Tryptophan: rip-off or remedy?

TRYPTOPHAN: RIP-OFF OR REMEDY?

Having trouble sleeping? Are you moody and blue? Perhaps you've been overeating or suffering from chronic pain. According to proponents, all you may need for quick relief is tryptophan, a "natural, hundred percent safe" amino acid.

Like other amino acids, tryptophan does occur naturally in protein foods. But the claims apply only to supplements that are taken in relatively large doses.

Can these supplements really alter mood and behavior safely and without side effects? Or are they ineffective, and perhaps even dangerous?

"Tryptophan is the first safe, non-toxic sleeping pill," asserts a University of Oklahoma professor in Nutrition News, a newsletter distributed in natural foods stores.

The same newsletter quotes a psychiatrist who used tryptophan to combat the pain of repeated spinal surgery. "It relieved my pain and stress so well that I was able to function with complete efficiency," he avows.

A Denver psychiatrist, claims the newsletter, has used it on about 50 patients "to fight the blues or beat depression." His patients "all report happier lives."

These testimonials are anything but scientific, but they do have some basis in fact. Tryptophan has been shown to promote sleep. Whether the amino acid effectively combats pain and depression is less clear. Although some studies have been promising, others show tryptophan to be no better than an inactive placebo.

Tryptophan and Serotonin. The notion that dietary tryptophan could be used to manipulate the mind first took root in 1961. [1] In that year, researchers showed that when rats were injected with tryptophan, the level of serotonin in the animals' brains increased.

Serotonin is one of several chemicals that send messages from one nerve to another within the brain. These chemical messengers--known as neurotransmitters--control an array of functions ranging from blood pressure and breating to alertness and appetite. Serotonin, in particular, is thought to soothe pain, reduce anxiety, combat depression, and induce sleep.

That tryptophan in the diet could increase serotonin in the brain surprised researchers. They had known that tryptophan was a forerunner, or precursor, of serotonin. But they also knew that the "blood-brain barrier" restricts the passage of many substances into the brain's semi-separate circulatory system. Usually, the barrier shields the brain from fluctuations in the blood levels of nutrients.

But tryptophan was an exception. Diet could indeed affect how much reached the brain ... and it did so in unexpected ways. Researchers found, for example, that even though protein contains tryptophan, eating protein foods doesn't raise the level of tryptophan in the brain. That's because tryptophan competes with several other amino acids for transport into the brain. Since protein contains relatively more of these other amino acids, protein-rich meals leave tryptophan behind in the race through the blood-brain barrier.

Surprisingly, the best way to raise tryptophan levels in the brain without taking supplements is to eat carbohydrates. Normally, low levels of all the amino acids circulate in the blood. After a carbohydrate meal, the pancreas releases insulin, which drives most of the amino acids out of the blood and into body tissues. But insulin has less effect on tryptophan. So eating carbohydrates clears the way for tryptophan to pass through the blood-brain barrier.

Sweet Sleep. It can be tough to get a good night's sleep. Americans spend more than $50 million each year on over-the-counter sleep medications and more than $140 million on prescription drugs for sleep.

But these preparations often produce unwanted effects, such as dry mouth, hangover, and dependency. It would be welcome news indeed if tryptophan could, as one natural food store handout suggested, "free people from barbiturate slavery."

Indeed, several well-conducted studies show that between one and five grams of tryptophan makes test subjects sleepy and helps them fall asleep more quickly, without distorting natural sleep. [2,3] After reviewing 43 studies, Ernest Hartmann, a Tufts University psychiatrist, concluded that tryptophan "has an effect in increasing sleepiness and inducing sleep in human beings and in animals."

For most people, one gram of tryptophan, taken one-half to one hour before bedtime, is enough to produce a maximum effect. (One to two grams to tryptophan is consumed daily in a normal diet, but it has a different effect when taken separately and in a single dose.) Individuals with more severe sleep disorders may need up to four grams, and for some, tryptophan may not work at all. [4]

Pscyhiatrist German Murcia, of the Stanford University Sleep Disorders Clinic, cautions that patients must be taught what to expect from tryptophan. "It doesn't work like other sleeping pills," says Murcia. "You often don't feel it, and it doesn't 'put you to sleep.' It simply makes it easier to fall asleep." Murcia finds tryptophan works best when taken along with carbohydrates, such as bread, pasta, or cold cereal.

