5-Hydroxytryptophan (5-HTP) is an amino acid precursor of serotonin with potential antidepressant, anti-anxiety, sleep, and weight management benefits, though it’s not without dangers. Read this post to learn more about the health benefits and downsides of supplementing with 5-HTP.
What is 5-HTP?
5-hydroxytryptophan (5-HTP) is an amino acid that serves as a precursor for the biosynthesis of serotonin and melatonin in the brain from the amino acid tryptophan.
Currently, depression is thought to caused (at least partially) by having low levels of serotonin in the brain, however, it is still not fully understood as to what exactly causes depression [1, 2].
5-HTP in supplement form is extracted from the plant Griffonia simplicifolia, an African shrub.
It is not possible to measure serotonin levels in a human brain without a brain biopsy. Indirect markers that are good indicators of serotonin levels in the brain are cortisol levels and blood or urinary HIAA levels [3, 4].
Primary Benefit of 5-HTP
The people who most commonly use 5-HTP are those who struggle with depression.
Note that 5-HTP supplements have not been approved by the FDA for medical use and generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.
In small clinical studies, 5-HTP alleviated depression better than a placebo. However, more large-scale and higher quality studies are necessary to confirm the safety and effectiveness of 5-HTP .
The antidepressant effects of 5-HTP have been comparable to those of some conventional antidepressants .
The combined use of 5-HTP and SSRIs seem to have strong synergistic effects on serotonin levels in rats and humans. Therefore, some research has investigated the use of slow-release 5-HTP in combination with SSRIs [7, 8, 9].
In a small clinical trial involving 52 healthy male subjects, 5-HTP and an SSRI enhanced serotonin levels by 35% and 100%, respectively. Together, however, they increased serotonin by 500% .
Additional clinical trials are required to demonstrate the safety and effectiveness of this approach. Do not combine 5-HTP and medications without the recommendation and supervision of a doctor.
Other Potential Benefits
5-HTP is currently under investigation for several other health benefits, for which the evidence is not as strong as in the case of depression. The available research here is considered insufficient, either because the human trials are small or because only animal studies exist. Talk to your doctor before using 5-HTP for any reason.
The following purported benefits are only supported by limited, low-quality clinical studies. There is insufficient evidence to support the use of 5-HTP for any of the below-listed uses. Remember to speak with a doctor before taking 5-HTP, and never use it in place of something your doctor recommends or prescribes.
2) Panic Attacks and Anxiety
In a small study of 15 young adults who suffer stress or anxiety from unreciprocated romanticism, 6-weeks of supplementation with 5-HTP decreased anxiety by 3 weeks. The authors attributed the positive results to increased BDNF and serotonin levels .
24 people who suffered from chronic panic attacks, due to lower availability of serotonin in the brain, found significant relief after taking 200 mg of 5-HTP .
In clinical trials, herbal extracts of 5-HTP were shown to activate GABA receptors or increase GABA levels, promoting a sense of relaxation and decreased anxiety .
While these results have been promising, more human trials are required to determine the role of 5-HTP in people with anxiety disorders.
3) Appetite, Cravings, and Weight Loss
Carbohydrates increase serotonin levels in the brain. Supplementing with 5-HTP can mitigate carbohydrate craving and appetite; thus, it could help with adherence to dietary interventions and weight loss [13, 14].
In small clinical trials, 5-HTP supplementation in obese women resulted in no mood changes but decreased food intake and caused weight loss [15, 15].
Dietary Intervention in Type II Diabetes
In a 2-week-long clinical trial involving 25 overweight diabetic subjects given no dietary restrictions, subjects who received 5-HTP had reduced caloric, carbohydrate, and fat intake compared to placebo. Subjects who received 5-HTP also have reduced body weight, blood sugar, insulin, and HbA1C levels after 2 weeks, possibly due to changes in the diet .
As always, talk to your doctor before using 5-HTP for this purpose. They can help you develop an appropriate weight loss plan, which may or may not include 5-HTP.
4) Sleep Quality
In a person with a genetic mutation that caused serotonin deficiency, it resulted in a lack of a circadian rhythm and overeating. For this person, supplementation with 5-HTP restored a normal circadian rhythm and food intake .
Over long periods of supplementation, production of GABA receptors increased, which assisted with natural sleep cycles and the promotion of healthy sleep .
A small clinical trial demonstrated that the use of 5-HTP in combination with GABA significantly improved sleep quality in 9 subjects with sleep disorders, in comparison to placebo .
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Nightmares in Children
Children aged 3 to 10 who suffer from nightmares had a 93.5% reduction after taking 2 mg/kg of 5-HT for a month every night before bed .
5-HTP supplementation has repeatedly been shown to improve symptoms of fibromyalgia since the early 1990s. People with fibromyalgia who take 5-HTP report reduced anxiety and depression, better sleep quality, and less pain .
The exact cause of migraines is still unknown, but many researchers and doctors now believe that low serotonin is at the root. To that end, many migraine medications increase serotonin, and 5-HTP has been found to decrease the frequency of migraine attacks when used regularly [22, 23, 24].
5-HTP Versus Tryptophan
5-HTP and tryptophan are both serotonin precursors, so what are the differences between them? Is one more effective than the other?
1) 5-HTP is Readily Made into Serotonin
The amino acid tryptophan is converted to 5-HTP before it is converted to serotonin. TPH1 and TPH2, the enzymes responsible for converting tryptophan to 5-HTP, are the slowest (rate-limiting) enzymes in serotonin production .
5-HTP is readily and freely converted to serotonin without biochemical inhibition.
2) The Blood-Brain Barrier
Tryptophan competes with leucine, valine, tyrosine, and isoleucine to cross the blood-brain barrier .
5-HTP, however, does not compete with other amino acids to enter the brain.
5-HTP readily crosses the blood-brain barrier without receptors or channels.
Serotonin does not cross the blood-brain barrier, so serotonin outside of the brain (in the gut, platelets, heart, and liver) stays separate from serotonin in the brain.
5-HTP gets converted into serotonin both inside and outside of the brain.
3) 5-HTP is Only Made Into Serotonin
While tryptophan can be used for protein synthesis and the production of niacin, 5-HTP can only be converted into serotonin .
4) Tryptophan Metabolites
Tryptophan can be converted into kynurenic acid and quinolinic acid, which are involved in psychiatric disorders such as schizophrenia, anxiety, depression, and ADHD .
These conversions happen more in individuals with inflammation, which may be a link between inflammation and psychiatric or neurological disorders [28, 29, 30].
5-HTP is not directly converted into neurotoxic metabolites .
Supplementing with 5-HTP
Remember that there have not been sufficient studies to determine a safe and effective 5-HTP dose for various ailments, and the FDA has not approved its use for any medical purpose or health claim. That being said, many clinical studies have found significant results using similar doses.
200 mg safely increased serotonin levels in the brain . Higher dosages increase the likelihood of side effects.
In obesity and weight loss intervention studies, up to 900 mg or 8 mg/kg of body weight of 5-HTP was safely used for 2 weeks, although side effects of nausea and vomiting were reported .
Talk to your doctor before supplementing to prevent adverse side effects and unexpected interactions.
5-HTP Absorption and Elimination
5-HTP is rapidly absorbed in the upper intestine, with 50% of 5-HTP absorbed in 1.5 hours .
Elimination of 5-HTP is also rapid .
Due to the rapid pharmacokinetics of 5-HTP, some researchers have suggested that slow-release supplementation of 5-HTP may be more beneficial to maintain serotonin levels in the brain .
About 70% of ingested 5-HTP is measurable in the bloodstream .
Patients who take 5-hydroxytryptophan have severely decreased levels of P450 expression .
