{"version":"2026.10.24.3","scope":"Selected evidence review, not completed systematic review or clinical guidance","topics":{"weight":"Weight & fat loss","glucose":"Glucose & diabetes","cardiovascular":"Heart & blood pressure","cancer":"Cancer","autophagy":"Autophagy","muscle":"Muscle & physical function","cognition":"Brain & cognition","immune":"Immunity & inflammation","longevity":"Longevity","liver":"Liver health","safety":"Safety & adverse effects","adherence":"Adherence & durability","religious":"Religious fasting"},"studies":[{"id":"catenacci","group":"benefits","kind":"Human randomized trial","author":"Catenacci et al.","year":"2025","title":"The Effect of 4:3 Intermittent Fasting on Weight Loss at 12 Months: A Randomized Clinical Trial","url":"https://pubmed.ncbi.nlm.nih.gov/40163873/","doi":"10.7326/ANNALS-24-01631","takeaway":"A modest additional weight benefit in an intensive support program.","population":"165 adults with overweight or obesity randomized; 125 completed 12 months.","comparison":"2 arms: 4:3 restriction (84) and daily calorie restriction (81). One active control; both received intensive behavioral support and an exercise goal.","protocol":"80% energy restriction on 3 nonconsecutive days each week versus 34% daily restriction; 12 months. Restricted days still included food.","result":"Primary weight outcome: 2.89 kg greater loss with 4:3 (95% CI 0.14–5.65 kg; P=.040), in the intention-to-treat analysis.","limitation":"Not a water-fast trial. Attrition, intensive support, and differences in achieved calorie restriction limit generalization and a calorie-independent explanation.","access":"Original indexed abstract; protocol and primary outcome. NIH funding reported. Registry NCT03411356.","topics":["weight","adherence"],"timelineTitle":"Does eating less three days a week help with weight loss?","timelineSummary":"People lost a little more weight than with daily calorie cutting, with intensive support.","explainer":{"who":"165 adults with overweight or obesity started; 125 finished the one-year study.","compared":"84 people ate much less on three days each week. The other 81 cut calories every day. Both groups received substantial coaching and exercise advice.","found":"The three-day group lost about 2.9 kg more, on average, after a year.","meaning":"This approach helped in a supported program. The study cannot show whether meal timing itself, eating fewer calories, or sticking to the plan explains the difference."},"populationType":"human","timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"liu","group":"benefits","kind":"Human randomized trial","author":"Liu et al.","year":"2022","title":"Calorie Restriction with or without Time-Restricted Eating in Weight Loss","url":"https://pubmed.ncbi.nlm.nih.gov/35443107/","doi":"10.1056/NEJMoa2114833","takeaway":"An eating window did not clearly improve on calorie restriction.","population":"139 adults with obesity randomized; 118 completed the 12-month visit.","comparison":"2 arms, one active control: calorie restriction with an 08:00–16:00 eating window (69) versus calorie restriction alone (70).","protocol":"Both groups received calorie targets for 12 months; only one also restricted meal timing.","result":"Mean weight change was −8.0 versus −6.3 kg. Adjusted between-group difference: −1.8 kg (95% CI −4.0 to 0.4; P=.11). Body-fat and metabolic outcomes did not establish additional benefit.","limitation":"A confidence interval spanning zero leaves benefit and little difference plausible; it does not prove the approaches identical. No mortality endpoint.","access":"Original abstract and publisher PDF enrollment table. Registry NCT03745612.","topics":["weight","glucose"],"timelineTitle":"Does an eight-hour eating window add to weight loss?","timelineSummary":"Adding a daily eating window did not clearly beat calorie cutting alone over one year.","explainer":{"who":"139 adults with obesity; 118 completed the one-year follow-up.","compared":"Both groups cut calories. One group of 69 also ate only between 8 a.m. and 4 p.m.; the other 70 kept their usual meal timing.","found":"Both groups lost weight. The study did not find a clear extra benefit from the eight-hour eating window.","meaning":"An eating window may be one way to organize a diet, but this study did not show that it works better than calorie cutting alone."},"populationType":"human","timelineYear":2022,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"trepanowski","group":"benefits","kind":"Human randomized trial","author":"Trepanowski et al.","year":"2017","title":"Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial","url":"https://pubmed.ncbi.nlm.nih.gov/28459931/","doi":"10.1001/jamainternmed.2017.0936","takeaway":"Alternate-day restriction was not superior and had more dropouts.","population":"100 adults randomized: 34 alternate-day fasting, 35 daily restriction, 31 no-intervention control.","comparison":"3 arms; two comparators for fasting: an active calorie-restriction program and usual behavior.","protocol":"6 months of weight loss, then 6 months of maintenance. During weight loss, alternate days supplied 25%/125% of energy needs; daily restriction supplied 75%.","result":"At 12 months, weight loss relative to control was about 6.0% versus 5.3% for alternate-day versus daily restriction, without a significant difference. Dropout: 38% versus 29% versus 26%.","limitation":"Adherence differed from assigned intake. “Fasting” meant modified fasting with calories. No evidence here of superior cardiovascular event prevention.","access":"Original publication abstract, design and results.","topics":["weight","cardiovascular","adherence"],"timelineTitle":"Is eating less every other day easier or more effective?","timelineSummary":"Weight loss was similar to daily calorie cutting, and more people dropped out.","explainer":{"who":"100 adults with obesity, followed for one year.","compared":"34 alternated low-food days with higher-food days, 35 cut calories every day, and 31 were asked to keep their usual habits.","found":"The two dieting groups lost similar amounts of weight. About 38% left the alternate-day group, compared with 29% in the daily-diet group.","meaning":"Alternate-day eating was not clearly more effective or easier to maintain. The low-food days still included calories; this was not a water-only fast."},"populationType":"human","timelineYear":2017,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"sutton","group":"benefits","kind":"Human randomized crossover","author":"Sutton et al.","year":"2018","title":"Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even Without Weight Loss in Men with Prediabetes","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5990470/","doi":"10.1016/j.cmet.2018.04.010","takeaway":"A small controlled-feeding experiment supports a timing effect.","population":"8 men with prediabetes completed both conditions; this is a completer count, not a large clinical trial.","comparison":"2 conditions in randomized order. Each participant was his own control: early 6-hour versus 12-hour eating window.","protocol":"5 weeks per condition; meals provided and intake adjusted to maintain weight. Early eating ended before 15:00.","result":"Insulin sensitivity and morning blood pressure improved with early eating; glucose measurements did not show the same benefit.","limitation":"Male-only, very small, short study. Different fasting lengths before testing complicate interpretation. Surrogate changes do not establish prevention of diabetes or heart attacks.","access":"Full text: study design, Results and limitations; meal provision verified.","topics":["glucose","cardiovascular"],"timelineTitle":"Can eating earlier help without losing weight?","timelineSummary":"A study of eight men found better insulin response and blood pressure. Larger trials are needed.","explainer":{"who":"Eight men with blood sugar above the normal range completed both eating schedules.","compared":"Each man tried a six-hour eating window ending before 3 p.m. and a twelve-hour window, for five weeks each. Food was provided to keep weight steady.","found":"Earlier eating improved how their bodies responded to insulin, the hormone that helps control blood sugar. Morning blood pressure also improved.","meaning":"This suggests timing might matter even without weight loss. Eight men are too few to show that the approach prevents diabetes or heart disease."},"populationType":"human","timelineYear":2018,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"yang","group":"benefits","kind":"Human randomized trial","author":"Yang et al.","year":"2023","title":"Effect of an Intermittent Calorie-restricted Diet on Type 2 Diabetes Remission: A Randomized Controlled Trial","url":"https://pubmed.ncbi.nlm.nih.gov/36515429/","doi":"10.1210/clinem/dgac661","takeaway":"Remission was more frequent with a structured dietary program.","population":"72 adults with type 2 diabetes; 36 assigned to each group.","comparison":"2 arms: Chinese Medical Nutrition Therapy (CMNT) versus usual diet/control. One control; no calorie-matched alternative dietary program.","protocol":"3-month intermittent restricted-calorie program with supplied meals, followed by follow-up. This was not water-only fasting.","result":"After intervention plus 3 months of follow-up, remission occurred in 17/36 (47.2%) versus 1/36 (2.8%). Remission required HbA1c below 6.5% for at least 3 months without diabetes medication. At 12-month follow-up, 16/36 intervention participants remained in remission.","limitation":"Small, selected population; diet composition, calorie reduction and medical management cannot be separated. Remission is not permanent cure and does not authorize stopping medication.","access":"Original abstract and publisher results/participant-flow text. Long-term HbA1c values differ between abstract and body; those values are not repeated here.","topics":["glucose","weight"],"timelineTitle":"Can a structured diet put type 2 diabetes into remission?","timelineSummary":"More people met the study’s remission criteria. That does not mean a permanent cure.","explainer":{"who":"72 adults with type 2 diabetes, split into two groups of 36.","compared":"One group received a three-month program of supplied meals and periods of reduced eating. The other continued its usual diet.","found":"After the program and three more months of follow-up, 17 people in the diet group met the study’s diabetes-remission criteria, compared with one in the usual-diet group.","meaning":"Here, remission meant blood sugar stayed below the diabetes threshold without diabetes medicine for at least three months. It is not a permanent cure, and this result does not justify stopping medication on your own."},"populationType":"human","timelineYear":2023,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"wei","group":"benefits","kind":"Human randomized trial","author":"Wei et al.","year":"2017","title":"Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6816332/","doi":"10.1126/scitranslmed.aai8700","takeaway":"Risk markers improved; disease prevention was not tested.","population":"100 generally healthy adults randomized: 52 FMD, 48 control. Initial randomized comparison had 39 FMD and 43 control completers; 71 eventually completed FMD after crossover.","comparison":"2 initial arms; one usual-diet control, later offered FMD. The 71 pooled completers are not a second independent trial.","protocol":"5-day low-calorie, low-protein fasting-mimicking diet each month for 3 months; ordinary eating between cycles.","result":"Randomized results favored FMD for weight, body fat, blood pressure and IGF-1. Larger improvements in higher-risk participants were post hoc analyses.","limitation":"Attrition, short duration and surrogate endpoints. Lower IGF-1 is not demonstrated cancer prevention; no human lifespan outcome.","access":"Full text: Results, participant flow and Tables 1–2. Commercial FMD interests, including L-Nutra relationships, disclosed.","topics":["weight","glucose","cardiovascular","longevity"],"timelineTitle":"Can a five-day fasting-style diet improve health markers?","timelineSummary":"Weight and some risk markers improved. The trial did not test disease prevention or longer life.","explainer":{"who":"100 generally healthy adults started: 52 assigned to the special diet and 48 to usual eating.","compared":"For three months, one group ate a low-calorie, low-protein diet for five days each month. The other initially kept its usual diet; some tried the special diet later.","found":"Weight, body fat, blood pressure and a hormone linked with growth improved in the diet group.","meaning":"These measurements may be useful clues, but the trial did not show fewer cancers, fewer heart attacks or longer life. Not everyone finished, and later diet users were not a separate trial."},"populationType":"human","timelineYear":2017,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"cramer","group":"benefits","kind":"Human randomized trial","author":"Cramer et al.","year":"2022","title":"Effects of Fasting and Lifestyle Modification in Patients with Metabolic Syndrome: A Randomized Controlled Trial","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9410059/","doi":"10.3390/jcm11164751","takeaway":"Some benefits, but the two primary outcomes were not positive.","population":"145 adults with metabolic syndrome randomized; 73 fasting plus lifestyle, 72 lifestyle alone. 15 per arm were lost during follow-up.","comparison":"2 arms; one active control with modified DASH diet, exercise and mindfulness.","protocol":"5-day modified fast before 10 weeks of lifestyle intervention; follow-up to 24 weeks. The fast included approximately 300–350 kcal/day of juice and broth.","result":"Neither 12-week ambulatory systolic pressure nor HOMA insulin resistance, the co-primary outcomes, differed significantly. At 24 weeks, secondary weight difference favored fasting by 2.7 kg (95% CI 0.5–4.8).","limitation":"Short-term improvements were not uniformly sustained. Multi-component intervention and secondary outcomes limit fasting-specific claims. Uric acid rose initially.","access":"Full text: Methods, Results, Tables 2–3. Parent trial of the Maifeld microbiome substudy; not independent replication.","topics":["weight","glucose","cardiovascular"],"timelineTitle":"Does a short fast add to a healthy-lifestyle program?","timelineSummary":"Some weight benefits appeared, but the two main blood pressure and insulin tests found no clear advantage.","explainer":{"who":"145 adults with a combination of risk factors such as high blood pressure, raised blood sugar or excess weight.","compared":"73 began with five days of very little food, including juice and broth, before a lifestyle program. The other 72 received the lifestyle program without that fast.","found":"The main blood-pressure and insulin-response tests showed no clear extra benefit after twelve weeks. A later weight measurement favored the fasting group.","meaning":"The results were mixed. A positive weight finding should not hide the lack of a clear difference in the two main tests."},"populationType":"human","timelineYear":2022,"cohort":"Maifeld reports a 71-person substudy of the 145-person Cramer program (NCT02099968)."},{"id":"maifeld","group":"benefits","kind":"Human randomized substudy","author":"Maifeld et al.","year":"2021","title":"Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients","url":"https://www.nature.com/articles/s41467-021-22097-0","doi":"10.1038/s41467-021-22097-0","takeaway":"A promising subgroup result needs its parent-trial context.","population":"71 participants: 35 fasting plus DASH, 36 DASH alone; a subset of the 145-person trial reported by Cramer.","comparison":"2 arms, one active DASH/lifestyle comparator; repeated microbiome and immune measurements.","protocol":"5 days of 300–350 kcal/day juice/broth, then 3 months of modified DASH and lifestyle support.","result":"The substudy reported sustained blood-pressure and weight improvements and changes in microbiome composition. Antihypertensive medication reductions were reported in 43% versus 17%.","limitation":"Exploratory subgroup and many molecular comparisons. Microbiome associations do not establish mediation. The larger trial did not meet its blood-pressure or HOMA co-primary endpoints.","access":"Full text: Table 1, Figure 2 and Methods; registry NCT02099968. Read with Cramer, not as a second confirming trial.","topics":["cardiovascular","immune"],"timelineTitle":"Could gut bacteria help explain blood pressure changes?","timelineSummary":"This smaller part of a larger trial found promising changes, but it was not independent confirmation.","explainer":{"who":"71 people from the larger Cramer trial: 35 in the fasting group and 36 in the comparison group.","compared":"Researchers compared five days of very low food intake followed by a healthy-lifestyle program with the lifestyle program alone. They also studied gut bacteria.","found":"This smaller group showed improvements in blood pressure and weight, alongside changes in gut bacteria.","meaning":"That does not prove the bacteria caused the improvement. These were some of the same participants as the larger trial, whose main blood-pressure result was not clearly positive."},"populationType":"human","timelineYear":2021,"cohort":"Maifeld reports a 71-person substudy of the 145-person Cramer program (NCT02099968)."},{"id":"arthritis","group":"benefits","kind":"Human randomized trial","author":"Kjeldsen-Kragh et al.","year":"1991","title":"Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis","url":"https://doi.org/10.1016/0140-6736(91)91770-U","doi":"10.1016/0140-6736(91)91770-U","takeaway":"A combined fasting/diet program improved symptoms in a small trial.","population":"53 patients: 27 assigned to the dietary program, 26 to control; examiner blinded to assignment.","comparison":"2 arms, one ordinary-diet control. Both began with 4-week residential stays, in different facilities.","protocol":"7–10-day subtotal fast, then 3.5 months of individually adjusted gluten-free vegan diet, followed by lactovegetarian eating for the remainder of the year.","result":"Joint symptoms, function and several inflammatory markers improved in the intervention group, with differences reported at one year.","limitation":"Small, older trial with many outcomes and a sustained dietary change. Cannot isolate fasting from the subsequent diet or setting; not evidence for replacing arthritis treatment.","access":"Original publication abstract. Full participant-flow tables and effect-size confidence intervals were not extracted.","topics":["immune"],"timelineTitle":"Can fasting followed by a vegetarian diet ease arthritis?","timelineSummary":"Symptoms improved in a small trial. The effects of fasting and the later diet could not be separated.","explainer":{"who":"53 people with rheumatoid arthritis, a condition in which the immune system attacks joints.","compared":"27 began with seven to ten days of very little food, then followed vegetarian diets for the rest of a year. The other 26 continued an ordinary diet.","found":"Joint symptoms, movement and several blood measurements improved in the diet-program group.","meaning":"The fast and the year of dietary changes were tested together. The study cannot tell us how much benefit came from fasting itself."},"populationType":"human","timelineYear":1991,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"pietzner","group":"prolonged","kind":"Human uncontrolled study","author":"Pietzner et al.","year":"2024","title":"Systemic proteome adaptions to 7-day complete caloric restriction in humans","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7617311/","doi":"10.1038/s42255-024-01008-9","takeaway":"A map of biological adaptation, not a timetable of benefits.","population":"12 volunteers: 5 women and 7 men.","comparison":"One fasting cohort; zero separate control groups. Measurements before, daily during, and after fasting.","protocol":"7-day water-only fast with approximately 3,000 blood proteins measured.","result":"Average weight loss was 5.7 kg. Broad protein changes became apparent after about 3 days. Genetic/protein analyses suggested potentially beneficial and adverse disease associations.","limitation":"No randomized comparator or observed disease reduction. Weight includes water and lean components. Protein changes at day 3 neither locate autophagy onset nor demonstrate that longer fasting improves health.","access":"Full text: study design, Results and Methods. Inferred health associations were distinguished from measured participant outcomes.","topics":["weight","safety"],"timelineTitle":"What changes during a week without food?","timelineSummary":"Blood proteins changed during a seven-day water fast. Those changes do not prove health benefits.","explainer":{"who":"Twelve volunteers: five women and seven men.","compared":"Everyone completed a seven-day water-only fast. Researchers compared daily blood samples with each person’s earlier samples; there was no separate group eating normally.","found":"Participants lost about 5.7 kg on average, and many blood proteins changed after roughly three days.","meaning":"Weight loss included more than body fat. Changes in proteins do not establish a health benefit, a safe fasting length, or the hour when cell recycling begins."},"populationType":"human","timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"scharf","group":"prolonged","kind":"Human uncontrolled study","author":"Scharf et al.","year":"2022","title":"The Effects of Prolonged Water-Only Fasting and Refeeding on Markers of Cardiometabolic Risk","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8951503/","doi":"10.3390/nu14061183","takeaway":"Favorable and unfavorable markers changed together.","population":"48 adults with overweight or obesity enrolled; 26 completed.","comparison":"One residential cohort; zero independent control groups. Baseline, end-of-fast and post-refeeding comparisons.","protocol":"Median 17-day water-only fast and 8-day refeeding with whole plant foods, under supervision.","result":"Weight, systolic blood pressure and LDL were lower after refeeding. Triglycerides and HOMA-IR were higher; median HOMA-IR was 1.4 initially, 1.1 at fast end, and 3.1 after refeeding.","limitation":"Large attrition, short follow-up and a changed refeeding diet prevent causal attribution. HOMA-IR is a surrogate and fasting/refeeding alter its interpretation.","access":"Full text: Results and Table 1 take precedence over ambiguous timing in the abstract. Specialist fasting-center setting limits generalizability.","topics":["weight","glucose","safety"],"timelineTitle":"What happens after a long water fast and refeeding?","timelineSummary":"Some health markers improved and others worsened after people started eating again.","explainer":{"who":"48 adults with overweight or obesity enrolled; 26 completed the study.","compared":"Researchers measured the same people before a supervised water fast, at its end, and after eating resumed. The typical fast lasted about seventeen days. There was no nonfasting group.","found":"Weight, blood pressure and one cholesterol measure fell. Other blood-fat and blood-sugar-control measures worsened after eating resumed.","meaning":"The changes were mixed, and many enrollees did not finish. Without a comparison group, the study cannot establish an overall health benefit from fasting."