How does tryptophan get into the brain

Dougherty, D. Experimental and Clinical Psychopharmacology, 23, International Journal of Tryptophan Research, 7, International Journal of Tryptophan Research, 3, International Journal of Tryptophan Research , 3, Alcohol and Alcoholism, 44, Marsh-Richard, D. International Journal of Tryptophan Research , 2, Psychopharmacology, , Badawy, A. All rights reserved. Another site by CC Communications.

Website Navigation. Participate in a Study. L-Tryptophan Over the last 30 years, serotonin function has been a topic of intense research for understanding a variety of behavioral and psychiatric disorders, many of which have a core feature of impulsive behavior. L-Tryptophan Manipulation The mechanisms that lead to synthesis of brain serotonin are fundamental to our ability to test how changes in brain serotonin affect impulsivity and other behaviors.

Dietary Sources of Tryptophan This table provides examples of common foods and the amounts of tryptophan and the competing amino acids CAAs in those foods. This table provides the amount of each of the 15 amino acids plus tryptophan for both the 50 g and g L-tryptophan depletion and loading formulations used in experimental research.

For perspective, recall see Table 1 that recommended daily intake for a lb 79 kg adult is to milligrams. The amounts listed below are measured in grams. Once serotonin has been produced from tryptophan in the body, it can be converted into another important molecule — melatonin.

In fact, research has shown that increasing tryptophan in the blood directly increases both serotonin and melatonin In addition to being found naturally in the body, melatonin is a popular supplement and found in several foods, including tomatoes, strawberries and grapes Melatonin influences the sleep-wake cycle of the body.

This cycle impacts many other functions, including the metabolism of nutrients and your immune system Several studies have shown that increasing tryptophan in the diet can improve sleep by increasing melatonin 24 , One study found that eating tryptophan-enriched cereal at breakfast and dinner helped adults fall asleep faster and sleep longer, compared to when they ate standard cereals Symptoms of anxiety and depression were also reduced, and it is likely that the tryptophan helped increase both serotonin and melatonin.

Other studies have also shown that taking melatonin as a supplement can improve sleep quantity and quality 26 , Many different protein-containing foods are good sources of tryptophan Some foods are particularly high in tryptophan, including poultry, shrimp, eggs, elk and crab, among others It has been estimated that a typical diet provides approximately 1 gram per day You can also supplement with tryptophan or one of the molecules it produces, such as 5-HTP and melatonin.

If you want to improve your sleep quality and well-being, tryptophan supplements are worth considering. However, you also have other options. You may choose to supplement with molecules that are derived from tryptophan.

These include 5-HTP and melatonin. If you take tryptophan itself, it may be used in other bodily processes besides making serotonin and melatonin, such as protein or niacin production. Those who want to improve their mood or cognition may choose to take tryptophan or 5-HTP supplements. Both of these can increase serotonin, although 5-HTP can be converted to serotonin more quickly 5. Doses of 5-HTP may range from — mg per day For those who are most interested in promoting sleep, supplementing with melatonin may be the best choice Doses of 0.

For those who take tryptophan itself, doses of up to 5 grams per day have been reported Since tryptophan is an amino acid found in many foods, it is assumed to be safe in normal quantities. Its possible side effects have been examined for over 50 years, and very few of them have been reported. However, occasional side effects like nausea and dizziness have been reported at doses above 50 mg per kilogram of body weight, or 3.

Side effects may be more prominent when tryptophan or 5-HTP is taken along with drugs that influence serotonin levels, such as antidepressants. When the activity of serotonin is excessively increased, a condition called serotonin syndrome can result It can cause several symptoms, including sweating, tremors, agitation and delirium Likewise, the dietary Trp content have been shown to affect endocrine and behavioral responses to stress in teleost fishes 10 , 19 , This review summarizes the results from previous studies on the effects of dietary Trp supplementation on the behavioral and neuroendocrine stress response, focusing on possible mechanisms involved in mediating these effects.

