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  #121   ^
Old Mon, Apr-22-19, 10:41
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Ms Arielle Ms Arielle is offline
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I think I have earned a PhD by now!!! Certainly know more about this than doctors!!
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  #122   ^
Old Mon, Apr-22-19, 10:46
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Ms Arielle Ms Arielle is offline
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Serotonin is a neurotransmitter that is responsible for your happiness! Most anti-depressants focus on the production of serotonin. To improve your mood and happiness you can discover tons of our favorite biohacks in our ebook, SelfHacked Secrets. Download the first chapter here for free.

What is Serotonin?
Serotonin, also called 5-Hydroxytryptamine (5-HT), is a biochemical messenger and regulator, synthesized from the essential amino acid L-Tryptophan.

In humans, it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets.

It mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity (R).

Beneficial Effects of Serotonin
1) Serotonin Affects Heart Function
5-Hydroxytryptamine can be considered as a significant circulating hormonal factor implicated in normal cardiovascular function either by acting directly on heart cells or by stimulating chemosensitive nerves from the heart (R).

Patients with carcinoid tumors (rare slow-growing cancers) have high levels of this regulator associated with arrhythmia, leading to heart block or to valvular fibroplasia (R).

Also, mouse embryos grown in the presence of either a high concentration of 5-Hydroxytryptamine or Serotonin-specific reuptake inhibitors show a decreased proliferation of myocardium, cardiac mesenchyme, and endothelium (R).

2) Serotonin Induces Intestinal Secretions
In the gastrointestinal tract, 5-HT initiates responses like nausea, intestinal secretion, and peristalsis and has been implicated in gastroenteric diseases like irritable bowel syndrome (R).

The secretory effects of 5-HT are mediated through different receptors: It induces secretion across human ileal mucosa, whereas a receptor of the 5-HT2A subtype appears to mediate the effect in the human sigmoid colon (R).

3) Serotonin Helps Control Body Temperature and Breathing
5-HT-producing cells in the mouse brain play an essential role in maintaining a healthy balance in body temperature and breathing (R).

One study in rats (Tph2 knockout) suggests that 5-HTP is important to balance the control systems for breathing and temperature during development (R).

Neurons in all of the nuclei that govern respiratory control have serotonin neurons (R).

4) Brain Serotonin Can Affect Your Mood
Acute tryptophan depletion (ATD) can result in lower mood and increase in irritability or aggressive responding.

Overall, studies manipulating tryptophan levels support the idea that low 5-Hydroxytryptamine levels can predispose subjects to mood and impulse control disorders.

Higher levels of 5-HT may help to promote more constructive social interactions by decreasing aggression and increasing dominance (R).

5) Serotonin Contracts Vascular Muscles
5-HT causes contraction of the vascular smooth muscle cells in most blood vessels studied in the lab (mainly due to the activation of S2-serotogenic receptors) (R).

The original intent of investigating 5-HT was for its vasoconstrictor effects. Early studies in dogs established a triphasic response to serotonin when injected intravenously (R).

An initial fall in blood pressure
A rise in blood pressure
Another fall in blood pressure
When released from activated platelets, 5-HT can induce vasoconstriction in most large arteries, large veins, and venules.

It can also indirectly contribute to vasoconstriction by amplifying the response of other vasoactive substances such as NET, angiotensin II, and histamine (R).

6) Serotonin May Impact Bone Regulation
5-HT receptors have been identified in all the major bone cell types (osteoblasts, osteocytes, and osteoclasts) (R).

Recent data suggest that gut-derived 5-Hydroxytryptamine may mediate the skeletal effects of LDL receptor-related protein 5.

Evidence suggests that SSRIs (Selective Serotonin Reuptake Inhibitors) are associated with reduced bone mass, increased bone loss, and increased risk of fractures (R).

Some studies suggest a direct stimulatory effect of 5-HT on bone formation pathways (R), whereas others have found inhibitory effects (R).

7) Serotonin Increases Hypertension
Early experiments with specific 5-HT receptor antagonists indicated that 5-HT1-like antagonism, as well as serotonin antagonism, corrected hypertension in animal models (R).

Several mechanisms were proposed to explain this including direct vasodilation, inhibition of adrenergic input, and stimulation of central areas contributing to correction of vasomotor tone.

5-hydroxytryptamine causes heart and lung tissue to replicate and grow (R, R, R).

In mice and people, high levels of 5-HT2B in the lungs are associated with the development of pulmonary hypertension (R, R).

8) Serotonin Affects Depression
Alterations in the serotogenic neuronal function in the central nervous system occur in patients with major depression, which can be evidenced by the reduced concentration of 5-HT in the postmortem brain tissue of the depressed.

In a pilot study in patients with major depression, alterations in 5-HT neurons showed to play a role in the cause of depression (R).

9) Serotonin Impacts Anorexia Nervosa
5-HTP is involved in almost all the behavioral changes observed in Anorexic patients.

Both genetic and environmental factors contribute toward anorexia. It is suggested that tryptophan supplementation may help anorexics (R).

Tryptophan is a precursor of serotonin and an essential amino acid only available in the diet, it is, therefore, likely that excessive diet restriction may lead to decreased brain 5-HT stores.

10) Serotonin Impacts Attention-Deficit Hyperactivity Disorder
In one controlled trial, families were studied to determine the link between the serotogenic system and Attention-Deficit Hyperactivity Disorder (ADHD). Preliminary data suggested an important role of the 5-HT system in the development of ADHD (R).

There is clear evidence that dopamine and 5-Hydroxytryptamine neuronal systems interact in ADHD (R).

