Protein Intake for Cancer Patients

Overseen By Anne Caretero, RD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alberta

Must not be taking: Hormone therapy, Immunotherapy

Disqualifiers: Diabetes, Class III obesity, Renal impairment, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 8.5 hours

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the protein requirements for individuals with colorectal or breast cancer to maintain muscle and stay healthy. The goal is to develop improved nutrition guidelines for these patients using a safe and simple method to measure protein needs. The trial involves administering phenylalanine, an amino acid, to assess its impact on muscle health. Suitable participants have colorectal or breast cancer at specific stages and can walk independently. As an unphased trial, this study provides a unique opportunity to contribute to the development of personalized nutrition guidelines for cancer patients.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have comorbidities or are on medications that interfere with the study, you may not be eligible to participate.

What prior data suggests that phenylalanine intake is safe for cancer patients?

Research has shown that phenylalanine is generally safe when used correctly. It lacks chemicals that cause cancer or birth defects, so it poses no serious health risks for most people.

However, individuals with phenylketonuria (PKU) face specific concerns, as they cannot process phenylalanine well, making it harmful to them. For those without PKU, phenylalanine is usually safe.

In this study, phenylalanine is used to understand protein needs in cancer patients, aiming to improve their health. Similar studies have reported no serious side effects, suggesting that the treatment is safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about phenylalanine intake for cancer patients because it explores a nutritional approach to support patients undergoing treatment. Unlike traditional cancer therapies that often focus on chemotherapy or radiation, this approach leverages phenylalanine, an amino acid, to potentially improve protein intake and nutritional status. This could be particularly beneficial in helping patients maintain muscle mass and strength, which are crucial during cancer treatment. By integrating dietary strategies, this treatment offers a complementary option that could enhance overall patient well-being alongside existing therapies.

What evidence suggests that phenylalanine intake might be an effective treatment for muscle loss in cancer patients?

Research has shown that protein and amino acid supplements, such as phenylalanine, can help cancer patients build muscle and gain strength. Muscle loss is a common issue for cancer patients, leading to additional health problems and reduced quality of life. Although chemotherapy does not alter phenylalanine levels in breast cancer patients, phenylalanine remains crucial for protein synthesis, which aids in muscle maintenance. Some studies have explored limiting phenylalanine and tyrosine in diets, but this differs from using supplements to support muscle health. In this trial, participants will receive phenylalanine as an experimental treatment to evaluate its potential in helping cancer patients maintain muscle strength, which is vital for their well-being. ^{6 7 8 9 10}

Who Is on the Research Team?

Carla Prado, PhD, RD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for outpatients aged 45-80 with stage II to III colorectal or breast cancer, who can visit the clinic within 4 weeks of starting chemo or after surgery if no chemo. They must be able to walk and provide samples. Excluded are those with kidney issues, abnormal glucose metabolism, severe allergies, premenopausal women, recent hormone/immunotherapy recipients, certain comorbidities or substance dependencies.

Inclusion Criteria

I am between 45 and 80 years old.

I can start the study visits within 4 weeks of beginning chemo or 4 weeks after surgery if I'm not on chemo.

I have stage II or III colorectal or breast cancer and am a new patient at the Cross Cancer Institute.

Exclusion Criteria

My kidney function is reduced with an eGFR below 60 mL/min.

Unable to eat the meals provided (i.e. receiving parenteral or enteral nutrition, severe allergies)

I do not have health conditions or take medications that would affect my participation in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants' protein needs are determined using a novel, non-invasive approach

8.5 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Phenylalanine

Trial Overview The study aims to determine protein needs in patients with colorectal or breast cancer using a new non-invasive method. This could lead to better nutritional guidelines and improve patient outcomes by maintaining muscle mass and overall health during treatment.

How Is the Trial Designed?

Group I: Phenylalanine intake Experimental Treatment 1 Intervention

Phenylalanine is already approved in European Union, United States for the following indications:

Approved in European Union as L-Phenylalanine for:

• Nutritional supplement in total parenteral nutrition (TPN)

Approved in United States as L-Phenylalanine for:

• Nutritional supplement in total parenteral nutrition (TPN)

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Published Research Related to This Trial

In a 60-day study involving four patients with advanced malignant melanoma, a diet severely restricted in phenylalanine and tyrosine was tolerated by most, but it led to significant decreases in serum albumin, total iron binding capacity, and cholesterol levels, indicating potential nutrient deficiencies.

Despite the dietary intervention, there were no observed tumor responses, suggesting that this approach may not be effective in managing advanced cancer in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a phenylalanine and tyrosine restricted diet on elemental balance studies and plasma aminograms of patients with disseminated malignant melanoma. Lawson, DH., Stockton, LH., Bleier, JC., et al.[2018]

A scoping review of 14 studies indicates that protein and amino acid supplementation can positively impact muscle strength in adult cancer patients, generally aligning with improvements in muscle mass.

Combining energy and protein intake, especially when oral intake is low, leads to more significant gains in muscle strength and mass, although the exact mechanisms behind this effect need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Protein Supplementation Targeted at Improving Muscle Mass on Strength in Cancer Patients: A Scoping Review. Zanetti, M., Gortan Cappellari, G., Barazzoni, R., et al.[2021]

In a study of 6,348 women with stage I to III breast cancer, higher protein intake was associated with a modest improvement in survival rates, particularly with animal protein, suggesting that protein consumption may be beneficial post-diagnosis.

The study found no significant differences in survival benefits based on insulin receptor status or specific types of amino acids, indicating that women with breast cancer may not need to restrict protein intake for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein Intake and Breast Cancer Survival in the Nurses' Health Study. Holmes, MD., Wang, J., Hankinson, SE., et al.[2019]

Cancer patients often experience disturbances in amino acid kinetics, leading to increased protein turnover and muscle breakdown, which can negatively impact their health outcomes.

Short-term supplementation with high protein meals or essential amino acids has shown potential benefits in improving muscle protein synthesis in cancer patients, suggesting that higher protein intake may be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino acid kinetics and the response to nutrition in patients with cancer. van der Meij, BS., Teleni, L., Engelen, MPKJ., et al.[2019]

Low muscle mass and malnutrition during chemotherapy and radiotherapy can lead to increased toxicity, reduced quality of life, and lower survival rates, highlighting the need for effective nutritional therapy.

Recent guidelines emphasize the importance of timely nutritional interventions for cancer patients, recommending collaboration between oncologists and nutrition specialists to ensure adequate nutritional support, including enteral or parenteral nutrition when necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional Therapy in Cancer Patients Receiving Chemoradiotherapy: Should We Need Stronger Recommendations to Act for Improving Outcomes? Cotogni, P., Pedrazzoli, P., De Waele, E., et al.[2020]

Restricting phenylalanine to 0.08% or less in the diet significantly prolonged survival and reduced tumor infiltration in mice with L1210 leukemia, particularly in tissues like bone marrow and brain.

The effectiveness of phenylalanine restriction in reducing tumor infiltration was compromised when the immune system was suppressed, indicating that the diet may enhance the host's immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved host defense against L1210 leukemia by deprivation of dietary phenylalanine. Pine, MJ.[2013]

In a study with inbred Wistar rats, oral administration of 6% L-phenylalanine significantly reduced the incidence and number of gastric adenocarcinomas induced by a carcinogen after 25 weeks of treatment.

The treatment with phenylalanine also altered hormone levels, increasing serum gastrin and decreasing norepinephrine in the gastric wall, suggesting a potential mechanism for its cancer-inhibiting effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protection by oral phenylalanine against gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Iishi, H., Tatsuta, M., Baba, M., et al.[2019]

In a study of 85 cancer patients undergoing chemotherapy, those receiving oral nutritional supplementation (ONS) with IMMAX® showed a significant increase in protein intake and caloric intake compared to those receiving nutritional counseling alone, indicating its efficacy in improving nutritional status.

The ONS was found to be safe and well-tolerated, with adverse events like anemia and nausea being similar between groups, and only a few patients experiencing constipation and diarrhea related to the supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Nutritional Supplementation in Cancer Patients Who Were Receiving Chemo/Chemoradiation Therapy: A Multicenter, Randomized Phase II Study. Faccio, AA., Mattos, CHPS., Santos, EASD., et al.[2021]

In a study of 166 malnourished advanced cancer patients undergoing chemotherapy, those who received 20g/day of whey protein isolate (WPI) along with nutritional counseling showed significant improvements in body composition and muscle strength compared to those who only received counseling.

