Diet & Fitness

Other amino acids may be beneficial in reducing pain. Animal research has shown that the brain chemical serotonin is involved in pain perception,² and some,^3,4 though not all,⁵ preliminary human studies have reported reduced pain sensitivity when people took 2.0 to 2.75 grams per day of L-tryptophan, a precursor of serotonin. In a double-blind study, patients recovering from gallbladder surgery reported less pain when they were given L-tryptophan intravenously in the amount of 7.5 to 15 mg per 2.2 pounds body weight.⁶ Double-blind research has also shown that oral L-tryptophan can increase tolerance to acute pain when taken in amounts of at least 2 grams per day.^7,8 Two double-blind trials found that 3 to 4 grams per day of L-tryptophan along with a low-protein, high-carbohydrate diet reduced pain in people with chronic pain.^9,10 However, one controlled study did not find L-tryptophan (50 mg per 2.2 pounds of body weight per day) helpful for people with chronic pain around the temporomandibular joint.¹¹ No research has been published investigating the pain control potential of 5-HTP (5-hydroxytryptophan), another serotonin precursor.

Interest in the effects of serotonin on the mechanisms of migraine has led to therapeutic trials using serotonin precursors such as L-tryptophan and 5-hydroxytryptophan (5-HTP).¹² Preliminary research has found abnormally low levels of serotonin in the brains of people suffering a migraine attack, which was reversed with L-tryptophan supplements.¹³ A small double-blind trial found that four of eight people had fewer and less intense migraines while receiving L-tryptophan (500 mg every six hours).¹⁴ Larger double-blind trials are needed to better evaluate L-tryptophan as a migraine prevention supplement.

In one study, 40 people with recurrent migraines received either 5-HTP (200 mg per day) or methysergide (a drug used to prevent migraines) for 40 days. Both compounds reduced the frequency of migraines by about 50%.¹⁵ Larger amounts of 5-HTP (600 mg per day) were also found to be as effective as medications for reducing migraine headache attacks in adults in two double-blind trials.^16,17 Migraine attacks were reduced in frequency, severity, and duration in 90% of those taking 400 mg per day of 5-HTP in a double-blind placebo-controlled trial,¹⁸ though another trial found no benefit of 5-HTP.¹⁹ In another controlled study, 400 mg per day of DL-5-HTP (another form of 5-HTP, equivalent to 200 mg per day of 5-HTP per day led to reduced consumption of pain-killing drugs and pain scores after one to two months.²⁰ Children who suffered from migraines and had problems sleeping had an improvement in both migraines and sleep disorders after taking 5-HTP in the amount of 20 mg for every 10 pounds of body weight in a controlled trial,²¹ though an earlier study showed 5-HTP had no better effect than placebo for children with migraines.²²

The amino acid, L-tryptophan, a serotonin precursor, taken in amounts of 1 to 4 grams at bedtime, has been used successfully for people with insomnia in many studies,^23,24, including double-blind trials.^25,26,27,28 Some research indicates that people with more severe forms of insomnia may need to take L-tryptophan for several nights before improvement in sleep is noticed.^29,24, One controlled trial found that newborns receiving a bottle feeding in which 420 mg of L-tryptophan per 2.2 lbs of body weight had been added entered quiet sleep sooner and slept for a longer time.³¹ Some preliminary and controlled trials have not found L-tryptophan effective,³² or have found L-tryptophan effective only for people who awaken more frequently at night compared with those who awaken less frequently.³³ Several studies combined L-tryptophan with a carbohydrate-containing meal to improve L-tryptophan uptake into the brain.^26,35 A related compound that occurs naturally in the body, 5-HTP is also converted into serotonin and might, therefore, be helpful for insomnia. In a double-blind study of people without insomnia, supplementation with 5-HTP (200 mg at 9:15 p.m. and 400 mg at 11:15 p.m.) increased rapid-eye-movement (REM) sleep, presumably indicating improved sleep quality.³⁶ In a preliminary study of people with fibromyalgia, supplementing with 100 mg of 5-HTP three times a day improved sleep quality.³⁷ However, additional research is needed to determine whether 5-HTP is safe and effective for people with insomnia.In a preliminary study, 5-HTP was also found to be an effective treatment for "sleep terrors,"³⁸ a common problem in children that causes sudden awakening with persistent fear or terror, screaming, sweating, confusion, and increased heart rate.