11) Serotonin Affects Carbohydrate-Craving And Obesity
5-HT-releasing brain neurons are unique in that the amount of neurotransmitter they release is normally controlled by food intake:

Carbohydrate consumption–acting via insulin secretion and the “plasma tryptophan ratio”–increases serotonin release; protein intake lacks this effect (R).

12) Serotonin May Play A Role In Kidney Activity
In kidney injury, tissue damage occurs and platelet activation is observed. Recent studies suggest that some factors, such as 5-Hydroxytryptamine, are released into microenvironment upon platelet activation following kidney injury (R).

Ways to Naturally Increase Serotonin
SSRIs increase serotonin levels in the brain and are safer than other antidepressants [R].

However, SSRIs still have many side effects. It can cause discontinuation syndrome, sexual dysfunction, nausea, skin reactions, weight gain, and sleep disturbances [R].

In rats, long-term SSRI use aggravated serotonin deficiency [R].

Thus, it is crucial that we find other alternatives to drugs that can increase serotonin levels.

Behavioral Methods
Making lifestyle changes can prevent depression, anxiety, and related disorders before they start. Below, we highlight a few natural ways to boost serotonin levels for mental and physical well-being.

1) Positive Thinking
Just as low serotonin levels negatively affect our mood, negative moods also cause serotonin levels to drop. This triggers a range of physical and mental health issues. Inducing positive moods by mental exercises is a good start to maintaining healthy serotonin levels [R].

Positive thoughts have a positive impact on one’s self-esteem and mood. On the other hand, over-thinking based on inaccurate beliefs has a causal role in depression [R].

Cognitive therapy is a safe and efficient treatment for depression. It requires one to identify thoughts that trigger negative emotions, distance themselves from those thoughts, and to question the validity of their beliefs through experiments [R].

Employing such an objective thought process in day-to-day life could be a natural way to keep depression at bay and raise serotonin levels [R].

2) Exercise
Aerobic exercise is scientifically proven to improve serotonin levels in the brain. In a study of 16 seniors, the long-term aerobic training helped increase serotonin activity [R, R].

In rats, short-term exercise also increased serotonin activity [R].

Additionally, exposure to bright sunlight naturally boosts serotonin. Therefore, exercising outdoors can increase serotonin levels and improve mood [R].

3) Listening to Pleasant Music
Listening to music with a positive vibe and lyrics based on positive emotions can improve mood [R].

In a study of 20 healthy subjects, listening to pleasant music increased their serotonin levels. Meanwhile, serotonin levels decreased when listening to unpleasant music [R].

4) Social Interactions
Social interaction and perceived facial expression have a strong correlation with serotonin levels [R].

Interactions with individuals exhibiting negative traits or emotional states, such as aggressive behavior, causes you to mirror their emotional states. However, the same holds true for positive emotional states [R].

5) Sleeping Right
Having a normal sleep schedule is important for serotonin balance. During sleep, the brain releases serotonin [R].

Sleep deprivation can desensitize serotonin receptors. This can cause problems with serotonin and increase the likelihood of depression [R].

6) Indulges
Partaking in fun activities such as nature walks, meditation and massages all have a positive effect on serotonin levels [R, R, R].

Nutritional Methods
Although bananas, plums, etc. contain serotonin, eating these foods will not increase our brain’s serotonin levels [R].

Consuming foods that contain tryptophan, an amino acid required for serotonin production, will also not boost serotonin levels in our brain [R].

1) Omega-3 Fatty Acids
Omega-3 fatty acids, such as EPA and DHA, increase serotonin levels [R].

Increasing omega-3 fatty acids through supplementation can increase serotonin release by the neurons to our brain, thereby keeping our minds sharp [R].

Foods rich in EPA and DHA include [R]:

Fatty fish (salmon and sardines)
2) Vitamin D
In the brain, serotonin synthesis, from tryptophan, needs Vitamin D. Vitamin D deficiency can contribute to dysfunctional serotonin activation and cause brain problems [R].

Vitamin D food sources include [R]:

Fish and shellfish
Milk also contains a protein called alpha-lactalbumin. It can increase tryptophan levels, and possibly serotonin [R].

3) Carbohydrates
We crave for carbs or sweets when we are sad. This is because carbohydrate intake increases serotonin levels in our body by secreting insulin [R].

Small amounts of carbohydrates can also increase tryptophan availability by letting it cross the blood-brain barrier to be turned into serotonin [R].

4) Herbs
In rats, St. John’s Wort supplementation increased serotonin formation by inhibiting the TDO enzyme [R].

Curcumin also helps enhance serotonin release. In rats, curcumin treatment had an anti-depression effect and increased serotonin and dopamine release [R, R].

Caution should be taken when including herbs in your diet. Overdose leads to possible side effects [R].

Technical Section
Various agents can inhibit 5-HT reuptake, including cocaine, dextromethorphan (an antitussive), tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs).
In animals including humans, 5-Hydroxytryptamine is synthesized from the amino acid L-tryptophan by a short metabolic pathway consisting of two enzymes: tryptophan hydroxylase and aromatic amino acid decarboxylase [R].
The essential amino acid tryptophan hydroxylates to 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase. In a second step, 5-HTP is decarboxylated to form 5-HT [R].


Definitely NOT understanding the first paragraph about affecting heart function-- a good thing or a bad thing.....??
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  #123   ^
Old Mon, Apr-22-19, 10:49
Ms Arielle's Avatar
Ms Arielle Ms Arielle is offline
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Posts: 10,323
Plan: atkins
Stats: 247/217/153 Female 5'8"
Progress: 32%
Location: Massachusetts

What Serotonin deficiency looks like!

