Video
Study shows fasting may help reduce breast cancer riskFasting and cancer prevention -
Emboldened by the striking findings, Hu and Amaral, along with Freedland, designed a clinical trial investigating the safety and efficacy of the dietary protocol, called DIET2TREAT. The multicenter, two-arm trial of glioblastoma patients across five sites will pit a ketogenic diet against a control arm, both in conjunction with standard of care.
Read: A Double-Edged Sword: Inflammation and Your Health. For decades, researchers have recognized the benefits of starving cancerous cells.
Without nourishment to grow and thrive, cancer cells become more vulnerable to chemotherapy and targeted treatments. At the same time, normal cells become more dormant heavy-duty hibernating , which helps protect them against the toxicities of treatments, including androgen deprivation therapy and even chemotherapy.
And according to pre-clinical findings from Stephen Pandol, MD, director of Basic and Translational Pancreas Research, fasting could play a role in preventing metastases to the liver. Building on this research, Freedland and his colleagues launched a Phase II, multicenter randomized trial to uncover whether following a five-day per month plant-based diet for six months, in conjunction with intensified androgen deprivation therapy, can improve cancer control and reduce the negative metabolic and cardiovascular side effects of treatment for patients with metastatic prostate cancer.
The diet called the fasting mimicking diet provides about 1, calories on day one, approximately calories per day on days two through four and calories on day five. Read: Could Walnuts Prove Beneficial for Prostate Cancer Patients? At the same time, Cedars-Sinai investigators, in collaboration with the University of Alabama at Birmingham, are embarking on one of the largest randomized controlled trials of time-restricted eating among patients with cancer in active treatment.
Read: Explaining the Link Between Prostate Cancer and Obesity. Patients are craving more control, and even the sickest patients who have the worst outcomes are hungry for guidance about diet, lifestyle and exercise.
In the Newsroom: An Updated Look at Prostate Cancer Disparities. Cedars-Sinai Discoveries Researchers Look to Fasting as a Next Step in Cancer Treatment. discoveries magazine.
Attacking the Toughest Tumors. Targeting Toxicities. Empowering Patients. Therefore, STF is a promising strategy to enhance the efficacy and tolerability of chemotherapy in cancer patients, especially as STF is an affordable and accessible approach and is potentially effective in a wide variety of tumors [ 12 ].
However, patients with severe weight loss, sarcopenia, cachexia or malnutrition are probably not good candidates for a STF intervention [ 27 , 28 ].
Recent guidelines recommend to increase protein and fat consumption in patients with cachexia [ 29 , 30 ]. Thus, STF may be particularly useful for relatively fit patients treated with neo adjuvant chemotherapy.
Moreover, it summarizes the available clinical data reflecting the impact of STF on the effects of chemotherapy in cancer patients. Finally, ongoing clinical studies of the effects of STF in cancer treatment will be critically reviewed. In healthy cells, nutrient deprivation shuts down pathways promoting growth to re-invest energy in maintenance and repair pathways Fig.
This results in increased cellular protection, contributing to enhanced resistance to distinct stressors including chemotherapy and radiotherapy [ 19 , 33 ].
In contrast, tumor cells are unable to activate this protective response, due to: 1 uncontrolled activation of growth pathways and self-sufficiency in growth signals caused by oncogenic mutations or autocrine production of growth factors, and 2 loss of anti-proliferative signals due to mutations in tumor suppressor genes [ 34 ].
Thus, acquiring the ability to increase growth, tumor cells lose the ability to adapt to extreme environments, including nutrient deprivation. Additionally, the persistent increased growth rate of tumor cells requires abundant nutrients [ 35 ].
Therefore, STF increases DSS of tumor cells to several chemotherapeutic agents, radiotherapy and tyrosine kinase inhibitors TKIs Table 1 [ 12 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 36 , 37 , 38 , 39 , 40 ].
Although the exact mechanism of DSR and DSS by STF is unknown, several growth factors and nutrient sensing pathways have been proposed to be key regulators, of which insulin-like growth factor-1 IGF-1 is the most examined [ 41 , 42 , 43 ].
Nutrient sensing pathways are activated or inhibited in response to a low amount of available nutrients and are highly conserved among distinct organisms to overcome periods of famine [ 44 ].