We also present a hypothesis on how the diet could be used to improve fish stress tolerance through interactions with the Trp metabolic pathways. In serotonergic neurons Trp serves as the precursor for 5-HT. The 5-HT metabolic pathway is initiated by Trp being hydroxylated to the intermediate 5-hydroxytryptophan 5-HTP , which is subsequently decarboxylated to become 5-HT. Tissue levels of 5-HTP are usually low since this substance is rapidly decaroxylated by the enzyme aromatic amino acid decarboxylase [for review see 21 ].

Thus, the rate limiting step in the biosynthesis of 5-HT is the hydroxylation of Trp which is catalyzed by the enzyme tryptophan hydroxylase TPH Figure 1. In amniotes 5-HT neurons are only present in the raphe area of the hind brain whereas in anamniotes, including teleosts, 5-HT cell bodies are also located in pretectal areas and basal forebrain.

Interestingly, TPH2 show a Km for its substrate which is in the range of in vivo brain levels of Trp Consequently, the rate of 5-HT synthesis in cells expressing TPH2 is drastically affected by changes in Trp availability, an effect which is probably not seen in 5-HTergic cells expressing other TPH isoforms Thus, changes in Trp availability may have direct effects on 5-HTergic tone.

Coherent to this, Russo et al. Dietary composition as well as stress, physical activity and immune system activation will all have effects on plasma Trp concentrations, and thus on brain Trp availability and raphe 5-HTergic activity Such Trp related changes in 5-HTergic activity could have direct effects on behavior as well as endocrine status through 5-HT projections to telencephalic and hypothalamic areas.

It could be argued that such effects may be less important in teleost fish since they have extra-raphe located 5-HT cell populations expressing the TPH1 isoform, making them less responsive to changes in Trp availability. However, in teleosts, as well as in other vertebrates, the raphe 5-HTergic cells have a wide projection pattern innervating most brain regions Still, it has to be acknowledged that very little is known about the role of telesost forebrain 5-HT cell population in the control of behavior and endocrine functions The essential amino acid Trp enters the brain in competition with other large neutral amino acids LNNAs; i.

Thus, the amount of Trp entering the brain depends on the plasma concentrations of Trp in relation to the other LNAAs [for references see reviews 26 , 27 ]. Hence, ingestion of a normal protein source, usually containing 0. Dietary carbohydrates, on the contrary, increase brain Trp levels. This differential amino acid uptake to skeletal muscles is caused by the fact that Trp in blood plasma is bound to albumin whereas other LNAA are not.

Trp influx to the brain is then promoted by the common LNAA transporter protein in the blood brain barrier having a much higher affinity for Trp compared to albumin Figure 2. Effects of the proteins and carbohydrates on influx of tryptophan Trp to the brain. Studies in rainbow trout Oncorhynchus myliss show that the amino acid composition of trout albumin differs from that of mammalians and lacks the binding site for indoles 29 , Thus, in rainbow trout, the majority of plasma Trp is in its free non-protein bound state 31 , This assumption is further strengthened by a study by Ruibal et al.

It is not known if the lack of Trp binding by albumin is specific for rainbow trout or if it represents a more general trait of teleost albumin. However, it is possible that in teleost fishes brain influx of Trp could be more dependent of the dietary amino acid composition than on carbohydrates.

In fact, only a minor fraction of the Trp pool is utilized for 5-HT biosynthesis. In mammals, the majority of Trp enters the kynurenic pathway and is converted to other bioactive substances than 5-HT, such as kynurenic acid and quinolinic acid Figure 3 [for references see review 11 ].

The first stage of this pathway is catalyzed by the hepatic enzyme tryptophan 2,3-dioxygenase TDO and the extrahepatic enzyme indoleamine 2,3-dioxygenase IDO , enzymes that are induced by glucocorticoids and pro-inflammatory cytokines, respectively Thus, chronic stress and infections can shunt available Trp toward the kynurenic pathway and thereby lowering brain 5-HT synthesis while simultaneously increasing the production of other Trp based bioactive substances.

