Lesser Known Facts About Tryptophan Side

Effects
The Case Against Taking L-Tryptophan Supplements
Tryptophan side effects, contrary to claims by many experts, are rather serious. Many nutritional supplement
manufacturers and promoters advertise and market the substance as an exceedingly safe natural health
product -with a preferential emphasis on numerous alleged benefits (e.g., fights depression, anxiety, attention
deficit hyperactivity disorder (A!", premenstrual syndrome (#M$", and is a natural sleeping aid".
%et, tryptophan side effects are seldom, if ever, mentioned or explained in a comprehensive manner, giving
the impression that such data doesn&t exist (or that there are only benefits of tryptophan".
The widespread unison agreement among experts and marketers in support of tryptophan&s safety (and
effectiveness" is reminiscent of an observation made by the entrepreneur and author $eth 'odin(
It's easy to pretend expertise when there's no data to contradict you.
)act is, there is plenty of solid data on tryptophan that contradicts the mainstream perspective. Tryptophan
side effects are numerous, and several of them are *uite problematic.
The plethora of scientific research suggests that it is best to avoid consuming + tryptophan as a stand-alone,
individual nutritional supplement on a long-term basis in order to prevent the deterioration of your health due
to some rather grave tryptophan side effects.
What Are The Problems With Tryptophan?
-Tryptophan Side Effects: Far From Harmless
'enerally, there are + tryptophan side effects of more minor importance and severity, such as most acute
transient events, and there are the more problematic tryptophan side effects that often have a long ,incubation
period- until, eventually, worrisome health issues become evident.
.n the body tryptophan is metaboli/ed, via two basic pathways, the indole-kynurenine-niacin pathway and the
serotonin-melatonin pathway (0hung 1 'adupudi, 2344". 5irtually all catabolites (besides niacin" are
implicated with significant tryptophan side effects.
Acute Tryptophan Side Effects
An experiment ('reenwood, et al., 4678" with a one-time dose of 8g of the amino acid evoked these
immediate tryptophan side effects(
9 rowsiness
9 :ausea
9 !eadaches
$imilar studies confirmed these acute outcomes, including di//iness, fatigue, and lethargy, among the more
customary actue tryptophan side effects (%uwiler, et al., 46;4< 0unliffe, et al., 466;".
:ow, let&s get on with tryptophan side effects of higher complexity and grimness...
Tryptophan Side Effects
!mpaired Li"er Function
A study (Trulson 1 $ampson, 46;=" demonstrated that high doses of +-tryptophan caused liver damage in
animals. Although the study authors reported that they used doses ,within the range commonly taken by
humans for sleep induction- it seems to contradict their methodological data.
According to the information in their study protocol, the amount they fed the animals would e*uate to around
=-;g>day of +-tryptophan for most people. A typical therapeutic tryptophan dosage (doses of + tryptophan for
insomnia and depression" is in the 83mg-?g range (@raverman, 233?". The apparent discrepancy could be
because higher doses of +-tryptophan, around ;-43g>day, were used not infre*uently by a fair number of
people during the 46;3s and prior.
A similar animal study to the Trulson 1 $ampson (46;=" experiment, using also comparably high doses of +
tryptophan (roughly A-=g>day for humans", didn&t lead to tryptophan side effects such as morphological
changes to the liver in healthy animals (@ucci, et al., 46;2". Tryptophan side effects only appeared in those
animals that had received a bypass treatment in their liver, which deranged their tryptophan metabolism. This
allowed for the accumulation of high plasma tryptophan levels upon the administration of the amino acid
(@ucci, et al., 46;2".
Bther studies on animals, however, raised more serious concerns about tryptophan and liver function...
+iver en/ymes form highly mutagenic +-tryptophan degradation products (e.g., ?-amino-4-methyl-8!-
pyridoCA,?-bDindole" that cause damage to the liver, including cancer (:emoto, et al., 4676< %ama/oe, et al.,
46;3 1 46;4< Ashida, et al., 466;< $u/uki, et al., 233;". .n health people a low salt intake activates the
serotonergic system and increases +-tryptophan decomposition substances ($harma, et al., 466?", raising the
risk for side effects of tryptophan.
An animal study indicated that the addition of miso, a fermented soybean product, prevented the liver inEury
that was caused by at least one of these mutagenic tryptophan breakdown components ($u/uki, et al., 233;".
A study with humans found similar protective effects by drinking coffee (@ichler, et al., 2337". $ulforaphane,
a constituent of broccoli, and curcumin, a constituent of the spice turmeric, are also antagonistic to the
mutagenic impact of some decomposition products of tryptophan ($hishu, et al., 2332< $hishu 1 Faur, 233?".
.t had been demonstrated that white tea, much more so than green tea, reduced tryptophan side effects, such
as mutagenic harm, from some of these poisonous metabolites ($antana-Gios, et al., 2334". Bther
investigations elucidated that some vitamins, such as beta-carotene, vitamin A, @= 1 H, have ameliorating
activities against these poisonous + tryptophan side effects from metabolites (Hdenharder, et al., 466;< 0hung
1 'adupudi, 2344".
Tryptophan Side Effects
#i$her %is& For Eye 'ama$e
The biologist Gaymond #eat, #h, pointed out how an animal study on + tryptophan demonstrated that the
amino acid may increase the risk for cataracts by disrupting the energy metabolism of the eye lens, and thus
#eat cautioned against the practice of using tryptophan supplements (#eat, $pring 233=".
Gesearch on human eye lenses revealed that at least some tryptophan metabolites bind with proteins in the
lenses and may be responsible for the yellowing of the lens that often becomes evident with aging (Takikawa,
et al., 233?". The catabolites& hampering of the metabolic energy processes in the lens, inducing a relative
energy shortage, could partly account for the clouding effect of the lens because of a proportional impairment
and inefficiency of removing cellular debris, such as cell components that got damaged by reactive oxygen
species (free radicals".
As far as tryptophan side effects from its melatonin end product concern, the neurohormone especially
shouldn&t be consumed -even occasionally- during the daytime because melatonin has been found to react
with sunlight (I5A rays", potentially leading to visual disturbances during daytime ('agnJ, et al., 2336" like
blurred vision (as experienced by some people", and eye damage (Kiechmann 1 B&$teen, 4662< $ugawara, et
al., 466;< Fim, et al, 4666< Kiechmann, 2332< Kiechmann, et al., 233;".
)ree radicals such as singlet molecular oxygen are among the principal light-induced harmful agents
responsible for inEury to the skin and eyes (Matus/ak, et al., 233?". Khile melatonin is said to be a strong
antioxidant it is capable of generating singlet molecular oxygen upon light stimulation, whether via I5 or
laser rays (Matus/ak, et al., 233?< MaharaE, et al., 2338". Melatonin is elevated in animals with retinal
damage (!awlina, et al., 4662". $imilarly, retinal dystrophy (Ldegeneration" upon the addition of melatonin
were found in research proEects involving humans (e.g., Mironova, et al., 46;6". Bcular tryptophan side
effects apparently encompass the use of melatonin.
Tryptophan Side Effects
'isturbed Protein (etabolism And !mpaired )rain Function
[...] the pharmaceutical industry's myth has led people to believe that serotonin is the chemical of
happiness, and that tryptophan is its benign nutritional precursor []. !"aymond #eat, #h$, %iologist, in
&''()
$ome studies (e.g., Met/ner, et al., 2338< )rMlund, et al., 2343< Hdwards, et al., 2344" found that + tryptophan
and some of its derivatives like 8-hydroxytryptophan and serotonin efficiently block a carrier protein for
numerous protective substances, including 'A@A (gamma amino butyric acid", short chain fatty acids,
glycine, proline (and for cancer drugs".
This indicates that + tryptophan supplements may excessively disrupt protein absorption in the intestine.
And, it may hamper optimal brain function since the transporter protein is also present in the brain (and some
other organs". Gelated research, for instance, indicated that certain tryptophan degradation substances may
block the glycine receptor in the brain ($tone, 466?".
These tryptophan side effects may partially explain the link between higher serotonin levels and migraines
and mood disorders (Mohammad-Nadeh, et al., 233;" since among the many 'A@A benefits is its protective
impact on brain cells (5aishnav 1 +utsep, 2332< Mir/oian, 233?" and 'A@A is reduced in people with mood
and anxiety disorders ($hiah 1 %atham, 466;< @rambilla, et al., 233?< Kinkelman, et al. 233;< $treeter, et al.,
2343" and also Al/heimer&s isease (Mohr, et al., 46;=". Bther tryptophan side effects, conferred by several
degradation products, encompass the direct suppression of the functioning of 'A@A (Narkovsky, 46;=<
'uilarte, et al., 46;;< Fanai, et al., 46;6".
'lycine and short chain fatty acids, like 'A@A, have an inhibitory calming action on the brain.
Animal studies (e.g., #echenova, et al., 46;?" have documented that tryptophan loading disturbs protein
synthesis, leading to protein deficiency. Tryptophan side effects from ,loading- the amino acid has also been
reported in humans. The infusion of tryptophan in healthy young men, at commonly used doses (4g>day,
?g>day, 8g>day", depleted the levels of many other amino acids such as tyrosine which is vital for brain
function -at all doses studied (!euther, et al., 4662".
$ome of tryptophan&s breakdown products act as potent neurotoxins, via elevating excitatory glutamate levels
and free radical production, while some metabolites (from tryptophan catabolism" appear to protect brain
cells (!uether, et al., 4666< $tone, 233?< $as, et al., 2337".
An in vitro study found that two tryptophan side effects were the depletion of brain antioxidants and
increased lipid peroxidation (free radical production" in brain tissues ()eksa, et al., 233=". These particular
tryptophan side effects, which are a result of an imbalance between neuroprotective and neurotoxic effects,
are implicated in a number of degenerative brain diseases such as Al/heimer&s, #arkinson&s, and !untington&s
isease, but also in epilepsy and strokes (:Jmeth, et al., 2338< )eksa, et al., 233=< $as, et al., 2337".
0losely related to these tryptophan side effects, in experiments it has been established that serotonin is
capable of (temporarily" impairing the protective blood-brain barrier (Kinkler, et al., 4668< Abbott, 2333<
$harma, 233A" which could lead to an increase in toxic events in the brain, such as edema (brain swelling"
and brain degeneration ($harma, 233A".
A researcher stated in his analysis that(
*levation of plasma and tissue serotonin occurs under a wide variety of neurological and psychiatric
conditions. !+harma, &'',)
0oncerning acute serotonin side effects and serotonin toxicity...
Bne of the worst case scenarios of an overload of serotonergic activity is the occurrence of the serotonin
syndrome (symptoms usually appear within a day or a few days", which kills numerous people every year
(%oung, et al., 233;". Isually, this is an outcome of doctor prescribed polypharmacy whereas a person
ingests numerous serotonin-boosting medications (such as selective serotonin reuptake inhibitors or $$G.s",
or instances of great exposure to a single serotonin-augmenting agent (Ables 1 :agubilli, 2343".
$ome of the symptoms of serotonin syndrome are mental and neuromuscular agitation, confusion
incoordination, sei/ures, fever, and organ failure (Ables 1 :agubilli, 2343".
Many years ago researchers (e.g., Oacobs, 4664" have already warned that the external stimulation or
manipulation of the serotonergic system by psychotropic drugs raises the levels of serotonin beyond the
range from living under normal conditions, more reflective of a pathological !-diseased) state.
%et, since around the 46;3s, when the medical-pharmaceutical industry began to heavily promote the type of
psychotropic drugs that specifically raise brain serotonin activity such as selective serotonin reuptake
inhibitors, or $$G.s, it has become Pcommon knowledgeP that serotonin -Pthe chemical of happinessP- is the
antidote to depression. The perpetual inundation of the public with the low-serotonin-depression paradigm
(in support of the Pchemical imbalanceP model" has earned the drug companies a fortune ever since from the
sale of serotonin-stimulating medications (i.e., $$G.s".
!owever, independent investigators, such as avid !ealy, M, the author of several books on psychoactive
drugs, stated that(
.[...] it is now widely assumed that our serotonin levels fall when we feel low [...]. %ut there is no evidence
for any of this, nor has there ever been.. !/ealy, &'',) [emphasis added]
Another researcher and author of a number of books on $$G.&s and other antidepressants, #eter G. @reggin,
M, pointed out that(
+cience does not possess the technology to measure biochemical imbalances in the living brain. 0he
biochemical imbalances speculation is actually a drug company mar1eting campaign to sell drugs.
