Life Extension Magazine May 2013
Better Brain Chemistry with Tryptophan
By Travis Harding
Aging is often accompanied by a spectrum of mood disorders that include irritability, stress, and anxiety. These symptoms, along with more severe ones like sleep disorders, depression, aggressive behavior, reduced motivation, and suicidal thinking have all been traced to depletion of brain levels of serotonin, a neurotransmitter that has been called the “happiness hormone.”1-3
With the progression of age, chronic, low-grade inflammation sets the stage for degenerative disease in almost every area of the body.4 While this inflammation often leads to diabetes, cancer, and heart disease, it also affects the brain by interfering with the production and release of serotonin.1-3,5
In order for your body to manufacture serotonin, it needs a sufficient supply of the natural amino acid, tryptophan.1 Much of what is now known about the role of serotonin in psychiatric and behavioral disturbances comes from studies of tryptophan depletion.6,7 Lowering tryptophan levels triggers a corresponding drop in brain serotonin production and can impact mood, impair memory, and increase aggression.7
Although you can’t supplement with serotonin itself, tryptophan is readily available as a safe, well-proven supplement.8 Supplementing with tryptophan helps normalize levels of serotonin and other neurotransmitters. As a result, it can reverse many of the behavioral symptoms of age, including irritability, mood disorders, anxiety, and stress.9
Tryptophan Helps Regulate Behavior
The scientific literature is clear: Tryptophan supplementation simply makes people nicer!10 With the close connection between tryptophan and the neurotransmitter serotonin, it shouldn’t be surprising that supplementing with tryptophan can regulate behaviors that involve serotonin signaling in the brain (such as mood, sleep, and anxiety).2,5
Studies in animals reveal marked decreases in territoriality and aggressive behavior when their diets are supplemented with tryptophan.11-13 Humans experience similar results.
For example, in studies of adults who are self-described as “quarrelsome,” 1,000 mg of tryptophan three times a day produced significant increases in measures of agreeableness and agreeable behaviors, and decreases in quarrelsomeness.10,14 Interestingly, men in one study experienced a reduction in dominance, whereas both men and women experienced a decrease in quarrelsome behavior along with an increase in agreeable behavior and their perception of agreeableness in others.14
A study of 10-year-old boys with elevated physical aggressiveness revealed the benefits of a single 500 milligram dose of tryptophan. In the supplemented group, boys were able to adjust their level of response based on the level of provocation, helping them avoid potentially violent encounters.15 The supplemented boys were able to take more mature perspectives and to be more helpful in the group—all behaviors that could be achieved by many older adults as well.
Other studies have demonstrated that low levels of tryptophan can have a negative effect on behavior. Patients receiving interferon therapy against hepatitis C infection, for example, experience decreases in plasma tryptophan levels. As a result, those undergoing this therapy are notoriously likely to experience emotional irritability and severe depression as side effects.16,17 As another example, mice lacking the gene necessary to convert tryptophan to serotonin display extreme compulsive and impulsive behaviors, including intense aggressiveness.18
People with naturally impulsive or aggressive personalities may receive the most benefit from supplementing with tryptophan, based on studies of deliberate tryptophan depletion in such patients. Those people react very poorly to low tryptophan levels, with an exaggerated impression of the intensity of fleeting angry expressions on others’ faces, and an increase in their angry mood state.19 Similar effects of tryptophan depletion are seen in adults with attention deficit-hyperactivity disorder, which is closely associated with aggression and impulsivity.20 Supplementation with tryptophan may offer relief to those patients and their long-suffering families.
Tryptophan Improves Sleep Quality
Poor sleep quality or sleep deprivation is a common cause of irritability and moodiness, especially in older people. Studies show that people who sleep poorly are more likely to consume fats or refined sugars, to eat fewer vegetable portions, and to have more irregular meal patterns.21
The two main biomolecules that are involved in the production of normal sleep—the neurotransmitter serotonin and the hormone melatonin—are both naturally made from tryptophan in the body.22 That makes tryptophan a tremendously valuable supplement for those whose sleep is lacking in either quantity or quality.
