Investigating the Serotonin-Liver Relationship

Serotonin, the hormone known to make people happy, may also be deeply involved in liver fibrosis.

The human body is a complexity, involving countless amazing feats at every moment. Nowhere is this seemingly miraculous series of events more pronounced than in the liver. An organ subjected to repeated abuse, the liver maintains a remarkable ability to regenerate itself upon incurring cellular damage. A new study published in a peer-reviewed journal has found that a hormone known predominantly for its link to emotional well-being also appears to play a role in liver cell regeneration.

Especially in the presence of the Hepatitis B or C virus, alcoholism, a fatty liver or an autoimmune disease, sometimes the balance required to repair liver cells gets disrupted. This disruption impairs the liver’s regenerative abilities so that it can no longer keep up with relentless liver cell injury – and scars form. The propensity to scar more than repair the cellular damage describes the course of chronic liver disease – and British researchers believe that a well-known hormone could be the key to regaining balance.

About Serotonin
A team led by Newcastle University researchers has identified serotonin as playing a healing role in liver tissue regeneration. Also known as 5-hydroxytryptamine, serotonin is a hormone found in many locations, including the brain, the digestive tract and blood platelets. In addition, serotonin is a neurotransmitter – a substance needed to transmit certain nerve impulses.

Serotonin’s wide range of functions partially depends on what type of receptor this hormone attaches to: sometimes serotonin’s binding to a receptor can encourage a physiological function while binding to a different receptor can discourage a physiological function. There are at least seven different types of serotonin receptors, each of which can have many subtypes. For those studying serotonin, the expansive nature of serotonin and its receptors confirms the complexity of human biology.

Often regarded as the ‘happy’ hormone, serotonin exerts a major influence on our overall sense of well-being. Serotonin is instrumental in:

•    Learning
•    Balancing mood
•    Aiding sleep
•    Vasoconstriction [is the narrowing (constriction) of blood vessels by small muscles in their walls.]
•    Regulating aggression, appetite and sexuality
•    Regulating body temperature and metabolism
•    Tempering anxiety
•    Relieving depression
•    Wound healing

Because a deficiency of serotonin levels in the brain typically affects mood, many antidepressant medications function to increase serotonin levels. Selective serotonin reuptake inhibitors (SSRI’s) are one of the most frequently prescribed medications for depression and mood disorders, contributing to the assumption that serotonin is primarily a hormone linked to emotional health. However, serotonin’s clinical applicability extends far beyond the emotions.

Serotonin and the Liver
Of particular interest to those with liver disease, the extent of liver damage depends on the balance between the generation of scar tissue and the regeneration of new liver cells. When scarring of this important organ becomes excessive, the liver’s ability to function is impaired. Also known as fibrosis, extensive liver scarring interferes with the liver’s ability to detoxify the blood and manufacture crucial hormones and clotting factors. Advanced cases of fibrosis can lead to cirrhosis – the permanent hardening and shrinking of the liver – and liver cancer.

As part of the normal healing process, scientists understand that blood platelets secrete serotonin when involved in tissue repair. However, serotonin exerts an undesirable effect on hepatic stellate cells, specialized cells that are the major source of liver damage in chronic liver disease. Researchers from Newcastle University have found serotonin to be involved in the balance between scar tissue formation and healthy liver cell regeneration. More specifically, their research indicated that:

•    when scar-forming cells (hepatic stellate cells) are present, serotonin influences them to increase scar tissue formation and switch off healthy cell production

•    the serotonin receptor 5-HT2B instructs hepatic stellate cells to switch off regeneration

•    substances that bind to 5-HT2B results in less liver scarring and more cellular regeneration

To make sense of this research, a bigger picture of serotonin and its receptors is helpful. Similar to a lock and key unit, serotonin inserts into a receptor to either “lock or unlock” a cell’s function. When serotonin binds with a receptor, there is less of it available in the spaces in between cells. In this case, serotonin binding with 5-HT2B gives hepatic stellate cells instructions to cease cellular regeneration. Blocking serotonin from binding to the 5-HT2B receptor interferes with its ‘cease cellular regeneration instruction’ and results in more serotonin circulating between cells.

Although only observed in an animal study, this research has a dramatic impact on our understanding of the mechanisms that dictate the balance of cellular regeneration and fibrogenesis. In addition, the study’s lead author, Professor Derek Mann indicated that their results suggest that chemicals targeting 5-HT2B (which are currently in clinical trials for mood disorders and pulmonary hypertension) could also help treat chronic liver disease.

Both liver scarring and cellular regeneration are a normal part of the liver’s response to injury. However, influencing the balance to favor cellular regeneration would be very beneficial to people with chronic liver disease.

The new information linking serotonin with liver scarring via the hepatic stellate cells is preliminary, and is insufficient for drawing conclusions. The Newcastle research does not imply that currently available SSRI’s are good or bad for liver health. Instead, their finding is exciting because it reveals that occupying a specific serotonin receptor provides a way to reduce liver scarring and encourage liver cell regeneration. As such, future studies zeroing in on 5-HT2B have the potential to improve the outlook for the millions of people living with chronic liver disease.

