(and reply by Nutritional Foods Association)
Aug 27 1998
original url: May Clinic
Mayo Clinic Press Release
Aug 27 1998
Mayo Clinic researchers report finding low levels of a potentially harmful contaminant in off-the-shelf samples of a popular dietary supplement, 5-Hydroxy-L-Tryptophan (5-OH-Trp or 5-HTP).
The contaminant, called "peak x," was linked to symptoms suffered by a family exposed to 5-HTP in 1991. It also has a similar chemical structure to contaminants found in batches of a related supplement, L-Tryptophan, which were linked to a 1989 outbreak of eosinophilia myalgia syndrome (EMS) that affected thousands of people.
The researchers say the finding is a "red flag" about the possibility of health risks from taking this supplement in large doses. Their report will be published in the September 1 issue of Nature Medicine.
Using sophisticated chemical analysis techniques, Mayo Clinic researchers analyzed pills from six samples of 5-HTP produced by six different manufacturers. Samples were purchased at health and nutrition stores in New York City and Rochester, Minn.
They found peak x in all six samples, both synthetic and natural extract preparations. The levels of peak x were only a fraction (between 3 and 15 percent) of the level that caused the illness in the earlier incident. The researchers warn, however, that, "as the intake of supplements is not medically supervised, the probability of increased doses of 5-OH-Trp and hence, peak x, being consumed is very real."
They point out that a current book (5-HTP: The Natural Way to Overcome Depression, Obesity and Insomnia) recommends consumption of 300 to 900 milligrams per day of the supplement. They say that if followed, this recommendation could bring the consumption level of peak x to levels associated with problems in the past.
The authors say that the potential health risks of dietary supplements were clearly demonstrated in the 1989 outbreak of EMS which killed at least 30 people and sickened more than 1,500. That outbreak was linked to consumption of a contaminated batch of the supplement L-tryptophan. Six different contaminants were linked to illnesses.
Mayo Clinic physicians and researchers diagnosed and treated many victims of that outbreak and played a key role in identifying the contaminants that were likely responsible for the illness.
Mayo Clinic researchers have characterized the chemical structure of peak x for the first time. They have discovered that peak x is, in fact, a family of nearly identical compounds. Their chemical structure is similar to two contaminants found in the L-tryptophan linked to EMS symptoms in 1989.
The Mayo researchers have previously raised similar questions about the purity of another popular dietary supplement, melatonin. In several recent publications, they report identification of contaminants in commercial preparations of melatonin whose chemical structure is very similar to some of the contaminants implicated in the L-tryptophan outbreak, as well as to peak x from 5-HTP.
The Mayo research team, led by Stephen Naylor, Ph.D. and Gerald Gleich, M.D., say that their study "emphasizes the need for tighter quality control for the production of both synthetic and 'naturally' produced nutritional supplements" to prevent the possibility of another epidemic in the future.
Mayo researchers have informed the Food and Drug Administration of their findings. They also have provided a description of testing methods used to the six manufacturers of 5-HTP included in the study so that they could confirm the study's findings.
Formal Reply by the National Nutritional Foods Association
Sep 1 1998
In a letter to the editor to be published tomorrow in the journal Nature Medicine, Mayo Clinic researchers claim to have discovered a potentially harmful contaminant in several products containing the amino acid 5-hyroxy-L-tryptophan (5-HTP), a widely used dietary supplement.
According to the National Nutritional Foods Association (NNFA), a trade association for the natural products industry, the letter contains more speculation than fact.
"My concerns about this article are far greater than any concerns I have about the safety of 5-HTP," said Michael Q. Ford, NNFA's executive director. "Even a cursory review of this letter raises serious questions about the conclusions reached by the researchers and their impartiality. It's more politics than science."
The numerous concerns raised by Ford include the following:
-- The article begins with an aggressive attack on the Dietary Supplement Health and Education Act (DSHEA) of 1994, showing the authors clear bias against the industry.
--The sensational nature of the article is revealed when the writers state that the deadly outbreak in the late 1980s of eosinophilia myalgia syndrome (EMS), due to contaminated L-tryptophan, typifies the dangers of dietary supplement usage. In fact, the safety record of dietary supplements is enviable when compared with that of heavily regulated prescription and over-the-counter medications.
--The authors state the purity of 5-HTP products is unknown. There are relatively few manufacturers of 5-HTP, which is extracted from the seed of the Griffonia tree. NNFA member suppliers would not accept any raw material, including 5-HTP, without first receiving a certificate of analysis from the supplier attesting to the products' purity.
