Low-Protein Diet for Cancer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: State University of New York at Buffalo

Must be taking: Immune checkpoint inhibitors

Must not be taking: Systemic corticosteroids, High dose calcitriol

Disqualifiers: ECOG status 2+, Systemic immunosuppressive therapy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The main idea of this study is that a low protein diet may alter the environment surrounding the tumor, enhancing the body's immune response leading to greater anticancer effects of treatment. This study intends to use a low-protein diet as a tool to enhance the immune response generated by immune check point inhibitor treatments.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic corticosteroids and high dose calcitriol (a form of vitamin D) at least 28 days before joining. Inhaled, intranasal, and topical steroids are allowed.

What data supports the effectiveness of the low-protein diet treatment for cancer?

The research suggests that a low-protein diet may influence the tumor environment and immune response, potentially enhancing the effectiveness of cancer treatments. However, other studies indicate that low-protein diets can increase cancer incidence in certain conditions, highlighting the complexity of its effects. ^{1 2 3 4 5}

Is a low-protein diet generally safe for humans?

Low-protein diets have been found to be safe and effective in managing chronic kidney disease, without negatively affecting quality of life. However, long-term adherence to high-protein diets may have adverse health consequences, suggesting that moderation and balance in protein intake are important for safety. ^{2 6 7 8 9}

How does a low-protein diet treatment differ from other cancer treatments?

A low-protein diet for cancer is unique because it focuses on reducing protein intake to potentially slow tumor growth, unlike traditional treatments that often involve drugs or surgery. This approach is based on studies suggesting that lower protein intake may inhibit tumor growth, although it is not a standard treatment and its effectiveness can vary depending on the type of cancer and individual patient conditions. ^{1 4 9 10 11}

Eligibility Criteria

Adults over 18 with solid tumor cancers suitable for immunotherapy can join this trial. They must have a certain level of white blood cells, platelets, and proper organ function. People on high-dose vitamin D, systemic steroids or immunosuppressants, those with poor physical status (ECOG >2), or infections needing antibiotics recently cannot participate.

Inclusion Criteria

My cancer is suitable for immunotherapy treatment.

Total bilirubin ≤ 2 x upper limit of normal (ULN)

My scans show cancer has spread to my bones or soft tissues.

Exclusion Criteria

I am taking more than 7.0 μg of calcitriol per week.

I am not on systemic corticosteroids, but I may use inhaled, nasal, or topical steroids.

I need medication to suppress my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immunotherapy combined with either a low-protein diet or a control diet for 3 cycles

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Diet

Trial Overview The study is testing if eating low-protein meals can boost the body's immune response to cancer when patients are also receiving treatments known as immune checkpoint inhibitors. The goal is to see if diet changes can make these cancer treatments more effective.

Participant Groups

Group I: Low-Protein Diet Arm Active Control 1 Intervention

intervention low-protein diet arm (10% protein content)

Group II: Control Diet Arm Active Control 1 Intervention

control diet arm (\~20% protein content)

Who Is Running the Clinical Trial?

State University of New York at Buffalo

Lead Sponsor

Trials

279

Recruited

52,600+

Findings from Research

A very-low-protein diet (5% casein) significantly increased the incidence and number of gastric cancers in Wistar rats after exposure to a carcinogen, indicating a potential risk factor for gastric cancer.

The increase in gastric cancer incidence may be linked to elevated norepinephrine levels in the gastric wall and increased proliferation of antral epithelial cells, suggesting a mechanism by which low-protein diets could enhance carcinogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats fed a low-protein diet. Tatsuta, M., Iishi, H., Baba, M., et al.[2018]

In a study of 91 older adults with advanced gastrointestinal cancer, a high protein diet (HPD) did not improve handgrip strength, indicating that increased protein intake may not enhance muscle function in this population.

However, patients on a high protein diet had a significantly longer overall survival (14.7 months) compared to those on a low protein diet (7.3 months), suggesting that HPD may help reduce cancer-related mortality and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High protein diet improves the overall survival in older adults with advanced gastrointestinal cancer. Pimentel, GD., Pichard, C., Laviano, A., et al.[2022]

Dietary protein or amino acid restriction can enhance the tumor-fighting abilities of macrophages, leading to reduced tumor growth and improved responses to immunotherapy in animal models of prostate and renal cancer.

The study identified a specific mechanism involving a ROS/mTOR pathway that explains how protein restriction reprograms macrophage function, suggesting that dietary changes could be a supportive strategy for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Protein Restriction Reprograms Tumor-Associated Macrophages and Enhances Immunotherapy. Orillion, A., Damayanti, NP., Shen, L., et al.[2021]

In a study involving 72 rats with implanted hepatoma, a protein-free diet led to significantly increased mortality rates and complications like hemorrhagic cystitis, indicating that protein deficiency can negatively impact overall health during cancer treatment.

While chemotherapy (cyclophosphamide) effectively reduced tumor size and metastases in rats on a regular diet, it did not show improved outcomes in rats on a protein-free diet, suggesting that protein deficiency does not enhance chemotherapy response but may hinder treatment due to increased health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of protein deficiency on growth and response of primary and metastatic hepatoma. Weber, TR., Dalsing, MC., Sawchuck, A., et al.[2019]

In a study involving 43 female C2H mice with mammary tumors, those on a standard protein diet had greater body weight but experienced increased tumor growth and reduced survival compared to those on a protein-depleted diet.

The results suggest that while protein intake supports the host's body weight, it may also enhance tumor growth, leading to a detrimental effect on overall survival in tumor-bearing animals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of protein-intake on tumor-growth and host survival in tumor-bearing animals. Torosian, M.[2019]

Low protein diets, whether from natural foods or amino acid supplements, are safe and effective in slowing the progression of chronic kidney disease (CKD) without negatively impacting patient outcomes during Renal Replacement Therapy.

These diets improve various health markers, such as reducing proteinuria and serum levels of uric acid and phosphate, while also decreasing the need for medications like hypotensive drugs and erythropoietin, ultimately enhancing patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low protein diets are mainstay for management of chronic kidney disease. De Santo, NG., Perna, A., Cirillo, M.[2022]

Low-protein diets (≤0.7 g/kg per day) have not been shown to significantly slow the progression of kidney disease, and compliance with such diets is often poor, making them less effective as a treatment strategy.

Restricting dietary protein can lead to declines in nutritional health for patients with chronic kidney disease, who are already at risk of malnutrition, suggesting that maintaining adequate protein intake is more beneficial than restriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary protein restriction as a treatment for slowing chronic kidney disease progression: the case against. Johnson, DW.[2022]

In a study of 29,017 postmenopausal women followed for 15 years, substituting vegetable protein for carbohydrates was linked to a 30% reduction in coronary heart disease (CHD) mortality, suggesting that plant-based proteins may be healthier than carbohydrates.

Conversely, higher intake of red meats and dairy products was associated with increased CHD mortality, indicating that not all protein sources are equally beneficial and that long-term high-protein diets could have negative health effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women. Kelemen, LE., Kushi, LH., Jacobs, DR., et al.[2023]

Research indicates that both underfeeding and optimal protein intake can inhibit tumor growth, suggesting that the quantity of protein consumed is more critical than its source in cancer prevention.

The relationship between protein intake and cancer risk is complex, as high protein diets may sometimes lower tumor incidence due to reduced overall food intake, highlighting the need for careful consideration of dietary factors in cancer studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary protein and experimental carcinogenesis. Visek, WJ.[2019]

In a study involving 50 rats with mammary tumors, those on a protein-depleted diet showed a significant reduction in tumor volume after 14 days compared to those on a standard protein diet, suggesting that lower protein intake may slow tumor growth.

The study found no changes in tumor cell cycle kinetics between the two diet groups, indicating that the reduced tumor growth may be due to tumor cells entering a dormant state or an overall increase in cell cycle duration rather than a shift in the distribution of cells across different phases of the cell cycle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of protein intake on tumor growth and cell cycle kinetics. Torosian, MH.[2003]

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]

References

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

Enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats fed a low-protein diet. [2018]

2. England pubmed.ncbi.nlm.nih.gov

High protein diet improves the overall survival in older adults with advanced gastrointestinal cancer. [2022]

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

Dietary Protein Restriction Reprograms Tumor-Associated Macrophages and Enhances Immunotherapy. [2021]

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

The effect of protein deficiency on growth and response of primary and metastatic hepatoma. [2019]

5. Greece pubmed.ncbi.nlm.nih.gov

Effect of protein-intake on tumor-growth and host survival in tumor-bearing animals. [2019]

6. Singapore pubmed.ncbi.nlm.nih.gov

Low protein diets are mainstay for management of chronic kidney disease. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Dietary protein restriction as a treatment for slowing chronic kidney disease progression: the case against. [2022]

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

Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women. [2023]

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

Dietary protein and experimental carcinogenesis. [2019]

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

Effect of protein intake on tumor growth and cell cycle kinetics. [2003]

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

Protein Intake and Breast Cancer Survival in the Nurses' Health Study. [2019]