Today, the term “stress” is generally associated with negative health implications. However, there are actually two different types of stress that one can experience —distress, the type of stress that can lead to feelings of overwhelm or anxiety, and eustress, a positive form of stress. Eustress, caused by practices like fasting and exercise, place a positive form of stress on your body and can provide many health benefits.
In recent years, intermittent fasting has become a popular method of achieving weight loss. However, intermittent fasting benefits many different aspects of our health, including our immune system.
What is intermittent fasting?
Intermittent fasting involves periodically abstaining from eating, eating ad libitum (as often as desired) between fasting periods. (23) There are many different intermittent fasting schedules; common forms include time-restricted feeding (e.g., eating for eight hours, then fasting for the other 16 hours of the day), alternate-day fasting (i.e., fasting every other day), and the 5:2 approach (i.e., fasting two days a week and consuming food ad libitum for the remaining days).
Immune benefits of intermittent fasting
There are many different benefits of intermittent fasting for our immune system. Intermittent fasting helps improve immune function, repair damaged cells, remove dysfunctional cells and pathogens, and modulate the immune system.
Inflammation involves swelling of your body’s tissues in response to injury or infection. This helps to recruit immune cells to the area to help resolve the issue. Short-term inflammation is a beneficial immune response, as it subsides after an insulting agent is eliminated. However, when inflammation becomes chronic due to persistent stimulus (e.g., food sensitivity), it can lead to progressive tissue destruction. Additionally, inflammation is a factor in many chronic illnesses, such as asthma and arthritis. (18) Fasting has been shown to induce anti-inflammatory effects. Many of the beneficial effects of fasting appear to be attributed to a change in metabolism, in which your body shifts from using glucose to lipids (fat) as a primary source of energy (2). Fatty acids that are produced from the breakdown of fat are transported into liver cells, where they are converted to produce the ketones β-hydroxybutyrate (BHB) and acetoacetate (11). BHB is a major ketone body that fuels many vital organs during fasting/starvation and also decreases inflammation. (25) Research has shown that BHB reduces the production of certain pro-inflammatory cytokines (IL-1β and IL-18). (25) Cytokines are cellular signals within the immune system, some of which promote inflammation.
In a study of 50 healthy volunteers, fasting was associated with a significant decrease in the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α (9). Another study conducted on subjects with obesity and asthma showed that, in addition to improvement of their condition, fasting was associated with significant reductions in inflammatory markers. (23)
In response to cellular stress, such as during restriction of nutrient intake, the body activates autophagy and upregulates autophagy-related proteins. (19) Autophagy is a process that breaks down dysfunctional, lethal, and mutant biomolecules, organelles, and invading pathogens, (10)(17)(21) which are then recycled or eliminated. This is done to produce sugars, nucleosides/nucleotides, amino acids, and fatty acids to maintain cellular homeostasis. (12) In this way, the body can obtain the nutrients that it needs and eliminate dysfunctional cells or pathogens that can become problematic.
Central to autophagy is the formation of autophagosomes, double-membrane vesicles responsible for delivering cytoplasmic material to lysosomes. (24) Lysosomes are cellular structures that contain digestive enzymes and aid in the process of breaking down unuseful materials. One animal study found that there was an increase in the number and size of autophagosomes in mice that underwent food restriction. (1)
Furthermore, autophagy, in addition to other processes, is involved in the presentation of pathogen components to the immune system, which acts to alert other immune cells and activates them to eliminate specific pathogens. (8)
Can help decrease autoimmunity
Autoimmunity occurs when an immune system is not working properly and it attacks its own healthy cells. (8) Some conditions involving autoimmunity include multiple sclerosis (MS), causing deterioration of the central nervous system, and rheumatoid arthritis (RA), causing destruction of joint tissue. (4)(6)
