What is tryptophan used for in the body

Readers should consult the cited manuscript for detailed descriptions of NIRS sample measurements and calibrations. The authors conclude that the developed NIRS calibrations enable fast and accurate predictions of essential amino acids in cereals. Zhang et al 25 used NIRS to measure the tryptophan content of milled rice samples. The method was less reliable for brown than for white rice.

The authors suggest that the method could be used to select rice seeds with high tryptophan content and for quality control during rice processing. The method with stable isotope-labeled analogues as internal standards was used to determine the concentrations of the metabolites in human plasma samples. Another assay developed for use in animal systems was developed by Sano et al 27 who devised a method for the detection of 15N 2 -labeled tryptophan, l -kynurenine, serotonin, and quinolinic acid in rat plasma.

These compounds were first transformed to acylated derivatives using pentafluoropropionic anhydride and pentafluoropropanol. The method was used to determine the isotope enrichment in plasma tryptophan over the course of a continuous infusion in pregnant rats.

The authors suggest that the method has the potential to facilitate our understanding of the 4 tryptophan metabolism pathways in animals and humans. Analytical methods have also been developed and used for determining free and protein-bound tryptophan in new varieties of maize, rice, and soybeans.

Indeed, the production of novel nutritionally enhanced major food crops via genetic engineering might help meet the worldwide need for inexpensive better-quality foods. Rosales et al 28 and Sarika et al 29 used the nonhydrolytic NIRS method to determine the protein, tryptophan, and lysine content of samples of quality protein maize that has on average twice the tryptophan content of normal maize.

The authors suggest that the efficient NIRS method is preferable to wet chemistry methods for the analysis of large numbers of samples generated in plant breeding programs. Sarika et al 29 found that despite the nutritional superiority of Opaque, a high-tryptophan and high-lysine maize mutant, the physico-biochemical characteristics of its endosperm are not affected. In an analysis of rice, Wakasa et al 30 found the amount of free tryptophan in a transgenic rice variety was about twice that in seeds in wild-type plants.

The protein-bound tryptophan level was also enhanced. This observation led the authors to suggest that the tryptophan content of rice seeds could be increased transgenetically to improve the nutritional value of the human diet and also animal feeds.

By contrast, Dubouzet et al 31 described a metabolic engineering method used to promote the transformation of tryptophan to serotonin and to serotonin-derived indole compounds in rice calli, suggesting that the method provides a novel approach for the production of tryptophan-derived bioactive compounds. Kita et al 32 discovered that transgenic soybean plants were found to accumulate free tryptophan to levels as high as 3.

For analysis, free tryptophan and other amino acids were extracted with sulfosalicylic acid and analyzed by the ninhydrin method using an automated amino acid analyzer.

The high-tryptophan soybeans can be used to increase the tryptophan content of mixed diets. A discussion of reported methods used to analyze the isomeric forms of amino acids simultaneously is beyond the scope of this article. By contributing to food security, a major worldwide challenge, these selected results, and related ongoing studies suggest that the production of novel nutritionally enhanced major food crops via genetic engineering might help meet the worldwide need for inexpensive better-quality foods.

There have been many studies on the utilization of tryptophan from different sources by humans and animals and some of these reports are included here to highlight the potential for tryptophan supplementation fortification.

Various studies have investigated the absorption of tryptophan into the human body. The authors suggest that negative effect of the corn protein zein probably reflects its poor digestibility, resulting in slower absorption of the amino acids from the gut. The effects of dietary tryptophan on the immune system have also been investigated. Tryptophan catabolites can have immunomodulatory functions, such as via the kynurenine pathway.

The dietary role of tryptophan in the immune system has therefore been the subject of study. Brain serotonin, derived from tryptophan, is known to influence affective events, such as mood disorders. They observed significant faster increases and longer-lasting improvement in the ratio with the hydrolyzed tryptophan source versus the intact or pure tryptophan.

In a related study, Markus et al 39 found that consumption of a tryptophan-rich egg protein hydrolysate by 17 participants with high and 18 with low chronic stress resulted in an increase in plasma tryptophan uptake into the brain and in improved mood and performance under acute stress exposure, suggesting the therapeutic value of the hydrolysate.

Similarly, Mitchell et al 40 investigated, using a double-blind crossover design, the dose-dependent effects of a tryptophan-rich egg protein hydrolysate on brain tryptophan availability.

The results suggest that the hydrolysate is a useful food ingredient that can increase tryptophan availability.

The availability of tryptophan in animal feed has also been investigated. These facts should be taken into account in the design of nutritionally improved poultry feed diets supplemented with tryptophan.

