Serotonin Series
We hear a lot about low serotonin in fibromyalgia (FMS) and chronic fatigue syndrome (ME/CFS), and it's usually in relation to its function as a neurotransmitter (chemical messenger in the brain.) However, serotonin is also busy in the rest of your body as a hormone, and body-wide serotonin dysregulation is believed to contribute to many of our symptoms and comorbid conditions.
The name serotonin is derived from its earliest discovered function, which is to narrow the blood vessels -- sero means serum, which is a component of blood. Blood flow irregularities have been noted in both of these conditions:
- In FMS, research shows abnormal blood-flow patterns in the brain, with more than normal in some areas and less than normal in others. We don't know the specific effects of this, but researchers do know that blood flow has a significant impact on brain function.
- Also in FMS, some researchers theorize that the horrible burning pains we get are due to ischemia (impaired blood flow), which basically means the area "falls asleep" and then gets those painful pins and needles as the blood, and therefore feeling, returns.
- In ME/CFS and to a lesser degree in FMS, some research has shown low blood volume, which results in cells that are starving for oxygen and nutrients. Picture being at a high altitude and struggling to catch your breath after not eating all day. That's what every cell in your body may be going through.
I feel like a broken record saying this, but at this point we don't have specific research on the possible relationship between serotonin dysfunction and these irregularities, but it's certainly a connection that seems logical.
The relationship of serotonin to fibromyalgia isn't fully understood but appears to be fairly straight forward. Not so for ME/CFS. This is one area where we have to look at the conditions separately.
Fibromyalgia & Serotonin
One of the most consistent findings in FMS is low serotonin. It's possible that our bodies don't produce enough, that they don't use it properly, or both. Many of us are helped by the supplement 5-HTP (triptophan), which our bodies use to create serotonin. Some of us are helped by serotonin-increasing foods. Most of the drugs used to treat us change the way our brains use serotonin in order to make more of it available. (For a detailed look at this see Understanding Reuptake.)
Low serotonin is also linked to migraine, which is considered a related condition. In migraines, low serotonin causes the blood vessels to dilate (open wide,) which causes inflammation in surrounding tissues. That makes for a lot of pressure and results in throbbing pain. FMS pain isn't exactly the same as migraine pain, but it's theorized that similar mechanisms may be involved.
Then consider this -- we all have a secondary set of nerves on our blood vessels and sweat glands that primarily deals with blood volume and sweat. Research published in late 2009 revealed that, at least in some people, these nerves also appear to transmit information about temperature. Researchers hypothesize that these often-ignored nerves may play a role in pain conditions including FMS and migraine. It makes a lot of sense, since we have blood flow problems and excessive sweating in addition to temperature sensitivity and heightened pain response. Hypersensitivity in those nerves could also help explain why ischemia could lead to such intense pain.
Chronic Fatigue Syndrome & Serotonin
Then there's ME/CFS. The common belief is that it, like FMS, involves low serotonin. The symptoms are consistent. The fact that serotonin-impacting treatments work for some people with this condition also lends support. However, it's not that simple. In fact, researching the role of serotonin in this condition is enough to short circuit your every brain cell.
We have some evidence showing that the serotonin-creation system is in overdrive, and some showing two serotonin-based subgroups -- one with high levels, one with normal levels. You'd think that would mean that, at least for the first subgroup, we'd need to lower serotonin levels. Like usual, ME/CFS is determined to defy logic.
That's because we also have evidence showing weak serotonin-related signal transmission in the central nervous system. The condition appears to feature hyperactive production but low function.
Is the body producing extra to compensate for an impairment in how it's used, like a type-2 diabetic who needs extra insulin to continue normal function? If so, are some areas getting flooded with too much serotonin while others are deprived? Is too much serotonin constricting blood vessels so the blood can't get around properly? We don't have answers yet, and research could well be muddled by the lack of proper, consistent subgrouping, in spite of research suggesting that several subgroups exist and are vastly different from each other. This could certainly explain the differences in how people with ME/CFS react to serotonin-affecting treatments (which I'll cover later in this series.)
What Does It All Mean?
The bottom line is that, in some way, most of us have serotonin dysregulation of some kind, and it seems likely that it contributes to blood-flow abnormalities that may cause a variety of our symptoms. This is something to keep in mind as you gauge the effects of treatments, which is really the only way for us to learn our individual degrees of serotonin dysregulation. (It's not something doctors test for outside of a research setting.)
- Get familiar with other symptoms of low serotonin: Serotonin Dysregulation in Fibromyalgia & Chronic Fatigue Syndrome.
Have you been treated for irregularities in blood flow or blood volume? Did it help? Did your doctor ever mention the possible role of serotonin? Have serotonin-affecting treatments helped with blood-flow-related symptoms? Leave your comments below!
See the rest of the Serotonin Series.
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- Neurotransmitter Dysfunction in FMS & ME/CFS
- Serotonin-Regulating Supplements: 5-HTP, SAM-e, Rhodiola rosea, Theanine
- Serotonin-Affecting Drugs: Cymbalta, Savella
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I have FMS and this article has been very informative! Thank you very much.
This is a very nice article on aspects of serotonin, a neurotransmitter with multi biological functions. Indeed a role on blood flow regulation along with autonomic mechanisms that link stress, thoughts and changes in blood flow, sweating, heart rate etc. Serotonin also plays a role in mood, sleep & pain. 5HT receptors are involved in nociceptive activity and one significant neural pathway is ‘driven’ by serotonin.
Understanding functional links is key to designing effective treatment programmes but also helpful in giving sufferers a sense of meaning through greater knowledge
The symptoms of my CFS are similar to those that are caused by too much serotonin, or not enough dopamine, whichever way you want to look at it. Anxiety, insomnia, GI disturbances, nausea etc. SSRI’s, melatonin and 5HTP all make my condition much worse. When I was pregnant with both of my children, I had terrible, morning sickness and migraines because estrogen/serotonin levels dominate or go up during pregnancy. For me, personally, the problem is not a lack of serotonin.
Serotonin: It’s Possible to Have Too Much of a Good Thing
Interesting chart: http://www.psychiatrist.com/pcc/brainstorm/br5812.htm
Good article.
Could you please comment on Low Dose Naltrexone as as treatment for FMS and CFS.
I really appreciate your articles and how you phrase these complicated issues so that the lay person or fibro fogged person can understand.
I’m looking forward to this series, as you called it. I hadn’t thought about serotonin before this article, but now I’m intrigued to know how it relates to my CFS. In particular, I’d like to know if there are any supplements or lifestyle changes I could try to influence my serotonin levels one way or the other.
This blog can really bring me hope some days. Even if it is guarded, realistic optimism, it’s better than despair.
I wish I could figure out whether my serotonin is high, low, producing but not being used effectively or not being produced because it has so many implications. The gut is another one where I read that excess in the gut causes diarrhea and too little – the opposite and since I go between the too – what am I supposed to do. I tried 5-htp and didn’t notice too much at the low dose of 50mg. However, I have taken 2 melatonin chewable tablets recently and it sent me to bed within 15 minutes with horrible dizziness and nausea and some gut spasms which luckily did not amount to anything but I have ibs along with mecfs and fibro. I think melatonin, seratonin, gut, brain and blood-heart-vascular system are ALL affected by seratonin but I am still having withdrawal symptoms from SSRI and I am still taking a small dose (I can only reduce like 1mg once every 6 months – what an ordeal with the head jumps) so I am really interested in the seratonin mechanics. Bring on the research!
I might be one of those with TOO MUCH serotonin, or the inability to process it properly. Serotonin-altering medications give me tardive dyskenisia (permanent) as well as more temporary symptoms of serotonin syndrome. In fact, I would venture to say an SSRI actually CAUSED my fibromyalgia as I was fine before that.
I thought I was the only person in the world who also had this problem with medication induced dyskinesia/dystonia involving serotonin-altering meds. Long story… 18 years and counting.
Hi Karen,
Do you take vitamin E? While it won’t cure you of the tardive dyskinesia, it can help to diminish the severity.
A doctor of mine (happens to be a psychiatrist who treats CFIDS/M.E. since he also has it – doesn’t do talk therapy – just the physical symptoms…but, he “gets it”) told me that 400 units of vitamin E can help to prevent tardive dyskinesia and even diminish it if already present.
Just a thought…hope this info helps.
Healing thoughts,
Sarah
Thanks for this very interesting article.
One other thing that’s good to know is that ME/CFS generally has abnormal blood flow to the brain also, which is not necessarily connected with low blood volume (if I remember right, it’s often present even when hypovalemeia is not). SPECT scans and xenon SPECT scans are good ways to check (and SPECT is a good keyword to look up the research).
Yes, my doctor tested for a lot of things including hypercoagulation, which I have. I go to Chronicity, formerly known as the Fibromyalgia and Fatique Centers, and I am getting treated in the way I need to be treated and improving.