!%reggin, &''2) [emphasis added]
(@ut it isn&t uncommon for the medical establishment to spread and sustain myths based on vested interests.
Bther examples are the myth of estrogen hormonal therapy, or the myth that mammograms do little harm and
prevent women from succumbing to an early death from breast cancer -see 0he 3ammogram 3yth4 0he
Independent Investigation 5f 3ammography 0he 3edical #rofession $oesn't 6ant 7ou 0o 8now 9bout."
Truth be told, there is disturbing, sound evidence on how the intake of $$G.s (e.g., #ro/ac, #axil, Noloft" can
lead to violence, suicide, and sexual dysfunction (@reggin, 4668 1 2334< 'lenmullen, 2333< !ealy, 233A<
@urwell 1 $tith, 233;". The drug company that created #ro/ac, for example, already knew before they began
to market the drug worldwide to the unsuspecting public that it significantly increases the risk of suicide
(!ealy, 233A". .n 233= a drug maker of one of these $$G.s admitted that the medication raises the risk of
suicide eight times (Oay, 2343".
.n an interview @reggin stated that(
.5ne of the things that in the past had been 1nown about depression is that it very, very rarely leads to
violence. It's only been since the advent of these new ++"I drugs that we have murderers, sometimes even
mass murderers, ta1ing antidepressant drugs..
Bther tryptophan side effects, or more accurately, serotonin side effects from the use of $$G.s, have been
uncovered.
$everal research reports found that the long-term use of $$G.s leads to osteoporosis and hip fractures in both
genders and at all age ranges, from adolescents to elderly people (iem, et al., 2337< !aney, et al., 2337 1
2343< Killiams, et al., 233;< 0alarge, et al., 2337 1 2344", probably by increasing prolactin concentrations
(0alarge, et al., 2337< Allport, 233;< #eat, $ept. 2344" and the stress hormone cortisol (#eat, :ov. 233;".
Melatonin, for example, was denoted to stimulate prolactin release in healthy young women and men
(Kebley, et al., 46;;< Bkatani, et al., 466A< Fostoglou-Athanassiou, et al., 466;". Hxperiments on animals
(e.g., Keinstock, et al., 46;8" corroborated that melatonin amplifies the stress hormone prolactin.
$erotonin raises both prolactin (OMrgensen, 2337< Bberweis 1 'ragnoli, 2342" and cortisol (#eat, :ov. 233;".
And, both of these substances contribute to osteoporosis (#eat, $ept. 2344".
.n addition, it was also discovered that serotonin in the intestine, rather than merely in the brain from the
influence of $$G.s, causes bone loss (#eat, $ept. 2344". Thus, ,plain- serotonin, rather than some
idiosyncratic effect of $$G.s, is causatively involved in osteoporosis. And arguably, the bone loss disease can
be included on the list of tryptophan side effects since the amino acid is the basic precursor to serotonin.
The lucrative trend surrounding the PartificialP up-regulation of serotonin by drugs to, supposedly, improve
brain function hadn&t gone unnoticed by promoters of nutritional supplements. To get their share of the
profitable marketing of serotonin as the vehicle to emotional bliss, and to distinguish themselves from the
drug companies, many supplement promoters have been claiming that tryptophan, the precursor for
serotonin, is an effective, cheaper alternative to the serotonin-enhancing medications, and that this alternative
is allegedly devoid of tryptophan side effects because it is a PnaturalP substance.
@esides the aleady mentioned reports on the destruction of brain antioxidants and the generation of free
radicals in neuronal tissue by the amino acid, other brain dysfunction has been linked to tryptophan side
effects from metabolites. Bne of the principal +-tryptophan catabolites, ?-hydroxy-kynurenine, augments
oxidative stress in the brain and is able to induce depression, epileptic sei/ures, and other brain damage
('uilarte 1 Kagner, 46;7< $tone, 233?< Kichers 1 Maes, 233A".
Among other brain-related tryptophan side effects are impaired learning capabilities from higher levels of
serotonin (#eat, $pring 1 $ummer 2336". This may relate to the findings of clinical investigations which
reported that serotonin strongly decreased blood flow in the brain ('rome 1 !arper, 46;?< !aEdu, et al.,
466?< Aleksandrin, et al., 2338". #oor cerebral circulation means that brain cells receive less nutrients,
oxygen, and energy, leading to poor cognitive performance.
)ocused attention is not compromised, but rather impro"ed, by a tryptophan deficiency in the brain
(Mendelsohn, et al., 2336". Alongside the positive cognitive ramifications of improved blood circulation in
the brain from a tryptophan deficiency, this is probably also the result of a corresponding lack of activation of
excitatory dopamine neurons by certain tryptophan catabolites (+inderholm, et al., 2337< Hrhardt, et al.,
2336". As might be expected, the excessive stimulation of brain cells by dopamine hampers cognitive
function which is evident in attention deficit disorder (A" and Attention-deficit>hyperactivity disorder
(A!". This speaks against the routine use of tryptophan for A! and A, as to prevent cognitive-
neurological tryptophan side effects.
@rain-related tryptophan side effects have also been reported in the scientific literature from one of the amino
acid&s end products, melatonin. $tudies (e.g., 0arman, et al., 467=< ubocovich, et al., 4663" found that the
addition of melatonin worsened depression, or, respectively, the suppression of melatonin improved
symptoms of despair.
Tryptophan Side Effects
Eosinophilia-(yal$ia Syndrome *E(S+?
HM$ is a group of debilitating inflammatory connective tissue disorders that tend to affect many organs and
tissues.
The 46;6 tryptophan eosinophilic myalgia incident killed a number of people and seriously disabled many
victims permanently (@raverman, 233?".
!owever, it was mainly a transient, epidemic catastrophe. The reason for this is that the tryptophan-HM$
disaster was virtually exclusively the result of product contamination by one particular nutritional supplement
manufacturer ($howa enko".
:evertheless, it appears likely that the development of tryptophan-associated HM$ is assisted and
augmented by inflammatory, natural tryptophan metabolites ('ross, et al., 4666< Gieber 1 @elohradsky,
2343" because untainted + tryptophan has been shown to lead to an increase of free radical production (lipid
peroxidation" in muscles (Gonen, et al., 4666". Myalgia (muscle pain" is a distinctive feature of HM$ and
fibromyalgia.
Another study, conducted by I$ government researchers, that compared H@T-tainted +-tryptophan (an
analogue toxin implicated in the tryptophan-HM$ epidemic of 46;6-4663" to pure tryptophan supplements on
rats (at a human e*uivalent dose of 8-=g>day over a prolonged time period" noted that(
.0his study also strongly suggests that control L-T! "#pure tryptophan$ alone plays an important role in
this [-*3+] and possibly other fibrosing illnesses, because it is associated with mild but significant
myofascial thic1ening and alterations in peripheral mononuclear cell phenotypes, as well as with significant
pancreatic pathology.. !:ove, et al., 2((;) [explanation < emphasis added]
That is, the ingestion of an unadulterated version of the amino acid led to tryptophan side effects, such as the
impairment of immunity, alterations in muscle tissue, and the growth of excessive connective tissues
(fibrosis" and other structural modifications in the pancreas, supporting the existing evidence that :=
tryptophan itself is problematic -at least at proportionally high, but not hugely excessive, doses since up to
?g>day is not considered a Phigh doseP (the average dose of contaminated tryptophan-associated HM$ victims
was at around 2g>day, with a range from 43mg to ?8g>day, and people who consumed Ag>day, and more, had
a greater likelihood to develop HM$ C0rist, 2338D".
.n a study report the authors stated in reference to the adulterated tryptophan eosinophilic myalgia disaster of
46;6(
+ince only a fraction of persons who ingested implicated batches of :0 [-:=tryptophan] developed disease,
additional factors li1ely played pathogenetic roles. !51ada, et al., &''() [explanation < emphasis added]
$ince there are indications that the uni*ue, most probable source of the 46;6 + tryptophan-HM$ catastrophe
still hasn&t been really resolved in the Inited $tates, it is conceivable that more tryptophan HM$ cases will
surface. At least one new tryptophan HM$ case has appeared in 2343 after the ingestion of a +-tryptophan
nutritional supplement from the Inited $tates, other tryptophan HM$ cases have also turned up in recent
times (for detailed information on the tryptophan-HM$ epidemic of 46;6 read my article + Tryptophan( The
Truth About The )A Tryptophan Gecall Bf 46;6".
Tryptophan Side Effects
Se"ere !nflammation
The amino acid&s significant inflammatory potential is prominent among many tryptophan side effects. )or
example, rats fed a higher tryptophan diet for a prolonged time experienced greater inflammation in their
lungs, leg muscles, and other organs, and tissue damage was intensified by a tryptophan metabolite ('ross, et
al., 4666". Bther investigations indicated that some inflammatory degradation products of + tryptophan have
diabetogenic activities (Hllis 1 #resley, 467?< 'erras, et al., 4677".
Khile serotonin, a product of tryptophan metabolism, can induce muscle degeneration (@eitner, et al., 46;?<
#eat, )all 233=", another fre*uent, and possibly more likely, culprit for this type of damage are +-tryptophan
decomposition substances.
KhyQ
@ecause the + tryptophan intake dose corresponds positively with inflammatory metabolites of the amino
acid (Bkuno, et al., 233;" and because most supplemental tryptophan doesn&t convert into serotonin in
humans (only about 4-8R C'lenmullen, 2333< #eat, March 2344D" but rather into inflammatory breakdown
elements ('reen, et al., 46;3< !euther, et al., 4662". These inEurious tryptophan decomposition products
remain elevated with longer term consumption of supplemental tryptophan ('reen, et al., 46;3", particularly
with higher doses (around 2-;gm>day".
.nflammatory + tryptophan metabolites dramatically increase the production of reactive oxygen species (free
radicals or oxidative stress" after the ingestion of a large dose (=gr" of the amino acid ()orrest, et al., 233A".
Bther inflammatory conditions are linked to tryptophan side effects.
$tudies (e.g., $mith 1 'arrett, 2338" indicate that the consumption of moderate-high dose tryptophan
supplements leads to an elevation of histamine, an inflammatory substance involved in many degenerative
diseases (including multiple sclerosis C#eat, :ov. 233;D", by blocking its degradation.
Tryptophan side effects also extend to inflammation involving melatonin. .n people with nighttime asthma
and rheumatoid arthritis, for example, it is melatonin side effects, such as increased inflammation, that
contribute to the longevity of the diseases ($utherland, et al., 233?< 0utolo, et al., 2338".
Tryptophan Side Effects
The Promotion ,f -ardio"ascular E"ents
$erotonin, which is increased by + tryptophan loading (Mateos, et al., 2336", is clearly implicated in
cardiovascular disease and other tryptophan side effects ('addum 1 !ameed, 468A< Foren-$chwart/er, et
al., 466A< Mohammad-Nadeh, et al., 233;< #eat, $ummer 2336< Maclean 1 empsie, 2336 1 2343".
.n an investigative paper the researchers commented on...
[...] the damaging effects of serotonin, whose concentration in plasma increases in many diseases and is
implicated as playing an important role in circulation distur%ances. !9ssouline=>ohen, et al., 2((?)
[emphasis added]
To briefly refer to the history of tryptophan, since the late 46th century it was noted that a compound, which
was identified in 46A; as serotonin, can induce platelet aggregation which leads to blood clumping or blood
clots (Koolley 1 $haw, 468A< onaldson 1 'ray, 4686". The observation led to the adoption of one of the
early names for the substance, thrombotonin, a derivative of thrombus (Lblood clot".
$ince the late 46?3s it had been recogni/ed that a substance, which turned out to be serotonin, is involved in
the development of high blood pressure by constricting blood vessels (onaldson 1 'ray, 4686". This
physiological event is analogous to serotonin&s ,contracting- effect in gut muscles causing intestinal
peristalsis which is the physiological process of rhythmically pushing food along in the gut ('addum 1
!ameed, 468A< Koolley 1 $haw, 468A".
There has been scientific evidence (e.g., Keinstock, et al., 46;8" demonstrating that tryptophan side effects
from serotonin, such as blood vessel constriction (vasoconstriction", leading to high blood pressure
(hypertension" , also occurs with melatonin.
Tryptophan Side Effects
-ancer !nitiation . Promotion
It could be concluded that tryptophan metabolites play a complementary role in promoting carcinogenesis
[]. !>hung < @adupudi, &'22)
$erotonin&s established involvment in the promotion of blood clotting (coagulation" has further ramifications.
Gesearch in the 46=3s by omenico Agostino, 5M and Hugene 0liffton, M showed that a greater
propensity of blood clotting correlates with a higher probability for cancer metastasis which is the spreading
around of cancer in the body (Martin, 4677". @y the way, this idea had first been proposed at around the mid
46th century (Trousseau, 4;=8< Marinho 1 Takagaki, 233;".
@lood clots develop because blood platelets become too numerous or very ,sticky- (platelet aggregation".
Agostino and 0liffton reasoned that cancer cells find a protective cover in blood clots by getting trapped
among the sticky cells, making it difficult or impossible for the immune system to detect them (Agostino 1
0liffton, 46=2 1 46=?". This process assists cancer cells in their growth, progression, and dispersion inside
the body (Agostino 1 0liffton, 46=2 1 46=?".
The link between clotting and metastasis is soundly corroborated (@occaccio 1 Medico, 233=< Mousa, 233=<
ten 0ate 1 )alanga, 233;".
.n a more recent research paper the author stated that(
/ypercoagulation is documented in virtually all cancer types, [...], and is the second leading cause of death
in cancer patients. !3ousa, &''A)
.n spite of the findings by Agostino and 0liffton decades ago, it is still better known that cancer cells can
activate excessive coagulation (blood clotting by platelet aggregation", rather than that hypercoagulation
assists and facilitates the progression of cancer into advanced metastasis (Mousa, 233=".
:otwithstanding, it establishes that one of the indirect tryptophan side effects, via serotonin, is the promotion
of metastatic cancer.
H*ually disturbing, a research investigation ()riedman, et al., 2336" that studied many types of
pharmaceutical medications found, for instance, that #ro/ac and #axil, two serotonin-activating drugs ($$G.
antidepressants", are *uite possibly carcinogenic (Lcancer-causing".
The inflammatory nature of several of the breakdown substances of + tryptophan, leads to one of the worst
direct tryptophan side effects( the causation and promotion of cancer.
.n the 4683s researchers demonstrated that specific tryptophan metabolites and the addition of ,unnatural-
+-tryptophan to the diet of test subEects cause bladder cancer in animals (unning, et al., 4683< #ipkin, et
al., 46=6". .n other experiments the same cancer-causing tryptophan breakdown compounds were recovered
after adding the ,natural- +-tryptophan (@rown 1 #rice, 468=".
At least some of these catabolic substances are highly mutagenic and, as mentioned, can induce liver cancer
(:emoto, et al., 4676< %ama/oe, et al., 46;3 1 46;4< Ashida, et al., 466;< $u/uki, et al., 233;". 0ertain
tryptophan degradation substances can also form carcinogenic nitrosamines which have been shown to cause
bladder cancer, including in humans (0ohen, et al., 4676< Katanabe, et al., 4676< Bhta, et al., 46;?< Abdel-
Tawab, et al., 46;=< Katanabe, 4667< 0hung 1 'adupudi, 2344". Tryptophan metabolites are also involved in
other types of cancers such as cervical cancer ()otopoulou, et al., 2344".
Two of the mutagenic tryptophan catabolites, ?-amino-4, A-dimethyl-8!-pyrido CA, ?-bDindole and ?-amino-
4-methyl-8!-pyridoCA,?-bDindole, are widely present in the envirionment and have been found in cigarette
smoke, airborne particles, rain water, and cooked food (Manabe 1 Kada, 4664". .n a study on rats, ?-amino-
4-methyl-8!-pyridoCA,?-bDindole significantly increased the incidence of liver and bladder cancer
(Takahashi, et al., 466?". $mokers have an increased risk of bladder cancer (@rennan, et al., 2334" and
probably of liver cancer too (!!$, 233A".
.n addition, there are tryptophan side effects associated with existing cancer. $pecifically, immune
dysfunction has been connected to tryptophan side effects, enabling the malignancy&s survival and promoting
its progression.
.nvestigators observed that in malignant tumors several tryptophan metabolites (kynurenine, etc.", nurtured
by the cataboli/ing en/ymes indoleamine-2,?-dioxygenase and tryptophan-2,?-dioxygenase, notably inhibit
,antitumor immune responses- by inducing apoptosis (Lcell suicide" in healthy cells of the immune system
()rumento, et al., 2332< Namanakou, et al., 2337< Bpit/, et al., 2344< #latten, et al., 2342". Tryptophan-
derived kynurenine is actively involved in human brain cancers (Bpit/, et al., 2344".
Thus, +-tryptophan is the only amino acid that is capable of causing cancer in humans (#eat, )all 233=". The
most likely way, besides through the nitrosamine-metabolite route, is by tryptophan&s role as an estrogen-
imitating agent (#eat, $pring 2336".
A moderate dose of 633mg>day of supplemental tryptophan, added to an experimental diet of six healthy
women, increased these carcinogenic metabolites very significantly, compared to receiving only the
experimental diet (Katanabe, et al., 4676". The excretion of the + tryptophan metabolites correspond
proportionally to the dietary>supplemental intake (@rown 1 #rice, 468=". Bne of the toxic tryptophan
catabolites, ?-hydroxykynurenine, apart from its implication in human bladder cancer, also ,has affinity for
the pancreas- (Katanabe, 4667". Another harmful metabolite or tryptophan poison, ?-amino-4,A-dimethyl-
8!-pyridoCA,?-bDindole, caused an increase in invasive pancreatic cancer in a study on hamsters (%oshimoto,
et al., 4666".
ogs excrete relatively large amounts of tryptophan metabolites and bladder cancer is rather common
(@rown 1 #rice, 468=". 0ats excrete practically none of these catabolic substances and are almost free of
bladder cancer (@rown 1 #rice, 468=". @ladder cancer is relatively common in humans and people with
bladder cancer excrete large doses of tryptophan degradation products after ingestion of the amino acid
compared to control subEects without disease (@rown 1 #rice, 468=< $earle, 467=". %et, the excretion of large
amounts of some tryptophan catabolites is mainly linked to a vitamin @= deficiency, rather than to the
incidence of bladder cancer (@irt, et al., 46;7".
A deficiency of vitamin @= seems to aggravate the synthesis of some of these inEurious metabolites if an
excess of + tryptophan is ingested ('erras, et al., 4677< 'reen, et al., 46;3< 'uilarte 1 Kagner, 46;7< 0hung
1 'adupudi, 2344". @ecause vitamin @= and niacin (vitamin @?" serve ,complementary- functions in at least
one of the tryptophan metabolic pathways (Hllis 1 #resley, 467?", and one of the health benefits of niacin, an
end product of the kynurenine pathway (+e )loc&h, et al., 2344", is that an increase of the vitamin also
reduces tryptophan catabolites (Alifano, et al., 46=A< %aryura-Tobias, et al., 4677".
There are other tryptophan side effects from unfavorable interactions with certain substances or products.
Hstrogen, as from !ormonal Geplacement Therapy (!GT" or the birth control pill, can increase certain
tryptophan degradation chemicals, even without consuming additional + tryptophan, by interfering with the
metabolic pathways that convert tryptophan to vitamin @? (Hllis 1 #resley, 467?". This positive relationship
between estrogen and tryptophan catabolites was verified in both women and men (Hllis 1 #resley, 467?".
Hstrogen can also increase serotonin (Murray 1 #i//orno, 466;< #eat, $ept. 2342".
.t is reasonable to conclude that these biological events are contributing aspects in the promotion of breast
cancer seen with the use of !GT (Gothenberg, 2338< Gavdin, et al., 2337". Kith the use of !GT, and the birth
control pill, and during pregnancy and menopause, and while under stress, there is an increased need for
vitamin @= and vitamin @? (Hllis 1 #resley, 467?< !offer, 466A".
The degree of effectiveness of vitamin @= to prevent the creation of (some" poisonous tryptophan
decomposition products depends on its dose. At least ?3mg>day of vitamin @= is re*uired for more
comprehensive protection in high-risk individuals (Hllis 1 #resley, 467?", and probably in people who
supplement with tryptophan.
#owe"er/// vitamin %A doesn't prevent all tryptophan side effects.
A randomi/ed double-blind study (e.g., :ewling, et al., 4668" revealed that a comparison between trial
subEects who received a vitamin @= supplement and those who got a placebo didn&t notably change the rate of
recurrent bladder cancer, despite that there were certain differences in the parameters of tryptophan
metabolites between the two study groups.
There are other scientific observations that suggest to not rely solely and faithfully on vitamin @= for the
prevention of (all" tryptophan side effects.
KhyQ
@ecause beyond the scope of vitamin @= and its modulating action on + tryptophan...
...serotonin and melatonin -alongside with tryptophan metabolites (Faminsky, et al., 4664"- interfere and
inhibit the energy-creating metabolic processes such as mitochondrial cell respiration and thyroid function
(Mueller, et al., 467=< Gom-@ugolavskaia, et al., 4667< Kright, et al., 4667 1 2333< #eat, )all 233=, $pring 1
$ummer 2336". Animal experiments demonstrated that one of the side effects of melatonin is its dampening
action on cellular energy output (Geyes-Toso, et al., 233? 1 233=< +Spe/, et al., 2336", and human studies
(e.g., 0arman, et al., 467=< Murphy, et al., 466=< $atoh 1 Mishima, 2334" showed that melatonin, even at a
low dose of 3.8mg, decreases body temperature -indicative of metabolic interference.
Another denotation of melatonin&s ,down-regulating- activities upon the human metabolism is that sleeping
for extended periods in total or near complete darkness, which naturally stimulates melatonin synthesis,
decreased melatonin output (anilenko, et al., 2336", suggesting a systemic defensive biological reaction of
the organism to prolonged exposure of the substance.
This basic anti-metabolic effect of serotonin, melatonin and tryptophan promotes fatigue and lowers
endurance (#eat, $pring 2336", and may be involved in the link between fibromyalgia and tryptophan, and
probably in many, if not most, negative tryptophan side effects. Melatonin, for example, is elevated in people
with fibromyalgia (Fors/un, et al., 4666", and chronic fatigue syndrome (Fnook, et al., 2333". :umerous
people reported feeling tired and groggy in the morning, or throughout the day, after taking a melatonin
supplement prior to going to sleep the night before -symptoms of what some people call a ,melatonin
hangover-.
Many people have noticed significant weight gain after taking melatonin supplements for some time. The
large use of tryptophan, melatonin, and serotonin-activating agents (e.g., $$G.s" may be a contributing factor
in the obesity epidemic, which is most prominent in the I$ with its great consumption of these substances.
And...
:one other than a Two-time :obel #ri/e Kinner, Btto !. Karburg, #h, M, (4;;?-4673" proved a long
time ago (in the 4623s>?3s" that the development of cancer begins with ,a respiratory defect- in normal cells(
>ancer cells originate from normal body cells []. [...] first [there] is the [...] inBuring of respiration
[]. !6arburg, 2(CA) [explanation added]
And...
%ecause no cancer cell exists, the respiration of which is intact, it cannot be disputed that cancer could be
prevented if the respiration of the body cells would be 1ept intact. !5tto /. 6arburg, #h$, 3$, in 2(AA)
Many people, for example the biologist Gaymond #eat, #h and the cancer researcher Thomas :. $eyfried,
#h, have subse*uently written about, or extended on, Karburg&s concepts, in some cases spanning over
several decades already.
$eyfried, for example, provided overwhelming evidence that cancer is a metabolic disease due to
respiratory>mitochondrial dysfunction ($eyfried, 2342".
Analogous and overlapping findings come from #eat&s research...
$erotonin, for which tryptophan is the precursor of, increases the stress hormone cortisol (#eat, :ov. 233;".
0ortisol and cortisone interfere with cellular energy metabolism ($imon, et al., 466;< #eat, :ov. 233;".