Reichl 42 has provided a comprehensive discussion of the kinetics of the absorption and metabolism of amino acids in tissues from the gut into the bloodstream in rodents, cows, pigs, and sheep.

The described results indicate that although tryptophan is well absorbed, its absorption is reduced by the presence of other amino acids. The following observations indicate that tryptophan has been shown to be of paramount importance in infant nutrition.

For example, Huang et al 43 discuss the tryptophan requirement of infants in the first month of life. This observation is reinforced by a study with infants breast-fed or fed with a tryptophan-fortified formula.

By contrast, no significant difference was apparent between the breast-fed group and the group fed the tryptophan-fortified formula, suggesting the need for tryptophan fortification to achieve plasma tryptophan levels similar to those in breast-fed infants. These diets are low in protein quality and quantity and in energy. To overcome these deficiencies, corn can be supplemented either with 2 limiting amino acids tryptophan and lysine or high-quality proteins such as soybean flour.

Serna-Saldivar 50 note that the consumption of tortillas flat cakes baked from lime-treated corn without supplementation with high-quality protein foods can lead to the Kwashiorkor disease in infants. This is due to the lack of 2 mentioned essential amino acids. These facts stimulated interest in exploring the nutritional potential of widely consumed corn flour-based tortillas fortified with lysine, tryptophan, and high-quality protein flours. Here, we briefly mention some of the reported studies,.

Tovar and Carpenter 51 found that it appears that the higher protein efficiency ratio, a measure of protein nutritional quality in rats, for corn with added tryptophan as the limiting amino acid as compared with added lysine was due to lower ad libitum food intake with the same weight gain.

Amaya-Guerra et al 54 found that soybean fortification of corn tortillas with high-tryptophan soy flour improved brain development of rats, suggesting that the fortification has the potential to enhance the nutrition quality of widely consumed corn tortillas. The cited studies suggest that fortifications of tortillas with tryptophan or with high-tryptophan soy proteins 55 have the potential to enhance the nutritional quality and health benefits of corn tortillas.

It is also worth noting that Delgado et al 56 found that tortillas prepared from high-anthocyanin pigmented maize have lower levels of potentially toxic acrylamide compared with those prepared from nonpigmented corn kernels, suggesting that the phenolic compounds are most likely responsible for the beneficial effect. Because tryptophan is widely used a dietary supplement for perceived benefits including sleep and mood regulation, there is a need for assessing its safety.

This value is generally reinforced by the following experimental observations on the safety of tryptophan in young women and rats. Two studies by Hiratsuka et al 58 , 59 showed that oral administration of tryptophan to 17 healthy Japanese young women at concentrations ranging from 1. The urinary excretion of nicotinamide and several other metabolites was directly related to consumed tryptophan levels.

The authors suggest that because 3-hydroxykinurenine was the most characteristic excreted urinary metabolite, it could serve as a surrogate biomarker for excess intake of tryptophan. These observations imply that use of tryptophan as a human food or animal feed dietary supplement might not have adverse effects.

Shibui et al 44 examined the safety of tryptophan in rats. Feeding an experimental diet with added tryptophan at doses 0 basal diet , 1. However, body weight gain and food consumption significantly decreased in men in the 2. These adverse effects were not observed after a 5-week recovery period, suggesting reversibility of the adverse effects. The no-observed-adverse-effect level was 1. The authors concluded that tryptophan has a low toxicity profile in rats. Although racemization rates of the 18 different l -amino acid residues in a protein vary, the relative rates in different proteins are similar.

Because the formation d -peptide bonds and cross-linked amino acids such as lanthionine and lysinoalanine can impair digestibility and nutritional quality, there is need to develop a better understanding of these events in order minimize adverse effects on protein nutritional quality and safety.

As part of a program to evaluate the chemistry and the nutritional and toxicologic aspects of novel amino acids formed during food processing, including d -amino acids, we compared the weight gain in mice fed with free amino acid diets in which d -tryptophan was substituted for l -tryptophan reviewed by Friedman and Levin 60 , The results indicate that the mice can utilize supplied d -tryptophan in the absence of l -tryptophan; ie, the mice must meet the entire need for l -tryptophan from the d -isomer.

The relative nutritional potency of d -tryptophan compared with l -tryptophan in mice is strongly dose dependent. The maximum growth weight gain of the mice with l -tryptophan was at concentrations of 0. Thus, the maximum growth of the mice when supplied with d -tryptophan was not achieved until its concentration was 2. Adapted using methods described in Friedman and Gumbmann 62 and Friedman and Levin. Using mostly methods of supplementing food proteins with free- d -tryptophan, Baker 63 describes variable outcomes for the utilization of d -tryptophan by different animal species.