Since restless legs syndrome is often accompanied by insomnia, and L-tryptophan has been helpful for promoting sleep,³⁷ one investigator treated two patients having both restless legs syndrome and insomnia with 1 to 2 grams of L-tryptophan at bedtime.³⁸ In both cases restless legs symptoms improved as well as insomnia. Controlled research is needed to confirm these findings.

Preliminary research suggests that imbalances of the neurotransmitter serotonin or its precursor, L-tryptophan, may be associated with PMS.³⁹ In a double-blind trial, women with PMS who took 6 grams per day of L-tryptophan during the second half of their menstrual cycle reported a one-third reduction in the severity of abnormal mood symptoms.⁴⁰ This confirmed the results of an earlier preliminary trial in which 2 grams per day of L-tryptophan taken during the second half of the menstrual cycle reduced depression and other symptoms associated with PMS.⁴¹

 

Serotonin, a hormone that helps regulate food intake and appetite, is synthesized in the brain from the amino acid L-tryptophan. Preliminary data suggest that some people with bulimia have low serotonin levels.⁴² Researchers have reported that bulimic women with experimentally induced tryptophan deficiency tend to eat more and become more irritable compared to healthy women fed the same diet,^43,44 though not all studies have demonstrated these effects.⁴⁵

Weight-loss diets result in lower L-tryptophan and serotonin levels in women,⁴⁶ which could theoretically trigger bingeing and purging in susceptible people. However, the benefits of L-tryptophan supplementation are unclear. One small, double-blind trial reported significant improvement in eating behavior, feelings about eating, and mood among women with bulimia who were given 1 gram of L-tryptophan and 45 mg of vitamin B6 three times per day.⁴⁷ Other double-blind studies using only L-tryptophan have failed to confirm these findings.^48,49 L-tryptophan is available by prescription only; most drug stores do not carry it, but “compounding” pharmacies do. Most cities have at least one compounding pharmacy, which prepares customized prescription medications to meet individual patient’s needs.

 

People with eating disorders who restrict their food intake are at risk for multiple nutrient deficiencies, including protein, calcium, iron, riboflavin, niacin,⁵⁰folic acid,⁵¹vitamin A, vitamin C,⁵² and vitamin B6,⁵³ and essential fatty acids.⁵⁴ A general multivitamin-mineral formula can reduce the detrimental health effects of these deficiencies.

Serotonin, a hormone that helps regulate food intake and appetite, is synthesized in the brain from the amino acid L-tryptophan. Preliminary data suggest that some people with bulimia have low serotonin levels.⁵⁵ Researchers have reported that bulimic women with experimentally induced tryptophan deficiency tend to eat more and become more irritable compared to healthy women fed the same diet,^56,57 though not all studies have demonstrated these effects.⁵⁸

Weight-loss diets result in lower L-tryptophan and serotonin levels in women,⁵⁹ which could theoretically trigger bingeing and purging in susceptible people. However, the benefits of L-tryptophan supplementation are unclear. One small, double-blind trial reported significant improvement in eating behavior, feelings about eating, and mood among women with bulimia who were given 1 gram of L-tryptophan and 45 mg of vitamin B6 three times per day.⁶⁰ Other double-blind studies using only L-tryptophan have failed to confirm these findings.^61,62 L-tryptophan is available by prescription only; most drug stores do not carry it, but “compounding” pharmacies do. Most cities have at least one compounding pharmacy, which prepares customized prescription medications to meet individual patient’s needs.

Preliminary research suggests that imbalances of the neurotransmitter serotonin or its precursor, L-tryptophan, may be associated with PMS.⁶³ In a double-blind trial, women with PMS who took 6 grams per day of L-tryptophan during the second half of their menstrual cycle reported a one-third reduction in the severity of abnormal mood symptoms.⁶⁴ This confirmed the results of an earlier preliminary trial in which 2 grams per day of L-tryptophan taken during the second half of the menstrual cycle reduced depression and other symptoms associated with PMS.⁶⁵