Melatonin, too, increases cortisol in older women (0agnacci, et al., 4668" and cortisol is increased in aged,
healthy people of both genders ()errari, et al., 4668". $ince tryptophan is the most fundamental precursor for
both serotonin and melatonin, this line of evidence suggests that the amino acid shouldn&t be raised (with
advancing age" to minimi/e the fostering of tryptophan side effects from serotonin-melatonin-cortisol
ramifications.
Khen the mitochondrial respiration of cells is impaired (as from cortisol, for instance" lactic acid will form
which in itself suppresses cellular energy production (#eat, $ept. 233;". $erotonin can raise lactate levels, by
activation of aerobic glycolysis, and lowers the principal energy substrate, AT#, in the brain and skin (Foren-
$chwart/er, et al., 466A< Ashkena/y-$hahar 1 @eitner, 4667< Assouline-0ohen, et al., 466;". $tress too,
whether physical or psychological in origin, elevates lactate levels (Iehara, et al., 2338".
+actic acid promotes mitogenesis (cell division" and increased levels of lactate is a core feature of cancer
(#eat, $ept. 233;". Hven a small increase of serotonin has been shown to stimulate mitogenesis (Nolkowska,
et al., 233=".
@esides serotonin&s amplification of lactate, it also directly inhibits mitochondrial en/ymes of respiration
(Medvedev, 4663< Medvedev 1 'orkin, 4664". Analogous to serotonin side effects on cell energy production
are the specific tryptophan side effects from nitrosamines. That is, nitrosamines restrict the blood circulation&s
ability to transport oxygen (Martin, 4677". Bxygen, of course, is essential for the efficient generation of
energy (oxidative respiration".
Bne of the health benefits of vitamin 0 is that it can effectively inhibit the formation of cancer-causing
nitrosamines from tryptophan decomposition products ($chlegel, et al., 4673< $chlegel, 4678< Tannenbaum,
46;6< Tannenbaum, et al., 4664", thereby greatly reducing :A damage to cells (Arran/, et al., 2337".
5itamin H, too, appears to have this restrictive impact on nitrosamines (Kagner, et al., 46;8".
Although these vital nutrients can restrict the dangers from a tryptophan poison (metabolite", they appear to
have no noticable influence on the energy-restrictive activities of serotonin.
@ottom line on tryptophan side effects from tampering with cellular energy metabolismQ
@ecause of the synthesis of serotonin and melatonin from tryptophan all of these substances are factors in
harmful energy-disruptive events. And because the chronic tampering of metabolic energy processes (as
could be expected from prolonged intake of tryptophan supplements" will decrease cellular metabolism
(Mela, et al., 467=", the use of a supplement of tryptophan seems ill adviced.
Hspecially since the addition of supplemental vitamin @=, vitamin 0, and other nutrients do not provide full
spectrum protection against all tryptophan side effects from the damaging tryptophan degradation elements,
and other tryptophan-derived culprits of carcinogenesis.
Tryptophan Side Effects
!ncreased A$in$ . (ortality
Khat is tryptophan used forQ
+-tryptophan is essential for growth ($egall 1 Timiras, 467=< e Marte 1 Hnesco, 46;=< $idransky, 2334".
Thus, the amino acid has a most vital role predominantly during marked times of development and
maturation which, for humans, occurs in the early period of life.
$imilar findings have been reported with animals. Blder animals, particularly females, seem less prone to
experiencing tryptophan side effects incurred from a deficiency of the amino acid, such as reduced growth or
diminished skeletal development, than young animals (Moehn, et al., 2342".
Apparently, the essential human re*uirement for +-tryptophan seems to diminish with age (#eat, )all 2336".
Hlderly people have less tryptophan in their blood than young people (0aballero, et al., 4664< $arwar, et al.,
4664". This makes the addition of tryptophan supplements in (advancing" adulthood proportionally
redundant, and *uite possibly even detrimental.
@ecause...
$tudies on animals (e.g., $egall 1 Timiras, 467=< e Marte 1 Hnesco, 46;=< Boka, et al., 46;;"
demonstrated that depriving young animals of tryptophan increased mortality, while the deficit of +
tryptophan decreased mortality in older animals.
@esides extending longevity, a tryptophan-deficient diet also increased the animals resistance to stressors,
reduced their risk of developing tumors, and extended their reproductive ability, and preserved their youthful
outward appearance longer, all of which is analogous to the beneficial effects observed from experiments
with calorie restriction ($egall 1 Timiras, 467=< $egall, 4677".
Bne of the insidious tryptophan side effects is that toxic degradation metabolites (e.g., kynurenic acid"
increase with aging (Fepplinger, et al., 2338". These substances can lead to the formation of mutagenic
nitrosamines (0hung 1 'adupudi, 2344". A reasonable assumption is that this is the result of the stimulating
action of estrogen, which increases in both women and men with age, on some tryptophan degradation
elements (Hllis 1 #resley, 467?".
The consumption of a supplement of tryptophan will likely augment the situation, by raising the inEurious
catabolites (particularly in the presence of vitamin @= and @? deficiencies". Hlevated levels of kynurenic acid
have also been found in people with schi/ophrenia, and the research indicates the substance is also involved
in allied psychiatric disorders (+inderholm, et al., 2337< Hrhardt, et al., 2336".
)urthermore, tryptophan side effects in regards to greater mortality were shown in animal experiments (e.g.,
0atrina, et al., 2334" using melatonin, whereas the study authors cautioned(
[...] melatonin had a deleterious effect on the survival rate raising the Duestion whether it is correct to
assume that the hormone shows lac1 of adverse reactions. [emphasis added]
.n regards to serotonin&s involvement in higher mortality, one of its anti-longevity effects is conceivably the
reabsorption of phosphate, a pro-inflammatory chemical, by the kidneys since klotho, an anti-aging protein,
facilitates the excretion of phosphate from the kidneys (#eat, :ov. 2342".
$ince tryptophan, serotonin, and melatonin meddle with basic energy production in cells, and since metabolic
efficiency and functionality decreases proportionally with aging ()annin, et al., 4666< B&Toole, et al., 2343"
due to various factors, it seems coherent in biological terms that these substances are less prevalent, thus less
,essential- or needed, in older people, as a further decrease of an already suboptimal general metabolic
working order will aggravate physiological function systematically, increase the risk for disease (as
exemplified and foreshadowed with tryptophan side effects", promote the aging process, and explains the
increased mortality related to the administration of these substances.
$everal tryptophan side effects, such as tryptophan&s carcinogenic activities, the deterioration of metabolic
energy function, and the promotion of hypertension, can rather readily account for a greater death rate.
Final -omments ,n The 0arious 'escribed Tryptophan Side Effects
[...] tryptophan is one of the most toxic amino acids. !51uno, et al., &''?)
Khile insufficient knowledge exists about the upper tolerable intake of +-tryptophan for humans, enough
scientific data has been generated to make valid generali/ations about its degree of toxicity. .t warrants
caution.
.nterestingly, glycine, another amino acid, may be the ideal antagonist to many unwelcoming + tryptophan
side effects (#eat, )all 233=", alongside vitamin @=.
$peaking of vitamin benefits...
The use of multivitamin supplements has also a general protective action. )or example, during the tryptophan
HM$ disaster in 46;6 those people who took multivitamin supplements prior to consuming the tainted $howa
enko amino acid supplement, had a substantially lower risk of experiencing severe HM$-tryptophan side
effects (!atch 1 'oldman, 466?".
.n people with HM$, harmful degradation substances of tryptophan are elevated due to a disturbance in
tryptophan metabolism (5arga, et al., 466?". .t is fair to presume that the use of multivitamin supplements
will (partly" correct this biological imbalance or defect, and conse*uently ameliorate (in part" certain
tryptophan side effects, even from HM$. After all, a deficiency of vitamin @=, for instance, leads to the
accumulation of noxious +-tryptophan decomposition products, exacerbating the disturbances in tryptophan
metabolism.
0ritical individual differences in the mode and utili/ation of nutritional supplements, therefore, may provide
part of the explanation that only a relative minor pool of people (4 in 283 -C@eisler, 2333D" fell ill with HM$
among the very many consumers who ingested the + tryptophan tainted by $howa enko (Murray 1
#i//orno, 466;".
Bf course, these beneficial findings to avert tryptophan side effects from inEurious impact should not be
misconstrued as some fundamental approval to ingest individual moderate-high doses of + tryptophan (click
on ,43 Tips To Avoid Gisks- off the home page, and see Tip T43 for a logical explanation for this".
.n the end, the research finding that + tryptophan, 8-hydroxy tryptophan, and serotonin can all block a carrier
substance of many compounds, including +-glycine (Met/ner, et al., 2338< )rMlund, et al., 2343< Hdwards, et
al., 2344", and that degradation elements of tryptophan can impair glycine receptors in the brain ($tone,
466?", plus tryptophan&s inflammatory-degenerative activities via serotonin, suggests to minimi/e the intake
of moderate-high doses of this amino acid by single-element supplementation to avoid adverse long term
effects of tryptophan.
1utritional Supplements And Side Effects
-Conclusions A%out Tryptophan Side Effects
0he use of supplements of tryptophan, hydroxytryptophan, or of the serotonin promoting antidepressant
drugs, seems to be biologically inappropriate. !"aymond #eat, #h$, %iologist, in &''()
$erotonin ,has a basic growth regulating and defensive function- (Gay #eat, #h, @iologist, #ersonal
0ommunication, 47-April-2344". This explains why normally about 68R of it is found in the (large" intestine
(onaldson 1 'ray, 4686< #eat, March 2344" where a huge number of potentially harmful bacteria dwell.
@ut from a biological point of view, it appears that serotonin&s defensive combative feature isn&t generally
re*uired in the rest of the body because only around 4-8R of serotonin is found in the brain and e*ually little
serotonin is made from +-tryptophan ('lenmullen, 2333< #eat, March 2344".
.n all probability, serotonin&s presence at increased amounts outside the intestine exerts suppressive
destabili/ing activities, especially over time. )or instance, its increased levels found in disturbances of
cardiovascular circulation appears to be testimony of that. .n situation of chronic inEury serotonin exerts
detrimental effects as in abnormal wound healing, the development of tissue fibrosis, and impaired organ
regeneration (Mann 1 Bakley, 2342". A plausible implication thereof is that the continuous2 sustained
upregulation or activation of the substance (by artificial means" may lead to various conse*uential
serotonin>tryptophan side effects as aforementioned.
Therefore, the truth about tryptophan appears to be that, generally, this amino acid shouldn&t be consumed as
an indi"idual product on a prolon$ed basis because of its plentiful presence in the environment and due to
its inherent higher risk profile. (.n $ide Hffects Bf ietary $upplements -Top 43 Tips To Avoid Them .
elaborated on why the intake of individual single nutrient supplements tends to increase the health risks from
dietary supplements."
@y consuming + tryptophan as a single-element supplement (or by taking a selective serotonin reuptake
inhibitor>$$G.", especially in conEunction with poor protein nutrition (inade*uate intake of high protein
foods" and sub-optimal micronutrient intake, you will probably assist in directing, over time, your body&s
physiology into an inflammatory-degenerative state, thereby increasing the risk for morbidity and mortality.
As a result...
... the omission of adding this serotonin>melatonin-producing single amino acid will likely forestall a host of
potentially harmful tryptophan side effects.
