Tryptophan Intake for Pregnancy

Overseen By Rajavel Elango, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of British Columbia

Disqualifiers: Multiple pregnancy, Metabolic disorder, Substance dependence, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your healthcare provider.

What data supports the effectiveness of the drug Tryptophan for pregnancy?

Research shows that L-tryptophan is important for brain serotonin production, which can affect mood and behavior. However, in pregnant mice, high levels of L-tryptophan reduced fetal growth, suggesting that while it has roles in mood regulation, its effects during pregnancy need careful consideration. ^{1 2 3 4 5}

Is tryptophan safe for use during pregnancy?

Research in animals suggests that high levels of tryptophan intake during pregnancy can lead to reduced fetal growth. However, moderate levels did not show adverse effects in mice, and specific safety data for humans is not available due to ethical constraints. ^{1 2 6 7 8}

How does the drug tryptophan differ from other treatments for pregnancy-related conditions?

Tryptophan is unique because it is a natural amino acid that plays a role in protein synthesis and the production of serotonin, which can affect mood and sleep. Unlike other treatments, tryptophan's role in the kynurenine pathway may help regulate immune tolerance and energy metabolism, which are crucial during pregnancy. ^{1 2 4 9 10}

What is the purpose of this trial?

Pregnancy is an important period of life where there is an increased need for nutrients including protein and amino acids from food. The current protein and amino acids dietary recommendations were all established using older methods done in adult men. Then protein and amino acids requirements for all stages of pregnancy were calculated without accounting for changing demands in each trimester. Therefore, another more precise method is needed to better understand how much amino acids (in this study tryptophan) women need during pregnancy. In the current study, the investigators are going to apply the Indicator Amino Acid Oxidation (IAAO) method to measure the dietary tryptophan needs in a healthy pregnancy. This method is a noninvasive, quick, and reliable technique that uses a stable isotope-labeled amino acid. The stable isotope tracer is a labeled amino acid, which is colorless, odorless, tasteless, and completely safe; they are present in the air, water and food. Amino acids are mostly made of Carbon-12 (12C), whereas the isotope tracer contains Carbon-13 (13C). The tracer can be detected in breath and urine samples with special equipment because it looks different than the rest of the amino acids in the body. In Elango lab, the investigators have done similar studies, using the same technique in children, nonpregnant women and pregnant women. This will allow us to measure tryptophan needs in pregnancy.

Research Team

Rajavel Elango, PhD

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for healthy pregnant women who are interested in contributing to research on nutritional needs during pregnancy. It aims to determine the right amount of tryptophan, an important amino acid, needed at this stage. Specific eligibility criteria were not provided.

Inclusion Criteria

I am a cisgender woman and currently pregnant.

Between 11-20 weeks of gestation or 31-40 weeks of gestation

I don't have long-term illnesses and can move around freely.

Exclusion Criteria

I am currently pregnant with multiples or was pregnant within the last 6 months.

I have had a miscarriage or preterm birth in the last 6 months.

I have had severe nausea or vomiting throughout my pregnancy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Pre-Study

Participants undergo fasting, anthropometric measurements, biochemical and dietary assessments, and screening for gestational diabetes and preeclampsia.

1 day

1 visit (in-person)

Study Day

Participants receive a test tryptophan intake and undergo sample collection for breath, urine, and blood to measure tryptophan needs.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the study day activities.

2-4 weeks

Treatment Details

Interventions

• Tryptophan

Trial Overview The study uses a safe and noninvasive method called Indicator Amino Acid Oxidation (IAAO) to measure dietary tryptophan requirements during pregnancy. Participants will consume a stable isotope tracer that can be detected in breath and urine samples.

Participant Groups

Group I: Tryptophan Intake Experimental Treatment 1 Intervention

Randomly assign the participant to receive a test tryptophan oral intake (ranging between 1 to 14 mg.kg.d) as an 8-hourly isocaloric and isonitrogenous meal that consist of a liquid formula shake and protein-free cookies.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

Excessive intake of L-tryptophan (L-Trp) during pregnancy negatively impacts fetal growth, as shown in a study with female mice fed varying levels of L-Trp.

Specifically, a diet with 5% L-Trp led to significantly lower pup weights compared to control and 2% L-Trp groups, indicating that keeping L-Trp intake below 3.3 g/kg body weight per day is crucial for maintaining healthy fetal growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-tryptophan metabolism in pregnant mice fed a high L-tryptophan diet and the effect on maternal, placental, and fetal growth. Tsuji, A., Nakata, C., Sano, M., et al.[2021]

Decreased levels of tryptophan in maternal blood during pregnancy are linked to a higher risk of complications such as depression, gestational diabetes, fetal growth restriction, spontaneous abortion, and preterm birth, indicating its potential as a biomarker for adverse outcomes.

Alterations in kynurenine metabolites, particularly kynurenic acid, were observed in women with preeclampsia, suggesting that monitoring these metabolites could help in understanding and managing pregnancy-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of the Kynurenine Pathway in the (Patho) physiology of Maternal Pregnancy and Fetal Outcomes: A Systematic Review. van Zundert, SK., Broekhuizen, M., Smit, AJ., et al.[2022]

L-tryptophan is crucial for protein synthesis and is the sole precursor for serotonin in the brain, which plays a significant role in mood, behavior, and cognition.

