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

Trial Summary

What is the purpose of this 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.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Fasting + Exercise, Fasting only for immune system and metabolism?

Research shows that short-term fasting combined with exercise can affect immune function by altering levels of certain immune cells and inflammation markers. Additionally, fasting alone has been found to reduce inflammation and improve outcomes in chronic inflammatory diseases without affecting the body's ability to respond to infections. ^{1 2 3 4 5}

Is fasting combined with exercise generally safe for humans?

Research shows that short-term fasting combined with exercise can affect immune function, sometimes increasing inflammation and immune cell changes. However, these effects are usually temporary and may return to normal after resuming regular eating and exercise habits. ^{1 2 4 6 7}

How does the Fasting and Exercise treatment differ from other treatments for immune system and metabolism issues?

The Fasting and Exercise treatment is unique because it combines short-term fasting with moderate exercise to influence immune function and metabolism. This approach is different from other treatments as it leverages the body's natural responses to fasting and physical activity, potentially enhancing immune markers and reducing inflammation without the use of medication. ^{1 8 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Combined effects of moderate exercise and short-term fasting on markers of immune function in healthy human subjects. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss. [2020]

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

Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool. [2020]

4. Italy pubmed.ncbi.nlm.nih.gov

Adverse effects of energy restriction on changes in immunoglobulins and complements during weight reduction in judoists. [2017]

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

Exercise restores immune cell function in energy-restricted rats. [2019]

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

Effect of exercise on in vitro immune function: a 12-month randomized, controlled trial among postmenopausal women. [2013]

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

Neutrophil-degranulation and lymphocyte-subset response after 48 hr of fluid and/or energy restriction. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

A Scoping Review on the Effects of Physical Exercise and Fitness on Peripheral Leukocyte Energy Metabolism in Humans. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Ramadan Fasting During the COVID-19 Pandemic; Observance of Health, Nutrition and Exercise Criteria for Improving the Immune System. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Fasting Induces IL-1 Resistance and Free-Fatty Acid-Mediated Up-Regulation of IL-1R2 and IL-1RA. [2021]

11. Switzerland 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. [2023]