Some technical nuance and practical advice about serotonin and mood-uplift
Serotonin is made from tryptophan
Bosting tryptophan boosts serotonin, although this can’t (ethically) be confirmed in humans
Tryptophan supplementation isn’t proven to have a substantial impact on mood
Serotonin. It’s an ancient signaling molecule found in almost every multicellular organism from carnivorous sea sponges to star-nosed moles. In the human body, it makes our guts work, our platelets function, and our organs develop properly. In the brain, neuroscientists and psychiatrists have long looked at serotonin as a molecular fascination, full of psychiatric possibility.
Over the past century, we’ve discovered lots of drugs that can tinker with serotonin. Psychiatrists use SSRI’s to improve our moods, alleviate our anxiety, and… well... treat just about any psychiatric issue. The drug Belviq helps people lose weight; the drugs lysergic acid diethylamide and psilocybin help people who are looking for strange and good times to find those strange and good times.
And so, all hail serotonin.
But on the other hand, who really wants to take SSRI’s? They give people dry mouths, drowsiness, and sexual dysfunction… there’s got to be a better way than neuroactive pharmaceuticals, right? Well, whole foods shoppers have long been excited about this one simple dietary trick that can naturally boost serotonin.
Serotonin is made from tryptophan. It’s like flour to bread. Start with a tryptophan, add an oxygen here, chop off a couple oxygens there, and you get serotonin. It made sense that serotonin concentrations would relate to tryptophan concentrations, but it was tested; scientists had a group of rats eat some tryptophan then sliced out their brains and found, you guessed it, more serotonin.
So, scientists of the world realized, forget the drugs; if serotonin makes us feel good, so should tryptophan. That turned out to be another empirical question. In this article, if you can make it through what I promise is only a short amount of caveat and technical nuance, the practical advice - can taking tryptophan make you happy?
SSRI’S Don’t Seem Like They Should Work at all
How serotonin works in the brain is an enormous area of research. There are 14 separate receptors, and they’re found in just about any brain region you can name. Drugs like SSRI’s, however, don’t target individual receptors, they don’t restrict themselves to particular brain regions, they don’t have precise temporal properties, they just don’t discriminate. Instead, SSRI’s bluntly boost serotonin everywhere, which is why it’s hard to believe that they work at all.
Think about it, say you were Amazon and you wanted to increase your revenue. You’re thinking, maybe logistics, and you think that maybe, it may sound crazy but maybe, you could try turning up the speed on all delivery vehicles. From now on, every airplane and delivery truck will boost their speed by 5 percent. It may be a stroke of logistical genius, or it may just end up in chaos (yes, Jeff Bezos, I am free for consulting). It’s definitely possible that cranking up serotonin can have an impact on mood or appetite, but it’s also possible, maybe even likely, that to manipulate something as seemingly complex as human psychology requires a little more nuance.
Serotonin-based drugs work, sorta, maybe...
But you know the acronym SSRI (selective serotonin reuptake inhibitors) because research has suggested that these drugs are effective. However, especially lately, their efficacy has become a very controversial topic.
Some analyses cite 30 years-worth of trials and question the clinical significance of SSRI’s, while others maintain that SSRIs can improve the symptoms of depression. What everyone can agree to is that SSRI’s are not effective for everyone, and that typically, they aren’t full cures even for those that do see a benefit.
But You Can’t Measure Serotonin in Humans
Biochemically, we know that human cells make serotonin from tryptophan. But whether brain serotonin is sensitive to fluctuations in tryptophan is another thing that needs proving; what if the enzymes that turn tryptophan into serotonin are maxed out, working at full capacity? In animals, the experiments worked out, eating more tryptophan increases serotonin in the brain. But is it true in humans?
Using brain imaging, you can look at serotonin receptors, or the production of serotonin. You could tap into cerebrospinal fluid and measure a serotonin metabolite called 5-HIAA. You could look in the bloodstream for serotonin. You could look in the bloodstream for indications of serotonin functionality in the brain. But unless you’re willing to undergo invasive neurosurgery, and unless you don’t mind a scientist sliding a little straw inside your cortex and sucking out some brain liquid, you can’t directly measure serotonin in the human brain.
As confident as we are that tryptophan increases serotonin, we don’t have direct confirmation in people.
Does Tryptophan Make People Happy?
So the real test. Forget all the theory, can eating a handful of tryptophan make you happy? Partially due to a deadly contamination issue in the 80’s, tryptophan hasn’t been nearly as thoroughly studied as serotonin. However, a few small randomized controlled trials have been conducted; some of which have shown a small beneficial effect, some haven’t found any benefits, and some found that the mood uplifting outcomes weren’t sustained. A meta-analysis from 2002 concluded that:
“A large number of studies appear to address the research questions, but few are of sufficient quality to be reliable. Available evidence does suggest these substances are better than placebo at alleviating depression. Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended.”
As far as recommendations go, people who eat more tryptophan report having (slightly) better moods, and there doesn’t seem to be much of a health risk to testing it out (at least at low, <2g doses). The results are far from definitive, larger trials need to be conducted, but a trip to the Whole Foods supplement aisle wouldn’t be completely unfounded.
Serotonin in the brain is complicated, so many receptors, so many brain regions; how serotonin impacts our psychology still remains a mystery. But with blunt tools, science has begun tapping into the system.
If we have to come to a conclusion about happiness, it seems like tryptophan can improve mood, at least a little bit. And so, the mythology of serotonin lives on, and so does that of tryptophan.
One day, this will all seem like a strange dream. We’ll look back at chemotherapy for cancer patients, immuno-suppressants for people with auto-immune disorders, and serotonin for people with mental illness, and be glad we live in 2050.
But until something much better comes along, psychiatrists won’t be quick to abandon the idea that manipulating bulk serotonin is the psychiatric remedy we need, and for some, that tryptophan might be our key to the kingdom.
Have you taken tryptophan supplements in your life and found any strange or interesting changes? Are there any other psychological supplements you want to learn more about? Reach out to AndrewNeff@Golgiproductions.com with your thoughts and questions.
Neel Shah ~ Sept '19
Andrew Neff ~ Sept '19
Andrew Neff ~ Sept '19