Clinical trials suggest that L-tryptophan supplementation may be effective in treating psychiatric disorders, especially when combined with other therapies, highlighting its potential as a therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Richard, DM., Dawes, MA., Mathias, CW., et al.[2023]

Plasma tryptophan levels significantly decrease during pregnancy and shortly after delivery, particularly in the early postpartum period, compared to non-pregnant women, indicating a potential link to immune activation.

Despite the reduction in plasma tryptophan, there was no significant correlation found between tryptophan availability and postpartum depression or anxiety symptoms in the early puerperium, suggesting that other factors may contribute to these mental health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of pregnancy and delivery on the availability of plasma tryptophan to the brain: relationships to delivery-induced immune activation and early post-partum anxiety and depression. Maes, M., Ombelet, W., Verkerk, R., et al.[2019]

In a study of 45 healthy pregnant women across all three trimesters, serum tryptophan levels significantly decreased as pregnancy progressed, indicating a potential link to immune system changes during pregnancy.

The ratio of kynurenine (a tryptophan breakdown product) to tryptophan increased throughout pregnancy, suggesting that the body's metabolism of tryptophan is altered, which may be associated with immune activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased plasma tryptophan in pregnancy. Schröcksnadel, H., Baier-Bitterlich, G., Dapunt, O., et al.[2023]

L-Tryptophan (L-Trp) is crucial for growth and can help prevent pellagra, making it an important nutrient, especially in underdeveloped countries.

Research suggests that the urinary excretory ratio of anthranilic acid to kynurenic acid could serve as a sensitive biomarker to predict the safe upper intake level of L-Trp, which is important for ensuring its safe use without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The metabolites in the tryptophan degradation pathway might be useful to determine the tolerable upper intake level of tryptophan intake in rats. Shibata, K., Fukuwatari, T.[2023]

In pregnant rats, administration of the serotonin precursor 5-hydroxytryptophan (5-HTP) significantly reduced plasma volume and fetal weight, indicating that increased serotonin levels may contribute to complications in pregnancy such as fetal growth restriction.

The negative effects of 5-HTP on plasma volume and fetal growth were reversed by preadministration of ketanserin, a 5-HT(2) receptor antagonist, suggesting that serotonin's action through these receptors plays a critical role in mediating these adverse outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnant rats treated with a serotonin precursor have reduced fetal weight and lower plasma volume and kallikrein levels. Salas, SP., Giacaman, A., Romero, W., et al.[2022]

Maternal tryptophan infusion significantly increased kynurenine levels in fetal plasma, but this effect was reduced in fetuses with embolized placentas, indicating that compromised placental function affects fetal metabolism.

Both kynurenic acid and quinolinic acid levels increased in the fetal brain after tryptophan loading, with greater increases observed in fetuses with embolized placentas, suggesting that placental dysfunction alters the metabolism of tryptophan and kynurenine in the developing brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kynurenine production and catabolism in fetal sheep with embolized or nonembolized placentas. Nicholls, T., Nitsos, I., Smythe, G., et al.[2013]

Tryptophan (Trp) is crucial during pregnancy for various functions, including protein synthesis, fetal development, and the production of important metabolites like serotonin and kynurenic acid, which protect neurons.

In pregnancy, maternal Trp levels are managed through complex mechanisms involving hormonal regulation and changes in albumin levels, which ensure sufficient Trp availability for both maternal and fetal needs, highlighting the importance of monitoring Trp metabolism for potential interventions in normal and abnormal pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tryptophan metabolism, disposition and utilization in pregnancy. Badawy, AA.[2023]

Oral administration of l-tryptophan and alpha-lactalbumin significantly increased free tryptophan levels in breast milk without affecting total tryptophan concentrations, suggesting a safe dietary approach for breastfeeding mothers.

The study involved 30 healthy breastfeeding women and indicates that dietary l-tryptophan could be further explored as a potential supplement to improve sleep and reduce the risk of postpartum depression, as the free tryptophan levels were comparable to those found in common infant formulas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No effect of oral L-tryptophan or alpha-lactalbumin on total tryptophan levels in breast milk. Dowlati, Y., Ravindran, AV., Maheux, M., et al.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

L-tryptophan metabolism in pregnant mice fed a high L-tryptophan diet and the effect on maternal, placental, and fetal growth. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

The Role of the Kynurenine Pathway in the (Patho) physiology of Maternal Pregnancy and Fetal Outcomes: A Systematic Review. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Effects of pregnancy and delivery on the availability of plasma tryptophan to the brain: relationships to delivery-induced immune activation and early post-partum anxiety and depression. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Decreased plasma tryptophan in pregnancy. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

The metabolites in the tryptophan degradation pathway might be useful to determine the tolerable upper intake level of tryptophan intake in rats. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Pregnant rats treated with a serotonin precursor have reduced fetal weight and lower plasma volume and kallikrein levels. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Kynurenine production and catabolism in fetal sheep with embolized or nonembolized placentas. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Tryptophan metabolism, disposition and utilization in pregnancy. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

No effect of oral L-tryptophan or alpha-lactalbumin on total tryptophan levels in breast milk. [2016]