For more than 30 years, L-tryptophan was used by over millions of people in the U.S. and around the world safely and effectively for insomnia and depression. But in October 1989, some people taking tryptophan started reporting strange symptoms to physicians — severe muscle and joint pain, high fever, weakness, swelling of the arms and legs, and shortness of breath. The syndrome was dubbed EMS (eosinophilia-myalgia syndrome).

Laboratory studies showed that the blood of subjects with EMS contained an very high level of eosinophils. In patients with EMS, eosinophils levels rose to levels of greater than 1,000 per mm³, roughly double the normal level, and the percentage of eosinophils often increased to levels above 30%.

The problem with such severe elevations in eosinophils is that these white blood cells contain packets that have high levels of histamine and other allergic and inflammatory compounds. When these compounds are released by eosinophils it leads to intense symptoms of an allergic and inflammatory nature--severe muscle and joint pain, high fever, weakness, swelling of the arms and legs, skin rashes, and shortness of breath. The exact type of symptoms experienced by people with EMS. What was suspected was that one or more newly introduced contaminants which activated eosinophils and other white blood cells had to be the reason behind EMS because L-tryptophan had been used successfully by over 30 million people worldwide without side effect.

Detailed analysis of all the evidence by the Centers for Disease Control (CDC) led to the conclusion that the cause of the EMS epidemic could be traced to one Japanese manufacturer, Showa Denko. Of the six Japanese companies which supplied L-tryptophan to the United States, Showa Denko was the largest supplying 50-60%. The L-tryptophan was used not only as a nutritional supplement, but also in infant formulas and nutrient mixtures used for intravenous feeding.

The L-tryptophan produced from October 1988 to June 1989 by Showa Denko became contaminated with substances now linked to EMS 's due to changes in the bacteria being used to produce the L-tryptophan and filtration process. The change in the filtration process resulted in the L-tryptophan being contaminated with impurities linked to EMS. Examination of the pre-filtered material indicated that it had no detectable levels of the impurities linked to EMS. Somehow the filtration process produced the contaminants. It is important to point out that 5-HTP is extracted from a seed of a plant (Griffonia simplicifolia) and is not produced via bacterial fermentation.

While the epidemic of EMS during the last half of 1989 was clearly related to the contaminated L-tryptophan produced by Showa Denko, there have been other reported cases of EMS in people who never took L-tryptophan. In other words, EMS itself can occur on its own. With this fact in mind, in 1994 researchers at NIH reported a 28 year old woman from Canada experienced EMS-like symptoms due to 5-HTP exposure. She did not take the 5-HTP herself but she prepared it for her two small children with an inherited disorder requiring lifelong 5-HTP use. The thought is that she may have absorbed the 5-HTP through her skin or possibly inhaled small amounts. Neither child developed EMS symptoms although both had very mild elevations in the number of eosinophils. The suspected culprit was a compound labeled "peak X" found in the particular batch of 5-HTP the family was using. This speculative association has yet to be proved. It is quite possible that something else caused the EMS-like symptoms in the woman, especially since she was not taking 5-HTP herself (she was only emptying the contents into juice for her children). As stated above, EMS can occur without exposure to tryptophan of any type. It is also important to point out that no children in the NIH study taking anywhere from 400 mg to 1850 mg of 5-HTP per day have developed EMS even though some of them were taking 5-HTP with peak X.

All of the 5-HTP on the marketplace is free from peak X as outlined in current FDA methodology. It is identical in quality to what has been referred to as "uncontaminated" 5-HTP in previous studies. Now, Mayo researchers claim in a recent letter to the journal Nature Medicine that they have identified trace levels of "peak X" in commercially available 5-HTP using a much more sensitive laboratory technique. While the significance of peak X remains to be determined (it is not related to the major contaminants linked to EMS from contaminated tryptophan), my calculation is that it would require a dosage of roughly 10 times the highest dosage range that I recommend in my book (300 mg to 900 mg for weight loss) and over 20 times higher than the typical dosage range of 150 to 300 mg daily given for other conditions to equal the dosage levels of "peak X" given to the two small boys.

It is interesting to note that the Mayo group has raised similar concerns about the safety of melatonin, yet no reported cases of EMS due to melatonin exist to my knowledge. There have also been no reported cases of EMS due to 5-HTP use despite its growing popularity. However, just to be on the safe side and relieve any fears, for people using higher dosages of 5-HTP (greater than 300 mg daily) for longer than 3 month periods, I would recommend getting a simple blood test to measure the level of eosinophils with every three months of use.

Sincerely,

Michael T. Murray, N.D.