Tryptophan
Tryptophan is an essential aminoacid. It is an aromatic α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a non-polar aromatic amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet like vitamin. Amino acids, including tryptophan, are used as building blocks in protein biosynthesis, and proteins are required to sustain life. Tryptophan is among the less common amino acids found in proteins, but it plays important structural or functional roles whenever it occurs. For instance, tryptophan and tyrosine residues play special roles in "anchoring" membrane proteins within the cell membrane. In addition, tryptophan functions as a biochemical precursor for the following compounds:
Tryptophan is a starting substance for serotonin production in the central nervous system. The enzyme tryptophan hydroxylase, which converts tryptophan to 5-hydroxytryptophan, is unsaturated at normal brain tryptophan concentrations; thus the synthesis of serotonin in the brain is dependent upon tryptophan availability and its uptake by the brain. Tryptophan uptake into the brain is by the large neutral amino acid transport system for which tryptophan competes with other essential amino acids for entry into the brain. It is possible to deplete plasma tryptophan may reduce its uptake by the brain due to competition between other essential amino acids that compete with tryptophan for transport into the brain across the blood-brain barrier. Some studies have shown that this results in decreased plasma tryptophan levels and decreases in brain tryptophan, serotonin and its metabolites.
Serotonin is a chemical that carries messages between nerve cells in the brain and throughout your body. Serotonin plays a key role in such body functions as mood, sleep, digestion, nausea, wound healing, bone health, blood clotting and sexual desire. Serotonin levels that are too low or too high can cause physical and psychological health problems.
Normal aging results in a reduction of tryptophan our brain needs to make serotonin. A serotonin deficiency can result in unwanted weight gain, mood swings, and disturbed sleep. Restoring tryptophan is often difficult in aging humans because it is rapidly degraded by pro-inflammatory cytokines. A new pharmaceutical-pure tryptophan has been combined with specific ingredients that prevent its excessive depletion, thus sparing tryptophan for conversion to serotonin in the brain. Why Aging People Become Depressed, Fatigued, and Overweight text after publication in Life Exteension Magazine.
Serotonin is a compound in the brain that promotes feelings of personal security, relaxation, and confidence. A serotonin deficiency can result in sleep disturbance, anxiety, depression, and a propensity to overeat, particularly carbohydrates like simple sugars.
Startling research reveals that serotonin levels decline as we age![1-3] These findings provide a biochemical rationale to explain common age-related disorders such as depressed mood and sleep difficulties. Based on these discoveries, aging people may appreciably improve their health by restoring serotonin to youthful levels.
The amino acid tryptophan is needed to produce serotonin in the brain.[4] While the amount of tryptophan in a typical diet meets basic metabolic requirements, it often fails to provide optimal brain serotonin levels.
Ever since the FDA restricted the importation of tryptophan for use in dietary supplements, there has been an upsurge in the percentage of overweight and obese Americans.
One could argue that a widespread serotonin deficiency is at least partially responsible for the record numbers of depressed, sleep-deprived, and overweight individuals.
Why Dietary Tryptophan Might Be Inadequate
Tryptophan is one of the eight essential amino acids found in the human diet. Essential amino acids are defined as those that cannot be made in the body and therefore must be obtained from food or supplements. (A ninth amino acid, histidine, is sometimes considered essential for children.)
Our bodies do need additional amino acids, but these other amino acids are made from the eight essential amino acids when we are in optimal health.
In any normal diet, be it omnivorous or vegetarian, tryptophan is the least plentiful of all amino acids. A typical diet provides only 1,000 to 1,500 mg/day of tryptophan, yet there is much competition in the body for this scarce tryptophan.
Tryptophan is used to make various protein structures of the body. In people with low-to-moderate intakes of vitamin B3(niacin), tryptophan may be used to make B3 in the liver at the astounding ratio of 60 mg tryptophan to make just 1 mg of vitamin B3.[5]
Yet even maintaining a minute amount of tryptophan provides little benefit in boosting serotonin in the brain due to competition with other amino acids for transport through the blood-brain barrier. Nutrients must be taken up through the blood-brain barrier by transport molecules. Tryptophan competes for these transport molecules with other amino acids.
The Human Body Requires the Following Eight Essential Amino Acids: |
|
Tryptophan | Threonine |
Lysine | Valine |
Methionine | Isoleucine |
Phenylalanine | Leucine |
Essential amino acids cannot be made in the body and therefore must be obtained like vitamins from food or supplements. (Children may require the amino acid histidine in addition to those listed above.) |
As one can see, diet-derived tryptophan contributes very little actual tryptophan to the brain. As you will soon read, even eating tryptophan-containing foods like turkey may not always provide the body with enough of this essential amino acid. One reason is that aging people make enzymes that rapidly degrade tryptophan in the body.Remember, tryptophan is the only normal dietary raw material for serotonin synthesis in the brain. Given all we now know about the difficulty in maintaining adequate tryptophan status, is it any wonder that so many aging humans suffer from disorders such as depression, insomnia, and excess weight gain associated with a serotonin deficiency?