In humans, the biological utilization of d -tryptophan in the male infant seems to be low, 66 suggesting the need for further exploration of the nutritional utilization in humans of pure d -tryptophan and of d -tryptophan—containing peptides and food proteins. There is also a need to find out how the biological and nutritional effects of d -tryptophan vary, depending on whether they are consumed in the free state or as part of a peptide or food protein.

Based on persuasive evidence, the authors suggest that fertility drops to below replacement levels owing to a high meat diet and that reducing variance in meat consumption might help stabilize the world population growth, a possible major challenge for future generations.

It is noteworthy that we found that the tryptophan content of minced beef is somewhat lower than in several widely consumed plant foods Table 2. Tryptophan has been implicated in a plethora of diseases and conditions because of its fundamental role as a precursor to many bioactive metabolites, leading to its consideration in the improvement of health and nutrition, and as a diagnostic tool.

The properties of tryptophan and its involvement in metabolic processes make it a suitable candidate for its investigation as a biomarker for diagnosis, examples of which are provided below.

Cataracts remain a global health issue and their sensitive detection is important. Gakamsky et al 72 found using MS and fluorescence steady-state and lifetime spectroscopy that fluorescence of tryptophan and its derivatives in the postsurgical human and porcine lens samples correlates strongly with cataract grade and age, suggesting that the method can be used to diagnose cataracts at the molecular level.

Using a photo-type multispectral imaging system optimized for the macroscopic imaging of tissues, Baner et al 74 found that tryptophan fluorescence of surgical specimens of colonic neoplasms and normal mucosa after resection could be useful in differentiating normal and cancerous cells because there is an increase in emission intensity from cancerous cells.

They also reported that in tissues tryptophan autofluorescence images corrected using green reflectance images might also be useful for displaying neoplasms. Whether this is generally the case with other proteins merits study. Based on an examination of serum-free amino acid and plasma-free amino acid profiles in samples from healthy controls and 56 patients with clear cell renal cell carcinoma, Lee et al 76 discovered that a combination of serum histidine and plasma tryptophan may be a useful biomarker to detect the renal carcinoma.

A study by Teraishi et al 77 showed that the oral administration of 13C-tryptophan to human volunteers having a major depressive disorder and controls correlated negatively with exhaled maximum 13CO 2 levels, suggesting that the 13C-tryptophan breath test could serve as a novel biomarker for detecting a subgroup of patients with altered increased tryptophan-kynurenine metabolism. The use of tryptophan to help combat diseases and conditions has also been extensively investigated in a variety of clinical areas.

Statistical correlations were observed between tryptophan levels and the severity of symptoms in different groups of patients. The authors conclude that the tryptophan level is critical and that intake of B vitamins and magnesium with the diet might influence its metabolic homeostasis.

Murr et al 79 found in a study with patients with coronary artery disease that low serum tryptophan is associated with immune activation and indicates reduced life expectancy. Mangge et al 80 hypothesize that disturbed tryptophan metabolism breakdown triggered by pro-inflammatory cascades in obese individuals seems to be associated with cardiovascular disease. This results in an increased serum kynurenine to tryptophan ratios, which can be measured for a better understanding of cardiovascular disease.

In addition, the depletion of tryptophan limits protein synthesis, including hemoglobin production that may be associated with a likelihood of fatal cardiovascular events through the reduction in oxygen supply causing anemia.

Because the breakdown of tryptophan is accelerated by exercise, the authors suggest that obese individuals should strive for a balance between food consumption and physical activity. It is worth mentioning that we previously suggested that acrylamide, a reactive molecule that is present in numerous processed plant foods that modifies hemoglobin after consumption, could also adversely affect oxygen transport to tissues. The authors conclude that an increase in the plasma tryptophan level was significantly associated with a decreased risk of cardiovascular disease and that the Mediterranean diet consisting of extra-virgin olive oil, nuts, fruits, vegetables, and cereals might counteract the deleterious effect of a high kynurenine risk score.

Schulman 83 describes the molecular events that take place during the inhibition of intestinal absorption of a tryptophan derivative by the drug AST that is expected to slow the progression of the chronic kidney disease in humans. The author mentions a phase 3 trial in progress with about subjects designed to confirm the preliminary data. Because a tryptophan-enriched diet is reported to prevent the age-induced decline of hippocampal serotonin 5-HT production that may contribute to age-related cognitive decline, Musumeci et al 84 further investigated the effect of tryptophan diets on these cellular events and associated multiple biomarkers in rats.

