5-hydroxytryptophan (5-HTP) is a by-product of the amino acid L-tryptophan, and a precursor to the neurotransmitter called serotonin (which is a neurotransmitter commonly associated with happiness) and is used to increase the production of serotonin, reduce stress and suppress appetite.
5-HTP is produced in the body but is derived from the African shrub Griffonia Simplicifolia when used as a supplement. Low serotonin levels are associated with sleep disorders such as insomnia, depression, weight gain, and anxiety – to name a few (1, 2).
As such, supplementation may be beneficial for even the simple reason of retaining homeostasis.
15-HTP can reduce depression. Since serotonin is associated with feelings of happiness and 5-HTP leads to serotonin production, the 5-HTP supplementation could potentially have some benefits for people who are depressed (3, 4, 5).
In a small clinical trial involving 52 healthy male subjects, either oral 5-HTP or antidepressant enhanced serotonin levels by 35% and 100%, but a combination between antidepressant and 5-HTP by 500% (6).
There is certainly potential for 5-HTP to be an effective means to be a part of a depression treatment program. The current research hasn’t shown that 5-HTP supplementation alone is enough to treat depression. However, it has shown preliminary signs of efficacy (9).
25-HTP can improve sleep. Quality and duration of sleep has been shown to increase with 5-HTP supplementation in normal patients and those with diagnosed sleep disorders (10).
One reason being that 5-HTP produces serotonin, which can be converted into the hormone melatonin. Moreover, since melatonin regulates your sleep cycle and quality, increasing melatonin availability via 5-HTP supplementation works wonders on sleep.
A 2010 human study published in the American Journal of Therapeutics showed that a combination of gamma-aminobutyric acid (GABA) and 5-HTP increased sleep duration, improved sleep quality and significantly reduced the time it took individuals to fall asleep (11).
35-HTP can help with weight loss. One study showed that 5-HTP may increase feelings of fullness (via serotonin secretion), causing you to eat less and lose weight (12).
Another study was done in 1998 and involved 20 people with diabetes who were randomly assigned to receive either 5-HTP or a placebo for two weeks. The results showed that the patients who received 5-HTP consumed approximately 435 fewer calories per day (mainly carbohydrates and fat) and reduced their body weight, compared to the placebo group (13).
Interestingly, 5-HTP has been shown to lead to a lower intake of carbohydrates, thereby increasing compliance with dietary restrictions (14).
It is important to note that 5-HTP does not directly lead to weight loss, but rather, leads to a change in eating behavior which then results in weight loss (19).
One 1986 study involving 124 people compared the ability of 5-HTP and methysergide, a common migraine medication, to prevent migraines. The study concluded that 71% of participants had a decrease in migraine attacks after supplementing with 5-HTP every day for six months prior (22).
The following year (1987) another study involving 48 students showed that a 70% decrease in headache frequency, was noted with 5-HTP supplementation versus a mere 11% decrease in the placebo group (23).
55-HTP helps with night terrors in children. A 2004 study published in the European Journal of Pediatrics showed that a 93.5% reduction in sleep terrors in children aged 3-10 after taking 2 mg of 5-HTP/kg every night before bed for a month (24).
65-HTP can help with fibromyalgia. Fibromyalgia is a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues. Researchers believe that fibromyalgia amplifies painful sensations by affecting the way your brain processes pain signals. There is currently no known cause of fibromyalgia, but low serotonin levels have been associated with the condition (25).
A 1996 study showed that people with fibromyalgia who were given monoamine oxidase inhibitors (MAOIs) (a type of antidepressant medication) in combination with 5-HTP reported significantly reduced pain (29).
In patients diagnosed with fibromyalgia, the use of 5-HTP has been preliminarily shown to improve symptoms within a 3 month period (30).
75-HTP can help reduce the likelihood of panic attacks. Low levels of serotonin alone have not been shown to lead to increased panic or anxiety (31).
However, the reduced serotonin may lead to increased susceptibility to panic or anxiety attacks (32).
85-HTP may lesson withdrawal symptoms from alcohol. A 2011 study involving 20 subjects going through alcohol withdrawal showed that 5 HTP in combination with glutamine, D-phenylalanine and some trace minerals decreased withdrawal symptoms over 40 days (35)
95-HTP can lower cortisol and stress responses. A 2010 study found that 5-HTP supplementation helped to reduce stress induced by a break-up for up to 3 weeks post break-up. The study looked at non-depressed youth who went through a recent break-up. After being given 12.8mg of 5-HTP for 6 weeks, twice per day, patients noted less romantic stress measured at the 3-week mark (36).
This is only preliminary research, but it suggests that 5-HTP may play a role in reducing the stressors of everyday life.
105-HTP can help combat anxiety. In young adults who suffer stress or anxiety from unreciprocated romanticism, a 6-week supplementation of 5-HTP decreased anxiety in 3 weeks by increasing blood BDNF levels and serotonin levels (37).
