Depression and 5 HTP

5 HTP and Serotonin

5 HTP is also known as 5-hydroxytryptophan. It is a precursor of serotonin or 5 HT.

5 HTP is a naturally occurring amino acid that is formed from another amino acid, L-tryptophan. Besides serotonin, 5 HTP is also an intermediate precursor in the synthesis of melatonin.

While 5 HTP is found only in very small amounts in foods, its precursor tryptophan is an essential amino acid present in different protein sources. Dietary sources of tryptophan include meat, poultry, pumpkin, potatoes, and greens.

Both 5 HTP and tryptophan can cross the blood-brain barrier. However, 5 HTP crosses more easily because tryptophan shares its transport mechanisms with other amino acids such as leucine, isoleucine, and valine.

5 HTP is converted to serotonin in tissues of the nervous system and the liver. Since serotonin cannot cross the blood-brain barrier, only the 5 HTP that crosses into the brain can be used to produce the serotonin needed to produce psychoactive effects on the neurons of the central nervous system.

Outside the brain, serotonin is released from the enterochromaffin cells of the gastrointestinal tract. In fact, 90% of the serotonin produced in the body is released from these cells.

Serotonin is also stored and transported in the platelets from which it is released to act as a vasoconstrictor, stop bleeding, and promote the healing of wounds. Serotonin also acts as a growth factor by promoting tissue repairs. This property can both be an advantage and a disadvantage.

In the central nervous system, serotonin is a monoamine neurotransmitter. It controls mood, sleep, and appetite as well as the consolidation of memory and learning.

This is the main reason 5 HTP preparations are sold as dietary supplements and promoted as antidepressants, appetite suppressants, and sleep aids. Other conditions for which 5 HTP is recommended include fibromyalgia, migraine, and weight loss.

All the psychoactive effects of 5 HTP including its use in the treating of depression are derived from its role as a precursor of serotonin.

There are 7 types of serotonin receptors in humans and each class of receptor has sub-types.

These receptors are responsible for the release and actions of other neurotransmitters such as dopamine, glutamate, GABA, norepinephrine, epinephrine, and acetylcholine. Therefore, serotonin receptors are capable of mediating inhibitory and excitatory responses. This makes the effect of the serotonin complex.

Serotonin receptors are also responsible for the release of hormones such as cortisol, vasopressin, prolactin, oxytocin, and substance P.

Outside the nervous and endocrine systems, serotonin is also important to the cardiovascular and musculoskeletal systems.

The levels of serotonin in the body are important. If serotonin levels are too high, a toxicity reaction called serotonin syndrome results. However, if the levels of the neurotransmitter in the central nervous system fall, it may cause sleep disturbance, eating disorders, weight gain, and depression.

What is Depression?

Depression is a state of low mood and loss of interest in daily activities. It is characterized by a pervasive disconnection from thoughts, behaviors, feelings, and self-perception.

People affected by depression lose interest in activities that once gave them pleasure; they have a difficult time concentrating, remembering, and/or making decisions; and they lose appetite or have sudden food cravings.

Feelings that are associated with depression include sadness, hopelessness, anxiety, guilt, irritability, low self-esteem, and worry. Therefore, depression may cause fatigue, sleeplessness, or excessive sleeping and aches.

There are different causes of depression. The most common is negative live events which may trigger temporary depression episodes. This form of depression is different from clinical depression.

Depression can also be caused by medications and illness (including psychiatry and non-psychiatric disorders).

Depression is a common health problem and it affects women more than men.

The Serotonin Theory of Depression

Most of the studies done on depression have concentrated on how serotonin, its precursors, its neurons, and the entire serotonergic pathway differ in people with clinical depression when measured against those who are not.

While the evidence gathered is not conclusive, serotonin is the major neurotransmitter associated with depression.

Depression can be caused by any of these factors that affect the serotonin system:

Therefore, depression is mostly treated by 5 HTP medications and natural supplements as well as antidepressants such as SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors).

