Comparing caloric restriction regimens for effective weight management in adults: a systematic review and network meta-analysis.

BACKGROUND: Randomized controlled trials have confirmed the effectiveness of four prevalent caloric restriction regimens in reducing obesity-related health risks. However, there is no consensus on the optimal regimen for weight management in adults. METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane CENTRAL up to January 15, 2024, for randomized controlled trials (RCT) involving adults, evaluating the weight-loss effects of alternate day fasting (ADF), short-term fasting (STF), time-restricted eating (TRE), and continuous energy restriction (CER). The primary outcome was body weight, with secondary outcomes including BMI, fat mass, lean mass, waist circumference, fasting glucose, HOMA-IR, and adverse events. Bayesian network meta-analysis was conducted, ranking regimens using the surface under the cumulative ranking curve and the probability of being the best. Study quality was assessed using the Confidence in Network Meta-Analysis tool. RESULTS: Data from 47 RCTs (representing 3363 participants) were included. ADF showed the most significant body weight loss (Mean difference (MD): -3.42; 95% Confidence interval (CI): -4.28 to -2.55), followed by TRE (MD: -2.25; 95% CI: -2.92 to -1.59). STF (MD: -1.87; 95% CI: -3.32 to -0.56) and CER (MD: -1.59; 95% CI: -2.42 to -0.79) rank third and fourth, respectively. STF lead to decline in lean mass (MD: -1.26; 95% CI: -2.16, -0.47). TRE showed benefits on fasting glucose (MD: -2.98; 95% CI: -4.7, -1.26). Subgroup analysis revealed all four caloric restriction regimens likely lead to modest weight loss after 1-3 months, with ADF ranked highest, but by 4-6 months, varying degrees of weight regain occur, particularly with CER, while interventions lasting 7-12 months may result in effective weight loss, with TRE potentially ranking first during both the 4-6 months and 7-12 months periods. ADF showing fewer and shorter-lasting physical symptoms. CONCLUSION: All four included regiments were effective in reducing body weight, with ADF likely having the most significant impact. Each regimen likely leads to modest weight loss after 1-3 months, followed by weight regain by 4-6 months. However, interventions lasting 7-12 months achieve greater weight loss overall. TRIAL REGISTRATION: PROSPERO: CRD42022382478.

The circadian rhythm regulates branched-chain amino acids metabolism in fast muscle of Chinese perch (Siniperca chuatsi) during short-term fasting by Clock-KLF15-Bcat2 pathway.

As an internal time-keeping mechanism, circadian rhythm plays crucial role in maintaining homoeostasis when in response to nutrition change; meanwhile, branched-chain amino acids (BCAA) in skeletal muscle play an important role in preserving energy homoeostasis during fasting. Previous results from our laboratory suggested that fasting can influence peripheral circadian rhythm and BCAA metabolism in fish, but the relationship between circadian rhythm and BCAA metabolism, and whether circadian rhythm regulates BCAA metabolism to maintain physiological homoeostasis during fasting remains unclear. This study shows that the expression of fifteen core clock genes as well as KLF15 and Bcat2 is highly responsive to short-term fasting in fast muscle of Siniperca chuatsi, and the correlation coefficient between Clock and KLF15 expression is enhanced after fasting treatment. Furthermore, we demonstrate that the transcriptional expression of KLF15 is regulated by Clock, and the transcriptional expression of Bcat2 is regulated by KLF15 by using dual-luciferase reporter gene assay and Vivo-morpholinos-mediated gene knockdown technique. Therefore, fasting imposes a dynamic coordination of transcription between the circadian rhythm and BCAA metabolic pathways. The findings highlight the interaction between circadian rhythm and BCAA metabolism and suggest that fasting induces a switch in KLF15 expression through affecting the rhythmic expression of Clock, and then KLF15 promotes the transcription of Bcat2 to enhance the metabolism of BCAA, thus maintaining energy homoeostasis and providing energy for skeletal muscle as well as other tissues.

Quality of life and illness perceptions in patients with breast cancer using a fasting mimicking diet as an adjunct to neoadjuvant chemotherapy in the phase 2 DIRECT (BOOG 2013-14) trial.

PURPOSE: In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness perceptions regarding the possible side effects of chemotherapy and the FMD were secondary outcomes of the trial. METHODS: 131 patients with HER2-negative stage II/III breast cancer were recruited, of whom 129 were randomly assigned (1:1) to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and the day of neoadjuvant chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires EORTC-QLQ-C30 and EORTC-QLQ-BR23; the Brief Illness Perception Questionnaire (BIPQ) and the Distress Thermometer were used to assess these outcomes at baseline, halfway chemotherapy, before the last cycle of chemotherapy and 6 months after surgery. RESULTS: Overall QoL and distress scores declined during treatment in both arms and returned to baseline values 6 months after surgery. However, patients' perceptions differed slightly over time. In particular, patients receiving the FMD were less concerned and had better understanding of the possible adverse effects of their treatment in comparison with patients on a regular diet. Per-protocol analyses yielded better emotional, physical, role, cognitive and social functioning scores as well as lower fatigue, nausea and insomnia symptom scores for patients adherent to the FMD in comparison with non-adherent patients and patients on their regular diet. CONCLUSIONS: FMD as an adjunct to neoadjuvant chemotherapy appears to improve certain QoL and illness perception domains in patients with HER2-negative breast cancer. Trialregister ClinicalTrials.gov Identifier: NCT02126449.

Fasting to enhance Cancer treatment in models: the next steps.

Short-term fasting (STF) is a technique to reduce nutrient intake for a specific period. Since metabolism plays a pivotal role in tumor progression, it can be hypothesized that STF can improve the efficacy of chemotherapy. Recent studies have demonstrated the efficacy of STF in cell and animal tumor models. However, large-scale clinical trials must be conducted to verify the safety and effectiveness of these diets. In this review, we re-examine the concept of how metabolism affects pathophysiological pathways. Next, we provided a comprehensive discussion of the specific mechanisms of STF on tumor progression, derived through studies carried out with tumor models. There are currently at least four active clinical trials on fasting and cancer treatment. Based on these studies, we highlight the potential caveats of fasting in clinical applications, including the onset of metabolic syndrome and other metabolic complications during chemotherapy, with a particular focus on the regulation of the epithelial to mesenchymal pathway and cancer heterogeneity. We further discuss the advantages and disadvantages of the current state-of-art tumor models for assessing the impact of STF on cancer treatment. Finally, we explored upcoming fasting strategies that could complement existing chemotherapy and immunotherapy strategies to enable personalized medicine. Overall, these studies have the potential for breakthroughs in cancer management.

How Far Are We from Prescribing Fasting as Anticancer Medicine?

(1) Background: the present review provides a comprehensive and up-to date overview of the potential exploitation of fasting as an anticancer strategy. The rationale for this concept is that fasting elicits a differential stress response in the setting of unfavorable conditions, empowering the survival of normal cells, while killing cancer cells. (2) Methods: the present narrative review presents the basic aspects of the hormonal, molecular, and cellular response to fasting, focusing on the interrelationship of fasting with oxidative stress. It also presents nonclinical and clinical evidence concerning the implementation of fasting as adjuvant to chemotherapy, highlighting current challenges and future perspectives. (3) Results: there is ample nonclinical evidence indicating that fasting can mitigate the toxicity of chemotherapy and/or increase the efficacy of chemotherapy. The relevant clinical research is encouraging, albeit still in its infancy. The path forward for implementing fasting in oncology is a personalized approach, entailing counteraction of current challenges, including: (i) patient selection; (ii) fasting patterns; (iii) timeline of fasting and refeeding; (iv) validation of biomarkers for assessment of fasting; and (v) establishment of protocols for patients' monitoring. (4) Conclusion: prescribing fasting as anticancer medicine may not be far away if large randomized clinical trials consolidate its safety and efficacy.

Effects of short-term fasting on the resistance of Nile tilapia (Oreochromis niloticus) to Streptococcus agalactiae infection.

Short-term feed deprivation or fasting is commonly experienced by aquaculture fish species and may be caused by seasonal variations, production strategies, or diseases. To assess the effects of fasting on the resistance of Nile tilapia to Streptococcus agalactiae infection, vaccinated and unvaccinated fish were fasted for zero, one, three, and seven days prior to infection. The cortisol levels of both vaccinated and unvaccinated fish first decreased and then increased significantly as fasting time increased. Liver glycogen, triglycerides, and total cholesterol decreased significantly after seven days of fasting, but glucose content did not vary significantly between fish fasted for three and seven days. Hexokinase (HK) and pyruvate kinase (PK) activity levels were lowest after seven days of fasting, while phosphoenolpyruvate carboxykinase (PEPCK) activity levels varied in opposition to those of HK and PK. Serum superoxide dismutase (SOD) and catalase (CAT) activity levels first increased and then decreased as fasting time increased; SOD activity was highest after three days of fasting. Interleukin-1beta (IL-1ß) and IL-6 mRNA expression levels first increased and then decreased significantly, peaking after three days of fasting. However, suppressor of cytokine signaling-1 (SOCS-1) mRNA expression levels were in opposition to those of IL-1ß and IL-6. Specific antibody levels did not vary significantly among unvaccinated fish fasted for different periods. Although specific antibody level first increased and then decreased in the vaccinated fish as fasting duration increased, there were no significant differences in the survival rates of fasted vaccinated fish after challenge with S. agalactiae. The final survival rates of vaccinated fish fasted for zero, one, three, and seven days were 86.67 ±â€¯5.44%, 80.00 ±â€¯3.14%, 88.89 ±â€¯6.28%, and 84.44 ±â€¯8.32%, respectively. Among the unvaccinated fish, the survival rate was highest (35.56 ±â€¯3.14%) in the fish fasted for three days and lowest (6.67 ±â€¯3.14%) in the fish fasted for seven days. Therefore, our results indicated that short-term fasting (three days) prior to an infection might increase the resistance of unvaccinated Nile tilapia to S. agalactiae.

Rat brown adipose tissue thermogenic markers are modulated by estrous cycle phases and short-term fasting.

Brown adipose tissue (BAT) converts chemical energy into heat to maintain body temperature. Although fatty acids (FAs) represent a primary substrate for uncoupling protein 1 (UCP1)-dependent thermogenesis, BAT also utilizes glucose for the same purpose. Considering that estrous cycle effects on BAT are not greatly explored, we examined those of 6-h fasting on interscapular BAT (iBAT) thermogenic markers in proestrus and diestrus. We found that the percentage of multilocular adipocytes was lower in proestrus than in diestrus, although it was increased after fasting in both analyzed estrous cycle stages. Furthermore, the percentage of paucilocular adipocytes was increased by fasting, unlike the percentage of unilocular cells, which decreased in both analyzed stages of the estrous cycle. The UCP1 amount was lower in proestrus irrespectively of the examined dietary regimens. Regarding FA transporters, it was shown that iBAT CD36 content was increased in fasted rats in diestrus. In contrast to GLUT1, the level of GLUT4 was interactively modulated by selected estrous cycle phases and fasting. There was no change in insulin receptor and ERK1/2 activation, while AKT activation was interactively modulated by fasting and estrous cycle stages. Our study showed that iBAT exhibits morphological and functional changes in proestrus and diestrus. Moreover, iBAT undergoes additional dynamic functional and morphological changes during short-term fasting to modulate nutrient utilization and adjust energy expenditure.

ROS-Induced Autophagy of Skeletal Muscle Confers Resistance of Rice Flower Carp (Cyprinus carpio) to Short-Term Fasting.

Starvation is one of the main stresses for fish due to food shortage, the evasion of predators, and intraspecific competition. This research evaluated the impact of brief fasting periods on reactive oxygen species (ROS) levels, antioxidant response, mRNA expression of antioxidants, autophagy-related signaling genes, and autophagosome development in the muscle tissue of rice flower carp. Following a three-day fasting period, the levels of ROS and MDA rose. Additionally, after 3 d of fasting, there was a notable upregulation of NRF2 and significant increases in the levels of GSH and the activities of enzymes such as SOD, CAT, GST, GR, and GPX, while the expression of the autophagy marker gene LC3B did not change (p < 0.05). After 7 d of fasting, the content of the ROS, the activity of SOD and GR, and the GSH content reached the maximum (p < 0.05). Concurrently, there was a significant rise in the quantity of autophagosomes. An RT-qPCR analysis revealed that seven d of starvation significantly elevated the mRNA expression of genes associated with the initiation and expansion of autophagosome membranes, vesicle recycling, and cargo recruitment, including ULK1, BECLIN1, LC3B, ATG3, ATG4B, ATG4C, ATG5, ATG9, and P62. After feeding resumed for 3 d, the mRNA level of BECLIN1, ATG3, ATG4B, ATG4C, ATG5, LC3B, and P62 still remained at a high level. The LC3II protein reached its highest level. All autophagy-related gene expression decreased in the 7-day resumed feeding group. Our data implied that short-term fasting can cause oxidative stress and disrupt the antioxidant system first and then induce autophagy in the muscles of rice flower carp. These findings shed light on how fasting affects muscle homeostasis in fish. ROS-induced autophagy of the skeletal muscle may confer the resistance of rice flower carp to short-term fasting.

The effects of early-age thermal manipulation and daily short-term fasting on performance and body temperatures in broiler exposed to heat stress.

This study was conducted to investigate the effects of thermal manipulation at 5 days of age and short-term fasting during the warmest part of the day on responses to prolonged heat stress of broilers. A total of 240-day-old Ross 308 female broiler chicks were divided into three groups: control, thermal manipulation (chicks were exposed to 36 °C for 24 h at 5 days of age) and short-term fasting during the warmest part of the day (10.00-17.00 h). Prolonged heat stress was induced daily from 28 to 42 days by heating until the ambient temperature reached 32-35 °C between 10.00 and 17.00 h. Both thermal manipulation and short-term fasting resulted in a decrease in rectal temperatures and haematocrit values at 35 and 41 days of age. Thermal manipulation improved body weight, feed consumption and feed conversion. However, short-term fasting caused a reduction in body weight and a deterioration in feed conversion. Short-term fasting lowered the percentages of carcass, whereas thermal manipulation highered breast yield. Both thermal manipulation and short-term fasting decreased heart mass and abdominal fat.

Short-term fasting and fasting mimicking diets combined with chemotherapy: a narrative review.

Many patients with cancer search for and use alternative and complementary treatments, aiming to improve the effectiveness of their anticancer treatment and a reduction in treatment-associated side effects. Short-term fasting (STF) and fasting mimicking diets (FMDs) are among the most commonly used dietary interventions. In recent years, different trials have reported the promising results of dietary interventions in combination with chemotherapy, in terms of slowing down tumor growth and reduction in chemotherapy-related side effects. In this narrative review, we identify and describe the current evidence about feasibility and effects of STF and FMDs in cancer patients receiving chemotherapy. The studies that examined the effects of STF when combined with chemotherapy suggest potential benefits regarding reduction in side effects and improved quality of life. We also conclude with a list of well-designed studies that are still recruiting patients, examining the long-term effects of STF.

Nutrient-sensing AgRP neurons relay control of liver autophagy during energy deprivation.

Autophagy represents a key regulator of aging and metabolism in sensing energy deprivation. We find that fasting in mice activates autophagy in the liver paralleled by activation of hypothalamic AgRP neurons. Optogenetic and chemogenetic activation of AgRP neurons induces autophagy, alters phosphorylation of autophagy regulators, and promotes ketogenesis. AgRP neuron-dependent induction of liver autophagy relies on NPY release in the paraventricular nucleus of the hypothalamus (PVH) via presynaptic inhibition of NPY1R-expressing neurons to activate PVHCRH neurons. Conversely, inhibiting AgRP neurons during energy deprivation abrogates induction of hepatic autophagy and rewiring of metabolism. AgRP neuron activation increases circulating corticosterone concentrations, and reduction of hepatic glucocorticoid receptor expression attenuates AgRP neuron-dependent activation of hepatic autophagy. Collectively, our study reveals a fundamental regulatory principle of liver autophagy in control of metabolic adaptation during nutrient deprivation.

Current Evidence and Directions for Intermittent Fasting During Cancer Chemotherapy.

Almost 40% of the adult population in the USA will be diagnosed with cancer in their lifetime. Diet is a modifiable factor which is known to affect cancer risk and recurrence. Yet, little is known about how diet influences cancer treatment outcomes. Intermittent fasting, characterized by periods of abstaining from foods and beverages alternated with periods of ad libitum intake, when adopted in the context of chemotherapy, has shown promise in preclinical models resulting in decreased vomiting, diarrhea, visible discomfort, and improved insulin sensitivity and efficacy of chemotherapeutic treatment. Although intermittent fasting during receipt of chemotherapy has been well-established in preclinical models, limited numbers of human studies are now being reported. This review aims to survey the current data examining the effect of intermittent fasting on chemotherapy efficacy, patient treatment outcomes, patient centered outcomes, and circulating biomarkers associated with cancer. Available data show that periodic fasting, a form of intermittent fasting, may hold potential to improve the effectiveness of chemotherapy, decrease treatment-related side effects and cancer-promoting factors such as insulin, while ameliorating treatment-related decreases in quality of life and daily functioning. Larger controlled periodic fasting trials, including exploration of alternate forms of intermittent fasting, are needed to better elucidate the effect of intermittent fasting on treatment and patient outcomes during chemotherapy.

Short-Term Fasting Synergizes with Solid Cancer Therapy by Boosting Antitumor Immunity.

Short-term fasting (STF), using a low caloric, low protein fasting mimicking diet (FMD), appears to be a promising strategy to enhance chemotherapy-based cancer efficacy, while potentially alleviating toxicity. Preclinical results suggest that enhanced tumor immunity and decreased growth signaling, via lowering of circulating insulin and insulin growth factor 1 (IGF-1) levels form the potential underlying mechanisms. STF may boost anti-tumor responses by promoting tumor immunogenicity and decreasing local immunosuppression. These findings warrant further studies focused on the combination of STF, not only with chemotherapy, but also with immunotherapy to evaluate the full range of benefits of STF in cancer treatment. Here, we delineate the underlying anticancer mechanisms of fasting. We summarize preclinical evidence of STF boosting antitumor immunity and alleviating immunosuppression, as well as the clinical findings reporting the immunomodulatory effects of STF during various cancer treatments, including immunotherapy.

Fasting Intervention for Children With Unilateral Renal Tumors to Reduce Toxicity.

Childhood renal tumors account for around 6% of all childhood cancers and 90% of these cases are Wilms tumor. In Europe, the SIOP-RTSG approach is considered standard of care and has resulted in five-year survival rates of over 90%. Efforts to decrease toxicity are now being pursued. Short-term fasting (STF), a short but strong reduction in calorie-intake, is associated with improved fitness, enhanced coping with acute physical stress and a lower risk of age-associated diseases. STF temporarily reduces growth to boost resilience, maintenance, and defense-mechanisms, by which toxic side-effects of (oxidative) damage and inflammation are largely prevented. Renal surgery for Wilms tumor carries a risk of acute kidney injury (AKI) and pediatric patients that had an episode of AKI are at increased risk for developing chronic renal disease. STF could mitigate surgery-induced stress and could further improve outcomes. We aim to investigate the effect of STF on renal function recovery after renal tumor surgery by conducting a single-center, prospective, randomized, non-blinded, intervention study. Children diagnosed with a unilateral renal tumor and opting for curative treatment are eligible for inclusion. The main study objective is to investigate the potential decrease in occurrence of AKI due to STF. Secondary objectives include renal function recovery, child's wellbeing, physical functioning, and feasibility of and adherence to STF in children with cancer.

Effects of short-term fasting and pharmacological activation of AMPK on metabolism of rat adipocytes.

AMP-activated protein kinase (AMPK) is a key intracellular energy sensor and regulates processes associated with energy metabolism. In the present study, effects of AICAR, a pharmacological activator of AMPK, on metabolism of adipocytes of non-fasted and 12-h fasted rats were compared. It was shown that in fat cells of control rats, epinephrine- and dibutyryl-cAMP-induced lipolysis was markedly reduced in the presence of AICAR. However, in adipocytes of fasted animals, the lipolytic response was not significantly affected by AICAR. Moreover, in cells of control rats, the inhibitory effect of insulin on epinephrine-induced lipolysis was markedly deepened in the presence of AICAR. However, this effect was not shown in fat cells of fasted rats. This indicates that pharmacological activation of AMPK by AICAR influences metabolism of adipocytes of non-fasted rats, however, AICAR fails to affect metabolism of these cells under conditions of fasting.

Effects of short-term fasting on ruminal pH and volatile fatty acids in cattle fed high-roughage versus high-concentrate diets.

We evaluated whether the dietary roughage-to-concentrate ratio affects ruminal pH and volatile fatty acids (VFAs) in response to a one-time morning fast. Four healthy rumen-cannulated Holstein steers 4-5 months old were used. Cattle were subjected to 2 weeks of adaptation (high-roughage or high-concentrate diet), and morning feed restriction was performed on the day after the adaptation period ended (Day 0). Thereafter, each diet was reintroduced on the evening of Day 0. Our results showed that the 1-hr mean ruminal pH from 0800 to 1900 on Day 0 was higher, and that from 1700 to 1900 on Day 1 was lower (P<0.05) than pH on 1 day before fasting (Day -1) in cattle fed both diets. On Day 0, total VFA levels decreased after morning fasting and were lower (P<0.05) than those on Day -1 irrespective of evening refeeding. Furthermore, blood non-esterified fatty acid and beta-hydroxybutyric acid levels on Day 0 increased and decreased, respectively, compared to Day -1 in cattle fed both diets. These results indicate that even a one-time feed restriction can disrupt ruminal fermentation, and the changes can persist to the next day after fasting.

Diet Supplementation with a Bioactive Pomace Extract from Olea europaea Partially Mitigates Negative Effects on Gut Health Arising from a Short-Term Fasting Period in Broiler Chickens.

The effects of supplementing chicken diets with an olive pomace extract (OE) from Olea europaea on performance and gut health after a challenge of intestinal permeability (IP) increase were studied. Treatments included a control diet with no additives (CF), and diets supplemented with 100 ppm of monensin (MF) or with 500 (OE500F) and 1500 ppm (OE1500F) of an OE. At 14 d, all birds, except those allocated in a control group (CNF), were submitted to a 15.5 h short-term fasting period to induce IP increase. Fasting increased (p < 0.05) lactulose/mannitol ratio and Alpha 1 Acid Glycoprotein concentration, and reduced (p < 0.001) villus/crypt ratio. Moreover, a down-regulation of Claudin-1 (p < 0.05), an up-regulation of TLR4 and IL-8 (p < 0.05) ileal gene expression was observed in CF birds compared to CNF. OE500F treatment reduced duodenal crypt depth compared to CF (p < 0.05; OE linear effect). Mannitol concentration and ileal IL-8 expression were reduced in OE500F compared to CF and OE1500F (p = 0.05). Fasting challenge induced an increase in IP triggering an inflammatory response. Supplementation of OE up to 1500 ppm did not affect growth performance and alleviated some of the negative effects of the fasting challenge.

Short-term fasting accompanying chemotherapy as a supportive therapy in gynecological cancer: protocol for a multicenter randomized controlled clinical trial.

BACKGROUND/OBJECTIVES: A few preliminary studies have documented the safety and feasibility of repeated short-term fasting in patients undergoing chemotherapy. However, there is a lack of data from larger randomized trials on the effects of short-term fasting on quality of life, reduction of side effects during chemotherapy, and a possible reduction of tumor progression. Moreover, no data is available on the effectiveness of fasting approaches compared to so-called healthy diets. We aim to investigate whether the potentially beneficial effects of short-term fasting can be confirmed in a larger randomized trial and can compare favorably to a plant-based wholefood diet. METHODS: This is a multicenter, randomized, controlled, two-armed interventional study with a parallel group assignment. One hundred fifty patients, including 120 breast cancer patients and 30 patients with ovarian cancer, are to be randomized to one of two nutritional interventions accompanying chemotherapy: (1) repeated short-term fasting with a maximum energy supply of 350-400 kcal on fasting days or (2) repeated short-term normocaloric plant-based diet with restriction of refined carbohydrates. The primary outcome is disease-related quality of life, as assessed by the functional assessment of the chronic illness therapy measurement system. Secondary outcomes include changes in the Hospital Anxiety and Depression Score and as well as frequency and severity of chemotherapy-induced side effects based on the Common Terminology Criteria of Adverse Events. Explorative analysis in a subpopulation will compare histological complete remissions in patients with neoadjuvant treatments. DISCUSSION/PLANNED OUTCOMES: Preclinical data and a small number of clinical studies suggest that repeated short-term fasting may reduce the side effects of chemotherapy, enhance quality of life, and eventually slow down tumor progression. Experimental research suggests that the effects of fasting may partly be caused by the restriction of animal protein and refined carbohydrates. This study is the first confirmatory, randomized controlled, clinical study, comparing the effects of short-term fasting to a short-term, plant-based, low-sugar diet during chemotherapy on quality of life and histological tumor remission. TRIAL REGISTRATION: ClinicalTrials.gov NCT03162289 . Registered on 22 May 2017.

Effects of short-term fasting on cancer treatment.

Growing preclinical evidence shows that short-term fasting (STF) protects from toxicity while enhancing the efficacy of a variety of chemotherapeutic agents in the treatment of various tumour types. STF reinforces stress resistance of healthy cells, while tumor cells become even more sensitive to toxins, perhaps through shortage of nutrients to satisfy their needs in the context of high proliferation rates and/or loss of flexibility to respond to extreme circumstances. In humans, STF may be a feasible approach to enhance the efficacy and tolerability of chemotherapy. Clinical research evaluating the potential of STF is in its infancy. This review focuses on the molecular background, current knowledge and clinical trials evaluating the effects of STF in cancer treatment. Preliminary data show that STF is safe, but challenging in cancer patients receiving chemotherapy. Ongoing clinical trials need to unravel if STF can also diminish toxicity and increase efficacy of chemotherapeutic regimes in daily practice.