intellectual activities, and without having that mental capacity, life would be pretty dull.

Durk So about 25 years ago we started looking into what was known about Alzheimer’s disease and age-related memory impairment—how they develop, what can be done to treat them, and how to prevent them. In that regard, I think there’s going to be a paradigm shift; actually I think it’s starting to happen right now with Alzheimer’s. The paradigm shift is neuroprotection and prevention rather than treatment after the fact.

Paradigm Shift

Durk Let me give you an example of the tremendous difference that the paradigm shift from treatment to protection and prevention made in cardiovascular disease. A hundred years ago, people were not thought to have cardiovascular disease until they developed exercise-induced angina or they had a stroke or a heart attack.

There were some treatments for it, such as nitroglycerin, but in general they weren’t satisfactory. There was little progress for about 50 years, and then something interesting happened. During the Korean War, American soldiers who had been killed in combat—young soldiers in their late teens and early 20s—were autopsied and found to have atherosclerotic plaques. These plaques were smaller than what you would expect to see in people in their 60s, but they were there, and they were the same type of plaque.

Sandy And even though it was clear that these soldiers were under a great deal of stress, which might promote atherosclerotic processes, the plaque nevertheless indicated that cardiovascular disease could start early in life and was an ongoing process. Once it began, it could take decades before people would show any symptoms or suffer an acute event, such as a heart attack.

Durk That meant that cardiovascular disease as an ongoing process was caused by something, and people wanted to know what it was. If you understood the causal mechanisms, you could do something to prevent the development of the disease rather than wait for a heart attack before trying to treat it. One of the earlier examples of this approach was the Framingham Study, which tried to correlate what people ate over the course of their entire lives with cardiovascular outcomes; this was the first large-scale epidemiological study of cardiovascular disease.

The existence of atherosclerotic plaque had been known since Leonardo da Vinci described it in old people whom he had autopsied, but the idea that it started when you were young rather than at 50 or 60 was relatively new—and people started looking for mechanisms.

Sandy A large number of epidemiological studies examined what people were eating and what health outcomes they had. The data from these studies showed many correlations between cardiovascular disease and certain dietary patterns. But these were not proof of causation, they were just correlations—they couldn’t indicate that a particular diet caused cardiovascular disease. What was needed was an understanding of the chemical processes that resulted from eating foods that were, say, high in saturated fats and low in antioxidants, versus those that were not.

Durk We’re seeing the same sort of thing now with respect to Alzheimer’s disease. A German paper published in 1933 on people over 65 who had no signs of mental deterioration when they died reported that over 80% of them had amyloid plaques and neurofibrillary tangles in their brains at autopsy—the same things you see in Alzheimer’s disease (Gellerstedt 1933). This was ignored for a long time because (as the reasoning went), although these plaques and tangles were known to occur in people with Alzheimer’s, they couldn’t be the cause of the problem since over 80% of those over 65 had them, but 80% of those over 65 didn’t have Alzheimer’s.

Then in the 1960s, some other papers showed a dose-response relationship; that is, the more plaques and tangles you had, the greater your mental deterioration (Roth et al. 1966, 1967). Yet you had to have a certain substantial amount of plaques and tangles before the deterioration became evident. That still didn’t prove causation, but it was getting a little closer. In Parkinson’s disease, scientists had found that, although the dopaminergic nervous system starts deteriorating when a person is young, there has to be as much as an 80% loss of dopaminergic motor neurons before symptoms of the disease develop.

Sandy That’s because the brain has an amazing capacity for compensation. For example, there was a recent brain functional imaging study on the cognitive capacities of alcoholics versus normal humans. Long-term damage occurred in the alcoholics’ brains. Yet the study showed that, although the alcoholics (who were not drunk during the tests) and the normal people would get similar results in some cognitive tests, the way the alcoholic brain handled the problems was completely different from that of the normal brain. In the alcoholics, many more areas of the brain were activated in handling a particular cognitive problem in order to get the same result as the normal people. The alcoholic brains were compensating by activating more areas to do the work, so you might not see anything on the outside that looks different . . .

Durk . . . until you get to a critical point where the alcoholics can’t compensate anymore, and then things go bad really fast.

Sandy But the fact is that brain deterioration is occurring while excessive drinking is going on.