},"populationType":"human","timelineYear":2022,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"commissati","group":"prolonged","kind":"Human uncontrolled study","author":"Commissati et al.","year":"2025","title":"Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12088818/","takeaway":"Prolonged fasting was not uniformly anti-inflammatory.","population":"20 adults (11 women, 9 men); proteomic analyses used 15. Six participants switched to broth and/or juice after symptoms.","comparison":"One prospective cohort, zero randomized controls. Comparisons with other datasets were external, not assigned control arms.","protocol":"Mean 9.8-day supervised fast and 5.3-day refeeding; intended water-only protocol had documented deviations.","result":"Inflammatory markers and platelet-related pathways rose; hsCRP increased 129%, generally returning toward baseline with refeeding. Weight also fell.","limitation":"Small, selected cohort; biomarkers do not prove heart attacks or other clinical harms. Protocol deviations and external datasets preclude clean regimen comparisons.","access":"Full text: participant/protocol Results, Table 1 and Figure 1. Clinic setting and mixed intake retained explicitly.","topics":["immune","safety"],"timelineTitle":"Does a long fast always reduce inflammation?","timelineSummary":"Inflammation markers rose during this small supervised study, even as people lost weight.","explainer":{"who":"Twenty adults in a supervised fasting program; fifteen contributed to the detailed blood-protein analysis.","compared":"Researchers compared measurements before, during and after about ten days of fasting. Six people switched to small amounts of juice or broth. There was no nonfasting group.","found":"Weight fell, but blood signs of inflammation and blood-clotting activity increased. They generally moved back toward earlier levels when eating resumed.","meaning":"Long fasting did not reduce every sign of inflammation in this group. Blood changes alone do not show whether people will develop or avoid disease."},"populationType":"human","timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"finnell","group":"prolonged","kind":"Human retrospective safety study","author":"Finnell et al.","year":"2018","title":"Is fasting safe? A chart review of adverse events during medically supervised, water-only fasting","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5819235/","doi":"10.1186/s12906-018-2136-6","takeaway":"Medical supervision did not eliminate significant adverse events.","population":"652 people contributed 768 eligible visits; 409 were women. Repeat visits are not independent participants.","comparison":"One clinic chart series; zero nonfasting control groups.","protocol":"Residential water-only fasting: median 7 days, range 2–41, followed by supervised refeeding.","result":"Two serious events required hospitalization: dehydration and hyponatremia. The highest adverse-event grade was 3 in 212 visits and 4 in one visit.","limitation":"Retrospective records, selection and repeat visits limit incidence estimates. These observations cannot establish safety at home or causation versus a control.","access":"Full text: Methods, adverse-event Results and Table 2. Counts used because the reported serious-event percentage is inconsistent with its denominator. Authors include clinic-affiliated researchers.","topics":["safety"],"timelineTitle":"What can go wrong during a supervised water fast?","timelineSummary":"Medical records included serious problems requiring hospital care. Supervision did not remove all risk.","explainer":{"who":"Medical records from 652 people covering 768 visits to a supervised water-fasting center.","compared":"Researchers reviewed symptoms and medical problems during fasting visits. They did not compare patients with a separate group eating normally.","found":"Two serious problems required hospital care: dehydration and dangerously low blood sodium. Other significant symptoms were also recorded.","meaning":"Medical supervision did not eliminate risk. These records cannot establish that a particular fasting length is safe at home, or how its risks compare with other diets."},"populationType":"human","timelineYear":2018,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"glycogen","group":"cancer-mechanisms","kind":"Human tissue + mouse experiments","author":"Clarke et al.","year":"2025","title":"Glycogen drives tumour initiation and progression in lung adenocarcinoma","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12116239/","doi":"10.1038/s42255-025-01243-8","takeaway":"A specific tumor dependency does not establish a fasting treatment.","population":"Human tissue comparison: 77 adenocarcinomas versus 68 squamous tumors; expanded adenocarcinoma cohort: 276. These cohorts must not simply be added.","comparison":"Mouse diet experiment: 2 arms, 6 animals each, sugar/fat gavage versus water vehicle. Genetic experiment: 4 cohorts: KP 6, glycogen-synthesis-deficient KPG 6, KPG vehicle 4, KPG diet 5.","protocol":"Human observational tissue analysis; mice received 2 weeks of dietary exposure before tumor induction, with tumor assessment around day 100.","result":"More tumor glycogen correlated with worse human prognosis. Raising glycogen accelerated mouse tumors; deleting Gys1 markedly suppressed tumor development.","limitation":"Gene deletion at tumor initiation is not dietary fasting of established cancer. No human fasting, ketone-treatment or cure comparison.","access":"Full text: Figures 1–3, Extended Data 4 and Methods; counts are experiment-specific.","topics":["cancer"],"timelineTitle":"Can stored sugar help lung tumors grow?","timelineSummary":"Blocking sugar storage suppressed tumor development in mice. Fasting as a human treatment was not tested.","explainer":{"who":"Human lung-tumor samples, plus separate mouse experiments. One tissue comparison used 77 tumors of one lung-cancer type and 68 of another; a larger set included 276 of the first type.","compared":"Researchers examined stored sugar in human tumors. In mice, they changed diets or disabled a gene that lets cells store sugar. They did not test fasting as a treatment in people.","found":"More stored sugar was linked with worse outcomes in the human samples. Blocking sugar storage strongly reduced tumor development in mice.","meaning":"Disabling a tumor’s sugar-storage gene is different from skipping meals. This study does not show that fasting empties tumors of sugar or cures lung cancer."},"populationType":"mixed","timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"owen","group":"cancer-mechanisms","kind":"Human physiological study","author":"Owen et al.","year":"1969","title":"Liver and kidney metabolism during prolonged starvation","url":"https://pubmed.ncbi.nlm.nih.gov/5773093/","doi":"10.1172/JCI106016","takeaway":"Ketosis does not mean that circulating glucose disappears.","population":"11 people with obesity underwent serial metabolic measurements; invasive organ measurements involved a subset.","comparison":"One fasting cohort; zero randomized nonfasting controls. Within-person and organ-balance measurements.","protocol":"Prolonged starvation, with liver/kidney measurements after several weeks.","result":"Blood glucose fell and stabilized while ketones increased. Organ measurements supported continued glucose production by liver and kidneys during prolonged fasting.","limitation":"Historical, small physiology study, not a safe-duration study or cancer-treatment trial. It undermines the premise that avoiding dietary carbohydrate removes all glucose from a tumor.","access":"Original indexed abstract; detailed individual organ-measurement denominators not extracted.","topics":["glucose"],"timelineTitle":"Does your body still make sugar during a long fast?","timelineSummary":"The liver and kidneys continued producing blood sugar as ketone levels rose.","explainer":{"who":"Eleven people with obesity; a smaller number had detailed liver and kidney measurements.","compared":"Researchers followed changes during prolonged fasting, including measurements after several weeks. Everyone fasted; there was no separate group eating normally.","found":"The liver and kidneys kept making blood sugar while ketones increased. Ketones are an alternative fuel made from fat.","meaning":"Not eating carbohydrate does not remove all sugar from the bloodstream. This small study did not test cancer treatment or establish a safe fasting duration."},"populationType":"human","timelineYear":1969,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"faubert","group":"cancer-mechanisms","kind":"Human tracer + laboratory study","author":"Faubert et al.","year":"2017","title":"Lactate Metabolism in Human Lung Tumors","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5684706/","doi":"10.1016/j.cell.2017.09.019","takeaway":"Human tumors can use fuels beyond directly supplied glucose.","population":"35 patients with non-small-cell lung cancer; 5 received labeled lactate. Eleven tissue fragments in that analysis came from those 5 people.","comparison":"Tracer study, not a randomized diet trial; matched tumor/adjacent lung and glucose/lactate tracing provided comparisons. Zero fasting-control arms.","protocol":"Stable-isotope infusions around tumor resection, with accompanying cell and mouse experiments.","result":"Lactate carbon entered tumor energy metabolism. Tumors differed in how they used circulating nutrients.","limitation":"Tracer incorporation is a metabolic observation, not evidence that a particular diet changes survival. Tissue fragments are not independent patients.","access":"Full text: Human Subjects and Figure 2. The human tracer experiment is the comparison summarized here; animal cohorts are not pooled into it.","topics":["cancer"],"timelineTitle":"Can lung tumors use fuels other than sugar?","timelineSummary":"Human lung tumors used lactate for energy, showing that their fuel choices can vary.","explainer":{"who":"35 people with lung cancer, with related work in cells and mice. Five patients received the special tracing test for lactate.","compared":"Researchers tracked where fuel molecules went in tumors and nearby lung tissue. This was a fuel-tracing experiment, not a comparison of fasting diets.","found":"Human lung tumors used lactate, a substance the body makes during normal energy use, as fuel. Tumors differed in which fuels they used.","meaning":"Cancer cells do not all depend on one fuel. The study did not show that changing a person’s diet would stop cancer growth or improve survival."},"populationType":"mixed","timelineYear":2017,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"defeyter","group":"cancer-mechanisms","kind":"Rat experiment","author":"De Feyter et al.","year":"2016","title":"A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4933488/","doi":"10.1093/neuonc/now088","takeaway":"Some brain-tumor models oxidized ketones instead of starving.","population":"Rats bearing 2 glioma models. Survival cohorts: 9L, 11 standard-diet and 10 ketogenic; RG2, 9 standard and 10 ketogenic. Tracer panels used 7 per group.","comparison":"2 diet arms within each tumor model; one standard-diet control per model. No human participants.","protocol":"Calorie-restricted ketogenic feeding began a week after implantation; serial imaging and labeled β-hydroxybutyrate traced metabolism.","result":"Tumors transported and oxidized ketones, with increased utilization on ketogenic diet. Neither model showed a significant survival benefit (P=.42 and .48).","limitation":"Two rat models cannot predict every human cancer. They do directly contradict the universal claim that cancer cells cannot use ketones.","access":"Full text: diet methods and Figures 2 and 6; survival and tracer denominators kept separate.","topics":["cancer"],"timelineTitle":"Can brain tumors use ketones as fuel?","timelineSummary":"Brain tumors in rats used ketones. A ketogenic diet did not clearly improve survival.","explainer":{"who":"Rats with two kinds of brain tumor. The survival comparisons included 21 rats with one tumor type and 19 with the other.","compared":"For each tumor type, researchers compared a normal diet with a calorie-reduced ketogenic diet: a diet low in carbohydrate that raises fat-derived fuels called ketones.","found":"The tumors used ketones for energy. Rats on the ketogenic diet did not clearly live longer.","meaning":"This is a direct counterexample to the claim that cancer cells cannot use ketones. It does not predict how every human cancer will respond."