I am wondering if the service you are receiving at Chronicity is beneficial. The drs I have gone to speak very poorly of the services at the Fatigue Clinics. I have been thinking of going to the Holtdorf Medical Group in CA. But it sounds like the c
Fatigue clinics use the same methods as the founder of the Holtdorf Medical Group. I would appreciate hearing from you.
thanks.
I am wondering if the service you are receiving at Chronicity is beneficial. The drs I have gone to speak very poorly of the services at the Fatigue Clinics. I have been thinking of going to the Holtdorf Medical Group in CA. But it sounds like the c
Fatigue clinics use the same methods as the founder of the Holtdorf Medical Group. I would appreciate hearing from you.
thanks.
I am wondering if the service you are receiving at Chronicity is beneficial. The drs I have gone to speak very poorly of the services at the Fatigue Clinics. I have been thinking of going to the Holtdorf Medical Group in CA. But it sounds like the c
Fatigue clinics use the same methods as the founder of the Holtdorf Medical Group. I would appreciate hearing from you.
thanks.
Two doctors from the FFCs (i.e., Chronicity, Inc, who has owned them for years but just changed the name) have been sanctioned by their respective medical boards within the last two years.
Look up James Stevens of Texas or Karen Bullington of Atlanta on the Texas or Georgia medical board web sites. Read their sanctions by the boards and tell me if you would want them to treat you. Or just search other sites like mdjunction, phoenixrising, or others and you can read many complaints by people who paid a lot of money and did not get better, or in some cases were severely harmed by their poorly studied treatments.
My doctor has regularly tested my Serotonin level for 3+ years. Originally I had very low Serotonin. It was 21 with the range being 0 – 400. Then I started taking Cymbalta and 5-HTP. The level started to drop and is now at 2. Has anyone had success with any other treatments?
This is all very confusing to me. I have both FMS and ME/CFS, and all I know is that I’ve been taking 300mg of 5_HTP (3 100-mg capsules) almost every night for three years. When I don’t take it, I can’t sleep. When I do, I sleep well, at least for 6 or 7 hours. Not sleeping is torture and not an option for me, since I get SO fatigued during the day after only one chore or activity anyway. If I don’t sleep I have to force every movement the next day. I started taking it in 2008 after reading the advice from one of the FMS doctors who had an article on this or a related site about the importance of it. He said it is also important to take it within 30 minutes of bedtime with grape juice, which i do in spite of having diabetes, because I use low-carb juice and only swallow 2-4 ounces with the capsules. I get terrible migraines, but they eventually get “fixed” by my chiropractor.
I took 5HTP and melatonin for a year, but they really didn’t do much besides cause gastritis. However, after I had a positive tilt table test and got diagnosed with orthostatic hypotension, I began drinking 2L salt water every day. What a difference; I was washing walls within two hours LOL. It increases my blood volume. I still struggle but I’m a lot better.
I have never been tested for my serotonin level, it is presumed to be low based on symptoms. My rheumatologist felt strongly that there is a connection to the fibro. I am also interested in others’ experience with low dose naltrexone. I have a script for it but haven’t filled it yet. Good article.
man,am i confused. i have fibro,cfs,ibs,yatta yatta yatta. i also been dx’d major depression. been on 90mg cymbalta a few years, and insurance (medicaid) said i could only have 60mg day unless my dr appeals. so i made a bad decision (sp?) and said, well i’m always depressed and in pain anyway, i used to take prozac about 20 yrs ago and felt pretty good. dah, me, everybody felt better 20 yrs ago. man, my pain doubled and i couldn’t stop crying, for days. i had been checking into 5htp cuz they said it was a precursor to seritonin. but as i am researching online, one place says do not take with ssri. i’m back to 60 mg cymbalta now and have stoped crying, pain leveling out to “normal” haha. but after reading all the above, i’m more confused then ever. i guess i’ll stick with the devil i know for now.God bless us all. kathy in tx
kathy in tx again, i just remembered i was told by a dr about 40 yrs ago when i was in my early 20’s that i probably had low blood flow to my brain. i think cuz i was having migraines. those stopped a long time ago, but i have had a couple of strokes that i knew i was having and some mini strokes that i didn’t realize i was having. i’ll be 60 yrs old this year, and got sick in1994. i have a good tip about getting your disability from ss. i got mine over 10 yrs ago. i told the people in the room that i wanted to make sure i got all my points accross well, and with my short term memory probs and fibro fog and anxiety, since this meant eating or having a place to live, since i had lost every thing, i would be reading from a prepared statement. i told them it was only fair to let me do that,otherwise this very important decision that would affect the rest of my life would be based on information given by a blithering idiot. then i sat down and wrote down every thing, and i mean everything, these diseases had taken from my life, and what i was left with, all the changes that had to be made to my life. write your heart out!! it got me my disability, like i said,over 10 years ago, before most people had even heard of fibro. good luck and God Bless. kathy in tx
To About.com:
Thank you for your indefatigable efforts to educate and offer support to those suffering with FM and/or M.E./CFIDS.