Disruptions in emotional well-being, including depression, have been linked to serotonin imbalances in the brain.⁶⁶ L-Tryptophan is the precursor to serotonin, and low body levels of L-tryptophan are associated with depression symptoms.⁶⁷ Furthermore, L-tryptophan supplements have been shown to increase serotonin levels.⁶⁸  Many uncontrolled studies report that 3 to 6 grams per day of L-tryptophan helps improve mood in depressed people.^69,70 Several controlled trials found that 3 to 6 grams per day of L-tryptophan were equally as effective as antidepressant medications.^71,72 Some,^73,74,75 though not all,^76,72 double blind studies reported that similar amounts of L-tryptophan were superior to a placebo for improving depression symptoms. Trials using amounts above 6 grams per day of L-tryptophan have often found no benefit for depression, suggesting that 3 to 6 grams per day is optimum.⁷⁸ 5-Hydroxytryptophan (5-HTP), a breakdown product of L-tryptophan and a serotonin precursor, has also been studied as a treatment for depression. Some trials using 200 to 300 mg per day of 5-HTP with people suffering from depression have shown signs of efficacy.^{79,80,81,82,83,84} However, much of the research was either uncontrolled or used 5-HTP in combination with antidepressant drugs. Depressed people interested in considering 5-HTP should consult a doctor.

Since disturbances of serotonin metabolism may be part of the cause of SAD,⁸⁴ and creating a deficiency of L-tryptophan, a precursor of serotonin, worsens symptoms of SAD,⁸⁵ L-tryptophan supplementation might be helpful. One case report describes a patient with SAD who improved after taking L-tryptophan daily, 1 gram with dinner and 1 gram at bedtime.⁸⁶ In a small, preliminary study, people with SAD who responded poorly or not at all to bright light therapy were given 3 grams per day of L-tryptophan for two weeks, in addition to light therapy. Nine of 14 people responded well to this combination.⁸⁷ Another small preliminary study found that one of five SAD patients that did not respond to light therapy did improve after L-tryptophan supplementation in the amount of 4 grams per day, increased to 6 grams per day if no improvement occurred at the lower dose.⁸⁸ A small controlled trial found that a combination of 1.5 grams of L-tryptophan, 50 mg of vitamin B6, 300 mg vitamin C, and eight ounces of fruit juice, taken three times daily, was more effective for reducing symptoms of SAD than the same combination without L-tryptophan.⁸⁹5-HTP (5-hydroxytryptophan) is a substance related to L-tryptophan that also increases serotonin production and has shown antidepressant activity.⁹⁰ It may also be useful in the treatment of SAD, but there is currently no research testing this possibility.

Animal research suggests that the brain chemical serotonin is involved in the mechanisms underlying anxiety,⁹¹ and double-blind studies have reported that creating deficiencies of L-tryptophan, a precursor of serotonin, worsens symptoms in people with anxiety disorders.^92,93 A small double-blind trial tested a food bar containing 250 mg of L-tryptophan plus carbohydrate compared with a placebo bar containing only carbohydrate in a people diagnosed with social anxiety disorder.⁹⁴ The bars were consumed one hour before doing a task designed to provoke anxiety, and anxiety was measured with two tests of heart rate changes and by ratings of anxiety by the participants. Only one of the two heart rate measures showed the L-tryptophan bar was more effective, and only slightly lower anxiety was reported when L-tryptophan was consumed.⁹⁴ A double blind study in China reported that 3 grams per day of L-tryptophan improved symptoms, including anxiety, in a group of people diagnosed with “neurosis.”⁹⁶ More research is needed to evaluate L-tryptophan as a treatment for anxiety disorders.

Tryptophan is the amino acid precursor to serotonin, a neurotransmitter with a critical role in mood, appetite, and metabolic regulation.⁹⁶ High serotonin levels in the brain are associated with a sense of fullness, while low levels are linked to hunger.⁹⁷ Unfortunately, low-calorie diets trigger decreased serotonin signaling, deterioration of mood, increased hunger and cravings, and higher likelihood of weight regain.⁹⁸ A study that included ten healthy normal-weight men found 2- and 3-gram doses of tryptophan reduced calorie intake compared to placebo when taken before a buffet-style meal,⁹⁹ and in a controlled trial, increasing doses of L-tryptophan from 1 gram to 2 grams to three grams before meals resulted in progressively fewer calories and carbohydrates being consumed during the meal.¹⁰⁰ In a crossover trial with eight participants who had chronic obesity and food cravings, taking 1 gram of L-tryptophan before each meal as part of a six-week weight loss program led to greater weight loss than placebo, but the difference was not statistically significant, partly due to the small size of the trial.¹⁰¹

Imbalances in the brain chemical serotonin, or low blood levels of its precursor, L-tryptophan, have been associated with ADHD in some,¹⁰² though not all,¹⁰³ studies.^104,105 Preliminary human studies report that creating deficiencies in L-tryptophan worsens some symptoms of ADHD. A small double blind trial found that giving children with ADHD a daily supplement of 100 mg L-tryptophan per 2.2 pounds body weight per day for one week improved behavior according to parents’ ratings, but not teachers’ ratings.¹⁰⁶ More studies are needed to better evaluate L-tryptophan as a treatment for ADHD.