How Tryptophan Functions in the Body
L-tryptophan converts into serotonin, primarily in the brain. Since serotonin is a neurotransmitter involved in controlling moods and appetite, tryptophan supplementation has been recommended for individuals suffering from a variety of conditions associated with decreased serotonin levels, including sleep disorders, depression and fibromyalgia, and eating disorders.[6-8]
It has been shown in human clinical studies that low levels of tryptophan contribute to insomnia.9 Increasing tryptophan may help to normalize sleep patterns.[10-12] It is known that raising tryptophan levels in the body may decrease cravings and binge eating – especially for carbohydrates – and help people lose weight.[13,14]
L-tryptophan serves as a precursor not only to serotonin, but also melatonin and niacin. Serotonin is a major neurotransmitter involved in many somatic and behavioral functions including mood, appetite and eating behavior, sleep, anxiety, and endocrine regulation.[6,15-17]
There are two possible sources for L-tryptophan: diet and tissue proteins, from which L-tryptophan has been recycled during protein turnover. Aging, chronic inflammatory diseases, and HIV infection are associated with tryptophan depletion, even in the absence of dietary tryptophan deficiency. An adult male needs 250 mg a day of tryptophan just to maintain nitrogen balance.[18] While a normal diet contains 1,000 to 1,500 mg of tryptophan per day,[19] the enzymatic breakdown of tryptophan increases with age,[20] and certain disease states can severely deplete tryptophan.
How Tryptophan is Metabolized in the Body
There are three potential fates for L-tryptophan once ingested:
● Incorporation into body tissue proteins.
● Conversion into serotonin (and melatonin).
● Conversion into indoleamines, carbon dioxide, water, adenosine triphosphate (ATP), and niacin.21
For every nutrient absorbed into the body, there are specific enzymes that convert the nutrient into other substances. There are two specific enzymes that can deprive the body of sufficient amounts of tryptophan. These enzymes are called L-tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO).
The liver enzyme TDO is induced when plasma concentrations of L-tryptophan exceed those needed for conversion into serotonin and/or protein. This enzyme oxidizes surplus L-tryptophan into carbon dioxide, water, and ATP.22,23
The other tryptophan-degrading enzyme IDO is more insidious because it can degrade L-tryptophan even when circulating levels of L-tryptophan are low.23,24 This enzyme has been found outside the liver on macrophages and dendritic cells and is increased in pro-inflammatory states, HIV infection, and normal aging.25-30 Once the TDO or IDO enzymes act on tryptophan, it is no longer available for conversion to serotonin or incorporation into protein. Consuming large amounts of oral L-tryptophan will not generate more serotonin because more TDO will be induced to deplete the tryptophan.
Tryptophan and its metabolite 5-hydroxytryptophan (5-HTP) are taken up into the brain across the blood-brain barrier by a transport system that is active towards all the large neutral amino acids.31 The affinity of the various amino acids for the carrier is such that there is competition between the large neutral amino acids for entry into brain. In fact, the best predictor of a given meal’s effect on brain tryptophan-serotonin levels is the serum ratio of tryptophan to the pool of large neutral amino acids.32
What You Need to Know: Tryptophan |
● Serotonin is a brain biochemical that promotes restful sleep, well-being, and satiety. When serotonin levels are low, people often experience depression, anxiety, insomnia, and the urge to overeat. ● The amino acid tryptophan is needed to produce serotonin in the body. While foods contain some tryptophan, the diet may not provide enough tryptophan to make adequate amounts of serotonin. Additionally, enzymes that are influenced by inflammation and aging can break down tryptophan before it converts to serotonin. ● Individuals suffering from the adverse effects of low serotonin levels can now restore sleep, appetite control, and mood by supplementing with an advanced L-tryptophan formulation. This formula combines L-tryptophan with nutrients and herbs that help optimize its ability to convert to beneficial serotonin in order to counteract appetite and sleep disorders, and low mood. |
More clinically relevant, however, is that serotonin levels are enhanced by carbohydrate ingestion.[33] The reason is that the high amount of insulin released in response to carbohydrate ingestion accelerates the serum removal of valine, leucine, and isoleucine that compete against tryptophan for transport into the brain. Similarly, a higher percentage of protein in the diet slows serotonin elevation (by providing competing amino acids for the blood-brain barrier).34,35]
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