Fasting and Exercise for Immune System and Metabolism Study

(FASTEX Trial)

Overseen By Jonathan Little Principal Investigator, Professor Little, Ph.D

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Anti-inflammatory drugs

Disqualifiers: Cardiometabolic, Inflammatory, Smoking, BMI over 30, others

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

Compensation: Varies

Number of Visits: 6

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how fasting, with or without exercise, affects the immune system and metabolism. Researchers aim to determine how a two-day fast might alter immune cell energy use and blood sugar control in healthy individuals. Participants will either fast for 48 hours while cycling daily or fast without exercising. The trial suits those who are physically active and exercise regularly but excludes individuals with certain health conditions or on specific diets. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on fasting and exercise.

Will I have to stop taking my current medications?

The trial requires that you stop taking anti-inflammatory drugs like ibuprofen, aspirin, and naproxen.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fasting can be safe and might even benefit the immune system. One study found that short-term fasting reduced certain immune cells, which helped lower inflammation in healthy individuals. Another study demonstrated that fasting can enhance immune cell function and support a healthy metabolism.

When combined with exercise, studies suggest fasting can further boost metabolism and reduce inflammation. This indicates that fasting, with or without exercise, might be well-tolerated and could positively impact health. However, individual responses vary, and what works for one person may not work for another. It is important to consider personal health and consult a healthcare professional before trying something new. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about exploring fasting combined with exercise because it could offer a natural boost to the immune system and metabolism without relying on medication. While traditional options for enhancing metabolism often involve dietary supplements or prescription drugs, this method leverages the body's natural processes. The fasting and exercise combination might enhance metabolic efficiency and immune response more effectively than fasting alone. This approach could lead to a new, holistic way to improve health and well-being, especially if it proves to be more sustainable and accessible than current methods.

What evidence suggests that fasting and exercise could be effective for immune system and metabolism?

This trial will compare the effects of fasting combined with exercise to fasting alone. Research has shown that combining fasting with exercise can positively affect energy use and support the immune system. Studies indicate that this combination can help the body switch from using carbohydrates to fats for energy, benefiting overall health. It may also lower inflammation and improve how the immune system handles stress.

Participants in the fasting-only arm will undergo intermittent fasting, which has been found to reduce inflammation and improve sugar processing. It can also boost immune health by promoting healthy gut bacteria and enhancing immune cell function. Both fasting with exercise and fasting alone offer potential benefits for metabolism and the immune system. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for healthy, active adults interested in the effects of a 48-hour fast on their immune system and blood sugar control. Participants should not have any chronic health conditions that could be affected by fasting or exercise.

Inclusion Criteria

Physically active (engaging in ≥150 minutes of weekly moderate to vigorous physical activity)

I am between 19 and 35 years old.

Exclusion Criteria

My BMI is over 30.

Cigarette/vaping smoking

I have a history of heart, metabolic, or inflammatory diseases like COPD or arthritis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Fasting + Exercise (FAST+EX)

Participants undergo a 48-hour fast with 60 minutes of cycling on each day of the fast.

2 days

3 visits (in-person)

Fasting only (FAST)

Participants undergo a 48-hour fast without any structured exercise.

2 days

3 visits (in-person)

Washout Period

A five-day washout period between the two fasting conditions.

5 days

Follow-up

Participants are monitored for safety and effectiveness after the fasting conditions.

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Fasting + Exercise
• Fasting only

Trial Overview The study looks at how a two-day fast affects immune cell function and body's ability to manage blood sugar. It compares people who just fast with those who combine fasting with exercise to see if there are differences.

How Is the Trial Designed?

Group I: Fasting only (FAST): Non-exercise fasting condition Experimental Treatment 1 Intervention

48-hour fast with no structured exercise on fasting days.

Group II: Fasting + Exercise (FAST+EX): fasting + exercise condition Experimental Treatment 1 Intervention

48-hour fast with 60 minutes of cycling on the first and second day of the fast.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

Acute exercise has a significant impact on the metabolism of leukocytes (white blood cells), which is similar to the effects seen in skeletal muscle, suggesting that exercise can enhance immune function.

Chronic exercise and improved physical fitness are associated with better cellular metabolic regulation and respiratory function in leukocytes, indicating that regular physical activity can strengthen the immune system and reduce inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Scoping Review on the Effects of Physical Exercise and Fitness on Peripheral Leukocyte Energy Metabolism in Humans. Hodgman, CF., Hunt, RM., Crane, JC., et al.[2023]

In a study of 42 healthy female physique athletes, significant changes in immune function were observed in those undergoing intense weight loss through energy deprivation, indicating potential immunosuppression during this period.

Most immune parameters returned to baseline levels during the weight regain phase, suggesting that while intense weight loss negatively impacts immune function, recovery can restore immune health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss. Sarin, HV., Gudelj, I., Honkanen, J., et al.[2020]

In a study involving 14 moderately trained male subjects, a 36-hour fasting period followed by moderate exercise led to significant changes in immune function markers, including increased T cell apoptosis and inflammatory markers after exercise compared to a non-fasting control.

The results suggest that short-term fasting may worsen immune function and inflammation responses during and after exercise, indicating potential risks for individuals engaging in exercise under fasting conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effects of moderate exercise and short-term fasting on markers of immune function in healthy human subjects. Mooren, FC., Krueger, K., Ringseis, R., et al.[2020]

Moderate-intensity exercise combined with intermittent fasting significantly improved immune system markers in rats on a high-fat diet, increasing lymphocyte and anti-inflammatory cytokine levels.

The study demonstrated that this combination reduced pro-inflammatory cytokines like TNF-α, suggesting a potential strategy for mitigating inflammation and enhancing immune function in high-fat diet conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Moderate-Intensity Physical Exercise on Some Serum Inflammation Markers and the Immune System in Rats Fed Intermittent Fasting with a High-Fat Diet. Günbatar, N., Bulduk, B., Bezgin, S., et al.[2023]

In a study of 49 college judoists, those who combined dietary restriction with exercise (WR group) experienced significant weight loss and reductions in immune markers like IgG and IgM after competition, indicating potential negative effects on immune function.

The findings suggest that while energy restriction can enhance weight loss, it may also worsen immune responses following intense exercise, raising concerns about the long-term health of athletes who frequently compete.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of energy restriction on changes in immunoglobulins and complements during weight reduction in judoists. Umeda, T., Nakaji, S., Shimoyama, T., et al.[2017]

A 24-hour fast significantly increased the expression of IL-1 receptor type 2 (IL-1R2) and IL-1 receptor antagonist (IL-1RA) in mice, suggesting that fasting enhances the body's ability to resist IL-1, a key player in inflammation.

Fasting not only protects against IL-1β-induced negative effects like weight loss and anxiety but also triggers increases in plasma free-fatty acids, which may signal the body to suppress immune responses during fasting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting Induces IL-1 Resistance and Free-Fatty Acid-Mediated Up-Regulation of IL-1R2 and IL-1RA. Joesting, JJ., Moon, ML., Gainey, SJ., et al.[2021]

Fasting during Ramadan, especially in the context of the COVID-19 pandemic, raises concerns about immune health, prompting the need for effective nutritional strategies and exercise programs to support immune function.

The study aims to explore the health effects of fasting on the immune system and provide guidance on maintaining health and nutrition for those observing Ramadan while facing the challenges posed by COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramadan Fasting During the COVID-19 Pandemic; Observance of Health, Nutrition and Exercise Criteria for Improving the Immune System. Moghadam, MT., Taati, B., Paydar Ardakani, SM., et al.[2021]

Short-term fasting significantly reduces the number of circulating monocytes and their inflammatory activity, which may help improve chronic inflammatory and autoimmune diseases.

The study found that this effect is regulated by dietary glucose and protein levels, with mechanisms involving the activation of AMPK in the liver and suppression of CCL2 production, linking caloric intake to immune response and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool. Jordan, S., Tung, N., Casanova-Acebes, M., et al.[2020]

Chronic moderate-intensity exercise improved the immune function of rats under energy restriction by enhancing lymphocyte proliferation and increasing the production of key cytokines like gamma-interferon and interleukin-1.

Despite these improvements, the exercise did not alter the Th1-type immune response induced by energy restriction, indicating that while exercise can help restore some immune functions, it may not fully counteract the effects of reduced food intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise restores immune cell function in energy-restricted rats. Dos Santos Cunha, WD., Giampietro, MV., De Souza, DF., et al.[2019]

In a 12-month randomized controlled trial involving 115 postmenopausal, overweight, or obese women, aerobic exercise did not improve in vitro immune function markers such as natural killer cell activity and T-lymphocyte proliferation, despite participants adhering to the exercise regimen and showing increased fitness levels.

The study demonstrated that while the exercise group significantly increased their physical activity and aerobic capacity, these changes did not translate into measurable enhancements in immune function compared to a stretching control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exercise on in vitro immune function: a 12-month randomized, controlled trial among postmenopausal women. Campbell, PT., Wener, MH., Sorensen, B., et al.[2013]

A 48-hour period of energy restriction (ER) and combined fluid and energy restriction (F+ER) significantly decreased circulating leukocyte and lymphocyte counts in healthy men, while fluid restriction alone did not have this effect.

Despite the reductions in leukocyte and lymphocyte counts during ER and F+ER, neutrophil counts and their degranulation remained unchanged, indicating that short-term dietary restrictions do not impair neutrophil function during exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neutrophil-degranulation and lymphocyte-subset response after 48 hr of fluid and/or energy restriction. Laing, SJ., Oliver, SJ., Wilson, S., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10011094/

Intermittent fasting and immunomodulatory effects IF could benefit health subjects by strengthening their circadian rhythms, migrating immune cells, lower inflammatory factors, and enriching microbials.

2. nature.com nature.com/articles/s41598-025-05164-0

Metabolic and hormonal effects of an 8 days water only ... Overall, combining fasting and exercise led to a metabolic shift from carbohydrates to fatty acids and hormonal adaptations to stress. These ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06737224

The Impact of a 48-hour Fast with or Without Exercise on ... 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 ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/imm.13829

A detective story of intermittent fasting effect on immunity The fasting state appears to decrease peripheral white blood cells, and IF with a fasting-refeeding switch appears to promote immune tolerance.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2212267224002545

A Narrative Review of Intermittent Fasting With Exercise Summary of findings: These data suggest that ADF combined with aerobic training may improve body weight by 4% to 7% in 8 to 12 weeks as well as significant ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2213231724004002

Time-restricted eating reveals a “younger” immune system ... Time-restricted eating (TRE) has been shown to extent lifespans in drosophila and mouse models by affecting metabolic and anti-inflammatory activities.

7. mdpi.com mdpi.com/2072-6643/15/10/2277

Intermittent Fasting and Physical Exercise for Preventing ... Healthy dietary interventions, such as intermittent fasting, coupled with regular physical exercise can improve several metabolic and inflammatory parameters.