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Review

The Relationship Between Autoimmune Disease and Intermittent Fasting: A Narrative Review

by
Krista Yasuda
1 and
Rebecca Jean Ryznar
1,2,*
1
College of Osteopathic Medicine, Rocky Vista University, 8401 S. Chambers Road, Englewood, CO 80112, USA
2
Department of Biomedical Sciences, College of Osteopathic Medicine, Rocky Vista University, 8401 S. Chambers Road, Englewood, CO 80112, USA
*
Author to whom correspondence should be addressed.
Immuno 2025, 5(4), 60; https://doi.org/10.3390/immuno5040060 (registering DOI)
Submission received: 9 November 2025 / Revised: 2 December 2025 / Accepted: 4 December 2025 / Published: 5 December 2025
(This article belongs to the Section Autoimmunity and Immunoregulation)
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Abstract

Autoimmune disease (AD) is a breakdown of self-tolerance by the immune system and has a variety of clinical manifestations and complications across all organ systems. One of the targets for treatment of AD aims at reducing inflammation and upregulating factors that eliminate autoreactive cells. Intermittent fasting (IF) has recently gained popularity as a dietary intervention for weight management, but has also been found to interact and positively interfere with pathways involved in the pathophysiology of AD. Methods include searching in the PubMed and Google Scholar databases for reviews and clinical trials studying any relationships between AD and IF. The search results have identified a variety of anti-inflammatory effects IF has on the immune system that can potentially reduce AD severity and several trials specifically studying IF’s effects on type I diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). Based on the findings, IF has potential anti-inflammatory effects that could assist with decreasing AD severity. Future directions include studies to further determine safety and efficacy of IF with AD, broader investigations to include IF’s impact on a wide variety of ADs, an ideal time frame of how long patients should remain on IF, and any potential interactions IF may have on current drug therapies used to treat AD. This review also aims to encourage more human studies of IF and its application to AD given that many of these results are largely from in vitro, cellular and molecular, and animal studies.

1. Introduction

AD is characterized as a loss of self-tolerance by the immune system [1]. AD has a diverse array of manifestations and can affect many organs and systems. Some of these include, but are not limited to, endocrine dysfunction and diabetes [2], renal failure [3], joint pain and destruction [4], gastrointestinal dysfunction and malabsorption [5], and neurodegeneration [6]. These diseases are also associated with significant morbidity and mortality [7]. The incidence of T1D in the U.S. has increased, with an estimated 4958 individuals under the age of 19 in 2001 and 7759 individuals in 2017 [8]. A 2021 study identified that the global prevalence of RA was approximately 1% [9]. Overall, 2.3 million people are also currently affected by MS worldwide, with a prevalence of >90/100,000 in the U.S. [6]. As a total overview, studies have shown that the worldwide incidence and prevalence of AD are increasing, and recent estimates demonstrate a global incidence of 19.1% and a prevalence of 12.5% [10,11]. With this increase in AD, much research has been dedicated to investigating etiologies, pathology, cellular/molecular mechanisms of disease, and treatments. Some of these include studying the involved inflammatory pathways [12,13], the antibodies involved in organ dysfunction and physiology disruption, and the development of treatments targeted towards these antibodies and inflammatory pathways [14,15,16], which will be further discussed below. After discussing these pathways, we will discuss how IF can potentially modulate the immune system through these pathways. The potential benefits and anti-inflammatory effects of IF will then be explored through a summary of clinical trials that investigated the effects of IF on various ADs. Through this review, we can potentially further close the research gap for alternative treatments for AD, especially given that the current mainstays of AD treatment are primarily pharmacologic. All references cited in this article were identified through the keywords “autoimmunity” and “intermittent fasting” through PubMed and Google Scholar and consist of reviews, in vitro studies, and a small number of human studies. The selected references were then used to help narrate the potential relationship between AD, IF, and anti-inflammatory effects in this review.

