Normal neuro transmittion
Serotonin is a neurotransmitter produced in the
brain known to influence the functioning of the
cardiovascular, renal, immune, and
Any disruption in the synthesis, metabolism or
uptake of this neurotransmitter has been found
to be partly responsible for certain
schizophrenia, depression, compulsive disorders
and learning problems.
Serotonin originates in neurons deep in the
midline of the brainstem. Because these
neurons profile diffusely throughout the...
Mind and Stomach
The brain and the gut have a lot in common, including the
ways in which nerve cells talk with each other.
Neurotransmitters are important chemicals that allow
nerve cells to communicate. Serotonin is one of the most
important neurotransmitters for that brain in your gut.
Serotonin is important for the functions of your brain and
your mood, but it is crucial to the function of your
digestive system. Your gut creates 95 percent of the
serotonin in your body. Changes in your levels of serotonin
and your sensitivity to serotonin signaling can change how
your bowel works.
What Does Serotonin Do?
Serotonin affects many aspects of your gut
It changes the motility of your bowels (how fast
food moves through your system).
It affects how much fluid, such as mucus, is
secreted in your intestines.
It affects how sensitive your intestines are to
sensations like pain and fullness.
Differences in serotonin levels between individuals also line up with the differences
between people who suffer from IBS. For example, people with IBS who have
constipation often have lower-than-normal levels of serotonin. The muscles in their
rectums are less reactive to serotonin, and they’re more likely to have hard or lumpy
stools. Others with IBS who have diarrhea have been shown to have higher-thannormal levels of serotonin. Their rectums are more reactive: more likely to empty too
There are fourteen different kinds of receptors in your intestines that react in different
ways to serotonin. Some receptors are responsible for sending messages to the brain
that signal nausea, bloating, and pain. Other receptors change your sensitivity to or
intensity of how distended or full your intestines feel.
Our body chemistry is complex; many different
hormones, neurotransmitters, and other substances
influence how we feel. Serotonin is one chemical that has
received a great deal of attention for its contribution to
mood. It's a neurotransmitter (a chemical involved in the
transmission of nerve impulses between nerve cells) that's
formed in the brain and primarily found in three parts of
the body — the brain, the lining of the digestive tract, and
in blood platelets. In the brain, serotonin's main effects
include improving mood and giving you that "satisfied"
feeling from food. It's also thought to help promote sleep
Carbohydrate-rich meals often increase serotonin levels.
However, manipulating serotonin levels through food may be very difficult to
achieve because serotonin's properties may have varying effects in different
people. Some people may experience a temporary lift in mood after a
carbohydrate-rich meal, while others may become relaxed or sleepy. Certain
foods that increase serotonin levels aren't the healthiest choices either.
Believe it or not, candy and sweets, which are simple carbohydrates, have the
greatest impact, but the effect will only last 1 to 2 hours. Complex
carbohydrates (rice, potato, pasta) may increase serotonin levels, but not to
the same extent because the protein content of these foods might actually
inhibit serotonin production.
Here's a brief explanation of the mechanism behind the effect of food on serotonin
levels: after consumption of a carbohydrate-rich meal, the hormone insulin is
secreted. Insulin lowers the blood levels of most amino acids (the building blocks of
protein), except for tryptophan (a precursor to serotonin). Amino acids compete for
transportation across the blood-brain barrier, and when there is a larger proportion of
tryptophan, it enters the brain at a higher rate, thus boosting serotonin production. To
make matters more interesting, tryptophan is present in many protein-rich
foods, which have been found to prevent serotonin production. So, you can see how
intricate and complex this system is
If you're having trouble falling asleep, try a small snack of carbohydraterich food. Warm milk may work for the psychological comfort, but also
because milk contains a moderate amount of carbohydrate in the form of
lactose (milk sugar).
If you tend to have only carbohydrates (e.g., plain bagel or muffin) before
class, and you often fall asleep during class, try adding some protein by
putting some hard cheese (cheddar, American, Swiss, etc.) or peanut
butter on the bagel. Or, have a yogurt or cottage cheese instead.
For those who are active (athletes or exercisers), don't be fooled by
carbohydrate's relaxing effects. You'll do best with a diet rich in
grains/starches, legumes (dried beans and peas), fruit, and vegetables in
order to get carbohydrates for muscle energy. Don't skimp on protein
either, which is necessary for muscle growth and repair.
Additionally, include some fat for satiety and healthy skin.
Since each of us is unique, in order to get a "desired effect" from food, you would need
to experiment eating different foods and observing how your body reacts to each of
them. You'll also need to take into consideration your other lifestyle choices — how
much sleep you get, whether or not you exercise regularly, the medications you
take, your stress levels, etc. — when figuring out what affects your moods in what
manners. If you have more questions about mood and food, consider scheduling an
appointment with a nutritionist at Health Services by calling x4-2284 or logging into
Open Communicator. If you're not at Columbia, ask for a referral to one from your
primary health care provider.
Serotonin is known as the happy molecule. As consumers of health advice, we’re
bombarded with top tips for boosting our serotonin levels – instant fixes for feeling
glum – based on the premise that low serotonin levels lead to feelings of sadness and
depression. According to the internet, we should all be pounding on treadmills and
scoffing turkey sandwiches to make ourselves feel better. But while it’s true that
turkey contains tryptophan – the essential amino acid that our bodies need to make
serotonin – the connection between serotonin and our state of mind is rather more
Mechanism of action of
According to the present model of SERT function, the first step occurs when Na+
binds to the carrier protein. Serotonin, in its protonated form (5HT+), then binds
to the transporter followed by Cl-. Chloride ions are not required for 5HT+
binding to occur but are necessary for net transport to take place. The initial
complex of serotonin, Na+, and Cl- creates a conformational change in the
transporter protein. The protein, which began by facing the outside of the
neuron, moves to an inward position where the neurotransmitter and ions are
released into the cytoplasm of the neuron. Intracellular K+ then binds to the
SERT to promote reorientation of the carrier for another transport cycle. The
unoccupied binding site becomes, once again, exposed to the outside of the cell
and the K+ is released outside the cell.
Chemistry of serotonin
Although serotonin may be obtained from a variety of dietary
sources, endogenous 5-HT is synthesized in situ from tryptophan
through the actions of the enzymes tryptophan hydroxylase and
aromatic L-amino acid decarboxylase. Both dietary and
endogenous 5-HT are rapidly metabolized and inactivated by
monoamine oxidase and aldehyde dehydrogenase to the major
metabolite, 5-hydroxyindoleacetic acid (5-HIAA).
Of the chemical neurotransmitter substances, serotonin is perhaps the most
implicated in the etiology or treatment of various disorders, particularly those
of the central nervous system, including anxiety, depression, obsessivecompulsive
disorder, schizophrenia, stroke, obesity, pain, hypertension, vascular
disorders, migraine, and nausea. A major factor in our understanding of the
role of 5-HT in these disorders is the recent rapid advance made in
understanding the physiological role of various serotonin receptor subtypes.
This review will summarize the physiological functions of serotonin--those
drugs currently available that act by mimicking or antagonizing the actions of
serotonin--and the future development of serotonergic agents.
Serotonin was first isolated from blood in 1948 by Page and coworkers and
was later identified in the central nervous system. As is the case for most
neurotransmitters, it has a relatively simple chemical structure but displays
complex pharmacological properties. Based on the similarity of this structure
to the structures of norepinephrine and dopamine, it is not surprising that
serotonin, like its catecholamine counterparts, possesses a diversity of
pharmacological effects, both centrally and peripherally. It is found in three
main areas of the body: the intestinal wall (where it causes increased
gastrointestinal motility); blood vessels (where large vessels are constricted);
and the central nervous system (CNS).
The most widely studied effects have been those on the CNS. The functions
of serotonin are numerous and appear to involve control of
appetite, sleep, memory and learning, temperature
regulation, mood, behavior (including sexual and hallucinogenic
behavior), cardiovascular function, muscle contraction, endocrine
regulation, and depression. Peripherally, serotonin appears to play a major
role in platelet homeostasis, motility of the GI tract, and carcinoid tumor
secretion. This represents quite a broad spectrum of pharmacological and
psychological effects, considering the fact that the average human adult
possesses only about 10 mg of 5-HT. Subsequent to his discovery of
serotonin, Page commented that no physiological substance known
possesses such diverse actions in the body as does 5-HT.
Chemical neurotransmitters (CNTs) produce their effects as a consequence of
interactions with appropriate receptors. As is the case with all the
CNTs, serotonin is synthesized in brain neurons and stored in vesicles. Upon a
nerve impulse, it is released into the synaptic cleft, where it interacts with
various postsynaptic receptors.
The actions of 5-HT are terminated by three major mechanisms: diffusion;
metabolism; and uptake back into the synaptic cleft through the actions of
specific amine membrane transporter systems. These events are summarized
in Figure 1. Thus, the actions of 5-HT can be theoretically modulated by
agents that stimulate or inhibit its biosynthesis (step 1); agents that block its
storage (step 2); agents that stimulate or inhibit its release (step 3); agents
that mimic or inhibit its actions at its various postsynaptic receptors (step 4);
agents that inhibit its uptake back into the nerve terminal (step 5); agents
that affect its metabolism (step 6).
by Debora-Dale Young
5-HTP (5-hydroxytryptophan) is an amino acid that is the active
intermediate between L-Tryptophan and the important brain
chemical serotonin. Serotonin supports
sleep, mood, appetite, temperature balance, sexual behaviour
and pain sensation. Lifestyle and dietary practices of many
people today result in lowered levels of serotonin. As a
result, many people are overweight, crave sugar experience
depression, headaches, and have muscle aches and pain.
- See more at: http://www.clinicians.co.nz/5htp/#sthash.iplGBiPA.dpuf
The introduction of the antidepressant Prozac (fluoxetine) whose mode of
action is to support ‘healthy serotonin’ levels, helped increase public
awareness regarding the role of serotonin as a ‘happy chemical’ for mood
support. Serotonin has a number of actions in the body, it is also involved in
sleep, eating, temperature regulation, movement and nervousness1 Natural
health practitioners on the other hand have used St. Johns wort and a
substance called 5-HTP for the same reason. So what is 5-HTP or 5Hydroxytryptophan as it is otherwise known? It is a precursor or building
block for the production of the neurotransmitter serotonin one of our ‘happy
chemicals.’ - See more at: http://www.clinicians.co.nz/5htp/#sthash.iplGBiPA.dpuf
The brain is a chemical factory that works 24 hours a day to produce a range of
neurotransmitters (mood messengers) and hormones involved in the regulation of
many body processes including the sleep/ wake cycle. To do this the brain and body
utilizes vitamins, minerals and amino acids from protein that must all be obtained
from dietary sources. Poor digestion, excess or ongoing stress and poor dietary choices
such as excess caffeine, alcohol and processed foods combined with insufficient
protein, rob the body of the building blocks and cofactors it requires for
neurotransmitter production. This can lead to low mood and poor quality sleep.
Dietary levels of the amino acid tryptophan are directly related to the body’s ability to
produce serotonin, which is also a precursor to the sleep hormone melatonin. The age
old recommendation of a hot milk or chocolate drink at night to support sleep comes
from milk and cocoa containing tryptophan. However 5-HTP which is commercially
obtained from the seeds of the Griffonia simplicifolia plant is a more efficient
precursor to serotonin than Tryptophan and is often used in dietary supplements to
support healthy sleep and mood, especially when combined with B-group vitamins
and magnesium as cofactors.2
- See more at: http://www.clinicians.co.nz/5-htp/#sthash.iplGBiPA.dpuf
Many individuals suffer from recurring migraine or tension headaches which
can significantly impact on their quality of life. Nutrients such as magnesium
and B-group vitamins have been shown to be supportive in some people.
There is also evidence from several studies in both children and adults that 5HTP may be effective in reducing headache severity and frequency, including
tension headaches and migraines. Fewer pain-relieving medications may be
needed when taken with 5-HTP. However, many of the available studies show
that more proven pharmaceutical drugs may work better than 5-HTP for
headaches. Further research is needed. - See more at:
Foods known to be high in Tryptophan include; spirulina, oat or wheat bran, wheat
germ, brewer’s yeast, dairy products, soy beans and soy protein. Other sources
include meats such as beef, chicken, turkey and pork and seafood such as crab and
tuna, pumpkin and pumpkin seeds, chocolate and cocoa powder and a range of nuts
and seeds.1 - See more at: http://www.clinicians.co.nz/5-htp/#sthash.iplGBiPA.dpuf
There is no substitute for a healthy diet, eating a wide variety of fresh
seasonal coloured fruits and vegetables along with lean meat and good
quality protein is important. Likewise avoiding or minimizing processed or
white foods such as cakes, biscuits, pasta and high calorie snack foods is a
good idea. These foods tend to be high in calories but deficient in the many
essential vitamins and mineral that the body needs for its many metabolic
processes. In fact these foods can often rob the body of essential nutrients.
The first approach to improve health should always be to improve your diet
and optimize digestion, reduce stress where possible, get sufficient sleep (7-8
hours per night) and exercise regularly. We all lead busy stressful lives and do
not always eat drink or sleep as we should. Taking a daily multivitamin and
some omega-3 fish oil or krill oil helps to provide nutritional insurance of a
daily basis to keep us on top of our game. Consult a health professional to
address any other health issues to ensure you choose the correct
supplements for your needs or for a referral to an appropriate health
- See more at: http://www.clinicians.co.nz/5-htp/#sthash.iplGBiPA.dpuf
Monoamine oxidase inhibitors (MAOIs) are chemicals which inhibit the activity of the
monoamine oxidase enzyme family. They have a long history of use as medications
prescribed for the treatment of depression. They are particularly effective in treating
atypical depression. They are also used in the treatment of Parkinson's Disease and
several other disorders.
MAOIs have been found to be effective in the treatment of panic disorder with
agoraphobia, social phobia, atypical depression or mixed anxiety
and depression, bulimia, and post-traumatic stress disorder, as
well as borderline personality disorder. MAOIs appear to be particularly effective
in the management of bipolar depression according to a recent retrospectiveanalysis. There are reports of MAOI efficacy in obsessive-compulsive disorder
(OCD), trichotillomania, dysmorphophobia, and avoidant personality disorder, but
these reports are from uncontrolled case reports.
MAOIs can also be used in the treatment of Parkinson's disease by targeting
MAO-B in particular (therefore affecting dopaminergic neurons), as well as
providing an alternative for migraine prophylaxis. Inhibition of both MAO-A
and MAO-B is used in the treatment of clinical depression and anxiety.
MAOIs appear to be particularly indicated for outpatients with "neurotic
depression" complicated by panic disorder or hysteroid dysphoria, which
involves repeated episodes of depressed mood in response to feeling
MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing
the breakdown of monoamine neurotransmitters and thereby increasing their
availability. There are two isoforms of monoamine oxidase, MAO-A and MAOB. MAO-A preferentially deaminates serotonin, melatonin, epinephrine, and
norepinephrine. MAO-B preferentially deaminates phenylethylamine and
trace amines. Dopamine is equally deaminated by both types.
MAO-A inhibition reduces the breakdown of primarily
serotonin, norepinephrine, and dopamine; selective inhibition of MAO-A
allows for tyramine to be metabolised via MAO-B. Agents that act on
serotonin if taken with another serotonin-enhancing agent may result in a
potentially fatal interaction called serotonin syndrome or with irreversible
and unselective inhibitors (such as older MAOIs), of MAO a hypertensive crisis
as a result of tyramine food interactions is particularly problematic with older
MAOIs. Tyramine is broken down by MAO-A and MAO-B, therefore inhibiting
this action may result in its excessive build-up, so diet must be monitored for
MAO-B inhibition reduces the breakdown mainly of dopamine
and phenethylamine so there are no dietary restrictions
associated with this. MAO-B would also metabolize tyramine, as
the only differences between dopamine, phenethylamine, and
tyramine are two phenylhydroxyl groups on carbons 3 and 4. The
4-OH would not be a steric hindrance to MAO-B on tyramine.
