Is 5-HTP Safe And Effective For Fibromyalgia? An Evidence Based Analysis

5-HTP for fibromyalgia

For those of us who have experienced mental health issues are aware of the neurotransmitter theory of our moods. These are chemicals in our brain that apparently dictate our mood, behavior, appetite, etc.

There is dopamine for motivation, there is epinephrine for the fight or flight response, and then there is serotonin ‘the happy hormone.’ Personally I think as a team they can contribute to an optimum mood rather than attributing them with specific functions.

But pharma and mainstream meds have a different approach; SSRIs or selective serotonin reuptake inhibitors are a type of antidepressants that help in recycling serotonin molecules in our brain to use them efficiently.

If you are wondering why am I talking about mental health in a fibro article, since fibro is a physiological condition …. you are right, but SSRIs are actively prescribed by physicians to manage chronic pain.

In fact, in this review study that involved 36 studies, 70% stated that SSRIs have a significant effect on chronic pain. But the researchers also noted the possibility of bias in most of these studies.

Serotonin apart from regulating mood also plays an important role in pain perception. Therefore SSRIs are recommended for chronic pain in fibromyalgia as they are more tolerable and have lesser side effects than other antidepressants.

So where is tryptophan in all of this? Read on..

What are 5-HTP and L-tryptophan and how can they help in fibromyalgia?

Previously I told you about SSRIs recycling serotonin; so it’s a plausible question: why recycle serotonin, why not produce or supplement with serotonin?

Here is where tryptophan comes into the picture. SSRIs are not designed to produce serotonin.

Tryptophan is the amino acid that is responsible for the production of serotonin. It is an essential amino acid- it has to be obtained from the diet and can’t be produced by the body.

Psychology Today explores the role of tryptophan in mood disorders and busts the myth of ‘turkey makes you feel sleepy coz of the tryptophan richness in it.’

Tryptophan is converted to 5-HTP (5-hydroxytryptophan) which is then converted to serotonin. Apart from this tryptophan is also involved in another pathway called kynurenine pathway which can affect immunity and inflammation.

Apart from trypthophan supplements, 5-hydroxytryptophan supplements are also available. They are prepared from the plant Griffonia simplicifolia, an African shrub.

Unlike tryptophan, 5-HTP crosses the blood-brain barrier and directly converts to serotonin. Therefore it is thought that its supplementation can boost serotonin levels and relieve related symptoms.

Tryptophan metabolism is found to disturbed in fibromyalgia and can contribute to
• pain,
• reduced immunity
• increase in inflammation as well as
• depressive and cognition related symptoms

This disrupted metabolism could be due to a variety of factors such as reduced absorption of tryptophan, genetic defects that affect the metabolism of this amino acid, unhealthy gut flora, etc.

Thus supplementing with serotonin’s immediate precursor, 5-HTP can help bypass this aberrant metabolism, produce serotonin and help relieve pain.

Now is this a valid and sound therapeutic basis? We will get to that by the end of this article.

But first up, we will explore the possible benefits of 5-HTP supplementation in fibromyalgia.

3 Evidence Based Benefits Of 5-HTP For Fibromyalgia

One study has explored the benefit of 5-HTP supplementation in fibromyalgia. Apart from that, there are other proven pharmacological properties of 5-HTP that could be relevant to fibro therapy.

1. It is proven to alleviate symptoms of fibromyalgia

A few studies conducted around 1999-2002 have identified that tryptophan metabolism may be disturbed in fibromyalgia patients.

Higher tryptophan levels are associated with reduced pain scores.

If you are aware of the various causative factors of fibromyalgia, then you must have come across this point that HPA axis is disturbed in this condition. This is also referred to as ‘neurohormonal aspect’ of fibromyalgia.

HPA axis or hypothalamus-pituitary-adrenal axis is a feedback mechanism linking the major hormone-secreting glands with the brain. This mechanism is intricately involved in stress and production of cortisol. Cortisol levels are elevated in fibro.

Supplementation with 5-HTP can help regulate HPA axis and normalize hormones in fibromyalgia.

