DURK: Everything that happens in your brain … every memory … every thought … every emotion … every innovation … every “wow, that’s great!” … is a result of the release of neurotransmitters. Neurotransmitters are not drugs; they are natural substances made by nerve cells in your brain that transmit messages from one nerve cell to another across the synapse that divides them. That’s why they are called neurotransmitters. They are made the nutrients in your diet, but there is a very good chance that even if you have a good diet, you’re not getting the optimum amount of the raw materials that your brain can use to make neurotransmitters.
The three most important neurotransmitters have been known for a long time: acetylcholine, noradrenaline, and dopamine. Acetylcholine is involved in memory and organization—the way you order things in your mind, the way you retrieve them in an orderly manner. It’s also involved in focus and concentration. A good example of what happens if you don’t have enough cholinergic activity can be found in a person who has taken the psychoactive drug atropine or any other anticholinergic drug. In many respects, they resemble someone with Alzheimer’s disease.
The latter are people who have suffered extensive damage to their cholinergic nervous system: they lose their memories, lose their focus, and lose their ability to concentrate.
What do you do to improve your cholinergic memory? Take choline and Vitamin B5. The vitamin B5 (also known as pantothenate) acts to convert the choline to acetylcholine more efficiently. Now there’s a very good reason to take choline as you get older, because as you get older the ability of your blood-brain-barrier to actively transport choline from your bloodstream into your brain drops dramatically. By the time you’re in your 60’s most people have perhaps 20 or 30 percent of their young adult capability of transporting choline from the blood stream into your brain.
SANDY: You can compensate for this by taking a choline supplement, choline plus vitamin B5, making it possible for more choline to be transported into your brain.
DURK: And if you don’t do this, something very unfortunate happens as you get older. The cholinergic system is a “use it or lose it” type system; that is, it requires continuous cholinergic stimulation to release neurotrophic growth factors. Without neurotrophic growth factors the cholinergic nerves start dying off. In fact, in order to make acetylcholine as you get older, your brain will start cannibalizing other brain cells for the choline contained in the cell membranes as phosphatidylcholine. Eventually, you start losing your cholinergic nervous system. You don’t notice the results of this immediately. Typically, it takes about an 80 percent neuron loss before people notice that they are doing more than just slowing down. Their memory isn’t quite as quick as it used to be or as sharp; it takes more time to do things. As time goes on, simple memory tasks become more and more difficult. So to keep your mind working properly especially as you get older or especially if you’re working very hard—like cramming for a test—you need more of these raw materials to make acetylcholine.
WILL: What is a good amount of choline and vitamin B5 to compensate for the loss, especially with age?
DURK: The U.S. Government asked the Institute of Medicine to determine whether choline was an essential nutrient or not. And they found that—yes—it is an essential nutrient for human beings; you can make a limited amount in your liver, but that’s not enough even when you’re young.
SANDY: They determined that about 550 mg a day would be required for a male adult.
DURK: And 425 mg for an adult female. However, all their data was derived from young college students who acted as subjects in medical experiments. They didn’t consider the fact that as people get older, their ability to transport choline into the brain—which is a major user of choline—is impaired. We think people should start out, for the first week, taking about 1 g of choline, and 2/3 of a gram of pantothenate each day. During the second week, these amounts should be doubled to 2 grams of choline and about a 1 1/2 gram of pantothenate per day. And in the third week, go to 3 grams of choline a day and a couple of grams of pantothenate per day. Now, it wouldn’t harm you to immediately jump to 3 grams per day. It’s just that you might possibly end up with a little constipation or tension headache because acetylcholine is what makes your muscles contract as well. If you take too much too fast, quicker than your body can adapt to the increased amount, you may end up with excessive muscle tension. The first symptom of this muscle tension is usually a stiff neck. I might add that choline is also important for cardiovascular health as well. One of the major risk factors for somebody dying of a heart attack is the inability of their heart to slow down rapidly after exercise. This pulse rate reduction is due to cholinergic stimulation by the vagus nerve. If you don’t have enough choline in your diet, you may be at increased risk for this particular problem.
SANDY: Acetylcholine is also involved in the relaxation of arteries. Which is another one of the things that deteriorates in the development of atherosclerosis; arteries simply do not dilate properly and as a result, your ability to control blood pressure is reduced.
DURK: In fact, the mechanism by which acetylcholine helps dilate arteries is by turning on an enzyme called nitric oxide synthetase found in the lining of the arteries. This enzyme turns the amino acid arginine into nitric oxide which then causes the arteries to dilate. That’s the same mechanism that gives you erections as well. Acetylcholine is involved in muscular contraction. You may think that if you have very intense and prolonged muscle contraction—like running a marathon—you might run low on choline and not be able to make the optimum amount of acetylcholine? And the answer to that is, absolutely yes.