Battling Pain. Tryptophan may offer relief to the pain-ridden as well as to the sleepless. Samuel Seltzer, a dentist and pain specialist at Temple University, found that a total of two to three grams of tryptophan reduces sensitivity to pain when taken in small doses throughout the day along with a high-carbohydrate, very low-fat (10 percent of calories), low-protein diet. [5,6]

Seltzer treats patients with chronic head and neck pain, including whiplash injuries. In one study, 15 patients taking tryptophan reported about a 30-point lower pain rating (on a scale of 0 to 100). The 15 patients taking a placebo reported only about a 10-point decline.

However, Ronald Dubner of the National Institute of Dental Research, the president of the American Pain Society, finds flaws in Seltzer's study. "Because the patients taking tryptophan experienced more side effects, they may have guessed their pills contained tryptophan," he points out. "In that case, the study was not double blind."

Richard Sternbach, a psychologist at the Scripps Clinic and Research Foundation, and president-elect of the pain society, is also skeptical. "There are many opinions based on impressions, but there is no good research literature in this area," he sayd. Sternbach reports that neurosurgeons at Scripps' Pain Treatment Center find that tryptophan helps their patients sleep, but does not relieve their pain.

Battling the Blues. "I suffered from intermittent but intense depression from the ages of fifteen to thirty-five," writes psychiatrist Priscilla Slagle in her book, The Way Up From Down (Random House, 1987). "[After] five years of psychoanalysis and seventeen thousand dollars, I was still running into those same moments of intense depression.

"Just as pscyhoanalysis wasn't the answer for me, neither were drugs. My depression was not constant enough to make me want to experience the side effects of antidepressant medication. But the desperate times continued.

"I began to look for some kind of biochemical way to change my feelings and was rewarded in my search by learning about specific nutrient substances that could directly influence certain mood-elevating brain chemicals. From then on, I applied to myself the kind of nutritional treatment I'm now recommending in this book. That was ten years ago and I have been depression-free since that time."

Slagle's story is inspiring. But her nutritional approach, which includes several other supplements along with tryptophan, has never been scientifically tested.

Researchers have, however, examined the effect of tryptophan supplements alone on patients suffering from depression and the excited mood state known as mania. Several reports suggested that tryptophan is effective. [7,8] These studies, however, only compared tryptophan to other antidepressant drugs or to electric shock therapy--not to a placebo. In most studies that did use a placebo--the acid test--tryptophan proved ineffective. [9,10]

Research Pitfalls. Several factors may help explain these inconsistent results.

* Depression is not one disease, but many, representing several types of chemical imbalance. Tryptophan may alleviate only one type--presumably, depression caused by low serotonin. Since it is difficult to distinguish among the types (and most of the studies did not even make the attempt), a specific effect of tryptophan could have gone undetected in many cases.

* Tryptophan seems to be most effective against depression when taken in daily doses of between three and six grams. [11] Some studies that showed no effect used higher doses.

* Differences between tryptophan preparations may produce differing results, according to Frederick Jacobsen, a National Institute of Mental Health psychiatrist and psychopharmacologist who specializes in depression. For example, capsules may be more effective than tablets.

Boosting Tryptophan. Tryptophan may be most effective when used along with certain other supplements. Author Priscilla Slagle, for example, recommends a complex nutritional program that, along with tryptophan, includes tyrosine (another amino acid), B vitamins, and other supplements.

NIMH's Jacobsen prescribes vitamin B-6 along with tryptophan, which he uses principally as an adjunct to other antidepressant drugs. "It is definitely effective in some patients," he says. "I don't believe it's merely a placebo effect, because when someone responds to it, they typically continue to respond."

Tryptophan can give other drugs an added kick. The majority of people suffering from serious depression (including depression that alternates with mania) respond well to prescription antidepressants. Studies show that tryptophan enhances the effect of some of these drugs, including Parnate and Anafranil. [11] Unfortunately, combining tryptophan with certain antidepressant drugs may increase the incidence of side effects, such as tremor.