},"populationType":"animal","timelineYear":2016,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"bhb","group":"cancer-mechanisms","kind":"Mouse + organoid + human tissue study","author":"Dmitrieva-Posocco et al.","year":"2022","title":"β-Hydroxybutyrate suppresses colorectal cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9448510/","doi":"10.1038/s41586-022-04649-6","takeaway":"A promising ketone-signaling mechanism, not proof of starvation.","population":"Multiple mouse and organoid experiments; human blood cohort 41, with single-cell tissue analyses from 9 patients.","comparison":"Diet screens, BHB versus vehicle, and receptor/gene-deficient controls; no randomized human treatment arms. Mouse sample sizes vary by panel and are tabulated in Supplementary Table 3.","protocol":"Ketogenic diets or administered BHB in colorectal-tumor models; organoids and observational human tissue analyses.","result":"BHB inhibited proliferation through HCAR2/HOPX signaling and reduced mouse tumor burden. Human samples showed related associations.","limitation":"Signaling-mediated growth suppression is different from inability to obtain energy. This was not a human cancer-cure trial. No study-wide animal total is supplied here.","access":"Full text and Extended Data 11; per-panel mouse denominators are in the linked supplement and were not completely extracted.","topics":["cancer"],"timelineTitle":"Could a ketone slow bowel cancer growth?","timelineSummary":"One ketone reduced tumors in mice through cell signaling. This was not proof that ketones starve cancer.","explainer":{"who":"Several experiments in mice and lab-grown tissue, plus blood samples from 41 people and detailed tissue samples from nine patients.","compared":"Researchers tested ketogenic diets or a ketone called BHB in bowel-cancer models. Human samples were studied for clues, not used in a randomized treatment trial.","found":"BHB slowed cell multiplication and reduced tumors in mice by changing signals inside cells.","meaning":"This was not evidence that the tumors were starving. A helpful result in mice does not establish that a ketogenic diet treats bowel cancer in people."},"populationType":"mixed","timelineYear":2022,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"xia","group":"cancer-mechanisms","kind":"Mouse + cell experiments","author":"Xia et al.","year":"2017","title":"Prevention of Dietary-Fat-Fueled Ketogenesis Attenuates BRAF V600E Tumor Growth","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5299059/","doi":"10.1016/j.cmet.2016.12.010","takeaway":"A ketone can also promote growth in a specific tumor model.","population":"Human melanoma xenografts in mice; zero human treatment participants. Figure 1A: 8 mice per arm for A375 and 7 per arm for SK-MEL-2; serum assays used 3 per group.","comparison":"A375: 3 arms (standard chow, solid high-fat diet, paste high-fat diet). SK-MEL-2: 2 arms (standard, paste high-fat). One standard-diet control per model; separate ketone/vehicle experiments.","protocol":"Diet began a week before tumor-cell injection and continued to the approximately 4-week endpoint.","result":"Acetoacetate enhanced BRAF V600E signaling and tumor growth; effects differed by mutation and ketone. The result was not a universal effect of all ketones.","limitation":"Preclinical, mutation-specific finding. It does not establish that ketogenic diets worsen human cancer generally. Dietary fat and administered ketones are distinct manipulations.","access":"Full text and original Figure 1 image: sample sizes checked in panel A, separately from serum assays in the legend. Use as a mechanistic counterexample, not a clinical effect estimate.","topics":["cancer"],"timelineTitle":"Could a ketone help some skin cancers grow?","timelineSummary":"One ketone promoted growth in a specific melanoma model. The result does not apply to every cancer.","explainer":{"who":"Mice carrying human skin-cancer cells, not people receiving cancer treatment. The highlighted experiments used seven or eight mice in each diet group.","compared":"Researchers compared normal and high-fat diets, and separately tested ketones, using skin-cancer cells with different gene changes.","found":"One ketone helped tumors with a particular gene change grow faster.","meaning":"Ketones can have different effects in different cancers. This experiment does not show that ketogenic diets make all human cancers worse."},"populationType":"animal","timelineYear":2017,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"direct","group":"cancer-clinical","kind":"Human randomized phase II trial","author":"de Groot et al. · DIRECT","year":"2020","title":"Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7311547/","doi":"10.1038/s41467-020-16138-3","takeaway":"Some response signals, without improved complete pathological response.","population":"131 randomized with HER2-negative stage II/III breast cancer; 129 analyzed after two exclusions: 65 FMD, 64 regular diet.","comparison":"2 arms, one regular-diet control; both received chemotherapy. Dexamethasone use differed between arms.","protocol":"4-day FMD around chemotherapy cycles (3 days before and the treatment day). Only 20% adhered through all cycles.","result":"Pathological complete response: 10.8% versus 12.7% (P=.735); toxicity did not significantly differ. Radiological response favored FMD (adjusted OR 3.17, 95% CI 1.06–9.45). A favorable pathological-response analysis was per protocol.","limitation":"Adherence selection, multiple endpoints and supportive-medication differences weaken inference. No demonstrated survival benefit or standalone fasting effect.","access":"Full text: participant flow, compliance and tumor-response Results. FMD-related commercial interests disclosed. Registry NCT02126449; distinct from the metabolic DIRECT trial.","topics":["cancer","safety"],"timelineTitle":"Does a fasting-style diet help breast cancer treatment?","timelineSummary":"Some tumor-response measures improved, but complete tumor clearance at surgery did not.","explainer":{"who":"131 people with a particular type of breast cancer joined. The final comparison included 129: 65 on the special diet and 64 eating normally.","compared":"Both groups received chemotherapy. One also followed a four-day, very-low-calorie diet designed to mimic fasting around treatment. The other continued its regular diet.","found":"Scans suggested better tumor shrinkage in some comparisons. But the diet did not clearly improve the chance of finding no remaining cancer at surgery, or reduce treatment side effects.","meaning":"Only about one in five followed the diet through every treatment cycle, and supportive medicines differed between groups. The trial did not establish longer survival or show that fasting alone treats cancer."},"populationType":"human","timelineYear":2020,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"ergo","group":"cancer-clinical","kind":"Human randomized trial","author":"Voss et al. · ERGO2","year":"2020","title":"ERGO2: A Prospective, Randomized Trial of Calorie-Restricted Ketogenic Diet and Fasting in Addition to Reirradiation for Malignant Glioma","url":"https://pubmed.ncbi.nlm.nih.gov/32619561/","doi":"10.1016/j.ijrobp.2020.06.021","takeaway":"Ketosis occurred, but the primary cancer outcome did not improve.","population":"50 patients with recurrent malignant glioma randomized 1:1; 4 left before treatment, and 20 completed the dietary intervention.","comparison":"2 arms of 25; one usual-diet control. Both arms received reirradiation.","protocol":"9-day intervention: 3 days restricted-calorie ketogenic diet, 3 days fasting, then 3 ketogenic days.","result":"17/20 dietary completers developed ketosis. Six-month progression-free survival was 20% versus 16%, without a significant difference; overall survival also did not differ.","limitation":"Small and short intervention in heavily treated disease. A favorable exploratory subgroup based on glucose cannot replace the negative randomized result.","access":"Original trial abstract. Registry NCT01754350. Later diet-diary and spectroscopy reports concern the same trial, not independent replication.","topics":["cancer"],"timelineTitle":"Does keto plus fasting improve brain cancer treatment?","timelineSummary":"The diet raised ketones but did not clearly improve cancer control or survival.","explainer":{"who":"Fifty people whose brain cancer had returned, assigned to two groups of 25.","compared":"Both groups received more radiation treatment. One also followed nine days of a low-carbohydrate diet and fasting; the other ate its usual diet.","found":"Most people who finished the diet produced more ketones, the fuels made from fat. But cancer control and survival were not clearly better.","meaning":"Producing ketones is not the same as stopping a tumor. This small trial did not demonstrate a treatment benefit from the diet-and-fasting plan."},"populationType":"human","timelineYear":2020,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"vernieri","group":"cancer-clinical","kind":"Human uncontrolled trial","author":"Vernieri et al.","year":"2022","title":"Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9762338/","doi":"10.1158/2159-8290.CD-21-0030","takeaway":"Metabolic and immune changes support further trials, not efficacy claims.","population":"101 selected patients with different cancers in the principal clinical cohort; molecular analyses used smaller subsets.","comparison":"Single-arm dietary trial with standard anticancer therapies; zero randomized diet-control arms. Additional tissue comparisons were exploratory.","protocol":"Repeated 5-day FMD cycles with nutritional monitoring and refeeding between cycles.","result":"Glucose and growth factors decreased; blood/tumor analyses showed changes consistent with potentially stronger antitumor immune activity.","limitation":"Safety and biomarker study, not a controlled survival trial. The title’s “safe” applies to selected monitored participants, not everyone with cancer. Standard treatment, selection and multiple analyses limit inference.","access":"Full text: clinical design and metabolic/immune Results. Commercial FMD relationships disclosed; registry NCT03340935. Online publication 2021, journal issue 2022.","topics":["cancer","immune"],"timelineTitle":"How does a fasting-style diet affect immunity in cancer?","timelineSummary":"Blood and immune changes were observed. Better cancer outcomes were not established.","explainer":{"who":"101 selected patients with different cancers. Some detailed blood and tumor tests used smaller groups.","compared":"Patients continued cancer treatment while repeating a five-day low-calorie diet designed to mimic fasting. There was no randomly assigned usual-diet group.","found":"Blood sugar, growth-related hormones and some immune-cell measurements changed in ways researchers considered worth studying further.","meaning":"Changes in blood or immune cells do not prove that tumors shrink or people live longer. Results from carefully selected, monitored patients do not establish safety for everyone with cancer."},"populationType":"human","timelineYear":2022,"cohort":"Ligorio’s 14-patient survival comparison is a subanalysis of NCT03340935, the broader trial reported by Vernieri; these are overlapping publications."},{"id":"harvie","group":"cancer-clinical","kind":"Human randomized screening trial","author":"Harvie et al.","year":"2025","title":"Randomised phase-2 screening trial of intermittent energy restriction plus resistance exercise versus resistance exercise alone during chemotherapy for advanced breast cancer","url":"https://www.nature.com/articles/s41416-025-03129-8","doi":"10.1038/s41416-025-03129-8","takeaway":"An encouraging signal under an exploratory statistical threshold.","population":"68 women with advanced breast cancer and BMI at least 24; 35 intervention, 33 control.","comparison":"2 arms; one active resistance-exercise control with written diet advice. Both received chemotherapy; additional dietitian support was in the intervention arm.","protocol":"2 reduced-energy days weekly plus an energy-restricted Mediterranean-style diet and resistance exercise, continued until progression.","result":"Median progression-free survival: 42.0 versus 26.1 weeks; adjusted HR 0.729 (95% CI 0.391–1.361), one-sided P=.160. Some quality-of-life measures favored intervention.","limitation":"The trial used one-sided α=.20 to screen for a signal. The confidence interval includes no effect; this is not confirmatory survival evidence. Multiple intervention components.","access":"Full text: Methods and Results. Registry ISRCTN12841416. Food-containing restriction, not complete fasting.","topics":["cancer","weight"],"timelineTitle":"Can eating less on some days help during breast cancer care?","timelineSummary":"An early trial suggested longer cancer control, but the result remains uncertain.","explainer":{"who":"68 women with advanced breast cancer: 35 assigned to the added diet program and 33 to the comparison group.","compared":"Both groups had chemotherapy and strength exercise. One also received dietitian support, lower food intake on two days a week, and broader diet changes.","found":"Cancer stayed controlled for longer in the diet group in this small trial, but the uncertainty was large enough that a real benefit is not yet established.","meaning":"The study was designed to look for an early signal, using a less demanding statistical threshold than a confirmatory trial. It needs a larger follow-up study."},"populationType":"human","timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"jameson","group":"cancer-clinical","kind":"Human randomized screening trial","author":"Jameson et al.","year":"2026","title":"A randomized phase II trial of gemcitabine, nab-paclitaxel, cisplatin with or without a medically supervised ketogenic diet for patients with metastatic pancreatic cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12980701/","doi":"10.1002/cncr.70343","takeaway":"Promising but imprecise results for ketogenic diet alongside chemotherapy.","population":"36 randomized; 32 evaluable, 16 per arm, with previously untreated metastatic pancreatic cancer.","comparison":"2 arms, one usual-diet control; both received the same triple chemotherapy. Ketogenic intervention included remote clinical support.","protocol":"Ongoing supervised ketogenic diet; target BHB 0.5–3.0 mM. This was not a fasting trial.","result":"Median progression-free survival: 8.5 versus 6.2 months, HR 0.53 (95% CI 0.21–1.37), one-sided P=.096. Overall survival: 13.7 versus 10.2 months, HR 0.58 (0.25–1.37).","limitation":"Screening α=.20, small evaluable sample and post-randomization exclusions. Both intervals include no effect. Cannot establish ketone-mediated starvation or diet-only benefit.","access":"Full text: statistical analysis and participant Results. Virta Health employment/equity relationships disclosed. Published March 2026.","topics":["cancer"],"timelineTitle":"Could a keto diet help pancreatic cancer treatment?","timelineSummary":"A small trial alongside chemotherapy had encouraging but uncertain survival results.","explainer":{"who":"36 people with pancreatic cancer that had spread joined; 32 were included in the main comparison, sixteen per group.","compared":"Both groups received the same chemotherapy. One also followed a medically supervised ketogenic diet, which sharply limits carbohydrate. This was not a fasting study.","found":"The ketogenic group had longer cancer-control and survival times in the trial, but the results were too uncertain to establish a real advantage.","meaning":"This was a small early trial that needs confirmation. It does not show that ketones starve pancreatic cancer or that diet can replace chemotherapy."},"populationType":"human","timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"padrao","group":"cancer-clinical","kind":"Mouse experiments + human biomarkers","author":"Padrão et al.","year":"2026","title":"Fasting boosts breast cancer therapy efficacy via glucocorticoid activation","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12823405/","doi":"10.1038/s41586-025-09869-0","takeaway":"A treatment-sensitizing pathway beyond simply depriving a tumor of fuel.","population":"Mouse xenografts and human cohorts: 15 receiving endocrine therapy plus FMD; 35 in DigesT. Figure 1 reports 6 tumors per arm, not 6 independently verified mice.","comparison":"Key mouse experiment: 4 arms: ordinary feeding, fasting, tamoxifen, combination (three comparators to combination). Human comparisons were paired before/after, without randomized diet controls.","protocol":"Mice: weekly 48-hour fasts over 4 weeks with/without tamoxifen. Humans: 5-day FMD cycles.","result":"Glucocorticoid-receptor signaling contributed to enhanced endocrine-treatment effects in mice; human hormone and tumor-marker changes were compatible with the mechanism.","limitation":"Mechanistic, not a confirmatory human survival trial. Human cohorts include previously studied material and must not be counted as independent efficacy replications.","access":"Full text: Figures 1–2 and clinical methods. Published online December 2025; January 2026 issue.","topics":["cancer"],"timelineTitle":"Can fasting make breast cancer hormone treatment work better?","timelineSummary":"Mouse findings suggest a possible mechanism. Small human samples do not establish a treatment benefit.","explainer":{"who":"Mouse experiments and two human groups of fifteen and 35. One highlighted mouse experiment reported six tumors per group, not necessarily six separate mice.","compared":"Mice received ordinary food, fasting, hormone treatment, or both fasting and treatment. Human measurements were taken before and after low-calorie diet cycles, without a randomly assigned usual-diet group.","found":"Fasting strengthened the effects of hormone treatment in mice through changes in hormone signaling. Human samples showed clues consistent with that idea.","meaning":"A possible explanation in mice is not proof of better survival in people. This was research into helping treatment work, not evidence that fasting alone kills cancer."},"populationType":"mixed","timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"jamshed","group":"autophagy","kind":"Human randomized crossover","author":"Jamshed et al.","year":"2019","title":"Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6627766/","doi":"10.3390/nu11061234","takeaway":"Autophagy-related gene expression is not the same as measured recycling.","population":"11 adults with overweight participated; assay-specific sample sizes were smaller for some endpoints.","comparison":"2 randomized crossover conditions; each person provided a control period. No independent third group.","protocol":"4 days per condition: 08:00–14:00 eating versus 08:00–20:00, with matched food.","result":"Early eating increased morning LC3A gene expression and ketones; mean 24-hour glucose was about 4 mg/dL lower.","limitation":"Measured blood-cell gene expression, not autophagic flux. Morning/evening samples cannot identify onset, peak or duration across organs. No cancer or longevity endpoint.","access":"Full text: Methods and gene-expression Results. The 18-hour daily fast was a protocol, not a proven activation threshold.","topics":["autophagy","glucose"],"timelineTitle":"Does eating earlier affect the body’s cell recycling?","timelineSummary":"Blood gene activity changed, but this did not show how much material cells actually recycled.","explainer":{"who":"Eleven adults with overweight; some blood tests included fewer samples.","compared":"Each person tried two eating schedules for four days each: 8 a.m. to 2 p.m. and 8 a.m. to 8 p.m. Food was matched between schedules.","found":"Earlier eating slightly lowered average blood sugar and changed the activity of a gene linked with cell recycling.","meaning":"A gene becoming more active does not prove cells recycled more material. The experiment cannot tell us when recycling starts during a fast or whether it improves health."},"populationType":"human","timelineYear":2019,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"bensalem","group":"autophagy","kind":"Human randomized substudy","author":"Bensalem et al.","year":"2025","title":"Intermittent time-restricted eating may increase autophagic flux in humans: an exploratory analysis","url":"https://onlinelibrary.wiley.com/doi/10.1113/JP287938","doi":"10.1113/JP287938","takeaway":"Direct human flux evidence is promising but exploratory.","population":"121 enrolled in the metabolic DIRECT substudy. Baseline flux available for 114: 47 intermittent restriction, 44 daily restriction, 23 standard care; later assay denominators vary.","comparison":"3 randomized arms; two comparators: active daily calorie restriction and standard-care booklet. Only dietary intervention arms received individual diet counseling.","protocol":"30% of energy needs before noon then a 20-hour fast on 3 days/week, versus 30% daily restriction, for 6 months. Blood sampled after a standardized overnight fast.","result":"Blood-cell flux change favored intermittent restriction versus standard care at 6 months (post hoc P=.04), not 2 months. No significant within-fasting-group increase; control decline may partly explain the difference.","limitation":"Blood immune cells do not represent every organ. No clinical cancer, lifespan or hour-by-hour outcome.","access":"Full publisher PDF: Table 1, Methods and Results. Assay-related patents disclosed. NCT03689608, unrelated to breast-cancer DIRECT.","topics":["autophagy"],"timelineTitle":"Does intermittent fasting increase cell recycling?","timelineSummary":"A small blood-cell study found an uncertain difference after six months, not a body-wide fasting timetable.","explainer":{"who":"121 adults joined this part of a larger trial; 114 had the starting blood measurement. They came from three groups: 47, 44 and 23 people.","compared":"For six months, people either ate very little before noon on three days a week, cut calories every day, or received a healthy-eating booklet. Researchers measured recycling activity in blood cells.","found":"An extra analysis found a difference between intermittent fasting and the booklet group at six months, but not at two months. A decline in the booklet group may explain part of it.","meaning":"This is an early clue, not proof that fasting increases recycling throughout the body. It gives no reliable start hour, best fasting length, cancer benefit or longer-life result."},"populationType":"human","timelineYear":2025,"cohort":"Bensalem is an autophagy substudy of the Teong trial (NCT03689608)."