Tryptophan

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

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]

continuation in next column

Tryptofan

Consequences of inadequate supply of tryptophan in the diet

Sleep Disorders

Tryptophan has been researched for sleep disorders for 30 years. Improvement of sleep normalcy has been noted³⁸ at doses as low as 1,000 mg.¹⁹ Increased stage 4 sleep has been noted at even lower doses – as low as 250 mg tryptophan. ¹⁹ Significant improvement in obstructive sleep apnea, but not central sleep apnea, has been noted at doses of 2,500 mg at bedtime, with those experiencing the most severe apnea demonstrating the best response.³⁹ While many sedative medications have opioid-like effects, L-tryptophan administration does not limit cognitive performance or inhibit arousal from sleep.⁴⁰

L-tryptophan depletion negatively impacts sleep. A significant decrease in serum tryptophan levels after a tryptophan-free amino acid drink was associated with an adverse effect upon sleep parameters (stage 1 and stage 2 time, and rapid eye movement sleep time).⁹ L-tryptophan is not associated with tolerance or difficulty with morning wakening and has been shown to be efficacious for sleep in several clinical trials of various designs and L-tryptophan dosages.

Mood deterioration

As previously mentioned, L-tryptophan is essential for the brain to synthesize serotonin, a neurotransmitter that has been shown to affect mood. Several studies have shown that acute tryptophan depletion can cause a depressive state in humans, especially patients who are in remission from depression.^41,42 In a study of the effects of acute tryptophan depletion on healthy women and patients with bulimia nervosa, both groups were given amino acid mixtures to consume to decrease their plasma tryptophan levels. In both groups an increase in depression occurred.⁴³

Plasma L-tryptophan levels can be raised through dietary intake of L-tryptophan, which raises serotonin levels in the brain, and thereby lessens the depressive state.44 In a study involving recovering alcoholic patients, it was found that the participants had severely depleted L-tryptophan levels accompanied by a high level of depressive state. When the patients were given supplemental doses of L-tryptophan over a short period of time, their depressive state lessened significantly.⁴⁵ The tryptophan metabolite, 5-hydroxytryptophan (5-HTP), has shown significant clinical response for depression in 2-4 weeks, at doses of 50-300 mg three times daily.^46-48

Premenstrual Syndrome

A daily dose of 6,000 mg of L-tryptophan significantly decreased mood swings, tension, and irritability in women with premenstrual syndrome.⁴⁹ The metabolism of tryptophan is impacted by the different phases of a woman’s cycle,⁵⁰ and therefore hormonal changes during the menstrual cycle may negatively affect the availability of tryptophan for conversion into serotonin.

Carbohydrate Cravings and Weight Gain

Some obese people consume carbohydrate-rich foods frequently and preferentially, because they have a persistently low plasma tryptophan ratio, as well as low tryptophan uptake into the brain.⁵¹ Remember that serotonin levels are enhanced by carbohydrate ingestion as insulin release accelerates the serum removal of other amino acids that compete for transport through the blood-brain barrier.

Increasing the L-tryptophan levels in blood plasma is also known to have an appetite-suppressing effect that mainly impacts carbohydrate consumption.^52,53 Presumably the supplemental tryptophan would enhance the release of serotonin from brain neurons to diminish appetite for carbohydrates, which helps with loss of body weight. In addition, obese subjects are often insulin-resistant, and diminished insulin action may cause low plasma tryptophan ratios³³ because of the peripheral effects of insulin on the uptake and utilization of other amino acids.

A study was done to measure L-tryptophan in the blood plasma of obese patients to assess the plasma tryptophan ratio to large neutral amino acids (tyrosine + phenylalanine + leucine + isoleucine + valine). The results showed the plasma tryptophan ratio was well below the normal ratio for humans.⁵¹ If elevation of the tryptophan in relation to large neutral amino acids occurs, more tryptophan is allowed into the brain to induce serotonin synthesis and influence functions of serotonin (mood, appetite, sleep, and hunger). This study helps show why obese people often have uncontrollable appetites, i.e., they have too little tryptophan in relation to other large neutral amino acids in their blood.

When these obese patients were given 1,000 mg, 2,000 mg, or 3,000 mg doses of L-tryptophan one hour before meals to raise the amount of tryptophan relative to the large neutral amino acids, a significant decrease in caloric consumption was observed. The majority of the reduction in caloric intake was due to the amount of carbohydrates, not protein, consumed. The only side effects observed were a mild decrease in mental alertness, mild dizziness, and mild drowsiness.⁵⁴

In a double-blind, placebo-controlled study, obese patients on protein-rich diets who received tryptophan (750 mg twice daily orally) had significant weight loss, compared with a placebo group. A moderate dose of tryptophan supplementation did not cause any side effects such as mid-day sleepiness or fatigue.⁵⁵ The effects of reducing tryptophan levels were also studied in a 7-year-old girl with severe anorexia. When tryptophan levels were reduced, spontaneous eating occurred for the first time in 4.5 years. The spontaneous eating ceased when the tryptophan intake was increased.⁵⁶

Tryptophan is present in all high protein food stuff.

Poultry

Turkey may well be the most well known dietary source of L-tryptophan, but all animal proteins contain some of the amino acid. A 4-ounce portion of either chicken or turkey breast provides 350 to 390 milligrams of L-triptophan, as well as a dose of the other eight essential amino acids. While red meats contain the amino acid as well, they tend to have a higher saturated fat content than can lead to high cholesterol.

Seafood

According to the George Mateljan Foundation for The World's Healthiest Foods, a not-for-profit organization focused on sharing information on the benefits of healthy eating, shrimp is the most nutrient-dense source of L-tryptophan with 330 milligrams per 4-ounce serving. Fish, such as tuna, halibut, salmon, sardines and cod, and scallops also contain between 250 and 400 milligrams of L-tryptophan per serving.

Diary Products

While dairy contains significantly less L-tryptophan per serving than meats and fish, cheese, milk and yogurt still provide you with a full essential amino acid set along with bone-healthy calcium. A 1-cup serving of reduced fat cow's milk provides 100 milligrams of the amino acid, while 1 cup of low-fat yogurt gives you 60 milligrams.

Nuts and Seeds

Nuts and seeds are a convenient way to supplement your L-tryptophan intake when you're short on time. With the highest dose of the amino acid per serving, pumpkin seeds provide 110 milligrams per one-fourth cup. Sunflower seeds, cashews, almonds and walnuts all contain over 50 milligrams of L-tryptophan per one-fourth cup.

Legumes

Legumes, such as beans, split peas, peanuts and lentils, offer a fiber- and protein-rich source of L-tryptophan. Kidney beans, black beans and split peas each contain 180 milligrams per cup, while one-fourth cup of peanuts contains 90 milligrams. In addition to the actual L-tryptophan content, legumes also contain B vitamins and iron, both necessary for the body to transform the amino acid into niacin.