Galantamine and Acetylcholine

Durk It’s been known for quite awhile that a particular system in the brain is attacked in Parkinson’s disease: the dopaminergic neurons. In Alzheimer’s disease, it’s the cholinergic neurons that substantially die off, and one of the first ideas for doing something about this was to increase acetylcholine levels in the brain. One way of doing that is to give a person a cholinesterase inhibitor (cholinesterase is the enzyme that breaks down acetylcholine). If you inhibit that enzyme, you end up with higher levels of acetylcholine. All the FDA-approved drugs for treating Alzheimer’s disease have cholinesterase-inhibitor properties.

But there’s another thing that can be done, and that is to use a compound that increases cholinergic activity. Now, one of the ways to do that is to take galantamine. Galantamine is interesting because it’s a cholinesterase inhibitor and a nicotinic cholinergic agonist—that is, it acts like acetylcholine at the nicotinic cholinergic receptors (Woodruff-Pak et al. 2001). In clinical trials, it has been shown to be effective in treating and reducing the symptoms of mild-to-moderate Alzheimer’s disease (Dal-Bianco et al. 1991; Raskind et al. 2000; Tariot et al. 2000).

Galantamine has been a part of herbal folk medicine for a very long time. In Homer’s Odyssey, Circe poisoned Odysseus’s men with an anticholinergic drug—probably atropine, hyoscyamine, and/or scopolamine (all closely related anticholinergic compounds)—which caused them to lose their memories. They forgot about their families, about where they were going, about their voyage, about their duties to their city-states, and so forth. They just ended up eating, rolling around in the mud, wandering aimlessly about, and so forth; in effect, they acted remarkably like someone with advanced Alzheimer’s disease.


The common snowdrop (Galanthus nivalis)
Odysseus got his men out of this horrible situation by having them eat the bulbs of the snowdrop, a flower that comes up early in the spring, when there’s still snow on the ground (Plaitakis et al. 1983). The bulbs contain an alkaloid called galantamine that has proved to be useful in treating Alzheimer’s. Preventing Alzheimer’s, however, is surely preferable to merely treating it after the fact, just as preventing cardiovascular disease gains you a whole lot more than treating it after a heart attack.

The point here is that the cholinergic nervous system is a use-it-or-lose-it system. Cholinergic neurons, when active, produce neurotrophic factors that prevent them from dying off and that cause them to repair themselves. But if you don’t have much cholinergic stimulation, you don’t produce enough neurotrophic factors, and the cholinergic neurons start dying.


Active brains tend to stay healthy.
Sandy That’s one reason why people who use their minds a lot, particularity in verbal activities such as reading, tend to be more resistant to developing Alzheimer’s compared to people who don’t use their minds very much. People who are mentally active are stimulating the cholinergic neurons, keeping them alive.

Durk In fact, doctors who work with Alzheimer’s patients are starting to suggest that people exercise their minds to prevent or delay the development of Alzheimer’s. I think galantamine can act not only as a treatment but also—probably more importantly and effectively—as a prevention.

Choline and Acetylcholine

Durk One of the things that were tried quite early in treating Alzheimer’s disease was giving people the precursor compound choline. Yet the results were not impressive, and the reason for that is understood. If you wait until someone actually has symptomatic Alzheimer’s, you’ve got so much cholinergic neuron die-off that there isn’t much choline acetyltransferase produced any more (that’s the enzyme that converts choline to acetylcholine).

Sandy And without enough of that enzyme, you’re not going to get the acetylcholine, no matter how much choline you take.

Durk So, after waiting for Alzheimer’s to develop, choline is not going to be very effective as a treatment. As a preventive measure, however, increasing the choline in your diet—along with vitamin B5 (pantothenate), which helps convert the choline to acetylcholine—could be useful. In fact, there’s an interesting article that appeared in JAMA called “Decreased Brain Choline Uptake in Older Adults” (Cohen et al. 1995). It showed that, as you get older, the ability of choline to enter your bloodstream is essentially unchanged. However, its ability to cross the blood-brain barrier into your brain drops dramatically. At the age of 65 or so, you may have only about 30% of your young-adult capability for transporting choline across the blood-brain barrier. This can be a real problem.