},{"id":"espinoza","group":"autophagy","kind":"Human randomized pilot","author":"Espinoza et al.","year":"2025 online","title":"Effect of fasting-mimicking diet on markers of autophagy and metabolic health in human subjects","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13601415/","doi":"10.1007/s11357-025-02035-4","takeaway":"A small pilot suggests formulation-specific changes in blood cells.","population":"30 adults: ProLon 11, FMD2 10, control 9; 83% women. Baseline BMI differed across arms.","comparison":"3 randomized arms: two FMD formulations and one food-containing control diet.","protocol":"6-day dietary intervention; sampling at baseline, days 4 and 6, and day 8 after 48 hours of refeeding.","result":"The study reported between-group differences in autophagic-flux markers by day 6; the favorable signal was associated with ProLon and was not consistent across formulations/timepoints.","limitation":"Small, unblinded pilot; LC3 protein-ratio assay in blood cells, not whole-body clearance. Does not determine the first hour of activation or a clinically beneficial duration.","access":"Full text: Table 1, autophagy Results and Discussion. Sponsored by L-Nutra; commercial formulations and relationships disclosed. NCT06115551.","topics":["autophagy"],"timelineTitle":"Can a fasting-style diet change cell recycling?","timelineSummary":"Blood-cell results differed between diet formulations. The small study did not establish a health benefit.","explainer":{"who":"Thirty adults: eleven on one low-calorie diet, ten on another, and nine on a comparison diet.","compared":"The two diets were designed to mimic parts of fasting while still providing food. Researchers took blood samples during six days of dieting and again after eating resumed.","found":"One diet showed a favorable change in blood-cell recycling measurements. The result was not consistent across both diets or all sample times.","meaning":"Thirty people are too few for a firm conclusion. Blood-cell measurements do not establish whole-body benefits or a precise fasting timetable."},"populationType":"human","timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"vendelbo","group":"autophagy","kind":"Human crossover physiology","author":"Vendelbo et al.","year":"2014","title":"Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4096723/","doi":"10.1371/journal.pone.0102031","takeaway":"A 72-hour muscle sample does not establish peak autophagy.","population":"8 healthy men studied under two fasting conditions.","comparison":"2 conditions in randomized order: overnight versus 72-hour fasting; each participant served as his own control. Insulin stimulation provided an additional physiological comparison.","protocol":"Muscle biopsies, amino-acid balance and insulin-clamp measurements.","result":"Net muscle phenylalanine release increased and mTOR signaling fell. LC3B-II and p62 findings did not allow a clear determination of increased autophagic flux.","limitation":"Static protein levels can reflect formation or impaired clearance. Small male-only experiment; increased muscle protein release is not evidence that all muscle is protected during fasting.","access":"Full text: subjects, experimental design and Discussion of LC3B/p62 interpretation.","topics":["autophagy","muscle"],"timelineTitle":"What happens to muscle during a three-day fast?","timelineSummary":"Signs of muscle protein breakdown increased. The study did not establish a peak time for cell recycling.","explainer":{"who":"Eight healthy men, each studied after two different fasting periods.","compared":"Researchers compared an overnight fast with a 72-hour fast. They sampled muscle and measured signs of protein breakdown and cell recycling.","found":"More of a building block of protein left the muscles during the longer fast. The recycling measurements did not give a clear answer about how much recycling increased.","meaning":"A muscle sample after three days cannot tell us when recycling peaks. The study also does not support a promise that fasting always protects muscle."},"populationType":"human","timelineYear":2014,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"mizushima","group":"autophagy","kind":"Mouse experiment","author":"Mizushima et al.","year":"2004","title":"In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC363084/","doi":"10.1091/mbc.e03-09-0704","takeaway":"Autophagy varies by tissue and does not simply rise forever.","population":"Reporter mice; Figure 7 quantitative values represent at least 5 mice per condition. No human participants.","comparison":"3 feeding states: fed control, 24-hour food deprivation, 48-hour deprivation; one fed comparator for the two fasting durations.","protocol":"Food withheld with water available; fluorescent LC3 structures assessed across organs.","result":"Some tissues showed substantial baseline activity. Starvation responses differed: liver markers rose at 24 hours and returned near baseline at 48 hours, while other tissues behaved differently.","limitation":"Autophagosome counts are not a universal flux meter. A 24-hour fast in a mouse is not physiologically interchangeable with 24 hours in a person.","access":"Full text: Methods, organ-specific Results and Figure 7. Counts describe measured panels, not one pooled study-wide animal total.","topics":["autophagy"],"timelineTitle":"Does fasting affect cell recycling equally in every organ?","timelineSummary":"In mice, responses differed across tissues and changed over time. There was no single body-wide pattern.","explainer":{"who":"Mice with a special marker that made parts of the recycling process visible. A key set of measurements used at least five mice per condition.","compared":"Researchers compared mice eating normally with mice without food for 24 or 48 hours. Water remained available.","found":"Organs did not respond alike. Some recycling-related measurements rose and then fell; some recycling was already happening before fasting.","meaning":"There is no single pattern for the whole body. A day without food also affects a mouse differently from a person, so these times are not human fasting targets."},"populationType":"animal","timelineYear":2004,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"takamura","group":"autophagy","kind":"Genetically modified mouse study","author":"Takamura et al.","year":"2011","title":"Autophagy-deficient mice develop multiple liver tumors","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3078705/","doi":"10.1101/gad.2016211","takeaway":"Normal cellular recycling can restrain tumor initiation.","population":"Key Atg5 comparison after 9 months: 17 deficient mice, 14 heterozygous controls and 4 floxed controls; separate Atg7/p62 experiments also reported.","comparison":"3 genotypes in the highlighted experiment; two genetic control groups. No fasting intervention and no human participants.","protocol":"Long-term loss of autophagy genes, with liver pathology and cellular-damage measurements.","result":"All 17 deficient mice in the highlighted cohort developed liver tumors, versus neither control group. Tumors were benign adenomas with abnormal mitochondria and damage signals.","limitation":"Removing essential autophagy is not the inverse of prescribing a fast. Preventing abnormal cells from arising and treating established malignant disease are different questions.","access":"Full text: Results and Figure 1. Denominators refer to the specified genetic comparison.","topics":["autophagy","cancer"],"timelineTitle":"Can normal cell recycling help prevent liver tumors?","timelineSummary":"Mice missing a recycling gene developed benign liver tumors. This was not a fasting experiment.","explainer":{"who":"In one main comparison, seventeen mice lacked a working cell-recycling gene. Two comparison groups contained fourteen and four mice.","compared":"Researchers altered genes and followed liver changes over time. The comparison mice did not have the same complete loss of the recycling gene. No fasting diet was tested.","found":"All seventeen mice in the main affected group developed noncancerous liver growths; neither comparison group did.","meaning":"Normal cell recycling can help prevent damage. But disabling a gene does not show that increasing recycling through fasting prevents cancer in people."},"populationType":"animal","timelineYear":2011,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"guo","group":"autophagy","kind":"Genetically modified mouse study","author":"Guo et al.","year":"2013","title":"Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3713426/","doi":"10.1101/gad.219642.113","takeaway":"Established tumor biology can depend on autophagy for survival.","population":"Kras-driven mouse lung-tumor models; Figure 1 histology/CT uses 3 mice per genotype/timepoint and lung-weight panels 5.","comparison":"Key comparison: autophagy-intact versus Atg7-deficient tumors; one tumor-bearing genetic control, plus normal-lung reference. Additional p53 comparisons are separate experiments.","protocol":"Kras activation with or without Atg7 deletion; tumor progression and mitochondrial/lipid metabolism followed.","result":"Atg7 loss reduced malignant tumor burden and shifted lesions toward oncocytomas with defective mitochondria. Autophagy supported tumor metabolic function.","limitation":"Genetic models do not show that fasting worsens all cancers or that inhibiting autophagy is universally beneficial. They contradict a universal “more autophagy kills cancer” rule.","access":"Full text: Results and Figure 1. No human participants or fasting-control arms.","topics":["autophagy","cancer"],"timelineTitle":"Can cell recycling also help lung tumors survive?","timelineSummary":"Disabling a recycling gene reduced malignant tumors in mice, showing why more recycling is not always better.","explainer":{"who":"Mice engineered to develop lung tumors. Key scans used three mice per gene group and timepoint; lung-weight measurements used five.","compared":"Researchers compared tumors with a working recycling gene against tumors missing that gene, with normal lung tissue as another reference.","found":"Removing the recycling gene reduced cancerous tumor growth and changed the kinds of tumors that developed.","meaning":"Cell recycling can help an existing tumor survive as well as help healthy cells. This does not prove that fasting worsens human cancer, but it challenges the idea that more recycling is always protective."},"populationType":"animal","timelineYear":2013,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"imada","group":"autophagy","kind":"Mouse + organoid study","author":"Imada et al.","year":"2024","title":"Short-term post-fast refeeding enhances intestinal stemness via polyamines","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12103248/","doi":"10.1038/s41586-024-07840-z","takeaway":"Regeneration and tumor growth can share biological pathways.","population":"Mouse intestinal models; key Figure 5 tumor comparisons used 7–13 mice per group across 3 experiments. No human intervention.","comparison":"Fed, 24-hour-fasted, and post-fast-refed states, including different refeeding durations; fed and fasted groups served as comparators for refeeding.","protocol":"Fasting/refeeding with experimentally induced Apc tumor-suppressor loss; lesions assessed at 1 and 3 weeks.","result":"Refeeding enhanced stem-cell proliferation and regeneration through mTORC1/polyamine pathways; Apc loss during this state produced more intestinal tumors.","limitation":"Requires a specific engineered tumor model. Does not demonstrate that ordinary fasting causes human cancer. Regeneration is not automatically selective for healthy cells.","access":"Full text: Figure 5 and Results; samples and controls vary by experiment.","topics":["cancer","autophagy"],"timelineTitle":"What happens in the gut when eating resumes after a fast?","timelineSummary":"Refeeding boosted gut repair in mice, but also tumor growth in a model with an altered cancer-related gene.","explainer":{"who":"Mice, with seven to thirteen per group in the highlighted tumor experiments. No people received a fasting intervention.","compared":"Researchers compared ordinary feeding, a 24-hour fast, and eating again after fasting. Some mice also had a cancer-protection gene deliberately switched off.","found":"Eating again boosted repair and cell growth in the gut. With the cancer-protection gene switched off, it also increased tumors.","meaning":"Repair and tumor growth can share some of the same machinery. This special mouse model does not establish that ordinary fasting or refeeding causes cancer in people."