Tryptophan: Uncertainty Reigns After Ban on Sales : Health: A $150-million-a-year market had grown for the amino acid. Now, experts are divided on whether the supplements are helpful or harmful.

If there is a golden rule of nutrition, it is a simple one: Too much of anything is bad for you.

Yet, when it comes to amino-acid nutritional supplements, Americans seem to cling more to the creed that if a substance occurs naturally within the human body, one can never have too much of it.

That philosophy resulted in the development of an estimated $150-million-a-year market for the amino acid tryptophan in the United States over the last few years. Sold over the counter merely as a “nutritional supplement,” it nonetheless has been used as an alternative drug by many people, sometimes on the advice of physicians.

The tryptophan boom was stopped cold last week by state and federal orders banning sales of tryptophan while officials determine whether the substance is behind 287 U.S. cases of a rare blood disorder, 24 of them in California.

If tryptophan supplements are indeed responsible for the outbreak of eosinophilia, contamination is a key suspected cause. However, because tryptophan has a complicated metabolic pathway in the body, there is also the possibility that excessive doses could have built up one or more byproducts to harmful levels, scientists say. Tryptophan advocates, who point to years of use of the amino acid, say they think an obscure virus is at fault for the outbreak of the blood disorder.

Whether or not the amino acid really is to blame, the situation highlights the rise in a quasi-medical underground that sees amino acid supplements as a “natural” way to remedy a host of ills.

Can’t sleep well? Eating too much? Depressed? Suffering premenstrual syndrome? Try tryptophan, popular books advise.

In training? Try arginine or ornithine to stimulate a “natural” steroid dose in your body that will bulk up muscles, the athletes’ grapevine says.

Or replenish your protein stores with leucine, isoleucine, valine and threonine, the grapevine also says.

But critics say the scientific research on which this type of advice is based is preliminary at best. More importantly, it was never followed up with the kinds of careful studies that would determine how much of these amino acids is enough--and how much is too much.

Consequently, critics express doubts about the usefulness of amino acid testing and therapy done in Southern California and elsewhere. In some cases, they suggest, amino acid supplementation could be dangerous.

But psychiatrist Priscilla Slagle says she uses “a wide variety” of amino acids to treat her patients in Los Angeles, Encino and Palm Springs. Among them have been “hundreds” of people given tryptophan.

“I do believe that amino acid treatment is a frontier treatment, and I believe they do have powerful medical uses,” Slagle said. “When people have illnesses and difficulties, their metabolic processes are disturbed. So we’re talking about correcting and creating a balance again.”

Because she has concerns about quality control, Slagle tells her patients to use only products formulated by Tyson & Associates of Santa Monica, which markets its amino acids only through doctors.

Don Tyson, president of the firm, said it does about $5 million a year in business through “a few hundred” doctors in the Los Angeles area and “a few thousand” throughout the United States and in Holland, Italy and Belgium.

But the vast majority of tryptophan and other amino acid supplements consumed by Americans comes not from firms that market through doctors but from manufacturers that sell through retail outlets. These manufacturers count on popular health books and word of mouth to build a clientele.

Because amino acid pills are classified as nutritional supplements, the U.S. Food and Drug Administration has no controls over their manufacture or sale.

Scientists and mainstream physicians have viewed the amino acid boom as relatively harmless, since they assume Americans taking the supplements are adequately nourished.

But for a marginally nourished or malnourished person, they suggest, amino acid supplements might be harmful. Animal research shows that, when an animal is getting barely enough of the amino acids it needs, giving it a high dose produces illness much more readily than in a well-nourished animal, said Dorothy Gietzen, a biochemist who directs the UC Davis psychiatry research lab.

In addition, some scientists worry about damage to the liver from having to break down unused amino acids and possible damage from accumulation of byproducts of the breakdown.

In the elegant chemical factory that is life, there are four major components:

* The genetic code provides a blueprint for all work the body does.

* Carbohydrates provide energy to do the work.

* Proteins direct the work.

* Fats store energy for use later.

Twenty-two different amino acids are known as building blocks in the protein division of this biochemical factory. Just as a child snaps together Legos to build a thousand fantastic structures, the body strings together amino acids in countless ways to make countless proteins.

(Amino acids come in L and D forms--the L form being the version that the body naturally uses and the version most commonly sold. The D form is a three-dimensional mirror image.)

When a human lifts a finger, has a thought, or just breathes, it is because enzymes and other proteins are causing chemical reactions to make this use of energy possible.

But the raw material for this comes only from taking in proteins in food, breaking them down in the gastrointestinal tract, and then absorbing the resulting amino acids into the bloodstream. Unused amino acids are broken down by the liver.