%eferences
o Abbott :O, ,.nflammatory mediators and modulation of blood-brain barrier permeability-, 0ell Mol
:eurobiol. 2333 Apr<23(2"(4?4-A7.
o Abdel-Tawab 'A, Aboul-A/m T, Hbied $A, el-Toukhy MA, Abdel-!amied !A, el- Fholy NA, el-
$haraky A$, ,The correlation between certain tryptophan metabolites and the :-nitrosamine content
in the urine of bilhar/ial bladder cancer patients-, O Irol. 46;= Apr<4?8(A"(;2=-?3.
o Ables AN, :agubilli G, ,#revention, recognition, and management of serotonin syndrome-, Am )am
#hysician. 2343 May 4<;4(6"(44?6-A2.
o Agostino , 0liffton HH, ,)actors affecting the development of metastatic cancer. Hffect of
alterations in clottin mechanism-, 0ancer. 46=2 Mar- Apr<48(27=-;?.
o Agostino , 0liffton HH, ,ecrease in pulmonary metastases( potentiation of nitrogen mustard effect
by heparin and fibrinolysin-, Ann $urg. 46=? Mar<487(A33-;.
o Aleksandrin 55, Tarasova ::, Tarakanov .A, ,Hffect of serotonin on respiration, cerebral circulation,
and blood pressure in rats-, @ull Hxp @iol Med. 2338 Oan<4?6(4"(=A-7.
o Alifano A, #apa $, Tancredi ), Hlicio MA, Uuagliariello H, ,Tryptophan-:icotinic Acid Metabolism
.n #atients Kith Tumors Bf The @ladder And Fidney-, @r O 0ancer. 46=A Oun<4;(?;=-6.
o Allport O, ,.ncidence and prevalence of medication-induced osteoporosis( evidence-based review-,
0urr Bpin Gheumatol. 233; Oul<23(A"(A?8-A4.
o Arran/ :, !a/a A., 'arcVa A, Gafter O, Morales #, ,#rotective effect of vitamin 0 towards :-
nitrosamine-induced :A damage in the single-cell gel electrophoresis ($0'H">!ep'2 assay-,
Toxicol .n 5itro. 2337 Bct<24(7"(4?44- 7. Hpub 2337 Apr 4A.
o Ashida !, $hiotani @, Adachi !, !ashimoto T, Fana/awa F, anno ', ,Tryptophan pyrolysis
products, Trp-#-4 and Trp-#-2 induce apoptosis in primary cultured rat hepatocytes-, @iosci
@iotechnol @iochem. 466; :ov<=2(44"(22;?-7.
o Ashkena/y-$hahar M, @eitner G, ,$erotonin decreases cytoskeletal and cytosolic glycolytic en/ymes
and the levels of AT# and glucose 4,=- bisphosphate in skin, which is prevented by the calmodulin
antagonists thiorida/ine and clotrima/ole-, @iochem Mol Med. 4667 Apr<=3(2"(4;7-6?.
o Assouline-0ohen M, @en-#orat !, @eitner G, ,Activation of membrane skeleton- bound
phosphofructokinase in erythrocytes induced by serotonin-, Mol 'enet Metab. 466; Mar<=?(?"(2?8-
;.
o @eisler O!, Pietary $upplements and Their iscontents( )A Gegulation and the ietary
$upplement !ealth and Hducation Act of 466A,P Gutgers +aw Oournal, Kinter 2333
o @eitner G, )rucht !, Faplansky M, ,0hanges in the levels of glucose 4,=- diphosphate and cyclic
'M#, and in the activities of phosphofructokinase and phosphoglucomutase induced by serotonin in
muscle-, .nt O @iochem. 46;?<48(7"(6?8-A3.
o @ichler O, 0avin 0, $imic T, 0hakraborty A, )erk ), !oel/l 0, $chulte-!ermann G, Fundi M,
!aidinger ', Angelis F, FnasmWller $, ,0offee consumption protects human lymphocytes against
oxidative and ?-amino-4-methyl-8!- pyridoCA,?-bDindole acetate (Trp-#-2" induced :A-damage(
results of an experimental study with human volunteers-, )ood 0hem Toxicol. 2337 Aug<A8(;"(4A2;-
?=. Hpub 2337 )eb 42.
o @irt ), Oulius A, !asegawa G, $t Oohn M, 0ohen $M, ,Hffect of +-tryptophan excess and vitamin
@= deficiency on rat urinary bladder cancer promotion-, 0ancer Ges. 46;7 Mar 4<A7(8"(42AA-83.
o @occaccio 0, Medico H, ,0ancer and blood coagulation-, 0ell Mol +ife $ci. 233= May<=?(6"(432A-7.
o @raverman HG, ,The !ealing :utrients Kithin-, ?rd Hdition, 233?
o @rambilla #, #ere/ O, @arale ), $chettini ', $oares O0, ,'A@Aergic dysfunction in mood disorders-,
Mol #sychiatry. 233? Aug<;(;"(724-?7, 748.
o @reggin #G, @reggin 'G, ,Talking @ack To #ro/ac( Khat octors Aren&t Telling %ou About Today&s
Most 0ontroversial rug-, 466A
o @reggin #G, PThe Antidepressant )act @ook( Khat %our octor KonXt Tell %ou About #ro/ac, Noloft,
#axil, 0elexa, and +uvoxP, 2334
o @rennan #, @ogillot B, 'reiser H, 0hang-0laude O, Kahrendorf O, 0ordier $, OYckel F!, +ope/-
Abente ', T/onou A, 5ineis #, onato ), !ours M, $erra 0, @olm-Audorff I, $chill K, Fogevinas
M, @offetta #, ,The contribution of cigarette smoking to bladder cancer in women (pooled Huropean
data"-, 0ancer 0auses 0ontrol. 2334 Oun<42(8"(A44-7.
o @rown GG, #rice OM, ,Uuantitative studies on metabolites of tryptophan in the urine of the dog, cat,
rat, and man-, O @iol 0hem. 468= Apr<246(2"(6;8- 67.
o @ucci +, .oppolo A, 0hiavarelli G, @igotti A, ,The central-nervous-system toxicity of long-term oral
administration of +-tryptophan to porto-caval-shunted rats-, @r O Hxp #athol. 46;2 Oun<=?(?"(2?8-A4.
o @urwell T, $tith G (irectors", ,Making a Filling( The Intold $tory of #sychotropic rugging-,
ocumentary, 233;
o 0aballero @, 'leason GH, Kurtman GO, ,#lasma amino acid concentrations in healthy elderly men
and women-, Am O 0lin :utr. 4664 May<8?(8"(42A6-82.
o 0agnacci A, $oldani G, %en $$, ,Melatonin enhances cortisol levels in aged but not young women-,
Hur O Hndocrinol. 4668 ec<4??(="(=64-8.
o 0alarge 0A, Nimmerman @, Zie , Fuperman $, $chlechte OA, ,A cross-sectional evaluation of the
effect of risperidone and selective serotonin reuptake inhibitors on bone mineral density in boys-, O
0lin #sychiatry. 2343 Mar<74(?"(??;-A7.
o 0alarge 0A, Hllingrod 5+, Nimmerman @, @li/iotes MM, $chlechte OA, ,5ariants of the serotonin
transporter gene, selective serotonin reuptake inhibitors, and bone mineral density in risperidone-
treated boys( a reanalysis of data from a cross-sectional study with emphasis on pharmacogenetics-, O
0lin #sychiatry. 2344 ec<72(42"(4=;8-63.
o 0arman O$, #ost GM, @uswell G, 'oodwin )F, ,:egative effects of melatonin on depression-, Am O
#sychiatry. 467= Bct<4??(43"(44;4-=.
o 0atrina $@, 0urca H, 0atrina A., Gadu 0, 0oculescu M, ,Melatonin shortens the survival rate of
Hhrlich ascites-inoculated mice-, :euro Hndocrinol +ett. 2334 ec<22(="(A?2-A.
o 0hung FT, 'adupudi '$, ,#ossible roles of excess tryptophan metabolites in cancer-, Hnviron Mol
Mutagen. 2344 Mar<82(2"(;4-43A. doi( 43.4332>em.238;;.
o 0ohen $M, Arai M, Oacobs O@, )riedell '!, ,#romoting effect of saccharin and +-tryptophan in
urinary bladder carcinogenesis-, 0ancer Ges. 4676 Apr<?6(A"(4237-47.
o 0rist KH, ,+etter to r. Killiam Golleston, 0hairman of the +ife $ciences :etwork-, May 4=, 2338
o 0unliffe A, Bbeid BA, #owell-Tuck O, ,A placebo controlled investigation of the effects of
tryptophan or placebo on subEective and obEective measures of fatigue-, Hur O 0lin :utr. 466;
Oun<82(="(A28-?3.
o 0utolo M, 5illaggio @, Btsa F, Aakre B, $ulli A, $eriolo @, ,-Altered circadian rhythms in
rheumatoid arthritis patients play a role in the disease&s symptoms-, Autoimmun Gev. 2338
:ov<A(;"(A67-832. Hpub 2338 Oun 4?.
o anilenko F5, #lisov .+, Kir/-Oustice A, !ebert M, ,!uman retinal light sensitivity and melatonin
rhythms following four days in near darkness-, 0hronobiol .nt. 2336 Oan<2=(4"(6?-437.
o e Marte M+, Hnesco !H, ,.nfluence of low tryptophan diet on survival and organ growth in mice-,
Mech Ageing ev. 46;= Bct<?=(2"(4=4-74.
o iem $O, @lackwell T+, $tone F+, %affe F, !aney HM, @li/iotes MM, Hnsrud FH, ,Ise of
antidepressants and rates of hip bone loss in older women( the study of osteoporotic fractures-, Arch
.ntern Med. 2337 Oun 28<4=7(42"(42A3-8.
o onaldson GM Or, 'ray $O, ,$erotonin and the 8-hydroxyindole pathway of tryptophan metabolism-,
AMA Arch .ntern Med. 4686 Aug<43A(2"(??3-;.
o ubocovich M+, Mogilnicka H, Areso #M, ,Antidepressant-like activity of the melatonin receptor
antagonist, lu/indole (:-377A", in the mouse behavioral despair test-, Hur O #harmacol. 4663 Oul
?<4;2(2"(?4?-28.
o unning K), 0urtis MG, Maun MH, ,The effect of added dietary tryptophane on the occurrence of 2-
acetylaminofluorene-induced liver and bladder cancer in rats-, 0ancer Ges. 4683 Oul<43(7"(A8A-6.
o Hdenharder G, Ferkhoff ', unkelberg !, ,Hffects of beta-carotene, retinal, riboflavin, alpha-
tocopherol and vitamins 0 and F4 on sister-chromatid exchanges induced by ?-amino-4-methyl-8!-
pyridoCA,?-bDindole (Trp-#-2" and cyclophosphamide in human lymphocyte cultures-, )ood 0hem
Toxicol. 466; :ov<?=(44"(;67-63=.
o Hdwards :, Anderson 0M, 'atfield FM, Oevons M#, 'anapathy 5, Thwaites T, ,Amino acid
derivatives are substrates or non-transported inhibitors of the amino acid transporter #AT2 (slc?=a2"-,
@iochim @iophys Acta. 2344 Oan<4;3;(4"(2=3-73.
o Hllis OM, #resley O, ,5itamin @= -The octor&s Geport-, !arper 1 Gow, 467?
o Hrhardt $, Blsson $F, Hngberg ', ,#harmacological manipulation of kynurenic acid( potential in the
treatment of psychiatric disorders-, 0:$ rugs. 2336<2?(2"(64-434.
o )annin $K, +esnefsky HO, $labe TO, !assan MB, !oppel 0+, ,Aging selectively decreases oxidative
capacity in rat heart interfibrillar mitochondria-, Arch @iochem @iophys. 4666 ec 48<?72(2"(?66-
A37.
o )eksa +G, +atini A, Gech 50, KaEner M, utra-)ilho 0$, de $ou/a Kyse AT, Kannmacher 0M,
,#romotion of oxidative stress by +-tryptophan in cerebral cortex of rats-, :eurochem .nt. 233=
Oul<A6(4"(;7-6?. Hpub 233= )eb 2?.
o )errari H, Magri ), ori , Migliorati ', :escis T, Molla ', )ioravanti M, $olerte $@,
,:euroendocrine correlates of the aging brain in humans-, :euroendocrinology. 4668 Apr<=4(A"(A=A-
73.
o )orrest 0M, Mackay 'M, $toy :, Hgerton M, 0hristofides O, $tone TK, arlington +', ,Tryptophan
loading induces oxidative stress-, )ree Gadic Ges. 233A :ov<?;(44"(44=7-74.
o )otopoulou 0, $ehouli O, #schowski G, 5B: !aehling $, omanska ', @raicu H., )usch ', Geinke
#, $chefold O0, ,$ystemic changes of tryptophan catabolites via the indoleamine-2,?-dioxygenase
pathway in primary cervical cancer-, Anticancer Ges. 2344 Aug<?4(;"(2=26-?8.
o )riedman ', Idaltsova :, 0han O, Uuesenberry 0# Or, !abel +A, ,$creening pharmaceuticals for
possible carcinogenic effects( initial positive results for drugs not previously screened-, 0ancer
0auses 0ontrol. 2336 ec<23(43"(4;24-?8.
