Food & mood.

Can what you eat make you happy, sleepy, or alert?

Do the nutrients in so-called "smart drinks" improve your memory, give you energy, or satisfy your appetite?

"It may surprise some people to learn that many food constituents can actually affect the chemical composition of the brain," says Richard Wurtman of the Massachusetts Institute of Technology. Among those constituents: certain amino acids (the building blocks of protein), choline (which isn't, but perhaps should be, considered an essential nutrient), and ordinary old carbohydrates.

Wurtman's findings are preliminary. He believes that some food constituents should be studied further, and that they should be regulated and sold as drugs.

You may or may not agree. Either way, his results are fascinating.

Q: Does what we eat affect our behavior?

A: Yes. That's because many food constituents can modify the production or release of neurotransmitters--the chemicals that carry signals from one nerve cell to another.

There are 30 or 40 neurotransmitters that are used by the ten million cells of the brain. Five or six can be affected by nutrients.

Q: How?

A: Nutrients are precursors of neurotransmitters, And in some cases, having more of the precursor means more of the neurotransmitter is produced.

Q: Can you give me an example?

A: Carbohydrates cause the pancreas to release insulin into the bloodstream. That lowers the blood levels of all amino acids except tryptophan, Tryptophan has to compete with some of the other amino acids in order to pass through the blood-brain barrier. So when the others get lowered, more tryptophan passes into. the brain. The brain cells convert tryptophan to serotonin, which is a neurotransmitter. From studies on drugs that increase serotonin levels in the brain, we know that it facilitates sleep, diminishes pain, and reduces appetite.

Q: Do all proteins keep tryptophan out of the brain?

A: Yes, and the more you eat, the more tryptophan gets blocked.

Q: Does that mean that a high-carbohydrate meal will make you calmer and more efficient?

A: It depends on when you eat it. If it's at dinner, it will relax you. A high' carbohydrate lunch may make you sluggish. When researchers fed a group of volunteers either a high-protein or a high-carbohydrate lunch, at least for those over 40, the high-carbohydrate lunch increased the number of mistakes they made in the afternoon. It made them sleepy.

Q: Do any other foods affect the brain?

A: Probably not. But some individual nutrients do.

An example is tyrosine, another amino acid. Pure tyrosine can increase the production of two neurotransmitters--dopamine and norepinephrine--as well as epinephrine, which is released from the adrenal gland when blood sugar falls too low or when you are under severe physical stress or acute, psychological stress that's great enough to raise your heart rate.

We rarely have enough change in tyrosine levels with normal food, but if you administer it alone, it can increase the production of neurotransmitters. Its actual effect on the brain depends on the state of the nervous system.

Q: What do you mean?

A: It works best on nerve cells that are firing frequently. For example, if a rat has high blood pressure, some of its brain cells are firing rapidly in an effort to lower the pressure. So if you give the rat tyrosine, it lowers its blood pressure.

On the other hand, if the rat is hemorrhaging, its blood pressure is low, and tyrosine has the opposite effect. Then the sympathetic nerve cells outside the brain are firing in an effort to raise blood pressure. And if you give tyrosine, it works on those cells, helping them raise blood pressure.

Q: What happens in humans?

A: In humans, tyrosine has anti-stress effects. It increases scores on performance tests. The Air Force is testing its ability to enhance performance under stress. That's because tyrosine is a precursor of norepinephrine, and in stress situations, nerve cells release ngrepi-nephrine faster than they can produce it, and ultimately run out.

Q: And does that mean blood pressure drops?

A: Yes. Norepinephrine keeps blood pressure up throughout the body. In the brain norepinephrine helps maintain vigilance, or the ability to focus. So when it runs out, attention is diminished.

Q: Is that good enough evidence to say that tyrosine offers some benefit?

A: In none of these cases will I say that any of these nutrients should now be used to treat disorders, because we need to prove to the FDA, in large-scale studies, that they are safe and effective. We do have adequate preliminary data to warrant conducting large-scale, well-controlled studies that are likely to show that they are effective. But when nutrients are taken to treat a disease or produce a physiological effect, they ought to be tested just like any drug.

Tryptophan is another good example. Few people doubt that it is a sleep inducer. In Germany and Canada, adequate data were presented to regulatory authorities to justify its sale as a prescription drug, not as a sleeping. aid, but for the treatment of depression in conjunction with MAO inhibitors. But in the U.S., it was never developed as a legitimate drug.

Instead, it was sold by mail order and in health food stores until a disaster occurred a few years ago when an impure batch of tryptophan killed about 35 people and sickened about 1,500 others with EMS--eosinophilia myalgia syndrome.

Q: Why did that happen?

A: There are probably two reasons. First, in the early 1970s we discovered that tryptophan is likely to increase serotonin. We didn't know about patents, so we didn't patent its use.

And once we had published the results of our studies, no one else could get a patent for discovering it. And without a patent, there probably was inadequate economic incentive for a pharmaceutical company to finance the studies that are needed to get it approved as a drug.

Second, Congress allowed it to be sold as a dietary supplement, which is a scam because no one in America suffers from malnutrition caused by isolated tryptophan deficiency. In fact, if someone had a generalized protein deficiency, taking supplemental tryptophan would only make the problem worse. It would lower blood levels of the other amino acids, making it even harder for the body to build proteins.

Q: What should have been done about tryptophan?

A: The same as with any potential drug.

First, scientists need to show that a substance has a useful effect. For example, we found that tryptophan can affect serotonin, and serotonin can affect pain, sleep, and other functions.

Then researchers should do preliminary laboratory studies to see how the substance can be used.

We've done that much with tryptophan.

Then we should do the usual small- and large-scale studies required by the FDA to find out whether the candidate drug is effective. Concurrently, full toxicological studies should be done to find out if it causes cancer, birth defects, or other problems.