In human 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 (38).
115-HTP is easily 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 (39).
5-HTP is readily and freely converted to serotonin without biochemical inhibition.
125-HTP effortlessly crosses the blood-brain barrier. Tryptophan competes with leucine, valine, tyrosine, and isoleucine to cross the blood-brain barrier (40).
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.
135-HTP is only converted into serotonin. While tryptophan can be used for protein synthesis and turning into niacin, 5-HTP can only be used for converting into serotonin (41).
This makes 5-HTP a super effective supplement at resolving serotonin-related body and brain issues.
15-HTP supplementation can cause nausea. 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.
Slow-released 5-HTP may be better tolerated and less likely to cause side effects (44).
2Other common side effects include headaches, fatigue, drowsiness and muscular pain (45).
3Serotonin Syndrome (an overdose of serotonin in the body) has been noted at higher doses using lab rats. However at the same dose (relative to body weight), this side effect has not been shown in humans; it is, however, worth noting (46).
With normal dosages of 5-HTP (typically around 300mg a day), however, side effects and the serotonin syndrome have not been observed in humans even with congestion of anti-depressants such as MAOIs (47).
4Long-term supplementation with 5-HTP can deplete dopamine, norepinephrine, and epinephrine. Serotonin shares the same conversion and breakdown enzyme (MAO) with other neurotransmitters (dopamine, norepinephrine, and epinephrine).
Long-term supplementation of 5-HTP can cause imbalances of these neurotransmitters, which can worsen neurological and psychiatric diseases. It is therefore recommended that 5-HTP supplementation is supervised by qualified clinicians and balanced with neurotransmitter precursors (48).
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 (49).
With increasing doses of 5-HTP, MAO activity increases. When this happens, MAO can then break down dopamine and cause it to decrease (50).
How much 5-HTP you should take depends on your reason for using it.
As a sleep aid, you should use 100-300mg 45 min before bed (51).
For appetite suppression to help with weight loss, take 250mg about 30 min before a meal (52).
For combating depression and elevating mood, take 50-100mg, 3 times per day with food. You need at least 7 days for it to saturate in your system before you will start to experience the full benefits (53).
Lastly to help deal with headaches, take 100-200mg, 3 times per day with food. You’ll need at least 21 days to feel the full effect (54).
Is 5-HTP dangerous? Generally no, 5-HTP is a safe supplement. However, too much 5-HTP in your system can cause a spike in serotonin levels, resulting in side effects such as anxiety, shivering, and serious heart problems.
Does 5-HTP help with anxiety? Evidence on the effects of 5-HTP for anxiety is unclear.
Does 5-HTP help with sleep? 5-HTP has been shown in scientific studies to promote relaxation and alleviate stress which are often the main culprits that fight against good sleep.
Does 5 HTP help with weight loss? Yes, 5-HTP can help increase satiety and thus help with weight loss.
When is the best time to take 5-HTP? It doesn’t matter as long as it is with food.
How much 5-HTP do you take for depression? 50–100 mg, 3 times per day with meals.
Does 5-HTP suppress appetite? 5-HTP dietary supplements raise the serotonin levels in the brain, which helps support mood and appetite balance. Low levels of serotonin can contribute to the development of depression and increased appetite.
Is it better to take 5-HTP or L-tryptophan? 5-HTP is a better choice for many reasons. It is only made into serotonin, crosses the brain blood-barrier with ease and doesn’t have the chance to turn into toxic metabolites, like it’s counterpart L-tryptophan.
Does 5-HTP make you sleep? While it’s the main effect, 5-HTP can make some individuals tired and sleepy.
Does 5-HTP raise blood pressure? No, in fact, 5-HTP may cause low blood pressure. Caution is advised for patients taking drugs that lower blood pressure already.
How long does 5-HTP take to work? In one to two weeks, the person should feel a difference and see some results. If nothing is noticed a dosage increase might be necessary. Always be sure to titrate slowly, jumping no more than 100mg upwards at a time.
Is it possible to test serotonin brain levels? Currently, 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 (55, 56).
What is the best way to take serotonin? 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, with 50% absorbed in 2 hours. Due to the rapid pharmacokinetics of 5-HTP, slow-release supplementation of 5-HTP may be more beneficial to maintain serotonin levels in the brain (57).
5-HTP is a precursor to serotonin, which is a neurotransmitter strongly associated with feelings of happiness. It acts to increase serotonin production which may lead to euphoric feelings, decreased appetite, increased satiety, increased quality of sleep and improvements in depression.
5-HTP appears to be safe and effective at moderate dosages of between 100 – 300mg but has not been properly evaluated for its safety in conjunction with prescription drugs. Promising research is being done to better understand the efficacy of 5-HTP supplementation.