Caruso et al. were the first to investigate the benefits of 5-HTP supplementation in fibromyalgia. In the 1990 study, they observed that 5-HTP significantly improved all symptoms of the condition. Side effects were mild and transient.

In 1992, they published findings of another similar study. 50 fibromyalgia patients were enrolled in the 90-day study.

The parameters observed here included anxiety, pain intensity, number of tender points, sleep quality and fatigue. 5-HTP was found to improve all these parameters.

50% of the patients experienced ‘good’ or ‘fair’ clinical improvement. 15 patients reported side effects, but only one patient withdrew from the study owing to side effects.

Researchers concluded that 5-HTP is effective in reducing symptoms of fibromyalgia and its therapeutic effect is maintained for the 90 day period.

Quick Gist: Serotonin is involved in pain perception, and tryptophan, as well as 5-HTP, are precursors of serotonin.
Tryptophan metabolism is disturbed in fibromyalgia. Thus supplementation with 5-HTP is found to reduce pain, fatigue, anxiety and improve sleep quality in fibromyalgia.

2. It can relieve mood-related symptoms in fibromyalgia

Apart from the concept that chronic pain can pave the way for depression and anxiety, some patients are diagnosed with mental health conditions with existing conditions like fibromyalgia and chronic fatigue syndrome.

Studies suggest that 5-hydroxytryptophan supplementation may benefit in depression. One of the reasons is that 5-HTP crosses the blood-brain barrier.

And also the conversion of L-tryptophan to 5-HTP is a rate-limiting step or the slowest step. So 5-HTP supplementation helps bypass this step and can deliver a quick therapeutic effect.

The Cochrane review (2002) on tryptophan and 5-HTP for depression reported that they are better than placebo for alleviating depressive symptoms, but further research is required to confirm their safety and efficacy.

A study published in Asian Journal of Psychiatry, 2013 demonstrated that 5-HTP supplementation is as effective as fluoxetine in treating patients with the first depressive episode. The antidepressant effect of 5-hydroxytryptophan was observed in 2 weeks.

A recent study published in The Journal of Clinical Psychopharmacology, 2017 demonstrated that a combination of creatine and 5-HTP helped reduce depressive symptoms in patients with SSRI or SNRI resistant depression.

Preliminary studies have also found it beneficial in managing anxiety disorders and panic attacks.

A case report demonstrated that tryptophan in combination with benzodiazepines helped relieve rapid cycling bipolar disorder as well as fibromyalgia in a patient

Quick Gist: 5-HTP supplementation may aid in reducing depressive and anxiety related symptoms better than placebo. Tryptophan supplementation may benefit in bipolar disorder.

This can benefit mood-related symptoms in fibromyalgia but more research is required to confirm these findings.

3. It can improve sleep

Adequate sleep is essential for every individual. Sleep deprivation does tend to make us irritable and reduces our focus the very next day. Frequent episodes of sleep disturbances can even affect our metabolic health.

Lack of sleep can contribute to fibromyalgia-like symptoms of malaise and pain even in healthy individuals. This suggests that sleep disturbances can contribute to worsening of fibromyalgic pain.

A recent study published in Sleep Medicine Reviews, 2015 reports that sleep complaints are more frequent in fibromyalgia than other rheumatic diseases.

L-tryptophan supplementation is proven to reduce sleep onset time and benefit in insomnia.

Shell et al. conducted a study where they examined the effect of GABA, 5-HTP as well as other nutrients on sleep disorders. GABA is a neurotransmitter.

18 patients with sleep disorders were enrolled in the study to receive either the active treatment or placebo. 5-hydroxytryptophan and other nutrients reduced the sleep onset time from 32.3 minutes to 19 minutes and increased sleep duration from 5 hours to 6.83 hours.

Overall it was observed that GABA and 5-HTP combination improved sleep quality, duration and reduced sleep onset time.

Quick Gist: Chronic pain in fibromyalgia can contribute to sleep complaints. Also, sleep deprivation can cause a feeling of malaise.