WPI supplementation also reduced the risk of chemotherapy-related toxicity, particularly severe events, indicating that it may enhance the safety and efficacy of nutritional support during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whey protein isolate supplementation improves body composition, muscle strength, and treatment tolerance in malnourished advanced cancer patients undergoing chemotherapy. Cereda, E., Turri, A., Klersy, C., et al.[2021]

The Phenylalanine Content of Foods system, revised to include 372 food items, provides essential dietary guidance for managing phenylketonuria (PKU) by detailing serving sizes and phenylalanine equivalents.

This system has been adapted to create a low protein equivalency system, which can also assist in designing low protein diets for other inherited metabolic disorders, enhancing dietary management options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revision of the Ontario phenylalanine equivalency system and development of a low protein equivalency system. Chan, L., Bell, L., Hanley, WB.[2013]

In a study involving 37 patients with advanced metastatic melanoma and breast cancer, only 6 patients started a low phenylalanine and tyrosine diet, indicating poor acceptability of this dietary intervention.

The diet led to negative outcomes, including weight loss and increased anxiety and depression, suggesting that it is not a viable treatment option for patients with advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability and tolerance of a low tyrosine and phenylalanine diet in patients with advanced cancer -- a pilot study. Harvie, MN., Campbell, IT., Howell, A., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10534874/

Investigation of the Impact of L-Phenylalanine and L ... This study introduces a novel analytical strategy utilizing ICP-MS and single cell ICP-MS (SC-ICP-MS) to assess the effectiveness of L-tyrosine and L- ...

2. withpower.com withpower.com/trial/phase-colorectal-neoplasms-3-2021-f2b37

Protein Intake for Cancer Patients Research suggests that protein and amino acid supplementation, which includes components like phenylalanine, can help improve muscle mass and strength in cancer ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002916523347361

The effect of a phenylalanine and tyrosine restricted diet on ... Previous studies indicate dietary phenylalanine and tyrosine restriction may be of value in managing advanced cancer patients.

4. mdpi.com mdpi.com/2072-6643/15/13/2879

Dietary Manipulation of Amino Acids for Cancer Therapy A study showed that a 5% Leu supplementation increased cancer growth in a syngeneic model of pancreatic cancer [49]. However, our recent studies in mice with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11497521/

The Correlation Between Essential Amino Acid Tryptophan ... Phenylalanine and lysine levels in breast cancer patients were not affected by chemotherapy regimens, and their levels did not affect the ...

6. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/31498m.pdf

Safety Data Sheet 63-91-2 L-Phenylalanine. · Identification number(s). · EC number: 200 ... Chemicals known to cause cancer: Substance is not listed.

7. sigmaaldrich.com sigmaaldrich.com/IN/en/sds/aldrich/p17008?srsltid=AfmBOorRrajZaKu31KiZV1sFcwVIV53yO5h05aDUJ5L5eDZ8Urky5-bS

SAFETY DATA SHEET This product does not contain any chemicals known to the State of California to cause cancer, birth, or any other reproductive defects. SECTION ...

8. fishersci.ie fishersci.ie/store/msds?partNumber=10101630&countryCode=IE&language=en

SAFETY DATA SHEET Remove and wash contaminated clothing and gloves, including the inside, before. Page 4. SAFETY DATA SHEET. L-Phenylalanine. Revision Date 20-Oct-2023 re-use.

9. ema.europa.eu ema.europa.eu/en/documents/scientific-guideline/information-package-leaflet-regarding-aspartame-and-phenylalanine-used-excipients-medicinal-products-human-use_en.pdf

Information for the package leaflet regarding aspartame and ... Phenylalanine derived from aspartame is the major safety concern related with aspartame use for patients suffering from PKU. The safe use of ...

10. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/L-Phenylalanine

L-Phenylalanine | C9H11NO2 | CID 6140 - PubChem Phenylalanine used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance ...