5-Hydroxytryptophan (5-HTP) Uses and Side Effects

What Is 5-HTP?

5-HTP (5-hydroxytryptophan) is a chemical your body makes from L-tryptophan, an essential amino acid you eat in foods like turkey and pumpkin. Once tryptophan is converted to 5-HTP, it’s then converted to the neurotransmitter serotonin.

Clinical studies show that 5-HTP supplements work by increasing serotonin production. Serotonin regulates sleep, body temperature, sexual behavior, and pain, which is why 5-HTP is a popular dietary supplement for a broad range of chronic health conditions.

5-HTP crosses the blood-brain barrier, which is unique when compared to other chemicals in the serotonin-melatonin pathway.

It’s not found in food sources, but 5-HTP is extracted from the Griffonia simplicifolia plant native to Africa. You may be able to naturally increase 5-HTP production by eating foods rich in tryptophan.

In the past, there were concerns about 5-HTP supplements because of contamination leading to a rare but serious condition called EMS. Today, high-quality 5-HTP supplements are generally considered safe as they are free from these contaminants, but some clinicians are still cautious about recommending them.

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Potential Benefits

Because serotonin levels affect so much of how the body functions, 5-HTP offers a wide range of possible health benefits. Below, I review some of the health conditions for which 5-HTP is most often used.

1. Depression

5-HTP creates similar effects as antidepressants known as SSRIs (selective serotonin reuptake inhibitors). SSRIs are thought to balance serotonin levels in the brain, which can reduce symptoms of depression.

Common SSRIs include:

• Sertraline (Prozac)
• Fluoxetine (Zoloft)
• Fluvoxamine (Luvox)

Some studies have compared the efficacy of 5-HTP with these antidepressants and found that they both relieve depression symptoms effectively. This may be due to the theory that depression is, in part, caused by a serotonin deficiency. 

One study compared 5-HTP to fluoxetine for depression and found that patients improved at the same rate. In an animal clinical trial, researchers suggested that 5-HTP may prove a helpful adjunctive therapy to SSRIs, meaning they improve serotonin levels better when taken together rather than when they’re taken alone.

Is 5-HTP better than antidepressants? Each patient is different, but multiple studies suggest that 5-HTP may be just as effective as some antidepressants. Because this supplement is associated with fewer side effects, some patients prefer it over prescription SSRIs. You should discuss any changes to depression treatment with your healthcare provider.

The standard 5-HTP dosage for depression and anxiety is between 50-100 mg, taken 3 times per day with food.

More thorough research is needed to prove the long-term efficacy of 5-HTP, but it may be a good natural depression treatment for people who do not respond well to SSRIs.

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2. Sleep Disorders

Some studies suggest that 5-HTP may help people with insomnia sleep better. Some insomniac patients have low levels of serotonin, which the body needs to make the sleep-regulation hormone melatonin.

In these cases, increasing serotonin by taking 5-HTP may also help balance melatonin.

A placebo-controlled study in 2021 found that 5-HTP improved sleep latency (the time it takes to fall asleep) in the short term. These effects didn’t improve more after 8 weeks.

In 2022, researchers conducted a small study with 18 patients with REM sleep behavior disorder caused by Parkinson’s disease. The patients who took 50 mg/day of 5-HTP had much better sleep quality compared to those who got the placebo. 

These results indicate that 5-HTP is “safe and effective in improving sleep stability in [Parkinson’s disease].”

3. Fibromyalgia

Fibromyalgia is a chronic condition that causes fatigue and pain throughout the muscles, tendons, and ligaments. 5-HTP may improve fibromyalgia for some patients.

Participants in a double-blind 5-HTP study experienced fewer symptoms of fibromyalgia with only mild side effects.

4. Migraine

5-HTP might reduce the intensity and frequency of migraine attacks because of the way it improves tryptophan synthesis. It may even be comparable to some prescription medications for migraines because it can reverse some central nervous system abnormalities that lead to these attacks.

When patients were treated with 5-HTP compared to propranolol for migraine, all of the patients had similar positive results. Propranolol (brand name Inderal) led to slightly better symptom improvement but with more frequent adverse effects.

5-HTP may be a promising natural alternative to prescription medications for migraine. However, no studies exist comparing this supplement to triptans, which are more modern prescription medicines used to treat migraine.

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5. Obesity

5-HTP supplementation may help people with obesity lose weight by helping them eat less, feel fuller, and want to eat carbohydrates less often. It may also prevent the buildup of belly fat, although this has only been observed in animals.

Research indicates a link between eating disorders and serotonin. 5-HTP supplementation may increase the feeling of fullness (satiety), causing a loss of appetite.

One study showed that 5-HTP may reduce stress-induced overeating. During a 12-week clinical trial, participants experienced faster satiety, consumed fewer calories and carbohydrates, and lost weight.

A recent animal study indicates that 5-HTP might prevent abdominal fat accumulation, partly due to how it affects the gut.

6. Gut Health

Serotonin, the “feel-good neurotransmitter,” is primarily produced in your gut. 5-HTP’s role in serotonin production is one way it may improve some gut health concerns.

5-HTP turns into serotonin in the gastrointestinal tract to help with motility (how food moves through the digestive tract).

Supplementing with 5-HTP may be beneficial for patients with:

• Irritable bowel syndrome (IBS): IBS is a complex disorder that involves activity by serotonin, tryptophan, and the central nervous system. 5-HTP may treat IBS because of how it affects serotonin production. A clinical trial suggests 5-HTP could reduce rectal pain in some IBS patients.
• Small intestinal bacterial overgrowth (SIBO): Preliminary research suggests that serotonin pathway changes are linked to SIBO, which is one reason 5-HTP may help with SIBO. But more research is needed, especially through randomized clinical trials, to understand if 5-HTP can be used to treat SIBO.

Read Next: The Best 12 Vitamins & Supplements for Stress Relief 

Food Sources

5-HTP is not found in food. However, foods high in the essential amino acid tryptophan may lead to higher levels of 5-HTP in the body.

Food sources of tryptophan include:

• Turkey
• Pumpkin seeds
• Sunflower seeds
• Bananas
• Chicken
• Spinach
• Turnip greens
• Collard greens
• Potatoes
• Milk
• Seaweed

Supplement Sources

Thanks to the African plant Griffonia simplicifolia, 5-HTP can be harvested and taken as a dietary supplement. 

5-HTP is available as a supplement that may be purchased online or in stores. It’s sometimes found in multivitamins and herbal products.

Note: Don’t confuse 5-HTP (5-hydroxytryptophan) with 5-HT (5-hydroxytryptamine). The latter is the chemical name for serotonin. Taking 5-HT in excess can lead to serotonin syndrome.

Dosage

Adults can safely take doses of 150-800 mg/day of 5-HTP. High doses beyond this point can cause side effects. Taking more than 6 grams of HTP may cause toxicity.

Can you take 5-HTP every day? It should be safe for adults to take 5-HTP daily for up to a year. However, you should talk to your provider about taking this supplement before adding it to your routine (including how long you should take it).

The best 5-HTP dosage depends on your target health condition. Based on available research, the recommended doses of 5-HTP are:

• Depression: 50-100mg, 3 times per day with food
• Insomnia: 100-300mg, 30-45 minutes before bedtime
• Fibromyalgia: 100mg, 3-4 times per day with food
• Headaches: 100–200mg, 2-3 times per day with food
• Weight loss/management: 250–300mg, 30 minutes before meals

These are the recommended ranges. Seek medical advice from a licensed healthcare professional to determine what exact amount will work for you.

How long can you take 5-HTP? In general, you should safely be able to take 5-HTP for up to one year at a dose of up to 800 mg/day.

Also, the FDA (Food and Drug Administration) does not test dietary supplements. Research the brands you purchase to ensure they’re high-quality and not likely to be contaminated.

Side Effects

Rare side effects of 5-HTP supplementation may include:

• Vomiting
• Diarrhea
• Nausea
• Heartburn
• Stomach pain
• Fatigue
• Drowsiness
• Sexual dysfunction
• Muscular problems

In some patients, 5-HTP may cause anxiety, especially if combined with other supplements or medications that affect the brain. It has also been associated with seizures in patients with Down syndrome.