Serotonin is the chemical that makes us happy. Symptoms as diverse as migraines, frequent infections, depression, insomnia, memory loss, IBS, social phobia, aggression, and even loss of sexual preference might be signs of serotonin deficiency. Do you identify yourself with some of these symptoms? Read on to learn about the negative health and brain effects of serotonin deficiency.

What Is Serotonin Deficiency?
Serotonin is synthesized from the amino acid tryptophan by a short metabolic pathway consisting of two enzymes. First, tryptophan is converted to 5-hydroxytryptophan (5-HTP) by the tryptophan hydroxylase.

In a second step, 5-HTP is converted to serotonin (5-HT) by the enzyme aromatic amino acid decarboxylase [R].

Serotonin is produced in the platelets of the blood and cells of the gut and distributed throughout the body to exert its effects.

This serotonin can’t cross the blood-brain barrier, while tryptophan and 5-HTP can. So, there is also serotonin production in the brain.

Any disruption of these mechanisms or damage to serotonin receptors can lead to a decrease in overall serotonin effects in the body.

When serotonin is lower than normal, it can result in impaired body functions and psychological disorders, which is known as serotonin deficiency [R].

You can learn more about serotonin and its beneficial effects in this post, while here we’ll focus on the causes and consequences of its deficiency.

Note from Joe:

There’s a growing position in the alternative health world that serotonin has nothing to do with mental health issues and that it’s something promoted by big pharma, etc. At SelfHacked, we can only look at what the available science says, so if you find conflicting or additional studies or something that is inaccurate, please do share. Thanks!

Potential Causes Of Serotonin Deficiency
Serotonin deficiency can be caused by:

Mutations in the TPH1 and TPH2 genes, which metabolize tryptophan and are ultimately responsible for the production of serotonin [R].
Mutations in the SPR gene, which codes for a key enzyme in serotonin production [R].
Inherited defects that decrease BH4, a cofactor required for the production of serotonin [R].
Serotonin receptor genes 5HT1A, 5HT1B, and 5HT2c mutations [R].
Mutations in the serotonin transporter gene (SERT/SLC6A4), which takes serotonin into the cells [R].
Mutations in the MAOA gene, which is responsible for breaking down serotonin [R].
Serotonin Depletion May Result In Bisexuality/Homosexuality
Interestingly, an animal study revealed that serotonin-deficient mice became more bisexual compared to controls.

This is not a bad thing (we didn’t include it under negative effects) nor does this imply that you can undo your sexual preference if you are gay or bisexual by taking serotonin since the body is quite complex and sexual preference is tied to more fixed brain structures. SelfHacked is apolitical, but we nevertheless found it and thought it was interesting to bring it down.

When animals were depleted of serotonin (by drugs or tryptophan-free diets), it increased a bisexual mating behavior (male-male sex) [R].

The lack of sexual preference seemingly has to do with a change in smelling pheromones. Males still had a sense of smell but seemed to gravitate toward other male pheromones [R].

In a similar study, female mice with serotonin deficiency preferred females over males [R].

A study on human males showed that heterosexual and homosexual men exhibit differences in neurotransmitter activity and respond differently to serotonin-increasing drugs [R].

Based on these studies, serotonin deficiency might be related to sexual preference in humans.

However, sexual preference is determined by many factors including neuronal structures in the brain which is not changeable by altering serotonin, so it’s unknown how much if at all, increasing or decreasing serotonin will change the sexual preference in the real world.

We can’t extrapolate from animal studies to humans. Also, the studies were only done on animals with severe serotonin depletion. We don’t know what would be the case in humans who only have a moderate deficiency.

Negative Health Effects Of Serotonin Deficiency
1) Leads To Digestive Tract Blockages
Muscle contraction in the gut (peristalsis) allows moving food and liquids through the digestive tract.

When serotonin levels are low, it alters the magnitude and length of muscle cell signals and decreases the amount of calcium released from the cells. Therefore, the ability of the digestive muscles to contract is impaired leading to blockages [R].

2) Impairs Blood Flow
Blood vessels need muscle contraction. Serotonin deficiency reduces the contraction of the blood vessels, therefore, impairing blood flow throughout the body [R].

3) Reduces Blood Clotting Ability
Serotonin plays a major role in clotting, which is internalized and stored in the platelets, where it can activate the clotting process. Thus, a significant decrease in serotonin can impair blood clotting [R].

Mutations that decrease serotonin transporters (SERT) counteracts the clotting effect of serotonin [R].

A pilot study on mice showed that due to low levels of serotonin, bleeding was prolonged even in the smallest cuts and scrapes, which was reverted by serotonin treatment [R].

4) May Cause Constipation-Predominant Irritable Bowel Syndrome
Nearly 95% of serotonin is produced and stored in the gut. A deficiency in serotonin can have a significant effect on gut function [R, R].

Low serotonin levels in the gut impair the function of its muscles causing constipation-predominant irritable bowel syndrome (IBS). Hence, muscle impairment reduces the motility or gut flow, making it more difficult to pass stools [R].

5) May Lead To Symptoms in Diverticulitis
Diverticulitis occurs when the bulging sacs that appear in the lining of your large intestine, or colon, get acutely infected or inflamed.

Altered gut flow is an important feature of diverticulitis, which can be caused by lower serotonin [R].

A pilot study of 51 patients showed that patients with diverticulitis had fewer serotonin transporters (SERT) in the gut [R].

While alterations in serotonin do not appear to be responsible for the development of diverticulitis, decreased SERT expression and function might be caused by the inflammation and contribute to some of the symptoms [R].

On the contrary, patients with celiac disease had increased levels of serotonin in the gut [R].