A few years ago, The Institute of Medicine recommended that choline be made an essential nutrient for humans, with a dose of 550 mg/day for men and 425 mg/day for women. Most American diets don’t provide that much. When you consider that your ability to transport choline into your brain drops by about 70%, your brain is going to be drastically choline-deficient by age 65 unless you’re taking a much larger choline supplement.

So, as part of our new brain-maintenance formulation, we provide 2 to 3 grams of choline per day in the form of a tasty drink mix. Even with a 70% reduction in the transport of choline into your brain, this will still give you choline levels that are higher than you would have had as a healthy young adult. We’re making sure that your brain isn’t starved for choline, because there’s a very serious consequence to that: not only can’t you make enough acetylcholine—which can cause neurons to die off—but insufficient choline can precipitate a cannibalistic process in your brain.

Sandy The brain can make choline only in small quantities, so it needs to get more from another source. It breaks down neuronal membranes, which contain phosphatidylcholine, one of the essential elements of the membranes. So it’s possible to maintain choline supplies by cannibalizing the neuronal membranes, but at the price of destroying the neurons (Wurtman 1992). Obviously you don’t want that sort of thing going on, and that’s a good reason to be taking a choline supplement.

Durk You should take two to three servings of our choline and vitamin B5 drink mix per day as an essential part of our brain maintenance and prevention program. And I’m glad to say that Sandy and I have been using this formulation in one form or another since the 1970s. Of course, back then we hadn’t figured out how to make it taste good—choline tastes absolutely hideous—but we kept taking it anyway because we wanted to make sure that the choline levels in our brains were really high. Moreover, our choline drink mix (which now tastes great) also has pantothenate to help convert the choline to acetylcholine.

Thus, we have two different kinds of cholinergic agents in our brain maintenance and prevention program. We have galantamine, which, acting as a cholinesterase inhibitor, retards the breakdown of acetylcholine and also acts as a nicotinic cholinergic agonist (stimulates the nicotinic cholinergic receptors, as acetylcholine does). And we have choline itself and vitamin B5 (pantothenate), which helps transform the choline to acetylcholine.

Why didn’t we just put the choline and pantothenate into capsules with the galantamine and the other relatively low-volume ingredients (see below)? We tried, but it required so many capsules that it caused mechanical discomfort in our stomachs. By formulating the high-volume ingredients, such as choline, pantothenate, and taurine (see Part II), as a drink mix, we were able to put the daily amount of galantamine and everything else into six size-0 capsules. Simply stir a tablespoon of our choline-containing drink mix into cold water, and use it to swallow two of the capsules. Do this two or three times per day.

Amyloid-Beta, Neurotoxicity, and Free Radicals

Durk But there’s actually a lot more going on. Mechanisms of damage in Alzheimer’s disease have been studied for a long time—over half a century. No one knew whether the amyloid-beta (also called beta-amyloid) plaques were just a consequence of the underlying disease or whether they had any causative effect in creating harm in the brain. Well, it’s been learned relatively recently that the amyloid-beta in the plaques does cause serious harm.

Sandy It’s neurotoxic, in fact.

Durk You can grow cholinergic neurons in tissue culture. If you add amyloid-beta to them, it kills them. The mechanisms have been studied extensively; they involve, at least in part, glutamate excitotoxicity and increased production of free radicals, which induce apoptosis in the cholinergic neurons.

Sandy Apoptosis is programmed cellular self-destruction, a kind of cell suicide.

Durk Worse than that, the free radical stress in these neurons causes the production of more amyloid-beta, and that in turn increases the free radical stress, which causes even more amyloid-beta to be produced, which . . . and you eventually end up with an exponential crash in your brain, where your cholinergic neurons get fried by free radicals produced by ever greater quantities of amyloid-beta. Obviously, you want to prevent this from happening. Fortunately, your brain has a limited ability to get rid of amyloid-beta—to remove and destroy it. Once you exceed a certain point, however, this positive feedback loop results in creating it faster than you can destroy it, and it builds up faster and faster, until you eventually develop symptomatic Alzheimer’s disease. (See Christen 2000 for a review of oxidative stress and Alzheimer’s.)

CONTINUED IN PART II

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CONTINUED IN PART II

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