Fasting has seen a real resurgence in medicine over the past few years, driven not just by the pioneering work of gerontologist Prof. Valter Longo, who has brought his longevity nutrition research to a wider audience through several popular books, but also by growing coverage of intermittent fasting in newspapers and blogs, extending the window between the last meal of one day and the first meal of the next. But what's actually behind fasting as a practice, and could it offer real benefits for autoimmune conditions?
Human studies looking specifically at fasting in autoimmune conditions are still limited, so no definitive conclusions can be drawn yet. Positive effects have been observed in studies with rheumatoid arthritis patients, and in various models and animal studies involving other autoimmune conditions. These benefits are partly explained by autophagy (more on this in the following).
A quick note on terminology before going further: fasting mimicking diets (FMDs) are dietary protocols that reduce calorie intake enough to bring the body into a fasting-like state, while still providing nutrient-dense, health-supporting food, reducing the physical strain compared to traditional fasting. Valter Longo's research popularized this particular approach.
Caloric restriction (CR) protocols reduce calorie intake by a set percentage relative to basal metabolic needs. In certain animal models and studies, this has also been linked to extended lifespan, though it isn't sustainable long term without negative consequences. [1]
What is autophagy?
Autophagy is an evolutionary process that allows cells to break down and recycle both their own components and foreign material present within the cell, such as viral or bacterial fragments. Through this cellular cleanup process, the body can repurpose material from old cell components to build new ones. [2]
Autophagy helps cells maintain homeostasis, or balance. This process is intensified by external stress signals such as low oxygen (hypoxia), food deprivation (fasting), DNA damage, and cytotoxic substances (like chemotherapy agents). [2]
The idea behind fasting as a disease prevention strategy and anti-aging approach is to regularly force the body into cleanup mode, breaking down lower-quality cellular components. With age, and in autoimmune conditions, poorly functioning cells tend to accumulate, dysfunctional lymphocytes, for example. Lymphocytes are a specific group of white blood cells responsible for, among other things, antibody production and immune defense. When lymphocytes stop functioning properly, the immune system's regulation can go awry. [1]
Fasting's effects on the body involve autophagy alongside several overlapping processes and signaling pathways, including the mechanistic target of rapamycin (mTOR) and Sirt-1. These biochemical processes are covered in more detail in a separate article on the potential benefits and drawbacks of autophagy.
Fasting and autoimmune conditions
Exactly how autophagy benefits autoimmune conditions is not fully understood yet, but dysregulated autophagy appears to play a role in Crohn's disease, multiple sclerosis, and systemic lupus erythematosus (SLE). [3]
In one study, researchers led by Valter Longo compared hyperactive immune cells, of the kind seen in autoimmune processes, to cancer cells, which develop similar energy-generation strategies to produce pro-inflammatory mediators. Periodic fasting could potentially lead the body's own immune system to remove and break down these overactive immune cells.
At the same time, the researchers note that caloric restriction does not consistently produce the same effects, such as extended lifespan, even under study conditions, and that research on fasting and calorie reduction needs to carefully account for differences in diet composition. It's still unclear what the ideal protein proportion should be, or how the overall nutrient ratio is best structured. [1]
Types of fasting used in scientific studies
Clinical studies use a wide range of fasting protocols, not all fasting looks the same. Approaches range from limiting calorie intake below basal metabolic needs, all the way to zero-calorie fasting. Valter Longo developed the fasting mimicking diet (FMD), which temporarily reduces calorie intake over a five-day period.
The fasting mimicking diet is designed to provide balanced, particularly nutrient-dense food throughout the five reduced-calorie days, helping avoid nutrient deficiencies and unwanted side effects associated with more extreme fasting approaches. [1]
The shorter duration combined with reduced (rather than eliminated) calorie intake also tends to feel considerably more manageable for people undertaking it. Because of its solid nutrient profile, it can also be used repeatedly, allowing people to benefit from fasting's positive effects several times a year.
Fasting in rheumatoid arthritis
In people with rheumatoid arthritis (RA), a 7-to-10-day fasting period led to measurable improvements, including reduced inflammatory markers and increased grip strength, compared to a control group switched to a lacto-vegetarian diet. The study authors concluded that fasting produced both subjective and objective improvements in RA, though these benefits were short-lived. The anticipated benefit of the lacto-vegetarian diet itself, which the study had hoped to demonstrate, did not materialize. [4]
Immune reactions to specific foods appear to play a role in RA, something fasting effectively sidesteps. Other studies show improvement in RA symptoms with dietary changes, such as switching to a gluten-free, vegan diet [5] or following an elemental diet for a period of time. [6] Individually eliminating foods that worsen a specific patient's symptoms tends to be particularly beneficial.
That said, drawing firm conclusions from these mostly very small studies is difficult. Other research found no definitive link between RA and meat consumption specifically, suggesting other factors are likely involved, such as the omega-3 to omega-6 ratio or fish intake. [7]
Many dietary intervention studies also had participants fast before transitioning to the new diet, making it unclear whether fasting itself or the subsequent dietary change was the more decisive factor. Despite these promising signals, there is still no consensus on a strategy that can be broadly recommended. [8] General recommendations are difficult here anyway, since the course of autoimmune conditions tends to vary considerably from person to person.
Fasting and systemic lupus erythematosus (SLE)
Fasting does not just affect regulatory T cells, which help regulate the immune system, through autophagy, it also works through the hormone leptin. Leptin influences hunger and satiety, as well as sex hormone and thyroid hormone production. [9]
In an experiment with mice affected by lupus (SLE), a state of hypoleptinemia (low blood leptin) was found to increase functional regulatory T cells. Regulatory T cells have an immune-modulating effect, helping suppress excessive immune responses. This effect was reversed once the previously reduced leptin levels were restored. [3] Leptin levels drop during fasting, likely as a result of reduced glucose and insulin levels. [10]
A review study concluded that caloric restriction has beneficial effects in systemic lupus erythematosus, for example on fatigue. Calorie reduction for weight loss and improved lipid levels is particularly recommended for overweight SLE patients. [11]
Beyond simply reducing calories, shifting toward a diet rich in omega-3 fatty acids while minimizing pro-inflammatory omega-6 fatty acids also appears to have a positive effect on SLE disease activity. [11]
Fasting and multiple sclerosis (MS)
Research into multiple sclerosis (MS) often relies on the murine EAE model (experimental autoimmune encephalomyelitis), essentially, the mouse model for MS. Both caloric restriction of 33 to 60% and a ketogenic diet with a 4:1 fat-to-carbohydrate/protein ratio showed preventive effects and reduced disease activity in this model, though neither approach fully halted disease progression. [1]
Alternate-day intermittent fasting (eating one day, fasting the next) also reduced disease activity in mice. While the underlying mechanisms aren't fully understood yet, the reduced disease activity is attributed to lower levels of cytokines such as IL-1β, IL-6, IL-12, IL-17, and TNF-alpha. [1] Cytokines are immune system messengers that influence how white blood cells behave, and by extension, how inflammation develops.
In MS specifically, treatment cannot just focus on suppressing the immune system, it also needs to support the regeneration of white blood cells and remyelination of existing lesions. Remyelination refers to rebuilding the myelin sheaths around nerves, which get damaged in MS.
Fasting and neurodegenerative conditions like Parkinson's disease
Autophagy plays an important role in neurodegenerative conditions through its function in clearing protein buildup within cells. Protein deposits are commonly associated with conditions like Parkinson's, Huntington's, and ALS. The deposits seen in Alzheimer's disease, known as plaques, are probably the best known example.
Genetic defects and other biochemical processes are known to promote oxidative stress and inflammation, both of which can drive the development of Alzheimer's disease. Altered autophagy processes have also been documented in Parkinson's disease. Regular fasting may help here by reducing these harmful processes and promoting autophagy. [12]
One study in mice found that caloric restriction can trigger neuroprotective processes. The researchers concluded that regular calorie reduction, as seen with fasting, could offer a simple, safe, and low-cost approach to achieving therapeutic benefits in neurodegenerative conditions. [13]
Conclusion
The fasting mimicking diet, or other fasting protocols, could represent an interesting additional treatment option for autoimmune conditions like rheumatoid arthritis, lupus, and MS, potentially reducing reliance on medication. That said, even though the FMD has proven safe in human trials, and a ketogenic diet showed positive results in a separate MS study, more research is still needed, ideally through larger, randomized controlled trials in humans rather than relying solely on animal models.
Long-term fasting and chronic caloric restriction also carry downsides for the body, including a weakened immune response and impaired wound healing. This means alternative approaches, like periodic fasting, are needed to capture fasting's benefits without the drawbacks of prolonged calorie restriction.
Choi, Lee, and Longo ultimately conclude that using a fasting mimicking diet on a periodic basis, one that's very low in both calories and protein, could help overcome the limitations associated with more extreme, continuous fasting approaches. [1]
References
[1] Choi IY, Lee C, Longo VD. Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence. Mol Cell Endocrinol. 2017;455:4-12. doi:10.1016/j.mce.2017.01.042
[2] Antunes F, Erustes AG, Costa AJ, et al. Autophagy and intermittent fasting: the connection for cancer therapy? Clinics. 2018;73. doi:10.6061/clinics/2018/e814s
[3] Liu X, Qin H, Xu J. The role of autophagy in the pathogenesis of systemic lupus erythematosus. Int Immunopharmacol. 2016;40:351-361. doi:10.1016/j.intimp.2016.09.017
[4] Sköldstam L, Larsson L, Lindström FD. Effect of fasting and lactovegetarian diet on rheumatoid arthritis. Scand J Rheumatol. 1979;8(4):249-255.
[5] Hafström I, Ringertz B, Spångberg A, et al. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatol Oxf Engl. 2001;40(10):1175-1179.
[6] Podas T, Nightingale JMD, Oldham R, Roy S, Sheehan NJ, Mayberry JF. Is rheumatoid arthritis a disease that starts in the intestine? A pilot study comparing an elemental diet with oral prednisolone. Postgrad Med J. 2007;83(976):128-131. doi:10.1136/pgmj.2006.050245
[7] Choi HK. Diet and rheumatoid arthritis: Red meat and beyond. Arthritis Rheum. 2004;50(12):3745-3747. doi:10.1002/art.20732
[8] Khanna S, Jaiswal KS, Gupta B. Managing Rheumatoid Arthritis with Dietary Interventions. Front Nutr. 2017;4. doi:10.3389/fnut.2017.00052
[9] Pschyrembel Online | Leptin. Accessed July 21, 2026. https://www.pschyrembel.de/Leptin/K0CRH
[10] Boden G, Chen X, Mozzoli M, Ryan I. Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab. 1996;81(9):3419-3423. doi:10.1210/jcem.81.9.8784108
[11] Constantin M-M, Nita IE, Olteanu R, et al. Significance and impact of dietary factors on systemic lupus erythematosus pathogenesis. Exp Ther Med. 2019;17(2):1085-1090. doi:10.3892/etm.2018.6986
[12] Condello M, Pellegrini E, Caraglia M, Meschini S. Targeting Autophagy to Overcome Human Diseases. Int J Mol Sci. 2019;20(3). doi:10.3390/ijms20030725
[13] Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton JL, Kiosses WB. Short-term fasting induces profound neuronal autophagy. Autophagy. 2010;6(6):702. doi:10.4161/auto.6.6.12376
