Activating the immune system to kill cancer cells is a promising therapeutic strategy for some patients with cancer. Unfortunately, current immune-targeting treatments do not work for patients with prostate cancer. In animal models of cancer, fasting can reprogram the body's metabolism and immune cell function to help immune cells kill cancer cells likely by increasing ketosis. The purpose of this study is to determine whether 7 days of water-only fasting or a ketogenic very low-calorie diet or ketone supplementation is safe and feasible for patients with prostate cancer. This will help the investigators develop future studies to test whether incorporating periods of fasting or very low calorie diets or a ketone supplement into treatment plans for prostate cancer can improve outcomes from this disease.

Seven days of water-only fasting is safe and feasible in healthy adults. Fasting enhances anti-tumor immunity in animal models of cancer likely through ketosis. The primary objective of this study is to determine if 7 days of water-only fasting or a ketogenic very low-calorie diet or ketone supplementation is safe and feasible in patients with prostate cancer.

Patients with prostate cancer will be instructed to perform a 7-day water-only fast followed by a 3-day refeeding protocol to evaluate safety and feasibility. Two cohorts will be evaluated including (1) patients with local prostate cancer and (2) patients with metastatic prostate cancer. Two additional cohorts, including patients with (3) local and (4) metastatic prostate cancer, will be instructed to drink a ketone supplement for 7 days to evaluate safety and feasibility.

Inclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

• Age ≥18 years

• Diagnosis of adenocarcinoma of the prostate

• If a soft tissue metastasis amenable to biopsy is present, then the participant must agree to biopsies.

• If the participant has local prostate cancer, then the participant must agree to prostate biopsy or radical prostatectomy on days 8, 9, or 10. -. Prostate-specific antigen (PSA) is not currently declining, as determined by most recent 2 measurements taken at least 1 week apart in previous 2 months.

• BMI between 20 and 35 kg/m2

• Prior treatment with any prostate cancer therapy is permitted if >2 weeks from last dose. Patients are not required to have received prior treatment for prostate cancer.

• Prior treatment with steroids is permitted if >2 weeks from last dose. Patients who cannot be weaned off steroids are not eligible.

• Acceptable liver function:

  1. Bilirubin < 2.5 times institutional upper limit of normal (ULN)
  2. Aspartate transaminase (AST) (SGOT) and Alanine transaminase (ALT) (SGPT) < 2.5 times ULN

• Acceptable renal function: glomerular filtration rate (GFR) of 50 mL/min/1.73 m2 or higher. GFR will be estimated by the 2021 chronic kidney disease epidemiology (CKD-EPI) creatinine equation1 using the online calculator found on UpToDate.

• Acceptable hematologic status:

  1. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
  2. Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
  3. Hemoglobin ≥ 8 g/dL.

• Acceptable electrolyte and acid/base status:

  1. Sodium 135-148 millimoles (mM)
  2. Potassium 3.5-5.1mM
  3. Carbon Dioxide 21-31mM
  4. Phosphorus 2.7-4.5mM
  5. Magnesium ≥1.6mM
  6. Lactate ≤2mM

• Ability to understand and willingness to sign a written informed consent document

Exclusion criteria:

• ECOG Performance status ≥2
• Unintentional weight loss greater than or equal to 5% in previous 3 months
• Diabetes mellitus, defined as HbA1c ≥6.5% or use of medications for diabetes
• Active uncontrolled infection. Patients with a history of HIV/AIDS may be eligible if CD4+ T cell counts are ≥ 350 cell/ul, the patients have had no opportunistic infection within the past 12 months, they have been on established antiretroviral therapy (ART) for at least four weeks, and the HIV viral load is less than 400 copies/ml prior to enrollment. Patients with a history of hepatitis C virus (HCV) infection are eligible if the patients have completed curative antiviral treatment and the HCV viral load is below the limit of quantification.
• Use of immunosuppressive medications including steroids
• Use of diuretics or beta blockers
• History of cardiac arrythmia, myocardial infarction, valvular heart disease, or pulmonary hypertension
• Abnormal screening EKG
• Daily alcohol consumption
• Any condition or mental impairment that may compromise the ability to give informed consent, patient's safety or compliance with study requirements as determined by the investigator