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We are consistently ranked by U. For example, studies show that fasting and calorie restriction are linked to reduced risk of age-related illnesses, such as hypertension, atherosclerosis, obesity, and diabetes. The research found that there was a rapid reduction in the number of circulating immune cells in animals that were not allowed to eat in the hours after they awoke.

The study has been published in Immunity. The researchers compared mice that could eat whenever they wanted with mice that had no access to food in the hours after they became active. Bone marrow generates monocytes, which normally patrol the body in search of pathogens.

The cells also play a role in inflammation and tissue repair. In further experiments, the scientists showed that during periods of fasting, the immune cells returned from the bloodstream to the bone marrow.

However, monocytes poured back into the bloodstream after feeding restarted, which resulted in unusually high concentrations of these immune cells, known as monocytosis. After a hour fast followed by 4 hours of feeding, they infected the mice with a bacterium called Pseudomonas aeruginosa , which is a common cause of pneumonia in hospitals.

Compared with mice that had free access to food throughout, the mice that fasted died sooner and in larger numbers, seemingly as a result of increased inflammation in their lungs.

Swirski explains that monocytes also play an important role in illnesses such as heart disease and cancer, so it will be important to understand exactly how fasting affects them. In further experiments, the scientists showed that fasting led to changes in the brains of the mice, which in turn triggered the release of the stress hormone corticosterone.

The immune system responded to this stress signal by recalling the immune cells to the bone marrow. This may help the animals to conserve resources in times of scarcity. Swirski told Medical News Today. The key to balancing the costs and benefits may be more measured forms of fasting and controlled re-feeding, as opposed to feasting after fasting, he added.

It is too early to say whether studies like this one in mice have implications for people who skip breakfast, or who fast in order to lose weight.

However, Dr. Some other studies have suggested that, though IF might have little effect on inflammation, it may greatly influence oxidative stress, which is linked to insulin resistance Interestingly, improvements in glucose metabolism were observed in two studies that reported decreased oxidative stress markers 6 , Significant changes in leptin, which is regarded as a special body weight regulating hormone, were also noted 29 , meaning that the resistance to leptin is partly improved in obese subjects.

Besides the ability to regulate metabolic syndrome, including lowering glucose and lipid synthesis 50 , leptin is one of the mediators responsible for the inflammatory state In addition to the findings about immune cells and inflammatory markers, other study conduct tests of gene expression.

found that genes related to oxidative stress were down-regulated such as SOD1 and SOD2 28 , and Mindikoglu et al. found that the expression of other genes including the tumor activators POLK , NIFK , SRGN , CAMP , and D , were downregulated 10 , which are consistent with remitting oxidative effect and lowering cancer risk by IF.

To sum up, besides the advantages of IF on obese subjects including losing body weight, regulate lipid metabolism and improve insulin resistance, which was almost suggested in all studies, IF could reduce oxidative stress and remit inflammatory state through macrophage adjustment and hormone secretion.

Moreover, although evidence is accumulating that gut microbial is involved in the etiology of obesity 52 and altered by modified IF 4 , relevant researches were still rare.

Another issue waiting for more studies was the influence between IF and nervous system on obese subjects. A study in obese rat showed that IF could prevent memory loss in comparison to ad libitum by regulating body metabolism 54 , which offering a new sight for the advantages of IF to remit neuroinflammation.

Pregnancy is a state of high oxidative stress, which contributes to preeclampsia and restriction of fetal growth Maternal IF resulted in detrimental influence on fetal development and maternal stress stage by changing the metabolite profiles in animal studies However, IF has no significant influence on the high oxidative stress and fetal development in the human study The reason could be the different circadian rhythms between rats and humans.

A case related with gestational diabetes mellitus was reported that IF is a useful intervention to reduce maternal body weight, plasma glucose, and psychological distress without any adverse effects Surgery is regarded as a shock or an acute stress, and IF is able to improve resistance to this stress.