6) Can Impair Fetal Development
Serotonin deficiency in pregnant women can severely impact fetal development, especially during early pregnancy.

During the zygote stage (fertilized egg), serotonin deficiency can impair cell division. After implantation in the uterus, it can impair the development of fetal organs, such as the brain, eyes, jaw, and blood vessels [R].

7) Impairs Immune System Function
Animal studies have shown that serotonin deficiency correlates with immune system suppression.

Fish with low levels of serotonin showed a decrease in the production and multiplication of immune cells, which weakens the immune system [R, R].

Also, mice that were depleted of serotonin showed a decrease in immune cells production [R, R].

8) Disrupts The Biological Clock
Low levels of serotonin may disrupt our biological clock (circadian rhythm). Particularly, an animal study showed that the depletion of serotonin impaired the circadian rhythm and altered the number of sleep hours [R, R].

Serotonin-depleted mice slept more during the day than at night [R].

Serotonin deficiency also resulted in symptoms of depression, providing a possible link between serotonin, insomnia, and depression [R].

9) Can Increase Salty Food Cravings
An animal study showed that serotonin-depleted mice exhibited a higher craving for sodium, as they ingested more sodium than the controls [R].

10) Anorexia Nervosa
5-HTP is involved in almost all the behavioral changes observed in anorexia patients.

Both genetic and environmental factors contribute to anorexia. Therefore, it is suggested that tryptophan supplementation may help anorexic patients [R].

Excessive diet restriction may lead to decreased brain serotonin stores.

Negative Brain Effects of Serotonin Deficiency
1) Leads To Major Depression
A review of several studies showed that increasing serotonin could treat depression [R].

Other studies have shown that serotonin deficiency may cause a relapse in patients with depression, but does not affect healthy people [R].

2) Causes Generalized Anxiety Disorder
Serotonin 5HT1A receptors contribute to anxiety disorders in mice lacking these receptors exhibited increased signs of anxiety [R].

Download our FREE eCourse on BioHacking Your Stress and Anxiety

3) May Increase Likelihood Of PTSD
An animal study showed that mice with altered serotonin transporter (SERT) or 5HT1A receptor genes were more susceptible to greater stress due to the presence of predators, such as cats [R].

4) Leads To ADHD
Tryptophan, a precursor of serotonin, considerably reduced ADHD symptoms, while variations in the 5HT1B receptor gene increased susceptibility to ADHD [R, R].

5) Leads To OCD
While it’s unknown how they work exactly, drugs that increase serotonin levels work better in treating OCD than placebos. These drugs block the reuptake of serotonin in the brain, increasing the amount of available serotonin [R].

6) May Cause Panic Disorder
A panic disorder involves both the brain and heart since an increased heart rate is its primary symptom.

Taking serotonin reuptake inhibitors reduces symptoms of panic disorder by increasing the availability of serotonin [R].

7) Can Lead To Social Phobia
Some studies linked serotonin deficiency to social phobia.

A study (DB-RCT) of 77 people diagnosed with social phobia showed that serotonin-increasing drugs improved anxiety and depression and social phobia symptoms [R].

Moreover, a meta-analysis showed that serotonin-increasing drugs are better in treating social phobia than others like benzodiazepines or antipsychotics [R].

8) Increases Aggression
A study showed that mice with serotonin deficiency or lacking serotonin 5HT1B receptors exhibit more aggressive behavior [R, R].

9) Causes Migraines
Serotonin plays a role in the onset of migraines, although the exact mechanism is still unknown. Recent findings indicate that a deficiency in tryptophan, a serotonin precursor, intensifies migraine symptoms [R].

10) Impairs Memory
The serotonin transporter (SERT) is involved in recall and memory by determining the strength and extent of serotonin signals and interacting with other neurotransmitters [R, R].

A recent study showed that serotonin-deficient rats, due to a lack of one or both copies of the SERT gene, had significantly impaired object memory, while those that were not deficient showed high-functioning memory [R].

How You Can Increase Serotonin
Serotonin levels can be increased in multiple ways, but serotonin itself can’t cross the barrier and enter the brain to exert many of its effects, while tryptophan and 5-HT can.

Bright light exposure, exercise, and increased tryptophan intake all increase serotonin levels [R].

Moreover, carbohydrate intake – acting via insulin secretion – leads to increased tryptophan levels, and, therefore, increased serotonin production. Conversely, protein intake seems to decrease serotonin synthesis [R].

Supplements that are good to increase serotonin include 5-HTP and tryptophan.

Drugs That Increase Serotonin
Selective serotonin reuptake inhibitors (SSRIs) are drugs that prevent the reuptake of serotonin outside of cells, therefore increasing serotonin availability [R].

Some examples are sertraline, fluoxetine, and paroxetine [R].

SSRIs treat effectively a variety of psychological disorders like depression, addictions, social phobia, anxiety, and OCD [R].

SSRIs are specific to serotonin and do not interfere with other neurotransmitters producing fewer side effects, which occurs with other antidepressants [R, R].

However, SSRIs may have side effects such as nausea, lowered libido, diarrhea, anxiety, tremors, or loss of bone mass [R, R].

Joe’s experience:

Some people are helped by SSRIs, but they are some of the least effective antidepressants based on my experience. Tianeptine and Mirtazapine are often more effective.
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  #124   ^
Old Mon, Apr-22-19, 10:59
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Ms Arielle Ms Arielle is offline
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Posts: 10,323
Plan: atkins
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Location: Massachusetts


"4) Leads To ADHD
Tryptophan, a precursor of serotonin, considerably reduced ADHD symptoms, while variations in the 5HT1B receptor gene increased susceptibility to ADHD [R, R].