Studies dating back to the late 1970s have demonstrated that taking between 1 and 15 grams of tryptophan at bedtime can help you fall sleep.23 Even doses as little as 250 milligrams were found to increase the quality of sleep by lengthening the amount of time spent in the deepest stage of sleep.23
During the 1980s, many additional studies demonstrated the benefits of taking 1,000 mg or more of tryptophan at bedtime. Significant improvements were shown in subjective reports of sleepiness such as a decrease in the time to fall asleep, decreased total wakefulness, and an increase in total sleep time.24-26 These studies showed their most impressive results in people with mild insomnia, or in those with above-average time it takes to fall asleep.27
Those who take tryptophan at bedtime are more likely to wake up with increased alertness, to have clearer thinking, and to perform better on attention-requiring tasks.25,28 Unlike sleeping pill drugs, tryptophan induces sleepiness but does not impair performance or produce dependence, nor does it make it harder to be roused from sleep when necessary.27,29
One study in older adults demonstrated significant improvements in total sleep time, a decrease in the time to fall asleep and sleep fragmentation or periods of broken sleep following a twice-daily serving of tryptophan-enriched cereal providing 60 milligrams of tryptophan per ounce.9 (A ten-ounce serving of this cereal would thus provide 600 mg of tryptophan.)
Tryptophan may also play a positive role in one of the most dangerous sleep-related complications, obstructive sleep apnea. This condition causes repeated episodes of near-awakening that viciously disrupt sleep cycles and places sufferers at greatly increased risk of developing cardiovascular disease in later life.30-32
In one study, patients with obstructive sleep apnea who took 2.5 grams of tryptophan at bedtime showed significant improvement from their baseline sleep patterns, with improvements in the amounts of time spent in “rapid eye movement” (REM) sleep, and shortened time to entering rapid eye movement sleep.33 Decreased rapid eye movement sleep is associated with poor next-day alertness and feelings of fatigue, sometimes resulting in involuntary falling asleep during daytime (narcolepsy).34
Tryptophan Helps Manage Depression
As with sleep disturbances, depression can contribute to irritability, impulsive behavior, and poor judgment.35 For nearly three decades, serotonin has been recognized as the neurotransmitter of central importance in managing depression; virtually all drug therapies in use today aim at raising levels of serotonin at the synapses where nerve cells communicate.
Boosting and balancing brain serotonin through tryptophan supplementation (as opposed to through drug therapy) is an innovative approach to depression that is gaining more and more traction—especially with the discovery that patients with major depression have low levels of tryptophan.36
Studies show that tryptophan compares favorably with prescription antidepressants, either when used alone or in combination with a prescription drug.37,38 Pharmaceutical antidepressants are slow-acting and may cause temporary or prolonged sleep disturbances. However, combining 2 grams/day of tryptophan with the prescription antidepressant fluoxetine (Prozac® and others) may speed the onset of action while limiting sleep disturbances. (See the Caution below)38
Studies show that lowering plasma tryptophan levels induces many of the symptoms of major depression in patients who have depression or are at familial risk for the disorder.39-41
Intriguingly, one of the major manifestations of depression is negative emotional processing, including a tendency to interpret facial expressions in a negative manner (this can reinforce feelings of sadness and hopelessness that are key features of depressive illness).42,43 Tryptophan depletion intensifies this effect, while tryptophan supplementation reverses it, creating a pleasant positive bias instead, a result shared with prescription antidepressants but without their side effects.42,44
In studies of the milder depressive syndrome known as seasonal affective disorder (SAD), or “winter depression,” treatment with bright light (to simulate the longer days of summer) is currently the standard of care. Recent studies, however, demonstrate that tryptophan supplementation is as effective as light therapy, and its effect lasts longer than that of light treatment.45,46
Tryptophan Reduces Anxiety and Stress
Anxiety and stress responses can have a major impact on social functioning. Extreme situations such as post-traumatic stress disorder can be especially debilitating. The natural protective response to stress and anxiety involve the serotonin signaling system, as well as hormone pathways in the brain, pituitary, and adrenal glands.47
The connection between tryptophan and serotonin explains why tryptophan supplementation has been found to help reduce anxiety and alleviate stress. Tryptophan supplementation reduces biochemical markers of stress, particularly the hormone cortisol that has many deleterious effects in the human body.
As further evidence, acute tryptophan depletion in people with anxiety disorder or with post-traumatic stress disorder leads to a temporary worsening of their symptoms.48-50