L-5-Hydroxytryptophan (5-HTP): Is it One of the Best Nootropics for Depression and Obesity?

L-5-Hydroxytryptophan (5-HTP) is a derivative of the essential amino acid L-tryptophan and a precursor of 5-hydroxytryptamine (serotonin). 5-HTP supplements are growing in popularity as there's considerable evidence they are a natural treatment for depression and obesity [1].

Since 5-HTP is converted to serotonin, the familiar "feel-good" neurotransmitter, it has nootropic properties throughout the body. Nootropics are compounds, whether naturally occurring or synthetic, that alter brain physiology to induce desirable psychological effects (such as an improved mood and sense of wellbeing).

5-HTP is commonly extracted from the seeds of an African plant species, Griffonia simplicifolia, and is thus sometimes referred to as Griffonia simplicifolia seed extract on supplement labels.

Read on to learn how 5-HTP works, as well as the health benefits and possible side effects of taking 5-HTP supplements.

Note: Do not take 5-HTP supplements, or any other dietary supplements, concurrently with any prescription medications that alter serotonin and/or melatonin levels, such as selective serotonin reuptake inhibitors (SSRIs), before consulting with your healthcare provider. This article is for informational purposes only and not intended as medical advice.

How Does 5-HTP Work?

The body endogenously produces L-5-Hydroxytryptophan from the amino acid L-tryptophan with the help of tryptophan hydroxylase. Another enzyme, aromatic amino acid decarboxylase, then transforms 5-HTP into serotonin (5-hydroxytryptamine/5-HT), which regulates mood, appetite, and other cognitive processes.

However, the possible metabolic fates of L-tryptophan are based on the body's demands (see the diagram below for reference). Hence, taking 5-HTP can increase serotonin more effectively than a tryptophan supplement.

Since 5-HTP readily crosses the blood-brain barrier, it is a clinically relevant treatment for depression [2]. The effects of 5-HTP supplements are ostensibly mediated by an increase in serotonin levels in the central nervous system. Serotonin may then be converted into melatonin, a hormone secreted by the pineal gland in the brain.

Melatonin is important for regulating the internal body clock and inducing sleep. Exposure to light environments (such as daylight or your smartphone screen) suppresses melatonin synthesis, while dark environments do the opposite. This is why normal circadian rhythms are imperative for proper melatonin production and healthy sleep-wake cycles. Naturally, taking 5-HTP can also help as a sleep aid.

Effects of 5-HTP on Serotonin Levels

After taking 5-HTP orally, the amount that reaches the central nervous system depends on the extent of 5-HTP conversion to serotonin in the peripheral nervous system. Oral 5-HTP supplements must first be absorbed through the gut and into the blood circulation before being transported to the blood-brain barrier.

As 5-HTP is taken up by cells of the periphery, it is converted to serotonin, the latter of which does not readily cross the blood-brain barrier [3]. Hence, any 5-HTP used for peripheral serotonin synthesis will not have the same psychological effects as 5-HTP that makes it to the brain before being metabolized.

So, why is serotonin a focus in the treatment of depression and obesity?

Well, serotonin is generally depleted in depressed individuals. It is also one of the two major neurotransmitters involved in feeding patterns/appetite regulation.

A few studies have characterized the brain sites and receptors involved in serotonin transmission that control feeding behaviors [4]. The findings suggest that serotonin influences energy balance and circadian eating patterns by activating satiety neurons in the hypothalamus [5].

More simply, serotonin helps relay the signal to your brain that you’re getting full. As an inhibitory neurotransmitter, serotonin also counteracts excitatory neurotransmitters like norepinephrine/adrenaline and adrenergic receptors, which typically amplify hunger signals [6].

While serotonin appears to regulate appetite signaling, research suggests it plays an important role in macronutrient selection (especially in obese people consuming large amounts of carbohydrate-rich food) [7]. As such, supplementing with 5-HTP may help control food intake and reduce body weight as part of a weight-loss regimen [8].

Health Benefits of 5-HTP Supplements

5-HTP may help treat various conditions, such as anxiety and depression, by increasing serotonin levels in the brain. Below are some relevant evidence-based health benefits of taking 5-HTP [9]:

• Supports relaxation and calmness
• Natural anxiolytic and stress-reducing properties
• Stimulates deeper sleep
• Enhances mood
• Promotes weight loss (in higher doses)
• Fights neurodegeneration
• Treats migraine headaches
• Alleviates pain associated with fibromyalgia and arthritis

Interestingly, clinical research suggests that 5-HTP may be as effective as several pharmaceutical antidepressants, such as SSRIs, albeit without as harsh of side effects [10]. Individuals with chronic inflammatory conditions may also benefit from 5-HTP supplementation as their serotonin levels are typically low [11].

However, 5-HTP, like many nootropics, should be used intermittently instead of continuously since it can lead to neurotransmitter imbalances (serotonin syndrome) in the brain and body over time. While serotonin is generally praised as a "good" neurotransmitter, too much serotonin (i.e., serotonin syndrome) can have toxic effects.

5-HTP Dosage Recommendations

The dose of 5-HTP you should take will depend on the desired effects and health benefits. For example, research suggests that larger 5-HTP dosages are necessary to treat things like obesity and migraine headaches as opposed to conditions like fibromyalgia [12].

5-HTP differs from L-tryptophan in that it doesn’t necessarily make you drowsy but instead works to calm your brain and help you relax while still being alert. Nevertheless, higher doses of 5-HTP may be useful for improving sleep quality since some of it will be converted to melatonin.

Here are general 5-HTP dosage guidelines based on various outcomes to get you started:

• For treating migraine headaches — 200 to 600 mg daily
• To alleviate pain associated with inflammation — 100 mg three times per day
• For general relaxation — 200-300 mg daily
• For better sleep — 200-500 mg roughly one hour before bedtime
• To support weight loss – 600 to 900 mg daily for no more than 12 consecutive weeks

It's prudent to cycle off of 5-HTP every five to six weeks for at least one week (unless otherwise noted above). It’s also advised to avoid taking 5-HTP supplements before operating a motor vehicle or performing any other activity that requires you to be alert and wakeful.

When to Take 5-HTP Supplements

When taking more than 500 mg of 5-HTP per day, take half in the morning before breakfast and half in the late afternoon/evening. Less than 500 mg can be taken as needed/whenever you want a mood boost. If you're using 5-HTP for better sleep, take it about one hour before bedtime.

Possible Side Effects of Taking 5-HTP Supplements

Most users will tolerate 5-HTP well with minimal side effects. As with most nootropics, some users may experience various side effects, including:

• Abdominal pain/gastrointestinal distress/diarrhea
• Absence of menstrual bleeding
• Dizziness/nausea/vertigo
• Increased blood cortisol or kynurenine
• Hypotension and/or hypocholesterolemia
• Psychic hyperkinetic syndrome
• Eosinophilia myalgia syndrome (EMS)

Dietary supplements containing 5-HTP should be used cautiously or avoided by individuals that meet any of the following criteria:

• Currently taking antidepressant medications (such as monoamine oxidase inhibitors [MAOIs], selective serotonin reuptake inhibitors [SSRIs], etc.) or any other medications that may affect/increase serotonin levels.
• History of mental disorders (e.g., schizophrenia, psychosis, and obsessive-compulsive disorder)
• Those with HIV/AIDS, particularly HIV-1 infection
• People with epilepsy or those using drugs that may lower the seizure threshold
• Currently using CNS depressants, including alcohol
• Currently using decarboxylase inhibitors (e.g., Carbidopa)
• Currently using “party pills,” psychedelics, or amphetamines
• Taking drugs, herbs, or supplements that lower blood pressure
• Those with eosinophilia syndrome
• Women who are pregnant or lactating

Taking excessive amounts of 5-HTP can lead to serotonin syndrome, which is lethal in some cases. To reiterate, do not take 5-HTP before consulting with a healthcare provider if you're currently using prescription medications for treating depression or other mood disorders.

5-HTP Supplement Take-Home Points

L-5-hydroxytryptophan (5-HTP) is a promising nootropic supplement with multiple therapeutic effects stemming from its ability to increase serotonin (and melatonin) levels. Pertinent health benefits of 5-HTP may include support for weight loss, better sleep, mood, inflammatory conditions, and treatment of depression.

When comparing 5-HTP to other nootropics, its major advantages are that it’s affordable, well-tolerated, and effective when used cyclically. The main thing to remember is to take periodic breaks from 5-HTP supplementation to avoid serotonin syndrome.

By the same token, if you take medication that alters serotonin and/or melatonin levels, be sure to consult with your healthcare practitioner before adding 5-HTP into your supplement regimen.