During nutrient scarcity, these pathways guide cells to invest energy in repair and maintenance rather than reproduction and growth [ 45 , 46 , 47 ], presumably to enhance survival of periods of famine. Analogously, infection-induced anorexia is a common sign of sickness and may be an important strategy for host defence [ 48 , 49 ].
IGF-1 and insulin stimulate proliferation and growth and inhibit apoptosis in response to calorie and protein availability through signalling via the IGF-1 receptor IGF-1R and insulin receptor isoform A IR-A , respectively [ 50 , 51 , 52 , 53 ].
Serum IGF-1 levels decrease during STF [ 54 , 55 , 56 ], because low insulin levels cause growth hormone GH resistance of the liver, which inhibits hepatic IGF-1 production [ 54 , 57 , 58 ].
For example, mice with a liver Igf1 gene deletion LID , which have decreased IGF-1 levels similar to those during STF [ 59 , 60 , 61 ], exhibit increased resistance to high doses of various chemotherapeutic agents [ 42 ] and this benefit was nullified through IGF-1 administration [ 12 , 42 ].
Thus, the IGF-1R pathway seems to be a key mediator of stress resistance in response to STF in healthy cells. Notably, resistance to the growth limiting effects of STF has been observed in cancer cells carrying mutations that cause a constitutive activation of the PI3K pathway, since these cells proliferate even in the absence of insulin or IGF-1 [ 65 ].
Therefore, the IGF-1R pathway is a key mediator of cancer cell growth and cancer resistance to commonly used therapeutics [ 42 , 66 , 67 ]. Thus, the reduction in circulating levels of IGF-1 and insulin during STF may contribute to the anticancer activity as well [ 68 ]. AMP-activated protein kinase AMPK may play a major part in DSR due to STF [ 69 ].
AMPK monitors cellular energy levels and becomes activated when ADP:ATP or AMP:ATP ratios in the cell increase [ 70 ]. AMPK inhibits energy consuming processes, such as cell proliferation and protein synthesis, and activates energy generating processes, such as glycolysis and fatty acid oxidation.
It inhibits cell growth and stimulates autophagy [ 71 ]. This adaptive response of the cell involves damaged protein and organelle degradation to generate amino acids as an alternative energy source [ 72 , 73 ]. Activation of AMPK and autophagy seems to play a major part in de protective effects of STF in healthy cells [ 17 ].
However, the effects of AMPK activation in distinct tumor cells may vary, as some tumors harbour constitutively active AMPK [ 74 , 75 ] and others exhibit low AMPK activity [ 76 , 77 , 78 ]. Tumors with diminished AMPK activity or autophagy may be highly sensitive to STF, as AMPK activation enhances immune surveillance [ 40 ], whereas tumors with highly active AMPK or autophagy may be resistant [ 77 , 79 , 80 , 81 , 82 ].
During STF, healthy cells, have the metabolic flexibility to cope with nutrient deprivation, since glucose can be replaced by ketone bodies and fatty acids as primary energy source.
In contrast, tumor cells depend on glucose to maintain the high rate of cellular proliferation [ 83 , 84 ]. Also, a counterintuitive increase in protein translation during STF increases unmet energy needs, leading to cell death [ 12 ].
Thus, a decrease in nutrient availability during STF makes cancer cells more vulnerable to any challenge, including chemotherapy. However, overconsumption after a STF period might accelerate tumor growth, due to high glucose conditions and increased glycolysis [ 86 ].
Chemotherapeutic agents inflict oxidative stress and DNA damage upon healthy cells, which are underlying mechanisms of toxicity [ 44 , 87 ]. STF dampens oxidative stress in healthy cells by down-regulating metabolic rate and increasing scavenging of reactive oxygen species ROS , which may contribute to DSR [ 33 , 44 ].
As serum glucose levels decrease during STF, fatty acids serve as the main energy source. Ketone bodies can also activate pathways involved in protection against ROS [ 88 ].
Moreover, STF presumably activates DNA repair processes in healthy cells [ 22 ]. In contrast, tumor cells exhibit increased ROS production if chemotherapy is combined with STF in vitro [ 12 ].
In breast cancer cells cultured in low glucose medium or serum of fasting mice, a fold increase in DNA damage was seen in response to chemotherapy, as compared to cells cultured in regular medium or in serum of ad libitum fed mice [ 12 ].
Chemotherapy causes bone marrow toxicity and depletion of circulating immune cells, especially myeloid cell depletion [ 89 , 90 ]. Fasting protects hematopoietic stem cells and circulating immune cells from the detrimental effects of chemotherapy in mice [ 22 , 91 ].
Additionally, more efficient immunity as a result of STF presumably causes a lower rate of infections and febrile neutropenia as well [ 92 ]. Thus, STF may promote immunity and presentation of tumor-associated antigens TAA , which promote efficient antitumor immunity contributing to increased efficacy of chemotherapy [ 94 ].
Preclinical data documenting the benefits of STF is abundant and promising. However, words of caution are appropriate regarding its application in patients with cancer. This is reassuring in the context of safety. However, it may also mean that humans need to fast for a much longer period of time than mice to obtain the same benefits see discussion below.
Therefore, carefully controlled clinical trials monitoring tumor growth as well as adverse effects of distinct dietary regimes are required before fasting mimicking diets FMDs can be applied in clinical practice.
Obesity is associated with an increased risk of developing several cancers, such as breast cancer, colon cancer, ovarian cancer, endometrial cancer and thyroid cancer [ 96 , 97 ] and IGF-1 levels are positively associated with the risk of developing breast and prostate cancer [ 98 , 99 ].
Moreover, obesity and high levels of insulin and IGF-1, as well as having diabetes mellitus are associated with worse survival in cancer [ , , , ]. Obese subjects are often hyperglycemic and hyperinsulinemic, as a result of insulin resistance. Moreover, preclinically, obesity is associated with macrophage accumulation in adipose tissue resulting in an immune suppressive microenvironment [ ].
These metabolic mechanisms may explain the increased risk of cancer as well as the worse prognosis of several cancers in obese subjects. Voluntary fasting has been performed for many centuries and purposes, such as religious, ethical and cosmetic [ 26 , ].
Hippocrates was probably one of the first advocates of fasting for medical purposes he recommended to fast during sickness. The first clinical study of medical fasting for the treatment of obesity was performed in [ ]. The authors reported that short periods of four to six days of fasting is a safe and effective method for reducing bodyweight in obese humans.
Fasting therapy was observed to be generally safe and well tolerated. Only mild side effects were reported, including headaches, dizziness, nausea, dyspepsia and fatigue [ , , , , , ]. Additionally, fasting is not suitable for patients with rare metabolic illnesses such as glycogen storage disease or disorders of gluconeogenesis [ ].
Benefits of fasting are improved cardiovascular risk factors, such as a decrease in blood pressure, improvement of lipid profile and insulin sensitivity, and weight loss in obese and non-obese subjects [ , ]. The weight loss during STF is approximately 0.
Various studies examined the potential of fasting in the treatment of mood disorders, rheumatic diseases, asthma, chronic pain syndromes, hypertension, and metabolic syndrome [ , ]. Additionally, STF may improve clinical outcome in patients undergoing a partial liver resection and may prevent acute kidney injury after cardiac surgery [ , ].
STF has profound metabolic effects in humans [ ]. Serum glucose levels drop after a few hours and are maintained at a lower level by endogenous glucose production, stimulated by glucagon. From then on, gluconeogenesis provides the brain with glucose as its major fuel source.
Fatty acids are the primary fuel for the rest of the body. Beta-oxidation of fatty acids produces ketone bodies, which can serve as auxiliary energy source for the brain and the rest of the body. Since the liver is resistant to GH during prolonged fasting, IGF-1 production is profoundly reduced [ ].
Diminished negative feedback control through reduction of circulating insulin and IGF-1 causes plasma GH levels to increase [ , ]. IGF binding proteins, which regulate the bio-availability of IGF-1, change during fasting as well [ 41 , , ].
IGF-BP3 levels decrease, while IGF-BP1 levels increase 5—fold [ ]. Moreover, fasting down-regulates the hypothalamus-pituitary-thyroid axis activity. It particularly lowers triiodothyronine T3 , while thyroid stimulating hormone TSH and free thyroxine fT4 are slightly decreased or not affected [ ].
Therefore, it is likely that the positive effects of STF will be enhanced if the period of fasting is prolonged. A low sugar, low protein FMD may be an alternative to ease the burden of fasting, as it mimics the effects of STF on metabolism [ 91 ].
To date, a few small clinical studies in humans exploring the effects of STF combined with chemotherapy have been published Table 2 [ 22 , , , , , ]. The design and results of these studies in humans are summarized below. Six of the ten patients fasted alternately during the chemotherapy cycles the other four fasted every cycle and side effects were compared between cycles combined with STF and chemotherapy alone.
Side effects were scored according to the Common Terminology Criteria for Adverse Events CTCAE 4. Besides hunger and dizziness, fasting had no significant side effects. The authors reported a decrease in chemotherapy-induced side effects, including fatigue, weakness, vomiting and diarrhea, when chemotherapy was combined with STF compared to chemotherapy alone.
In five patients the tumor volume evaluated with PET or PET-CT or tumor markers PSA or CA were evaluated. STF did not diminish chemotherapy-induced reduction of tumor volume and tumor markers, suggesting that STF did not interfere with the efficacy of chemotherapy.
In the King Fahad Medical City a clinical trial NCT was conducted to evaluate the safety and feasibility of combining chemotherapy and intermittent fasting including liquids during the Ramadan [ ].
Eleven patients, with distinct types of malignancies, received one gift of chemotherapy. The authors concluded that combining fasting and chemotherapy during the month of Ramadan was well tolerated and safe.
Side effects of chemotherapy tended to be less. However, because the study group was small, no statistics were performed. We performed a randomized pilot study NCT to evaluate the effects of short-term fasting on tolerance to neo adjuvant chemotherapy in HER2-negative breast cancer patients in the Leiden University Medical Center LUMC [ ].
Toxicity in the two groups was compared as well. Additionally, chemotherapy-induced DNA damage was quantified in peripheral blood mononuclear cells PBMCs by the level of γ-H2AX, as determined by flowcytometry.
Thirteen patients were included, of whom seven were randomized to the STF arm. STF was well tolerated in our study. Plasma glucose levels increased and insulin levels remained constant in response to STF.
We inferred that this phenomenon was the result of the concomitant use of dexamethasone, which was administered as an anti-emetic, for reduction of fluid retention and dampening of hypersensitivity reactions in response to docetaxel.
Non-hematological toxicity did not differ between the groups. Moreover, Dorff et al. Eligible patients had distinct cancer types for which platinum-based combination chemotherapy was given with curative or palliative intent.
Metabolic parameters glucose, insulin, IGF-1 and IGF-BP1 at baseline and immediately before chemotherapy were compared. Moreover, toxicities and chemotherapy-induced DNA damage in PBMCs determined by the COMET assay between the three groups were compared. The fasting was feasible and fasting-related toxicities were limited to grade 1 according CTCAE 4.
Finally, Bauerfeld et al. published a randomized cross-over trial NCT evaluating the effect of STF on quality of life in breast cancer and ovarian cancer patients treated with chemotherapy [ ].
After three cycles the patient crossed over to the other group of nutrition Mediterranean diet or fasting. The design of the study allows intra-individual comparisons regarding side effects of treatment, but precludes conclusions as efficacy of chemotherapy. In total, 50 patients were included in the study, but only 34 were analyzed because of early study discontinuation.
The fasting was safe and feasible and five patients Moreover, 31 patients declared that they would fast again during chemotherapy, while only 3 patients declared that they would not fast again during chemotherapy.
These first clinical studies lack enough power to draw definite conclusions. However, the first results suggest that STF is safe, while it reduces toxicity of chemotherapy. Large scale randomized studies are required to get more insight in the benefits of STF in cancer treatment in humans.
The first clinical studies have shown that STF combined with chemotherapy is safe and feasible in small patient groups [ , , ]. Moreover, STF may reduce chemotherapy-induced toxicity.
Additionally, chemotherapy-induced DNA damage in healthy cells may be decreased due to STF. However, large randomized clinical studies are required to generate more insight and validate the possible benefits of STF during chemotherapy.
In Table 3 , an overview is shown of the ongoing trials with STF combined with cancer treatment. One study to date investigates the effects of STF on the effects radiotherapy. This randomized study NCT conducted in Johann Wolfgang Goethe University Hospitals, includes patients with recurrent glioblastoma or gliosarcoma.
The primary endpoint of the study is progression free survival. A phase II study NCT , ongoing in the University of Southern California, examines the effects of an FMD on toxicity of chemotherapy in patients with breast and prostate cancer.
In this study prophylactic dexamethasone is omitted in the FMD arm during the AC and FEC chemotherapy cycles to reduce its potentially counteractive metabolic effects.
Final results of the study are awaited [ 68 ]. The same FMD will be used to investigate the effect on circulating tumor cells in non-small cell lung cancer during treatment with carboplatin, pemetrexed and pembrolizumab.
Another FMD, described by Bauerfeld [ ], is tested in two studies NCT, NCT conducted in the Charité University in Berlin, one in advanced metastatic prostate cancer and another in ovarian or breast cancer. Primary endpoint of both studies is QOL.
Clinical research evaluating the potential of STF is still in its infancy and more research is needed as the exact mechanism and effects are not established yet.
Furthermore, it is potentially effective in a wide variety of tumors, although there is evidence that tumors with PI3K mutations or highly active AMPK are not sensitive [ 65 , 82 ]. Reduction of side effects would improve quality of life and potentially reduce costs of hospitalization and the use of drugs such as anti-emetics or antibiotics.
Moreover, STF may broaden the therapeutic window of cancer treatments, allowing for an increase of the dosage of chemo therapeutic agents, thereby enhancing their efficacy. However, STF might be only feasible in chemotherapeutic regimens characterized by: 1 bolus infusions on one day, to keep the fasting period short, 2 a long interval between two cycles, to ensure sufficient recovery time between cycles and 3 low dose or no use of corticosteroids, to avoid hyperglycemia, which might interfere with the benefits of STF [ ].
Patients at risk for malnutrition or cachexia may not be candidates for STF, as it may be unsafe to further limit nutrient intake in these patients for even a short time [ 27 ]. However, notably, in preclinical setting caloric restriction showed even preservation of muscle strength in cancer cachexia [ ].
Therefore, robust clinical trials are needed to establish the safety and efficacy of FMD in patients at high risk of cachexia. Close monitoring of patients by nutritionists with expertise in fasting may be needed to increase compliance in future studies and to prevent patients unacceptable weight loss.
Moreover, in our opinion, STF or FMDs should only be applied in the context of clinical research in patients with cancer until there is robust evidence for their safety and benefits. Abundant and convincing preclinical evidence shows that STF can decrease toxicity and simultaneously increase efficacy of a wide variety of chemotherapeutic agents.
Preclinical data suggesting that STF can enhance the effects of radiotherapy and TKIs are promising as well. In clinical studies, STF emerges as a promising strategy to enhance the efficacy and tolerability of chemotherapy.
It appears safe as an adjunct to chemotherapy in humans, and it may reduce side effects and DNA damage in healthy cells in response to chemotherapy. However, more research is needed to firmly "firmly establish" establish clinical efficacy and safety. Dirx MJ, Zeegers MP, Dagnelie PC, van den Bogaard T, van den Brandt PA.
Energy restriction and the risk of spontaneous mammary tumors in mice: a meta-analysis. Int J Cancer. Article CAS PubMed Google Scholar.
Effect of limited food intake on survival of mice bearing spontaneous mammary carcinoma and on the incidence of lung metastases. Cancer Res. De Lorenzo MS, Baljinnyam E, Vatner DE, Abarzua P, Vatner SF, Rabson AB. Caloric restriction reduces growth of mammary tumors and metastases.
Article PubMed PubMed Central CAS Google Scholar. Mai V, Colbert LH, Berrigan D, Perkins SN, Pfeiffer R, Lavigne JA, et al. Calorie restriction and diet composition modulate spontaneous intestinal tumorigenesis in Apc min mice through different mechanisms. CAS PubMed Google Scholar.
Lv M, Zhu X, Wang H, Wang F, Guan W. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis. PLoS One. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, et al.
Caloric restriction delays disease onset and mortality in rhesus monkeys. Article CAS PubMed PubMed Central Google Scholar. Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor IGF -I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis.
Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, et al. A 2-year randomized controlled trial of human caloric restriction: feasibility and effects on predictors of health span and longevity.
J Gerontol A Biol Sci Med Sci. Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period.
Article PubMed Google Scholar. Racette SB, Weiss EP, Villareal DT, Arif H, Steger-May K, Schechtman KB, et al. One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue.
Masoro EJ. Overview of caloric restriction and ageing. Mech Ageing Dev. Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Article PubMed PubMed Central Google Scholar.
Safdie F, Brandhorst S, Wei M, Wang W, Lee C, Hwang S, et al. Fasting enhances the response of glioma to chemo- and radiotherapy. Bianchi G, Martella R, Ravera S, Marini C, Capitanio S, Orengo A, et al. Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models.
Shim HS, Wei M, Brandhorst S, Longo VD. Starvation promotes REV1 SUMOylation and pdependent sensitization of melanoma and breast cancer cells. Di Biase S, Longo VD.
Fasting-induced differential stress sensitization in cancer treatment. Mol Cell Oncol. Article PubMed CAS Google Scholar. Di Biase S, Shim HS, Kim KH, Vinciguerra M, Rappa F, Wei M, et al. Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.
PLoS Biol. Brandhorst S, Wei M, Hwang S, Morgan TE, Longo VD. Short-term calorie and protein restriction provide partial protection from chemotoxicity but do not delay glioma progression.
Exp Gerontol. Raffaghello L, Lee C, Safdie FM, Wei M, Madia F, Bianchi G, et al. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci U S A. Huisman SA, Bijman-Lagcher W, IJzermans JN, Smits R, de Bruin RW.
Fasting protects against the side effects of irinotecan but preserves its anti-tumor effect in Apc15lox mutant mice. Cell Cycle. Tinkum KL, Stemler KM, White LS, Loza AJ, Jeter-Jones S, Michalski BM, et al. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival.
CAS PubMed PubMed Central Google Scholar. Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, et al. Cell Stem Cell. Huisman SA, de BP, Ghobadi Moghaddam-Helmantel IM, IJzermans JN, Wiemer EA, Mathijssen RH, et al.
Fasting protects against the side-effects of irinotecan treatment but does not abrogate anti-tumor activity in mice. J Pharmacol. Franny Jongbloed SAH, Harry van Steeg, Jeroen L. Pennings, Jan N. IJzermans, Martijn E. Dollé and Ron W. de Bruin. The transcriptomic response to irinotecan in colon carcinoma bearing mice preconditioned by fasting.
Schumacher B, Garinis GA, Hoeijmakers JH. Age to survive: DNA damage and aging. Trends Genet. Kerndt PR, Naughton JL, Driscoll CE, Loxterkamp DA. Fasting: the history, pathophysiology and complications. West J Med. Caccialanza R, De Lorenzo F, Gianotti L, Zagonel V, Gavazzi C, Farina G, et al.
Nutritional support for cancer patients: still a neglected right? Support Care Cancer. Caccialanza R, Aprile G, Cereda E, Pedrazzoli P.
Fasting in oncology: a word of caution. Nat Rev Cancer. Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, et al. ESPEN guidelines on nutrition in cancer patients. Clin Nutr. Arends J, Baracos V, Bertz H, Bozzetti F, Calder PC, Deutz NEP, et al.
ESPEN expert group recommendations for action against cancer-related malnutrition. Bishop NA, Guarente L. Genetic links between diet and lifespan: shared mechanisms from yeast to humans.
Nat Rev Genet. Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Ward PS, Thompson CB.
Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell. D'Aronzo M, Vinciguerra M, Mazza T, Panebianco C, Saracino C, Pereira SP, et al. Fasting cycles potentiate the efficacy of gemcitabine treatment in in vitro and in vivo pancreatic cancer models.
Shi Y, Felley-Bosco E, Marti TM, Orlowski K, Pruschy M, Stahel RA. BMC Cancer. Saleh AD, Simone BA, Palazzo J, Savage JE, Sano Y, Dan T, et al.
Caloric restriction augments radiation efficacy in breast cancer. Caffa I, Longo VD, Nencioni A. Fasting plus tyrosine kinase inhibitors in cancer. Aging Albany.
Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, et al. Caloric restriction mimetics enhance anticancer Immunosurveillance.
Thissen JP, Ketelslegers JM, Underwood LE. Nutritional regulation of the insulin-like growth factors. Endocr Rev. Lee C, Safdie FM, Raffaghello L, Wei M, Madia F, Parrella E, et al.
Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Hursting SD, Lavigne JA, Berrigan D, Donehower LA, Davis BJ, Phang JM, et al. Diet-gene interactions in pdeficient mice: insulin-like growth factor-1 as a mechanistic target.
J Nutr. Lee C, Longo VD. Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Kirkwood TB, Shanley DP. Food restriction, evolution and ageing. Kirkwood TL, Kapahi P, Shanley DP. Evolution, stress, and longevity.
J Anat. Heilbronn LK, Ravussin E. Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr. Murray MJ, Murray AB. Anorexia of infection as a mechanism of host defense. Exton MS. Infection-induced anorexia: active host defence strategy. Giovannucci E, Pollak M, Liu Y, Platz EA, Majeed N, Rimm EB, et al.
Nutritional predictors of insulin-like growth factor I and their relationships to cancer in men. Cancer Epidemiol Biomark Prev. CAS Google Scholar. Prisco M, Romano G, Peruzzi F, Valentinis B, Baserga R. Insulin and IGF-I receptors signaling in protection from apoptosis. Horm Metab Res. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO.
Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. Belfiore A, Malaguarnera R, Vella V, Lawrence MC, Sciacca L, Frasca F, et al. Insulin receptor isoforms in physiology and disease: an updated view.
Ketelslegers JM, Maiter D, Maes M, Underwood LE, Thissen JP. Nutritional regulation of insulin-like growth factor-I. Henning PC, Scofield DE, Rarick KR, Pierce JR, Staab JS, Lieberman HR, et al. Effects of acute caloric restriction compared to caloric balance on the temporal response of the IGF-I system.
Snel M, Wijngaarden MA, Bizino MB, van der Grond J, Teeuwisse WM, van Buchem MA, et al. Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.
Beauloye V, Willems B. de C, V, frank SJ, Edery M, Thissen JP. Impairment of liver GH receptor signaling by fasting. Leung KC, Doyle N, Ballesteros M, Waters MJ, Ho KK. Insulin regulation of human hepatic growth hormone receptors: divergent effects on biosynthesis and surface translocation.
J Clin Endocrinol Metab. Yakar S, Liu JL, Stannard B, Butler A, Accili D, Sauer B, et al. Normal growth and development in the absence of hepatic insulin-like growth factor I.
Anzo M, Cobb LJ, Hwang DL, Mehta H, Said JW, Yakar S, et al. Targeted deletion of hepatic Igf1 in TRAMP mice leads to dramatic alterations in the circulating insulin-like growth factor axis but does not reduce tumor progression.
Wu Y, Yakar S, Zhao L, Hennighausen L, LeRoith D. Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis.
Kawaguchi T, Takemura G, Kanamori H, Takeyama T, Watanabe T, Morishita K, et al. Prior starvation mitigates acute doxorubicin cardiotoxicity through restoration of autophagy in affected cardiomyocytes.
Cardiovasc Res. Withers SS, Kass PH, Rodriguez CO, Jr. Djiogue S, Nwabo Kamdje AH, Vecchio L, Kipanyula MJ, Farahna M, Aldebasi Y, et al. Insulin resistance and cancer: the role of insulin and IGFs.
Endocr Relat Cancer. Kalaany NY, Sabatini DM. Tumours with PI3K activation are resistant to dietary restriction. Zhang Y, Moerkens M, Ramaiahgari S, de BH, Price L, Meerman J, et al. Breast Cancer Res. de Groot S, Charehbili A, van Laarhoven HW, Mooyaart AL, Dekker-Ensink NG, van de Ven S, et al.
S de Groot RL, MJ Welters, I Ehsan, MP Vreeswijk, VT Smit, H de Graaf, JB Heijns, JE Portielje, AJ van de Wouw, AL Imholz, LW Kessels, S Vrijaldenhoven, A Baars, E Meershoek-Klein Kranenbarg, M Duijm-de Carpentier, E van Leeuwen-Stok, H Putter, VD Longo, JJ van der Hoeven, JW Nortier, H Pijl and JR Kroep.
Abstract P1— DIetary REstriction as an adjunct to neoadjuvant ChemoTherapy for HER2-negative breast cancer: Final results from the DIRECT trial BOOG — American Association for Cancer Research. Jiang W, Zhu Z, Thompson HJ. Dietary energy restriction modulates the activity of AMP-activated protein kinase, Akt, and mammalian target of rapamycin in mammary carcinomas, mammary gland, and liver.
Hardie DG. AMP-activated protein kinase: a cellular energy sensor with a key role in metabolic disorders and in cancer. Biochem Soc Trans. Mihaylova MM, Shaw RJ. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism.
Nat Cell Biol. Mizushima N. Autophagy: process and function. Genes Dev. Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell. Vidal AP, Andrade BM, Vaisman F, Cazarin J, Pinto LF, Breitenbach MM, et al. AMP-activated protein kinase signaling is upregulated in papillary thyroid cancer.
Eur J Endocrinol. Zadra G, Batista JL, Loda M. Dissecting the dual role of AMPK in Cancer: from experimental to human studies. Mol Cancer Res. Hadad SM, Baker L, Quinlan PR, Robertson KE, Bray SE, Thomson G, et al. Histological evaluation of AMPK signalling in primary breast cancer.
Leprivier G, Remke M, Rotblat B, Dubuc A, Mateo AR, Kool M, et al. The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation.
Zheng L, Yang W, Wu F, Wang C, Yu L, Tang L, et al. Prognostic significance of AMPK activation and therapeutic effects of metformin in hepatocellular carcinoma.
Clin Cancer Res. Wang L, Shang Z, Zhou Y, Hu X, Chen Y, Fan Y, et al. Autophagy mediates glucose starvation-induced glioblastoma cell quiescence and chemoresistance through coordinating cell metabolism, cell cycle, and survival. Cell Death Dis. Sato K, Tsuchihara K, Fujii S, Sugiyama M, Goya T, Atomi Y, et al.
Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation. Petibone DM, Majeed W, Casciano DA.
Autophagy function and its relationship to pathology, clinical applications, drug metabolism and toxicity. J Appl Toxicol. van Niekerk G, Hattingh SM, Engelbrecht AM. Enhanced therapeutic efficacy in Cancer patients by short-term fasting: the autophagy connection.
Front Oncol. PubMed PubMed Central Google Scholar. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.
Cell Metab. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Lankelma J, Kooi B, Krab K, Dorsman JC, Joenje H, Westerhoff HV.
Fasting, or Anti-obesity lifestyle eating food Citrus bioflavonoids and oral health prevenrion extended period Fastinf time, is Fating as a religious diet practice. Strengthen your energy reserves abd are also beginning Safe snacks for athletes use Fasting and cancer prevention for specific health benefits. Over the pfevention several anf, many studies have been published showing that intermittent fasting or a fasting-mimicking diet can reduce risk factors for and reverse symptoms of serious health conditions including cancer. Intermittent fasting is fasting on a schedulealternated with times of eating. For example, you may eat normally for most of the week, but on Tuesdays and Thursdays only eat for an 8-hour period and fast for the remaining 16 hours. Some also call this a fasting-mimicking diet. Potential Role andd Mechanisms in Treatment, Strengthen your energy reserves, and Vancer. Intermittent fasting, especially Non-toxic allergen control feeding" or "prolonged nighttime fasting" Fasting and cancer prevention become preventioj popular, and questions about its potential role canced both cancer prevention and treatment Citrus bioflavonoids and oral health been raised. Early evidence suggests that this strategy has the potential to improve the effectiveness of treatments and reduce side effects, but thus far, only a limited number of studies have been done. With regard to breast cancer, there is evidence that prolonged nighttime fasting may lower the risk of recurrence, a risk we are learning can remain for decades after treatment. We will take a look at some of the studies that have been done, the potential mechanisms by which it may affect cancer cells, and the potential risks and side effects.
Und was jenes zu sagen hier?
Es ja!
Wacker, die bemerkenswerte Phrase und ist termingemäß