5-HTP & Depression

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5-HTP is one of the more well-known alternative treatments for depression. It targets the same process that many antidepressants target – the serotonin process. The interesting piece of all this, though, is that despite its popularity, the research on it is not clear cut. Multiple studies have shown a clear benefit with 5-HTP use; however, many of these studies do not meet the stringent standards set forth in the medical community – things such as sample size, placebo controlled (meaning some patients receive 5-HTP and some receive a placebo) double blind (meaning neither researcher nor patient know who is receiving the treatment and who is receiving the placebo), etc.

But let’s start at the beginning with what 5-HTP is and how it works in our bodies, why you might need a boost, and how to take it.

What is 5-HTP?

As a supplement 5-HTP comes from an African bean called Griffonia simplicifolia. It is also a byproduct that our bodies naturally produce from the amino acid tryptophan. It then becomes a precursor to serotonin, which is also a precursor for the hormone melatonin (which helps regulate our sleep):

Serotonin is the key ingredient when talking about 5-HTP and depression. It is a neurotransmitter that balances our mood and gives us feelings of happiness and well-being. We have various neurotransmitters (dopamine, glutamate, GABA, etc.) that all have different roles to play, but, in general, they help our brain and body communicate. It is thought that one reason for depression is a lack of serotonin, which is why many antidepressants target this molecule, and it is why 5-HTP is a common remedy for depression.

5-HTP Process

We can convert 5-HTP from tryptophan, an amino acid most commonly found in animal protein (turkey, beef, pork, dairy, chicken, eggs, etc). Amino acids are the building blocks of protein and different protein sources provide different amino acids. Some amino acids are essential, meaning our bodies cannot produce them and we must get them through food, and others are non-essential, meaning our bodies can create them from other amino acids. Foods that contain all nine essential amino acids are called complete proteins. Tryptophan is considered an essential amino acid, so we must get it from our diet.

When you eat and digest protein, that protein gets broken down into its separate amino acids. Once protein is broken down into its component amino acids, they are then combined in various ways to be used for tasks such as muscle building, nutrient transport, immune support, etc. In this case, we take in tryptophan which can be converted into 5-HTP, serotonin, and finally melatonin.

However, there are a couple limitations to this conversion process. First, you need calcium, magnesium, vitamin D, and B vitamins for the conversion process to take place. Additionally, tryptophan must cross what is called the blood-brain barrier, which is a barrier that protects the brain and limits what can reach it. Both tryptophan and 5-HTP can cross this barrier, but while 5-HTP can freely cross, tryptophan needs an escort molecule to get through. However, these escort molecules are in short supply and are also needed to transport other amino acids. And because tryptophan is the least abundant amino acid in protein and is competing against all the other amino acids in protein to cross, you may not get a surge in serotonin from your high protein meal. You may in fact get more tryptophan after a carbohydrate rich meal (which I would not necessarily recommend, but that is a topic for another day). When you eat a lot of carbohydrates insulin is secreted, which decreases the levels of other amino acids that would normally compete with tryptophan.

Tryptophan’s final limitation for increasing serotonin levels is that it is used to make other compounds so eating a lot of tryptophan does not necessarily lead to a large increase in serotonin.

This all leads to 5-HTP having several advantages over tryptophan. It does not need other nutrients in order to be converted, it freely crosses the blood brain barrier while tryptophan needs an escort molecule, and 5-HTP is not lost in the making of other compounds.

History of 5-HTP

As a natural remedy for insomnia, obesity, and depression, tryptophan supplements became popular in the 1980’s. However, in 1989 an outbreak characterized by severe muscle pain sickened over 1500 people and caused 38 deaths. The outbreak was linked to tryptophan supplements from a specific manufacturer in Japan that was contaminated with a substance called Peak X. The following year the FDA banned tryptophan supplements, which brought 5-HTP to the forefront as an alternative. At first 5-HTP was only available via prescription but in 1995 the FDA approved it as an over-the-counter supplement.

Studies on the effectiveness of 5-HTP

There have been a number of studies looking at the effects of 5-HTP and depression and many have shown a significant improvement in depression scores. However, a couple different meta-analysis (a review that looks at multiple studies) found that many of the studies were not of sufficient quality to draw definitive conclusions; for example, the sample size was too small, it was a short trial, there was no placebo, etc. Many of these studies took place in the 80’s and 90’s and much of the published research is at least two decades old. It is generally recognized that there is a need for an updated study that meets all the standard definitions for quality.

