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 be 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) Serotonin Deficiency 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) Serotonin Deficiency 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) Serotonin Deficiency Reduces Blood Clotting Ability

Serotonin plays a major role in clotting, which it 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) Serotonin Deficiency 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) Serotonin Deficiency 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) Serotonin Deficiency 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) Serotonin Deficiency 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) Serotonin Deficiency 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) Serotonin Deficiency 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) Serotonin Deficiency in Anorexia Nervosa

5-HTP is involved in almost all the behavioral changes observed in anorexia patients.

Both genetic and environmental factors contribute toward 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) Serotonin Deficiency 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) Serotonin Deficiency Causes Generalized Anxiety Disorder

Serotonin 5HT1A receptors contribute to anxiety disorders since mice lacking these receptors exhibited increased signs of anxiety [R].

3) Serotonin Deficiency 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) Serotonin Deficiency 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) Serotonin Deficiency 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) Serotonin Deficiency May Cause Panic Disorder

A panic disorder involves both 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) Serotonin Deficiency Can Lead To Social Phobia

Some studies linked serotonin deficiency to social phobia.

A study (DB-RCT) on 77 people diagnosed with social phobia showed that serotonin-increasing drugs improved anxiety and depression, 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) Serotonin Deficiency Increases Aggression

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

9) Serotonin Deficiency 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) Serotonin Deficiency 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.

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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22 COMMENTS

  • Kelly

    Omg, I HAVE MCAS AND MEGA-LOW SEROTONIN!!! (35, and it may have decreased in the 2 months since testing…I feel a LOT worse!!).
    Can you share any further info on this, Lisa?

  • Lisa

    Unfortunately there is some important research missing here! There IS a disease which has been associated with Abnormally low serotonin levels. Mast Cell Activation Diseases are the cause for extremely low levels of Serotonin and in these patients the majority of them have chronic gastrointestinal disturbances which encompass pretty much ALL of your list above and even more so.

    Although anxiety and depression is seen in these patients, it is not the rule, in spite of the extremely low levels. However, elevated serontonin levels can also be seen. Researchers have not fully blamed the mast cell, however, since the Mast Cell is defective in these patients, the dysfunctional mediator release of a great many neurotransmittors and other mediators have a major impact upon subsequent mediators being released throughout the body.

    This is the link to the research on this finding. If you are interested in more understanding into this condition, I´ll be happy to correspond.

    By the way, even with absurdly low serotonin levels, NOBODY would ever accuse me of depression!!! haha

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795418/

  • Whitney

    Is tianeptine a good choice for someone with both DRD2 and TPH2 mutations? SSRIs have always left me depressed and suicidal but I am dealing with anhedonia and low motivation, clear signs of serotonin and dopamine deficiency. Pharmaceuticals have not helped me and I’ve tried many!

  • Mike

    I think Joe means based on experience with clients that Tianeptine and Mirtazapine work better, not that he takes them. Joe, can you confirm?

  • Bodil Fjellanger

    I have used Paxil with great success for 20 years due to severe OCD (atypical). I was recently diagnosed with MS. This summer I was about to have my third MS attack, when I suddenly noticed that my OCD was becoming a huge problem once again. I doubled my dose of Paxil and tingeling, extreme fatigue and anxiety diasappeared in about two weeks time. This led me to research the connection between serotenin and MS (and Parkinson’s and Rheumatism), and to my surprise I found plenty of papers dealing with this. I know that Paxil may have side effects, escpecially in the long run, and I am very much into alternative medicine, but for some people it is a lifesaver. And in the future it may be possible to avoid medication if the culprit is identified in heavily predisposed individuals at an early stage and adequately corrected. BTW, for me Paxil is tolerable compared to MS medication…Some links:
    https://www.ncbi.nlm.nih.gov/pubmed/26227286
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870621/
    https://www.ncbi.nlm.nih.gov/pubmed/16178854
    https://www.ncbi.nlm.nih.gov/pubmed/21088435
    https://www.ncbi.nlm.nih.gov/pubmed/21232166
    https://www.karger.com/Article/Abstract/334095
    https://www.ncbi.nlm.nih.gov/pubmed/18450787
    https://www.ncbi.nlm.nih.gov/pubmed/20819014
    https://www.ncbi.nlm.nih.gov/pubmed/23783007
    https://www.ncbi.nlm.nih.gov/pubmed/19931427

  • Richard Rosen

    Article by Matt Stone, “The Sadder Side of Serotonin”:

  • C.A.

    There are articles possibly at lef.org describing how saffron produced better results than SSRIs.