In MS animal models, a diet mimicking fasting led to improved MS symptoms and reduced autoimmunity. (5)(7) These improvements were associated with reduced levels of pro-inflammatory cytokines (IL-17) and increased numbers of immune cells called T regulatory (Treg) cells. Treg cells support the activity of other immune cells and help to prevent autoimmunity. Similarly, a human clinical trial in patients with relapse-remitting MS found that a fasting-mimicking diet was associated with improved disease severity and quality of life as measured using the Expanded Disability Status Scales (EDSS). (5)
Furthermore, similar fasting benefits were noted in patients with RA. In one study, 53 patients with RA were separated into control diet or fasting groups for a period of seven to ten days, after which they followed a vegan diet. Patients in the fasting group reported a significant improvement in the number of swollen and tender joints, pain score, duration of morning stiffness, and grip strength. Improvements in certain laboratory parameters related to RA disease severity, such as erythrocyte sedimentation rate and C-reactive protein, were also demonstrated. (15)
Increases DNA repair
Our DNA is under constant attack by endogenous and exogenous reactive molecules that can cause damage and negatively impact health. (14) Commonly encountered exogenous sources include ultraviolet light from the sun, ionizing radiation (e.g., X rays), and pollutants (e.g., herbicides such as paraquat used to eliminate weeds). (16) Luckily, our bodies have various mechanisms to repair DNA, and fasting has been shown to help support these mechanisms. Intermittent fasting was shown to upregulate expression of a key DNA repair protein, known as CEP164. (20) This DNA repair protein is involved in recruiting DNA repair proteins to DNA sites damaged by ultraviolet and ionizing radiation. (22) On average, researchers found a 45-fold increase in the level of CEP164 at the end of a 30-day intermittent fasting period compared to levels before fasting. (15)
Benefits gut microbiota
Gut microbiota refers to the microbes that live within our gastrointestinal tract. Since eating may introduce pathogens into our bodies, a healthy gut microbiota plays a significant role in defending us against these pathogens. In animal models, intermittent fasting has led to increased gut bacteria diversity, specifically with Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families. (7)
Intermittent fasting safety
Intermittent fasting may not be appropriate for children, women who are pregnant or lactating, or other populations that have higher nutrient needs. (3) Similarly, patients who are nutritionally compromised due to conditions associated with malabsorption or limited caloric intake (e.g., inflammatory bowel disease) are advised to consult their integrative healthcare provider before following an intermittent fasting regimen. (13)
Caution should also be exercised for patients who have diabetes, as fasting can lead to a life-threatening complication where the body starts to produce ketones at a rate that is too fast, which can cause the blood to become acidic. (7)
The bottom line
While intermittent fasting for weight loss has become popular, it also has great potential to benefit your immune health through the various pathways that are induced once your body goes into a fasted state. Not only can intermittent fasting help strengthen your immune system by increasing autophagy, DNA repair and gut microbiota diversity, but it can also help modulate an overactive immune system by helping to decrease inflammation and autoimmunity. Simple yet rewarding, intermittent fasting can help to balance out immune function and give your immune system a boost.
- Alirezaei, M., Kemball, C. C., Flynn, C. T., Wood, M. R., Whitton, J. L., & Kiosses, W. B. (2010). Short-term fasting induces profound neuronal autophagy. Autophagy, 6(6), 702–710. https://doi.org/10.4161/auto.6.6.12376
- Anton, S. D., Moehl, K., Donahoo, W. T., Marosi, K., Lee, S. A., Mainous, A. G., Leeuwenburgh, C., & Mattson, M. P. (2017). Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity, 26(2), 254–268. https://doi.org/10.1002/oby.22065
- Bazzano, A. N., Potts, K. S., & Mulugeta, A. (2018). How do pregnant and lactating women, and young children, experience religious food restriction at the community level? A qualitative study of fasting traditions and feeding behaviors in four regions of Ethiopia. PLOS ONE, 13(12), e0208408. https://doi.org/10.1371/journal.pone.0208408
- Centers for Disease Control and Prevention. (n.d.). Rheumatoid Arthritis (RA) | Arthritis | CDC. Retrieved June 20, 2021, from https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html
- Choi, I., Piccio, L., Childress, P., Bollman, B., Ghosh, A., Brandhorst, S., Suarez, J., Michalsen, A., Cross, A., Morgan, T., Wei, M., Paul, F., Bock, M., & Longo, V. (2016). A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms. Cell Reports, 15(10), 2136–2146. https://doi.org/10.1016/j.celrep.2016.05.009
- Choi, I. Y., Lee, C., & Longo, V. D. (2017). Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence. Molecular and Cellular Endocrinology, 455, 4–12. https://doi.org/10.1016/j.mce.2017.01.042
- Cignarella, F., Cantoni, C., Ghezzi, L., Salter, A., Dorsett, Y., Chen, L., Phillips, D., Weinstock, G. M., Fontana, L., Cross, A. H., Zhou, Y., & Piccio, L. (2018). Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota. Cell Metabolism, 27(6), 1222–1235.e6. https://doi.org/10.1016/j.cmet.2018.05.006
- Crotzer, V. L., & Blum, J. S. (2009). Autophagy and Its Role in MHC-Mediated Antigen Presentation. The Journal of Immunology, 182(6), 3335–3341. https://doi.org/10.4049/jimmunol.0803458
- Faris, M. A. I. E., Kacimi, S., Al-Kurd, R. A., Fararjeh, M. A., Bustanji, Y. K., Mohammad, M. K., & Salem, M. L. (2012). Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects. Nutrition Research, 32(12), 947–955. https://doi.org/10.1016/j.nutres.2012.06.021
- Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., Cuervo, A. M., Debnath, J., Deretic, V., Dikic, I., Eskelinen, E., Fimia, G. M., Fulda, S., Gewirtz, D. A., Green, D. R., . . . Kroemer, G. (2017). Molecular definitions of autophagy and related processes. The EMBO Journal, 36(13), 1811–1836. https://doi.org/10.15252/embj.201796697
- Gano, L. B., Patel, M., & Rho, J. M. (2014). Ketogenic diets, mitochondria, and neurological diseases. Journal of Lipid Research, 55(11), 2211–2228. https://doi.org/10.1194/jlr.r048975
- Hannan, M. A., Rahaman, Rahman, S., Sohag, A. A. M., Dash, R., Hossain, K. S., Farjana, M., & Uddin, M. J. (2020). Intermittent fasting, a possible priming tool for host defense against SARS-CoV-2 infection: crosstalk among calorie restriction, autophagy and immune response. OSF Preprints. Published. https://doi.org/10.31219/osf.io/jt738
- Hoffman, R., & Gazella, K. A. (2020, July). Recommending Intermittent Fasting. Natural Medicine Journal. https://www.naturalmedicinejournal.com/journal/2020-07/recommending-intermittent-fasting
- Kaina, B., & Fritz, G. (2006). DNA Damaging Agents. Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine, 416–423. https://doi.org/10.1007/3-540-29623-9_2270
- Kjeldsen-Kragh, J., Borchgrevink, C., Laerum, E., Haugen, M., Eek, M., Førre, O., Mowinkel, P., & Hovi, K. (1991). Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. The Lancet, 338(8772), 899–902. https://doi.org/10.1016/0140-6736(91)91770-u
- Krumova, K., & Cosa, G. (2016). Chapter 1. Overview of Reactive Oxygen Species. Comprehensive Series in Photochemical & Photobiological Sciences, 1–21. https://doi.org/10.1039/9781782622208-0000
- Levine, B., & Klionsky, D. J. (2004). Development by Self-Digestion. Developmental Cell, 6(4), 463–477. https://doi.org/10.1016/s1534-5807(04)00099-1
- Longo, V., & Mattson, M. (2014). Fasting: Molecular Mechanisms and Clinical Applications. Cell Metabolism, 19(2), 181–192. https://doi.org/10.1016/j.cmet.2013.12.008
- Mijaljica, D., Prescott, M., & Devenish, R. J. (2012). The Intriguing Life of Autophagosomes. International Journal of Molecular Sciences, 13(3), 3618–3635. https://doi.org/10.3390/ijms13033618
- Mindikoglu, A. L., Abdulsada, M. M., Jain, A., Choi, J. M., Jalal, P. K., Devaraj, S., Mezzari, M. P., Petrosino, J. F., Opekun, A. R., & Jung, S. Y. (2020). Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function in healthy subjects. Journal of Proteomics, 217, 103645. https://doi.org/10.1016/j.jprot.2020.103645
- Rahman, M. A., Saha, S. K., Rahman, M. S., Uddin, M. J., Uddin, M. S., Pang, M. G., Rhim, H., & Cho, S. G. (2020). Molecular Insights Into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells. Frontiers in Cell and Developmental Biology, 8. https://doi.org/10.3389/fcell.2020.00283
- Sivasubramaniam, S., Sun, X., Pan, Y. R., Wang, S., & Lee, E. Y. H. (2008). Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA, and CHK1. Genes & Development, 22(5), 587–600. https://doi.org/10.1101/gad.1627708
- Stockman, M. C., Thomas, D., Burke, J., & Apovian, C. M. (2018). Intermittent Fasting: Is the Wait Worth the Weight? Current Obesity Reports, 7(2), 172–185. https://doi.org/10.1007/s13679-018-0308-9
- Xie, Z., & Klionsky, D. J. (2007). Autophagosome formation: core machinery and adaptations. Nature Cell Biology, 9(10), 1102–1109. https://doi.org/10.1038/ncb1007-1102
- Youm, Y. H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D’Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., Kang, S., Horvath, T. L., Fahmy, T. M., Crawford, P. A., Biragyn, A., Alnemri, E., & Dixit, V. D. (2015). The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nature Medicine, 21(3), 263–269. https://doi.org/10.1038/nm.3804