o )rMlund $, !olm G, @rodin @, :ielsen 0I, ,The proton-coupled amino acid transporter, $+0?=A4
(h#AT4", transports 'ly-'ly, 'ly-$ar and other 'ly-'ly mimetics-, @r O #harmacol. 2343
Bct<4=4(?"(8;6-=33.
o )rumento ', Gotondo G, Tonetti M, amonte ', @enatti I, )errara '@, ,Tryptophan-derived
catabolites are responsible for inhibition of T and natural killer cell proliferation induced by
indoleamine 2,?-dioxygenase-, O Hxp Med. 2332 Aug 46<46=(A"(A86-=;.
o 'addum O!, !ameed FA, ,rugs which antagoni/e 8-hydroxytryptamine-, @r O #harmacol
0hemother. 468A Oun<6(2"(2A3-;.
o 'agnJ AM, anilenko F5, Gosolen $', !Jbert M, ,.mpact of oral melatonin on the
electroretinogram cone response-, O 0ircadian Ghythms. 2336 :ov 46<7(4A.
o 'erras 0, et al. (Hditors", ,The 0omplete @ook Bf 5itamins-, Godale #ress, 4677
o 'lenmullen O, ,#ro/ac @acklash( Bvercoming the angers of #ro/ac, Noloft, #axil, and Bther
Antidepressants Kith $afe, Hffective Alternatives-, 2333
o 'reen AG, Aronson OF, 0ur/on ', Koods !), ,Metabolism of an oral tryptophan load. .( Hffects of
dose and pretreatment with tryptophan-, @r O 0lin #harmacol. 46;3 ec<43(="(=3?-43.
o 'reenwood M!, +ader M!, Fantameneni @, 0ur/on ', ,The acute effects of oral (--"-tryptophan
in human subEects-, @r O 0lin #harmacol. 4678 Apr<2(2"(4=8-72.
o 'rome OO, !arper AM, ,The effects of serotonin on local cerebral blood flow-, O 0ereb @lood )low
Metab. 46;? Mar<?(4"(74-7.
o 'ross @, Gonen :, !onigman $, +ivne H, ,Tryptophan toxicity--time and dose response in rats-, Adv
Hxp Med @iol. 4666<A=7(837-4=.
o 'uilarte TG, Kagner !: Or, ,.ncreased concentrations of ?-hydroxykynurenine in vitamin @=
deficient neonatal rat brain-, O :eurochem. 46;7 ec<A6(="(464;-2=.
o 'uilarte TG, @lock +, Kagner !: Or, ,The putative endogenous convulsant ?- hydroxykynurenine
decreases ben/odia/epine receptor binding affinity( implications to sei/ures associated with neonatal
vitamin @-= deficiency-, #harmacol @iochem @ehav. 46;; Oul<?3(?"(==8-;.
o !aEdu MA, McHlmurry GT, !eistad , @aumbach '+, ,Hffects of aging on cerebral vascular
responses to serotonin in rats-, Am O #hysiol. 466? Oun<2=A(= #t 2"(!24?=-A3.
o !aney HM, 0han @F, iem $O, Hnsrud FH, 0auley OA, @arrett-0onnor H, Brwoll H, @li/iotes MM<
for the Bsteoporotic )ractures in Men $tudy 'roup, ,Association of low bone mineral density with
selective serotonin reuptake inhibitor use by older men-, Arch .ntern Med. 2337 Oun
28<4=7(42"(42A=-84.
o !aney HM, Karden $O, @li/iotes MM, ,Hffects of selective serotonin reuptake inhibitors on bone
health in adults( time for recommendations about screening, prevention and managementQ-, @one.
2343 Oan<A=(4"(4?-7.
o !atch +, 'oldman +G, ,Geduced severity of eosinophilia-myalgia syndrome associated with the
consumption of vitamin-containing supplements before illness-, Arch .ntern Med. 466? Bct
28<48?(23"(2?=;-7?.
o !awlina M, Oenkins !', .keda !, ,iurnal variations in the electroretinographic c-wave and retinal
melatonin content in rats with inherited retinal dystrophy-, oc Bphthalmol. 4662<76(2"(4A4-83.
o !ealy , P+et Them Hat #ro/ac( The Inhealthy Gelationship @etween the #harmaceutical .ndustry
and epressionP, 233A
o !euther ', !aEak ', Geimer A, #oeggeler @, @lYmer M, Godenbeck A, GWther H, ,The metabolic fate
of infused +-tryptophan in men( possible clinical implications of the accumulation of circulating
tryptophan and tryptophan metabolites-, #sychopharmacology (@erl". 4662<436(A"(A22-?2.
o !!$ (I$ epartment of !ealth and !uman $ervices", ,The !ealth 0onse*uences of $moking( A
Geport of the $urgeon 'eneral-, Atlanta, 'A( I$ epartment of !ealth and !uman $ervices, 0enters
for isease 0ontrol and #revention, :ational 0enter for 0hronic isease #revention and !ealth
#romotion, Bffice of $moking and !ealth< 233A.
o !offer A( $chi/ophrenia( An Hvolutionary efense Against $evere $tress-, Oournal of
Brthomolecular Medicine, 5ol. 6, :o. A, #gs. 238-224, 466A
o !uether ', et al. (Hditors", ,Tryptophan, $erotonin, and Melatonin( @asic Aspects and Applications-,
Advances .n Hxperimental Medicine And @iology, 5olume A=7, 4666
o Oacobs @+, ,$erotonin and behavior( emphasis on motor control-, O 0lin #sychiatry. 4664 ec<82
$uppl(47-2?.
o Oay H, P#ill #oppersP, @@0 Two (!ori/on", 23-Oan-2343
o OMrgensen !$, ,$tudies on the neuroendocrine role of serotonin-, an Med @ull. 2337
:ov<8A(A"(2==-;;.
o Faminsky $M, +evy B, 'arry MT, 0arrasco :, ,.nhibition of the :a[>.- symporter by harmaline and
?-amino-4-methyl-8!-pyrido(A,?-b"indole acetate in thyroid cells and membrane vesicles-, Hur O
@iochem. 4664 Aug 48<233(4"(23?-7.
o Fanai %, Aosaki T, Kada B, Manabe $, ,$uppression of 'A@A-induced chloride current by ?-amino-
4-methyl-8!-pyridoCA,?-bDindole (Trp-#-2"-, Hur O #harmacol. 46;6 Aug ?<4==(?"(88?-=.
o Fepplinger @, @aran !, Fain/ A, )erra/-+eite !, :ewcombe O, Falina #, ,Age- related increase of
kynurenic acid in human cerebrospinal fluid - .g' and beta2-microglobulin changes-, :eurosignals.
2338<4A(?"(42=-?8.
o Fim %B, 0hung !O, 0hung $T, Fim O!, #ark O!, Fil F$, 0ho !, ,#hototoxicity of melatonin-,
Arch #harm Ges. 4666 Apr<22(2"(4A?-83.
o Fnook +, Favelaars A, $innema ', Fuis K, !eiEnen 0O, ,!igh nocturnal melatonin in adolescents
with chronic fatigue syndrome-, O 0lin Hndocrinol Metab. 2333 Bct<;8(43"(?=63-2.
o Foren-$chwart/er :, 0hen-Nion M, @en-#orat !, @eitner G, ,$erotonin-induced decrease in brain
AT#, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin< the protective
action of calmodulin antagonists-, 'en #harmacol. 466A Bct<28(="(4287-=2.
o Fors/un A, $ackett-+undeen +, #apadopoulos H, @rucksch 0, Masterson +, Hngelberg :0, !aus H,
emitrack MA, 0rofford +, ,Melatonin levels in women with fibromyalgia and chronic fatigue
syndrome-, O Gheumatol. 4666 ec<2=(42"(2=78-;3.
o Fostoglou-Athanassiou ., Treacher ), Kheeler MO, )orsling M+, ,Melatonin administration and
pituitary hormone secretion-, 0lin Hndocrinol (Bxf". 466; Oan<A;(4"(?4-7.
o +e )loc&h :, Btten K, Merlot H, ,Tryptophan metabolism, from nutrition to potential therapeutic
applications-, Amino Acids. 2344 :ov<A4(8"(4468-238.
o +inderholm FG, Andersson A, Blsson $, Blsson H, $nodgrass G, Hngberg ', Hrhardt $, ,Activation
of rat ventral tegmental area dopamine neurons by endogenous kynurenic acid( a pharmacological
analysis-, :europharmacology. 2337 ec<8?(;"(64;-2A. Hpub 2337 $ep 23.
o +Spe/ A, 'arcVa OA, Hscames ', 5enegas 0, Brti/ ), +Spe/ +0, Acu\a- 0astrovieEo , ,Melatonin
protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential,
and superoxide anion production-, O #ineal Ges. 2336 Mar<A=(2"(4;;-6;. Hpub 233; :ov 46.
o +ove +A, Gader O., 0rofford +O, Gaybourne G@, #rincipato MA, #age $K, Trucksess MK, $mith MO,
ugan HM, Turner M+, et al, ,#athological and immunological effects of ingesting +-tryptophan and
4,4&-ethylidenebis (+- tryptophan" in +ewis rats-, O 0lin .nvest. 466? Mar<64(?"(;3A-44.
o Mac+ean MG, empsie %, ,$erotonin and pulmonary hypertension--from bench to bedsideQ-, 0urr
Bpin #harmacol. 2336 Oun<6(?"(2;4-=. Hpub 2336 Mar 4?.
o Maclean MG, empsie %, ,The serotonin hypothesis of pulmonary hypertension revisited-, Adv Hxp
Med @iol. 2343<==4(?36-22.
o MaharaE $, Molell !, Antunes HM, MaharaE !, Maree M, :yokong T, 'lass @, aya $,
,Melatonin generates singlet oxygen on laser irradiation but acts as a *uencher when irradiated by
lamp photolysis-, O #ineal Ges. 2338 Apr<?;(?"(48?-=.
o Manabe $, Kada B, ,0arcinogenic tryptophan pyrolysis products in the environment-, O Toxicol $ci.
4664 )eb<4= $uppl 4(=?-72.
o Mann A, Bakley ), ,$erotonin paracrine signaling in tissue fibrosis-, @iochim @iophys Acta. 2342
$ep 26. pii( $3628-AA?6(42"3324;-6. doi( 43.434=>E.bbadis.2342.36.336. CHpub ahead of printD
o Marinho )0, Takagaki T%, ,!ypercoagulability and lung cancer-, CArticle in Hnglish, #ortugueseD, O
@ras #neumol. 233; May<?A(8"(?42-22.
o Martin K, ,Medical !eroes 1 !eretics-, evin-Adair, 4677
o Mateos $$, $]nche/ 0+, #aredes $, @arriga 0, GodrVgue/ A@, ,0ircadian levels of serotonin in
plasma and brain after oral administration of tryptophan in rats-, @asic 0lin #harmacol Toxicol. 2336
Oan<43A(4"(82-6.
o Matus/ak N, @ilska MA, Ges/ka FO, 0hignell 0), @ilski #, ,.nteraction of singlet molecular oxygen
with melatonin and related indoles-, #hotochem #hotobiol. 233? :ov<7;(8"(AA6-88.
o Medvedev AH, ,Gegulation by biogenic amines of energy functions of mitochondria-, CArticle in
GussianD, 5opr Med Fhim. 4663 $ep-Bct<?=(8"(4;- 24.
o Medvedev AH, 'orkin 5N, ,The role of monoamine oxidase in the regulation of mitochondrial
energy functions-, CArticle in GussianD, 5opr Med Fhim. 4664 $ep-Bct<?7(8"(2-=.
o Mela +, 'oodwin 0K, Miller +, ,.n vivo control of mitochondrial en/yme concentrations and
activity by oxygen-, Am O #hysiol. 467= ec<2?4(="(4;44- =.
o Mendelsohn , Giedel KO, $ambeth A, ,Hffects of acute tryptophan depletion on memory, attention
and executive functions( a systematic review-, :eurosci @iobehav Gev. 2336 Oun<??(="(62=-82. Hpub
2336 Mar 4;.
o Met/ner +, Fottra ', :eubert F, aniel !, @randsch M, ,$erotonin, +- tryptophan, and tryptamine
are effective inhibitors of the amino acid transport system #AT4-, )A$H@ O. 2338 $ep<46(44"(4A=;-
7?.
o Mironova HM, #avlova B:, Gonkina T., ,The early diagnosis, evaluation of treatment results and
modelling of certain aspects of the pathogenesis of retinal dystrophy-, CArticle in GussianD, Bftalmol
Nh. 46;6<(;"(A=6-7?.
o Mir/oian G$, , :europrotective and cerebrovascular effects of 'A@A mimetics-, CArticle in
GussianD, Hksp Flin )armakol. 233? Mar-Apr<==(2"(8?-=.
o Moehn $, #enchar/ #@, @all GB, ,+essons +earned Gegarding $ymptoms of Tryptophan eficiency
and Hxcess from Animal Ge*uirement $tudies-, O :utr. 2342 Bct 47. CHpub ahead of printD
o Mohammad-Nadeh +), Moses +, 'waltney-@rant $M, ,$erotonin( a review-, O 5et #harmacol Ther.
