Tryptophan

Tryptophan is a nutrient belonging to the essential amino acid class.

Tryptophan is known as L-Tryptophan, L-Triptofano, L-Trypt, L-2-amino-3-(indole-3-yl) propionic acid, L-Tryptophane.

Tryptophan is necessary for vital bodily processes such as the production of serotonin and melatonin, regulating mood, sleep, and appetite, supporting cognitive function, and maintaining overall mental and emotional well-being.

Tryptophan deficiency can cause symptoms, which include mood swings, insomnia, low serotonin, depression, anxiety, and decreased cognitive ability.

Tryptophan may be found naturally in various meals that are high in protein from both plant and animal sources. Foods like peanuts, soybeans, sunflower seeds, sesame seeds and pumpkin seeds are examples of plant sources, whereas products like meat( chicken and turkey), fish, egg whites, and dairy (milk and cheese) are examples of animal sources.

In the small intestine, Tryptophan is absorbed and transported to many organs, including the brain. It serves as a precursor for neurotransmitters like histamine. Decarboxylation occurs throughout metabolism, and excess Tryptophan is eliminated through the urea cycle at the influence of genetics and nutrition.

The common side effects of Tryptophan include GI disturbances, drowsiness, stomach pain, vomiting, diarrhoea, headache and blurry vision.

Tryptophan is available in tablets, capsules and oral powders.

Biochemical action of Tryptophan

Tryptophan belonging to the essential amino acid class, acts in several biochemical processes. It works via the kynurenine pathway.

Tryptophan is a necessary amino acid that the body serves as a precursor for several neurotransmitters and hormones. It is mainly metabolised via the kynurenine pathway, where serotonin can be generated and further processed to produce melatonin or other byproducts.

The brain's 5-HT1A and 5-HT2A receptors are two primary receptors of the many receptors that serotonin acts on after being converted from Tryptophan to serotonin by the enzyme tryptophan hydroxylase. Further, serotonin may be converted into the hormone melatonin, which regulates the sleep-wake cycle. Serotonin-N-acetyltransferase (SNAT) facilitates this conversion, which activates melatonin receptors in the pineal gland.

Also, the control of appetite and food intake is enhanced by Tryptophan. It contributes to the production of the hormone ghrelin, which increases hunger and is essential for controlling appetite. Ghrelin promotes the feeling of hunger and increases food intake by activating its receptor, the growth hormone secretagogue receptor (GHSR).

Thus, Tryptophan's biological activity is its conversion into serotonin and melatonin, influencing mood, behaviour, sleep, and appetite control. These neurotransmitters and hormones' actions are mediated by several receptors, including 5-HT1A, 5-HT2A, melatonin receptors, and GHSR, contributing to overall physiological and psychological well-being.

Tryptophan is available in tablets, capsules and oral powders.

• Tablets: To be swallowed whole with water/liquid, as applicable.
• Capsules: To be swallowed whole with water/liquid, as applicable.
• Powders, oral: Powders must be mixed thoroughly with the appropriate amount of liquid and stirred well to dissolve the powder, as applicable.

When the intake of Tryptophan through diet is inadequate, tryptophan supplements might be used.

Supplementing with Tryptophan may increase the efficacy of traditional smoking cessation therapy.

Supplemental Tryptophan could help treat seasonal affective disorder and reduce mood fluctuations, stress, and irritation in PMDD-affected women.

Supplemental Tryptophan may be used to decrease carbohydrate cravings and enhance sleep quality, and REM sleep.

Individuals with insomnia might benefit from taking tryptophan supplements.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Tryptophan can help to support as a supplement for the following health benefits:

• Healthy sleep: One of the main objectives of taking Tryptophan for improved sleep is to increase melatonin levels. The sleep hormone ' melatonin' is stimulated by the conversion of Tryptophan to serotonin, which then undergoes a transformation into melatonin in the pineal gland as a result of day-night cycles. Tryptophan supplements of any amount can improve the quality of sleep. One gram of Tryptophan significantly increased the time spent sleeping in a 1979 research. Deep sleep was benefited by even 250 mg. Tryptophan may also help with sleep apnea symptoms. 2.5 grams taken before bedtime in patients with obstructive sleep apnea improved breathing, prolonged REM phase, and decreased REM latency, but not in patients with central sleep apnea.
• Mood: Researchers thoroughly examined the impact of Tryptophan and serotonin on perception and mood in the journal "Nutrients" in 2016. There are several studies that show tryptophan insufficiency impacts mood, especially in people with a history of depression or anxiety. Serotonin, a neurotransmitter linked to mood modulation, is derived from the amino acid tryptophan. Tryptophan supplementation boosts happy emotions and lessens the signs of sadness or poor mood.
• Anxiety: Serotonin, which is derived from Tryptophan, helps in the management of stress. Supplements containing Tryptophan may help reduce anxiety and encourage calmness. An investigation on the effects of Tryptophan on depression was conducted in 2016, and potential links between altered tryptophan metabolism, neurotoxic production, and depression were found. Dietary shortages, inflammation, and stress hormones might bring on this change. Combining Tryptophan with a superior multivitamin or specialised nutritional combination is essential to maximising its benefits.
• Appetite: Tryptophan has a role in controlling appetite and feeling fuller. By affecting serotonin levels, utilising tryptophan supplements may help control food cravings and overeating.
• Fibromyalgia: According to some research, tryptophan supplementation may reduce pain perception and affect serotonin levels, which may help with the symptoms of fibromyalgia, a chronic pain disease. However, more research is needed to understand its potential benefits for individuals with fibromyalgia fully.
• Cognitive: Serotonin can affect memory and cognitive function, and Tryptophan is necessary for its production. Although there is still much to learn about the relationship between serotonin, Tryptophan, and cognition, tryptophan supplementation may help people concentrate and perform cognitively better.

Tryptophan supplementation may be administered orally.

Orally: Tryptophan supplements are available as tablets, capsules and powders that can be taken orally. It is advised to take the supplement at night, preferably an hour before bed or on an empty stomach 30 minutes before eating or two hours after.

Taking tryptophan supplements before sleep may promote relaxation and improve sleep quality for some individuals.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets: 500 mg, 1000 mg
• Capsules: 400mg, 500mg
• Powder, oral: 1.77 oz (50 mg), 2 oz (57 mg)

Dosage Adjustment for Adult Patients

Depression

8-12 g/d PO divided QID/TID

Tryptophan is available in tablets, capsules and oral powders.

Tryptophan should be a supplement that helps in several biological processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.

• Stay within your daily calorie needs.

• Keep away from high-protein meals and beverages, especially those that include other amino acids, since these may hinder the absorption of Tryptophan.

• When using tryptophan supplements, limit or avoid meals high in protein, such as meat, beans, and nuts, since this may reduce the absorption as well as potential advantages of the supplement.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of Tryptophan is 4 mg/kg body weight per day.

Upper Tolerable Intake (UTL):

The UTL of Tryptophan is not established.

Tryptophan supplementation may be contraindicated in the following conditions:

• Hypersensitivity: sensitive to Tryptophan.
• Chronic liver disease
• Chronic kidney disease (CKD)
• Kidney failure
• Achlorhydria
• Bladder cancer
• Cataracts
• Diabetes mellitus
• Female infertility
• Psoriasis
• Individuals who are on antidepressant medications.

High-dose supplements should be used cautiously in pregnancy and the elderly.

Before taking Tryptophan, individuals with renal or liver disorders should see a physician since the dosage may need to be adjusted in order to prevent adverse effects.

It is recommended to use tryptophan supplements cautiously since prolonged usage may result in adverse reactions or allergies.

In case of any underlying health conditions like white blood cell disorder called eosinophilia, it is recommended to use this drug cautiously as it is associated with the development of eosinophilia-myalgia syndrome (EMS).

To avoid potential interactions, it is recommended to use only one amino acid supplement or dietary supplements.

Theres is no sufficient scientific evidence traceable regarding the use and safety of Tryptophan for this specific population.

There is no sufficient scientific evidence traceable regarding the use and safety of Tryptophan for this specific population.

Limit the consumption of foods and beverages limit or avoid meals high in protein, such as meat, beans, and nuts, since this may reduce the absorption as well as potential advantages of the supplement.

The adverse reactions related to Tryptophan can be categorised as:

• Common: Gastrointestinal discomfort, anorexia, nausea, and mild dizziness
• Less Common: Headache, dry mouth, sexual dysfunction and altered taste perception.
• Rare: Serotonin syndrome, such as agitation, rapid heart rate, and confusion.

The clinically relevant drug interactions of Tryptophan are summarized here:

• CNS depressants: Tryptophan can cause sleepiness and reduce the rate of breathing. Sedatives are a class of drugs that can also cause tiredness and reduce breathing rate. Combining L-tryptophan with sedative drugs may result in difficulty breathing and excessive drowsiness
• Serotonergic drugs: Serotonin is a brain molecule that L-tryptophan may enhance. This effect is also seen in several drugs. Combining L-tryptophan with specific drugs may result in an excessive rise in serotonin. Serious adverse effects, including cardiac issues, seizures, and vomiting, might result from this.
• Lithium: By providing a lower lithium dosage, tryptophan administration may improve the therapeutic effectiveness of lithium and enable fewer side effects- thus beneficial when used together.
• Allopurinol: L-tryptophan and allopurinol co-administration may help treat depression, particularly in situations when other treatments have failed- thus beneficial when used together.