Editor’s Note: In response to the confusion posted by several readers, this article has been updated. It seems that the role of serotonin on tissue healing and regeneration is specific to the receptor type and the cell type.

References:

http://www.acnp.org/g4/GN401000039/Ch039.html, Serotonin Receptor Subtypes and Ligands, Richard A. Glennon, et al, Retrieved April 1, 2012, American College of Neuropsychopharmacology, 2012.

http://www.healthcanal.com/medical-breakthroughs/23858-Manipulating-serotonin-can-promote-healthy-repair-chronic-liver-disease.html, Manipulating serotonin can promote healthy repair in chronic liver disease, Retrieved November 28, 2011, HealthCanal.com, 2011.

http://www.medicalnewstoday.com/articles/232248.php, What is Serotonin?, Christian Nordqvist,  Retrieved December 4, 2011, Medical News Today, 2011.

http://www.ncbi.nlm.nih.gov/pubmed/11586470, Hepatic stellate cell behavior during resolution of liver injury, Iredale, JP, Retrieved April 1, 2012, Seminars in Liver Disease, August 2001.

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2490.html, Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease, Mohammad R Ebrahimkhani, et al, Retrieved November 28, 2011, Nature Medicine, November 2011.

  • Ljm3713

    I’m reading all this and thinking of my beloved mother-in-law who passed of cirrhosis on Easter Sunday, May you rest in Peace Mom!  I have a rare liver disease- Liver Adenomatosis- and I’m wondering now whether to get back on my  Prozac and Wellbutrin. I took myself off all meds because I just got tired of it all, and recently made an appt with my doc to get back on them because I am depressed and get so easily aggrevated.  I’m so confused after reading this article! I’m scared to get back on these meds if they are hurting my liver but with the depression and irritability, I’m scared not to. Any thoughts would be appreciated. 

  • Yarbrough Terrinell

    I hear some of you say about a brain fog and i wonder if that is what is wrong with me?Ihave HCV with a non-alcholholic fatty liver and COPD and severe depression! Does my inability to think,retain thought, learn a new thing(can not grasp to learn) foggy headed , tired beyond beleif, cry everyday and tryed to opt myself out of life because i am no longer what i once was, i cannot function somedays!!! I start on Herbalife and it so helped but some days i pray al day to have energy and think and remember(it is hard) so is it possible it is HCV doing it to me!!

    • Carol H.

      It is also the COPD that gives us problems w/the brain.  If you’re not getting enough oxygen, brain can’t think straight.  Depression affects the brain greatly.  I also found since unable to work, I have to push my brain every day, doing puzzles, reading a library book to learn a new subject,etc.  If you’ve ever been on Hepatitis C treatment,  many of us keep those side effects, brain not up to speed.  They recently found that clinical depression is a major side effect of Hepatitis C.  Herbalife must have good combination of amino acids, proteins, vitamins that just help a person get in better health.
        Maybe you can get a good gastroenterologist, get the right anti-depressant (right strength), find a support group and start handling things a little better and these things are weapons against that STUPID, FRUSTRATING, LIFE-CHANGING, HORRIBLE Hepatitis C.  People w/this disease are some of the strongest people I’ve ever seen and you will surprise yourself six months from now if you ask for help.  Most of us were in the prime of our lives and then..this.
        But, you are not alone.  I don’t think you were meant for the option you mentioned.  That’s not fair, you have a purpose, think, pray, etc. and find it.  The trick – the hard part – is living as long and as fully as you can.  You are not a coward, you just got to a huge bump in the road.  But, you can do it. 

    • Lovehopejoy2004

       I have had hcv for 32 yrs and all of your symptoms are related to the desease. I have found a product called Xango to help me. It is natural juice from the mangosteen fruit. I also take ultra thistle from Zand. It helps to pace yourself and to get out and help others, like the aged or visit a nursing home. I also take a whey protein shake every morning, but chose carefully. At a certain point the liver has trouble getting rid of extra iron so keep an eye out for stuff high in iron, it will be bad for you. hoping this info helped. Terri

  • Ali

    So if it is wound healing… That is precisely what we want less off a hep c cirrhosis.. Because it is by trying to heal itself that our livers go overboard and create the scarring.. Our livers are trying to protect themselves from the hep c invader but doing too good a job ,
    So it sounds like serotonin may encourage them to do it more. The article is very confusing and a distinction needs to be made between people with hep c and ongoing liver attach and people with other cirrhosis who may be able to reverse there condition by altering their lifestyle.

  • Antomann

    I think this article indicates that it is important to find some joy in our life while living with Hep C. It’s the power of positive thinking and Serotonin is a naturally occurring hormone.

    My Health Practitioner reminds me to “love my liver” and to think of my liver as the powerful amazing organ that it is. I have weened myself off the SSRI’s a couple of years ago and feel that I’m better off.

    I’m grateful that I found out about my Hep C when I did and I was able to make changes in my life to improve my health. Gratitude increases my happiness, and helps me love my liver.

