(Dr. Mady Hornig recently reported that preliminary results from the Chronic Fatigue Initiative’s microbiome study suggested a subset of people had low gut serotonin levels.  She noted that serotonin is an important immune modulator, and proposed that serotonin’s precursor, tryptophan, could be being metabolized into kynurenine metabolites instead of serotonin.  Kynurenine pathway activation occurs in many neuropsychological and neurodegenerative diseases. In a later discussion with a patient she suggested low serotonin levels could contribute to the “low resilience” some people with ME/CFS have towards stress.

  Thanks to Darden for adding to this picture by allowing Health Rising to present this adaptation of her original blog on serotonin and fibromyalgia. Darden has fibromyalgia. Find out more about her here.)

Serotonin – An Important Part of the Fibromyalgia Picture?

Serotonin, also known as 5-hydroxytryptamine (5-HT) is an important chemical neurotransmitter found in the human body. Serotonin is manufactured in the brain and the intestines. The majority of the body’s serotonin (90%) is found in the gastrointestinal tract where it regulates intestinal movements that stimulate gut motility. The remainder is found in the central nervous system and blood platelets where it plays a role in the formation of blood clots through vasoconstriction. It is synthesized along with its metabolite 5-hydroxtryptophan (5-HTP) from the amino acid L-tryptophan.


Serotonin does much more than effect mood

Serotonin is popularly thought to contribute to feelings of well-being and happiness. There is no scientific evidence, however, that low levels of serotonin contribute to depression. Antidepressant medications such as selective reuptake inhibitors (SSRIs) are thought to inhibit the re-absorption or serotonin and norepinephrine neurotransmitters. This increases the levels of serotonin in the synapse of the nerves in the brain resulting in an elevation of mood. Recreational drugs such as MDMA and cocaine are also thought to inhibit the re-absorption of serotonin to create their highs. Scientists, however, are still not sure precisely how these drugs work.

Early research connected serotonin with mood disorders but more recent research has revealed that serotonin affects many parts of the body.  It has been associated with pain, sleep, pain, bone density  platelet aggregation, gut functioning, the immune system and others.

A recent review focusing on serotonin’s immune modulating effects suggested serotonin may be affecting immune functioning in many inflammatory diseases.  Serotonin is necessary for the proper Many immune cells are littered with serotonin receptors and require it in order to respond to infections. Serotonin affects the migration, activation and cytokine production of many immune cells.

In fact, the authors asserted studies indicated that the serotonergic system is altering immune cell functioning in fibromyalgia, depression, arthritis, allergies, asthma and Alzheimer’s disease. Studies suggest low serotonin levels are present in the serum and cerebrospinal fluid of FM patients. A recent study suggested low serotonin levels may be making ME/CFS worse in some patients.


It is possible to raise serotonin levels in the body by taking tryptophan and its metabolite 5-HTP. Tryptophan was taken off the market in 1984 when thousands of people developed a severe blood disorder called Eosinophilia – Myalgia Syndrome (EMS). The cause was later traced to a contaminant found in batches of tryptophan manufactured by a Japanese company.

The FDA rescinded its restriction of sales of tryptophan in 2001. Both tryptophan and 5-HTP, which is made from the seeds of an African plant Griffonia simplicifolia are readily available in stores that sell nutritional supplements and online.

5-HTP is also a precursor to melatonin, a hormone that regulates sleep-wake cycles. As a supplement it’s used to help individuals with insomnia, and is advertised to improve mood and reduce food cravings. Natural ways to increase serotonin include increasing exposure to sunlight and exercise.

An 1992 open-label and a 1992 double-blinded study suggested that tryptophan could be beneficial in fibromyalgia. Dr. Murphree is strong proponent of using 5-HTP. He reports that

” I’ve consistently found that many of the most troubling symptoms associated with fibromyalgia, poor sleep, fatigue, chronic pain, IBS, mood disorders, and “brain fog,” are diminished (sometimes dramatically) when serotonin levels are boosted and normal circadian rhythms restored.”

Because serotonin levels are already low Murphree does not believe SNRI’s will help many people with FM.  Find out more on Dr. Murphree’s thoughts on 5-HTP and serotonin in fibromyalgia and his 5-HTP sleep protocol in Health Rising’s Resource section.

My Experience

In the fall of 2014 I consulted a naturopathic physician who ordered a laboratory test for neurotransmitters from Pharmasan Labs. The test measured levels of serotonin, GABA, glycine, glutamate, histamine, PEA, dopamine, DOPAC, norepinephrine, epinephrine, cortisol and melatonin. My test results showed that all these substances were within normal levels with the exception for serotonin, which was quite low.


Tryptophan is the precursor to serotonin

At that same time I was being treated for Small Intestine Bacterial Overgrowth (SIBO), a condition that causes IBS and fibromyalgia. For more about that read my post on SIBO. The treatment of SIBO includes taking a prokinetic agent that stimulates gut motility to prevent bacteria from staying in the small intestine.One of those prokinetic agents is the drug Resolor that binds to serotonin receptors in the gut. Resolor does not, in fact, raise serotonin levels; after three months of taking the drug I retested my serotonin levels and they were slightly lower than before.


I then decided to take 5-HTP. I started with a small dose gradually increasing  until I was taking 100 mg. three times a day for 6 weeks. When I retested my serotonin levels they were slightly above normal levels so I decreased my dose slightly. My gastrointestinal symptoms and fibromyalgia have subsided over the past year with SIBO treatments and the addition of 5-HTP seems to have helped with this recovery.

Taking 5-HTP did not improve my sleep which remains disturbed with multiple awakenings throughout the night. I suppose that is not surprising since I do not have low melatonin levels and I have never experienced improvement in my sleep by taking melatonin supplements.

People with fibromyalgia may be typically deficient in serotonin. Since serotonin regulates gut motility serotonin deficiency may be a contributing factor to developing gastrointestinal dysfunction, IBS, SIBO and fibromyalgia. Because serotonin can also affect mood, pain and immune functioning it could also play a role in problems there.

Getting tested for neurotransmitters and raising serotonin levels to normal levels by taking 5-HTP could be an important part of the treatment of fibromyalgia.

Have you tried 5-HTP? Let us know how that went here:

Health Rising’s 5-HTP Resources


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