Tryptophan for Healthy Aging

Overseen By Zhiyao Wang, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Hospital for Sick Children

Must not be taking: Steroids

Disqualifiers: HIV, Diabetes, Significant weight loss, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 24 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the amount of tryptophan, an essential amino acid, that older adults need for healthy aging. Tryptophan plays a crucial role in protein synthesis and is linked to serotonin and nicotinic acid, which are vital for mood and metabolism. The study will test different levels of tryptophan in individuals aged 60 to 90 who are generally healthy and not experiencing major health issues. This research could lead to improved diets for seniors, focusing on maintaining muscle and reducing age-related health problems. As an unphased trial, it offers participants the chance to contribute to valuable research that could enhance dietary recommendations for seniors.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that affect protein or amino acid metabolism, like steroids.

What prior data suggests that tryptophan is safe for older adults?

Research shows that tryptophan is usually safe as a dietary supplement for short periods. People often take it to aid sleep and mood. Some studies indicate it can cause mild side effects like drowsiness, stomach pain, and vomiting. However, a rare but serious condition linked to tryptophan, called eosinophilia-myalgia syndrome (EMS), can be dangerous.

Tryptophan is an essential amino acid, meaning the body needs it but cannot produce it, so it must come from food or supplements. While many people use it, the exact amount needed for older adults remains unclear. This study aims to determine how much tryptophan individuals over 60 might need, which could help ensure safe and effective use. As with any supplement, consulting a healthcare provider before starting tryptophan is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Tryptophan is unique because it's a naturally occurring amino acid that plays a key role in producing serotonin, a neurotransmitter important for mood regulation and overall brain health. Unlike other treatments for aging-related issues, which might involve pharmaceuticals that directly target cognitive decline or physical symptoms, tryptophan potentially enhances overall well-being by naturally supporting brain chemistry. Researchers are excited about tryptophan because it offers a more holistic approach to healthy aging, possibly improving mood and mental health without the side effects often associated with traditional medications.

What evidence suggests that tryptophan might be an effective treatment for healthy aging?

Research has shown that tryptophan might help reduce inflammation and cell damage in aging mice, potentially benefiting health as people age. Some studies suggest a link between tryptophan and improved sleep and reduced anxiety. While tryptophan is known to boost serotonin levels, little evidence supports its direct treatment of depression. Additionally, researchers have studied substances formed when the body breaks down tryptophan for their impact on physical performance in older adults. This trial will test various levels of tryptophan in adults over 60 to explore its potential benefits for healthy aging. Overall, these findings suggest tryptophan could support healthy aging, but more research is needed to fully understand its effects. ^{2 4 6 7 8}

Who Is on the Research Team?

Glenda Courtney-Martin, PhD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 60 to 90 who are in good general health as confirmed by medical history, physical exam, and blood tests. Participants must have a BMI under 30 kg/m2 and be willing to participate in the study.

Inclusion Criteria

BMI <30 kg/m2

Consent provided

Fasting blood glucose, hemoglobin A1c (HbA1c), urea, creatinine

Exclusion Criteria

Inability to tolerate the diet (i.e. allergy)

I am not willing to have blood drawn or undergo certain tests for this study.

Significant weight loss during the past month or consumption of weight reducing diets

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive varying levels of tryptophan in a controlled diet to determine the requirement in adults over 60 years

up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tryptophan

Trial Overview The study aims to determine the necessary amount of tryptophan (an essential amino acid) for older adults. Tryptophan is crucial for protein synthesis and serves as a precursor for serotonin and nicotinic acid.

How Is the Trial Designed?

Group I: Tryptophan in Adults >60y Experimental Treatment 1 Intervention

Tryptophan levels, up to 7 levels, will be tested in a random order in all subjects

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

Higher serum levels of the essential amino acid tryptophan (trp) are associated with a lower risk of hip fractures, with a hazard ratio of 0.75 per standard deviation increase in trp levels, based on a study of 262 participants over 12 years.

No significant associations were found between tryptophan's oxidized or nonoxidized metabolites and hip fractures, mortality, or frailty, indicating that further research, including randomized clinical trials, is needed to explore the potential benefits of increasing trp intake for bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Tryptophan and Its Metabolites With Incident Hip Fractures, Mortality, and Prevalent Frailty in Older Adults: The Cardiovascular Health Study. Carbone, L., Bůžková, P., Fink, HA., et al.[2023]

Rats that were previously fed a tryptophan-deficient diet for 6-22 months showed significant recovery in body weight and improved survival rates after being switched to a normal diet, indicating potential long-term benefits of dietary interventions.

These rats not only had a longer average lifespan (36.31 months) compared to control rats (30.5 months), but also demonstrated enhanced recovery from hypothermia and delayed onset of tumors, suggesting that early dietary deficiencies may influence health outcomes later in life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term tryptophan restriction and aging in the rat. Segall, P.[2013]

Research indicates that systemic factors, particularly the kynurenine pathway (KP) of tryptophan metabolism, play a significant role in the aging process and the decline of organ function.

Circulating kynurenine levels are associated with higher mortality rates in humans, suggesting that tryptophan derivatives could serve as biomarkers for frailty in the elderly and that targeting the KP may offer therapeutic opportunities for age-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical insights into the kynurenine pathway in age-related diseases. Kim, BJ., Lee, SH., Koh, JM.[2021]

In a study involving Fischer 344 rats and B6C3F1 mice, L-Tryptophan showed little toxic effect, with minimal body weight loss and high survival rates in rats, indicating it is safe at the tested doses.