5) Leads To OCD
While it’s unknown how they work exactly, drugs that increase serotonin levels work better in treating OCD than placebos. These drugs block the reuptake of serotonin in the brain, increasing the amount of available serotonin [R]."
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  #125   ^
Old Mon, Apr-22-19, 11:01
Ms Arielle's Avatar
Ms Arielle Ms Arielle is offline
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Posts: 10,323
Plan: atkins
Stats: 247/217/153 Female 5'8"
Progress: 32%
Location: Massachusetts

I talked t o an ADD specialist about memory/recall failures and got crap.... vindicated!

10) Impairs Memory
The serotonin transporter (SERT) is involved in recall and memory by determining the strength and extent of serotonin signals and interacting with other neurotransmitters [R, R].

A recent study showed that serotonin-deficient rats, due to a lack of one or both copies of the SERT gene, had significantly impaired object memory, while those that were not deficient showed high-functioning memory [R].
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  #126   ^
Old Mon, Apr-22-19, 11:14
Ms Arielle's Avatar
Ms Arielle Ms Arielle is offline
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Posts: 10,323
Plan: atkins
Stats: 247/217/153 Female 5'8"
Progress: 32%
Location: Massachusetts

Top 13 Tryptophan Benefits + 10 Deficiency Dangers + Foods
By Joe Cohen, BS Reviewed By Dr. Evguenia Alechine, PhD (Biomedical Sciences) Last updated: April 18, 2019
Evidence Based
Sleeping man
Tryptophan is an amino acid that produces serotonin, melatonin, and kynurenine. Tryptophan supplements help with depression, anxiety, and insomnia. However, there are also side effects and contraindications of these supplements. Read on to find out if tryptophan supplements are right for you and how they can improve your health.

What is Tryptophan?
Tryptophan is one of the 8 essential amino acids, meaning it is vital but cannot be produced by the body. Hence, tryptophan must be supplied through either diet or supplements [R].

There are different types of tryptophan:

L-tryptophan is the natural version of the amino acid and a building block of the proteins in the body.
In humans, tryptophan is not stored for long periods and therefore has the lowest concentration in the body among all the amino acids. However, only small amounts of tryptophan are required and it’s usually not necessary in excess [R].

Tryptophan Foods
Some common foods that contain tryptophan include oats, bananas, dried prunes, milk, tuna fish, cheese, bread, chicken, turkey, peanuts, and chocolate [R].

Why is Tryptophan Important?
Tryptophan is converted to 5-hydroxytryptophan (5-HTP) in the brain, which produces serotonin [R, R].

Tryptophan absorption into the brain is influenced by diet.

A high carbohydrate, low protein diet will release insulin, which ultimately increases the absorption of tryptophan into the brain and can, therefore, increase serotonin [R]. This is the mechanism by which eating carbs can increase serotonin.

BCAAs compete with tryptophan absorption into the brain. Eating a high protein diet (high BCAAs) will cause less tryptophan to enter the brain, thus reducing serotonin levels [R].

However, higher protein diets usually have higher tryptophan, which can cancel out the effect from the BCAAs.

Health Benefits of Tryptophan
1) Helps with Sleep and Insomnia
Tryptophan produces melatonin in the brain (pineal gland), the gut, the retina, and immune cells. Melatonin regulates the circadian rhythm and sleep patterns and is used as a supplement itself to help people sleep [R, R].

A blind randomized controlled study of 5 healthy volunteers (3 received the supplement for the first 10 nights and placebo the next 10, the other 2 had the reverse procedure) showed that L-tryptophan supplementation increased average total sleep. All of them noticed some form of drowsiness half hour before sleep [R].

A study on 7 insomniac patients showed that L-tryptophan supplementation increased total sleep (by 28%). The supplementation also decreased early-morning wakefulness by an average of 37 minutes [R].

Tryptophan supplementation even helped induce sleep in manic patients. A blind and controlled study of 10 patients with mania showed improvements in total sleep after L-tryptophan supplementation [R].

A dose-response study of 15 insomniac patients showed that ¼ gram of L-tryptophan increased stage 4 sleep (deep sleep). Normal dietary intake of tryptophan is usually around ½-1 gram of L-tryptophan, so even minimal amounts of tryptophan can increase deep sleep [R].

Tryptophan supplementation may also improve obstructive sleep apnea (airflow blockage during sleep). A study on 12 patients showed that L-tryptophan supplementation increased sleep in those with obstructive sleep apnea during non-rapid eye movement (REM) sleep. However, patients with central sleep apnea showed no improvements [R].

Tryptophan Benefits due to Serotonin
One of tryptophan’s biggest roles is producing serotonin [R].

Serotonin is commonly used to fight depression, anxiety, and insomnia. Therefore, conversion of tryptophan to any of its other metabolites (e.g. kynurenine) can induce depression in some people [R].

However, through another pathway, tryptophan can be converted into tryptamine, which can act as both an activator and inhibitor of serotonin [R].

2) May Help Depression
Depressed patients often have problems creating serotonin from tryptophan. Instead, they create other metabolites such as quinolinic acid, which can be toxic. For these patients, tryptophan supplementation may not help [R].

However, many depressed patients also suffer from insomnia and other sleep-depriving conditions. Therefore, tryptophan’s ability to help with insomnia could aid these depressed patients [R, R].

A randomized study of 25 young adults showed that high tryptophan diets increased mood and decreased depressive symptoms and anxiety [R].

Two meta-analyses of tryptophan’s effects on depression do show some positive effects. However, there is a lot of conflicting data as well [R, R].

The conflicting evidence of tryptophan studies shows that tryptophan might not treat depression by itself, but can complement other antidepressants (amitriptyline, clomipramine) [R].