In a study by Ginhoyen et al. Compared with subjects in the non-fasting group, subjects in the restriction group showed a more moderate postoperative inflammatory response. For healthy people in special physiological states, such as those observed during the perioperative period, IF could reduce acute stress.

More trials are needed to identify the influence on pregnant subjects, including the fetal and maternal safety, anti-stress effect and body metabolism regulation.

It is worth nothing that study include in this review on pregnant subjects was a Ramadan IF trial, which might be less convincing as subjects in this study had experienced such interventions before. PCOS is an endocrine condition closely linked to metabolic disorders.

Because obesity is closely related to PCOS, it is not surprising that IF could provide benefits by reducing insulin resistance and easing hyperandrogenemia Whether IF could be applied in subjects with cancer remains unclear 57 , because it may also affect chemotherapy.

In a study of subjects with CML, Yassin et al. reported that fasting did not result in significant immunological effects with measurements including BCR-ACL levels and hematological parameters It was suggested that IF in some patients who have cancer could be capable of decreasing chemotherapy-related toxicity and tumor growth, however 58 , more clinical trials were needed to clarify.

MS is an autoimmune disease characterized by degeneration of the central nervous system The epidemiology of this condition includes a history of childhood obesity. Although no significant changes in leptin or adiponectin levels have been observed in studies of IF in MS, an observed difference in T-cell subsets in intestines might explain the immunological effects of IF that have been reported in studies 33 , 60 , which was also a kind of possible therapy for MS The components of the intestinal microbiome could also raise the propensity to develop MS strongly Researches about gut microbial of the influence of IF on subjects who have MS were expected as a result of migration of intestine immune cell subsets.

As mentioned before, IF is beneficial for nervous system by cellular, metabolic and circadian mechanisms and a promising therapy for brain disorders, future research should disentangle whether positive effects of IF could be applied in clinical situations Besides IF, other types of diet, including energy-restricted fasting and ketogenic diet 62 , were also evaluated as nutrition therapy for MS More results was put forward that the improvement of this diet was related with immune system, including reducing inflammatory cytokines and immune cell migration.

However, these diets might cause deficiency of various nutrients in long term To sum up, a special diet could serve as a unique nutrition therapy for MS with disadvantages of nutrition deficiency, which was nowadays a popular and promising topic.

The different evidence levels should be taken into consideration when analyzing the results of these studies. Of the 28 selected trials, 19 were randomized, controlled, parallel, or crossover studies. Some trials were cohort studies, and the trial focusing on CML was a retrospective study; the lack of a control group in that trial may lead to inaccurate conclusions.

Trials differed in terms of baseline characteristics, study durations, meal types, and IF types. These differences may interfere with the final results. For example, Gasmi et al. studied whether young people and old people would act differently while undertaking IF 17 , Paoli et al.

compared all factors in a 2-month trial and in a 1-year trial 1 , and Varady et al. focused on whether the influence of IF would vary with different durations of eating windows 6.

In the future, more studies on this topic should be conducted to provide new data. This systematic review finds substantial evidence that IF can modulate the immune system in non-obese healthy people, obese people, and subjects in other physiological or pathophysiological states and these effects were clinically relevant with cognitive improvement, lipid and metabolism regulation, and inflammatory state remission.

The mechanisms influenced and regulated to drive changes in each population differ. For example, non-obese healthy people can metabolize lipids and glucose efficiently, so the immunomodulatory effect is reflected in immune cell subset migration, lower inflammatory factors, upregulation of circadian rhythm—related gene expression, and greater microbial diversity.

Although weight reduction has also been observed in healthy people, changes in parameters of lipid and glucose metabolism remained insignificant in most cases. In obese people, IF contributes to body health by regulating macrophages, which is related to the inflammatory stage of adipose tissue.

Although many inflammatory factors did not show significant changes in obese subjects, other important factors, including 9-isoprastane, leptin, and galectin-3, had significant changes.

The gene expression of cancer activators and lipid oxidative activators provides insights into the mechanisms behind these immunomodulatory effects. In pregnant women, IF seems safe to be conducted and possibly useful to treat endocrine disorders during pregnancy.

Moreover, IF is able to improve resistance to the stress of surgery. IF can be beneficial for the immune system of individuals with PCOS by improving endocrine function. Limited trials studying the effects of IF on cancer have been conducted.

For nervous system, IF is believed to be applicable to treat anxiety and cognitive disorders by cellular, metabolic and circadian mechanisms. However, more trials are needed to better understand the effects and mechanisms by which IF modulates the immune system.

Our systematic review, analyzing data from IF studies in different populations, suggests that IF could have immunomodulatory effects in healthy people, obese people, and people with special physiological and pathophysiological conditions.

Different mechanisms may contribute to these effects. IF can benefit non-obese healthy individuals by strengthening circadian rhythms, migrating immune cells, lower inflammatory factors, and enriching microbial diversity.

Physiological stress by surgery and pathophysiological disorders by endocrine diseases may be partly eased with IF. ZH, HX, HY, and YM contributed to conception and design of the study.

ZH and HX organized the methodology, investigation, and data collection. ZH and CL performed the statistical analysis. ZH wrote the first draft of the manuscript.

All authors contributed to manuscript revision, read, and approved the submitted version. This work was supported by grants from CAMS Innovation Fund for Medical Sciences CIFMS No. We would like to thank Editage www. cn and Charlesworth www. cn for English language editing. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Moro, T, Tinsley, G, Pacelli, FQ, Marcolin, G, Bianco, A, and Paoli, A. Twelve months of time-restricted eating and resistance training improves inflammatory markers and Cardiometabolic risk factors.

Med Sci Sports Exerc. doi: PubMed Abstract CrossRef Full Text Google Scholar. Trepanowski, JF, Kroeger, CM, Barnosky, A, Klempel, MC, Bhutani, S, Hoddy, KK, et al. Effect of alternate-day fasting on weight loss, weight maintenance, and Cardioprotection among metabolically healthy obese adults: a randomized clinical trial.

JAMA Intern Med. Harder-Lauridsen, NM, Rosenberg, A, Benatti, FB, Damm, JA, Thomsen, C, Mortensen, EL, et al. Ramadan model of intermittent fasting for 28 d had no major effect on body composition, glucose metabolism, or cognitive functions in healthy lean men.

Guo, Y, Luo, S, Ye, Y, Yin, S, Fan, J, and Xia, M. Intermittent fasting improves Cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. J Clin Endocrinol Metab. Varady, KA, Bhutani, S, Klempel, MC, Kroeger, CM, Trepanowski, JF, Haus, JM, et al.

Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial. Nutr J. Cienfuegos, S, Gabel, K, Kalam, F, Ezpeleta, M, Wiseman, E, Pavlou, V, et al.

Effects of 4-and 6-h time-restricted feeding on weight and Cardiometabolic health: a randomized controlled trial in adults with obesity. Cell Metab. Fang, Y, Gu, Y, Zhao, C, Lv, Y, Qian, J, Zhu, L, et al. Impact of supervised beego, a traditional Chinese water-only fasting, on thrombosis and haemostasis.

BMJ Nutr Prev Health. Razavi, R, Parvaresh, A, Abbasi, B, Yaghoobloo, K, Hassanzadeh, A, Mohammadifard, N, et al. The alternate-day fasting diet is a more effective approach than a calorie restriction diet on weight loss and hs-CRP levels. Int J Vitam Nutr Res. Moro, T, Tinsley, G, Longo, G, Grigoletto, D, Bianco, A, Ferraris, C, et al.

Time-restricted eating effects on performance, immune function, and body composition in elite cyclists: a randomized controlled trial. J Int Soc Sports Nutr. Mindikoglu, AL, Abdulsada, MM, Jain, A, Jalal, PK, Devaraj, S, Wilhelm, ZR, et al.

Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome. Sci Rep. Liu, T, Xing, Y, Fan, X, Chen, Z, Zhao, C, Liu, L, et al.