  • Jon

    If we feel good, we heal better, simple. When we feel good, we are secreting more serotonin throughout our bodies. The concurrent use of vit D3 with conventional treatment for hepC has been shown to reduce the depressive and anxious symptoms that the treatment provokes. Taking SSRI’s longterm, has been associated with increased incidence of hepatic inflammation, so not a good idea, even the longterm use of proton-pump-inhibitors, like nexium/losec, has been associated with hepatitis, also not a good idea. For depression, rather use CES (cranio-electro-stimulation) treatments: such as the Elexoma device, or Neuro-stim. Combine with vitD3 and even lithium orotate can be helpful. Strongly suggest using energy-psychotherapy tools, such as EFT or Psych-K, drug free and powerfully effective to aid healing. Always remember: there are many ways up the mountain, not just what big-Pharma allow us to know!!
    Be Well

    • Yarbrough Terrinell

      I was on 3 antidepression meds 1 with this seratonin and i tried to opt myself and would have succeded if my dautghter had only not come by that day and i ended up in the ICU and now i am here and i am off allmeds except down to only 1 sllep med  the doctors do not want you when you have NO insurance and i can not afford those meds so i take Herbalife instead and it keeps me alive and going and most days feel happy or at least like i am alive and with purpose i take care of my 4 grandkids and without Herbalife i could NOT do that so seratonin did not work for me with HCV with a nonalcoholic liver,the doctors could NOT believe i DO NOT drink and i do not drink alchohol and i foind out from Carol that it is COPD that is affecting my brain in which the doc. in ICU found dried blood in my head did not know how it got there and could tell i had HCV for a LONG LONG time but they will go NO further than that just save this life and move them along out of here i lost my hearing and my eye sight is getting worse everyday so oh boy Life, ain’t it great!

  • William Johnson

    I wouldn’t think of using any SSRI drug. The latest study in the NEMJ is enlightening to say the least and why would anyone want to take a drug(s) that were designed to replace things like, Thorazine and Haldol for the truly violent and psychotic and now handed out to even children like candy? You folks at Liver Central need to get a grip and read the latest studies on such drugs before posting them here.

  • Clayre

    I agree with the confusion. Please for those of us battling liver disease clarify!!!

  • Linda Reynolds

    ?????

  • elaine

    I think what this is saying is that the make up of serotonin includes a recptor 5-HT2B. While the other element of serotonin can stimulate the growth of scar tissue the action of the binding of certain substances to receptor 5-HT2B can counter act that increase in scar tissue generation. That’s why the Brittish researchers are looking for a way to restore the balance of serotoin activity. When serotonin isn’t functioning properly it stimulates scar tissue growth, when functioning properly it aids in liver regeneration.

  • Camille

    This article contradicts itself and someone should update and clarify it ASAP. If you’re going to publish something, get it right please……..

  • Errol Harding

    OK which is it, good or bad for the liver???

  • hmblower

    Once again statements about liver disease, searching and researching for answers about this important organ, years of it and still a mystery, will this article encourage the use of anti ads, which appears to be promoted for all sorts of illness’s, all of these findings are suspicious as many just dont go anywhere, its getting to the point of switching off.

  • Tess

    I have so much brain fog it sounded good the first time I read it but after reading the comments I missed the uh oh moment. I take nothing for the depression and I am so depressed on some days I just sit and cry but this is my decision. I just do not want to add another medications to a liver that is barely treading water with Hep C and sweveral other meds I have to take for other things unrelated or as I think related to Hep C……CAD, High BP, Osteoporous etc. I think I will go cry some more….because this article is so not making sense.

    • Carol H.

      I wish you a little peace from crying.  It’s so tough, but you’re tougher. (or @ least don’t let the darn disease think you’re not!)

  • Peg

    This article is very confusing. First it states ” identified serotonin as playing a healing role in liver tissue regeneration.”

    Then it states ” when scar-forming cells (hepatic stellate cells) are present, serotonin influences them to increase scar tissue formation and switch off healthy cell production ”

    So which is it? Liver regeneration or increased scar tissue?

    Am I missing something here???

  • Jefri

    So is it a yes serotonin good or bad? I take prozac daily because of treatment for hep c.

  • Richard

    I agree with Veda. In fact, all three bullet points in this article are ambiguous and contradictory. Does it mean that serotonin is bad because it increases scar tissue formation? Or does it say serotonin is good because it reduces scar tissue formation? Please clarify!

  • Barbara Henderson

    I agree with Veda. That statement confused me also. As someone who takes a SSRI for depression, I can’t tell if serotonin is implicated in fibrosis or is helpful to prevent fibrosis. Please explain. Thanks.

  • Veda

    Is this sentence I copied from the article a mistake – it sounds like it’s contrary to what the article is saying:
    “when scar-forming cells (hepatic stellate cells) are present, serotonin influences them to increase scar tissue formation and switch off healthy cell production”

  • http://www.whatisserotonin.com Kent

    Serotonin is known to regulate several key aspects of liver biology and these functions include hepatic blood flow, innervation and wound healing.

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