233; Oun<?4(?"(4;7-66.
o Mohr H, @runo ', )oster :, 'illespie M, 0ox 0, !are TA, Tamminga 0, )edio #, 0hase T:,
,'A@A-agonist therapy for Al/heimer&s disease-, 0lin :europharmacol. 46;=<6(?"(287-=?.
o Mousa $A, ,Gole of current and emerging antithrombotics in thrombosis and cancer-, rugs Today
(@arc". 233= May<A2(8"(??4-83.
o Mueller '#, Twohy 0#, 0hen !T, Advis O#, Meites O, ,Hffect of +-tryptophan and restraint stress on
hypothalmic and brain serotonin turnover, and pituitary T$! and prolactin release in rats-, +ife $ci.
467= Apr 4<4;(7"(748-2A.
o Murphy #O, Myers @+, @adia #, ,:onsteroidal anti-inflammatory drugs alter body temperature and
suppress melatonin in humans-, #hysiol @ehav. 466= Oan<86(4"(4??-6.
o Murray MT, #i//orno OH, ,Hncyclopedia Bf :atural Medicine-, Gevised 2nd Hdition, 466;
o :Jmeth !, Toldi O, 5Jcsei +, ,Gole of kynurenines in the central and peripheral nervous systems-,
0urr :eurovasc Ges. 2338 Oul<2(?"(2A6-=3.
o :emoto :, Fusumi $, Takayama $, :agao M, $ugimura T, ,Metabolic activation of ?-amino-8!-
pyridoCA,?-bDindole, a highly mutagenic principle in tryptophan pyrolysate, by rat liver en/ymes-,
0hem @iol .nteract. 4676 Bct<27(2-?"(464- ;.
o :ewling K, Gobinson MG, $mith #!, @yar , +ockwood G, $tevens ., e #auw M, $ylvester G,
,Tryptophan metabolites, pyridoxine (vitamin @=" and their influence on the recurrence rate of
superficial bladder cancer. Gesults of a prospective, randomised phase ... study performed by the
HBGT0 'I 'roup. HBGT0 'enito-Irinary Tract 0ancer 0ooperative 'roup-, Hur Irol.
4668<27(2"(443-=.
o Bberweis @, 'ragnoli 0, ,#otential role of prolactin in antipsychotic-mediated association of
schi/ophrenia and type 2 diabetes-, O 0ell #hysiol. 2342 Aug<227(;"(?334-=.
o Bhta T < $u/uki $ < Furechi T, ,)ormation of mutagen by the reaction of nitrite with several
tryptophan decomposition products resulting from acid hydrolysis of protein-, Mutat Ges< 444 (4".
46;?. ??-A2.
o Bkada $, Famb M+, #andey O#, #hilen GM, +ove +A, Miller )K, ,.mmunogenetic risk and
protective factors for the development of +-tryptophan-associated eosinophilia-myalgia syndrome and
associated symptoms-, Arthritis Gheum. 2336 Bct 48<=4(43"(4?38-44.
o Bkatani %, Bkada M, $agara %, ,$timulation of prolactin secretion by melatonin is not mediated by
opioids-, !orm Ges. 466A<A4(4"(?;-A2.
o Bkuno A, )ukuwatari T, $hibata F, ,Irinary excretory ratio of anthranilic acid>kynurenic acid as an
index of the tolerable amount of tryptophan-, @iosci @iotechnol @iochem. 233; Oul<72(7"(4==7-72.
Hpub 233; Oul 7.
o Boka !, $egall #H, Timiras #$, ,!istology and survival in age-delayed low- tryptophan-fed rats-,
Mech Ageing ev. 46;; Apr<A?(4"(76-6;.
o Bpit/ 0A, +it/enburger IM, $ahm ), Btt M, Tritschler ., Trump $, $chumacher T, Oestaedt +,
$chrenk , Keller M, Ougold M, 'uillemin 'O, Miller 0+, +ut/ 0, Gadlwimmer @, +ehmann ., von
eimling A, Kick K, #latten M, PAn endogenous tumour-promoting ligand of the human aryl
hydrocarbon receptor-, :ature. 2344 Bct 8<A7;(7?=;"(467-23?.
o B&Toole O), #atel !5, :aples 0O, )uEioka !, !oppel 0+, ,ecreased cytochrome c mediates an age-
related decline of oxidative phosphorylation in rat kidney mitochondria-, @iochem O. 2343 Mar
48<A27(4"(438-42.
o #eat G, ,The Transparency Bf +ife( 0ataracts As A Model Bf Age-related isease-, Gay #eat&s
:ewsletter, $pring 233=
o #eat G, ,Tryptophan, $erotonin, And Aging-, Gay #eat&s :ewsletter, )all 233=
o #eat G, ,+actate 5s. 0o2 .n Kounds, $ickness, And Aging< The Bther Approach To 0ancer-, Gay
#eat&s :ewsletter, $ept. 233;
o #eat G, ,0ontrolling $ymptoms .n Multiple $clerosis And $tress-Gelated iseases-, Gay #eat&s
:ewsletter, :ov. 233;
o #eat G, ,$erotonin, epression, And Aggression( The #roblem Bf @rain Hnergy-, Gay #eat&s
:ewsletter, $pring 2336
o #eat G, ,Thyroid, .nsomnia, And The .nsanities( 0ommonalities .n isease-, Gay #eat&s :ewsletter,
$ummer 2336
o #eat G, ,'elatin, $tress, +ongevity-, Gay #eat&s :ewsletter, )all 2336
o #eat G, ,$erotonin( Hffects .n isease, Aging And .nflammation-, Gay #eat&s :ewsletter, March 2344
o #eat G, ,Bsteoporosis, Aging, Tissue Genewal, And #roduct $cience-, Gay #eat&s :ewsletter, $ept.
2344
o #eat G, ,!ot )lashes, Hnergy, And Aging-, raft :ewsletter, #ersonal 0ommunication, ?-$ept-2342,
Ahead Bf #rint.
o #eat G, ,#hosphate, Activation, And Aging-, Gay #eat&s :ewsletter, :ov. 2342
o #echenova T:, $ushkova 55, $olodova H5, 'ulyi M), , Hffect of tryptophan excess in a diet on
amino acid composition of skin collagen and on an initial stage of protein biosynthesis in rat live-,
CArticle in IkrainianD, Ikr @iokhim Nh. 46;? Mar-Apr<88(2"(4A=-83.
o #ipkin 'H, $chlegel OI, :ishimura G, $hult/ ':, ,.nhibitory effect of +- ascorbate on tumor
formation in urinary bladders implanted with ?- hydroxyanthranilic acid-, #roc $oc Hxp @iol Med.
46=6 Oun<4?4(2"(822-A.
o #latten M, Kick K, 5an den Hynde @O, ,Tryptophan 0atabolism in 0ancer( @eyond .B and
Tryptophan epletion-, 0ancer Ges. 2342 Bct 22. CHpub ahead of printD
o Gavdin #M, 0ronin FA, !owlader :, @erg 0, 0hlebowski GT, )euer HO, Hdwards @F, @erry A,
,The decrease in breast-cancer incidence in 233? in the Inited $tates-, : Hngl O Med. 2337 Apr
46<?8=(4="(4=73-A.
o Geyes-Toso 0), Gicci 0G, de Mignone .G, Geyes #, +inares +M, Alborno/ +H, 0ardinali #,
Naninovich A, ,.n vitro effect of melatonin on oxygen consumption in liver mitochondria of rats-,
:euro Hndocrinol +ett. 233? Bct<2A(8"(?A4-A.
o Geyes-Toso 0), Gebagliati .G, Gicci 0G, +inares +M, Alborno/ +H, 0ardinali #, Naninovich A,
,Hffect of melatonin treatment on oxygen consumption by rat liver mitochondria-, Amino Acids.
233= Bct<?4(?"(266-?32. Hpub 233= Mar 2A.
o Gieber :, @elohradsky @!, ,A!G activation by tryptophan--pathogenic hallmark of Th47-mediated
inflammation in eosinophilic fasciitis, eosinophilia-myalgia- syndrome and toxic oil syndrome-,
.mmunol +ett. 2343 )eb 4=<42;(2"(48A-8. Hpub 2336 :ov 2A.
o Gom-@ugolavskaia H$, $hcherbakova 5$, Fomarova .5, ,The effect of melatonin and mexamine on
the human thyroid under in-vitro conditions-, CArticle in GussianD, Hksp Flin )armakol. 4667 Oul-
Aug<=3(A"(A=-6.
o Gonen :, +ivne H, 'ross @, ,Bxidative damage in rat tissue following excessive +-tryptophan and
atherogenic diets-, Adv Hxp Med @iol. 4666<A=7(A67-838.
o Gothenberg 0O, ,The Gise and )all of Hstrogen Therapy( The !istory of !GT-, !arvard +aw $chool,
0lass of 2338, April 28, 2338
o $antana-Gios ', Brner 'A, Amantana A, #rovost 0, Ku $%, ashwood G!, ,#otent antimutagenic
activity of white tea in comparison with green tea in the $almonella assay-, Mutat Ges. 2334 Aug
22<A68(4-2"(=4-7A.
o $arwar ', @otting !', 0ollins M, ,A comparison of fasting serum amino acid profiles of young and
elderly subEects-, O Am 0oll :utr. 4664 ec<43(="(==;- 7A.
o $as F, Gobotka !, Toldi O, 5Jcsei +, ,Mitochondria, metabolic disturbances, oxidative stress and the
kynurenine system, with focus on neurodegenerative disorders-, O :eurol $ci. 2337 Oun 48<287(4-
2"(224-?6. Hpub 2337 Apr 28.
o $atoh F, Mishima F, ,!ypothermic action of exogenously administered melatonin is dose-
dependent in humans-, 0lin :europharmacol. 2334 :ov-ec<2A(="(??A-A3.
o $chlegel OI, ,#roposed uses of ascorbic acid in prevention of bladder carcinoma-, Ann : % Acad $ci.
4678 $ep ?3<28;(A?2-7.
o $chlegel OI, #ipkin 'H, :ishimura G, $hult/ ':, ,The role of ascorbic acid in the prevention of
bladder tumor formation-, O Irol. 4673 )eb<43?(2"(488-6.
o $earle 0H (Hditor", ,0hemical 0arcinogens-, A0$ Monograph 47?, Kashington, 0( American
0hemical $ociety, 467=, pg. AA?
o $egall #, ,+ong-term tryptophan restriction and aging in the rat-, Aktuelle 'erontol. 4677
Bct<7(43"(8?8-;.
o $egall #H, Timiras #$, ,#atho-physiologic findings after chronic tryptophan deficiency in rats( a
model for delayed growth and aging-, Mech Ageing ev. 467= Mar-Apr<8(2"(436-2A.
o $eyfried T:, P0ancer as a Metabolic isease( Bn the Brigin, Management, and #revention of
0ancerP, 2342
o $harma AM, $chorr I, Thiede !M, istler A, ,Hffect of dietary salt restriction on urinary serotonin
and 8-hydroxyindoleacetic acid excretion in man-, O !ypertens. 466? ec<44(42"(4?;4-=.
o $harma !$, ,42 - .nfluence of $erotonin on the @lood-@rain and the @lood- $pinal 0ord @arriers-,
#ages 447^487, from &@lood-$pinal 0ord and @rain @arriers in !ealth and isease&, Academic #ress,
233A
o $hiah .$, %atham +:, ,'A@A function in mood disorders( an update and critical review-, +ife $ci.