5-HTP may help ameliorate sleep disturbances in fibromyalgia and aid in improving sleep quality and duration.

Is 5-HTP Safe? Few Factors To Consider Before Supplementing With 5-HTP or Tryptophan

As we have understood the role of serotonin in fibromyalgia, it is logical that 5-hydroxytryptophan supplementation can help relieve its symptoms.

But serotonin metabolism is a complex mechanism, and one must take into account various factors that can regulate 5-HTP levels.

This part gets a bit geeky (if it’s too much then move to the Quick Gist for this section) but it is essential to understand this before supplementing with 5-HTP.

Decreased levels of tryptophan in fibromyalgia may be due to various factors

Tryptophan is an essential amino acid and needs to be derived from the diet. Interestingly the body maintains low levels of tryptophan.

Tryptophan depletion is observed in fibromyalgia and depression. Depletion of this amino acid could occur due to a number of reasons.

Genetic factors could be responsible for this and cause abnormal tryptophan metabolism.

Irritable bowel syndrome diagnosis is common in fibromyalgia patients, and this could cause malabsorption of tryptophan leading to its deficiency.

Gut health, food intolerances, and abnormal gut flora could also lead to low tryptophan levels.

Chronic infections could increase the requirement for various vitamins and tryptophan. Thus in addition to tryptophan one may need to supplement with B complex vitamins.

Apart from genetic reasons, if other conditions cause tryptophan depletion such as poor gut health, reduced absorption or infections, then these need to be treated first before opting for 5-HTP supplements.

Tryptophan and 5-HTP metabolism is regulated by various factors

Studies indicate that level of 5-HTP and serotonin is dependent on the levels of tryptophan.

However increased dietary intake of tryptophan does not result in high levels of 5-HTP and serotonin. This is because tryptophan can regulate its levels and stimulate its breakdown at high levels.

Various enzymes are responsible for the conversion of tryptophan to other metabolites. Surprisingly, high levels of pro-inflammatory agents may stimulate these enzymes to break down tryptophan into metabolites other than 5-HTP and serotonin.

That means high levels of inflammation can indirectly deplete serotonin levels, and in this case, exogenous 5-HTP supplementation may benefit.

Tryptophan hydroxylase is the enzyme that converts l-tryptophan to 5-HTP. Interestingly this enzyme is inhibited by various factors such as
• Stress
• vitamin B6 deficiency
• magnesium deficiency
• insulin resistance
• and even high levels of tryptophan.

These are also the same factors which make tryptophan unavailable for production of serotonin.

Genetic alterations in the genes related with this enzyme could also be responsible for reduced 5-HTP synthesis and hence the resultant symptoms.

Another influencing factor is melatonin. Melatonin is the hormone that is actively involved in sleep regulation and is derived from serotonin.

Increase in tryptophan and 5-HTP levels can boost serotonin levels which may elevate melatonin levels.

But high melatonin levels can induce the activity of pro-inflammatory agents in the body, and these again can deplete tryptophan and serotonin reserves.

Tryptophan metabolism is a complex mechanism involving various enzymes, metabolites, and co-factors that support the enzymes. Supplementation with tryptophan alone may not be the answer; it may require supplementation with other vitamins and minerals.

Also, we may have to eliminate or treat the cause of inflammation to support optimumconversion of tryptophan to serotonin.

5-HTP conversion to serotonin may require addition of an enzyme inhibitor

L-amino acid decarboxylase is the enzyme that converts many l-amino acids to neurotransmitters. For example, it converts L-DOPA to dopamine in Parkinson’s.

Similarly, this enzyme converts 5-HTP to serotonin. But the catch here is that: this enzyme can cause this conversion in the periphery as well as in the central nervous system. By periphery, it means organs other than the brain and nervous system.

Serotonin produced in the periphery does not reach the brain as it cannot cross the blood-brain barrier. Also, this peripheral conversion leads to reduced availability of 5-HTP to the brain.

This conversion in the periphery can be blocked by administering an enzyme inhibitor or decarboxylase inhibitor. As in case of Parkinson’s, carbidopa is the enzyme inhibitor given with levodopa.