A study (DB-RCT) of 24 patients showed that clomipramine (a drug for depression) and L-tryptophan were more effective in improving depressed mood, suicidal intent, and anxiety compared to clomipramine alone [R].

When tryptophan is converted to kynurenine and not serotonin, depression may worsen. Some kynurenine metabolites are toxic and animal models have shown increased depressive symptoms with increased kynurenine [R].

Another study shows that kynurenic acid (KYNA), a derivative of kynurenine, protects the brain while 3-hydroxykynurenine (3-HK) (also a kynurenine derivative) is toxic. High levels of 3-HK and low levels of KYNA can cause depression [R].

3) May Reduce Anxiety
Tryptophan supplements decreased anxiety symptoms in cats [R].

However, other studies show that in social anxiety disorder, serotonin is increased, and tryptophan supplementation could do more harm than good [R].

Interestingly, a study (DB-RCT) of 16 people trying to quit smoking showed that L-tryptophan and a high-carbohydrate diet along with regular smoke-ceasing therapies decreased anxiety and withdrawal symptoms. People given tryptophan supplements smoked fewer cigarettes compared to placebo [R].

4) Reduces Appetite
A study (DB-RCT) on 15 healthy volunteers showed that those receiving L-tryptophan supplementation ate 19 – 20% fewer calories and more proteins than carbohydrates [R].

A rat study showed that after 24 hours of fasting, the rats given L-tryptophan not only ate less on their first meal, but also their post-meal interval between the first and second meal was longer [R].

Moreover, reduced tryptophan levels and absorption into the brain might also be responsible for carbohydrate cravings [R].

5) Can Improve PMS (Premenstrual Dysphoria Symptoms)
The breakdown of tryptophan via the kynurenine pathway is affected by the phase of the menstrual cycle, which can also indirectly affect serotonin production. After ingesting tryptophan, kynurenine was 40% higher during the luteal phase than in the follicular phase [R].

A study (DB-RCT) of 37 patients showed that L-tryptophan supplementation improved the following symptoms in women suffering from premenstrual dysphoria (a severe type of PMS) [R]:

Mood swings
Mood improved by 34.5% in those given L-tryptophan supplements [R, R].

6) May Treat Mania
In a study (DB-RCT) of five patients with mania, L-tryptophan supplementation improved the treatment with chlorpromazine hydrochloride (CPZ) and reduced side effects [R].

In another study (DB-RCT) on 24 patients with acute mania, L-tryptophan supplementation decreased manic symptoms by 43% outperforming a previous treatment with lithium (41%). Those who stopped receiving tryptophan showed worsening of the symptoms [R].

7) Tryptophan Supplementation can Decrease Dementia Symptoms
A study of 24 patients with dementia showed that serotonin levels in the brain were significantly lower in dementia patients compared to healthy people [R].

The same study showed that patients with dementia had less tryptophan absorption than healthy individuals [R].

When patients with low tryptophan absorption were supplemented with tryptophan, only those who increased absorption showed mental improvement [R].

8) May Help Reduce Post-hypoxic Intention Myoclonus
Post-hypoxic intention myoclonus is when someone has sudden muscle contractions or relaxations due to lack of oxygen to the tissues and can be caused by serotonin deficiency [R].

Tryptophan or 5-HTP supplementation improves myoclonus. However, tryptophan or 5-HTP can also worsen the effects of myoclonus in some people [R].

Tryptophan Effects due to Kynurenine
90% of the tryptophan in the body is converted to kynurenine, which dilates the blood vessels during times of inflammation and controls aspects of the immune system [R].

A change in the kynurenine pathway can induce depression. Certain metabolites like 3-hydroxykynurenine are toxic to the brain and increased production of these molecules can cause depression [R].

Increased kynurenine production also means decreased serotonin production and therefore decreased melatonin production leading to improper circadian rhythms. Disturbances in melatonin production have also been linked to depression [R].

Kynurenine can be converted into both kynurenic acid and quinolinic acid. Quinolinic acid in high amounts is toxic for the brain [R, R].

Niacin is also produced by the kynurenic/quinolinic pathway [R].

9) Can Help Protect the Eyes
Kynurenine is the UV filter that protects the eyes against UV damage from the sun and other sources [R, R].

This protection decreases with age leading to discoloration and fluorescence of the eyes (lenses). The loss of protection can sometimes lead to cataracts [R, R].

10) Can Help Prevent Pellagra (Niacin Deficiency)
Niacin deficiencies can lead to a disease called pellagra, which is characterized by diarrhea, dermatitis, and dementia [R].

Pellagra is caused by insufficient niacin or tryptophan intake [R].

However, the recommended dosage of niacin is 16 mg/day for men and 14 mg/day for women, which is almost always reached through normal diets and eating habits [R].

Tryptophan Effects due to Other Hormones
Tryptophan supplementation also increases levels of hormones beta-endorphin, prolactin, and growth hormone [R, R].

11) Can Improve Exercise Performance
In a study (DB-RCT) of 20 patients, tryptophan supplementation led to substantial increases in beta-endorphin, a neurotransmitter/hormone that is released in response to physical processes such as pain [R, R].

A study on twelve sportsmen showed that when the athletes were given L-tryptophan supplements, their total exercise time was 49.4% greater than usual [R].

The L-tryptophan supplements lowered the athletes’ perceived exertion, most likely due to the increased pain tolerance [R].

12) Helps Breastfeeding
A study (DB-RCT) of 5 patients showed that tryptophan supplementation increased prolactin, which helps postnatal women produce milk [R].