As for tryptophan by itself, many practitioners remain unimpressed. "The idea that tryptophan would combat depression was a good hypothesis," says Robert Prien, a psychologist who heads the Somatics Treatments Program at the National Institute of Mental Health, "but it really hasn't worked. Theoretically, tryptophan has merits, but practically, it leaves a lot to be desired."

Jack Rosenblatt, a Bethesda, Maryland psychiatrist who publishes a newsletter about psychiatric drugs, concurs. "Tryptophan doesn't have a consistent enough or robust enough effect," he maintains. "I would use it, but only if other drugs didn't work."

A Drug is a Drug. Even if tryptophan by itself is less likely to be effective than standard antidepressants, mightn't it be worth a try for someone who is plagued with black moods but doesn't want the risks and side effects of drugs? "Taken as a supplement," responds Alan Gelenberg, a psychiatrist and drug specialist at Massachusetts General Hospital, "tryptophan is a drug. It can cause gastrointestinal upset liver damage, and other adverse effects."

Patients have reported nausea when taking 1/2 gram of tryptophan six times a day. [12] After a dose of 5 grams, "at least half" of ten subjects became nauseated, and two actually vomited. [13]

Concern about liver damage is based largely on animal studies. Rats develop fatty livers when given large doses of tryptophan (equal to 35 grams for an adult). [14] The amino acid may also be toxic to the nervous system, leading to problems such as impaied coordination. [15]

The body converts tryptophan to other chemicals, and animal studies show that some of these tryptophan metabolites promote bladder cancer. Since vitamin B-6 tends to reduce the level of tryptophan metabolites in the bladder, people who take more than a gram or two a day of tryptophan should also take a vitamin B-6 supplement. [11] Fifty to one hundred milligrams per day is a low-risk dose; 2000 milligrams is definitely hazardous. (The RDA is 2 milligrams per day.)

High doses of tryptophan may increase the risk that cataracts will form, particularly in individuals heavily exposed to the sun or other sources of ultraviolet light. And the amino acid should be used cautiously, if at all, by pregnant women and patients with diabetes. [11]

Tryuptophan has been widely used as an antidepressant in Great Britain for many years, at doses of six to nine grams per day, with few apparent problems. [16] But the amino acid hasn't gone through the kind of systematic safety testing FDA requires for new drugs. And because tryptophan can't be patented (since it is found in nature), it's unlikely that any company will spend the money to thoroughly test its safety.

Self-dosing with tryptophan for pain or depression may be foolhardy. But people suffering from chronic pain, or those who have not been helped by standard antidepressants, might want to try the amino acid under medical supervision.

Taking tryptophan for sleep may be less risky, because a lower dose--1 gram--usually suffices. In fact, both Hartmann and Murcia prefer the amino acid to over-the-counter preparations such as Nytol and Sominex, because tryptophan has fewer side effects.

Tryptophan has at least one proven use--sleep induction--and much unfulfilled promise. Many hope that this is only the beginning. We still have a lot to learn about how tryptophan--and other nutrients--can influence mind and mood.

[1] Br. Med. Bull. 36: 95, 1981.

[2] Am. J. Psychiat. 134: 366, 1977.

[3] Br. J. Clin. Pharm. 2: 165, 1975.

[4] Nutr. Rev. 44 (supplement): 71, 1986.

[5] Pain 13: 385, 1982.

[6] J. Psychiat. Res. 17: 181, 1983.

[7] Psychol. Med. 12: 741, 1982.

[8] Arch. Gen. Psychiat. 30: 56, 1974.

[9] Arch. Gen. Psychiat. 32: 22, 1975.

[10] Brit. J. Psychiat. 132: 555, 1978.

[11] Wurtman, R.J. and J.J. Wurtman, eds. Nutrition and the Brain, Vol. 7. (Raven Press, New York) 1986, pp. 96, 68, 60, 62.

[12] J. Psychiat. Res. 17: 181, 1983.

[13] Brit. J. Clin. Pharmac. 2: 165, 1975.

[14] Biochim Biophys. Acta 144: 223, 1967.

[15] New Engl. J. Med. 267: 1338, 1962.

[16] J. Nutr. 117: 1314, 1987.