Earlier studies suggested that IDO1 arose by a gene duplication in mammals However, recent phylogenetic analyses show that IDO1 are present in reptiles and in teleosts, indicating that the gene duplication occurred in the common ancestor of vertebrates In mammals, the activation of dendritic cells results in IDO1 induction with the depletion of Trp levels locally or systemically, a mechanism by which interferons inhibit the growth of certain bacteria, intracellular parasites, and viruses Moreover, an elevation of the activity of the kynurenic pathway also inhibits T lymphocyte replication which results in immunosuppression and tolerogenicity.

In line with this, IDO1 have been suggested to play an important role in preventing fetal rejection and in facilitating immune escape of tumor cells In addition, some products of the kynrunic pathway may act anti-inflammatory 38 , The Trp catabolizing efficiency of IDO2 and non-mammalian IDO1 seems to be lower than mammalian IDO1, and their function and involvement in the immune response in comparative model species is far less understood However, recently, it has been demonstrated that treatment with bacterial lipopolysaccharide LPS induces and upregulation of IDO expression in rainbow trout, suggesting that this enzyme is involved in the immune response in non-mammalian vertebrates This suggests that systemic infection may decrease Trp influx to the brain of teleost fishes in the same way as in mammals, and result in behavioral and physiological changes see section Kynurenine pathway.

As discussed above chronic stress may result in lowered brain Trp availability as a consequence of a stress-induced activation of the kynurenine pathway. However, acute stress has been reported to have the opposite effect elevating brain Trp levels in both mammals 41 , 42 and teleost fish 3 , This stress-induced increase in brain Trp concentrations appears at least in part related to a sympathetic activation and elevated levels of circulating plasma catecholamines Plasma catecholamines stimulate lipolysis, resulting in elevated plasma levels of non-esterified fatty acids, which in turn could compete with Trp for binding to albumin and thus elevate the plasma pool of free Trp available for uptake into the brain [reviewed by 44 ].

However, as discussed above, rainbow trout albumin appears to lack the Trp binding site, suggesting that mechanisms based on competition between Trp and non-esterified fatty acids are not involved in stress-induced increase in brain Trp in teleosts, at least not in rainbow trout.

It has also been suggested that sympathetic activation results in increased permeability of the blood-brain barrier, another mechanism that could increase brain Trp influx As mentioned earlier in this review, the positive relationship between Trp availability and brain 5-HT production is well conserved within the vertebrate linage. Coherent to this, the involvement of 5-HT in the neuroendocrine regulation of the stress response seems to be similar within this linage.

This, mainly through its effects on the release of corticotropin-releasing factor CRF from the hypothalamus 45 , In addition, extra hypothalamic 5-HT appears be involved in appraisal and stress coping mechanisms, modulating behavioral and neuroendocrine responses to stressors 47 , Furthermore, as mentioned in section The Kynurenic pathway and Acute stress, stress by itself can influence the Trp influx to the brain, and thereby affect 5-HT signaling and the stress response.

Thus, the link between Trp and the 5-HT system and how they control behavioral and neuroendocrine stress responses appears complex with 5-HT having context dependent effects 19 , 22 , Long-term effects of Trp dietary manipulations on the neuroendocrine stress response have been observed in both mammals and teleost fishes [for a review see 49 ].

For instance, in pigs, elevated dietary Trp had stress suppressive effects, including elevated hypothalamic 5-HT and lowered post stress plasma cortisol levels, effects that peaked after 5 days of dietary Trp enrichment Similarly, 51 showed that post-stress plasma cortisol levels returned to baseline earlier after social stress in pigs fed Trp enriched feed for 7 days.