No significant increase in tumor incidence was found in rats, and while some hematopoietic tumors appeared in mice, they were not statistically significant, leading to the conclusion that L-Tryptophan is not carcinogenic under the study conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioassay of L-Tryptophan for Possible Carcinogenicity (CAS No. 73-22-3). [2020]

A No Observed Adverse Effect Level (NOAEL) of 30 g/d for dietary arginine and an upper limit of safe intake (ULSI) of 4.5 g/d for dietary tryptophan have been established for healthy young adults, indicating safe consumption levels for these amino acids when taken as supplements.

For elderly individuals, a proposed ULSI for leucine is 500 mg · kg-1 · d-1, emphasizing the need for tailored dietary recommendations based on age and health status, which could influence regulatory and nutritional practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly. Cynober, L., Bier, DM., Kadowaki, M., et al.[2023]

A study on aged mice revealed that a TRP-deficient diet led to significant changes in gut bacteria and increased inflammatory markers, indicating that low tryptophan can negatively impact gut health and inflammation.

Mice fed a high-tryptophan diet showed a healthier gut microbiome and reduced inflammatory responses, suggesting that adequate tryptophan intake is crucial for maintaining gut health and managing inflammation in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Tryptophan-Deficient Diet Induces Gut Microbiota Dysbiosis and Increases Systemic Inflammation in Aged Mice. Yusufu, I., Ding, K., Smith, K., et al.[2022]

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 a study involving 35 middle-aged to elderly participants, consuming cereals enriched with tryptophan significantly improved sleep quality and reduced symptoms of anxiety and depression over a 3-week period.

The higher tryptophan intake led to increased levels of melatonin and serotonin metabolites in urine, suggesting that this dietary approach may help restore sleep/wake cycles affected by aging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin, and total antioxidant capacity levels and mood in elderly humans. Bravo, R., Matito, S., Cubero, J., et al.[2022]

The EFSA Panel initially could not determine the safety of l-Tryptophan as a feed additive due to insufficient information about its genetic modification, particularly regarding antibiotic resistance genes.

After reviewing additional data, the EFSA Panel concluded that l-Tryptophan is safe for target animals, consumers, users, and the environment, confirming its efficacy as a nutritional additive for all animal species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of l-tryptophan technically pure, produced by Escherichia&#160;coli CGMCC&#160;3667, for all animal species based on a dossier submitted by GBT Europe GmbH. Rychen, G., Aquilina, G., Azimonti, G., et al.[2020]

A single oral dose of tryptophan at 100 mg/kg body weight is generally well tolerated, with only minor gastric side effects reported, indicating its potential safety for therapeutic use.

There is a lack of comprehensive data on the chronic toxicity and therapeutic index of tryptophan and its metabolites, highlighting the need for further research before clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity and tolerance of tryptophan and its metabolites]. Montenero, AS.[2015]

A diet containing 0.4% tryptophan significantly reduced oxidative stress and inflammation in aging mice, likely through the regulation of AMPK and NF-κB pathways.

The tryptophan diet also increased beneficial gut bacteria (Akkermansia) and improved neurohealth by potentially enhancing brain-derived neurotrophic factor (BDNF) levels, suggesting a link between tryptophan, gut microbiota, and brain health in aging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ameliorative Effect of Dietary Tryptophan on Neurodegeneration and Inflammation in d-Galactose-Induced Aging Mice with the Potential Mechanism Relying on AMPK/SIRT1/PGC-1α Pathway and Gut Microbiota. Yin, J., Zhang, B., Yu, Z., et al.[2022]

In a study involving 1574 participants and 109 cerebrospinal fluid donors, aging was linked to increased levels of kynurenine metabolites (like quinolinic acid) and a decrease in tryptophan, suggesting significant metabolic changes associated with aging.

Higher levels of kynurenine metabolites were correlated with frailty and mortality, indicating that the kynurenine pathway may play a role in adverse health outcomes as people age, although it's unclear if this activation is harmful or beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kynurenine Pathway Metabolites in the Blood and Cerebrospinal Fluid Are Associated with Human Aging. Solvang, SH., Hodge, A., Watne, LO., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-healthy-aging-5-2024-58d84

Tryptophan for Healthy Aging Additionally, tryptophan has shown potential in reducing inflammation and oxidative stress in aging mice, which could be beneficial for overall health during ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0022316623008143

Tryptophan Intake in the US Adult Population Is Not ... Tryptophan intake was inversely associated with self-reported level of depression and positively associated with sleep duration.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6158605/

Analysis, Nutrition, and Health Benefits of Tryptophan - PMC The results show that consumption of the higher tryptophan cereals increased sleep efficiency and sleep time and improved anxiety and ...

4. webmd.com webmd.com/vitamins-and-supplements/l-tryptophan-uses-and-risks

L-tryptophan: Uses and Risks L-tryptophan can boost serotonin levels, but research hasn't shown it is effective for treating depression. There is limited research to back ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/11786469211069951

Association Between Tryptophan Metabolites, Physical ... This study explored the relationship between TRP metabolites and physical performance in an older population. Our results showed that serum KYNA ...

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

L-Tryptophan - Uses, Side Effects, and More 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, ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/tryptophan-oral-route/description/drg-20064453

Tryptophan (oral route) - Side effects & dosage L-tryptophan is used along with other medications to treat mental depression. Also, L-tryptophan is used along with lithium to treat bipolar disorder.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06283706

The Tryptophan Requirement in Healthy Adults Also called a data safety and monitoring board, or DSMB. Early Phase 1 ... Thus, the purpose of this study is to find out how much tryptophan older adults need.