2. Autoimmune Disease Pathophysiology

In a healthy individual, the immune system has many regulatory processes in place to ensure a balance between effectively recognizing and eradicating foreign pathogens without attacking itself. To maintain self-tolerance, all developing lymphocytes undergo a positive and negative selective process to ensure the degradation of any lymphocytes that are reactive toward self-antigens. T regulatory cells (Tregs) are also produced for surveillance and deletion of any mature lymphocytes in circulation that are reactive to self [17]. A breakdown in any of the steps along the lymphocyte maturation pathway or a failure of Tregs to function can result in the development of AD. One of the potential triggers that has been identified with this breakdown of self-tolerance is systemic chronic inflammation. During chronic inflammation, multiple inflammatory pathways are continuously activated along with continued high levels of pro-inflammatory cytokines. This elevated and continuous activity disrupts the normal physiology of immune function, including T cell function. Some of these inflammatory pathways and cytokines will be further discussed below. Multiple factors that induce stress are chronic infections, obesity, diet, intestinal dysbiosis, psychological stress, and disruptions in circadian rhythms, and these can lead to a state of constant low-grade systemic inflammation, which can predispose an individual to multiple diseases, including AD [12,13]. These inflammatory trigger pathways and disruptions in Treg function are detailed in Figure 1.
During inflammation and activation of the innate immune response, numerous pro-inflammatory cytokines and acute-phase proteins, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor-necrosis factor-α (TNF-α), and C-reactive protein (CRP) are increased in circulation [18]. IL-1β is an endogenous pyrogen that is also closely associated with the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. The NLRP3 inflammasome is one of the key mediators of systemic inflammatory processes [19]. IL-6 works to promote antibody production, BCL6-dependent follicular CD4+ differentiation, T helper 17 (Th17) cell differentiation, further IL-6 release from non-immune cells to induce cyclic inflammation, and nuclear factor-kappa B (NF-κB) activation [20]. TNF-α is a major signaling molecule involved in the regulation of inflammatory responses [21]. CRP helps promote the production of pro-inflammatory cytokines and amplifies the loop of inflammation [22]. These factors, in combination with many other proteins and factors, all work together to create systemic inflammation within the body. The stress factors mentioned above all have the potential to increase and influence these markers and inflammatory pathways.
In addition to decreasing the efficacy of self-tolerance of the immune system, systemic inflammation is commonly seen in AD states and serves as one of the markers for active disease. Elevations in pro-inflammatory cytokines can be seen overlapping in a wide variety of ADs, including RA, SLE, MS, and T1D [23]. CRP has also been shown to be elevated across multiple ADs, including giant cell arteritis, anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis, RA, and certain manifestations of SLE [24]. Other cellular and molecular processes that are commonly disrupted in AD include overactivity of the NLRP3 inflammasome [25], Treg deficiency/dysfunction [26], an increased Th17/Treg ratio [27], and dysregulation of autophagy [28].

3. Current Therapies for Autoimmune Disease

With inflammation being one of the main culprits in the development and pathology of AD, multiple pharmacological therapies have been introduced over the years that target some of these inflammatory pathways and dampen the immune system. Corticosteroid therapy was one of the first main pharmacologic treatments for AD and has broad immunosuppressive functions and is effective for acute flare-ups of inflammation [14,15]. Some of the more recent therapies include biologic drugs [16] that have specific targets, such as depletion of B cells (Rituximab) [29], enhancement of Treg immunosuppression through mammalian target of rapamycin (m-TOR) inhibition [30], increased growth and survival of Tregs through IL-2 [31], and increased regulation of inflammation, oxidative stress, and immune response through Sirtuin 1 (SIRT1) [32]. The most well studied are currently Rituximab, which has shown efficacy in the treatment of RA [16], and IL-2 has had broad efficacy effects in remission for SLE, psoriatic arthritis, Sjogren’s syndrome, and polymyositis/dermatomyositis [31]. Overall, a variety of treatments have been developed over the years and are currently available for the management of AD. Given that the predominant management for AD is currently pharmacotherapy, research for alternative therapies, especially natural interventions, is needed to broaden therapeutic options for a diverse array of patient populations with different health desires and goals.

4. Diet, Gut Metabolism, and Autoimmune Disease

While inflammation has been thoroughly studied and identified as one of the main pathways involved in the pathogenesis of AD, another area that has been studied more recently in the pathology of AD is the gut microbiome and the effects of dietary hormones and proteins. It has been found that gut microbiome dysfunction and dysbiosis could potentially predispose an individual to AD [33,34]. Microbiota dysbiosis has also been identified in several individuals with MS, T1D, and SLE [35]. The hormone leptin also seems to closely interact with the pathways and pathology of AD. Leptin is mainly produced by adipocytes and has multiple endocrine functions and effects on bone metabolism [36]. It also has a role in the generation and maintenance of low-grade inflammation and has been potentially implicated in AD [36]. With its role in helping induce inflammation, other pro-inflammatory effects have also been observed in association with this hormone, including increased Th1 responses and elevations in TNF-α, IL-2, and IL-6 secretion [37]. Studies have also demonstrated leptin’s potential effects on experimental autoimmune/allergic encephalomyelitis (EAE) mice in disease progression and severity, potentially implicating leptin’s role in increasing risk for development of AD and in potentiating detrimental neurological damage in MS [38,39]. Rises in leptin levels have also shown a similar increase in disease severity in SLE [39]. Additional dietary factors that have been shown to affect the immune system include high glucose intake and adipokine levels. With high glucose intake, exacerbation of colitis and disease severity in EAE mice was observed through increased induction of Th17 cells and elevations in mitochondrial ROS in T cells [40]. Adipokines are soluble mediators that affect a wide variety of immune functions and have also been shown to potentially exacerbate and increase the predisposition for AD [41]. Based on these studies, it seems that diet, nutritional status, and certain metabolic pathways can influence disease course and risk predisposition in AD.

5. Intermittent Fasting and Autoimmune Disease

Given the potential impact of diet on immune function, research has been conducted to explore possible connections between dietary metabolic pathways and immune response pathways. One dietary intervention of current interest and study is intermittent fasting (IF). IF consists of many different fasting regimens, in which individuals restrict caloric intake within variable periods of time [42]. During IF, individuals typically engage in eating patterns dedicated to certain time periods followed by a period of fasting ranging from 12 h to several days with consumption of little or no calories [43]. Table 1 summarizes some of the main approaches to IF and describes the different protocols of each [43]. IF gained its initial popularity for its potential in the treatment of obesity and assistance in weight loss. Numerous studies have also demonstrated that IF shows promise for maintaining a healthy weight [44]. IF has also been shown to provide potential benefits in other disease processes as well, such as hypertension, diabetes, metabolic syndrome, dementia, and cancer [45,46].
In terms of the immune system, IF particularly impacts neutrophils, lymphocytes, inflammatory and oxidative stress pathways, and gut microbiota interactions/relationships with immune function [47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69]. Understanding the various areas of the immune system and the potential effects of IF on these pathways is essential for evaluating its therapeutic benefits for AD.
Based on previous studies, the immune cell types that seem to be most affected by IF are neutrophils and B and T lymphocytes. One of the cellular processes that has been shown to increase because of IF is autophagy. Autophagy is a lysosomal degradation process to eliminate damaged organelles, long-lived misfolded proteins, and invading pathogens [47]. In addition to maintaining homeostasis, autophagy also serves to rejuvenate the innate immune system, boost function against invading pathogens, and improve neutrophil function [48,49]. IF can also further help rejuvenate the immune system through increasing the lymphoid:myeloid ratio [50]. Lower levels of T effector cells and elevations in Treg cells have also been observed in IF and other similar fasting states, as a result of the state of starvation [51]. One of the proposed mechanisms for these changes seen in T cells is that the restriction of food intake can decrease IGF-1 levels and downregulate the phosphatidylinositol-3 kinase (PI3K)/Akt/mTOR signaling pathways, leading to the changes in T lymphocyte population ratios [52].
IF has also been shown to have numerous effects on the inflammatory and oxidative stress pathways as well. IF seems to have an anti-inflammatory effect as well as reducing oxidative stress [53,54,55,56,57]. IF induces increased production of ketone bodies to maintain energy homeostasis. It has been observed that these ketone bodies can potentially increase protection from oxidative damage [58]. IF has also been observed to reduce pro-inflammatory cytokine levels of CRP, IL-6, IL-8, and TNF-α while increasing anti-inflammatory cytokines, such as IL-10 [59,60,61,62]. The weight loss and improved glycemic state resulting from IF can further modulate and reduce these pro-inflammatory cytokine levels and decrease macrophage activation [63,64,65].
Modulatory effects on gut microbiota have also been observed with IF, and these changes have been shown to influence the immune system [66]. During IF, levels of lymphocytes in Peyer’s patches in the intestine are reduced with an increase in migration of B cells back to the bone marrow [67]. Initial studies have also demonstrated that IF can modulate gut microbiota favorably to decrease chronic intestinal inflammation, through increased representation of the Lactobacillaceae, Bacteroidaceae, and Firmicutes families [68]. IF further encourages a decrease in intestinal inflammation through improved regulation of metabolic regulators, such as cAMP response element-binding protein (CREB), activated protein kinase (AMPK), mTOR, peroxisome proliferator-activated receptor gamma (PPARg), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), which help protect against DNA damage, promote longevity, and control inflammation [69].
With the multiple anti-inflammatory effects IF potentially has on the immune system, this dietary intervention would potentially be an efficacious method to help manage AD through natural mechanisms [70]. Figure 2 highlights key pathways through which IF may contribute to reducing inflammation in the body. Research and reviews have examined the effects of IF on animal and human subjects with AD, highlighting its potential therapeutic effects. The main ADs that have been studied with this dietary intervention thus far are T1D, SLE, RA, IBD, and MS.

5.1. Intermittent Fasting and Type I Diabetes

T1D is a chronic autoimmune condition where islet autoantibodies are produced against pancreatic beta cells, resulting in hyperglycemia and eventual multi-organ damage if left untreated [2]. With IF, animal studies have found that overall pro-inflammatory leptin levels in T1D mouse models decrease [71] while also inducing partial reversal of insulin deficiency defects in beta cells [72], conferring protection from this AD. Downregulation of IL-4 and IL-6 with upregulation of IL-10 is also seen with IF in humans [73]. In addition to the anti-inflammatory effects of IF, an initial human trial identified patients with improved glycemia, decreased body weight, and increased quality of life [74]. Further human studies are needed to confirm the replication of these positive outcomes in association with IF.

5.2. Intermittent Fasting and Systemic Lupus Erythematosus

SLE is a chronic relapsing-remitting AD with autoantibodies attacking multiple organ systems, resulting in a wide variety of clinical manifestations and commonly presents with renal pathology/decline [3]. One animal study identified a decrease in pro-inflammatory leptin levels in mouse models [71]. Another cellular and molecular in vitro study also found that IF led to increased adipokine levels of omentin, which is associated with inhibition of NF-κB [71]. Further studies are needed to ascertain the effects of IF on quality of life in patients with SLE, how disease severity can be impacted by this specific diet, and whether patients with SLE experience positive outcomes after maintaining an IF diet compared to patients on a regular diet.

5.3. Intermittent Fasting and Rheumatoid Arthritis

RA is one of the most common systemic ADs and is characterized by synovial inflammation, joint destruction, and eventual extra-articular manifestations [4]. In studying how IF particularly affects the pathophysiology of RA, in vitro cellular and molecular studies have found that fasting causes transient immunosuppression and decreased T-cell activation [71] in addition to protective effects from decreased leptin [75]. Multiple human studies have also found that patients have reported improvement in RA symptoms following an IF diet and a decrease in circulating immune complexes (CIC), indicating a decrease in disease activity and severity [72,73,76,77,78,79,80,81]. One particular human trial reported that patients diagnosed with RA who participated in an IF diet experienced decreased pain, stiffness, and a reduced number of tender/swollen joints [77]. Another human study showed an improvement in overall symptomatic and disease severity through lower Disease Activity Score 28 (DAS-28) with IF [80]. Other human trials have identified reductions in IL-6 and CRP in RA patients following IF [78]. While initial human studies have identified some reduction in inflammatory markers, disease activity scores, and improvement in quality of life, only a small number of human studies have been conducted, and further investigation is needed to see if results can be replicated and to observe the long-term safety and efficacy of this diet [76,77,78,79,80,81].

5.4. Intermittent Fasting and Inflammatory Bowel Disease

IBD is a group of chronic ADs, primarily consisting of Crohn’s disease and ulcerative colitis, that cause inflammation in the intestines [5]. As mentioned above, IF has many effects on gut metabolism, including decreased intestinal inflammation and modulation of gut microbiota. The modification of the microbiome through IF leads to decreased IL-17-producing T-cells and increased Treg cells in the GALT, which helps regulate and increase the destruction of autoreactive immune cells [82]. Studies on mouse models have also shown that alteration of gut microbiota by IF helps decrease inflammatory responses in the gut [83]. Another in vitro study on human cells further identified the benefit of IF by partial reversal of IBD-related pathology through reduced intestinal/systemic inflammatory changes, decreased leukocytosis, and increased regenerative markers [84]. A human study with ulcerative colitis patients showed an improvement in clinical colitis activity index, which represents an overall decrease in frequency of bowel movements, urgency, blood in the stool, extracolonic features, and increased general well-being [85]. Limitations include long-term safety and feasibility of maintaining an IF diet in patients with IBD, and additional human studies for both Crohn’s and ulcerative colitis disease are needed for replication of positive outcomes [85].

5.5. Intermittent Fasting and Multiple Sclerosis

MS is a chronic AD where inflammation results in demyelination, neuronal loss, gliosis, and causes multiple, recurrent neurological manifestations [6]. In studying the pathophysiology of MS, it has been found that pro-inflammatory cytokines have a detrimental effect on neurons and cause neurodegeneration [86]. Increased ratio levels of Th1/Th17 have also been identified in active disease states [87]. However, several studies have identified that IF can have a potential impact on slowing disease progression and improving clinical symptoms.
IF has demonstrated to confer neuroprotection through decreased ROS, activation of the SIRT1 pathway, and autophagy induction in an in vitro study [88]. The anti-inflammatory effects of IF through increased adiponectin, decreased leptin, and increased Treg/Th17 ratio also assist in reducing neuronal damage and potentiate increased synaptic plasticity and enhanced neurogenesis [88,89]. Several animal studies on mice with EAE on an IF diet showed a reduction in inflammation, demyelination, axonal damage, and overall symptom improvement [72,90,91,92,93]. Further investigation into these studies has specifically identified increased Tregs and naïve T-cells, decreased memory cells and IL-17 T-cells, and enhanced brain-derived neuron factors (BDNF), Sox-2, and SIRT1 pathways, resulting in overall anti-inflammatory effects, increased oligodendrocyte differentiation, and reduced demyelination [90,91,92,93]. These activated pathways were also found in in vitro studies with human cells under a fasting state as well [94,95,96]. The alteration of gut metabolism and microbiome by IF also has a positive effect on EAE mouse models. Trials on EAE mice on IF showed enriched gut microbiomes with more antioxidant protection, and the decreased levels of leptin reduced their disease severity compared with controls [97,98]. Improvement of clinical symptoms, quality of life, and emotional well-being has also been reported in a few human studies with MS patients [99,100,101,102]. One human trial found that patients with an acute relapse in MS had a reduction in overall disability status through lower expanded disability status scale (EDSS) scores following a 2-week IF diet [100]. Another human study identified MS patients reporting subjective improvement of symptoms following an IF diet [101]. Additional safety studies are also needed for long-term maintenance and efficacy of IF in patients with MS and to further identify if the same neuroprotection benefits are also applicable to humans as seen in the EAE mice [88,89,90,91,92,93,94,95,96,97,98,99,100,101].

5.6. Summary

In summary, IF has anti-inflammatory effects that can potentially assist with decreasing clinical disease severity and symptoms. Table 2 reviews the cellular/molecular mechanisms of the key underlying pathology in each AD and the mechanistic effects of IF on these inflammatory/immune pathways. Table 3 summarizes the human clinical trials referenced in this review for each AD and further discusses the trial type, inclusion and exclusion criteria, key result findings, and limitations of each study.

6. Aging Effects of Intermittent Fasting

In addition to the potential anti-inflammatory effects of IF, this dietary intervention has also been studied in the process of aging, and some of these effects have been thought to result from the anti-inflammatory effects of IF. Due to the decreased ROS species and pro-inflammatory markers, which are both processes that help accelerate aging, IF has been theorized to slow down this trajectory [103]. This has been shown in human studies from a review where two studies identified decreased TNF-α in healthy individuals, two studies with decreased leptin in healthy obese and overweight individuals, and one other study with increased anti-inflammatory adiponectin in healthy sedentary individuals [104]. More specifically, IF has been associated with decreased levels of soluble intercellular adhesion molecule-1 (sICAM-1), a pro-inflammatory marker associated with aging [105,106]. IF also has additional antiaging effects, such as reducing certain pro-aging amino acids, including methionine, encouraging stem cell dynamic growth and function, and increasing autophagy to replace lost and damaged cells [107]. While these initial studies are encouraging for demonstrating a slower progression of aging, these studies are also limited in that they only discuss the reduction in pro-inflammatory cytokines and pro-aging markers and do not specifically demonstrate an explicit decrease in clinical or physical aging [103,104,105,106,107]. Further research is encouraged to investigate the effect of IF on the aging process.

7. Limitations of Intermittent Fasting

Given the potential anti-inflammatory, antiaging, and healthy weight management benefits, IF appears as an ideal dietary intervention that protects against multiple pathological conditions. However, several limitations to this diet need to be considered before starting an individual on IF. Given that some of the IF protocol regimens have more intensive caloric intake restrictions, it may be challenging for individuals to stick to this dietary intervention on a long-term basis. There are limited studies of humans on long-term IF, and a few studies conducting IF in human trials have identified higher dropout rates in the fasting group due to increased hunger, more adverse events, and non-sustainable changes in eating behavior [108]. Another systematic review discussed some of the specific adverse events individuals may experience during a fasting diet, including headaches, reduced energy levels, feeling cold, constipation, light-headedness, reduced concentration, pre-occupation with food, and mood swings [109]. Some of these risks and additional limitations for each fasting diet can also be referenced back in Table 1. Another potential risk identified in rodent studies showed reduced left ventricular diastolic compliance and diminished cardiac reserve [110]. However, this risk has not been identified in humans yet, and overall studies show a decrease in cardiovascular risk factors [110]. Lastly, if using IF as a potential supplemental treatment for T1D, there is increased risk for adverse effects of hypoglycemia, ketoacidosis, dehydration, hypotension, and thrombosis [111]. However, several studies have demonstrated the feasibility and safety of IF in humans with T1D and T2D [112,113,114]. Additional studies have also shown the safety of being on an IF diet in patients with MS [113,114].

8. Conclusions, Limitations, and Future Directions

As discussed above, there are many different factors and complex pathways involved with AD, and IF positively interferes with some of these pathways and has the potential to improve disease activity in certain AD states. Studies on mouse models and a small handful of human clinical trial investigations have shown a variety of benefits following an IF diet. Figure 3 summarizes some of the main benefits that have been seen with IF for the ADs discussed previously. With the effect IF can have on AD, this dietary intervention has anti-inflammatory effects that could potentially contribute to improvement in symptoms and clinical disease severity in conjunction with current pharmacotherapy.
However, given the limited human studies, further studies should be carried out to further investigate this dietary intervention and how it specifically affects human subjects with AD. No human trials have specifically been found in this review studying IF in individuals with SLE, which is another limitation, and further investigation should also be carried out regarding this specific disease to determine if the same positive benefits are observed. Studies of IF on ADs outside of T1D, RA, IBD, and MS should also be prioritized for investigation to see whether IF has any effects on other ADs as well. Although some initial studies have demonstrated the safety of IF in diabetes and MS, additional studies are needed to further establish the safety of this diet on both healthy individuals and those with AD [113,114]. These additional studies will also help determine how feasible and/or difficult it would be for patients to adhere to this new dietary intervention, as it requires significant lifestyle modifications and adjustments on behalf of the individuals. If future studies prove the safety of IF, it would also be important to further investigate IF’s effect on AD through more human trials, as many of the studies discussed in this review were in vitro, cellular, and molecular, or animal studies. These additional human studies would help determine if these same positive results are reproducible in human subjects and would be applicable in a clinical setting.
Many of the human trials conducted on IF and AD typically had patients fast for anywhere from 1 week to 3 months for observation of any potential effects of fasting on AD [73]. Based on how the initial human clinical trials have only used IF on a short-term basis, it would also be beneficial to narrow down and investigate whether IF would be more effective for helping manage AD with short-term or long-term use. Many of these trials also primarily focused on monitoring levels of autoantibodies, cytokines, and immune cell count [73]. It would also be essential to carry out specific studies to see whether IF has any potential effects or interactions with current AD pharmacotherapies, as most patients would still likely need to remain on their medication regimens for full management of their AD.
As discussed above, the summarized findings in this narrative review are largely based on in vitro, cellular, molecular, and animal studies, limiting this review’s potential to conclude IF’s positive effects on AD. However, this article aims to encourage further research and human studies in studying IF and its application to AD. Based on these current findings, IF has potential anti-inflammatory effects that could assist with some clinical and symptomatic improvement of AD. If future studies continue to demonstrate a positive impact on clinical symptoms, improvement of disease severity, and anti-inflammatory effects on ADs, IF could serve as a potential alternative dietary regimen that patients may attempt to assist with symptomatic/clinical improvement and increased quality of life in addition to their current pharmacotherapy regimen.

Author Contributions

Conceptualization, K.Y. and R.J.R.; methodology, K.Y.; validation, K.Y., R.J.R.; formal analysis, K.Y.; investigation, K.Y.; resources, K.Y., R.J.R.; data searching, K.Y.; writing—original draft preparation, K.Y.; writing—review and editing, K.Y., R.J.R.; supervision, R.J.R.; project administration, K.Y., R.J.R. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

All data referenced in this review were found through Google Scholar and PubMed databases. Please see the References section for the specific articles used when writing this review.

Acknowledgments

A special thank you would like to be made to Rebecca Jean Ryznar, who has provided continuous support and assistance in helping draft and edit this manuscript. We would also like to acknowledge and thank Biorender for providing a platform to help create the Figures and illustrations used within the article.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Mechanisms linking inflammatory pathways, cytokine dysregulation, and Treg/T cell dysfunction to autoimmune disease predisposition. Combinations of disruptions in Treg/T cell function, elevated pro-inflammatory cytokines and ROS, and hyperactive inflammatory pathways, such as the NLRP3 inflammasome, can increase predisposition for AD. Created in BioRender. Ryznar, R. https://BioRender.com/2aq0a9j (accessed on 2 December 2025).
Figure 1. Mechanisms linking inflammatory pathways, cytokine dysregulation, and Treg/T cell dysfunction to autoimmune disease predisposition. Combinations of disruptions in Treg/T cell function, elevated pro-inflammatory cytokines and ROS, and hyperactive inflammatory pathways, such as the NLRP3 inflammasome, can increase predisposition for AD. Created in BioRender. Ryznar, R. https://BioRender.com/2aq0a9j (accessed on 2 December 2025).
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Figure 2. Mechanisms of IF-induced anti-inflammatory effects. IF creates an anti-inflammatory state in the body through decreased pro-inflammatory cytokines, decreased ROS, increased autophagy, and modulation of the gut microbiome to encourage a reduction in intestinal inflammation. Created in BioRender. Ryznar, R. https://BioRender.com/sobix8n (accessed on 2 December 2025).
Figure 2. Mechanisms of IF-induced anti-inflammatory effects. IF creates an anti-inflammatory state in the body through decreased pro-inflammatory cytokines, decreased ROS, increased autophagy, and modulation of the gut microbiome to encourage a reduction in intestinal inflammation. Created in BioRender. Ryznar, R. https://BioRender.com/sobix8n (accessed on 2 December 2025).
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Figure 3. Key benefits of intermittent fasting in chronic inflammatory and autoimmune diseases. IF leads to an overall decrease in pro-inflammatory cytokines, leptin, and gut microbiome modulation to decrease intestinal inflammation. IF has also been found to confer some neuroprotection, serving as a potential protective mechanism in the pathology of MS. Created in BioRender. Ryznar, R. https://BioRender.com/2l3cvcy (accessed on 2 December 2025).
Figure 3. Key benefits of intermittent fasting in chronic inflammatory and autoimmune diseases. IF leads to an overall decrease in pro-inflammatory cytokines, leptin, and gut microbiome modulation to decrease intestinal inflammation. IF has also been found to confer some neuroprotection, serving as a potential protective mechanism in the pathology of MS. Created in BioRender. Ryznar, R. https://BioRender.com/2l3cvcy (accessed on 2 December 2025).
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Table 1. Approaches to IF. Some of the main forms of IF include time-restricted eating (consuming all calories within a small time window), periodic fasting (longer periods of fasting without caloric intake), and caloric restriction (a low-calorie diet on certain days of the week). Limitations and risks of each fasting diet are also provided. Additional risk assessments also need to be conducted for individuals with hormonal imbalances, pregnant and breastfeeding women, young children, and adults of advanced age, as these populations may be at higher risk for adverse effects [43].
Table 1. Approaches to IF. Some of the main forms of IF include time-restricted eating (consuming all calories within a small time window), periodic fasting (longer periods of fasting without caloric intake), and caloric restriction (a low-calorie diet on certain days of the week). Limitations and risks of each fasting diet are also provided. Additional risk assessments also need to be conducted for individuals with hormonal imbalances, pregnant and breastfeeding women, young children, and adults of advanced age, as these populations may be at higher risk for adverse effects [43].
Time Restricted EatingDescription of Fasting DietLimitations/Risks
20/4, 18/6, 16/8Food is consumed over a 4, 6, or 8-h period, and the individual fasts the rest of the dayAdverse effects during the fasting period: hypoglycemia, dizziness, and weakness.
