The Impact of a 48-hour Fast with or Without Exercise on Immune Cell Metabolism and Glycemic Control in Healthy Active Adults

The Impact of a 48-hour Fast with or Without Exercise on Immune Cell Function, Bioenergetics, and Glycemic Control in Healthy Active Adults: a Randomized Crossover Trial

Many individuals engage in fasting for its purported health benefits but the effects of fasting on immune cell and whole body metabolism are not well understood in humans. Moreover, how exercising during a prolonged fast impacts immunometabolic outcomes is unclear. This study will determine how a 2 day fast - performed with or without daily exercise - impacts immune cell bioenergetics, immune cell function, and whole-body glycemic control in healthy active individuals.

Participants will perform two, 48-hour fasts separated by 5 days while wearing a continuous glucose monitor to measure glycemic responses. The order of the trials will be randomized for each participant. The two trials will include an exercise condition (FAST+EX) and a control, non-exercise condition (FAST). During the FAST+EX trial, participants will perform 60 minutes of cycling on each of the two days of the fast. Each bout of exercise will be 60 minutes in duration and consist of 50 minutes of cycling at 60% of predicted heart rate reserve (HRR) followed by 5 x 1-minute intervals at 90% of predicted HRR with 1-minute of passive recovery between each interval. During the FAST trial, participants will be asked to refrain from any structured exercise during the days of the fast. To start the trial, participants will arrive at the lab following an overnight fast. They will consume a standardized meal replacement (Ensure Plus Calories) and blood will be drawn 2 hours post-ingestion. Participants will come to the lab 24 and 48 hours later for subsequent blood draws prior to breaking their fast with the same standardized meal replacement. Another blood sample will be taken 2 hours post-prandial. Participants will be asked to replicate food consumption in each condition for the 24-hour period after they break their fast, and consume the same standardized meal replacement on the morning following the completion of each fast to measure free-living glycemic control 24-hours after a fast performed with or without exercise. There will be a five-day wash out period in between the completion of both trials for all participants.

Inclusion Criteria:

• Aged between 19 and 35 years.
• Physically active (engaging in ≥150 minutes of weekly moderate to vigorous physical activity).

Exclusion Criteria:

• History of cardiometabolic diseases or inflammatory diseases (e.g., chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, cardiovascular disease).
• Individuals currently following a ketogenic diet, low-calorie diet, periodic fasting regimen, or consuming ketogenic supplements (e.g., exogenous ketone drinks).
• Cigarette/vaping smoking.
• Physical limitation that will impair the ability of the participant to perform exercise.
• Individuals having a body mass index (BMI) over 30 kg/m2.
• Cancer diagnosis in the past 5 years.
• Taking anti-inflammatory drugs (e.g., ibuprofen, aspirin, naproxen).
• Being unable to read or communicate in English.