If we had patented tryptophan as a treatment for insomnia, it might have provided an incentive for companies to spend the money to do those trials.

Q: But if amino acids were regulated as drugs, wouldn't that make them more expensive?

A: Testing should make them more expensive. But not for tryptophan, because it was already overpriced--unconscionably so. It was priced at what sleeping pills would cost.

And, amino acids are drugs. When you give a compound not for nutritional purposes, but to treat a disease or get a physiological effect, it's a drug. That's what the law says.

In pure form, a nutrient is metabolically different than if it's eaten as part of food. If you eat a food that contains tryptophan, the other amino acids in the food will cause the tryptophan to be converted back to protein and they also suppress its entry into the brain. If you take tryptophan alone, some of it does get into the brain.

Q: But if these substances are safe, what's the harm in making them available for less cost?

A: You can't use their safety as a food constituent to say that they are safe as a drug. When you take a drug, a package insert and a label tell you what the drug should be used for, what the dosage range should be, and what the side effects and contraindications are.

For example, the label might say that tryptophan is contraindicated while drinking alcoholic beverages, because tryptophan and alcohol enhance each others effects.

Another big danger has to do with taking other drugs. Neither tryptophan nor tyrosine should be taken with an MAO inhibitor like Parnate, which alleviates depression by slowing the natural degradation of serotonin. Nor should they be taken with Prozac, which blocks the reabsorption of serotonin, or with Deprenyl, an MAO inhibitor used in Parkinson's disease. Both amino acids would accentuate the effects of the antidepressants, perhaps to dangerous levels.

Q: Phenylalanine, another amino acid, is now being marketed in "smart drinks" that "boost energy" and "satisfy the appetite. "Does it?

A: As far as I know, there is never any reason for giving anyone supplemental phenylalanine. We once thought it might be useful to increase brain norepinephrine. In fact, MIT holds an old patent on using it for that purpose. Phenylalanine turns out to have the opposite effect. So if you'd like to own a patent, I'll see if MIT will donate it to you.

Q: Is it just amino acids and carbohydrates that affect the brain?

A: No. Choline also can. Whether amino acids get into the brain and are converted to neurotransmitters depends on other amino acids. Choline doesn't. The more you take, the more gets into your brain.

The committee that sets the Recommended Dietary Allowances doesn't presently consider choline an essential nutrient. But there's an impetus to put it back on the RDA list.

Stephen Zeisel at the University of North Carolina has recently shown that when normal volunteers were put on a choline-free diet, it interfered with their nerve-muscle transmission and increased liver transaminases, a sign of liver damage.

And! think it's possible that people are eating diets that are marginally deficient in choline. How many times did you eat eggs or liver in the last week?

Q: None.

A: Liver and eggs are the dominant sources of choline in the diet. But people are avoiding them because of their cholesterol. Where you have choline, you have cholesterol.

Choline intake is probably low enough in some diets to cause transaminase problems. We studied 37 people who ran the Boston marathon. All but one had a major reduction in choline levels. My guess is that they were borderline deficient to begin with and that the stress of running made it worse.

Q: What would that do?

A: It would make them tired and perhaps impair their memory.

Q: What does choline do?

A: It's both a nutrient and a drug. If you use it to treat the common cold, it's a drug. If there's an RDA and most people are beneath it, and if a deficiency has consequences, it's a genuine nutrient.

Q: Why should it work like a drug?

A: Choline is converted into the neurotransmitter acetylcholine, which is involved in memory. David Drachman of the University of Massachusetts at Worcester showed that if you give normal people drugs that block acetylcholine, they flunk a memory test. If you give them a drug that inhibits cholinesterase, the enzyme that breaks down acetylcholine, they pass the test. He didn't study choline, though.

Q:Many people take lecithin, which contains choline, to improve their memory. Does it?

A: We have no good evidence that any compound improves memory in either normal people or Alzheimer's patients. We're waiting for more data.

Q: Do any of the "smart drugs" or "smart drinks" work?

A: I know of no convincing evidence that any of them are effective in making normal people smarter. But there is solid evidence that they can--like any other drug---cause side effects.

Ads may be correct when they say that these drugs enhance mental function four times better than the ineffective drug Hydergine. But four times zero is still zero. Claiming that any of these drugs prevent or treat Alzheimer's disease is pure hogwash.

There are some drugs that will increase test scores--amphetamines, for example. But these compounds can be very dangerous and have been taken off the over-the-counter market.

Of course it is possible that, one day, good scientific studies will show that some drug actually can improve mental performance. It's just as possible that studies will show that it doesn't.

Q: Rumor has it that an FDA task force is going to advise the Commissioner to regulate amino acids as drugs. Do you think it should?

A: I devoutly hope so. The amino acids are accidents waiting to happen. It's likely that some of them will turn out to be useful in treating some disorders. But if they're not regulated as drugs, we'll never know.

Richard Wurtman is a professor of neuroscience and the director of the Clinical Research Center at the Massachusetts Institute of Technology. He has co-authored some 800 scientific papers and co-edited an eight-volume series called Nutrition and the Brain. We interviewed him by telephone in July. His views do not necessarily reflect those of NAH.

In the brain, neurotransmitters like serotonin and norepinephrine carry signals from one nerve cell to the next across the gap (synapse) between the two. Tryptophan enters the presynaptic nerve cell, where it is converted to serotonin. As more tryptophan enters the cell, more serotonin gets released into the synapse.

Anti-depressant drugs exert a powerful influence to keep more of the neurotransmitters in the synapse. Prozac blocks the reabsorption of serotonin back into the pre-synaptic nerve cell. MAO inhibitors like Parnate block the enzyme monoarnine oxidase, which breaks down serotonin and norepinephrine.