Two MAO-Bi drugs, selegiline and rasagiline have been approved
by the FDA without dietary restrictions, except in high-dosage
treatment, wherein they lose their selectivity
Catechol-O-methyltransferase (COMT; EC 18.104.22.168) is one of several enzymes
that degrade catecholamines such as dopamine, epinephrine, and
norepinephrine. In humans, catechol-O-methyltransferase protein is encoded
by the COMT gene. As the regulation of catecholamines is impaired in a
number of medical conditions, several pharmaceutical drugs target COMT to
alter its activity and therefore the availability of catecholamines. COMT
was first discovered by the biochemist Julius Axelrod in 1957.
In the brain, COMT-dependent dopamine degradation is of particular
importance in brain regions with low expression of the presynaptic dopamine
transporter (DAT), such as the prefrontal cortex. This process is
supposed to take place in postsynaptic neurons, as, in general, COMT is
located intracellularly in the CNS.
Catechol-O-methyltransferase is involved in the inactivation of the
catecholamine neurotransmitters (dopamine, epinephrine, and
norepinephrine). The enzyme introduces a methyl group to the
catecholamine, which is donated by S-adenosyl methionine (SAM). Any
compound having a catechol structure, like catecholestrogens and catecholcontaining flavonoids, are substrates of COMT.
Levodopa, a precursor of catecholamines, is an important substrate of COMT.
COMT inhibitors, like entacapone, save levodopa from COMT and prolong the
action of levodopa. Entacapone is a widely used adjunct drug of levodopa
therapy. When given with an inhibitor of dopa decarboxylase (carbidopa or
benserazide), levodopa is optimally saved. This "triple therapy" is becoming a
standard in the treatment of Parkinson's disease.
Chocolate Consumption and Effects on Serotonin Synthesis
The ingestion of carbohydrates stimulates the release of
insulin which, along with its anabolic effects, promotes
amino acids in the blood to enter muscle cells, except for
tryptophan.2 This will cause a relative increase of
tryptophan over other amino acids, which compete for
passing the blood-brain barrier. As a consequence, more
tryptophan enters the brain, and there is an increase in
the synthesis of serotonin,3 a neurotransmitter
postulated to have a major role in mood disorders and a
target of many psychopharmaceuticals.
Chocolate may also make a person feel better by directly interacting with the
brain. One of the ingredients in chocolate is tryptophan, an essential amino
acid needed by the brain to produce serotonin. Serotonin is a moodmodulating neurotransmitter, the brain's "happy chemical." High levels of
serotonin can give rise to feelings of happiness.
Chocolate contains another neurotransmitter, anandamide. Anadamine
targets the same brain structure as THC (tetrahydrocannabinol), the active
ingredient in cannabis. Chocolate also contains two chemicals that slow the
normal breakdown of anandamide and prolong the action of this natural
stimulant in the brain. The BBC's Hot Topic article on Chocolate provides an
excellent Flash animation demonstrating how chocolate might prolong the
effects of anadamine. (1) However, one must note that experts estimate the
levels of these substances are so low in most chocolate, that a person would
need to eat several pounds of chocolate in order to substantially impact the
brain's own normal anandamide levels.
Many people consume chocolate during moments of emotional distress, for
its comforting properties, ability to improve mood and restore a sense of well
being. The comforting, mood-elevating properties are most likely caused by
the release of endorphins resulting from chocolate consumption
not all types of chocolate are healthy. When choosing
chocolate for the health benefits consider the type of
cocoa bean, the processing method used and what
other ingredients have been added to the chocolate.
