© 1991-2010 Jerry Emanuelson THE TRYPTOPHAN STORY Tryptophan is a naturally occurring amino acid that is found in many foods, most significantly in egg white, milk and poultry.  (Tryptophan is also the dominant amino acid in bananas, although the overall amino acid content of bananas is very low.) This amino acid is essential to the human body for the production of serotonin, a brain chemical necessary for sleep and for mood regulation.  Tryptophan is also the nutrient that the body uses to make melatonin. Tryptophan occurs in foods in lower concentrations than many other amino acids.  Because of the relative importance of tryptophan in producing many critical brain chemicals, nature has provided a way for getting tryptophan preferentially into the human brain.  When carbohydrates are consumed along with tryptophan, the human body produces insulin, which drives many of the more common amino acids into skeletal muscles, leaving tryptophan to cross the blood-brain-barrier into the brain without the competition of the other, more common, amino acids.  This causes the combination of tryptophan and carbohydrates to have a significant mood-altering effect when these things are consumed together in significant amounts. According to the January 12, 1991 issue of the Journal of the American Medical Association (JAMA), the U.S. Food and Drug Administration (FDA) said, "L-Tryptophan has no approved indication for marketing as a prescription or over-the-counter drug. During the 1980s, however, tryptophan was widely available as a supplement in health food stores and other major retail outlets such as supermarkets and drug stores.  Individuals used it for sleeping difficulties, premenstrual syndrome, stress, depression and alcohol and other drug abuse." In November, 1990 tryptophan was taken off the market by the FDA because of its statistical connection to a dangerous blood disease.  Physicians in New Mexico and Minnesota had noted that persons with this unusual disease had all been taking tryptophan supplements.  The blood disease, Eosinophilia-Myalgia Syndrome (EMS), is characterized by severe muscle pain and a dramatic increase in the number of eosinophils, a type of white blood cell.  Eosinophils are one of the blood components measured in a routine blood count.  A slight elevation in eosinophil count is common in people with allergies.  A significantly high eosinophil count is usually associated with a parasitic infection or severe allergy.  EMS, however, produces an unusual cluster of symptoms. Between July, 1989 and December, 1990, more than 1500 cases of EMS were reported in the United States to the Centers for Disease Control (CDC) in Atlanta, and 27 deaths were reported.  The CDC said that virtually all of these cases were linked to the use of tryptophan. According to a letter sent to British physicians by the Chief Medical Officer of the Department of Health of the United Kingdom, no cases of EMS had been reported by November, 1989, in England where tryptophan was also a popular nutritional supplement.  EMS was virtually unknown in the United States before 1989, although tryptophan had been a popular nutrient for many years. These facts led to a search for a contaminant in certain batches of the nutrient rather than a problem with use of tryptophan as a nutritional supplement. The contaminant was found by researchers from the CDC and from the Oregon Health Division of the State of Oregon.  The contaminant was also pinpointed in a separate study by scientists from the Minnesota Department of Health and the Mayo Clinic.  The contaminant appeared in tryptophan manufactured during January through June 1989, by Showa Denko K.K., one of six Japanese manufacturers that provided nearly all of the tryptophan to the United States. In the July 11, 1990 issue of JAMA, the Oregon researchers reported that Showa Denko claimed to have provided 50 to 60 percent of the tryptophan used in the United States. The Minnesota researchers reported that the contaminant first appeared after Showa Denko changed their manufacturing process for tryptophan.  The manufacturing process at Showa Denko involved a fermentation using a selected strain of bacteria. The contaminant appeared when, at the end of 1988, the process was altered to allow the company to reduce the amount of activated charcoal purification by using a genetically engineered bacteria (Bacillus Amylo-liquefaciens, Strain V) in the manufacturing process. According to Minnesota researcher Dr. Gerald Gleich of the Mayo Clinic, it is unclear whether the new strain of bacteria, the reduction in charcoal purification, or a combination of both, led to the appearance of the EMS-producing contaminant. The Minnesota researchers reported in the August 9, 1990 issue of the New England Journal of Medicine that the contaminant is apparently a very potent agent for producing EMS because its concentration in the tryptophan was extremely low.  The contaminated batches were more than 99.6 percent pure tryptophan.  This exceeded the U.S. FDA purity standard of 98.5 percent for tryptophan for human consumption.  