The body needs all 22 amino acids to work properly, and a deficiency in any one of them becomes the limiting factor for protein synthesis. However, in adults only eight “essential” amino acids--including tryptophan--must be derived from food. The other 14 important amino acids can be synthesized adequately by the body from the essential amino acids. (Babies need histidine but develop the ability to synthesize it as they grow.)

Over short periods, the body harmlessly makes up for shortages of essential amino acids by digesting protein-rich muscle cells of its own gastrointestinal tract. Over long periods or in a marginally nourished person, deficiency results in disease, such as pellagra, caused by lack of vitamin B-6, which is produced when the body breaks down tryptophan.

Where advocates of amino acid supplements and their critics disagree is in whether it is useful or harmful to try to boost the protein-building process by taking amino acid supplements.

Tyson, of the Santa Monica amino acid firm, says keeping track of his amino acid levels and augmenting them keeps him from getting sick.

Slagle and her patients say adding tryptophan to their daily health care rituals helps them sleep better and cures depression.

Tryptophan is thought to do this by boosting the brain’s level of the chemical serotonin.

But the same effect can be gotten at less expense and with less risk of overloading the body by merely drinking a glass of milk at bedtime, said Richard Wurtman, a Massachusetts Institute of Technology researcher whose work showing the serotonin link helped popularize tryptophan.

Wurtman said he worries that the unregulated use of tryptophan means people are overloading their bodies with it and are doing so without knowing basic precautions. It will amplify the effects of certain antidepressant, hypertensive or antipsychotic drugs, and should never be taken before driving or dangerous activities, he noted.

Tryptophan’s perceived status as a nutritional good guy provides an interesting contrast to the negative image of a sister amino acid, the flavor enhancer monosodium glutamate.

The “glutamate” part of MSG is an amino acid and, like tryptophan, is a neurotransmitter, affecting the delicate cells of the brain and nervous system. It is excesses of glutamate that are blamed for that lethargic, headachy condition often called Chinese restaurant syndrome.

Yet the same people who worry that a Chinese restaurant is using MSG might go home at night and pop a tryptophan pill to help them sleep.

Part of the difficulty in determining whether amino acid supplements are good or bad is that their various paths through the body and interactions with one another are complicated and, so far, not very well studied.

“The point is we know very little about what happens in terms of flows of material in the body, especially for amino acids like tryptophan,” said Dwight Matthews, associate professor at Cornell Medical College in New York City. Matthews tacks radioactive atoms onto amino acids and then traces their biological paths.

“You can go back to almost any eating studies and look at how amino acid levels change after a meal, but there’s not a lot in terms of the kinetics--what happens to it later,” Matthews said.

At UC Davis, biochemist Gietzen noted that studies of rats show that concentrations of amino acids in blood vary widely depending on whether the animal has been fasting or has just eaten, the composition of the most recent meal, and the time of day.

Citing a paper she uses as a reference, Gietzen said there are wide variations in amino acid levels in plasma that are considered average. For tryptophan, the average range in men is from 30 to 90 nanograms per milliliter of plasma; for women, it ranges from 24 to 76.

With that wide a range, how can “normal” be determined, she asked. Before an individual’s amino acid deficiencies could be reliably determined, she said, multiple blood samples would be required over the course of the day, for several days.

“If they had a consistent pattern, you could maybe recommend adding something to the diet--but it would be better to add it to the diet than it would be to give it to them in pills,” Gietzen said, “because they can tolerate it better in a combination with other amino acids than singly.”

Federal health officials who are investigating the outbreak of the blood disease eosinophilia might shed some light on how much tryptophan is too much if they find evidence of large doses in people who acquired the disease.

However, the fact that supplements have been widely used for years is seen as an indication that the problem may be due instead to contamination of the crystalline tryptophan powder imported from overseas.

Matthews of Cornell noted that, for his studies, he has to verify the purity of the amino acid powder before administering it to research subjects--and he frequently finds contamination.

“Time and time again I find some very strange impurities,” Matthews said. “That, in my opinion, is one of the best places to look.”

The Japanese have developed good methods for assuring purity of their product, but a change in procedures could result in contamination of new batches, he said. In addition, the high price of Japanese amino acids would put economic pressure on U.S. companies to mix them with cheaper products produced with less quality control, he said.

He noted that the complex chemical methods used for making tryptophan and other amino acids often involve toxic substances such as hydrogen cyanide.

“We’re not talking about natural foods,” he said. “We’re talking about specially prepared individual compounds. And in almost any case you can get the same effect just by eating right. You can pick natural foods that are a little bit richer in specific amino acids and get along just fine.”

Wurtman, in his role as inadvertent father of the tryptophan craze, wants the FDA to classify amino acids as drugs.

“The sad truth is it probably works,” he said of tryptophan. “But I would hope very much that the perception that these amino acids sold by the present route may be causing big problems will cause us to rethink completely whether we should allow them to be sold as so-called nutritional supplements.”