Thus it is thought that giving carbidopa with 5-HTP may help increase the efficiency of the supplement and mitigate side effects. However, carbidopa itself has its side effects.

5-HTP can be converted to serotonin in organs other than the brain. In such a case the serotonin developed would not reach the brain and lead to depletion of 5-HTP.

To promote 5-HTP conversion in the brain, it may require administration of an enzyme inhibitor such as carbidopa to yield potential effects.

High levels of 5-HTP may deplete other neurotransmitters

Though science has identified various neurotransmitters and attributed certain traits as a dominant function of these neurotransmitters, we must understand that each of these chemicals exists in our body in a fine balance.

The serotonin pathway is unique, but the enzyme required to produce serotonin and dopamine is the same. Also the enzyme necessary to utilize or breakdown serotonin and dopamine is the same.

Thus the neurotransmitters and their precursors compete with each other to interact with these enzymes and are maintained in a delicate balance.

Fairly old studies have shown that supplementation with 5-HTP alone may cause serotonin to play the role of dopamine and lead to depletion of dopamine.

Similar results have been observed in case of high levels of 5-HTP and norepinephrine (the one involved in our stress response).

Even amino acid precursors other than tryptophan and 5-HTP such as L-tyrosine (the one required to produce dopamine) if taken in excess may deplete other neurotransmitters.

This applies to L-DOPA as well; its supplementation may deplete other neurotransmitters and amino acid precursors. Also, this explains why long-term treatment with levodopa may cause other cognitive and motor defects to develop in Parkinson’s.

However, these findings must be verified by further research. And also these studies cover 5-HTP in isolation and do not comment on Griffonia simplicifolia extract.

A few studies conducted in the late 70s and early 80s have reported that treatment with a combination of amino acids may help balance neurotransmitter levels and deliver better therapeutic effects.

This would mean a combination of l-tryptophan and l-tyrosine or 5-HTP and l-tyrosine would be more effective than 5-HTP or tryptophan alone.

High levels of 5-HTP may lead to depletion of other neurotransmitters. Therefore nutrients and amino acids should be administered in a way such that all neurotransmitter levels are balanced.

Quick Gist: A few factors need to be considered before supplementing with 5-HTP:
• Low tryptophan levels in fibromyalgia may be due to various reasons such as poor gut health or infections and resolving these can help normalize its levels.
• Tryptophan metabolism depends on many factors and nutrients. Supplementation with certain minerals and vitamins , before resorting to l-tryptophan and 5-HTP supplementation, may help in some cases.
• Inflammation may lower tryptophan levels. Curbing inflammation may be the first step towards treatment.
• Promoting conversion of 5-HTP to serotonin in the brain rather than in other organs may require administration of an enzyme inhibitor for better therapeutic effects.
• High levels of isolated 5-HTP or long-term treatment with it may cause depletion of other neurotransmitters and increase the risk of other side effects.

Does that mean 5-HTP supplements are not safe for fibromyalgia?

5-HTP supplements may help and prove to be safe in fibromyalgia if taken for a short period (3 months) and cycled (taking breaks from the supplement) regularly.

5-HTP supplements are used by many without observing any side effects.

This could be because 5-HTP supplements are made from Griffonia simplicifolia and the herb extract may have much more than just 5-HTP. These undiscovered bioactives may help mitigate the side effects that could occur with taking 5-HTP alone.

Studies in humans using 5-HTP or Griffonia simplcifolia extract alone have used it for a short period of 1-3 months.

It is advisable to opt for 5-HTP supplements on short term and not for periods longer than 3-6 months at the most. Consult a health practitioner before taking it.

Dosage of 5-HTP for Fibromyalgia

There is no prescribed dosage of 5-HTP for fibromyalgia. The study that has explored the same topic utilised a dose of 100mg of 5-HTP 3 times a day for 90 days.

Start with a low dose of 5-HTP (50mg) and increase gradually. It is important to identify what works for you as high doses may cause gastric side effects as well as mood disturbances or hypomania.

