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5-HTP vs Tryptophan
Both tryptophan and 5 HTP are amino acids and precursors of serotonin. They are also both available as over-the-counter dietary supplements for treating depression, obesity, sleep disorders etc. Find out which of the 2 is the better supplement for increasing serotonin levels in the brain.
by Brad Chase
Tryptophan is one of the essential amino acids commonly found in human diet. It is available in 2 forms: D- and L- isomers.
The L- isomer is more common and it is the form of tryptophan found in proteins in the body.
Tryptophan is found in most dietary proteins but it is especially abundantly found in meat, poultry, milk, yogurt, egg, fish, banana and peanut.
While some believe that turkey is the richest source of tryptophan and plants are poor in the amino acid, both beliefs are untrue: turkey contains no more tryptophan than other poultry and meat, and excellent plant sources of tryptophan are abundant.
Even though there are several dietary sources of L-tryptophan, different studies have found that these food sources cannot dramatically increase the blood levels of the amino acid. Therefore, tryptophan is widely sold as a dietary supplement and even drug.
As a drug/supplement, L-tryptophan is used because it is a precursor of serotonin, an important neurotransmitter in the brain. L-tryptophan is first converted to 5-hydroxytryptophan or 5 HTP (another dietary supplement) which is then converted to serotonin or 5 HT in the brain.
However, these biochemical reactions happen in the brain, therefore, tryptophan has to cross the blood-brain barrier.
L-tryptophan only represent about 1% of the amino acids available in dietary proteins. Since the other amino acids also want to get into the brain, there is a competition for the transport mechanisms that carry them across this blood-brain barrier.
For example, L-tryptophan shares the same transport mechanism with valine, leucine and isoleucine.
Therefore, the extent of absorption of this amino acid is much reduced especially from protein-rich foods. To improve the uptake of tryptophan into the brain, carbohydrates are required.
After the ingestion of carbohydrates, the body releases insulin in response. Fortunately, insulin drives valine, leucine and isoleucine (but not tryptophan) into the cells of the body. Therefore, the proportion of tryptophan among the amino acids left in the blood is increased and this increases the chances of tryptophan crossing into the brain.
The use of tryptophan as a dietary supplement was banned for most of the 1990s. This is because of cases of eosinophilia-myalgia syndrome (EMS) associated with the amino acid.
This syndrome was blamed on bacterial contaminants left in the final product by one major supplier of the amino acid. This was never conclusively proven and some other experts believe that the large doses of tryptophan taken are responsible (tryptophan metabolites block the breakdown of histamine and the symptoms of EMS resembles the effect of prolonged action of histamine).
However, tryptophan is now commonly sold as dietary supplement and drug. It is obtained from high-quality sources and regarded as safe.
5 HTP is a naturally occurring amino acid produced from L-tryptophan. There are no dietary sources of 5 HTP although the 5 HTP used in supplements is obtained from the seeds of Griffonia simplicifolia, a plant native to Africa.
5 HTP is a direct precursor of serotonin and an intermediate in the synthesis of melatonin, a neurohormone.
The conversion of 5 HTP to serotonin is catalyzed by 5 HTP decarboxylase, an enzyme whose cofactor is vitamin B6. All the effects of 5 HTP are solely due to its ability to increase serotonin levels in the brain.
However, 5 HTP is also converted to serotonin in the liver. In fact, more serotonin is produced outside the brain than inside. But since serotonin cannot cross the blood-brain barrier, only the amount of 5 HTP crossing into the brain can increase the level of serotonin in the central nervous system and also the psychoactive effect of the neurotransmitter.
The serotonin produced outside the brain is released from the enterochromaffin cells found in the gastrointestinal tract. In the gut, serotonin promotes intestinal motility.
The excess serotonin released from these cells are removed by the veins draining the gut. While in the blood, serotonin is carried through the circulatory system and stored in platelets. Therefore, the serotonin produced from 5 HTP can reach the cardiovascular and musculoskeletal systems.
5 HTP is commonly sold as a dietary supplement and marketed as a sleeping aid, antidepressant and appetite suppressant. It is usually prepared in 50 mg and 100 mg capsules.
Besides the uses listed above, 5 HTP is also taken to treat fibromyalgia and anxiety disorders.
Although 5 HTP supplementation has not been extensively studied in large clinical trials but in the 60 years that it has been used, there are only very few reports of serious side effects.
Moderate doses of 5 HTP is safe and well tolerated but it may cause vomiting and diarrhea. These gastrointestinal side effects are due to the increased production of serotonin outside the body. When released from the enterochromaffin cells, the increased serotonin levels increase gastrointestinal movement.
5 HTP supplements were also believed to cause EMS due to contamination during production. However, such cases have not been reported since FDA’s GMP (Good Manufacturing Practice) regulations came into place.
Although tryptophan and 5 HTP are both amino acids and used as dietary supplements for the same indications, they do differ. The major differences between these 2 precursors of serotonin are discussed in the table below.
Precursor: 5 HTP is the direct precursor of serotonin and an intermediate in the synthesis of melatonin while tryptophan is the direct precursor of 5 HTP. In addition, tryptophan is also used in the syntheses of other biochemicals including niacin, proteins and enzymes.
Source: The L-tryptophan used in dietary supplements is obtained from the bacterial fermentation of serine and indole. 5 HTP is extracted from the seeds of Griffonia simplicifolia, a wild plant native to Ghana and Ivory Coast.
Uses: Both 5 HTP and tryptophan are used to treat diseases arising from serotonin deficiency including depression, anxiety disorders, sleep disorders and obesity. However, L-tryptophan is also used to treat tryptophan deficiency since it is the one among other essential amino acids that is most commonly deficient in diet.
Administration: Because nausea is a common symptom of 5 HTP supplementation, it should be taken with food. Tryptophan, on the other hand, can be taken with or without food. However, since tryptophan competes with other aromatic and branched chain amino acids such as itself, it is best to take the supplement with low or no protein diet but with carbohydrates to help reduce the competition.
5 HTP is a better supplement than L-tryptophan for increasing serotonin levels in the central nervous system because of the following reasons.
Because 5 HTP and tryptophan increase the level of serotonin in the body, some people may be tempted to use both supplements at the same time. This practice should be discouraged especially since it can dramatically increase the side effects of both drugs and cause serotonin toxicity.
Mild gastrointestinal side effects such as nausea, vomiting and diarrhea are immediately triggered.
Taking 5 HTP and tryptophan concurrently will increase the synthesis of serotonin in the liver and in the central nervous system. This may cause serotonin syndrome in the nervous system and cardiac fibrosis in the cardiovascular system
Of the two, serotonin syndrome appears first. It is characterized by the mild and serious symptoms. Mild symptoms include shivering, sweating, tremor, restless limbs and headache while serious symptoms include hypertension, hyperthermia, mania, hallucination and ataxia.
These symptoms will subside 24 hours after stopping both supplements but the more serious symptoms may need urgent medical attention.
Cardiac fibrosis is caused by high doses and prolonged use of drug combinations that increase serotonin levels.
In the circulatory and cardiovascular systems, serotonin acts as a vasoconstrictor and healing factor. It repairs damaged tissue by promoting the production of fibrins to cover the site of damage.
However, the kind of connective tissue caused by serotonin action is thicker and less flexible than normal connective tissue. This causes cardiac fibrosis and heart failure from thickened right heart valve.
Although these serious side effects of 5 HTP and tryptophan combination are rarely in medical literature that is mainly due to lack of large-scale and thorough clinical studies on the use of this dietary supplements.
Therefore, the potential for these side effects should be considered when 5 HTP is combined with tryptophan.
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