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A diet that includes a variety of anti-inflammatory foods such as colorful fruits and vegetables that supply nutrients and natural antioxidants helps to boost a patient’s immune health and wellness.1,2 Integrating other dietary approaches into therapeutic nutritional strategies based on a patient’s needs may also help to enhance immune resiliency. Fasting strategies, for example, may benefit clinical treatments for a range of health areas, from cardiometabolic disorders to mitochondrial dysfunction.3,4 Different types of fasting approaches have also shown potential benefit for immune health through modulating immune responses, enhancing immune memory, and suppressing inflammation.5 What mechanisms and markers of immune function are impacted during fasting treatments? How is the gut microbiome involved, and how can personalized therapeutic strategies that incorporate different levels of fasting help to optimize a patient’s immune health?
In the following video, IFM educator Monique Class, MS, APRN, BC, IFMCP, highlights health impacts of fasting, from reducing inflammation and oxidative stress to increasing autophagy, a beneficial “housecleaning” process where damaged cells and pathogens are removed from the body. She also discusses clinical approaches when incorporating fasting cycles into personalized nutrition interventions.
Fasting Developments: Mechanisms & Immune Pathways
Both animal and human studies continue to elucidate the effects of fasting cycles on the immune system and to help researchers identify the mechanisms involved. Studies have suggested that different forms and lengths of fasting impact distinct immune responses, cells, and pathways.6 Results from a small clinical trial found that after 72 hours of water-only fasting, autophagy levels of leukocytes were enhanced through upregulation of upstream signaling and apoptosis was reduced through the downregulation of apoptotic gene expression.7 In addition, components of the innate immune system were boosted compared to baseline measurements. Specifically, analysis indicated increased peripheral neutrophils and an upregulation of the CD45+ protein expressed on leukocytes.7
A 2022 clinical study investigated the safety and biological effects of a fasting-mimicking diet (FMD) in patients diagnosed with a variety of cancers such as breast, colorectal, lung, and prostate.8 In combination with their standard antitumor therapies, patients followed an average of four FMD cycles (i.e., five-day FMD followed by 16 to 23 days of refeeding). Consistent decreased blood glucose and growth factor concentrations were reported. Additional investigation found that FMD cycles reshaped systemic and intratumor immunity by increasing immune cell populations believed to be involved in the antitumor immune response and by reducing biomarkers associated with immune suppression.8
A recent randomized controlled trial (n=20) compared inflammatory biomarker measurements between participants in a normal diet control group and a time-restricted eating (TRE) intervention group.9 The experiment lasted 12 months, and the normal diet group consumed meals three times per day at 8 am, 1 pm, and 8 pm. The TRE group consumed three meals per day within an eight-hour time frame at 1 pm, 4 pm, and 8 pm. After 12 months of TRE, inflammatory markers (interleukin 6, interleukin 1-beta, and TNF-alpha) were reduced, and both insulin sensitivity and lipid profiles were significantly improved compared to controls.9
intestinal homeostasis & GUT microbiota populations
Much of the body’s immune response depends upon the gastrointestinal microbiome, and the influence of dietary approaches on this complex, bidirectional, gut-immune relationship continues to be explored. Research findings based on both animal models and some human studies have highlighted the potential benefits of fasting on gut-immune health such as decreased intestinal inflammation and an expansion of protective gut bacteria.10-13
Some fasting protocols may also help positively shape intestinal immune-related responses through microbial metabolic pathways.14 Most recently, a 2021 randomized controlled trial (n=39 patients with metabolic syndrome) investigated potential health benefits of intermittent fasting.15 The intervention consisted of eight weeks of a two-day intermittent fast (75% energy restriction for two nonconsecutive days a week). Results indicated that compared to controls, intermittent fasting enhanced beneficial gut bacteria populations and improved gut-related metabolites, including an increase in short-chain fatty acids that promote healthy immune function and a decrease in circulating levels of lipopolysaccharides.15
Personalized Nutrition Interventions: A Fasting Component
Lifestyle-based interventions such as dietary treatments are core tools and strategies in the functional medicine approach to health. As part of nutrition interventions, fasting may be appropriate for some patients, and research continues to expand the data for clinical application of fasting protocols. For example, a randomized controlled trial has been proposed to investigate the immune and metabolic impacts of an anti-inflammatory diet combined with a fasting component.16 In addition, interventional trials continue to evaluate autophagy-inducing nutritional approaches and their potential cancer-preventative or therapeutic effects.17
Appropriate fasting may help support a patient’s immune health, and functional medicine provides a framework within which practitioners may collaborate with patients to develop the most effective and sustainable personalized nutrition intervention. With many different types and methods of fasting, fasting-related research continues to evolve, with a focus on therapeutic applications.