Some suggest taking green tea extract with it as green tea antioxidants are a natural alternative to carbidopa and can help in preventing the breakdown of 5-HTP before it reaches the brain. Adequate research is required to ascertain the safety of this combination.

Some studies have used other amino acids such as L-theanine, L-creatine, and L-glutamine in combination with 5-HTP. If deficient in B vitamins, their supplementation may be necessary.

Its combination with magnesium may deliver better therapeutic effects.

There is a quite a bit of conflict on the idea of benefits of dietary tryptophan, but it wouldn’t hurt to include a few good sources of tryptophan in your diet. Additionally, if they are a quality protein source, they can provide other essential amino acids as well.

I have come across one study which shows that dietary protein source of tryptophan (deoiled gourd seeds) with carbs is as effective as pharmaceutical tryptophan in relieving insomnia. That’s a promising study, and more research is required to examine benefits of dietary tryptophan

Precautions

5-HTP may cause gastric side effects such as nausea, vomiting, heartburn, stomach spasms. This is mostly observed at high doses.

Since it regulates serotonin levels, it may affect mood, cause irritation and agitation in some.

At low doses, oral 5-HTP is found to act as a psychoactive substance and can affect decision making.

To prevent the risk of high serotonin or serotonin syndrome, it is advised not to combine SSRIs or other antidepressants and 5-HTP; however many studies have found the combination safe.

Further research is required to confirm the safety of the combination. Till then it is best to avoid co-medicating or one should maintain a minimum 3-4 hour gap between the two.

One animal study has reported that Griffonia simplicifolia may adversely affect female sexual behavior.

FDA had banned tryptophan supplements in 1989 due to the presence of contaminants which caused eosinophilic myalgia syndrome. However, that was related to the quality and purity of the supplement, and no such cases have been reported since then.

UMM states that 5-HTP may have drug interactions with antidepressants, carbidopa, triptans, dextromethorphan, tramadol, and meperidine.

If suffering from metabolic health issues, please consult a doctor about 5-hydroxytryptophan safety in such conditions. Avoid 5-HTP in pregnancy and lactation.

Please consult a health practitioner before taking 5-HTP supplements.

Conclusion

5-HTP is a precursor to serotonin and benefits in fibromyalgia by elevating serotonin levels and reducing pain as well as other symptoms. There have been only two studies conducted on it back in 1999-2002.

More research is required to confirm the benefits and safety of 5-HTP. This amino acid derivative is found to benefit significantly in mood disorders as far as patient reviews are concerned.

But the one really important aspect that needs to be taken into consideration is that high levels of 5-HTP may deplete other neurotransmitters.

It is quite possible that when using a plant-derived 5-hydroxytryptophan source, this may not occur as the herb may contain other extracts that help balance neurochemistry. But since little is known about this, it best to use it on short term.

If opting for 5-HTP for fibromyalgia keep a few things in mind:
• Avoid co-medicating with it.
• Use for short-term (3 months or 6 months at the most).
• Please take a break from the supplements intermittently after awhile.
• Start with small doses (50mg) and scale up gradually.
• Ensure your diet has a complete protein source and is well balanced (includes vitamins and minerals).
• For women with fibromyalgia, you could use it just before the menstrual cycle to prevent worsening of the symptoms.

5-hydroxytryptophan will help if you experience serious cognitive or psychological symptoms along with chronic pain in fibromyalgia.

If you have been diagnosed with a genetic defect of tryptophan metabolism, 5-hydroxytryptophan supplementation may seem valid.

Otherwise, there are other safer approaches to fibro treatment such as magnesium or vitamin B supplementation in combination with natural anti-inflammatory agents. By safer, it means that you won’t have to worry about overdosing or cycling (taking a break) from the supplements.

Do share how 5-HTP has worked out for you in fibromyalgia. Also if you did find this article beneficial do share it on social media and like our Facebook page (the box is the right hand column).

Learn whether 5-HTP is a safe natural therapy for fibromyalgia.

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