Why you might need a boost in serotonin

Whenever I hear that a supplement could be beneficial for my health, I wonder why I need it in the first place. Our bodies are amazing – they are capable of amazing feats like climbing Everest and healing from chronic illnesses like cancer. So, what is causing the need to boost my body’s amazing capabilities? There can be a few reasons – poor diet, lack of exercise, caffeine and alcohol consumption, and even extreme physical and mental stress can all rob our brain if its ability to make serotonin. Food sources can also vary in their tryptophan content. The wild game that we used to eat was much higher in tryptophan than the conventional meat we eat today. And vegetarian sources of protein contain a lot less tryptophan than animal sources of protein, so vegetarians may struggle a little more. However, let us be clear – that does not mean it is your fault that you need more serotonin. Two people could live the exact same lives and eat the exact same foods and one would not need more serotonin and the other would. We are still figuring out those nuances.

If you are interested in understanding your serotonin levels, there is a free online test available. It is by no means diagnostic and it does have its critics (in large part because it is not diagnostic and in part because it only looks at four neurotransmitters while we know we have over 100). But it is an interesting starting point. It is called the Braverman test and you can find it here: https://www.bravermantest.com/. The first part of the test looks at which of the four amino acids is your dominant nature (Dopamine, Acetylcholine, GABA, or Serotonin) and the second part looks at deficiencies.

Other ways to increase serotonin

If you are interested in trying to increase serotonin but do not want to use supplements, there are a few options. Exercise is great for depression in general and releases tryptophan into your blood and decreases the amount of other amino acids, allowing more tryptophan to cross the blood-brain barrier. Spending time in sunshine also appears to help increase serotonin levels, along with providing a host of other benefits. Finally, massage therapy can help increase both serotonin and dopamine and decrease the stress related hormone cortisol.

Other benefits of 5-HTP supplementation

While this blog is focused on depression it is always helpful to understand how else something could be impacting your health. 5-HTP can also help with:

Insomnia: serotonin helps with both falling and staying asleep and it increases both REM and deep sleep. A 2018 study on fruit flies, rats, and mice showed that a combination of 5-HTP and GABA enhanced sleep quality and duration. Another study indicated 5-HTP may help with sleep terrors and sleepwalking.
Appetite: 5-HTP supplementation appears to suppress appetite which results in reduced food intake.
Pain (including certain types of headaches): serotonin enhances our body’s own pain relief system
Fibromyalgia: like the conditions mentioned above, serotonin helps with pain sensation, mood, and sleep
PMS

How to Take 5-HTP

One of the great things about 5-HTP is that it can work quickly – even in 30 minutes, although some people may need a couple weeks to notice any affect. Many people will need to take it 2-3 times per day as the effects can wear off. Start with 50mg three times per day and after a couple weeks you can increase the dosage to 100mg three times per day. The max dosage should be 150mg four times daily, with the most common dosage being between 150-800 mg for 2-6 weeks. It has been used safely in doses up to 400mg daily for up to one year. It can be taken both with and without food.

One downside to 5-HTP is that it can reduce the amount of other neurotransmitters, specifically dopamine (the pleasure and focus neurotransmitter) and norepinephrine (which is both a hormone and neurotransmitter). This is most likely to occur when taking 5-HTP for a long time, in which case it is sometimes recommended to take it alongside L-dopa (the precursor to dopamine) or Tyrosine (the pre-cursor to both dopamine and norepinephrine).

You will know it is time to back off your supplementation if you feel better for a while, but the symptoms come back. 5-HTP also causes a slight risk in serotonin syndrome, which causes very high heart rates and blood pressure, fever, insomnia, agitation, confusion, sweating, and diarrhea. Serotonin syndrome is less likely to occur when starting with low doses and gradually increasing. 5-HTP can also cause eosinophilia-myalgia syndrome (EMS) which is characterized by extreme muscle tenderness and blood abnormalities.

Other potential side effects of 5-HTP include heartburn, stomach pain, nausea, vomiting, diarrhea, and drowsiness.

There are a few groups of people who should not supplement:

Do not take 5-HTP at least two weeks before surgery, as some drugs used before surgery can also increase serotonin
Do not take 5-HTP if you are currently on antidepressant medications. This could lead to too much serotonin
Women who are pregnant or breast feeding
Parkinson’s patients taking carbidopa
People with peptic ulcer disease, platelet disorders, or renal disease
Talk to your doctor before giving 5-HTP to kids

One place to start with 5-HTP is this version with 50mg, potentially increasing to 100mg. This one is another great option (note the serving size of 2 capsules is equal to 200mg)

Bottom Line

5-HTP is one of the more well-known supplements for easing depression symptoms and exerts its influence by increasing serotonin levels in the brain. While many people do report feeling better after supplementing, the studies that have been done have not always met the strictest criteria for quality and there is a need for updated data.