The three main forms of chocolate available are: (4, 21-23)
Dark, Semisweet Chocolate
Unsweetened chocolate combined with added sweeteners and cocoa
butter which contain at least 35% chocolate liquor.; the fat content
averages 27%. Dark chocolate has two to four times (or more) the
amount of flavonoids than milk chocolate.
-Unsweetened chocolate with added cocoa butter, milk, sweeteners
and flavorings. All milk chocolate made in the U.S. contains at least 10
% cocoa mass and 12 % whole milk.
Contains cocoa butter but no nonfat cocoa solids. It is the term used to
describe products made from cocoa butter, milk solids and nutritive
carbohydrate sweeteners. White chocolate contains no cocoa solids or
chocolate liquor, so it provides none of the health benefits from
Recommendations for Choosing a Life with Chocolate
For many people chocolate remains a favorite food and beverage. Results
show both positive and negative aspects about consuming chocolate. It is
important to consider the various components of chocolate and the complex
interplay of both nutrition and health before making a decision to include
chocolate as part of a diet plan. (
One theory is that carbohydrates stimulate serotonin production
and thus eating them is an attempt to self-medicate depression.
Studies focused on this link do seem to back this up. High
carbohydrate meals raise serotonin1 while fatty or protein rich
meals tend to lower it.
The type of carbohydrate chosen seems to be based upon it's
glycemic index, or how high it causes blood sugar levels to peak.
The higher glycemic index carbohydrates like sugar have a
greater effect2 on serotonin than starchy, lower glycemic index
foods like potatoes
Certain alkaloids3 have been isolated in chocolate that may raise
brain serotonin levels. Scientists now speculate that
"chocoholism" may actually have a real biological basis4 with a
serotonin deficiency being one factor. Another mechanism5 that
has been proposed for why chocolate has such a powerful
influence on mood is that chocolate has 'drug-like' constituents
including anandamines, caffeine, and phenylethylamine.
If you slip, don't beat yourself up over it. You're a work in
progress. Mistakes will happen. Dust yourself off and keep trying.
Don't completely deprive yourself. Find healthier substitutes for
what you're craving. Try eating a sugar free chocolate pudding
instead of that large chocolate bar. Or allow yourself a small
portion of the dessert that you are coveting so much. No food is
totally bad. It's all in how much you eat of it.
Be mindful of what you are consuming rather than grazing all
day. A food journal can be very helpful.
Strangely, eating chocolate also causes an increased activation of
the motor cortex – the area of the brain which controls voluntary
movement. This may not mean however that after eating
chocolate people can move better or faster – even just reading a
verb which relates to the arm, face or leg will increase activation
of the motor cortex.
The brain functions by producing chemicals called
neurotransmitters which transmit messages from one part of the
brain to another. Increased brain activity is due to increased
levels of these neurotransmitters. Three major
neurotransmitters are called dopamine, serotonin, and opioids –
all are commonly affected by drugs and both have been found to
be affected by chocolate.
serotonin has many roles in the brain, including regulating sleep, appetite and
mood. There has been evidence that chocolate increases serotonin levels of
people who are deficient, including people with seasonal affective disorder or
non-typical depression. This increase in serotonin is through an indirect
mechanism using the carbohydrates in chocolate (such as sugar); however
this effect is counteracted by protein and fat. There is a limit at how much
protein or fat a food can contain before it stops this increase of
serotonin, and, sadly, chocolate has too much of both, suggesting
thatchocolate does not in fact increase serotonin at all.
When activated, opioids cause the release in the brain of endorphins, a
chemical which causes a pleasurable feeling. Opioids can be released in the
brain in response to sweet foods, including chocolate, and this opioid release
caused by sweet foods can lead to an analgesic feeling from endorphin
Depression strikes some 35 million people
worldwide, according to the World Health
Organization, contributing to lowered quality of life as
well as an increased risk of heart disease and suicide.
Treatments typically include psychotherapy, support
groups and education as well as psychiatric
medications. SSRIs, or selective serotonin reuptake
inhibitors, currently are the most commonly prescribed
category of antidepressant drugs in the U.S., and have
become a household name in treating depression.