• Clorazepate: When used together, may have potential competition between drugs and Tryptophan may interfere with drug activity. It is advised to use these doses separately.
• Tramadol: The brain chemical serotonin is susceptible to the effects of tramadol. L-tryptophan can also have an impact on serotonin. If L-tryptophan and tramadol are used together, there may be excessive serotonin in the brain and consequent adverse effects such as disorientation, shivering, and muscle spasms.

The common side of Tryptophan includes the following:

• Drowsiness
• Stomach pain
• Vomiting
• Diarrhea
• Headache
• Blurry vision
• Heartburn
• Belching
• nausea
• Loss of appetite
• Sexual dysfunction
• Dry mouth

Tryptophan should be prudent in the following group of special populations.

• Pregnancy:

Pregnancy Category: C Safe during pregnancy, but when taken in high doses, use with caution if the benefits outweigh the risks.

Animal studies have shown that 8g/day can be teratogenic.

It is advised to avoid tryptophan supplements unless it is recommended by a healthcare professional while pregnant.

• Paediatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of Tryptophan for paediatric populations.

Dosage Adjustment for Paediatric Patients

There are no specific dosage adjustments provided.

• Geriatrics:

Geriatrics who use tryptophan supplements may have better mood, sleep, and eating control. To ensure safe and efficient usage, however, taking into account specific medical needs and prescriptions, consultation with healthcare professionals is necessary. Human studies have shown that 7g/150 lb of body weight in the elderly might cause nausea, vomiting, and head twitching.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of Tryptophan for lactating mothers populations. Avoid tryptophan supplements unless advised by a healthcare professional while lactating.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Tryptophan. Overconsumption of Tryptophan can result in a condition known as serotonin syndrome, a disorder characterised by symptoms including agitation, disorientation, tachycardia, elevated blood pressure, dilated pupils, and, in severe cases, muscular rigidity and seizures.

There is no specific antidote or treatment for excessive intake of supplemental Tryptophan. Tryptophan supplements should be terminated immediately when an overdose is suspected or experience any unusual symptoms after tryptophan supplement use or dietary intake. Fluid intake should be increased along with electrolyte monitoring. Induce vomit, gastric lavage, or activated charcoal may also be used if ingestion is recent but only under the supervision of a medical professional. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of Tryptophan

Tryptophans consist of a heterocyclic indole ring attached to a side chain. It is an essential amino acid with a wide range of metabolic actions because it has an amino group, a carboxyl group, and an indole ring structure.

The production of essential biomolecules such as serotonin, melatonin, and niacin (vitamin B3) starts with the synthesis of Tryptophan. Tryptophan is a dietary source of 5-hydroxytryptophan (5-HTP), produced by the enzyme tryptophan hydroxylase. Serotonin, a neurotransmitter that controls mood, sleep, and hunger, is subsequently generated from 5-HTP.

Melatonin, a hormone that regulates the sleep-wake cycle, is subsequently produced through the metabolism of serotonin. Additionally, Tryptophan may be used in the kynurenine pathway, which produces niacin, an essential compound for cellular and energy metabolism. Due to its incorporation into elongating polypeptide chains during translation, Tryptophan also contributes to the synthesis of proteins. The availability of this amino acid for protein synthesis might be limited by its relative deficit in the diet compared to other amino acids.

Additionally, Tryptophan can affect intestinal health and has immune-modulating properties.

Kinetic profile:

• Absorption: Tryptophan is absorbed by active transport via the intestinal epithelial cells and competes with other amino acids for absorption.
• Distribution: Tryptophan absorbs into the body and then distributed to various tissues via the bloodstream. Some tryptophan reaches the brain through the blood-brain barrier to be used to produce serotonin.
• Metabolism: Tryptophan is metabolised mainly by two pathways: the kynurenine pathway, which results in the production of niacin, and the serotonin pathway, which results in the production of serotonin. Tryptophan dioxygenase initiates the kynurenine pathway.
• Elimination: The liver continues metabolising Tryptophan and its byproducts, which are mainly eliminated through the urine. Kynurenine and its derivatives, which are eventually excreted, can be produced during the metabolism of excess Tryptophan.

1. https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf
2. https://www.ndhealthfacts.org/wiki/Tryptophan
3. https://www.vitaminexpress.org/en/tryptophan-information

4. Friedman, Mendel. “Analysis, Nutrition, and Health Benefits of Tryptophan.” International journal of tryptophan research : IJTR vol. 11 1178646918802282. 26 Sep. 2018, doi:10.1177/1178646918802282