},"populationType":"animal","timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"lifespan","group":"autophagy","kind":"Randomized mouse lifespan study","author":"Di Francesco et al.","year":"2024","title":"Dietary restriction impacts health and lifespan of genetically diverse mice","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11485257/","doi":"10.1038/s41586-024-08026-3","takeaway":"Strong animal longevity evidence is still not human longevity evidence.","population":"960 genetically diverse female mice assigned; 937 survived to intervention at 6 months. Survival groups: 188, 188, 190, 189 and 182.","comparison":"5 arms: unrestricted food (188), 1 fasting day/week (188), 2 consecutive fasting days/week (190), 20% calorie restriction (189), 40% restriction (182). One unrestricted control plus active dietary comparisons.","protocol":"Assigned diets maintained through natural lifespan; repeated health assessments.","result":"Both intermittent fasting and calorie restriction extended lifespan; genetics had a larger influence on variation in lifespan than diet. Health-marker improvements did not consistently track longer survival.","limitation":"Female mice, not people. Does not establish a human fasting duration, an autophagy-mediated explanation, or that maximum restriction is desirable.","access":"Full text: Figure 1, design and Results; original 960 and survival-analysis 937 distinguished.","topics":["longevity"],"timelineTitle":"Do fasting mice live longer?","timelineSummary":"Fasting and calorie cutting extended lifespan in female mice. This does not establish longer life in people.","explainer":{"who":"960 female mice were assigned to diets; 937 reached the point when the diets began.","compared":"Five groups ate freely, fasted one day a week, fasted two days a week, or received one of two daily calorie reductions. Researchers followed their lifespans.","found":"Both fasting and daily calorie cutting extended lifespan in these mice. Genetic differences influenced lifespan more than diet did.","meaning":"This is meaningful evidence in female mice, not proof that a fasting schedule adds years to human life. Better health-test results did not always predict longer survival."},"populationType":"animal","timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"singh","group":"autophagy","kind":"Human randomized crossover","author":"Singh et al.","year":"2026","title":"Reduced dietary protein intake does not alter autophagy in human blood: A randomized crossover study in healthy adults","url":"https://pubmed.ncbi.nlm.nih.gov/42721581/","doi":"10.1016/j.clnu.2026.106778","takeaway":"A plausible nutrient-sensing theory did not predict the human result.","population":"74 healthy adults randomized; 63 completed both periods.","comparison":"2 diet conditions; each participant was his/her own control: 10% versus 20% of energy from protein, with intended energy balance.","protocol":"Two 4-week periods, separated by a 4-week washout. Whole-blood immune-cell flux assay.","result":"Adjusted flux difference: −8.46 ng LC3B-II/mg protein/hour (95% CI −24.06 to 7.14; P=.28), without a significant benefit from lower protein.","limitation":"This is not a fasting trial. It cautions against assuming that manipulating one nutrient-sensing pathway reliably increases human autophagy.","access":"Original journal abstract and PubMed record; published October 2026. Related assay patents disclosed.","topics":["autophagy"],"timelineTitle":"Does eating less protein increase cell recycling?","timelineSummary":"Blood-cell measurements showed no clear increase. This was a protein study, not a fasting trial.","explainer":{"who":"74 healthy adults started; 63 completed both diets.","compared":"Each person spent four weeks on a lower-protein diet and four weeks on a higher-protein diet, with a four-week gap between them. Calories were intended to stay similar.","found":"Eating less protein did not clearly increase the measured recycling activity in blood cells.","meaning":"This was not a fasting experiment. It shows why a theory about nutrient intake needs direct testing before it becomes a promise about cell recycling."},"populationType":"human","timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"lin","author":"Lin et al.","group":"benefits","kind":"Human randomized trial","topics":["weight"],"year":"2023","title":"Time-Restricted Eating Without Calorie Counting for Weight Loss in a Racially Diverse Population : A Randomized Controlled Trial","doi":"10.7326/m23-0052","pmid":"37364268","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11192144/","takeaway":"A practical alternative to calorie counting, without a demonstrated advantage.","population":"90 adults with obesity randomized; 77 completed 12 months.","comparison":"3 arms, 30 each: time restriction, calorie restriction, usual diet. Two comparators; counseling in both active arms.","protocol":"12:00–20:00 eating for 6 months, then a 10-hour maintenance window; comparator prescribed a 25% calorie deficit.","result":"At 12 months, time restriction versus control: −4.61 kg (95% CI −7.37 to −1.85). Versus calorie restriction: +0.81 kg (−3.07 to 4.69; P=.68).","limitation":"Small trial; active arms received more support than control. Secondary comparisons were not all multiplicity-adjusted.","access":"Full text, participant flow and outcomes. NCT04692532.","timelineTitle":"Can a daily eating window replace calorie counting?","timelineSummary":"Both approaches helped with weight loss over a year. Neither clearly outperformed the other.","explainer":{"who":"Ninety adults with obesity, thirty in each group. Seventy-seven completed a year.","compared":"One group used a daily eating window, one counted and cut calories, and one kept its usual diet. The eating window widened during the second half of the year.","found":"Both supported dieting approaches helped people lose weight. The eating-window group did not clearly outperform the calorie-counting group.","meaning":"An eating window may be a useful alternative to counting calories. This trial does not establish that it has a special weight-loss effect independent of eating less."},"populationType":"human","timelineYear":2023,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"lowe","author":"Lowe et al.","group":"benefits","kind":"Human randomized trial","topics":["weight","muscle"],"year":"2020","title":"Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial","doi":"10.1001/jamainternmed.2020.4153","pmid":"32986097","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7522780/","takeaway":"A midday eating window did not produce extra weight loss.","population":"141 randomized; 116 supplied weight data (59 time restriction, 57 control); 105 completed. Body-composition subgroup: 50.","comparison":"2 arms: 12:00–20:00 eating versus three structured meals daily; one active meal-pattern control.","protocol":"12 weeks, without prescribed calorie reduction or exercise changes.","result":"Between-group weight difference: −0.26 kg (95% CI −1.30 to 0.78; P=.63). An appendicular lean-mass loss signal appeared in the smaller subgroup.","limitation":"25 randomized people contributed no weight data. Subgroup composition findings require replication; lean mass is not identical to muscle protein.","access":"Full text and participant flow. November 2020 Figure 2C correction and 2021 participant-message clarification identified. NCT03393195.","timelineTitle":"Does eating from noon to 8 p.m. help with weight loss?","timelineSummary":"A twelve-week trial found no clear extra weight loss compared with three structured meals a day.","explainer":{"who":"141 adults were assigned to eating plans. Only 116 supplied weight data, and 105 completed the study. A smaller group had body-composition scans.","compared":"For twelve weeks, one group ate only between noon and 8 p.m. The comparison group ate three structured meals a day. Neither was given a calorie-cutting target.","found":"The eating window did not produce clearly greater weight loss. Some scan results raised questions about loss of lean tissue, which includes muscle and water.","meaning":"Missing results and the small scan group make firm conclusions difficult. This study does not support assuming that a shorter eating window automatically burns extra fat or preserves muscle."},"populationType":"human","timelineYear":2020,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"helena","author":"Schübel et al.","group":"benefits","kind":"Human randomized trial","topics":["weight","glucose"],"year":"2018","title":"Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: a randomized controlled trial","doi":"10.1093/ajcn/nqy196","pmid":"30475957","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6915821/","takeaway":"5:2 and daily restriction produced similar longer-term weight changes.","population":"150 adults with overweight or obesity; arm-specific allocation and final missingness were not extracted from the original full text.","comparison":"3 arms: 5:2 restriction, daily calorie restriction, no advice to restrict calories. Two comparators.","protocol":"12 weeks intervention, 12 maintenance and 26 follow-up; both active prescriptions targeted approximately 20% weekly restriction.","result":"Week-50 weight change: −5.2%, −4.9%, −1.7%; 5:2 versus daily restriction P=.89. No advantage in the 82 selected adipose-tissue genes.","limitation":"A nonsignificant difference is not formal proof of equivalence. Gene expression and biomarkers do not establish disease prevention.","access":"Original indexed abstract; full-text extraction incomplete. NCT02449148.","timelineTitle":"Is the 5:2 diet better than cutting calories every day?","timelineSummary":"Both approaches produced similar weight changes after nearly a year.","explainer":{"who":"150 adults with overweight or obesity, followed for about a year.","compared":"One group ate much less on two days a week, another cut calories every day, and a third received no advice to cut calories. Both dieting plans targeted a similar weekly calorie reduction.","found":"The two dieting groups lost similar amounts of weight by the final follow-up.","meaning":"The two-day approach did not clearly work better. Similar results in one trial do not prove that every version of the diets will have exactly the same effects."},"populationType":"human","timelineYear":2018,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"jamshed2022","author":"Jamshed et al.","group":"benefits","kind":"Human randomized trial","topics":["weight","cardiovascular"],"year":"2022","title":"Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial","doi":"10.1001/jamainternmed.2022.3050","pmid":"35939311","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9361187/","takeaway":"Early eating added weight loss, but the primary fat-loss result was uncertain.","population":"90 adults with obesity randomized, 45 per arm; 59 completed all assessments.","comparison":"2 arms: early 8-hour window plus energy restriction versus at least 12-hour eating plus energy restriction.","protocol":"07:00–15:00 eating; 14 weeks with weight-loss support in both groups.","result":"Additional weight change: −2.3 kg (95% CI −3.7 to −0.9; P=.002). Body-fat difference: −1.4 kg (−2.9 to 0.2; P=.09).","limitation":"20 withdrawals and 11 pandemic-related missing assessments. Positive completer-only fat results should not replace the main analysis.","access":"Full text and flow diagram; primary outcomes distinguished. NCT03459703.","timelineTitle":"Does eating earlier help with weight loss?","timelineSummary":"An early eating window added weight loss, but the extra body-fat loss was uncertain.","explainer":{"who":"Ninety adults with obesity, 45 assigned to each group. Only 59 completed every assessment.","compared":"Both groups cut calories for fourteen weeks. One also ate between 7 a.m. and 3 p.m.; the other spread eating across at least twelve hours.","found":"The early-eating group lost about 2.3 kg more weight on average. Its extra loss of body fat was less certain.","meaning":"Scale weight and body fat are different outcomes. Missing assessments and the short study make it harder to know how much benefit would last."