13) Tryptophan Supplementation Can Help Children Grow
Tryptophan supplementation also increases growth hormone, which stimulates growth in children [R].

Limitations of Tryptophan Supplementation
1) Contradictory Research
Although there is much research showcasing the beneficial effects of tryptophan supplementation, there is also a lot of contradictory work by other researchers. For instance, in a clinical trial done on 10 female mania patients, the L-tryptophan supplementation did not perform better than placebo [R].

A study (DB-RCT) of 6 depressed patients showed that L-tryptophan supplementation did not help and the patients needed further treatment before release [R].

Depression is caused by many different factors. Therefore, treatments using L-tryptophan can be ineffective when the depression is not due to low serotonin levels. One study proved this by splitting up depressed patients by tryptophan levels. Only the low-level tryptophan patients showed improvements [R, R].

The studies on exercise also have been contradictory. One study shows that exercise performance increased after L-tryptophan supplementation while another shows that L-tryptophan had no effect [R, R].

A meta-analysis of 108 clinical trials on L-tryptophan supplementation effects on depressed patients found that only two of the trials could be fully considered. Many of the trials were discarded due to no placebo control, a very small number of patients, or improper randomizing and controlling [R].

Some of the trials could not be considered because they did not look at tryptophan alone [R].

Negative Effects of Tryptophan Deficiency
Studies on the effects of tryptophan deficiency deplete this amino acid through a process called acute tryptophan depletion, where the patient is given a beverage of 15 different amino acids excluding tryptophan [R].

Drinking the beverage produces two effects:

Stored tryptophan is decreased when the liver produces proteins [R].
Other amino acids compete with tryptophan in crossing the blood-brain barrier thereby reducing the levels of tryptophan in the brain [R].
People suffering from a condition that is linked with tryptophan deficiency can be helped by taking tryptophan supplements if their condition is caused by tryptophan depletion.

1) Motion Sickness
A study of 39 people with migraines and 37 controls showed that tryptophan depletion intensifies dizziness, nausea, and the illusion of movement after induced motion sickness. The depletion caused the same symptoms in the controls as people with migraines [R].

2) Tryptophan Depletion Leads to Lowered Mood
Depression worsened in healthy males after tryptophan depletion [R].

A study (DB-RCT) showed that patients with a family history of mental disorder were more likely to worsen their mood after tryptophan depletion [R].

Another study was able to show that women were more likely to feel the mood-worsening effect since gender affects serotonin production (males produce serotonin 52% faster than females) [R, R].

3) Memory Decline
A study (DB-RCT) of 30 patients showed that patients with lowered tryptophan levels did worse in pattern recognition tests [R].

Another double-blind trial of 27 volunteers showed that tryptophan depletion impaired long-term memory in word recall and recognition tests [R].

These effects have been shown in word replication and memory tests such as visual and auditory remembrance of words and abstract shapes [R, R].

Another study showed that women were more prone to these memory-damaging effects than men [R].

4) Major Depressive Disorder
A study (DB-RCT) of 21 patients on antidepressants showed that lowering tryptophan levels caused the patients to return to their depressed states more often [R].

5) Seasonal Affective Disorder (SAD)
SAD is a disorder where the patient experiences depression based on seasons, mainly during the winter.

A study on 11 SAD patients with depleted tryptophan found that seven out of the eight patients who relapsed in the summer subsequently developed SAD the following winter [R].

SAD is usually treated with light therapy but only up to ⅓ of patients improve [R].

In one study, when 14 patients with SAD were given L-tryptophan supplements along with light therapy, 64% showed very good clinical responses to combined treatment and minimal side effects [R].

6) Bipolar Disorder
A double-blind study of 7 bipolar patients on lithium treatment showed that after tryptophan depletion, manic symptoms reappeared [R].

7) Increased Food Intake in those with Bulimia Nervosa
Bulimia nervosa is a disorder of distorted body image with periods of excessive food intake followed by periods of self-induced vomiting, which is linked to changes in serotonin [R].

A study of 20 women showed that those with bulimia nervosa took in more calories (39% more) and showed increased agitation and mood irritability due to tryptophan depletion [R].

8) PMS
In a study done on 16 women with PMS, depletion of tryptophan led to severe premenstrual symptoms, especially irritability [R].

9) Panic Disorder
A double-blind study on 22 patients with panic disorder showed that after tryptophan depletion, the patients had more anxiety and panic attacks. The controls, however, did not panic after tryptophan depletion [R].

10) Aggressive and Impulsive Behavior
A study of 12 patients with previous aggressive behavior and 12 without showed that after tryptophan depletion, those with aggressive tendencies became agitated and exhibited hostile behavior. Non-aggressive patients, however, decreased their aggression [R].

Tryptophan depletion increases impulsivity leading to aggression [R].

A study on 22 highly and low impulsive patients with ADHD. After tryptophan depletion, the low impulsive patients became highly impulsive [R].

Violent Behavior in Alcoholics
A study of 9 AD patients with or without a history of blacked-out violent impulsive behavior found that violent patients had lower tryptophan levels than the non-violent [R].

Another study showed that tryptophan levels decreased by 10% 30 minutes after alcohol consumption and up to 20 – 25% 1.5 to 2 hours after alcohol consumption [R].

While drugs that enhance serotonin receptor activity reduce alcohol intake, decreased serotonin due to tryptophan depletion triggered violent behaviors in alcoholic people [R].

Rat studies showed that continued alcohol consumption desensitizes the serotonin systems in the brain’s reward system (nucleus accumbens) [R].

Tryptophan Side Effects
1) May Induce Nausea
Nausea is one of the most common side effects of tryptophan supplementation [R].

