5-HTP:
Serotonin Deficiency Syndrome

Every once in a while, there is a paradigm shift in science that forces researchers to zoom out from their narrow focus and take in the big picture. Such a shift may be underway in the treatment of depression and anxiety disorders.

Long viewed as separate but somehow related disorders, results of new studies using the naturally occurring amino acid 5-hydroxytryptophan (5-HTP), suggest that depression and anxiety, insomnia, being overweight, and even migraines, are all different symptoms of the same illness - a common deficiency in the neurotransmitter serotonin (5-HT). Let's call it serotonin deficiency disorder, or SDS.

How SDS manifests in a given individual may depend on other neurochemical conditions, or it may depend on their personality or other environmental factors. The most likely scenario is all of the above. It is interesting to note, though, that it is very common for some or all of these symptoms to cluster in a single person. People with depression often also have problems with anxiety, insomnia, weight control, and/or headaches.

The Key Study
The concept of a serotonin deficiency syndrome grew out of the work of a group of Swiss and German psychiatric researchers, headed by Dr. W. Pöldinger of the Psychiatrische Universitäts-klinik in Basel, Switzerland.¹ In a key study that led them to propose their paradigm-smashing concept, Pöldinger and his colleagues showed that capsules containing 5-HTP were as effective as or better than a state-of-the-art antidepressive drug in treating patients with clinical depression. 5-HTP also caused fewer and less severe side effects. That drug, fluvoxamine, is a member of a class known as selective serotonin reuptake inhibitors (SSRI).

Although both 5-HTP and SSRIs work their antidepressive magic in different ways, the end product of both is the same, a rise in the amount of serotonin (5-HT) that is available in the synapse. 5-HTP is an intermediary step in the conversion of tryptophan to 5-HT. Tryptophan is converted to 5-HTP, and 5-HTP, in turn, is converted to 5-HT. Just as in-creasing tryptophan leads to a rise in 5-HT, so does increasing 5-HTP, but more directly.

SSRIs, by contrast, increase available 5-HT by preventing nerve endings from soaking up recently released 5-HT molecules that have been floating around in the synapse. This soaking up process is known as re-uptake, which explains why the drugs are called "re-uptake inhibitors."

In addition to depression, Pöldinger noted that 5-HTP, SSRIs, along with other, older types of antidepressants, have been used with some success to treat all the disorders associated with a serotonin deficiency. However, they note that directly supplying new 5-HT molecules - or substitution therapy - is probably a better solution than trying to enhance the recycling of old 5-HT molecules.

On the other hand, direct substitution of 5-HT is not feasible, because most of the amino acid is destroyed before it ever reaches the synapse. "Why not take the closest precursor crossing the blood-brain barrier and let the brain itself do the finishing step?" they ask.¹ Two precursors of serotonin readily lend themselves to this purpose, tryptophan and 5-HTP.

5-HTP vs Tryptophan
Tryptophan has been used for years to treat anxiety and depressive disorders, but it has two major problems. First, many of the clinical results from tryptophan are ambiguous, possibly because its metabolism to 5-HT, when taken by mouth, is problematic, especially due to the lack of several cofactors which are not usually present in the diet in adequate amounts.

Second, of course, you can't get tryptophan, anymore. Thanks to our benevolent protectors in Bethesda, tryptophan sales have been banned in the US for more than 8 years. The FDA questionably based its tryptophan prohibition on a single contaminated batch of tryptophan produced by a Japanese company in the late 1980s, which was linked to serious illness and even deaths in many people who used it. In order to cut corners, this company altered the time-honored manufacturing procedure for tryptophan and introduced a new and untested procedure while abbreviating an important filtering step.

5-HTP, on the other hand, has produced clear and significant improvements in people with depression and other disorders, and it is legally and readily available. 5-HTP is a natural product that has never been associoated with any serious adverse side effects and does not fall under the tryptophan prohibition.
Pöldinger takes the scientific community to task for ignoring the therapeutic benefits of 5-HTP. "With all due deference to scientific skepticism shown by some authors of recent textbooks on the subject and by others, to concede 5-HTP its place among acknowledged pharmacotherapeutics routinely applied against depression does not seem warranted, neither on empirical nor theoretical grounds," they write.¹

In their study comparing 5-HTP and the SSRI fluvoxamine in depression, the clinical effects of these two treatments, one an inexpensive, naturally occurring amino acid, and the other an expensive, hi-tech prescription drug, were virtually indistinguishable.P>

Pöldinger and colleagues also point out that the action of fluvoxamine (like most SSRIs) is highly specific to serotonin re-uptake, with virtually no activity on noradrenergic (NA) and dopaminergic (DA) (ie, catecholaminergic) activity. The actions of 5-HTP, however, may be less specific, because it is converted to serotonin not only in serotonergic neurons, but also in dopaminergic and noradrenergic neurons. This means that it can act as a "false transmitter" and stimulate both serotonergic and catecholaminergic neurotransmission, which may explain why 5-HTP has been found to be superior to both tryptophan and SSRIs as an antidepressant.²

If you are bothered by depression, anxiety, insomnia, weight control, or migraines, new data suggest that you may have a deficiency in serotonin. Although many expensive (and dangerous) drugs have been developed to treat these conditions, some of which increase the availability of serotonin, it appears that 5-HTP, a metabolic precursor to serotonin, may be a safe, natural, and inexpensive solution to these problems.

References

1. 1. Pöldinger W, Calanchini B, Schwarz W. A functional-dimensinal approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology. 1991;24:53-81.
2. van Praag HM, Lemus C. Monamine precursors in the treatment of psychiatric disorders. In: Wurtman R, Wurtman J, eds. Food Constituents Affecting Normal and Abnormal Behavior: Nutrition and the Brain. New York: Raven Press; 1986:80-138.