Health - 5-htp may cause heart valve disease

[lulz]

This is from an archive of Usenet newsgroup discussions, the main participant (Stephen B. Harris) is a doctor whose archived discussions range across a variety of medical topics (which can be found here - http://yarchive.net/med/index.html )

The first posting gives a quick summary of his message:

From: sbharris@ix.netcom.com(Steven B. Harris)
Subject: 5-HTP + B6 = Trouble; Doc Harris Presents Green Banana Award (was: US
ban on tryptophan)
Date: 29 Dec 1996
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<<
------------------------------------------------------------

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-hydroxyindoleac-
etic 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.

Here he explains why the same warning does not apply to tryptophan:

From: sbharris@ix.netcom.com(Steven B. Harris)
Subject: Re: 5-HTP + B6 = Trouble; Doc Harris Presents Green Banana Award (was:
US ban on tryptophan)
Date: 30 Dec 1996
Newsgroups: sci.med.nutrition,sci.med,sci.pharmacy,misc.health .alternative,
sci.life-extension,alt.support.depression

In <5a75t6$91d@camel2.mindspring.com> cntxguy@mindspring.com (Robert A.
Walston) writes:

>Does anyone else have information regarding 5-hydroxy tryptophan and
>the heart fibrosis problem Dr. Harris discusses? I just ordered some
>50 mg capsules (without B-6), and now I am hesitant to take them.
>Would the same warning apply to tryptophan itself? Were all of us who
>received such wonderful relief from insomnia from tryptophan before
>the FDA took it off the market endangering our lives? If tryptophan
>itself doesn't create excess serotonin in the bloodstream and 5HTP
>does, then maybe I should have ordered pharmaceutical grade tryptophan
>(available as a veterinary supplement) instead! Also, is there a real
>risk from taking just 50 mg of 5HTP a night (and no supplemental B-6)?
>Any information would be appreciated.
>
>-Bob Walston
>


The same warning does NOT apply to tryptophan, because the
hydroxylation of tryptophan to 5-HTP is rate limiting, and happens
essentially only in nervous system tissue. It's bypassing this by
eating 5-HTP or serotonin which is the problem. Pure tryptophan is not
dangerous.

Whether taking 50 mg of 5-HTP will give you problems, I don't know, as
I do not know what is the lowest dose of serotonin which has been
reported to cause the cardiac fibrosis (I'll let you know after some
further research). And also (again) whether all of a 50 mg dose of
5-HTP gets turned into serotonin in your liver, will depend on your
vitamin status. If you don't take any supplements at all, you're in
much better shape in this regard, than if you do. As I noted, the only
way to really be sure is to do a 24 hour urine collection for the
serotonin metabolite 5-HIAA (5-hydroxyindole acetic acid).

Steve Harris, M.D.

He answers other questions about 5-htp and tryptophan, but the whole discussion would be too long to copy/paste so here's the link: http://yarchive.net/med/5-htp.html I have the whole page copied on my hard drive in case the site goes down.

Reputation Comments on this post:

good heads up

[Micklemouse]

Dr Harris's rantings have been the subject of debate for some time now, & I'm sure have been covered here before. As I remember, he was very cagey about revealing his sources for the "information" he puts forward, & when he does finally give a reference it was for a small study involving an already compromised group, although without re-reading the whole lengthy news-group posting I couldn't quote, & unfortunately I don't have the time right now to trawl through it - I'll come back to this later...

Hardly convincing stuff to my mind, especially as over 10 years down the line nothing further has arisen to my knowledge backing this claim up, & the product is still widely available without warnings specific to people suffering from cardiac problems.

[lulz]

Perhaps his position is too strongly argued, but the bones of reasoning are solid from my reading of it.

1) 5-htp is unnatural to our diet, and we have not evolved a mechanism to sufficiently limit peripheral decarboxylation

2) Raising peripheral levels of serotonin is medically dangerous, i.e. fen-phen caused vascular heart disease as a result of this

Also, wouldn't 5-htp increase the risk of acute pulmonary hypertension when taken with certain recreational drugs that affect serotonin levels in the body? It might not be as safe to use for "preloading" as many people seem to think.

[0utrider]

but this has been long known, 5-htp in daily high doses may cause fibrosis and other heart diseases due to serotonin in organs etc.. just read the wikipedia article

[Micklemouse]

Originally Posted by outriderx

b.. just read the wikipedia article

...and see that there is no proof offered that 5-htp actually causes cardiac fybrosis. It is theoretically possible -

It has yet to be reported to be associated with valve disease or other fibrosis, but for the previous theoretical reasons, it has been suggested as a possible danger.

, http://en.wikipedia.org/wiki/Cardiac_fibrosis

but then it is theoretically possible that repeatedly slamming your head in the fridge door will help you achieve Nirvana!

Use some common sense, don't directly mix it with other serotonergic drugs, don't use if you are at risk of fybrosis (family history, using meds that heighten the chances, etc), be careful preloading, don't eat a jar a day & the chances of getting this condition will be so slim as to be very slim indeed.

[lulz]

Points taken. This was just meant to raise attention to a possible health risk, as a search on DF didn't return any threads on the subject.

[radiometer]

I have read countless reports of the ingestion of large amounts of 5-HTP while under the effects of monoamine releasers such as MDMA. If excessive peripheral serotonin were such a issue with 5-HTP, surely there would be some reports of serotonin syndrome from such combination. Yet I have never seen one.

Though I continue to use it, I can't shake the suspicion that, in normal doses, 5-HTP doesn't do much of anything really.

[0utrider]

same here..

[Hover]

Correct Swim if he is wrong but Swim's understanding of Harris' article is that this physician maintains that 5-HTP could be toxic to a specific organ because patients with serotonin-producing hindgut carcinoids are prone to develop problems with this organ.

Swim is a little confused by Harris's position. He is after all talking about people dealing with serious health issues whose cardiac problems could be induced by much more than a single factor. It remains to be seen if excess serotonin in tumor-free individuals that do not belong to a "tribe of South Sea islanders" can produce heart toxicity, since most of the otherwise uncommon health problems found in specific small population groups living in geographically isolated areas tend to have their origins in genetic factors.

Reputation Comments on this post:

Thanks for taking the time to actually read through this and think about the research process. You make a very valid poi...

[pasties]

SWIM has been taking 100mg of 5-HTP (almost always with added B6) as well as an "A-Z" vitamin supplement for around 6 years, seemingly with no ill effect. He also used to preload to increase the effects of serotegenic drugs until he learnt of the potential risks of Serotonin Syndrome. He still doubles his dose to 200mg 48hrs after taking drugs such as MDMA and more recently, Mephedrone and Methylone.

Perhaps SWIRadiometer, SWIoutriderx, and any other regular 5-HTP using swimmer should give Dr Harris the benefit of the doubt and take his advise to undertake have 5-HIAA urine monitoring?

Would any pharma-headed swimmer like to comment on Carbidopa and it's potential for protecting the liver from 5-HTP? Further to the theorised risks to the heart, SWIM would like to ensure his 5-HTP isn't wasted.

[psyche]

SWIM has had a funny feeling in his heart when using 5-HTP and that's propably why he discontinued it's use. He has had his doubts about peripheral serotonin and it feels slightly toxic.

I have read countless reports of the ingestion of large amounts of 5-HTP while under the effects of monoamine releasers such as MDMA. If excessive peripheral serotonin were such a issue with 5-HTP, surely there would be some reports of serotonin syndrome from such combination. Yet I have never seen one.

I don't think MDMA increases serotonin anywhere else than in the brain. Peripheral serotonin is the issue here.

[pasties]

@psyche

SWIM used to experience terrible comedowns from MDMA until he discovered 5-HTP 6 years ago (see post above). With a tapered regime of 200mg > 100mg of 5-HTP over the 4 days following MDMA usage, he completely avoided "Terrible Tuesday". Not a sausage! Some is definitely getting into the brain, but how much?

If what Dr. Harris is saying is correct; that excess B6 is the issue, then perhaps the artificial decarboxylase inhibitor, Carbidopa, should be investigated more thoroughly.

lulz -

Points taken. This was just meant to raise attention to a possible health risk, as a search on DF didn't return any threads on the subject.

The Wikipedia entry on Carbidopa has this -

Carbidopa is also used in combination with 5-HTP, a naturally occurring amino acid which is a precursor to the neurotransmitter serotonin and an intermediate in tryptophan metabolism. Carbidopa prevents 5-HTP's metabolism in the liver, which can lead to elevated levels of serotonin in the bloodstream. Research shows that co-administration of 5-HTP and carbidopa greatly increases plasma 5-HTP levels. Without the use of carbidopa, there is a significant risk of heart valve disease when taking 5-HTP, due to serotonin's affect on the heart.[2][3] In Europe, 5-HTP is prescribed with carbidopa to prevent the conversion of 5-HTP into serotonin until it reaches the brain.[4]

Check out the Wikipedia entry for references.

SWIM buys his 5-HTP with added B6 as is the case with most health supplement vendors. Maybe he and other 5-HTP loving swimmers should see a doctor as Dr. Harris suggests and have their piss tested/attempt to get Carbidopa prescribed?

[Tamis]

Originally Posted by psyche

SWIM has had a funny feeling in his heart when using 5-HTP and that's propably why he discontinued it's use. He has had his doubts about peripheral serotonin and it feels slightly toxic.

Same here says swim !
He took around 100mg one morning and had like a takeoff, with cardiac (tight & speedy) signs, jaw locked tigh... had to lay down several times ! Start extrasystols too...

swim will definatly be vary carefull with this product that really gets him going though

[psyche]

Originally Posted by pasties

SWIM buys his 5-HTP with added B6 as is the case with most health supplement vendors. Maybe he and other 5-HTP loving swimmers should see a doctor as Dr. Harris suggests and have their piss tested/attempt to get Carbidopa prescribed?

Yes, either that or just simply replace 5-HTP with l-tryptophan. It seems to be as effective without the side-effects. It doesn't take that much longer to be metabolised into 5HT.

I'm under the impression that testing for neurotransmitter metabolites from urine costs a few hundred euros or dollars. Correct me if I'm wrong.

Reputation Comments on this post:

helpful info

[pasties]

I hadn't considered the cost. SWIM lives in the UK where he gets free health care. That said, I doubt NICE (National Institute for Clinical Excellence) would finance that kind of frivolity where there are safer alternatives.

I thought Tryptophan still was banned after the EMS contamination incident in the US. Thank you very much for pointing that out psyche.

[Impure157]

Originally Posted by pasties

I thought Tryptophan still was banned after the EMS contamination incident in the US. Thank you very much for pointing that out psyche.

Nope, it was banned in the early 90's but a law in '94 basically said that dietary supplements don't have to be FDA approved or even '"safe" to be sold as long as they State on the package that they haven't been FDA reviewed/approved.

So while I've never seen it for sale in the US it technically isn't banned anymore.