  • Marc Anderson

    ways to measure neurotransmitter levels are discussed on Quora

  • Marc Anderson
  • Marc Anderson

    Dopamine is a NT and there is no shortage of evidence that people with Parkinson’s (such as myself) for example, are missing 70% – 80% of their dopamine. They know this from DATscans, MRIs, spinal taps, and autopsies, among other ways.

  • Betsy

    I recently had a test done called the Organic Acids Test – it is done on urine. One of the things that it measured was 5-hyrdoxyindoleacetic or 5-HIAA. Mine was very low and the notes said this could indicate lower production of the neurotransmitter serotonin. Since I eat mostly protein and very few carbs, this actually correlates to what I have read about protein suppressing serotonin and carbs increasing it. I also have some of the symptoms of low serotonin, Just thought I would post this since many people are saying you can’t measure serotonin.

  • D Worden

    Had no idea there were so many physical effect of serotonin deficiency although I have long been aware of the psychological ones. Sad to see that you have had to take pharmaceuticals and — sort of — recommend them. Getting a prescription for distorted, liver-toxic molecules does not fall into the self-hacked category!! Eating the right food to increase serotonin body levels or efficiency does. Yet, there is not even a passing mention of turkey!!! “Food is a drug we take three times a day.” Let’s pay attention to it.

  • DOUG

    EVGUENIA ALECHINE: If serotonin cannot be measured, then it’s not possible to establish “normal”, thus notions of deficiency and excess are contrived. And how can one determine if transporters, receptors, etc are working “properly”?

    1. Evguenia Alechine

      Both deficiency and transporters, receptors, etc. functions are defined based on the ultimate effects of serotonin, which is known mainly from cell and animal research. Also, genes encoding these proteins can be screened for mutations in humans.

  • Julia Pace

    Interesting article. One might think that if bi-sexual and gay people are low in serotonin then they would also be socially awkward but I haven’t found that to be true at all. Probably more data needed.

  • Doug

    I guess I would throw it back to you guys — where are the studies showing that neurotransmitters can be accurately measured in a living human? If they could, and if the results consistently showed correlation between mood/behavioral/cognitive disorders and deficiency or excess of NT’s, then I’d expect docs and pharma co’s would be shouting from the rooftops that everyone must have this test done. They are not… but of course such a test is always around the corner, as someone said. And if NT’s cannot be measured, then why are people still talking about deficiency of serotonin?

    BTW, Robert Whitaker’s “Anatomy of An Epidemic” does a good job of debunking the whole paradigm. He cites insiders/experts and lots of research, including studies showing sketchy results with attempts at measuring NT’s in cerebrospinal fluid.

    1. Evguenia Alechine

      The main causes of serotonin deficiency are not due to the actual lack of serotonin as a molecule (except low tryptophan intake), but it has to do with its ineffectiveness. One might have a normal amount of serotonin, but if the receptors, transporters, or metabolizing enzymes don’t work properly, the effects of serotonin won’t be achieved. That’s the reason why, even if one could measure serotonin (which is currently not possible because you have to measure it in the synapses), the measurement won’t make much sense. As you might have seen, the main causes of serotonin deficiency are genetic (which can be studied) and it’s diagnosed based on the symptoms. The importance of this knowledge relies on the possibility to know the actual cause of one’s symptoms and biohack this deficiency.

  • Doug

    Surprised SelfHacked is echoing the specious biological reductionism of the Pharma neurotransmitter marketing narrative. Last I heard there is still no valid way to measure neurotransmitters and no valid evidence that one can have a “deficiency”. Just because a drug or other substance produces some change in mood or function or behavior, does not mean a deficiency has been corrected. It means biochemistry or metabolism has been altered in some way. And seems in the case of SSRIs they actually introduce pathology into the brain. That’s how they work.

    1. Joseph M. Cohen

      We’re just echoing what’s in the scientific literature. If you have other studies you’d like to share that conflicts or adds to what is in this article, we will include them in the article.

      Thanks,
      SelfHacked Team

  • Missskitttin

    The information on this article is a pile of nonsense unsupported and salacious. Where did you finf this? The Enquirer?

    1. Joseph M. Cohen

      Which part exactly is not true and what’s your evidence?

  • Nejc

    One could also use so called “psychobiotics” such as lactobacillus helveticus (e.g.
    R1: https://www.ncbi.nlm.nih.gov/pubmed/26408987 and
    R2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102282/).
    This article also reminds me of Paul Jaminet’s “Mice Who Tear Their Fur Out and The Psychiatrists Who Treat Them”.

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