Greater risk for high fluctuating glucose concentrations and hypoglycemia in adults of advanced age.
Potential vitamin and other micronutrient deficiencies.
B2 Regimen2 large meals per day: 4 h morning period for breakfast, 4 h afternoon period for lunch, and no dinnerAdverse effects during the fasting period: hypoglycemia, dizziness, and weakness (overall lower risk).
Greater risk for high fluctuating glucose concentrations and hypoglycemia in adults of advanced age.
Potential vitamin and other micronutrient deficiencies.
Periodic Fasting
1–2 Day Fasting Weekly24 h fast with no calorie intake 1–2 times per week, with regular eating for the rest of the days of the weekAdverse effects on fasting days: hypoglycemia, dizziness, and weakness.
Adherence difficulties with more time-intensive fasting.
Greater risk for high fluctuating glucose concentrations and hypoglycemia in adults of advanced age.
Potential vitamin and other micronutrient deficiencies.
Caloric Restriction
5:22 days of a very low-calorie diet, with regular eating the rest of the days of the weekAdverse effects on fasting days: hypoglycemia, dizziness, and weakness.
Adherence difficulties with more time-extensive fasting.
Greater risk for high fluctuating glucose concentrations and hypoglycemia in adults of advanced age.
Potential vitamin and other micronutrient deficiencies.
Table 2. Pathophysiology and Cellular/Molecular Effects of IF on AD, including T1D, SLE, RA, IBD, and MS. The pathophysiology section describes the key underlying mechanistic cellular and molecular dysfunction for each AD. The cellular and molecular effects of the IF section describe the specific processes that take place when placed in an IF state. These results are primarily based on in vitro and animal studies in mice models, unless otherwise specified in the table [67,68,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98].
Table 2. Pathophysiology and Cellular/Molecular Effects of IF on AD, including T1D, SLE, RA, IBD, and MS. The pathophysiology section describes the key underlying mechanistic cellular and molecular dysfunction for each AD. The cellular and molecular effects of the IF section describe the specific processes that take place when placed in an IF state. These results are primarily based on in vitro and animal studies in mice models, unless otherwise specified in the table [67,68,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98].
ADPathophysiologyCellular and Molecular Effects of IF
T1DAutoantibodies and pro-inflammatory cytokines → pancreatic beta cell destruction
  • Decrease in leptin, IL-4, and IL-6 inflammatory markers.
  • Increase in IL-10 anti-inflammatory markers.
SLEAuto-reactive T-cells/autoantibodies → increase in pro-inflammatory cytokines → organ → dysfunction (renal decline, etc.)
  • Decrease in leptin inflammatory marker.
  • Increase in omentin → inhibition of NF-κB.
RAAuto-reactive T-cells/autoantibodies (anti-CCP/CIC) → infiltration, inflammation, and destruction of synovial membranes and joint spaces
  • Decrease in T-cell activation.
  • Decrease in IL-6, leptin, and CRP inflammatory markers.
  • Decrease CIC in human subjects.
IBDAuto-reactive T-cells, epithelial barrier dysfunction, dysbiosis → increase in pro-inflammatory cytokines and markers → intestinal inflammation and dysfunction
  • Decrease in IL-17-producing T-cells and increased Treg cells in the GALT → increased destruction of autoreactive immune cells.
  • Decrease in Peyer’s patches lymphocytes and increase in migration of B cells back to the bone marrow.
  • Increase in gut microbiota of Lactobacillaceae, Bacteroidaceae, and Firmicutes → decrease in intestinal inflammation.
MSIncrease in Th1/Th17 → increase in pro-inflammatory cytokines and markers → demyelination, neuronal loss, gliosis
  • Decrease in ROS and leptin inflammatory marker.
  • Increase in Treg/Th17 → decrease in neuronal damage, increase in synaptic plasticity, and neurogenesis enhancement.
  • Reduction in inflammation, axonal damage, and demyelination.
  • Increase in Tregs and naïve T-cells, decrease in memory cells and IL-17 T-cells, and enhanced BDNF. Sox-2 and SIRT1 pathways → increase in oligodendrocyte differentiation and decrease in demyelination.
Table 3. Summary of the human clinical trials referenced in this review in investigating IF’s effect on AD, including T1D, RA, IBD, and MS. Specific human studies regarding IF and SLE have not yet been identified. Trial design is briefly described with relevant inclusion and exclusion criteria. Results discuss specific related results to the IF diet. Potential limitations of each trial were also included for future directions on continued investigation [72,73,74,77,78,79,80,81,85,100,101].
Table 3. Summary of the human clinical trials referenced in this review in investigating IF’s effect on AD, including T1D, RA, IBD, and MS. Specific human studies regarding IF and SLE have not yet been identified. Trial design is briefly described with relevant inclusion and exclusion criteria. Results discuss specific related results to the IF diet. Potential limitations of each trial were also included for future directions on continued investigation [72,73,74,77,78,79,80,81,85,100,101].
ADTrialInclusion/Exclusion CriteriaResultsLimitations
T1DPilot randomized clinical trial with a 5-day fasting diet/month for 3 months vs. a regular diet [74]Exclusion: Non-compliance with dietary protocol, previous eating disorders, extremes of under- or overweight, and other concomitant diseases.Decreased fasting blood glucose levels and body weight after the third fasting cycle.Limited long-term follow-up after the IF diet
Small sample size (38).
RA7-day fast vs. 7-day ketogenic diet [80]Inclusion: Patients who met criteria for the American College of Rheumatology for RA, prednisolone dosage < 7.5 mg/day and stable dose 4 weeks before study entry, and stable DMARD therapy at least 3 months before study entry.Decreased IL-6, ESR, and CRP serum levels.
Decreased tender joints.
Decreased DAS-28 scores.		Short-term fasting period with no long-term follow-up.
Small sample size (23).
Fasting diet at Health Farm vs. ketogenic diet at home.
7-day fast in comparison with a control regimen in a crossover trial [78]Inclusion: Patients with classical or definite RA according to the American Rheumatism Association criteria.
Exclusion: Treatment with gold salts, penicillamine, levamisole, antimalarials, or cytostatic drugs within the last 3 months before the trial. Obvious extremes of under- or overweight. Other concomitant diseases.		Decreased ESR.
Decreased clinical joint inflammation.
Decreased neutrophil locomotion after reference serum induction.		Short-term fasting period with no long-term follow-up.
Small sample size (13).
7–10 day fast followed by a 9-week lactovegetarian diet vs. a regular diet [76]Exclusion: Previous eating disorders, extremes of under- or overweight, and other concomitant diseases.Reduced pain/joint stiffness and consumption of analgesics.Short-term fasting period with no long-term follow-up.
Small sample size (26).
Combined fasting and lactovegetarian diet in the experimental arm.
Single-blind, randomized controlled trial of 7–10 fast followed by a 3.5-month vegan diet and lactovegetarian diet for the rest of the year [77]Exclusion: Previous eating disorders, extremes of under- or overweight, and other concomitant diseases.Decreased tender/swollen joints
Improved Ritchie’s articular index.
Decreased pain scores and duration of morning stiffness.
Decreased ESR and CRP.
Sustained clinical benefit at 2-year follow-up.		Short-term fasting period
Multiple diet regimens: fasting, vegan, and lactovegetarian.
IBDCohort study with fasting diet associated with Ramadan [85]Inclusion: Diagnosis of IBD currently in remission.
Exclusion: Previous eating disorders, extremes of under- or overweight, and other concomitant diseases.		Decreased mean score of colitis activity index in males with ulcerative colitis.Non-standardized/variable fasting diet among participants in the fasting arm.
MSRandomized controlled pilot trial of a 2-week fasting diet vs. regular diet [100]Inclusion: Diagnosis of relapsing remitting MS.
Exclusion: Previous eating disorders, extremes of under- or overweight, and other concomitant diseases.		Decreased EDSS scores.Short-term fasting period with no long-term follow-up.
Other forms of MS not been studied.
Randomized controlled pilot trial of 8-week caloric restriction diet vs. fasting diet vs. regular diet [101]Inclusion: Diagnosis of relapsing remitting MS with relapse in the past 2 years, disease duration of <15 years, EDSS < 6, stable on current therapy.
Exclusion: Previous eating disorders, extremes of under- or overweight, kidney disease, warfarin use, major surgery in the past 3 months, chemotherapy in the past year, and pregnancy/breastfeeding.		Improvement in emotional well-being/depression scores.
Decreased body weight.		Short-term fasting period with no long-term follow-up.
Reduced adherence in the fasting diet experimental arm
Subjective patient data reporting.
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Yasuda, K.; Ryznar, R.J. The Relationship Between Autoimmune Disease and Intermittent Fasting: A Narrative Review. Immuno 2025, 5, 60. https://doi.org/10.3390/immuno5040060

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Yasuda K, Ryznar RJ. The Relationship Between Autoimmune Disease and Intermittent Fasting: A Narrative Review. Immuno. 2025; 5(4):60. https://doi.org/10.3390/immuno5040060

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Yasuda, Krista, and Rebecca Jean Ryznar. 2025. "The Relationship Between Autoimmune Disease and Intermittent Fasting: A Narrative Review" Immuno 5, no. 4: 60. https://doi.org/10.3390/immuno5040060

APA Style

Yasuda, K., & Ryznar, R. J. (2025). The Relationship Between Autoimmune Disease and Intermittent Fasting: A Narrative Review. Immuno, 5(4), 60. https://doi.org/10.3390/immuno5040060

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