They found that a high tryptophan diet improved passive avoidance impairment of aged rats and partially rescued the age-induced inhibition of transcription factors involved in synaptic plasticity and memory. The authors suggest that the results indicate that enhanced tryptophan intake and the potential increases in 5-HT neurotransmission might help prevent age-related detrimental aspect by inhibiting hippocampal apoptosis. Because excess tryptophan inhibits the 2 enzymes involved in serotonin synthesis, and increased cerebral levels of neuroactive kynurenine, Badawy 85 hypothesizes that moderate use of tryptophan and decreased anxiety associated with exercise could explain behavioral effects of androgenic anabolic steroids associated with tryptophan metabolism.

In a related study, Badawy 86 discusses the utilization and function of tryptophan in pregnancy. Chen et al 88 assessed the possible association of tryptophan with the development of type 2 diabetes in individuals in China, 51 with diabetes and who remained healthy during a year period. They determined tryptophan levels using ultra-performance liquid chromatography triple quadrupole MS and found that a the serum tryptophan level was positively and independently associated with the onset risk of diabetes; b patients with higher tryptophan levels had a higher degree of insulin resistance, secretion of triglycerides, and blood pressure; and c the addition of tryptophan seems to enhance the value of existing acid predictors, suggesting that tryptophan might represent a new biomarker associated with diabetes risk, but this awaits validation in other and larger populations.

In the consideration of diabetes, it is also worth mentioning that Imahori et al 89 isolated 2 known compounds 4-quinlylaldoxime and indolealdehyde and 2 novel compounds formed during the in vitro reaction of tryptophan and glucose at physiological temperature and pH.

One of the novel compounds, indolealdehyde, was mutagenic in the Salmonella Typhimurium assay. Although 4-quinlylaldoxime was detected in rat diabetes extracts, the isolated new compounds were not detected in rat plasma.

The authors suggest that genotoxic amino-carbonyl reaction products may be formed under diabetic conditions that can induce genetic damage to tissues. Strasser et al 90 discuss the bioanalytical procedures for the determination of the concentrations of tryptophan and phenylalanine and their respective first stable intermediates kynurenine and tyrosine. The authors suggest that these immunometabolic parameters, along with other biomarkers, should be monitored in studies of the mechanisms of progression of inflammation-associated with depression and potential therapy.

Nikolaus et al 92 reported that the serum levels of tryptophan were significantly lower in patients with inflammatory bowel disease IBD than in controls, with a stronger reduction in levels in patients with Crohn disease. These observations and a detailed examination of associated biomarkers and metabolites, especially quinolinic acid, show a high activity of tryptophan degradation in patients with IBD, suggesting that tryptophan deficiency could contribute to the development or aggravation of the disease.

Administration of high doses of metabolites nicotinamide, indolealdehyde might modify the microbiome and shunt tryptophan metabolism toward anti-inflammatory pathways. Because the oxidation of tryptophan owing to immune induction of the enzyme indoleamine 2,3 dioxygenase is considered the main cause of tryptophan depletion in patients with HIV, Bipath et al 93 examined plasma tryptophan levels in low-income sub-Saharan HIV-infected patients and 60 HIV-negative controls.

The results show that the plasma tryptophan levels of the South African patients were The decrease in tryptophan levels in patients with HIV from developed countries was much lower, Tryptophan levels correlated with the pro-inflammatory indicators neopterin, interleukin-6, and C-reactive protein. The authors suggest that the most probable causes in the lower tryptophan levels are food insecurity and higher levels of inflammatory activity and that inflammation-induced tryptophan depletion in the patients with HIV forms a much wider effect of pro-inflammatory activity on the nutritional profile of HIV-infected patients.

Will dietary tryptophan supplementation help mitigate the course of the HIV infection? The data also show that the ratio of subjects taking the placebo who experienced upper respiratory tract infections was increased 2.

It seems that catabolism of tryptophan might contribute to the function of the immune system that helps protect against infections. Also worth noting are related studies on the complex mechanistic relationship between tryptophan metabolism, exercise, weight loss, and inflammation-associated depression.

Chacko et al 97 discovered that the greater sensitivity of the human Chlamydia pneumoniae pathogenic microorganism than animal strains to tryptophan availability appears to be an adaptation that reflects the chronic nature of the infection in the human host. The human strain has sensitivity to tryptophan deficiency and can adapt accordingly.