466;<=?(48"(42;6-?3?.
o $hishu, $ingla AF, Faur .#, ,.nhibitory effect of curcumin and its natural analogues on genotoxicity
of heterocyclic amines from cooked food-, .ndian O Hxp @iol. 2332 ec<A3(42"(4?=8-72.
o $hishu, Faur .#, ,.nhibition of mutagenicity of food-derived heterocyclic amines by sulforaphane--a
constituent of broccoli-, .ndian O Hxp @iol. 233? Mar<A4(?"(24=-6.
o $idransky !, ,Tryptophan( @iochemical and !ealth .mplications-, 2334
o $imon :, Oolliet #, Morin 0, Nini G, Irien $, Tillement O#, ,'lucocorticoids decrease cytochrome c
oxidase activity of isolated rat kidney mitochondria-, )H@$ +ett. 466; $ep 44<A?8(4"(28-;.
o $mith MO, 'arrett G!, ,A heretofore undisclosed crux of eosinophilia-myalgia syndrome(
compromised histamine degradation-, .nflamm Ges. 2338 :ov<8A(44"(A?8-83.
o $tone TK, ,:europharmacology of *uinolinic and kynurenic acids-, #harmacol Gev. 466?
$ep<A8(?"(?36-76.
o $tone TK, Mackay 'M, )orrest 0M, 0lark 0O, arlington +', ,Tryptophan metabolites and brain
disorders-, 0lin 0hem +ab Med. 233? Oul<A4(7"(;82-6.
o $treeter 00, Khitfield T!, Bwen +, Gein T, Farri $F, %akhkind A, #erlmutter G, #rescot A,
Genshaw #), 0iraulo A, Oensen OH, ,Hffects of yoga versus walking on mood, anxiety, and brain
'A@A levels( a randomi/ed controlled MG$ study-, O Altern 0omplement Med. 2343
:ov<4=(44"(44A8-82. Hpub 2343 Aug 46.
o $ugawara T, $ieving #A, .uvone #M, @ush GA, ,The melatonin antagonist lu/indole protects retinal
photoreceptors from light damage in the rat-, .nvest Bphthalmol 5is $ci. 466; :ov<?6(42"(2A8;-=8.
o $utherland HG, Hllison M0, Fraft M, Martin GO, ,Hlevated serum melatonin is associated with the
nocturnal worsening of asthma-, O Allergy 0lin .mmunol. 233? $ep<442(?"(84?-7.
o $u/uki !, $one !, Fawamura F, .shihara F, ,+iver inEury due to ?-amino-4- methyl-8h-pyrido CA,?-
bD indole (Trp-#-2" and its prevention by miso-, @iosci @iotechnol @iochem. 233; Aug<72(;"(22?=-;.
Hpub 233; Aug 7.
o Takahashi M, Toyoda F, A/e %, )uruta F, Mitsumori F, !ayashi %, ,The rat urinary bladder as a new
target of heterocyclic amine carcinogenicity( tumor induction by ?-amino-4-methyl-8!-pyridoCA,?-
bDindole acetate-, Opn O 0ancer Ges. 466? Aug<;A(;"(;82-;.
o Takikawa B, Truscott GO, )ukao M, Miwa $, ,Age-related nuclear cataract and indoleamine 2,?-
dioxygenase-initiated tryptophan metabolism in the human lens-, Adv Hxp Med @iol. 233?<827(277-
;8.
o Tannenbaum $G, ,#reventive action of vitamin 0 on nitrosamine formation-, .nt O 5itam :utr Ges
$uppl. 46;6<?3(436-4?.
o Tannenbaum $G, Kishnok O$, +eaf 0, ,.nhibition of nitrosamine formation by ascorbic acid-, Am O
0lin :utr. 4664 Oan<8?(4 $uppl"(2A7$-283$.
o ten 0ate !, )alanga A, ,Bverview of the postulated mechanisms linking cancer and thrombosis-,
#athophysiol !aemost Thromb. 233;<?=(?-A"(422-?3.
o Trousseau A, ,0lini*ue Medicale de +&!otel ieu de #aris-, 2nd Hdition, +ondon, :ew $ydenham
$ociety, 5ol ?, #g 6A, 4;=8
o Trulson MH, $ampson !K, ,Iltrastructural changes of the liver following +- tryptophan ingestion in
rats-, O :utr 46;=< 44=(4436-4448.
o Iehara T, $umiyoshi T, Matsuoka T, Tanaka F, Tsunoda M, .toh !, Furachi M, ,Hnhancement of
lactate metabolism in the basolateral amygdala by physical and psychological stress( role of
ben/odia/epine receptors-, @rain Ges. 2338 ec 4A<43=8(4-2"(;=-64. Hpub 2338 :ov 2?.
o 5aishnav A, +utsep !+, ,'A@A agonist( clomethia/ole-, 0urr Med Ges Bpin. 2332<4; $uppl 2(s8-;.
o 5arga O, Oimene/ $A, Iitto O, ,+-tryptophan and the eosinophilia-myalgia syndrome( current
understanding of the etiology and pathogenesis-, O .nvest ermatol. 466? Oan<433(4"(67$-438$.
o Kagner A, $huker H, @ilma/es 0, Bbied/inski M, @aker ., %oung 5G, Tannenbaum $G, ,Hffect
of vitamins 0 and H on endogenous synthesis of :- nitrosamino acids in humans( precursor-product
studies with C48:Dnitrate-, 0ancer Ges. 46;8 ec<A8(42 #t 4"(=846-22.
o Kakabayashi F, Fim .$, Furosaka G, %amai/umi N, Ishiyama !, Takahashi M, Foyota $, Tada A,
:ukaya !, 'oto $, et al., ,.dentification of new mutagenic heterocyclic amines and *uantification of
known heterocyclic amines-, #rincess Takamatsu $ymp. 4668<2?(?6-A6.
o Karburg B, ,Bn the Brigin of 0ancer 0ells-, $cience, 5ol. 42? no. ?464 pp. ?36-?4A, 2A )ebruary
468=
o Katanabe M, Takahashi T, %oshida M, $u/uki M, Muramatsu $, ,Gelationship between tryptophan
intake and urinary excretion of ?-hydroxy-kynurenine, ?- hydroxyanthranilic acid, xanthurenic acid
and kynurenic acid-, O :utr $ci 5itaminol (Tokyo". 4676<28(2"(448-22.
o Katanabe M, , Microanalysis of tryptophan metabolite-, CArticle in OapaneseD, %akugaku Nasshi.
4667 :ov<447(43-44"(=87-=A.
o Kebley 'H, @Yhle A, +eidenberger )A, ,#ositive relationship between the nocturnal concentrations
of melatonin and prolactin, and a stimulation of prolactin after melatonin administration in young
men-, O #ineal Ges. 46;;<8(4"(46-??.
o Keinstock M, @lotnick $, $egal M, ,$easonal variation in the development of stress-induced systolic
hypertension in the rat-, O !ypertens $uppl. 46;8 ec<?(?"($437-6.
o Kichers M0, Maes M, ,The role of indoleamine 2,?-dioxygenase (.B" in the pathophysiology of
interferon-alpha-induced depression-, O #sychiatry :eurosci. 233A Oan<26(4"(44-7.
o Kiechmann A), B&$teen KF, ,Melatonin increases photoreceptor susceptibility to light-induced
damage-, .nvest Bphthalmol 5is $ci. 4662 May<??(="(4;6A-632.
o Kiechmann A), ,Gegulation of gene expression by melatonin( a microarray survey of the rat retina-,
O #ineal Ges. 2332 Bct<??(?"(47;-;8.
o Kiechmann A), 0hignell 0), Goberts OH, ,.nfluence of dietary melatonin on photoreceptor survival
in the rat retina( an ocular toxicity study-, Hxp Hye Ges. 233; )eb<;=(2"(2A4-83.
o Killiams +O, !enry MO, @erk M, odd $, Oacka ):, Fotowic/ MA, :icholson '0, #asco OA,
,$elective serotonin reuptake inhibitor use and bone mineral density in women with a history of
depression-, .nt 0lin #sychopharmacol. 233; Mar<2?(2"(;A-7.
o Kinkelman OK, @uxton BM, Oensen OH, @enson F+, B&0onnor $#, Kang K, Genshaw #), ,Geduced
brain 'A@A in primary insomnia( preliminary data from AT proton magnetic resonance spectroscopy
(4!-MG$"-, $leep. 233; :ov<?4(44"(4A66-83=.
o Kinkler T, $harma !$, $t_lberg H, Blsson %, ey #F, ,.mpairment of blood- brain barrier function
by serotonin induces desynchroni/ation of spontaneous cerebral cortical activity( experimental
observations in the anaestheti/ed rat-, :euroscience. 4668 Bct<=;(A"(4367-43A.
o Koolley K, $haw H, ,$ome neurophysiological aspects of serotonin-, @r Med O. 468A Oul
47<2(A;;3"(422-=.
o Kright M+, #ikula A, @abski AM, +abieniec FH, Kolan G@, ,Hffect of melatonin on the response of
the thyroid to thyrotropin stimulation in vitro-, 'en 0omp Hndocrinol. 4667 :ov<43;(2"(26;-?38.
o Kright M+, 0uthbert F+, onohue MO, $olano $, #roctor F+, ,irect influence of melatonin on
the thyroid and comparison with prolactin-, O Hxp Nool. 2333 May 4<2;=(="(=28-?4.
o %ama/oe %, .shii F, Famataki T, Fato G, $ugimura T, ,.solation and characteri/ation of active
metabolites of tryptophan-pyrolysate mutagen, TG#- #-2, formed by rat liver microsomes-, 0hem
@iol .nteract. 46;3 May<?3(2"(428-?;.
o %ama/oe %, .shii F, Famataki T, Fato G, ,$tructural elucidation of a mutagenic metabolite of ?-
amino-4-methyl-8!-pyridoCA,?-bDindole-, rug Metab ispos. 46;4 May-Oun<6(?"(262-=.
o %aryura-Tobias OA, @hagavan !:, :e/iroglu ), ,Tryptophan and #erceptual $chi/ophrenias-, +etter
to the Hditor, Brthomolecular #sychiatry, 5ol. =, :o. 2, #ps. 46?-46A, 4677
o %oshimoto M, Tsutsumi M, .ki F, $asaki %, TsuEiuchi T, $ugimura T, Kakabayashi F, Fonishi %,
,0arcinogenicity of heterocyclic amines for the pancreatic duct epithelium in hamsters-, 0ancer +ett.
4666 $ep 4<4A?(2"(2?8-6.
o %oung #, )inn @0, Alvare/ ), 5erdaguer M), @ottaro )O, @ruetman OH, ,$erotonin syndrome( four
report cases and review of the literature-, CArticle in $panishD, An Med .nterna. 233; Mar<28(?"(428-
?3.
o %uwiler A, @rammer '+, Morley OH, Galeigh MO, )lannery OK, 'eller H, ,$hort- term and repetitive
administration of oral tryptophan in normal men. Hffects on blood tryptophan, serotonin, and
kynurenine concentrations-, Arch 'en #sychiatry. 46;4 Oun<?;(="(=46-2=.
o Namanakou M, 'ermenis AH, Faranikas 5, ,Tumor immune escape mediated by indoleamine 2,?-
dioxygenase-, .mmunol +ett. 2337 Aug 48<444(2"(=6-78. Hpub 2337 Oul 2.
o Narkovsky AM, ,The inhibitory effect of endogenous convulsants *uinolinic acid and kynurenine on
the pentobarbital stimulation of C?!Dflunitra/epam binding-, #harmacol @iochem @ehav. 46;=
May<2A(8"(4248-7.
o Nolkowska , Gothman G@, @aumann M!, ,Amphetamine analogs increase plasma serotonin(
implications for cardiac and pulmonary disease-, O #harmacol Hxp Ther. 233= Aug<?4;(2"(=3A-43.
Hpub 233= Apr 27.