One of the most important hypotheses for depression is based on serotonin. This is the substance that is responsible for “feeling happy”. In fact, the “drugs” offered by doctors are based on it, SSRIs (without going into details) increase its level. And in principle it works, a person feels happier to some extent, except that under normal conditions, the level of serotonin is very tightly regulated in the brain by the body, if you artificially “pump it up”, you can damage the regulatory mechanisms.

Personally, when analyzing the organic causes of depression, I would rather bet on complex mechanisms: on the one hand, the level of serotonin obviously decreases, but on the other hand, the volume of the areas in the brain responsible for feeling happiness decreases (which is supposed to be counteracted by omega 3), as well as the overall activity of brain cells decreases (which is supposed to be counteracted by, for example, zinc or selenium). Whichever way you look at it, serotonin seems to play a very big role.

What does tryptophan have to do with it? It is the raw material from which the body produces serotonin. If its levels drop, inevitably there’s a shortage of everything it’s used for. And in fact, patients with depression are very deficient in this amino acid, and what’s more, preliminary clinical trials have shown that supplementation is effective, improves mood and works just like the drugs offered by doctors, but without their side effects. It also improves overall health, as tryptophan is an essential amino acid for life, without it a host of other problems arise.

Many other remedies with similar effects are often recommended, the most popular of which is probably 5HTP, which is its active form in a much lower concentration, but I would suggest the pure amino acid (sometimes also described as l-tryptophan), because the idea is to have a long-term effect, to supplement a severe nutritional deficiency, which is supposed to guarantee that even after discontinuing the capsules, the disease will not return.

It is not entirely clear why this substance disappears from the bodies of sick people. It is present in food quite commonly and there should be no problems. There are hypotheses that an excess of protein blocks its assimilation, although it is a protein itself, but it is one of the largest amino acids and all others have “priority” before it in the intestines. In other words, after eating protein, the body breaks it down into individual amino acids and then can assimilate a specific pool of them, starting with the smallest ones. Tryptophan is at the bottom of the list and sometimes it just can’t get there.

Another hypothesis is that it is consumed during various inflammatory conditions. There is a point to this, people with rheumatoid arthritis also have much lower levels, as do AIDS patients. It is also involved in many functions in the digestive system, any kind of inflammation in that part of the body can block absorption or accelerate consumption.

Supporting the treatment of depression is not its only advantage, tryptophan in clinical trials has been shown to be an effective treatment for insomnia, premenstrual syndrome, bipolar disorder, schizophrenia (reduced aggressiveness and improved memory in patients), anxiety attacks, restless legs syndrome, and even preliminary studies suggest efficacy in migraines.

Around 1990 there was an epidemic caused by poisoning with tryptophan supplements, which is still used by pharmaceutical companies selling competing tablets as a “scare” to discourage people from buying them. This poisoning had nothing to do with the substance we are interested in, it was caused by contamination of one batch of tablets during the production process in one factory in Japan, only people who took supplements from this one manufacturer from this one batch got sick and for 25 years there have been no new cases.

Interestingly, the same company that released the defective pills is responsible for Minamata disease, a mercury poisoning caused by eating fish. They discharged mercury-containing sewage into the river, causing nearly 700 people to become severely ill, many of whom died. Warning against tryptophan today because of that unfortunate accident makes about as much sense as refraining from drinking tap water because people in one village in Japan once got poisoned that way. Some scientists claim that these poisonings were related to tryptophan as such, however, and it cannot be ruled out that they are wrong.

How to use. Start with low doses, on the order of 500 mg per day, and you can move gradually to higher doses, up to 2 grams per day. Higher ones have sometimes been used, but I wouldn’t risk it without checking with your doctor. It is important to maintain at least a two-hour interval between high-protein meals. This supplement should not be combined with SSRIs (selective serotonin reuptake inhibitors), as this can lead to the so-called “serotonin syndrome”.

Finally, it is worth noting that “dietary tryptophan deficiency” is not likely to be the cause of depression, rather some other factors lead to its decrease. From this it follows that supplementation is admittedly a good temporary solution, but long-term efforts should be made to identify the cause of lowering blood levels of this amino acid.

An analysis of studies showing that tryptophan was an effective treatment for depression, although more research is needed to say this with certainty:

Meta-analysis of 24 studies confirming lower tryptophan levels in people with depression:

My blog post on the subject: