The purpose of this study is to compare the 16/8 intermittent fasting method with the 5:2 Method in a subset of patients with chronic lymphocytic leukemia or small lymphocytic lymphoma at BC Cancer- Victoria. The purpose is to find out which is the preferred method by patients and which has the greatest effect on:

• cancer cells (lymphyocyte count),
• metabolism (autophagy activation),
• inflammation (CRP),
• gut microbiome (metabolomic analysis).

Participants will have already completed our previous trial, "Intermittent Fasting in CLL/SLL" (ClinicalTrials.gov Identifier: NCT04626843) where they followed the 16/8 Fasting Method followed by a minimum of a 3 months washout period, and will now follow the 5:2 Method for 90 days. The same samples and outcome measures will be collected in order to directly compare the two diets in the same patient cohort.

BACKGROUND: Interest in intermittent fasting (IF) is growing rapidly for its potential to improve health outcomes. IF is a diet regime that cycles between fasting and eating for a defined period. There are many variations of IF, most altering the length of the fasting window but some may include caloric restriction.

The investigators are nearing completion a feasibility study on the effects of IF on chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) at BC Cancer- Victoria. This clinical trial, "IF in CLL/SLL" (ClinicalTrials.gov Identifier: NCT04626843) investigates the biochemical effects of the 16/8 Method on CLL/SLL tumor control, markers of inflammation, and autophagy induction in a case-controlled study. Preliminary findings demonstrate excellent compliance and early feedback and findings are overwhelmingly positive. It is unknown, however, how the 16/8 Method compares to other IF regimens in terms of patient acceptability and biologic effects.

OBJECTIVE: The aim is to examine the two most common regimens, the 16/8 Method (16 hr fast) and the 5:2 Method (2 day per week of caloric restriction of 800 kcals). The primary research questions are, which IF strategy has the greatest effect on, (1) tumour burden (lymphocyte count), (2) autophagy induction and gut microbiome composition, (3) inflammation, (4) and is preferred by patients.

METHODS: This study is an extension of the investigators' current, single-arm trial to expand to a case crossover design, allowing each participant to serve as their own control. Following completion of a 90 day trial on the 16/8 Method during the "Intermittent Fasting in CLL/SLL" study (ClinicalTrials.gov Identifier: NCT04626843) and following a minimum of a 3 month washout period, participants will now follow the 5:2 Method for 90 days. Data collection will match previous current study protocol to allow for statistical comparison between lymphocyte count, inflammation, metabolomic profiles, autophagy status, and the gut microbiome (optional). Participants will complete a semi-structured interview on their experiences with the 16/8 Method and 5:2 Method that will be qualitatively analyzed.

Inclusion Criteria:

• Diagnosis of CLL or SLL
• Age < 85 years
• Peripheral blood lymphocytes >20 x 109/L
• Hemoglobin > 90g/L
• Platelets > 90 x 10*9/L
• BMI of >=20kg/m2
• ECOG Performance Status >=2
• Completion of "IF in CLL/SLL Study" (ClinicalTrials.gov Identifier: NCT04626843) followed by minimum of 3 month ad libitum eating

Exclusion Criteria:

• Patient unable to give consent
• Patient on medications required to be taken with food during the fasting window
• Pregnancy
• Diabetes mellitus
• BMI drop to < 18.5kg/m2 at any time during study
• Anti-lymphoma therapy within the past 3 months
• Expected to require initiation of anti-lymphoma therapy within the next 3 months