During pregnancy and breastfeeding: Don’t take 5-HTP if you’re pregnant or breastfeeding, as it’s not clear if 5-HTP is safe to use during these times.

For children: 5-HTP might be safe for children if taken in the right amounts. For kids under 12, taking up to 5 mg/kg of body weight every day seems safe, but not for more than 3 years.

Before surgery: Because 5-HTP and some drugs used during surgery both increase serotonin, you should stop taking 5-HTP at least 2 weeks before surgery. If there’s too much serotonin in the brain, it can cause serious problems like heart issues, shivering, and anxiety (known as serotonin syndrome).

Discontinue your use of 5-HTP and call your doctor immediately if you experience side effects after taking this supplement.

Drug and Supplement Interactions

5-HTP may interfere with certain conditions or medications. It should not be combined with other drugs or supplements that cause similar effects.

Talk to your healthcare provider before starting 5-HTP if you take these medications:

• Carbidopa: Carbidopa, used in Parkinson’s disease, may cause a scleroderma-like illness when taken with 5-HTP. If you experience this rash-like condition, your skin may feel thick, hard, and inflamed.
• Serotonergic compounds: Combining 5-HTP with other SSRIs, MAOIs, pain relief drugs, dextromethorphan (found in cough syrups), or triptans (used to treat migraines) may cause an overproduction of serotonin. This can lead to serotonin syndrome.
• Sedative compounds: Because it may cause some sedative effects, combining 5-HTP and other sedative medicines (such as zolpidem) could lead to problems. You should also be cautious combining 5-HTP with natural sedatives like melatonin or valerian root.
• Compounds that affect brain chemistry: Use caution when combining 5-HTP with medications or supplements that affect amino acid production, like carbidopa, St John’s wort, and SAM-e. Combining these supplements may cause anxiety, rapid speech, or other serious side effects.
• Anesthesias: 5-HTP may interfere with certain medications often used in surgical procedures. If you’re scheduled for surgery, stop taking 5-HTP at least 2 weeks before the procedure.

5-HTP and EMS

Quick Summary: Contaminated 5-HTP and L-tryptophan supplements caused patients to develop EMS (eosinophilia-myalgia syndrome) a few times between 1989 and 1999. The active ingredients weren’t to blame, but healthcare providers are often still cautious about recommending 5-HTP due to this connection.

Here’s the full story:

In 1989, L-tryptophan supplementation was connected to an outbreak of EMS, a serious medical condition that can cause extreme muscle tenderness and blood abnormalities.

The batch of L-tryptophan (LTR) responsible was contaminated by a substance called Peak E and originated from only a single manufacturer in Japan — Showa Denko. However, all L-tryptophan supplements were banned in the United States from 1989-2005 in response to this epidemic.

Manufacturers then began selling 5-HTP, the chemical precursor to the banned ingredient.

In 1994, 1996, and 1999, multiple cases of EMS were documented following 5-HTP supplementation. All of these cases were also linked to contamination, this time with a substance known as Peak X.

Since the 2005 ban was lifted, 3 cases of EMS connected to 5-HTP have been documented. However, these were all determined to be incidental; the supplements weren’t contaminated and also didn’t appear to be what caused the patients to develop EMS.

In 2006, an animal study was conducted to test the possibility that 5-HTP supplementation could cause EMS. After a full year of high-dose 5-HTP, the rats in the study developed no signs of the condition. 

This study, and the fact that no human trials of 5-HTP have resulted in EMS symptoms, indicate that it’s unlikely 5-HTP itself causes the condition. But out of an abundance of caution, clinicians are still hesitant to suggest this supplement to some patients.

When I or my colleagues prescribe 5-HTP, we closely monitor patients for signs of any adverse effects. Make sure to do the same with your provider if you take this supplement.

FAQs

Talk to Your Provider About 5-HTP

5-HTP may offer an effective and affordable alternative to prescription medications for several chronic conditions. It is always best to use precaution and get thorough testing when considering new supplementation or medicine. 

Talk to your healthcare provider if you think 5-HTP might be right for you. If you’re in Denver and dealing with depression, gut conditions, migraine, sleep issues, or other chronic conditions, set up a free 15-minute consultation with PrimeHealth to learn how we can help you find relief.

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