--The authors cite two cases of EMS "associated" with 5-HTP use, "most recently" in 1991 (reported in 1994) and the other "as far back as 1980." They use data from the former as the benchmark against which to measure potential EMS risk in the current samples of 5-HTP. In fact, these two cases represent the only connections reported in the literature of a link between EMS and 5-HTP, and both are inconclusive. In the words of the authors of the 1994 article, "The role of 5-HTP in the eosinophilia of this patient is (thus) uncertain."
--The authors allege that they have discovered a chemical structure called "peak x," which represents contamination in 5-HTP and can cause EMS. To verify this, NNFA supplier members had various batches of 5-HTP tested by independent laboratories using the same methodology as the Mayo Clinic researchers. While these laboratories were able to identify a distinct peak, none has been able to replicate the Mayo Clinic's findings that this peak is the same or similar to the contaminant found in L-tryptophan.
--The authors concede that "one possible reason" no new cases of EMS-like symptoms have been reported in connection with 5-HTP is due to the low dosage recommendations on the label. Yet they state, "since the intake of supplements is not medically supervised," higher dosages are bound to be consumed. Unless one is a patient in a hospital under close supervision, it is highly unlikely that ingestion of any substance --food, medication or supplements -- would ever be supervised by a medical professional.
--The authors quote, but do not identify, Richard Wurtman as saying 5-HTP is "another accident (epidemic) waiting to happen." Wurtman is a physician whose company, Interneuron Inc. holds the patent on Redux, a product banned by the FDA last year for causing heart defects. Redux is a serotonin generator, an effect 5-HTP has been reported to induce, raising serious questions about Wurtman's vested interests and bias.
--At the end of their letter, the authors thank several people and institutions, among them Dateline NBC "for supplying commercial preparations" of 5-HTP. It is incredible that an institution with the reputation of the Mayo Clinic would allow such a questionable procedure as obtaining samples from a television newsmagazine for use in testing. Ford said his own association employs the rigorous chain-of-custody procedure sanctioned by the Drug Enforcement Agency in testing commercial samples of member products. That a scientific institute would not use a similar protocol raises serious questions of ethics and bias.
"Clearly, all involved -- the researchers, FDA, Dateline NBC and Wurtman -- had a vested interest in a negative outcome in testing 5-HTP," Ford said. "But in the end, any link between alleged contamination of 5-HTP and L-tryptophan remains unproven. This isn't good science and it certainly shouldn't be news." September 6, 1998
Aug 27 1998
Mayo Clinic researchers report finding low levels of a potentially harmful contaminant in off-the-shelf samples of a popular dietary supplement, 5-Hydroxy-L-Tryptophan (5-OH-Trp or 5-HTP).
The contaminant, called "peak x," was linked to symptoms suffered by a family exposed to 5-HTP in 1991. It also has a similar chemical structure to contaminants found in batches of a related supplement, L-Tryptophan, which were linked to a 1989 outbreak of eosinophilia myalgia syndrome (EMS) that affected thousands of people.
The researchers say the finding is a "red flag" about the possibility of health risks from taking this supplement in large doses. Their report will be published in the September 1 issue of Nature Medicine.
Using sophisticated chemical analysis techniques, Mayo Clinic researchers analyzed pills from six samples of 5-HTP produced by six different manufacturers. Samples were purchased at health and nutrition stores in New York City and Rochester, Minn.
They found peak x in all six samples, both synthetic and natural extract preparations. The levels of peak x were only a fraction (between 3 and 15 percent) of the level that caused the illness in the earlier incident. The researchers warn, however, that, "as the intake of supplements is not medically supervised, the probability of increased doses of 5-OH-Trp and hence, peak x, being consumed is very real."
They point out that a current book (5-HTP: The Natural Way to Overcome Depression, Obesity and Insomnia) recommends consumption of 300 to 900 milligrams per day of the supplement. They say that if followed, this recommendation could bring the consumption level of peak x to levels associated with problems in the past.
The authors say that the potential health risks of dietary supplements were clearly demonstrated in the 1989 outbreak of EMS which killed at least 30 people and sickened more than 1,500. That outbreak was linked to consumption of a contaminated batch of the supplement L-tryptophan. Six different contaminants were linked to illnesses.
Mayo Clinic physicians and researchers diagnosed and treated many victims of that outbreak and played a key role in identifying the contaminants that were likely responsible for the illness.
Mayo Clinic researchers have characterized the chemical structure of peak x for the first time. They have discovered that peak x is, in fact, a family of nearly identical compounds. Their chemical structure is similar to two contaminants found in the L-tryptophan linked to EMS symptoms in 1989.