Regarding increasing serotonin, it’s important to note that one should avoid SSRIs as well as anything that can dramatically elevate the levels (melatonin even) of serotonin even if naturally…IF manic-depression/bipolar syndrome runs in one’s family. Good psychiatrists have found that even if one does not suffer from manic-depression, increasing serotonin “can” trigger a manic episode…temporarily or permanently. Basically, one “can” have a “dormant” gene that is awakened. It doesn’t mean you have manic-depression, but it does mean that you might have a “connection.” That’s the simplest explanation.
It’s very tricky, so if you do have a direct family member with manic-depression/bipolar syndrome, please always mention it to your doctor. They’ll often disagree with you (as they’re not informed enough), but look up the literature.
I find that non-psychiatrists are prescribing anti-d’s way too often and not qualified enough to do so. Yes, Savella/Milnacipran is for Fibro, but it’s still an anti-d.
Always research whatever your doc wants you to try. Be your own best advocate, and never be shy to ask questions or “challenge” your healthcare professionals. We’re talking about your health, your well-being, and as much as we need doctors, they’re not God.
Remember that YOU are paying THEM to help YOU get better…so they’re sort of like your “employee!” lol
I confess that I’m fortunate to live in a city that has some of the top M.E. and FM docs in the world, so I’ve been exposed to the best treatments, but even with that, I am still on disability…not asymptomatic or in remission…but learning is a never-ending experience.
To better days…and don’t lose hope!
S
P.S.
If we don’t educate ourselves, how will the public perceive us accurately and with more respect?!? Yes, I’m an adovocate, so I think about these things. 
(Pardon any typos – migraine and facial peripheral neuritis going on for months now – wow – just when I thought I had experienced every symptom…I was “UNpleasantly” surprised with this one!)
It’s best not to use the term “CFS” since, as I always say, we don’t call Parkinson’s Disease “Chronic ‘Shakiness’ Syndrome” or Alzheimer’s Disease “Chronic ‘Forgetfulness” Syndrome as that would be inaccurate, misleading and completely insulting, right? Well, “fatigue” is a symptom of pretty much EVERY chronic illness. Also, I describe what everyone calls “fatigue” as a debilitating weakness like someone is gradually poisoning me…it’s a “sickly weakness.” Think about it. Fatigue means tired. Tired people usually sleep well after partying or working too much and feel rejuvenated. They’re not “weak” and feeling “sickly.”
Sarah
I agree about the nomenclature: “fatigue” is not only vague and incorrect but trivialises the symptoms. Have you tried DHEA and pregnenolone? It is almost a miracle. From the weighed down, gasping for breath with every move weakness, I can drive again and do many more of the everyday chores, as well as feeling happy “for no reason” with a smile plastered on my face. Before the DHEA, I would feel anxiety, depression, hopelessness. Always refused the antidepressants, that great untested experiment and profitable scam which only makes things worse. I take the tablets sublingually so they work faster and less is needed. Some days need to take it 2 or 3 times. See the research which shows how great DHEA is for osteoporosis, heart function, etc. as well.
Hi Maria,
Thank you for your suggestion. I was on DHEA (25mg/daily) for a few months way back in the day. My hormone levels were “off.” It definitely helped to normalize them. My thyroid, strangely enough, is fine, but I do have a small pituitary adenoma/tumor.
Also, while I don’t have depression or anxiety, I DO have hemicrania continua (chronic head…ache/pressure – incessant!) which is a nightmare in and of itself. And, the treatment for it is worse than the daily, perpetual head pain/pressure I feel, so I go for acupuncture and when my insurance used to pay for it, myofascial/cranialsacral massage/release. I know – so, I never got the depression or anxiety, but I DID develop chronic head pain/pressure…over 11 years of this symptom. Crazy…
Thanks again for taking the time to reply!!
To healthier days!
Sarah
I have diagnoses of CFS & FMS and am being treated for. Hypercoagulation Disorder as well as for extremely low serotonin levels. The treatment includes nutritional supplements (Coag Clear) and bioidentical serotonin in addition to Cymbalta and Trazodone. I am also on a wide array of other nutritional supplements. It is hard to say which supplements or meds are helping the most, but the frequency of flares has diminished and my brain fog is not as bad.
I am still surprised that so little time and money is spent doing research on Fibromyalgia that affects so many millions of people. It’s because it’s primarily a woman’s complaint, I think. This illness so changes our lives, we have to find ways to live around it. Managing it is a full time job.
I’ve been taking Prozac for it for many years now. When my father, (who had this disease), was finally given Prozac in his nursing home, he was pleasant again. What a change in personality. Irritability all changed to joy. Wish he could have had Xyrem for restorative sleep. Why is this medicine kept so under wraps? Just because it has been used by criminals in date-rape? It’s a life saver for fibro patients. I’ve been using it for 5 years now, and am no longer bed ridden, on high doses of pain killers. Doing so much better thanks to Xyrem.
This is a good article. I’m very glad you addressed both problems concerning serotonin. Meaning, I’m glad you included those of us who can’t take these medications and our symptoms are made much worse by taking them. This has been a huge issue for me over the past decade and longer. Some professionals tend to think and say, “take anti-depressants it will fix your problem and if you don’t you are the problem”. For some of us this issues has created much frustration. Thanks for the article for information and validation.
me, again again, thanks for what you said sarah about manic dep. that runs in my family real big time. had 2 half brothers commit suicide. my father had it, and am sure my son does as well, but he fights going to a dr, but he does take effexor. my life is hell, used to have many interests, can’t bring myself to do a thing, been dx’d agorahphobic(scared to leave house) about 35 yrs ago, but that is some better. been dx’d major depressive after an 8 hour exam. the only thing holding my feet to this earth is my faith in Jesus and my fear of hell. i am back on 60mg cymbalta a day, so at least i’ve quit crying. but after reading all this stuff, i’m too afraid to try anything different, for fear of wigging out. i’m gonna be 60 this year, so all i’m doing is waiting to die. i live with the above mentioned son, but have to move out so he can have my room for his new family. just waiting on a section 8 apt to open up. don’t mean to be a downer, but i’m just being honest.
to kathy r: If you are safe in the arms of the Lord Jesus, have given yourself to Him for His keeping of your soul, and if you’re trusting in Him alone–in His work on the cross–to make you ready for Heaven, you have no need to fear Hell. Though our outward man may be perishing, our inward man can be renewed day by day when we read and understand His Word.
Hi Kathy R.,
I’m sorry I didn’t see your response or I would’ve replied sooner!
My heart completely breaks for you. While I don’t suffer from depression, I do know how difficult, saddening and frustrating it is to live with and watch a loved one suffer from manic depression. We often feel helpless…and, to make matters worse, we feel helpless when trying to treat OURSELVES with our own illnesses. You’re not alone. I know it sounds like a very small consolation, but there ARE many people in the same boat/situation as you.
Please, please do not lose hope! I appreciate your honesty and do not think you’re a “downer” or anything. In fact, I prefer when people are very honest – even brutally honest if need be. There are those who overcompensate by “sounding” so positive and “alive” when, in fact, it’s their way of coping with the distress they really feel.
I’m not a doctor, but as a 36 year “young” lady (lol) who started to develop FM at 21 and crashed with fevers, swollen glands, spasms, ubiquitous pain, dizziness, head pain (not “simple” migraines – if only!), etc., at 25 1/2 years young, it’s been a “challenge.” But, I eventually put together a good health care team, and while I’m still on disability, at least I’m not bedridden anymore and can overcome the relapses and flare-ups a tad faster. They still hit, but such is the nature of both FM and CFIDS/M.E.
I’m sorry you don’t have familial support or a good support system when it comes to friends. Do you have a therapist or psychiatrist who also does talk therapy? You shouldn’t have to just “wait life out.” There really is hope, and I’m a cynical scorpio, so if I say there’s hope…believe me!
I never give false hope because there are no guarantees in life…more to come…ran out of space! 
I have been diagnose with fibromyalgia for a about 10 years now. I also have degenerative disc disease! I take two different antidepressants, I take tramadol, gabapentin, and meloxicam for pain. I also have pennsaid gel to rub on. I am extremely stiff in the morning. Neck hurt and lower back is extremely painful. If I do not take my medicine, I will be extreme wishing for it to be over with! People who do not suffer from this disease do not have a clue as to what we go through! I am also taking nuycenta and also getting trigger point injections. I work because I have no choice. Disability would not be enough to pay all my bills!