Beast80 said:
Bryan, could you elaborate more? I'm using 5 htp for mild depression and to curb the mood swings, I feel it is helping. But how come it's dangerous? is there something else I can take that's good?
Here's a long and detailed discussion of the dangers of 5-HTP by Dr. Steven Harris, a very well-known gerontologist who posts a lot on various medical newsgroups and Web sites:
Newsgroups: sci.med.nutrition,sci.med,sci.pharmacy,misc.health.alternative, sci.life-extension,alt.support.depression
Simon Friedman <freemind@earthlink.net> wrote:
Jack Challem wrote:
> If you look around, you will find a few companies now selling
tryptophan supplements to doctors in the US. The molecular
structure is slightly different, basically just the immediate
precursor molecule. I checked with my FDA contact, and he said
yes, it's true.<
>>You can also buy 5-hydroxytryptophan from at least 2 mail-order
outlets that I know of. 5-HTP is the next step in metabolism from
trypophan on its way to become serotonin.
Simon<<
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Comment: Yes, and in fact 5-HTP needs only one more step to become serotonin-- a decarboxylation. The sequence is:
Tryptophan --> 5-HTP --> Serotonin.
An exactly analogous sequence is:
Tyrosine --> L-DOPA --> Dopamine
In both cases the end product neurotransmitter does not get across the blood brain barrier very well, but all of the precursor molecules above are transported by the brain's large neutral amino acid pump, and they get into the brain fine. Thus, if you are a Parkinson's patient who wants to raise dopamine levels, you must take L-DOPA, not dopamine. Similarly, it would do you no good to take serotonin-- you must take tryptophan or 5-hydroxytryptophan (5-HTP).
Now for the complications. (Aren't there always complications in life?) The final reaction to the neurotransmitter in both the case of dopamine and serotonin, is decarboxylation, and the same enzyme (the aromatic L-amino acid decarboxylase) is involved in both conversions. This decarboxylase enzyme is present in the liver, and it acts in the case of L-DOPA to convert the compound to dopamine before it can make it into the brain (and if this happens, the L-DOPA is wasted). The decarboxylase enzyme uses B6 as a cofactor for this reaction, and for this reason a Parkinson's disease patient taking L-DOPA cannot take more than the RDA of B6, because doing so would act to neutralize oral L-DOPA too quickly. These days, almost all Parkinson's patients on L-DOPA take the drug in a combination with an artificial decarboxylase inhibitor, called Carbidopa (the combination is called Sinemet). But even with Carbidopa, Parkinson's patients are advised not to exceed a daily dose of B6 of 25 mg, since more will overwhelm the Carbidopa effect, and cause pharmacologic L-DOPA to be destroyed in the liver before it can get into the brain.
Now, Carbidopa, because it acts on the same metabolizing enzyme in the liver, performs exactly the same preservative service for 5-HTP as for L-DOPA. For this reason, neurologists have experimented with giving Carbidopa to people who needed to take 5-HTP to raise brain serotonin (this in the days before selective serotonin re-uptake inhibitor antidepressants like Prozac were available). The problem today with 5-HTP-selling companies bypassing doctors and going to laymen, is that a lot of health enthusiasts with problems who are enthusiastically taking 5-HTP are NOT taking Carbidopa, but they ARE taking a lot of B6 in one form or another. Yet without Carbidopa, more than a few milligrams of extra B6 per day would be expected to insure that most dietary 5-HTP gets turned into serotonin before it can get into the brain.
Alas, one company I know packages their 5-HTP in 50 mg capsules with 10 mg of B6. They do this ostensibly so that 5-HTP can be converted to serotonin in the brain. Duh. This insures that any 5-HTP will get converted to serotonin in the liver instead, and thus never make it to the brain. Vitamin B6 is the *LAST* thing you want in an 5-HTP product.
At the very best, people who take B-vitamins with 5-HTP, or who take 5-HTP products with B6, waste their money. All this would be merely humorous (caveat emptor) were it not for some other facts. At worst, ignorant people fooling with 5-HTP actually risk their health, since serotonin in the peripheral blood is not benign. Serotonin causes not only harmless flushing and diarrhea, but people with serotonin secreting tumors (hindgut carcinoids) also have problems with fibrosis of the endocardium and valves in their right hearts, which can cause heart failure. This fibrosis is caused by the serotonin. This effect can also be seen with dietary intake of only modest amounts of serotonin, and there has actually been described in the medical literature a tribe of South Sea islanders with right heart fibrosis as a result of eating green banana mash (matuki), which poisons them with its serotonin content. No, I'm not making this up. The hydroxylation of tryptophan is a rate-limiting step in the peripheral production of serotonin, and one bypasses it at one's peril.
How much does it take? Several hundred milligrams of 5-HTP taken per day, if converted to serotonin, would result in a urinary excretion of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) of several hundred milligrams also-- an amount well within the urinary excretion range of the average person with a serotonin producing carcinoid. Such a dose of 5-HTP certainly would result in a serotonin blood load comparable to that of green-banana-diet eating people who have serotonin-induced heart valve disease. Normally, people do not excrete breakdown products of more than 10 mg of serotonin metabolites per day. If you take one capsule per day of 50 mg 5-HTP with 10 mg B6, however, you would be expected to go to at least 50 mg per day of 5-HIAA in the urine. Less metabolism in the liver (less B6) would result in less 5-HIAA in the urine. If you are going to take 5-HTP, therefore, you probably need 5-HIAA urine monitoring, to figure out just how big a dose of systemic serotonin you're actually getting (and incidentally, how much 5-HTP you're wasting). See a doctor!
For all the reasons outlined above, I am presenting those vitamin companies who sell 5-HTP with B6, or who sell it alone but don't warn their customers about 5-HIAA monitoring or B6 intake, a special award: the Green Banana Award. This honor is for those supplement-sellers who monkey around with people's health before consulting with some really good nutrition and medical specialists to make sure they don't f*&% up and hurt somebody. Hopefully, companies which receive the Green Banana Award will contemplate its message, and will thereby change their behavior in order to avoid some of the less-coveted awards which otherwise await them in the future: the Civil Damage Award, for instance, or even the All-Expense-Paid Guest of the Federal Government Award.
Steven B. Harris, M.D.