SANDY: In long marathons, choline resources are limited.
DURK: It has been found that giving marathon runners choline, which is completely legal under athletic association rules, that you can run a marathon a little bit faster. And that is a lot when the time separating the winner from the second best may only be a matter of seconds. So especially as you get older you want to be sure you’re providing your brain with adequate amounts of choline and vitamin B5 to be sure you can make acetylcholine to help maintain youthful type mental function, rather than slowly tapering off into the sunset.
WILL: We reported recently on a paper in the American Journal of Clinical Nutrition that showed a correspondence between choline deficiency and high homocysteine levels.
DURK: Yes, in fact choline is involved in converting homocysteine back into cysteine. Homocysteine… you think of toxic byproducts as being something that oil refineries or automobiles make when they burn fuel. Yes, they make toxic byproducts, but—surprise … surprise—your own body makes toxic byproducts as well. And one of them is homocysteine. And in fact, choline can act as a methyl group donator to turn homocysteine—which can cause atherosclerosis and is associated with strokes—back into cysteine, which is a useful antioxidant nutrient amino acid, unlike homocysteine which is pro-oxidant and is causally involved in causing an increase in the incidents of strokes as well as hypertension.
WILL: Moving over to the other two neurotransmitters …
DURK: Noradrenaline is nature’s natural speed. It is your “get up and go” juice. But unlike speed, it doesn’t cause free radical damage that burns out the neurons in your brain. Noradrenaline … if you have enough of it you’re full of energy, you’re excited, you’re self confident. If you don’t have enough of it …
SANDY: You can be depressed, but you’re certainly going to be having less energy, less drive. You may just lose interest in doing most things.
DURK: If you have a hard time getting out of bed in the morning and maybe even feel like you’d like to go jump out a window, except its too much trouble…. chances are you’re suffering from an inadequate supply of noradrenaline. Now, if you’re seriously depressed you do need to go see a doctor because there are a lot of other things that could be responsible. Such as hypothyroidism or some things that are a lot more complicated like too much cortisol being produced.
But in the case of people who, getting older, don’t have the spring to their mental step they did when they were teenagers, it’s because their noradrenaline levels drop off with age. And noradrenaline also causes the release of neurotrophic factors that help the noradrenergic nerve grow as well. So again, it’s a case of “use it or lose it.” Fortunately, you can make noradrenaline from either the essential amino acid tyrosine or the nonessential amino acid phenylalanine. You also need the help of some essential nutrients, specifically vitamin B6, C, and the mineral copper. And a lot of people are deficient in copper; a lot of people aren’t getting the RDA of copper. So its not surprising that the number one complaint people bring to their physicians is they just don’t have enough energy. And part of it may be because they’re only getting 6 hours of sleep a night, and part of it may be because they’re getting older and they’re making less noradrenaline.
Now in our formulations, we use phenylalanine rather than tyrosine because you cannot convert tyrosine into a neuromodulator called beta-phenethylamine. Neuromodulators modulate the effect of neurotransmitters, they turn up the effects or turn them down. Beta-phenethylamine turns up the effects of noradrenaline and by giving the person a phenylalanine, vitamin B6, copper, vitamin C combination, we’re actually able to give people the system of nutrients that their brain can use to make more beta-phenethylamine and more noradrenaline. So if you’re “get up and go” has “got up and went,” get yourself one of our formulations with the phenylalanine and the necessary nutrient cofactors to make it into noradrenaline.
WILL: Would you say that beta-phenethylamine is kind of a kick start modulator?
DURK: It sure is … and in fact it is thought to be involved in the mechanism, the euphoria of being in love. Beta-phenethylamine levels do go up when people are in love, but I’ll also add that it’s found in chocolate. Chocolate is probably your richest food source of it. But you can make the stuff in your brain if you have adequate phenylalanine (not tyrosine), vitamin B6 and adequate copper which we provide in all of our phenylalanine-containing formulations. Now, noradrenaline works very well in conjunction with caffeine. That first cup of coffee you drink in the morning gives you a real lift. It makes you work faster and harder and more accurately and with less effort. Yet, by the middle of the afternoon, drinking another cup of coffee may just make you space out, jittery, nervous, bad tempered. What’s going on here is pretty simple. There are two mechanisms by which caffeine works. One is that it antagonizes adenosine receptors and this is something we won’t get into, but it is one of the mechanisms by which caffeine keeps you awake. Another is that it makes you release noradrenaline in your synapses and also makes you more sensitive to noradrenaline because it preserves the effect of the second neurotransmitter, cyclic AMP…
SANDY: It’s called the second messenger.