Interestingly, a similar time frame for the suppressive effects of dietary Trp supplementation on glucocorticoid release has also been demonstrated in fish for references see Table 1. For instance, studies in rainbow trout show that suppression of the neuroendocrine stress response is present after 7, but not after 3 or 28 days of treatment with dietary Trp supplementation Furthermore, in the earlier studies showing a suppressive effect of elevated dietary Trp on the neuroendocrine response to an acute stressor the effects were investigated during or directly following a period of dietary Trp supplementation 10 , However, in recent studies in sea water reared Atlantic salmon Salmo salar , the suppressive effect on post-stress plasma cortisol seems to appear between 2 and 8 days after terminating the Trp supplementation.

Moreover, in Atlantic salmon, this suppressive effect was still present at 21 days post Trp supplementation 7 , Basic et al. Moreover, these long-term alternations of HPI axis reactivity was not related to changes in hypothalamic 5-HT neurochemistry.

Instead they coincided with changes in dopaminergic neurochemistry in this brain part, effects which may be related to elevated activity of the kynruneric pathway, as discussed in section The Kynurenic pathway. The latter study also included telencephalon and 5-HT activity followed the same general pattern as cortisol in this brain part.

Table 1. Effects of dietary tryptophan supplementation on the behavioral and endocrine stress response in teleost fishes. Generally, teleost fishes have a remarkable neurogenic and regenerative capacity throughout ontogeny, and it has been suggested that structural changes may underlie long-lasting effects on telencephalic neurochemistry induced by elevated dietary Trp in teleost fishes 7.

This type of brain architectural changes is supported by mammalian studies, showing that the 5-HT system is involved in the organization and development of its own neural projection pattern In addition, a positive relationship between dietary Trp content and neural proliferation markers, such as exogenous 5-bromodeoxyuridine and brain derived neurotrophic factor BDNF has been demonstrated in rats 66 , which lends further support for the suggestion that dietary Trp can induce structural changes in the brain.

There are studies in teleost fishes showing effect of longer Trp treatment periods than 7 days Table 1. For example, Tejpal et al. Moreover, longer Trp treatment periods have also been shown to act stimulatory on plasma cortisol responses. For example, an immune challenge by i. Furthermore, there is a rather high variability in the effect of elevated dietary Trp on baseline cortisol values Table 1.

This variability could reflect interspecific differences in Trp metabolism and neuroendocrine mechanisms For example, in the studies performed by Lepage et al. We also cover the difference between serotonin and tryptophan, the importance of carbohydrates , and other tips for boosting serotonin and mood. Tryptophan is an amino acid that is important for the production of serotonin in the body. It is also key to brain function and has a role in healthy sleep. Eating a healthful, balanced diet is an essential way to support mental as well as physical health.

Including sources of tryptophan in the diet can have positive benefits on energy levels, mood, and sleep. Tryptophan, which goes into making serotonin, is commonly found in foods that contain protein. Although meat is often a key source of protein for many people, there are also many vegetarian and vegan sources.

This oily fish is also a source of omega-3 fatty acids, which are important for health. These fatty acids can help support strong bones, healthy skin, and eye function. Salmon is also a source of vitamin D , which is essential for strong bones and teeth, and healthy muscles. Eating two portions of oily fish per week should provide enough tryptophan for most people. Vegans and vegetarians can get omega-3 from pumpkin seeds, walnuts, and soya.

Poultry includes chicken, turkey , and goose. Lean poultry, such as chicken breast, will usually be high in protein and low in fat. Some ways of cooking and preparing eggs are more healthful than others.

Frying an egg adds a lot of fat, which makes it a less healthful option. Boiling or poaching an egg does not add any additional fat. Making an omelet and eating it with a salad can be a good option for a light meal. Spinach is also a good source of iron. Iron helps the body to make healthy red blood cells. A lack of iron in the diet can lead to anemia , low energy, or difficulty breathing. Seeds do not contain as much tryptophan as oily fish, poultry, or eggs.