The brain chemical serotonin may play a role in blood pressure regulation, and animal research suggests L-tryptophan, a precursor of serotonin, might be helpful in the prevention and treatment of hypertension.¹⁰⁷ A preliminary study in 14 subjects with hypertension found 3 to 4 grams per day of L-tryptophan had an immediate blood pressure-lowering effect.¹⁰⁸ However, because long-term use of L-tryptophan may alter serotonin metabolism, it is unclear whether it would be effective for preventing or treating high blood pressure.¹⁰⁷ Another pilot trial reported blood pressure reductions in eight of nine volunteers with mild to moderate high blood pressure treated with 4 grams of tryptophan daily and five of eight similar subjects treated with 800 mg of 5-hydroxytryptophan (a breakdown product of tryptophan and a direct precursor of serotonin) per day.¹¹⁰

Metabolism of the amino acid L-tryptophan may be abnormal in schizophrenia,¹¹⁰ and initially low blood levels of L-tryptophan rise when symptoms of schizophrenia improve but remain low in cases of poor recovery.¹¹¹ L-tryptophan supplementation has occasionally been helpful for specific symptoms associated with schizophrenia. A small double-blind trial found that 4 to 8 grams per day of L-tryptophan reduced aggressive symptoms.¹¹² Another double-blind trial found 1 gram per day of L-tryptophan improved memory function in schizophrenics.¹¹³ Schizoaffective disorder has features of both schizophrenia and mood disorders. A preliminary study reported that 8 grams per day of L-tryptophan improved mood symptoms in a group of patients with schizoaffective disorder, and a small, double-blind trial found that adding 9 grams per day of L-tryptophan to drug therapy was more effective for stabilizing mood in schizoaffective disorder than drug therapy plus a placebo.¹¹⁴ In contrast, other symptoms of schizophrenia have not responded to L-tryptophan in amounts from 1 to 20 grams per day, according to double-blind studies.^113,116 In fact, a small preliminary study reported that schizophrenic patients on a low-tryptophan diet had improved scores on certain tests of brain function and also had small improvements in psychotic symptoms.¹¹⁷

L-tryptophan is the amino acid used by the body to produce serotonin, a chemical messenger important for proper brain function. Supplementation with L-tryptophan has led to improvement in depression in many studies,^117,118 but information is limited about its effect on bipolar disorder. Case reports on two bipolar patients treated with lithium or an antidepressant drug described marked improvements when they were given 12 grams daily of L-tryptophan.^119,120 Two trials using 6 grams of L-tryptophan daily for acute mania in patients with bipolar disorder found little or no improvement,^121,122 but another double-blind, controlled study using 9.6 grams daily reported better results.¹²³ L-tryptophan is converted to 5-HTP (5-hydroxytryptophan) before it becomes serotonin in the body. In a controlled trial, 200 mg daily of supplemental 5-HTP had antidepressant effects in bipolar patients, though it was not as effective as lithium.¹²⁴ In a double-blind trial, patients with bipolar disorder had greater improvement with a combination of 5-HTP at 300 mg daily plus an antidepressant drug than with 5-HTP alone.¹²⁵

Animal research suggests that the brain chemical serotonin is involved in the mechanisms underlying anxiety,¹²⁶ and double-blind studies have reported that creating deficiencies of L-tryptophan, a precursor of serotonin, worsens symptoms in people with anxiety disorders.^127,128 A small double-blind trial tested a food bar containing 250 mg of L-tryptophan plus carbohydrate compared with a placebo bar containing only carbohydrate in a people diagnosed with social anxiety disorder.¹²⁹ The bars were consumed one hour before doing a task designed to provoke anxiety, and anxiety was measured with two tests of heart rate changes and by ratings of anxiety by the participants. Only one of the two heart rate measures showed the L-tryptophan bar was more effective, and only slightly lower anxiety was reported when L-tryptophan was consumed.¹²⁹ A double blind study in China reported that 3 grams per day of L-tryptophan improved symptoms, including anxiety, in a group of people diagnosed with “neurosis.”¹³¹ More research is needed to evaluate L-tryptophan as a treatment for anxiety disorders.