The Mayo researchers have previously raised similar questions about the purity of another popular dietary supplement, melatonin. In several recent publications, they report identification of contaminants in commercial preparations of melatonin whose chemical structure is very similar to some of the contaminants implicated in the L-tryptophan outbreak, as well as to peak x from 5-HTP.
The Mayo research team, led by Stephen Naylor, Ph.D. and Gerald Gleich, M.D., say that their study "emphasizes the need for tighter quality control for the production of both synthetic and 'naturally' produced nutritional supplements" to prevent the possibility of another epidemic in the future.
Mayo researchers have informed the Food and Drug Administration of their findings. They also have provided a description of testing methods used to the six manufacturers of 5-HTP included in the study so that they could confirm the study's findings.
Formal Reply by the National Nutritional Foods Association
Sep 1 1998
In a letter to the editor to be published tomorrow in the journal Nature Medicine, Mayo Clinic researchers claim to have discovered a potentially harmful contaminant in several products containing the amino acid 5-hyroxy-L-tryptophan (5-HTP), a widely used dietary supplement.
According to the National Nutritional Foods Association (NNFA), a trade association for the natural products industry, the letter contains more speculation than fact.
"My concerns about this article are far greater than any concerns I have about the safety of 5-HTP," said Michael Q. Ford, NNFA's executive director. "Even a cursory review of this letter raises serious questions about the conclusions reached by the researchers and their impartiality. It's more politics than science."
The numerous concerns raised by Ford include the following:
-- The article begins with an aggressive attack on the Dietary Supplement Health and Education Act (DSHEA) of 1994, showing the authors clear bias against the industry.
--The sensational nature of the article is revealed when the writers state that the deadly outbreak in the late 1980s of eosinophilia myalgia syndrome (EMS), due to contaminated L-tryptophan, typifies the dangers of dietary supplement usage. In fact, the safety record of dietary supplements is enviable when compared with that of heavily regulated prescription and over-the-counter medications.
--The authors state the purity of 5-HTP products is unknown. There are relatively few manufacturers of 5-HTP, which is extracted from the seed of the Griffonia tree. NNFA member suppliers would not accept any raw material, including 5-HTP, without first receiving a certificate of analysis from the supplier attesting to the products' purity.
--The authors cite two cases of EMS "associated" with 5-HTP use, "most recently" in 1991 (reported in 1994) and the other "as far back as 1980." They use data from the former as the benchmark against which to measure potential EMS risk in the current samples of 5-HTP. In fact, these two cases represent the only connections reported in the literature of a link between EMS and 5-HTP, and both are inconclusive. In the words of the authors of the 1994 article, "The role of 5-HTP in the eosinophilia of this patient is (thus) uncertain."
--The authors allege that they have discovered a chemical structure called "peak x," which represents contamination in 5-HTP and can cause EMS. To verify this, NNFA supplier members had various batches of 5-HTP tested by independent laboratories using the same methodology as the Mayo Clinic researchers. While these laboratories were able to identify a distinct peak, none has been able to replicate the Mayo Clinic's findings that this peak is the same or similar to the contaminant found in L-tryptophan.
--The authors concede that "one possible reason" no new cases of EMS-like symptoms have been reported in connection with 5-HTP is due to the low dosage recommendations on the label. Yet they state, "since the intake of supplements is not medically supervised," higher dosages are bound to be consumed. Unless one is a patient in a hospital under close supervision, it is highly unlikely that ingestion of any substance --food, medication or supplements -- would ever be supervised by a medical professional.
--The authors quote, but do not identify, Richard Wurtman as saying 5-HTP is "another accident (epidemic) waiting to happen." Wurtman is a physician whose company, Interneuron Inc. holds the patent on Redux, a product banned by the FDA last year for causing heart defects. Redux is a serotonin generator, an effect 5-HTP has been reported to induce, raising serious questions about Wurtman's vested interests and bias.
--At the end of their letter, the authors thank several people and institutions, among them Dateline NBC "for supplying commercial preparations" of 5-HTP. It is incredible that an institution with the reputation of the Mayo Clinic would allow such a questionable procedure as obtaining samples from a television newsmagazine for use in testing. Ford said his own association employs the rigorous chain-of-custody procedure sanctioned by the Drug Enforcement Agency in testing commercial samples of member products. That a scientific institute would not use a similar protocol raises serious questions of ethics and bias.
"Clearly, all involved -- the researchers, FDA, Dateline NBC and Wurtman -- had a vested interest in a negative outcome in testing 5-HTP," Ford said. "But in the end, any link between alleged contamination of 5-HTP and L-tryptophan remains unproven. This isn't good science and it certainly shouldn't be news." September 6, 1998