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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to better understand the tryptophan needs of pregnant women at various pregnancy stages. Researchers will use a safe method involving a special, detectable form of tryptophan to measure this requirement. The trial seeks healthy pregnant women carrying one child, who are either 11-20 weeks or 31-40 weeks into their pregnancy. Participants should not have chronic illnesses or severe pregnancy-related issues. As an unphased trial, this study offers participants the chance to contribute to important research that could enhance nutritional guidelines for pregnant women.

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 prior data suggests that this method is safe for measuring tryptophan needs in pregnancy?

Research has shown that tryptophan, a nutrient found in many foods, is safe to consume in amounts up to 5 grams per day during pregnancy. This conclusion is based on studies that found no harm from tryptophan supplements at this level. However, opinions vary regarding its safety in amounts higher than those typically found in food. Some studies suggest that tryptophan and its byproducts might be linked to pregnancy issues, such as early delivery. While tryptophan can aid in baby development, it is important to adhere to safe amounts. Always consult a healthcare provider before altering your supplement routine during pregnancy. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike typical pregnancy supplements that focus on vitamins and minerals, tryptophan intake introduces an amino acid-based approach to prenatal nutrition. Tryptophan is unique because it plays a crucial role in producing serotonin, which is important for mood regulation and sleep. Researchers are excited about tryptophan's potential to enhance maternal well-being and possibly influence fetal development positively. This approach represents a novel way to support pregnancy health beyond the usual nutrients.

What evidence suggests that this method is effective for determining tryptophan needs during pregnancy?

Studies have shown that tryptophan is crucial during pregnancy for building proteins and aiding the baby's growth. Research indicates that as the baby develops, its need for tryptophan increases. In animal studies, higher tryptophan levels led to better pregnancy outcomes, such as improved blood flow to the placenta. Additionally, tryptophan and its byproducts might serve as important indicators of pregnancy health, suggesting a broader role in supporting a healthy pregnancy. These findings support the idea that tryptophan is both beneficial and necessary during pregnancy. Participants in this trial will receive a test tryptophan oral intake to further evaluate its effects during pregnancy. ^{1 4 6 7 8}

Who Is on the Research Team?

Rajavel Elango, PhD

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4626867/

Tryptophan metabolism, disposition and utilization in ... These data demonstrate the increased requirement of the fetus for Trp. In addition to its essential role in protein synthesis and hence fetal growth, Trp ...

2. frontiersin.org frontiersin.org/journals/reproductive-health/articles/10.3389/frph.2024.1453714/full

Tryptophan as a biomarker of pregnancy-related immune ... Conclusion: TRP and its metabolites hold promise as biomarkers for various pregnancy-related outcomes. Future research should aim to clarify the ...

3. jci.org jci.org/articles/view/164219

The curious case of tryptophan in pregnancy Replacement of l-kynurenine during pregnancy in uninephrectomized mice results in improved placental blood flow, reduced placental sFLT1 levels, ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022316625002779

Maternal Tryptophan Supplementation Enhances Sow ... Dietary tryptophan supplementation may enhance the pregnancy outcome of sows through the increase of tryptophan metabolites to strengthen steroid hormone ...

5. academic.oup.com academic.oup.com/humrep/article/39/5/912/7631261

First trimester maternal tryptophan metabolism and embryonic ... Higher 5-hydroxytryptophan (5-HTP) concentrations are associated with reduced embryonic growth and fetal growth and with an increased risk of small-for- ...

6. webmd.com webmd.com/vitamins/ai/ingredientmono-326/l-tryptophan

L-Tryptophan - Uses, Side Effects, and More Pregnancy: It is possibly unsafe to take L-tryptophan in amounts greater than those found in foods during pregnancy. It might harm the unborn child.

7. ogscience.org ogscience.org/journal/view.php?number=101

The tryptophan utilization concept in pregnancy Application of the Trp utilization concept in pregnancy offers several physiological advantages favoring fetal development and successful outcome.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/002432058390187X

Tryptophan feeding adversely influences pregnancy Relatively small doses of exogenous serotonin have been reported to cause abortions in several vertebrate species (1, 2, 3, 4, 5).