5 Hydroxytryptophan and Fibro

5 HT is a monoamine neurotransmitter that is also commonly called serotonin.

It is formed from the amino acid, tryptophan in the gastrointestinal tract, and the central nervous system. L-tryptophan is first converted to 5-hydroxy-L-tryptophan or 5 HTP before being converted to serotonin or 5 HT.

90% of the 5 HT produced in the body is made by the enterochromaffin cells of the gut. In the gut, 5 HT is responsible for intestinal movements.

However, it is the smaller amount produced in the central nervous system especially in the brain that produces most of the important therapeutic and side effects of 5 HT.

Elsewhere, 5 HT is also found in the platelets of the blood. The platelets are responsible for removing excess serotonin from the gastrointestinal tract. These platelets not only act as storage sites for serotonin but are also used to transport 5 HT to the parts of the body where it is needed.

Outside the central nervous system, 5 HT has some effects on the cardiovascular, endocrine, and musculoskeletal systems. It is a vasoconstrictor when released in the blood vessels and it can help stop blood clots as well as promote healing.

5 HT is also involved in the release of hormones such as insulin; it is also required for the release of insulin-like growth factors and it can act as a growth factor itself.

In the central nervous system, 5 HT plays a central role in the regulation of appetite, mood, and sleep as well as in learning and memory.

There are 7 types of 5 HT receptors and each class has many sub-types.

These receptors are found in the central and peripheral nervous systems as well as in other organ systems in the body. Each 5 HT receptor can produce either inhibitory or excitatory responses.

5 HT receptors also contribute to the release and activity of other neurotransmitters such as dopamine, glutamate, GABA, norepinephrine, epinephrine, and acetylcholine. They fulfill a similar role for hormones by contributing to the release of cortisol, vasopressin, prolactin, oxytocin, and substance P.

Because of its many effects on multiple organ systems in the body, both low and high levels of 5 HT can have profound effects.

While high levels of 5 HT cause a toxicity reaction called serotonin syndrome, low levels of 5 HT can cause several medical conditions including weight gain, depression, and fibromyalgia.

What is Fibromyalgia?

Fibromyalgia is a medical condition characterized by persistent, chronic pain and heightened painful responses to pressure and non-painful stimuli all over the body.

However, pain is not the only presentation of fibromyalgia. Other symptoms of the disorder are fatigue, muscle spasms, stiff joints, disturbed sleep, numb and tingling sensations, difficulty swallowing as well as gastrointestinal and bladder disorders.

Fibromyalgia also shares some symptoms with neurological disorders. Such symptoms include cognitive dysfunction, depression, anxiety, and stress disorder.

However, not everyone living with fibromyalgia experience the full spectrum of these symptoms.

With these sets of symptoms, fibromyalgia can either be classified as a musculoskeletal disease or a neuropsychiatric disorder. This is another way it is tied to 5 HT and serotonergic pathways since serotonin affects both the musculoskeletal system as well as the central nervous system.

Fibromyalgia affects 2 – 4% of the population and it is estimated to be 9 times more common in women than men.

There are some genetic components to fibromyalgia. Clinical data suggests that it is an inheritable condition and that it involves multiple genes including those responsible for other disorders such as depression, chronic fatigue, and irritable bowel syndromes.

Different causes have been proposed for fibromyalgia. The table below lists the common causes.

Since the exact cause of fibromyalgia is still unknown and there are no definitive laboratory tests to guide diagnosis, some experts still contest that it is a separate disease and not the presentation of the sum of the symptoms of other diseases.

Furthermore, most drugs used in the treatment of fibromyalgia only work for some subsets of patients and not others. This shows that the disorder can have multiple causes.

Where the level and/or metabolism of 5 HT is the suspected cause, fibromyalgia patients respond well to serotonin drugs such as SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors).

Different studies and clinical data suggest that SNRIs produce better results than SSRIs.

However, the use of antidepressants such as SSRIs and SNRIs in the treatment of fibromyalgia is only to reduce symptoms such as depression, pain, fatigue, and sleep disturbance.

