A 67-year-old woman with proven diagnosis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) was admitted to stationary treatment twice to receive a complex therapy with methods of natural medicine comprising fasting as its main treatment element. Both times, a discrepancy between the course of markers of the acute phase on the one hand, and subjective as well as objective clinical outcome on the other hand could be observed.This may point to special conditions of this chronic inflammatory disease as compared to e.g.rheumatoid arthritis, but also to specific problems in assessing possible effects of the treatments chosen, particularly fasting therapy, as compared to effects of conventional therapies.

Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation. Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role on aging and metabolic homeostasis. Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women.

Dietary restriction has been recognized as a healthy and natural therapy for cancer. It is reported that different forms of dietary restriction can promote anti-tumor immunity. However, it is not clear how fasting affects tumor-associated macrophages (TAMs). This study aims to investigate the relationship between fasting and antitumor immunity in terms of tumor-associated macrophages. In vivo, the results showed that alternate day fasting for 2 weeks inhibitted the tumor growth of mice without causing a reduction of body weight. Meanwhile, M2 polarization of tumor-associated macrophages in tumor tissues of alternate day fasting group was also decreased. In vitro, fasting induced the autophagy of CT26 cells, decreased the generation of extracellular adenosine by supressing the expression of CD73 in CT26 cells. Decreasing adenosine inhibitted M2 polarization of RAW264.7 cells through inactivating JAK1/STAT3 signal pathway in fasting condition. Eventually, the proliferation of CT26 cancer cells declined on account of fasting-facilitated antitumor immunity. These results suggested that fasting suppressed M2 polarization of tumor-associated macrophages to inhibit tumor growth through decreasing the level of adenosine in the tumor microenvironment both in vivo and in vitro. This process was associated with increasing autophagy of tumor cells.

Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. A 24 hr fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cytometry. Expression of lypolysaccharide (LPS)-induced activation markers (vimentin, αSMA) was evaluated by qPCR and immunoblotting. Liver fibrosis and inflammation were evaluated in a mouse model of steatohepatitis exposed to cycles of fasting, by histological and biochemical analyses. A 24 hr fasting-induced changes were also analyzed on the proliferation/viability/glucose uptake of human HCC cells exposed to Sorafenib. An expression panel of genes involved in survival, inflammation, and metabolism was examined by qPCR in HCC cells exposed to fasting and/or Sorafenib. Fasting decreased the proliferation and the activation of HSC. Repeated cycles of short term starvation were safe in mice but did not improve fibrosis. Fasting synergized with Sorafenib in hampering HCC cell growth and glucose uptake. Finally, fasting normalized the expression levels of genes which are commonly altered by Sorafenib in HCC cells. Fasting or fasting-mimicking diet diets should be evaluated in preclinical studies as a mean to potentiate the activity of Sorafenib in clinical use.

New therapeutic approaches are needed to treat leukemia effectively. Dietary restriction regimens, including fasting, have been considered for the prevention and treatment of certain solid tumor types. However, whether and how dietary restriction affects hematopoietic malignancies is unknown. Here we report that fasting alone robustly inhibits the initiation and reverses the leukemic progression of both B cell and T cell acute lymphoblastic leukemia (B-ALL and T-ALL, respectively), but not acute myeloid leukemia (AML), in mouse models of these tumors. Mechanistically, we found that attenuated leptin-receptor (LEPR) expression is essential for the development and maintenance of ALL, and that fasting inhibits ALL development by upregulation of LEPR and its downstream signaling through the protein PR/SET domain 1 (PRDM1). The expression of LEPR signaling-related genes correlated with the prognosis of pediatric patients with pre-B-ALL, and fasting effectively inhibited B-ALL growth in a human xenograft model. Our results indicate that the effects of fasting on tumor growth are cancer-type dependent, and they suggest new avenues for the development of treatment strategies for leukemia.

Recent studies have demonstrated that repeated short-term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered"growth arrest and DNA damage-inducible"GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre-diabetes and type 2 diabetes, in both mice and humans. Using whole-body knockout mice as well as liver/hepatocyte-specific gain- and loss-of-function strategies, we revealed arole for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity-driven hyperglycaemia. In summary, fasting stress-induced GADD45β represents a liver-specific molecular event promoting adaptive metabolic function.

In the laboratory, food restriction has been shown to induce neuroadaptations in brain reward circuitry which are likely to be among those that facilitate survival during periods of food scarcity in the wild. However, the upregulation of mechanisms that promote foraging and reward-related learning may pose a hazard when food restriction is self-imposed in an ecology of abundant appetitive rewards. For example, episodes of loss of control during weight-loss dieting, use of drugs with addictive potential as diet aids, and alternating fasting with alcohol consumption in order to avoid weight gain, may induce synaptic plasticity that increases the risk of enduring maladaptive reward-directed behavior. In the present mini-review, representative basic research findings are outlined which indicate that food restriction alters the function of mesoaccumbens dopamine neurons, potentiates cellular and behavioral responses to D-1 and D-2 dopamine receptor stimulation, and increases stimulus-induced synaptic insertion of AMPA receptors in nucleus accumbens. Possible mechanistic underpinnings of increased drug reward magnitude, drug-seeking, and binge intake of sucrose in food-restricted animal subjects are discussed and possible implications for human weight-loss dieting are considered.

Fermentable dietary fiber has been shown to cause fat loss and to increase peptide-YY (PYY) and glucagon-like peptide 1 (GLP-1) levels in rodents. In single meal tests, humans have an increase in PYY and GLP-1 to dietary fiber, but the response of these hormones to longer-term treatment is not known. Viscofiber (Cevena Bioproducts Inc., Edmonton, AB, Canada) is a high-viscosity fermentable dietary fiber made by a proprietary process from oats and barley. Seven healthy overweight and obese subjects were treated with a calorie-restricted diet, a lifestyle change program, and 4 g of Viscofiber/day for 16 weeks. Hunger, satiety, PYY, and GLP-1 were measured before and 1 hour after a standard meal test before and at week 14 of the study. Hunger and satiety were measured by Visual Analog Scales. PYY and GLP-1 were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Weight was reduced 3.07 +/- 3.13 kg (P<.05) over the 16 weeks. Fasting PYY increased 8.67 +/- 6.62 pg/mL (P<.05) and fasting GLP-1 increased 2.67 +/- 0.84 pmol/L (P<.01) at 14 weeks compared to baseline. Satiety increased 1.78 +/- 1.43 cm (P<.01) at the 1-hour post-meal time point on week 14 compared to the study baseline. We conclude that 14 weeks of treatment with Viscofiber at 4 g/day along with a lifestyle change program and diet causes weight loss and increases fasting PYY, fasting GLP-1, and satiety at 1 hour following a standard meal, which extends the single meal test observations in humans.

The FoxO transcription factors may be involved in the antiaging effect of calorie restriction (CR) in mammals. To test the hypothesis, we used FoxO1 knockout heterozygotic (HT) mice, in which the FoxO1 mRNA level was reduced by 50%, or less, of that in wild-type (WT) mouse tissues. The WT and HT mice were fed ad libitum (AL) or 30% CR diets from 12 weeks of age. Aging- and CR-related changes in body weight, food intake, blood glucose, and insulin concentrations were similar between the WT and HT mice in the lifespan study. The response to oxidative stress, induced by intraperitoneal injection of 3-nitropropionic acid (3-NPA), was evaluated in the liver and hippocampus at 6 months of age. Several of the selected FoxO1-target genes for cell cycle arrest, DNA repair, apoptosis, and stress resistance were up-regulated in the WT-CR tissues after 3-NPA injection, while the effect was mostly diminished in the HT-CR tissues. Of these gene products, we focused on the nuclear p21 protein level in the liver and confirmed its up-regulation only in the WT-CR mice in response to oxidative stress. The lifespan did not differ significantly between the WT and HT mice in AL or CR conditions. However, the antineoplastic effect of CR, as indicated by reduced incidence of tumors at death in the WT-CR mice, was mostly abrogated in the HT-CR mice. The present results suggest a role for FoxO1 in the antineoplastic effect of CR through the induction of genes responsible for protection against oxidative and genotoxic stress.

OBJECTIVE:To evaluate the effects of acute and daily consumption of high-oleic peanuts (HOP) on inflammation and glucose homeostasis in overweight/obese men.

METHODS:In a 4-week randomized clinical trial, males with body mass index of 29.8± 2.3 kg/m(2) and aged 18-50 years were assigned to the groups: control (CT, n = 22); conventional peanuts (CVP, n = 22); or HOP (n = 21). They followed a hypocaloric-diet with or without 56 g/day of CVP or HOP. Main outcomes were changes in fasting blood biomarkers and postprandial insulin, glucose, tumor necrosis factor-alfa (TNF-α), and interleukin-10 (IL-10) responses after acute peanut intake.

RESULTS:At baseline, HOP showed significantly lower postprandial responses of glucose, insulin, and TNF-α than CVP and CT. Changes in fasting blood biomarkers did not differ between groups after the 4-week intervention. However, within groups, total cholesterol decreased in CT, and all groups reduced High-density lipoprotein (HDL-c). Triglycerides were reduced in HOP and CVP. IL-10 increased significantly in all groups while only the CT and CVP showed increased TNF-α after intervention.

CONCLUSION:Acute high-oleic peanut consumption leads to stronger moderation of postprandial glucose, insulin, and TNF-α concentrations than CVP and control meal intake. Whether daily intake of high-oleic peanuts has additional benefits to CVP remains uncertain.

Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented inyoung and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.

Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16-48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer's disease Parkinson's disease and stroke. Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging.

Rett syndrome (RTT) is a rare X-linked autistic-spectrum neurological disorder associated with impaired energy metabolism, seizure susceptibility, progressive social behavioral regression, and motor impairment primarily in young girls. The objective of this study was to examine the influence of restricted diets, including a ketogenic diet (KD) and a standard rodent chow diet (SD), on behavior in male Mecp2(308/y) mice, a model of RTT. The KD is a high-fat, low-carbohydrate diet that has anticonvulsant efficacy in children with intractable epilepsy and may be therapeutic in children with RTT. Following an 11-day pretrial period, adult wild-type and mutant Rett mice were separated into groups that were fed either an SD in unrestricted or restricted amounts or a ketogenic diet (KetoCal) in restricted amounts for a total of 30 days. The restricted diets were administered to reduce mouse body weight by 20-23% compared to the body weight of each mouse before the initiation of the diet. All mice were subjected to a battery of behavioral tests to determine the influence of the diet on the RTT phenotype. We found that performance in tests of motor behavior and anxiety was significantly worse in male RTT mice compared to wild-type mice and that restriction of either the KD or the SD improved motor behavior and reduced anxiety. We conclude that although both restricted diets increased the tendency of Rett mice to explore a novel environment, the beneficial effects of the KD were due more to calorie restriction than to the composition of the diet. Our findings suggest that calorically restricted diets could be effective in reducing the anxiety and in improving motor behavior in girls with RTT.

Calorie restriction (CR) produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF) and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL) animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals. Two pilot studies were undertaken to examine the effects of ADF and CR on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human hepatoma cells and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period). Cells cultured in serum from ADF participants, showed a 20% increase in Sirt1 protein which correlated with reduced triglyceride levels. ADF serum also induced a 9% decrease in proliferation and a 25% increase in heat resistance. Cells cultured in serum from CR participants induced an increase in Sirt1 protein levels by 17% and a 30% increase in PGC-1alpha mRNA levels. This first in vitro study utilizing human serum to examine effects on markers of health and longevity in cultured cells resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity. The use of this in vitro technique may be helpful for predicting the potential of CR, ADF and other dietary manipulations to affect markers of longevity in humans.

Intermittent fasting has been demonstrated to protect against Alzheimer's disease (AD), however, the mechanism is unclear. Histone acetylation and lipoprotein lipase (LPL) are involved in AD progression. Importantly, LPL has been documented to be regulated by histone deacetylases (HDACs) inhibitors (increase histone acetylation level) in adipocyte and mesenchymal stem cells, or by fasting in adipose and muscle tissues. In brain, however, whether histone acetylation or fasting regulates LPL expression is unknown. This study was designed to demonstrate intermittent fasting may protect against AD through increasingβ-hydroxybutyrate, a HDACs inhibitor, to regulate LPL. We also investigated microRNA-29a expression associating with regulation of LPL and histone acetylation. The results showed LPL mRNA expression was increased and microRNA-29a expression was decreased in the cerebral cortex of AD model mice (APP/PS1), which were alleviated by intermittent fasting. No significant differences were found in the total expression of LPL protein (brain-derived and located in capillary endothelial cells from peripheral tissues) in the cerebral cortex of APP/PS1 mice. Further study indicated that LPL located in capillary endothelial cells was decreased in the cerebral cortex of APP/PS1 mice, which was alleviated by intermittent fasting. LPL and microRNA-29a expression were separately increased and down-regulated in 2 μM Aβ-exposed SH-SY5Y cells, but respectively decreased and up-regulated in 10μM Aβ-exposed cells, which were all reversed byβ-hydroxybutyrate. The increase of HDAC2/3 expression and the decrease of acetylated H3K9 and H4K12 levels were alleviated in APP/PS1 mice by intermittent fasting treatment, as well in 2 or 10 μM Aβ-exposed cells byβ-hydroxybutyrate treatment. These findings above suggested the results from APP/PS1 mice were consistent with those from cells treated with 2 μM Aβ. Interestingly, LPL expression was reduced (0.2-folds) and microRNA-29a expression was up-regulated (1.7-folds) in HDAC2-silenced cells, but respectively increased (1.3-folds) and down-regulated (0.8-folds) in HDAC3-silenced cells. Furthermore, LPL expression was decreased in cells treated with microRNA-29a mimic and increased with inhibitor treatment. In conclusion, intermittent fasting inhibits the increase of brain-derived LPL expression in APP/PS1 mice partly throughβ-hydroxybutyrate-mediated down-regulation of microRNA-29a expression. HDAC2/3 may be implicated in the effect of β-hydroxybutyrate on microRNA-29a expression.

Charcot-Marie-Tooth type 1A (CMT1A) neuropathies linked to the misexpression of peripheral myelin protein 22 (PMP22) are progressive demyelinating disorders of the peripheral nervous system. In this study we asked whether dietary restriction by intermittent fasting (IF) could alleviate the neuropathic phenotype in the Trembler J (TrJ) mouse model of CMT1A. Our results show that neuropathic mice kept on a five month long IF regimen had improved locomotor performance compared to ad libitum (AL) fed littermates. The functional benefits of this dietary intervention are associated with an increased expression of myelin proteins combined with a thicker myelin sheath, less redundant basal lamina, and a reduction in aberrant Schwann cell proliferation. These morphological improvements are accompanied by a decrease in PMP22 protein aggregates, and enhanced expression of cytosolic chaperones and constituents of the autophagy-lysosomal pathway. These results indicate that dietary restriction is beneficial for peripheral nerve function in TrJ neuropathic mice, as it promotes the maintenance of locomotor performance.

Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity.

Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1β, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen.

OBJECTIVE:To examine the effectiveness of intermittent energy restriction in the treatment for overweight and obesity in adults, when compared to usual care treatment or no treatment.

INTRODUCTION:Intermittent energy restriction encompasses dietary approaches including intermittent fasting, alternate day fasting, and fasting for two days per week. Despite the recent popularity of intermittent energy restriction and associated weight loss claims, the supporting evidence base is limited.

INCLUSION CRITERIA:This review included overweight or obese (BMI≥25 kg/m) adults (≥18 years). Intermittent energy restriction was defined as consumption of ≤800 kcal on at least one day, but no more than six days per week. Intermittent energy restriction interventions were compared to no treatment (ad libitum diet) or usual care (continuous energy restriction ∼25% of recommended energy intake). Included interventions had a minimum duration of 12 weeks from baseline to post outcome measurements. The types of studies included were randomized and pseudo-randomized controlled trials. The primary outcome of this review was change in body weight. Secondary outcomes included: i) anthropometric outcomes (change in BMI, waist circumference, fat mass, fat free mass); ii) cardio-metabolic outcomes (change in blood glucose and insulin, lipoprotein profiles and blood pressure); and iii) lifestyle outcomes: diet, physical activity, quality of life and adverse events.

METHODS:A systematic search was conducted from database inception to November 2015. The following electronic databases were searched: MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, ISRCTN registry, and anzctr.org.au for English language published studies, protocols and trials. Two independent reviewers evaluated the methodological quality of included studies using the standardized critical appraisal instruments from the Joanna Briggs Institute. Data were extracted from papers included in the review by two independent reviewers using the standardized data extraction tool from the Joanna Briggs Institute. Effect sizes were expressed as weighted mean differences and their 95% confidence intervals were calculated for meta-analyses.

RESULTS:Six studies were included in this review. The intermittent energy restriction regimens varied across studies and included alternate day fasting, fasting for two days, and up to four days per week. The duration of studies ranged from three to 12 months. Four studies included continuous energy restriction as a comparator intervention and two studies included a no treatment control intervention. Meta-analyses showed that intermittent energy restriction was more effective than no treatment for weight loss (-4.14 kg; 95% CI -6.30 kg to -1.99 kg; p ≤ 0.001). Although both treatment interventions achieved similar changes in body weight (approximately 7 kg), the pooled estimate for studies that investigated the effect of intermittent energy restriction in comparison to continuous energy restriction revealed no significant difference in weight loss (-1.03 kg; 95% CI -2.46 kg to 0.40 kg; p = 0.156).

CONCLUSIONS:Intermittent energy restriction may be an effective strategy for the treatment of overweight and obesity. Intermittent energy restriction was comparable to continuous energy restriction for short term weight loss in overweight and obese adults. Intermittent energy restriction was shown to be more effective than no treatment, however, this should be interpreted cautiously due to the small number of studies and future research is warranted to confirm the findings of this review.