In the December 21, 1990 issue of Science, Arthur Mayeno of the Mayo Clinic (and others) reported that the contaminant is a new synthetic amino acid that is chemically somewhat similar to naturally occurring tryptophan. The U.S. Centers for Disease Control in Atlanta independently confirmed the chemical structure of the contaminant.  This accidentally synthesized new amino acid has been identified as 1,1, ethylidenebis[tryptophan], commonly called EBT.  It is logical to conclude that if this new synthetic amino acid were incorporated into the proteins in the human body, all kinds of problems might be expected ranging from cells that do not function properly to reactions where the body becomes allergic to some of its own cells.  Research into this new amino acid, accidentally synthesized by Showa Denko during the first actual genetic engineering catastrophe continued for a long period of time. Separate scientific surveys conducted by the Oregon researchers and the Minnesota researchers showed that about two percent of the population had been using tryptophan supplements before the problem was discovered.  The Minnesota researchers also reported that tryptophan use more than doubled between 1988 and 1989.  According a UPI report, CDC medical epidemiologist Dr. Leslie Swygert placed the estimate even higher, stating that as many as 14 million Americans were using tryptophan supplements at the time of the FDA recall. The FDA had no criteria for the lifting of the ban on tryptophan and kept it out of the reach of U.S. consumers for more than 16 years after the problem was found.  In fact, the FDA tried, unsuccessfully, to ban all amino acids from over-the-counter nutritional products.  Most makers of tryptophan nutritional supplements purchased at least some of their tryptophan from Showa Denko during 1989 and 1990.  Therefore, the use of any tryptophan purchased during this period could have been dangerous, even fatal. For several years, uncontaminated tryptophan was one of the most difficult substances to obtain in the U.S.  Several people have pointed out that harmful substances such as heroin and cocaine were far easier for U.S. citizens to obtain than uncontaminated tryptophan.  Tryptophan finally became available by prescription through compounding pharmacies in the late 1990s, but few people were aware of its prescription availability. Uncontaminated high-purity tryptophan was available for animal consumption throughout most of the 1990s and was sold without restriction.  It remained perfectly legal for humans to consume veterinary tryptophan.  It was not legal during this time for suppliers of veterinary tryptophan to sell it to you if you indicated it was for human consumption. Many important prescription drugs increase brain serotonin levels by mechanisms that are different from tryptophan.  Prozac, and the other anti-depressants in its class (selective serotonin reuptake inhibitors), work through the selective enhancement of serotonin. Dexfenfluramine is an appetite suppressor that is very effective in reducing carbohydrate-craving.  It had been available in Europe for many years.  It was approved by the FDA after the tryptophan ban, but was subsequently removed from the market because of isolated, but sometimes lethal, side effects. Dexfenfluramine works by mimicking serotonin in the brain.  Even before the FDA approval, the safety of dexfenfluramine was called into question by one important study that showed it to cause brain damage in monkeys. A substitute for tryptophan that is usually quite safe is 5-hydroxy-tryptophan, sometimes called 5-HTP.  Tryptophan is converted in the body to 5-hydroxy-tryptophan, then 5-hydroxy-tryptophan is converted to serotonin.  Even though 5-hydroxy-tryptophan is much more expensive than tryptophan, it is about ten times as effective as tryptophan in getting converted into serotonin.  Unfortunately, much of the conversion to serotonin may occur outside of the brain, especially in those who are taking vitamin B6 supplements.  A excess of serotonin outside the brain has the potential for causing serious health problems, but these problems have not been noted in people taking 5-hydroxy-tryptophan.  In Europe, 5-hydroxy-tryptophan is often used with the prescription drug carbidopa, which can inhibit the conversion of 5-hydroxy-tryptophan to serotonin outside the brain. Normally, 5-hydroxy-tryptophan is sold in 50 mg. capsules, whereas tryptophan is typically sold in a 500 mg. capsules. In 1996 and 1997, 5-hydroxy-tryptophan became available from some suppliers of nutritional supplements, and it is now commonly available.  Dosage should be limited to 50 mg. per day unless it is being used under the supervision of a knowledgeable physician who can do a simple urine test for serotonin metabolites to watch for potential problems. In 2007, tryptophan finally became widely available once again in the United States as a nutritional supplement.  Tryptophan, in 500 mg. capsules is now very commonly available as a nutritional supplement.     Next Chapter:  Green Tea Polyphenols   Table of Contents   Back to the FUTURESCIENCE Home Page