Fasting and overfeeding affect the expression of the immunity-or inflammation-related genes in the liver of poultry via endogenous retrovirus. Poult Sci. Adawi, M. The effects of the Ramadan fasting on metabolic and immunological disorders.

Isr Med Assoc J. Google Scholar. Wilhelm, C, Surendar, J, and Karagiannis, F. Enemy or ally? Fasting as an essential regulator of immune responses. Trends Immunol. CrossRef Full Text Google Scholar. Okawa, T, Nagai, M, and Hase, K.

Dietary intervention impacts immune cell functions and dynamics by inducing metabolic rewiring. Front Immunol. Wegman, MP, Guo, MH, Bennion, DM, Shankar, MN, Chrzanowski, SM, Goldberg, LA, et al.

Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism. Rejuvenation Res. Moro, T, Tinsley, G, Bianco, A, Marcolin, G, Pacelli, QF, Battaglia, G, et al.

J Transl Med. Gasmi, M, Sellami, M, Denham, J, Padulo, J, Kuvacic, G, Selmi, W, et al. Time-restricted feeding influences immune responses without compromising muscle performance in older men. Stekovic, S, Hofer, SJ, Tripolt, N, Aon, MA, Royer, P, Pein, L, et al.

Alternate day fasting improves physiological and molecular markers of aging in healthy. Non-obese Humans Cell Metab. McAllister, MJ, Pigg, BL, Renteria, LI, and Waldman, HS. Time-restricted feeding improves markers of cardiometabolic health in physically active college-age men: a 4-week randomized pre-post pilot study.

Nutr Res. Zeb, F, Wu, X, Chen, L, Fatima, S, Haq, IU, Chen, A, et al. Effect of time-restricted feeding on metabolic risk and circadian rhythm associated with gut microbiome in healthy males.

Br J Nutr. Xie, Z, Sun, Y, Ye, Y, Hu, D, Zhang, H, He, Z, et al. Randomized controlled trial for time-restricted eating in healthy volunteers without obesity. Nat Commun.

Bhutani, S, Klempel, MC, Berger, RA, and Varady, KA. Improvements in coronary heart disease risk indicators by alternate-day fasting involve adipose tissue modulations. Obesity Silver Spring.

Intermittent fasting has become all the rage in recent years because it promotes weight loss by depriving the body of glucose, which forces it to break down fat to produce an alternative fuel source called ketones. Intermittent fasting could also boost immunity and help combat disease, going by a finding in mice showing that immune cells more effectively fend off infections and cancer when using ketones as an energy source.

It is widely believed that cells prefer glucose for energy. So, what are they using to make [it]? Read more:. He and his colleagues collected data from three other studies that genetically analysed T cells responding to infections and tumours.

They found that, compared with dysfunctional T cells, effective T cells had increased activity in genes involved in breaking down ketones, indicating that they derived energy from ketones when fighting disease. They found that, on average, the normal mice had 50 per cent more T cells producing substances to kill off pathogens, called cytokines, than the engineered animals, and that these animals could churn out more cytokines per T cell as well.

In other words, the ability to break down ketones made T cells more effective at fighting off infections in mice. Or, as Jones says, it increased the number of soldiers and ammunition on the front line. Get the most essential health and fitness news in your inbox every Saturday.

Jones and his team also injected cancerous cells into the mice and found that after 22 days, tumours in the mice that were unable to break down ketones were twice the size of those in the mice that could. Together, these findings suggest that immune cells are more effective at fighting disease when using ketones rather than glucose for fuel, says Jones.

They also explain why previous research has shown that fasting for 12 or more hours daily improves immune function in mice, says Satchidananda Panda at the Salk Institute for Biological Studies in California, who was not involved in the study.

If anyone is interested I fast every Monday for about hours. My last meal is Sunday evening and I start eating again Tuesday lunch. Feel free to text or email me and we can fast together! The benefits of IF on the immune system include: Reduced immunosenescence, which is aging of the immune system Lower white blood cell numbers including lymphocytes, natural killer cells, and neutrophils Lowered inflammation and fewer pro-inflammatory markers Protection against inflammatory-related conditions Now the question is, how long should you fast?

I am sure you are thinking, HOW CAN I FAST FOR 3 DAYS? That is impossible! Press Release. New York, NY August 22, Tags: Hematology Oncology , Icahn School of Medicine at Mount Sinai , Marc and Jennifer Lipschultz Precision Immunology Institute , Mount Sinai Health System , Mount Sinai Tisch Cancer Center , Patient Care , Radiation Oncology , Miriam Merad, MD, PhD , Research.

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The latest science suggests that intermittent fasting may help your body's defenses. Here's what you need to know. A recent review in the journal Immunology Letters suggests that the timing of meals can give your immune system an edge. In a nutshell, the extended calorie drought prompts your body to look for a refuel by converting damaged cells into nutrients, which reduces inflammation caused by those cells, says Herman Pontzer, Ph.

com , a new look at metabolism. What time frame triggers this calorie-restricted signal to the body? An earlier analysis of intermittent fasting in the New England Journal of Medicine found that fitting meals into six-or eight-hour windows say, from noon to 6 p.

or 11 a. is beneficial in reducing inflammation compared with a typical day of eating, but a hour window is less so, says Mark Mattson, Ph. But you do reap some benefits without being at the more restrictive end, says Marie Spano, R. If you're looking to shrink your eating window, Mattson suggests you do so gradually to acclimate with fewer hunger pangs.

If a six- or eight-hour eating period is your aim, Spano recommends "making your meals nutrient dense and eating a meal at the start of your window, in the middle, and at the end. To further fend off inflammation , keep up the exercise. We are consistently ranked by U.

New York Eye and Ear Infirmary of Mount Sinai is ranked No. org or find Mount Sinai on Facebook , Twitter and YouTube. Share Facebook Twitter Linkedin Email Home About Us Newsroom. A decrease in natural killer cells is mainly linked to a decrease in IL-2 or IGF Neither of which were measured in the trial by Madeo et al.

Besides IGF-1, other measurements also show significant changes. High level of adiponectin would stimulate fatty acid oxidation in skeletal muscle and inhibit glucose production in the liver, which benefit to energy homeostasis Meanwhile, adiponectin is an anti-inflammatory agent, a reduction of inflammatory markers including CRP and TNF-α could be observed in some studies 1 , 5.

Changes in gene expression provide more information on immunomodulatory effects: Wegman et al. concluded that an increase in SIRT1 and sirtuin3 SIRT3 expression could be detected after a 3-week trial For SIRT1 , other studies have also shown an increase level SIRT1 is linked to circadian rhythms and cellular mechanisms, such as cell repair, division, metabolism, and growth It could be concluded that IF could protect bodies from cardiovascular diseases.

SIRT3 is a member of the sirtuin family of histone deacetylases, which are primary mitochondrial protein deacetylases. Moreover, it could regulate cell metabolism, thus maintaining myocardial energy steady.

SIRT3 is also believed as a protection for cardiomyocytes from oxidative stress-mediated cell damage Besides that, some animal studies showed more exciting results through SIRT3 regulation of IF.

A study by Mao et al. investigated clock genes and showed that levels of genes such as BMAL1 and PER2 were elevated in a five-week trial 21 , indicating that IF could partly modulate the immune system by improving the circadian rhythm. The reinforcement of circadian rhythm could benefit body immune through promoting system recovery and the clearance of harmful cellular element Another potential immunomodulatory effect involves microbial diversity in two studies 20 , 21 : Low gut microbial diversity is associated with metabolic disease 42 , and high diversity may be due to the high expression of SIRT1 and high levels of HDL 20 and improve body immune system, such as liver function mentioned in the study by Li et al.

Emerging evidence showed that SIRT1 could promote gut microbial population shifts by influence inflammation and circadian rhythm It has also been suggested that IF could benefit healthy people lose weight 9 , even cyclists and men who practice resistance training 9 , After the trial, it was concluded that IF could lose almost fat and maintain muscle mass with the measurement of muscle area of the thigh and arm.

Healthy individuals might already have high insulin sensitivity at baseline; thus, IF seems to have less influence on glucose metabolism in these non-obese and healthy individuals Things were similar when focusing on lipid metabolism.

A decrease in leptin was found in many studies 1 , 16 , which might suggest that IF could partly strengthen lipid metabolism in healthy individuals. To sum up, IF could benefit immune system of healthy people through migration of immune cells, regulation of oxidative-related and circadian-related genes, increasing gut microbial diversity and improvement of muscle-fat ratio.

Trials with longer durations and more factors including anxiety degree, cognition state, microbial diversity 44—46 , key gene expression, and inflammatory markers are needed to better clarify the immunomodulatory effects of IF on healthy people.

Most obese subjects would harbor inflamed adipose tissue, which could cause a persistent, low-grade, inflammatory response. Obesity is often associated with the metabolic syndrome, because fat accumulation would cause insulin resistance And evidence accumulated that persistent inflammation of adipose tissue is a central mechanism through which obesity promotes cancer risk From the perspective of immune cells, A decrease in macrophages was observed in a study by Heilbronn et al.

Most cytokines that are produced by adipose tissue originate from nonfat cells and macrophages 29 , thus the result confirmed that IF could be beneficial for inflammation associated with obesity. Recent studies have suggested that IF inhibits the nuclear factor kappa-B signaling pathway, which is an important regulator of downstream parameters including TNF-α and IL-6 25 , which is consistent with the results that IF could partly eliminate the inflammation caused by adipose tissue, with lower CRP and TNF-α There were insignificant changes of some inflammatory markers in some studies, which might be related with short trial duration and inadequate weight loss 6.

The concentration of galectin-3, which plays various roles in humans, was measured increasingly by Horne et al.

in It has been shown that galectin-3 could stimulate the expression of some antiviral genes and protect against inflammation, which may result in improvements in glucose metabolism.

Although changes in inflammatory factors were less significant in obese people compared with healthy subjects, the immunomodulatory effect of IF observed in obese people might reflect a suppression of oxidative stress found that the ketone bodies, especially β-hydroxybutyrate, which protects against lipotoxicity and stimulates lipid oxidation, was significantly elevated in obese subjects As it was regarded as an epigenetic regulator in terms of histone methylation, acetylation, IF could help to delay various age-related diseases.

A decrease in 8-isoprostane, a marker of oxidative stress in lipids, was observed in two studies 6 , Oxidative stress is a definition of the imbalance between the production and elimination of reactive oxygen species Some other studies have suggested that, though IF might have little effect on inflammation, it may greatly influence oxidative stress, which is linked to insulin resistance Interestingly, improvements in glucose metabolism were observed in two studies that reported decreased oxidative stress markers 6 , Significant changes in leptin, which is regarded as a special body weight regulating hormone, were also noted 29 , meaning that the resistance to leptin is partly improved in obese subjects.

Besides the ability to regulate metabolic syndrome, including lowering glucose and lipid synthesis 50 , leptin is one of the mediators responsible for the inflammatory state In addition to the findings about immune cells and inflammatory markers, other study conduct tests of gene expression.

found that genes related to oxidative stress were down-regulated such as SOD1 and SOD2 28 , and Mindikoglu et al. found that the expression of other genes including the tumor activators POLK , NIFK , SRGN , CAMP , and D , were downregulated 10 , which are consistent with remitting oxidative effect and lowering cancer risk by IF.

To sum up, besides the advantages of IF on obese subjects including losing body weight, regulate lipid metabolism and improve insulin resistance, which was almost suggested in all studies, IF could reduce oxidative stress and remit inflammatory state through macrophage adjustment and hormone secretion.

Moreover, although evidence is accumulating that gut microbial is involved in the etiology of obesity 52 and altered by modified IF 4 , relevant researches were still rare.

Another issue waiting for more studies was the influence between IF and nervous system on obese subjects. A study in obese rat showed that IF could prevent memory loss in comparison to ad libitum by regulating body metabolism 54 , which offering a new sight for the advantages of IF to remit neuroinflammation.

Pregnancy is a state of high oxidative stress, which contributes to preeclampsia and restriction of fetal growth Maternal IF resulted in detrimental influence on fetal development and maternal stress stage by changing the metabolite profiles in animal studies However, IF has no significant influence on the high oxidative stress and fetal development in the human study The reason could be the different circadian rhythms between rats and humans.

A case related with gestational diabetes mellitus was reported that IF is a useful intervention to reduce maternal body weight, plasma glucose, and psychological distress without any adverse effects Surgery is regarded as a shock or an acute stress, and IF is able to improve resistance to this stress.

In a study by Ginhoyen et al. Compared with subjects in the non-fasting group, subjects in the restriction group showed a more moderate postoperative inflammatory response. For healthy people in special physiological states, such as those observed during the perioperative period, IF could reduce acute stress.

More trials are needed to identify the influence on pregnant subjects, including the fetal and maternal safety, anti-stress effect and body metabolism regulation. It is worth nothing that study include in this review on pregnant subjects was a Ramadan IF trial, which might be less convincing as subjects in this study had experienced such interventions before.

PCOS is an endocrine condition closely linked to metabolic disorders. Because obesity is closely related to PCOS, it is not surprising that IF could provide benefits by reducing insulin resistance and easing hyperandrogenemia Whether IF could be applied in subjects with cancer remains unclear 57 , because it may also affect chemotherapy.

In a study of subjects with CML, Yassin et al. reported that fasting did not result in significant immunological effects with measurements including BCR-ACL levels and hematological parameters It was suggested that IF in some patients who have cancer could be capable of decreasing chemotherapy-related toxicity and tumor growth, however 58 , more clinical trials were needed to clarify.

MS is an autoimmune disease characterized by degeneration of the central nervous system The epidemiology of this condition includes a history of childhood obesity.

Although no significant changes in leptin or adiponectin levels have been observed in studies of IF in MS, an observed difference in T-cell subsets in intestines might explain the immunological effects of IF that have been reported in studies 33 , 60 , which was also a kind of possible therapy for MS The components of the intestinal microbiome could also raise the propensity to develop MS strongly Researches about gut microbial of the influence of IF on subjects who have MS were expected as a result of migration of intestine immune cell subsets.

As mentioned before, IF is beneficial for nervous system by cellular, metabolic and circadian mechanisms and a promising therapy for brain disorders, future research should disentangle whether positive effects of IF could be applied in clinical situations Besides IF, other types of diet, including energy-restricted fasting and ketogenic diet 62 , were also evaluated as nutrition therapy for MS More results was put forward that the improvement of this diet was related with immune system, including reducing inflammatory cytokines and immune cell migration.

However, these diets might cause deficiency of various nutrients in long term To sum up, a special diet could serve as a unique nutrition therapy for MS with disadvantages of nutrition deficiency, which was nowadays a popular and promising topic.

The different evidence levels should be taken into consideration when analyzing the results of these studies. Of the 28 selected trials, 19 were randomized, controlled, parallel, or crossover studies. Some trials were cohort studies, and the trial focusing on CML was a retrospective study; the lack of a control group in that trial may lead to inaccurate conclusions.

Trials differed in terms of baseline characteristics, study durations, meal types, and IF types. These differences may interfere with the final results. For example, Gasmi et al. studied whether young people and old people would act differently while undertaking IF 17 , Paoli et al.

compared all factors in a 2-month trial and in a 1-year trial 1 , and Varady et al. focused on whether the influence of IF would vary with different durations of eating windows 6. In the future, more studies on this topic should be conducted to provide new data.

This systematic review finds substantial evidence that IF can modulate the immune system in non-obese healthy people, obese people, and subjects in other physiological or pathophysiological states and these effects were clinically relevant with cognitive improvement, lipid and metabolism regulation, and inflammatory state remission.

The mechanisms influenced and regulated to drive changes in each population differ. For example, non-obese healthy people can metabolize lipids and glucose efficiently, so the immunomodulatory effect is reflected in immune cell subset migration, lower inflammatory factors, upregulation of circadian rhythm—related gene expression, and greater microbial diversity.

Although weight reduction has also been observed in healthy people, changes in parameters of lipid and glucose metabolism remained insignificant in most cases. In obese people, IF contributes to body health by regulating macrophages, which is related to the inflammatory stage of adipose tissue.

Although many inflammatory factors did not show significant changes in obese subjects, other important factors, including 9-isoprastane, leptin, and galectin-3, had significant changes.

The gene expression of cancer activators and lipid oxidative activators provides insights into the mechanisms behind these immunomodulatory effects. In pregnant women, IF seems safe to be conducted and possibly useful to treat endocrine disorders during pregnancy.

Moreover, IF is able to improve resistance to the stress of surgery. IF can be beneficial for the immune system of individuals with PCOS by improving endocrine function. Limited trials studying the effects of IF on cancer have been conducted.

For nervous system, IF is believed to be applicable to treat anxiety and cognitive disorders by cellular, metabolic and circadian mechanisms. However, more trials are needed to better understand the effects and mechanisms by which IF modulates the immune system.

Our systematic review, analyzing data from IF studies in different populations, suggests that IF could have immunomodulatory effects in healthy people, obese people, and people with special physiological and pathophysiological conditions.

Different mechanisms may contribute to these effects. IF can benefit non-obese healthy individuals by strengthening circadian rhythms, migrating immune cells, lower inflammatory factors, and enriching microbial diversity. Physiological stress by surgery and pathophysiological disorders by endocrine diseases may be partly eased with IF.

ZH, HX, HY, and YM contributed to conception and design of the study. ZH and HX organized the methodology, investigation, and data collection. ZH and CL performed the statistical analysis. ZH wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

This work was supported by grants from CAMS Innovation Fund for Medical Sciences CIFMS No. We would like to thank Editage www. cn and Charlesworth www.

cn for English language editing. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Moro, T, Tinsley, G, Pacelli, FQ, Marcolin, G, Bianco, A, and Paoli, A.

Twelve months of time-restricted eating and resistance training improves inflammatory markers and Cardiometabolic risk factors. Med Sci Sports Exerc. doi: PubMed Abstract CrossRef Full Text Google Scholar. Trepanowski, JF, Kroeger, CM, Barnosky, A, Klempel, MC, Bhutani, S, Hoddy, KK, et al.

Effect of alternate-day fasting on weight loss, weight maintenance, and Cardioprotection among metabolically healthy obese adults: a randomized clinical trial. JAMA Intern Med. Harder-Lauridsen, NM, Rosenberg, A, Benatti, FB, Damm, JA, Thomsen, C, Mortensen, EL, et al.

Ramadan model of intermittent fasting for 28 d had no major effect on body composition, glucose metabolism, or cognitive functions in healthy lean men. Guo, Y, Luo, S, Ye, Y, Yin, S, Fan, J, and Xia, M.

Intermittent fasting improves Cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. J Clin Endocrinol Metab. Varady, KA, Bhutani, S, Klempel, MC, Kroeger, CM, Trepanowski, JF, Haus, JM, et al. Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial.

Nutr J. Cienfuegos, S, Gabel, K, Kalam, F, Ezpeleta, M, Wiseman, E, Pavlou, V, et al. Effects of 4-and 6-h time-restricted feeding on weight and Cardiometabolic health: a randomized controlled trial in adults with obesity.

Cell Metab. Fang, Y, Gu, Y, Zhao, C, Lv, Y, Qian, J, Zhu, L, et al. Impact of supervised beego, a traditional Chinese water-only fasting, on thrombosis and haemostasis. BMJ Nutr Prev Health.

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