This observation suggests the possibility that tryptophan might help in the treatment of individuals having pneumonia. An investigation of the effect of dietary tryptophan enrichment 0. The authors conclude that the high intake of tryptophan does not seem to affect liver and kidney function or carbohydrate metabolism but was inversely associated with the self-reported level of depression and positively associated with sleep duration.

The results show that consumption of the higher tryptophan cereals increased sleep efficiency and sleep time and improved anxiety and depression symptoms. A review by Steenbergen et al concludes that tryptophan supplementation seems to improve control over social behavior in individuals having disorders associated with dysfunctions in serotogenic functioning, presumably by affecting 5-HT brain levels, whereas it seems to promote social behavior in healthy individuals.

The authors suggest that tryptophan could be a promising tool for modulating social behavior. The nutritionally essential amino acid tryptophan contributes to protein synthesis and the regulation of numerous physiological mechanisms. These include serving as a precursor for the neurotransmitter serotonin and the vitamin niacin. It is therefore important to be able to analyze tryptophan levels accurately and sensitively but unfortunately this is not straightforward; protein-bound tryptophan is degraded in the acid hydrolysis used for analysis of all amino acids.

A number of methods have therefore been developed that can overcome this problem, including the nonhydrolytic acid ninhydrin method that might be preferable over basic hydrolysis by sodium or barium hydroxide as well as the nonhydrolytic NIRS assay, widely used to analyze large numbers of samples from plant breeding and plant engineering programs. When needed, L-tryptophan can also be converted in the body to niacin also called vitamin B3 , a type of essential B vitamin that helps support the metabolism, circulation, a healthy central nervous system and the production of enzymes needed for digestive functioning.

There can be large differences in the actual needs of individuals when it comes to daily tryptophan intake. Research suggests that most healthy adults consume around 3. Dieting, being chronically stressed , consuming too little calories, exercising a lot, and having any form of inflammatory gastrointestinal disorders or liver damage can all lead to less tryptophan being absorbed and therefore a possible deficiency.

However, you might benefit from consuming more if you notice signs of moodiness, irritability, fatigue and trouble sleeping well. According to the University of Michigan Health Department, the dosages below are general guidelines for supplementing with tryptophan based on your goals: A benefit of consuming tryptophan from natural food sources is that this can help with absorption and also offer other benefits, such as providing other essential amino acids and healthy fats.

Research shows that your diet can play a major role in helping you synthesize enough serotonin and controlling your moods, sleep and stress response. Doctors now recommend that the best way to obtain tryptophan from your diet and take advantage of its benefits is to vary the sources of proteins and carbohydrates you eat, since this allows for the most serotonin to be produced overall.

Whole food sources of amino acids like tryptophan can raise serotonin production and also provide needed calories energy that prevent fatigue, low blood sugar levels, cravings and other problems especially if the meal contains both carbs and proteins.

One way to make sure you get enough tryptophan and other amino acids in your diet is to aim for having about 20—30 grams of protein with each meal, varying the types of high protein-foods or snacks you eat since different types offer different levels of amino acids. For the best results and strongest calming effects, combine the protein foods below with a small serving of unrefined carbohydrates like potatoes, veggies, beans or even fruit in order to help tryptophan cross the blood-brain barrier, where it can boost serotonin levels.

Complete protein sources , meaning those that contain all essential and nonessential amino acids, provide tryptophan along with many other essential amino acids, which all compete with one another to cross the blood-brain barrier at the same time. For people struggling with mood disorders, insomnia or addictions, supplementing with 5HTP can be a good way to directly increase serotonin.

Low doses should be taken at first, and you should look for out side effects, including nausea, diarrhea, drowsiness, lightheadedness, headache or dry mouth. Josh Axe is on a mission to provide you and your family with the highest quality nutrition tips and healthy recipes in the world What Is Tryptophan?

Benefits Tryptophan vs. Foods Risks and Side Effects. More Nutrition Dr. Axe on Facebook 1 Dr. Axe on Twitter 22 Dr. Axe on Instagram Dr. Axe on Google Plus Dr. Eating garlic provides many health benefits, including improved immune function. It can help prevent the common cold and the flu. Health Conditions Discover Plan Connect. What Is Tryptophan? Foods with tryptophan Side effects Health benefits Health risks Common uses Takeaway Tryptophan is an essential amino acid that serves several important purposes, like nitrogen balance in adults and growth in infants.

You can get tryptophan through certain foods or a supplement in powder form. Foods with tryptophan. Side effects of tryptophan.

Health benefits. Health risks. Common uses. Read this next. Medically reviewed by Amy Richter, RD. Medically reviewed by Natalie Butler, R.

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