DURK: Noradrenaline crosses the synaptic gap, and the reason it produces a signal in the receiving nerve is that is causes the production of cyclic AMP, the second messenger. Caffeine slows the rate at which the cyclic AMP is destroyed. Just like Viagra® slows the rate at which nitric oxide-stimulated cyclic GMP is destroyed. And so you get a stronger message. If you take a little bit of caffeine along with the phenylalanine and cofactors combination, you get a much better lift, and much longer lasting lift than taking just the caffeine alone. In fact, Sandy and I always take our choline formulation and our phenylalanine plus cofactors plus a little bit of caffeine formulation before we do any lectures and that’s the reason we’re able to remember all of this stuff and put it together in a way people can understand.
SANDY: We’ve discovered by experience that getting up far earlier than we normally do in the morning and having to do television shows during which you’re lucky if you get two minutes, you have to talk very fast, and have answers to questions. Meaning, you can’t spend any time thinking about the answers. Do this all day and it totally fatigues you; you’re depleting your supply of neurotransmitters like acetylcholine and noradrenaline and you just don’t have the ability to do a very good job of answering questions real fast. So that is originally how we developed these formulas, in order to help us to perform better while we were on publicity tours for our first book, Life Extension: A Practical Scientific Approach.
DURK: We developed a choline formulation back in the late 1970’s and it had a dramatic effect on Sandy. We started writing the book in ’78 and didn’t yet have a word processor so we were typing all of this stuff up. I literally had to take scissors and cut Sandy’s stuff apart and reassemble it in a different order. What she said was right but not well organized and it was literally cut and paste. Naturally, Sandy got a bit pissed off about that but once she started taking the choline supplement it was like everything flowed in the proper order. It was all organized when it came out of her fingers to the typewriter.
SANDY: It was effortless. It was one of those things that if youre a writer and the words are flowing it just feels completely differently than when you’re writing and it feels as though you’re squeezing the last toothpaste out of the tube.
DURK: We had our choline formulation for the first tour for Life Extension, but we had not yet developed the phenylalanine plus cofactors formulation. And after 5 weeks on the road doing all those TV and radio shows, newspaper, magazine interviews—boy—“our get up and go” “got up and went.” So we decided to figure out what was going; we were using noradrenaline a heck of a lot faster than we were able to make it. So we fixed that by providing the right formula to enable us to make more and the next tour was so much easier.
SANDY: It was easier to do a good job all day and we felt better at the end of the day….we weren’t as fatigued.
WILL: How much phenylalanine do you recommend people take on a daily basis? Or is it dependent upon what they’re doing?
DURK:Well, it depends on what they’re doing. For example, I particularly like a version of our formulation which has green tea polyphenols in it that are potent antioxidants, and have some psychoactive effects … they make colors brighter, make you feel cheerful, they’re a natural upper. In addition, it has phenylalanine and cofactors and 40 mg of caffeine which is the same amount you would get in a Coke®—which is actually about 50 mg. It’s the same amount you have in two cups of green tea. I normally use about 2 servings a day. One as soon as I get up, and the other in mid-afternoon when I start slowing down. But if I’m doing something really complex and mind numbing, like filing out my income tax with schedule A, B, C, D, E and F, I’ll use more. When I’m doing something really mind numbing like that or writing for a deadline, I may consume 5 or 6 servings a day. However, you don’t want to take it too close to bedtime or you are not going to get to sleep.
Now if you don’t like the effects of caffeine, we have our formulation, which has the phenylalanine and cofactors, but no caffeine. There are some people who are sensitive to caffeine and don’t like it. If we have to do a lecture at 10 o’clock at night, we’re certainly not going to take caffeine because we won’t get to sleep that night, but we will take phenylalanine along with our choline plus vitamin B5 formulation.
WILL: I’m curious, has anyone every attempted to determine the essentiality of phenylalanine or tyrosine, and set daily values? And if not, why not?
DURK: Well, tyrosine is an essential nutrient. And phenylalanine can be converted to tyrosine in your body so that is not considered an essential nutrient because you can replace it with tyrosine. However, as I mentioned tyrosine doesn’t help you make beta-phenethylamine. Scientists conducted a double-blind, placebo-control study on human beings that were subjected to very long hours of hard work; they were basically taking a test for several hours. They found that the tyrosine was an anti-fatigue agent that didn’t produce an excitatory effect, it didn’t act as an upper whereas the phenylalanine acted both for anti-fatigue and as an upper. So we prefer the phenylalanine for that reason.
WILL: You recommend between 1 and 3 grams of choline plus cofactors per day. What are your recommendations for phenylalanine plus cofactors?
DURK: For phenylalanine, it depends on the individual. Any where from half a gram to 3 grams per day. And I might add the choline plus vitamin B5 formulation can be taken at any time, including with food though of course, if the food remains in your stomach while being digested for awhile, there will be a delay before the choline is absorbed. In the case of the phenylalanine plus cofactors supplement, for best effects you want to take that on an empty stomach because other large amino acids in the diet can interfere with the passage of phenylalanine across the blood brain barrier.
SANDY: Certain amino acids compete to be carried across and there is limited capacity for carrying them …
DURK: For example, if you eat a big hamburger you could easily get yourself a half a gram of phenylalanine, however its likely to put you to sleep rather than waking you up because there are other things in there like the amino acid tryptophan that will interfere with phenylalanine crossing the blood brain barrier and that acts as a sedative. So you want to take phenylalanine on an empty stomach.
WILL: What about dopamine?
DURK: Now dopamine is closely related to noradrenaline; dopamine is involved in memory and motor coordination and…
SANDY: And it’s also involved importantly in reward. Whenever you do something that makes you feel good about doing it; that is due to release of dopamine.
DURK: In fact, the reason that opiates are rewarding is that they cause the release of dopamine in part of your brain. You might think that everything that’s going to give increased amounts of dopamine is going to be potentially addictive. The answer to this is “no, it isn’t” and for a very simple reason. The dopamine can be made from tyrosine and phenylalanine, so when you take our phenylalanine plus cofactors you’re able to make more dopamine too. And why isn’t this addictive? It has very simply been a normal part of the diet for a billion years. The bugs have been worked out. When you take something like opium, which hasn’t been a part of the diet, you can get into trouble, like addiction. When you take phenylalanine, you’re not going to have that problem because all of those problems are buried back about a billion years. A good example of what happens when you don’t have enough dopamine is Parkinson’s disease. In addition to problems with memory, the person is very unhappy because their reward system isn’t working, and further, they lack adequate motor coordination. In general, there is a real detriment in the quality of life. And again, this is something that happens gradually as you get older. You don’t start getting Alzheimer’s disease or Parkinson’s the day you’re diagnosed.
SANDY: Actually, you have to have about 80% destruction of the dopamine neurons before you notice any symptoms of Parkinson’s. So what that means is that by the time Parkinson’s shows up, you’ve already suffered the majority of the damage you’re going to experience.
DURK: And our formulations can be helpful in getting you off stimulants such as cocaine, because cocaine works by causing a release of noradrenaline and blocking the synaptic reuptake and recycling of dopamine. So you only temporarily have more noradrenaline and dopamine. The problem is very simple: cocaine doesn’t help you make any more neurotransmitters, and so you get the same effect, you have to take more and more and more…
SANDY: Your supply gets depleted in addition to the free radical damage that takes place. And when you deplete your noradrenaline and dopamine supply you suffer a crash—the notorious crash that takes place for people who use cocaine or speed. And at that point, people can become extremely depressed and it’s a very serious problem.
DURK: In fact we knew a very talented rock singer who wrote very energetic, speedy music and he was hooked on methamphetamine, and he knew it was killing him. He asked us if we knew anything that could help. He didn’t like the effects of caffeine at all, so we suggested the use of phenylalanine and suggested that this might help him use less. He surprised us by going off meth entirely. He was able to kick speed and continue to write energetic music through the use of phenylalanine. We certainly don’t want to guarantee that will happen to everyone, but if you’re using stimulants, I might suggest that the phenylalanine formulations might really help you reduce the amount you’re taking or help you find something you like better.
WILL: Are there any other neurotransmitters worth mentioning?
DURK: Yes, nitric oxide which is made from arginine. In fact, it is a neurotransmitter. Acetylcholine, noradrenaline, and dopamine have been known for three quarters of a century, whereas knowledge of nitric oxide as a neurotransmitter is much more recent. It’s important in learning and memory and the mechanism by which a short term memory is turned into a long turn memory has only been known for about 15 years. And nitric oxide is also involved in learning a new motor sequence; for example, if you want to learn to play golf you want to have plenty of arginine in you.
SANDY: Nitric oxide is also needed to allow your arteries to dilate, to widen, in order to allow more blood flow. This is the way your body is able to adjust blood flow to areas that need more such as muscles during muscle activity.