5 HTP medications increase the production of serotonin by increasing the amount of 5 HTP that gets through the blood-brain barrier. Direct supplementation with 5 HTP medications is known to increase both plasma concentration of serotonin as well as the levels of the neurotransmitter in the cerebrospinal fluid.

SSRIs and SNRIs, on the other hand, work by blocking the clearance of serotonin from nerve endings. This allows serotonin to work longer.

Lastly, the serotonin theory is further supported by the strong correlation between gender differences and the incidences of depression in both men and women.

Women metabolized serotonin differently from men. In fact, the liver enzyme responsible for breaking down serotonin has greater activity in women than men.

Different studies have identified that women store up more serotonin in brain neurons more than men, and they are more affected by variations in serotonin levels. Also, the 5 HT receptors are very sensitive to estrogen.

Depressed women also have lower plasma concentrations of L-tryptophan than depressed men and they respond better to 5 HTP supplementation.

The Neurogenesis Theory of Depression

There have been concerns among researchers that low serotonin levels do not fully explain depression.

The first reason to think that depression involves more than serotonin is that simply increasing serotonin production does not work for everyone. Surely, antidepressants work for 60% of patients diagnosed with major depression but if increasing serotonin levels is the simple solution then the success rate should be higher than observed.

Furthermore, in those patients that do respond to antidepressants, it takes a few weeks before the first positive signs start to show.

Since serotonin production does not require such a long wait to build up, researchers and physicians believe that other mechanisms are at work besides simply increasing serotonin levels.

Finally, the evidence for low serotonin levels in depressed patients is inconclusive. For one, it is impossible to directly measure brain serotonin levels in living depressed patients. Secondly, reducing serotonin levels does not always lower mood or cause depression in everyone.

Since antidepressants do work for some patients, researchers began to look beyond serotonin levels.

It happens that another benefit of antidepressants is increasing the production of new brain cells. This is called neurogenesis and it accounts for some of the therapeutic profiles of antidepressants.

For example, neurogenesis takes a while to happen and it could be the reason antidepressants take some weeks to produce results. It could be that the antidepressants were stimulating the growth of new neurons in the brain.

Already, this theory has been demonstrated in animal models and reduced neurogenesis has been observed to be directly linked to depression.

However, not all clinical studies have supported the neurogenesis theory. Some researchers have found no difference in neurogenesis between the brains of depressed patients and those who are not.

Therefore, even though the neurogenesis theory does not have universal support and conclusive evidence, the serotonin theory does not measure up too. This means that a better understanding of depression is needed, and it could be that both serotonin levels and neurogenesis are only part of the answer.

Taking 5 HTP for Depression

Very few large studies have been done on the clinical efficacy of 5 HTP in the treatment of depression. However, several small studies and a few large studies agree that 5 HTP works better than a placebo in the treatment of depression.

Some studies have actually found that 5 HTP performs just as well as new antidepressants such as SSRIs in the treatment of depression. However, 5 HTP has the advantage of being better tolerated by most patients.

The recommended dose of 5 HTP in the treatment of depression is 200 – 300 mg per day.

The most common side effects of 5 HTP are gastrointestinal disturbances such as nausea, vomiting, and diarrhea. Other side effects include headache, insomnia, and rapid heartbeats. These side effects usually disappear with time and can be minimized by reducing the dose of 5 HTP.

Care should be taken especially when combining 5 HTP with antidepressants such as MAOIs (monoamine oxidase inhibitors), SSRIs, and SNRIs. Before using such combinations, be sure to consult your physician because the combination could result in a form of serotonin toxicity called serotonin syndrome.

Because safety studies are lacking regarding the use of 5 HTP during pregnancy and lactation, it should not be used by pregnant and breastfeeding women.

Also, people with liver or kidney diseases should consult their physicians before using 5 HTP.

Since there have been cases of contaminated 5 HTP products, you should make sure to buy 5 HTP from trusted manufacturers.