The relationship between 5 HT and fibromyalgia is even more complex. For example, one of the effective serotonin drugs used in treating fibromyalgia is a 5 HT3 receptor antagonist which reduces the activity of serotonin.

Study Results On Fibromyalgia & 5 HT, 5 HTP, and Tryptophan

In a 1989 paper published by I.J. Russell, it was first discovered that some fibromyalgia patients suffer from low serum levels of serotonin.

Another study by the same author found out that there was also a lower level of serotonin metabolites in fibromyalgia patients. The same outcome was observed in patients suffering from rheumatoid arthritis.

Other studies have found that serum levels of serotonin and tryptophan are usually low in fibromyalgia patients. Also, the levels of tryptophan and 5 HTP in the cerebrospinal fluid are usually low in these patients.

A 1995 paper in the Journal of Musculoskeletal Pain found out that in fibromyalgia patients, a competing synthesis pathway diverts tryptophan from the serotonin pathway leading to low 5 HTP and 5 HT levels.

A 1992 study published in the Journal of Rheumatology also found out that low serotonin levels caused increased sensitivity to pain.

Another important naturally produced compound found in low levels in fibromyalgia patients is IGF-1 (insulin-like growth factor).

Since serotonin directly controls the release of IGF-1, it is expected that low serotonin levels will contribute to low IGF-1 levels. However, IGF-1 is a growth factor needed for building up new muscles, therefore, myalgia and muscle wasting seen in fibromyalgia patients are indirectly caused by low 5 HT levels.

The increased sensitivity to pain experienced by fibromyalgia patients is believed to be caused by increased levels of substance P.

Substance P is produced in the peripheral nervous system but then moves into the central nervous system especially when serotonin levels are lowered. Substance P is known to reduce the pain threshold when it gets to the central nervous system.

Lastly, some experts believe fibromyalgia is more common in women than men precisely because women have a lower capacity for producing serotonin than men.

5 HTP and Fibromyalgia

Of the 2 precursors of serotonin, 5 HTP is the one usually used to treat fibromyalgia.

Tryptophan is not used for several reasons but the most important of these are the large dose of amino acid required and the increased degradation by an enzyme that is produced in large amounts in response to high concentrations of the amino acids.

Of the 8 essential amino acids, tryptophan is the one found in the least amount of proteins. It also shares the same transport mechanism as leucine, isoleucine, and valine to cross the blood-brain barrier.

The competitive pressure reduces the extent of absorption of tryptophan from dietary sources and makes it necessary to take very large doses via oral supplementation.

However, when large amounts of tryptophan do cross into the brain, the enzyme known as tryptophan pyrroles is upregulated to break down more tryptophan.

Unlike tryptophan, 5 HTP does not face the same competition to get into the brain since it uses a separate transport mechanism to get through the blood-brain barrier. Also, once tryptophan is converted to 5 HTP it is fully reserved for serotonin synthesis.

Therefore, 5 HTP preparations are the best natural supplements to help increase serotonin levels when treating fibromyalgia.

In a 1990 study published in the International Journal of Medical Research, the efficacy of 5 HTP was compared against placebo in the treatment of fibromyalgia. The study involved given 100 mg of 5 HTP to 50 fibromyalgia patients 3 times daily over a period of 30 days.

After the study, the patients were evaluated for clinical signs such as sleep patterns, anxiety, morning stiffness, and pain. The result showed that 5 HTP improved all 4 clinical parameters significantly more than placebo did, and that side effects are mild and resolved quickly.

The study was expanded 2 years later. The new study done by the same researchers covered 90 days and arrived at the same results.

The most common side effect of 5 HTP is nausea which can be reduced by taking it with meals.

Different studies place the dose of 5 HTP needed to increase serotonin levels and resolve fibromyalgia at 200 – 1000 mg per day. Where the serum levels of tryptophan and serotonin are both low, vitamin B6 and niacinamide should be added to tryptophan and 5 HTP therapy.

Vitamin B6 is needed to increase the conversion of 5 HTP to serotonin while niacinamide prevents the conversion of tryptophan to niacin (a competing use of tryptophan).