Tryptophan, an essential amino acid, plays a crucial role in various bodily functions, including the production of serotonin and melatonin. This article explores the multifaceted benefits of tryptophan, with a particular focus on its potential role in weight management and metabolic health.
Understanding Tryptophan
Tryptophan is an essential amino acid, meaning the body cannot produce it and it must be obtained through diet. It serves as the sole precursor to serotonin, a neurotransmitter vital for regulating mood, sleep, appetite, and other functions. After absorbing L-tryptophan from food, the body converts some of it to 5-HTP and then to serotonin. The body also converts some tryptophan to nicotinamide adenine dinucleotide (NAD), which is why tryptophan is also considered a dietary source of niacin.
Foods rich in tryptophan include animal products like chicken, turkey, fish, eggs, cheese, and milk, as well as plant-based sources like nuts, soy, pumpkin seeds, sesame seeds, and tofu.
Tryptophan and Metabolic Syndrome
Metabolic syndrome (MetSyn) is a cluster of conditions that increase the risk of heart disease, stroke, and type 2 diabetes. Rapidly accumulating evidence suggests the involvement of the brain’s serotonergic system in MetSyn, according to its influences on many behaviors (eg eating, sleep, and stress responses), as well as autonomic functions (eg thermogenesis, cardiovascular control, circadian rhythms, and pancreatic function). Previous research has linked dietary tryptophan with some component features of MetSyn, such as blood pressure and triglycerides.
A study using longitudinal data from the China Health and Nutrition Survey (CHNS) aimed to estimate the association between dietary tryptophan and the incidence of MetSyn, as well as to determine whether sleep duration partially mediates this association, through mediation analysis. The study, conducted in accordance with the Declaration of Helsinki, was organized by the Carolina Population Center at the University of North Carolina at Chapel Hill and the National Institute for Nutrition and Health (former National Institute of Nutrition and Food Safety) at the Chinese Center for Disease Control and Prevention (CCDC).
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The CHNS is a longitudinal household survey designed to investigate health and nutritional status in Chinese populations, and to reflect the effects of social, economic, and demographic transformations in China on health and nutritional status. The study used a multistage random-cluster sampling process to select participants from nine provinces varying according to geography, economic development, and health indicators, and involved eight surveys from 1991 to 2011.
Study Findings on Tryptophan and MetSyn
The study identified 1290 MetSyn cases in the CHNS cohort from 1997 to 2011. The results indicated that a higher intake of tryptophan was inversely associated with the risk of MetSyn. After controlling for various factors such as sex, age, BMI, WHR, living site, smoking status, drinking status, physical activity, urban index, cardiovascular disease, AHEI, SFA, fiber, sugar, fruit, vegetable, and energy intake, those with the highest intake of tryptophan had a significantly lower risk of MetSyn.
The study also found that dietary tryptophan was positively associated with sleep duration and negatively associated with FPG, HbA1c, TC, LDL-C, and APO-B. Sleep duration partially mediated the association between tryptophan and MetSyn.
Tryptophan and Weight Management
Tryptophan's influence on serotonin production has implications for weight management. Serotonin plays a crucial role in regulating appetite and metabolism. High serotonin levels in the brain are associated with a sense of fullness, while low levels are linked to hunger.
Tryptophan's Impact on Appetite and Calorie Intake
Research suggests that tryptophan consumption may regulate the basic components of MetSyn, such as weight gain, glucose metabolism, blood pressure, and lipids.
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A study including healthy, normal-weight men found that 2- and 3-gram doses of tryptophan reduced calorie intake compared to a placebo when taken before a buffet-style meal. A controlled trial revealed that increasing doses of L-tryptophan before meals resulted in progressively fewer calories and carbohydrates being consumed during the meal.
The Role of Serotonin in Satiety
The brain chemical serotonin is involved in pain perception, and some, though not all, 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.
Animal studies have revealed potential mechanisms for these effects. Dietary tryptophan could reduce food intake and was then translated into a decrease in weight, which came from the effect of brain serotonin on satiety.
Tryptophan and Sleep
Numerous studies have reported that dietary tryptophan is related to sleep and that sleep can exert effects on MetSyn risk.
The CHNS study found that participants in the highest tertile of cumulative intake of dietary tryptophan had longer sleep duration compared to those in the lowest tertile.
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The Link Between Sleep and Metabolic Health
Sleep can exert effects on MetSyn risk. A mediation analysis model was constructed to examine whether the association between tryptophan intake and risk of MetSyn was mediated by sleep time after adjusting for covariates.
Tryptophan Supplementation
Tryptophan can also be obtained through supplementation, such as 5HTP, or L-tryptophan, in capsule form. While tryptophan consumed through food is typically safe, some people experience adverse effects from the supplement form.
L-tryptophan supplements are possibly safe when taken for up to 3 weeks. L-tryptophan can cause some side effects such as drowsiness, stomach pain, vomiting, diarrhea, headache, blurry vision, and others.
Considerations for Supplement Use
According to the National Organization for Rare Disorders, tryptophan supplements were linked to over 1,500 reports of eosinophilia-myalgia syndrome (EMS) and 37 deaths in an epidemic in the late 1980s. However, the EMS cases were traced back to a manufacturer whose tryptophan supplements were tainted. Because of this, the medical problems were likely due to contamination of the supplements rather than tryptophan itself.
As it’s best to err on the side of caution, avoid taking tryptophan if you’re pregnant, trying to become pregnant, or breastfeeding.
Potential Interactions with Medications
Tryptophan can help treat symptoms of some conditions, but it may raise your serotonin levels too much, especially if combined with medications like tricyclic antidepressants (TCAs), MAO inhibitors (MAOIs), pain relievers like tramadol and meperidinetriptan migraine medications, and cough syrup that contains dextromethorpan.
The increased serotonin from the tryptophan can contradict the purpose of the SSRIs. Several common depression medications fall under this category, including citalopram (Celexa), fluoxetine (Prozac), and sertraline (Zoloft).
Alpha-Methyl-L-Tryptophan (α-MLT)
Alpha-Methyl-L-tryptophan (α-MLT) is currently in use as a tracer in its 11C-labeled form to monitor the health of serotonergic neurons in humans. In a study, this compound was found to function as an effective weight-loss agent at pharmacological doses in multiple models of obesity in mice. The drug was able to reduce the body weight when given orally in drinking water (1 mg/ml) in three different models of obesity: normal mice on high-fat diet, Slc6a14-null mice on high-fat diet, and ob/ob mice on normal diet.
α-MLT and Weight Reduction in Mice
Only the l-enantiomer (α-MLT) was active while the d-enantiomer (α-MDT) had negligible activity. The weight-loss effect was freely reversible, with the weight gain resuming soon after the withdrawal of the drug. All three models of obesity were associated with hyperglycemia, insulin resistance, and hepatic steatosis; α-MLT reversed these features.
There was a decrease in food intake in the treatment group. Mice on a high-fat diet showed decreased cholesterol and protein in the serum when treated with α-MLT; there was however no evidence of liver and kidney dysfunction. Plasma amino acid profile indicated a significant decrease in the levels of specific amino acids, including tryptophan; but the levels of arginine were increased.
Additional Benefits of Tryptophan
Beyond weight management and metabolic health, tryptophan has been studied for its potential benefits in various other areas:
- Insomnia: 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,including double-blind trials.
- Pain Tolerance: Double-blind research has also shown that oral L-tryptophan can increase tolerance to acute pain.
- Premenstrual Syndrome (PMS): 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.
- Depression: Supplementation with L-tryptophan has led to improvement in depression in many studies.
- Obsessive-Compulsive Disorder (OCD): One preliminary human study reported improvement in OCD symptoms when 6 grams per day of L-tryptophan was added to therapy with a serotonin-enhancing drug.
- Schizophrenia: A small double-blind trial found that 4 to 8 grams per day of L-tryptophan reduced aggressive symptoms.
- Seasonal Affective Disorder (SAD): One case report describes a patient with SAD who improved after taking L-tryptophan daily, 1 gram with dinner and 1 gram at bedtime.
- Anxiety: Double-blind studies have reported that creating deficiencies of L-tryptophan, a precursor of serotonin, worsens symptoms in people with anxiety disorders.
- Bulimia: 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.
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