In one study, a patient has nausea after L-tryptophan supplementation; however, it stopped by lowering the dosage [R].

2) May Induce Distress in the Gut
Another common side effect of tryptophan or 5-HTP supplementation is distress in the gut [R].

Gut problems such as constipation have been seen in up to 25% of patients taking L-tryptophan [R].

3) Linked to Eosinophilia-Myalgia Syndrome (EMS)
Between 1988-1999, an EMS outbreak prompted the FDA to recall and cease over-the-counter tryptophan supplements. However, this was because one company in Japan that made synthetic tryptophan altered their creation process, which caused the outbreak. After this was caught and fixed, the FDA lifted the ban in 2001 [R].

4) May Decrease Tyrosine Absorption
Tryptophan and tyrosine use the same mechanisms to get into the brain. Therefore, excessive tryptophan supplementation decreases tyrosine absorption [R].

Tyrosine produces neurotransmitters such as dopamine, norepinephrine, and epinephrine. Reducing tyrosine absorption also decreases the production of these neurotransmitters [R].

Tyrosine is also used for depression. Therefore, tryptophan supplementation could decrease the effectiveness of tyrosine therapy. For those taking tryptophan to fight depression, the supplement could hinder the results [R].

5) May Decrease Branched Chain Amino Acid (BCAA) Absorption
Tryptophan and BCAAs compete to cross the blood-brain barrier [R].

BCAAs such as leucine play a part in muscle recovery and energy production and, therefore, tryptophan supplementation may reduce these effects [R, R].

6) Other Side Effects
Blurred Vision
Poor Concentration
Dizziness [R]
Tryptophan Reviews
Mainly, tryptophan supplementation relieves many symptoms, such as anxiety, panic, and depression [R].

But, most people said that tryptophan helped with their insomnia [R].

Many users say that the supplement has changed their lives for the better. One user suffering from anxiety and panic attacks that had tried previous medications such as Paxil, Prozac, Celexa, and Clonazepam has scrapped all these for the L-tryptophan [R].

Tryptophan Dosage
While the usual dosage of L-tryptophan is 500 mg, many people take more and supplement’s instructions recommend 3 pills before bedtime.

Less than 8 grams per day for 8 weeks shouldn’t produce any side effects. However, an upper limit for tryptophan supplementation is still uncertain [R].

Drug Interactions
1) Supplementation with Schizophrenic Drugs
A study showed that tryptophan supplementation with iproniazid, a schizophrenia medication, can increase its beneficial effects [R].

2) Supplementation with Antidepressants
In one study, combining L-tryptophan with a monoamine-oxidase inhibitor (MAOI) improved the effects of L-tryptophan alone [R].

However, another study indicates that L-tryptophan with an MAOI can cause serotonin syndrome or dangerously high serotonin levels. Common symptoms of serotonin syndrome include [R]:

The use of L-tryptophan with MAOI has also led to extreme mania [R].

A double-blind study of 115 patients showed that L-tryptophan supplementation with amitriptyline was better than placebo, while other studies showed an improvement from L-tryptophan with nicotinamide or clomipramine [R, R, R].

However, other studies showed that L-tryptophan along with pyridoxine was less beneficial than other depression therapies [R, R].

3) Supplementation with Anti-cough Drugs
Tryptophan supplementation along with anti-cough drugs such as dihydrocodeine, noscapine, and dextromethorphan increased cough resistance [R].

Contraindications of Tryptophan
1) Should not be Taken by Those with Liver Diseases
A study of 40 patients and 14 healthy subjects showed that liver cirrhosis blocks tryptophan breakdown increasing its concentration in the blood by 3-fold [R].

2) Should not be Taken by Those with Kidney Diseases
A clinical study showed that those with kidney problems showed decreased levels of tryptophan in their blood [R].

In healthy individuals, tryptophan supplementation was able to increase the kidney filtration rate, but those with kidney diseases showed no improved effect [R, R].

3) Should not be Taken by Those with Social Anxiety Disorder
A study on 18 patients with social anxiety disorder showed increased serotonin compared to healthy individuals [R].

Therefore, people suffering from social anxiety disorder may do worse with tryptophan supplementation [R, R].

Genetic Mutations that Affect Tryptophan Breakdown
In patients with chronic hepatitis C virus, a tryptophan metabolizing agent (indoleamine 2,3-dioxygenase) is compromised, most likely due to polymorphisms in the IL28B SNP [R].

A study on the IL28B SNP proved that it controls the metabolizing rate of tryptophan. Patients with the C/C genotype at the IL28B SNP have the highest tryptophan breakdown rate while the T/T genotype have the lowest [R].

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Old Wed, Apr-24-19, 05:19
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Ms Arielle Ms Arielle is offline
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The test uses a urine sample to check concentrations of a type of sugar -- glycosaminoglycans -- that ordinarily coat cells lining blood vessels and other surfaces inside the body. In septic shock, the body sheds fragments of these sugars, and the team found that higher concentrations portend death. The test is used in clinical settings, and the insight has helped doctors search for more effective therapies.

Their next step tested whether a link exists between the sugars and mental aging associated with septic shock. Research published in the February edition of the Journal of Clinical Investigations showed that, during septic shock, fragments of the sugar heparan sulfate crossed the blood-brain barrier and entered the hippocampus, a region of the brain critical to memory and cognitive function. Evidence indicated that the heparan sulfate might be binding with brain-derived neurotrophic factor (BDNF), which is critical to hippocampal long-term potentiation, a process responsible for spatial memory formation. The researchers also found that presence of an enriched heparan sulfate in the blood plasma of septic patients upon admission to an intensive care unit predicted cognitive impairment detected 14 days after discharge.
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