Risks and Side Effects of 5-HTP Supplementation
This is not intended to be a complete list of all possible side effects of 5-HTP. To avoid these and other adverse events and interactions, talk to your doctor before supplementing.
1) Nausea and Vomiting
Since serotonin in the digestive system controls gut movement, all interventions that increase serotonin levels, including 5-HTP supplementation and SSRI antidepressants, can cause nausea, vomiting, and diarrhea.
The most commonly reported side effects of 5-HTP in all clinical trials in humans are nausea and vomiting as the quick surge of serotonin throughout the body is not well tolerated (35, 36).
Slow-released 5-HTP may be better tolerated and less likely to cause side effects .
2) Dopamine, Norepinephrine, and Epinephrine Depletion
Serotonin shares the same conversion (AAAD) and breakdown enzyme (MAO) with other neurotransmitters (dopamine, norepinephrine, and epinephrine).
Long-term supplementation of 5-HTP can cause imbalances of these neurotransmitters. It is therefore recommended that 5-HTP supplementation is supervised by qualified clinicians and balanced with neurotransmitter precursors .
In cases where there is too much 5-HTP, it will reduce dopamine synthesis as a result of overwhelming the AAAD enzyme through competitive inhibition, leading to depletion of dopamine, norepinephrine and other neurotransmitters .
With increasing doses of 5-HTP, MAO activity increases. When this happens, MAO can then break down dopamine and cause it to decrease .
3) Serotonin Syndrome
5-HTP is freely converted to serotonin without biochemical feedback inhibition. When infinitely high amounts of 5-HTP are administered, it is theoretically possible to achieve extremely high levels of serotonin. One limiting factor is the availability of the enzyme L-aromatic amino acid decarboxylase (AAAD), which is an enzyme that converts 5-HTP to serotonin .
Serotonin syndrome explains a set of symptoms caused by very high levels of serotonin, which can be very serious and life-threatening .
Mild symptoms include shivering, sweating, tremor, restless limbs, and headache. Serious symptoms include hypertension, fever, mania, hallucination, and ataxia .
Serotonin syndrome is almost exclusively caused by SSRI and MAOI combinations, causing excessive levels of serotonin in the brain .
5-HTP or 5-HTP in combination with SSRI has not been reported to cause serotonin syndrome [9, 40]. But if it’s taken with SSRIs, it might theoretically increase the risk of serotonin syndrome.
4) Eosinophilia-Myalgia Syndrome
Eosinophilia-myalgia syndrome (EMS) is a disease causing severe, disabling, chronic muscle pain, skin symptoms, and other neurotoxic reactions which have affected over 1,500 people and caused at least 38 deaths. The FDA estimated that there are 10 EMS cases associated with 5-HTP worldwide .
It seems more likely that it is caused by bacterial contamination in the supplement than tryptophan or 5-HTP itself. No new cases of supplement-related EMS have been reported since 1990 .
Other Side Effects
Other rare side effects of 5-HTP include hypomania, lightheadedness, headache, and heart palpitations [43, 40].
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5-HTP is an amino acid precursor to serotonin which is currently under investigation as a potential treatment for depression and other conditions associated with low serotonin. The most promising clinical studies thus far have been of 5-HTP in combination with SSRIs. However, we advise strongly against using 5-HTP alongside SSRIs without a doctor’s prescription, as 5-HTP can increase the risk of serotonin syndrome.
Small clinical studies have also found possible benefits of 5-HTP for anxiety, appetite control, fibromyalgia, migraines, and disrupted sleep, but these are not well-supported.
Unlike tryptophan and serotonin, 5-HTP readily crosses the blood-brain barrier. It is also easily absorbed from the gut and metabolized in the bloodstream. The most common side effects of 5-HTP include nausea and vomiting, while supplementation may also cause serotonin syndrome and depletion of other neurotransmitters like dopamine, epinephrine, and norepinephrine.