IFM’s Intermittent Fasting: Therapeutic Mechanisms & Clinical Applications course provides an evidence-based overview of several of the fasting methods listed above and outlines potential contraindications and points of personalization for each patient’s unique health needs and goals.
- Iddir M, Brito A, Dingeo G, et al. Strengthening the immune system and reducing inflammation and oxidative stress through diet and nutrition: considerations during the COVID-19 crisis. Nutrients. 2020;12(6):1562. doi:3390/nu12061562
- Childs CE, Calder PC, Miles EA. Diet and immune function. Nutrients. 2019;11(8):1933. doi:3390/nu11081933
- Tsitsou S, Zacharodimos N, Poulia KA, Karatzi K, Dimitriadis G, Papakonstantinou E. Effects of time-restricted feeding and Ramadan fasting on body weight, body composition, glucose responses, and insulin resistance: a systematic review of randomized controlled trials. Nutrients. 2022;14(22):4778. doi:3390/nu14224778
- Zhao Y, Jia M, Chen W, Liu Z. The neuroprotective effects of intermittent fasting on brain aging and neurodegenerative diseases via regulating mitochondrial function. Free Radic Biol Med. 2022;182:206-218. doi:1016/j.freeradbiomed.2022.02.021
- Okawa T, Nagai M, Hase K. Dietary intervention impacts immune cell functions and dynamics by inducing metabolic rewiring. Front Immunol. 2021;11:623989. doi:3389/fimmu.2020.623989
- Buono R, Longo VD. When fasting gets tough, the tough immune cells get going—or die. Cell. 2019;178(5):1038-1040. doi:1016/j.cell.2019.07.052
- Qian J, Fang Y, Yuan N, et al. Innate immune remodeling by short-term intensive fasting. Aging Cell. 2021;20(11):e13507. doi:1111/acel.13507
- Vernieri C, Fucà G, Ligorio F, et al. Fasting-mimicking diet is safe and reshapes metabolism and antitumor immunity in patients with cancer. Cancer Discov. 2022;12(1):90-107. doi:1158/2159-8290.CD-21-0030
- Moro T, Tinsley G, Pacelli FQ, Marcolin G, Bianco A, Paoli A. Twelve months of time-restricted eating and resistance training improves inflammatory markers and cardiometabolic risk factors. Med Sci Sports Exerc. 2021;53(12):2577-2585. doi:1249/MSS.0000000000002738
- Cignarella F, Cantoni C, Ghezzi L, et al. Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab. 2018;27(6):1222-1235.e6. doi:1016/j.cmet.2018.05.006
- Rangan P, Choi I, Wei M, et al. Fasting-mimicking diet modulates microbiota and promotes intestinal regeneration to reduce inflammatory bowel disease pathology. Cell Rep. 2019;26(10):2704-2719.e6. doi:1016/j.celrep.2019.02.019
- Schmidt NS, Lorentz A. Dietary restrictions modulate the gut microbiota: implications for health and disease. Nutr Res. 2021;89:10-22. doi:1016/j.nutres.2021.03.001
- Pinto FCS, Silva AAM, Souza SL. Repercussions of intermittent fasting on the intestinal microbiota community and body composition: a systematic review. Nutr Rev. 2022;80(3):613-628. doi:1093/nutrit/nuab108
- Matías-Pérez D, Hernández-Bautista E, García-Montalvo IA. Intermittent fasting may optimize intestinal microbiota, adipocyte status and metabolic health. Asia Pac J Clin Nutr. 2022;31(1):16-23. doi:6133/apjcn.202203_31(1).0002
- Guo Y, Luo S, Ye Y, Yin S, Fan J, Xia M. Intermittent fasting improves cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. J Clin Endocrinol Metab. 2021;106(1):64-79. doi:1210/clinem/dgaa644
- Papamichou D, Panagiotakos DB, Holmes E, et al. The rationale and design of a Mediterranean diet accompanied by time restricted feeding to optimise the management of type 2 diabetes: the MedDietFast randomised controlled trial. Nutr Metab Cardiovasc Dis. 2022;32(1):220-230. doi:1016/j.numecd.2021.09.031
- Hofer SJ, Kroemer G, Kepp O. Autophagy-inducing nutritional interventions in experimental and clinical oncology. Int Rev Cell Mol Biol. 2022;373:125-158. doi:10.1016/bs.ircmb.2022.08.003