},"populationType":"human","timelineYear":2022,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"dote","author":"Dote-Montero et al.","group":"benefits","kind":"Human randomized trial","topics":["weight"],"year":"2025","title":"Effects of early, late and self-selected time-restricted eating on visceral adipose tissue and cardiometabolic health in participants with overweight or obesity: a randomized controlled trial","doi":"10.1038/s41591-024-03375-y","pmid":"39775037","url":"https://pubmed.ncbi.nlm.nih.gov/39775037/","takeaway":"Changing eating-window timing did not clearly reduce visceral fat further.","population":"197 adults: 49 usual care, 49 early, 52 late and 47 self-selected time restriction.","comparison":"4 arms; one usual-care comparator with Mediterranean-diet education. Three 8-hour windows added to that care.","protocol":"12 weeks; primary outcome was MRI-measured visceral adipose tissue.","result":"Between-group differences versus usual care: −4% (95% CI −12 to 4), −6% (−13 to 2), −3% (−11 to 5), respectively. All nonsignificant.","limitation":"Short duration. A favorable weight result does not establish an advantage for the primary visceral-fat endpoint.","access":"Original publisher abstract; five mild adverse events, no serious events reported. NCT05310721.","timelineTitle":"Does the timing of an eating window change belly fat?","timelineSummary":"Early, late and self-chosen windows did not clearly add to loss of fat around internal organs.","explainer":{"who":"197 adults with overweight or obesity, divided among four groups.","compared":"Everyone received Mediterranean-diet education. Three groups also used an eight-hour eating window: early, late, or at a time they chose. The fourth had no added window.","found":"After twelve weeks, scans showed no clear extra reduction in fat around internal organs from any of the eating windows.","meaning":"This trial did not establish a best time of day for losing this type of belly fat. Changes on the scale cannot substitute for the scan result."},"populationType":"human","timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"hajek","author":"Hajek et al.","group":"benefits","kind":"Human randomized trial","topics":["weight","adherence"],"year":"2021","title":"A randomised controlled trial of the 5:2 diet","doi":"10.1371/journal.pone.0258853","pmid":"34788298","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8598045/","takeaway":"Simple 5:2 advice was feasible, but adherence fell substantially.","population":"300 adults with obesity, 100 per arm.","comparison":"3 arms: brief conventional advice, 5:2 self-help, or 5:2 with six group sessions. Two active comparators.","protocol":"One-year follow-up; 5:2 restricted intake on two days each week.","result":"At one year, self-help 5:2 and conventional advice produced about −1.9 and −1.8 kg. Reported 5:2 adherence fell from 74% at six weeks to 22% at one year.","limitation":"Additional early group support did not establish a sustained advantage. Self-reported adherence and attrition limit interpretation.","access":"Full text; ISRCTN79408248. Public funding and no competing interests reported.","timelineTitle":"Can people stick with the 5:2 diet for a year?","timelineSummary":"Fewer people kept following the plan over time. Weight loss was similar to conventional advice.","explainer":{"who":"300 adults with obesity, with 100 in each group.","compared":"Researchers compared ordinary brief weight-loss advice, a self-help 5:2 plan, and the same 5:2 plan with six group-support sessions. They followed people for a year.","found":"The 5:2 plan and ordinary advice produced similar average weight loss. Reported use of the 5:2 plan fell from 74% at six weeks to 22% at a year.","meaning":"A diet has to remain workable over time. Extra early support did not establish a lasting advantage in this trial."},"populationType":"human","timelineYear":2021,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"trim","author":"Maruthur et al.","group":"benefits","kind":"Human randomized trial","topics":["weight","glucose"],"year":"2024","title":"Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity : A Randomized Controlled Trial","doi":"10.7326/m23-3132","pmid":"38639542","url":"https://pubmed.ncbi.nlm.nih.gov/38639542/","takeaway":"A controlled-feeding trial found no calorie-independent weight advantage.","population":"41 adults with obesity and prediabetes or diet-controlled diabetes; all completed. 93% women and 93% Black.","comparison":"2 isocaloric feeding arms, allocated 1:1; exact arm counts not extracted. Early 10-hour versus usual extended eating.","protocol":"12 weeks; matched nutrients and calories. Early arm ate 80% before 13:00; comparator at least 50% after 17:00.","result":"Weight changes −2.3 versus −2.6 kg; difference +0.3 kg (95% CI −1.2 to 1.9). Glucose measures did not differ.","limitation":"Small, single-site study with baseline weight imbalance; estimates do not rule out all timing effects.","access":"Original indexed abstract; NCT03527368. American Heart Association funding.","timelineTitle":"Does meal timing matter when calories stay the same?","timelineSummary":"With food provided, an earlier eating window did not produce extra weight loss or better blood sugar.","explainer":{"who":"41 adults with obesity and raised blood sugar or diet-controlled diabetes. All finished the study.","compared":"Researchers supplied food for twelve weeks, matching calories and nutrients. One group ate within ten hours, mostly earlier in the day; the other ate over a longer period, mostly later.","found":"Both groups lost some weight. The early eating window did not clearly add weight loss or improve blood sugar.","meaning":"When calories were similar, changing the clock did not produce a clear extra benefit here. The trial was small, so it cannot rule out every possible timing effect."},"populationType":"human","timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"pavlou","author":"Pavlou et al.","group":"benefits","kind":"Human randomized trial","topics":["weight","glucose"],"year":"2023","title":"Effect of Time-Restricted Eating on Weight Loss in Adults With Type 2 Diabetes: A Randomized Clinical Trial","doi":"10.1001/jamanetworkopen.2023.39337","pmid":"37889487","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10611992/","takeaway":"Time restriction helped versus control, without clear superiority to calorie restriction.","population":"75 adults with type 2 diabetes and obesity, 25 per arm; 69 completed.","comparison":"3 arms: 8-hour eating, 25% calorie restriction, usual-diet control.","protocol":"Six months; 12:00–20:00 window. Medication management and glucose monitoring accompanied the intervention.","result":"Weight difference versus control: −3.56% (95% CI −5.92 to −1.20). Direct comparison with calorie restriction: −1.78% (−4.09 to 0.53). HbA1c improved similarly in both active arms.","limitation":"Small study. One arm being significant versus control and another not does not prove the active arms differ.","access":"Full text, outcome table and participant flow; NCT05225337.","timelineTitle":"Can an eating window help with weight and type 2 diabetes?","timelineSummary":"It helped compared with usual eating, but did not clearly beat a calorie-cutting diet.","explainer":{"who":"75 adults with type 2 diabetes and obesity, 25 in each group. Sixty-nine completed six months.","compared":"One group ate between noon and 8 p.m., one cut calories by counting them, and one continued its usual diet. Blood sugar and medication needs were monitored.","found":"The eating-window group lost more weight than the usual-diet group. Both dieting approaches improved blood sugar, without a clear difference between them.","meaning":"Beating usual eating does not mean beating another supported diet. These results came with medical monitoring and should not be used to adjust diabetes medicine independently."},"populationType":"human","timelineYear":2023,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"carter","author":"Carter et al.","group":"benefits","kind":"Human randomized trial","topics":["glucose","weight","safety"],"year":"2018","title":"Effect of Intermittent Compared With Continuous Energy Restricted Diet on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Noninferiority Trial","doi":"10.1001/jamanetworkopen.2018.0756","pmid":"30646030","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6324303/","takeaway":"Intermittent and continuous restriction met the planned HbA1c equivalence test.","population":"137 adults with type 2 diabetes: 70 intermittent, 67 continuous; 97 completed 12 months.","comparison":"2 active dietary arms; no untreated comparator.","protocol":"500–600 kcal on two nonconsecutive days versus daily restriction. Medication-reduction protocol in place.","result":"HbA1c difference +0.2 percentage points (90% CI −0.2 to 0.5), within the prespecified ±0.5 margin. Early hypo/hyperglycemic events occurred in 16/46 insulin or sulfonylurea users.","limitation":"Substantial attrition. HbA1c equivalence does not prove weight equivalence or safety without medical monitoring.","access":"Full text; ACTRN12615000383561. Read with the 24-month follow-up.","timelineTitle":"Can eating less twice a week help manage diabetes?","timelineSummary":"Blood sugar results were similar to daily calorie cutting under medical supervision.","explainer":{"who":"137 adults with type 2 diabetes: seventy assigned to intermittent calorie cutting and 67 to daily calorie cutting. Ninety-seven finished a year.","compared":"One group ate very little on two days each week. The other reduced food every day. The program included planned medication adjustments and glucose monitoring.","found":"The two diets produced similar long-term blood-sugar test results under the study’s rules. Some people taking insulin or certain other diabetes medicines had episodes of high or low blood sugar.","meaning":"The result supports a possible supervised alternative, not fasting without medication review. Many people did not finish, and later follow-up did not preserve the same conclusion."},"populationType":"human","timelineYear":2018,"cohort":"Carter’s 12- and 24-month reports follow the same randomized cohort (ACTRN12615000383561)."},{"id":"carterfollow","author":"Carter et al.","group":"benefits","kind":"Human trial follow-up","topics":["glucose","adherence"],"year":"2019","title":"The effect of intermittent compared with continuous energy restriction on glycaemic control in patients with type 2 diabetes: 24-month follow-up of a randomised noninferiority trial","doi":"10.1016/j.diabres.2019.03.022","pmid":"30902672","url":"https://pubmed.ncbi.nlm.nih.gov/30902672/","takeaway":"The same trial’s later follow-up did not preserve the equivalence conclusion.","population":"Follow-up of the original 137-person Carter cohort; exact 24-month completer count not extracted.","comparison":"Same two originally randomized dietary groups; no new independent trial.","protocol":"24 months from baseline, including 12 months after the supported intervention ended.","result":"HbA1c rose above baseline in both groups. The 90% CI for their difference (−0.31 to 0.83 percentage points) exceeded the ±0.5 equivalence margin.","limitation":"Durability and missing follow-up matter. Earlier short-term improvement is not permanent diabetes remission.","access":"Original indexed follow-up abstract; linked to ACTRN12615000383561.","timelineTitle":"Do diabetes improvements last after diet support ends?","timelineSummary":"Blood sugar rose again in both diet groups. This was follow-up of the same trial, not a new study.","explainer":{"who":"The same people originally enrolled in the 137-person Carter trial. This paper is follow-up, not another independent trial.","compared":"Researchers checked the two diet groups at two years, including a year after the supported program ended.","found":"Average blood sugar rose above starting levels in both groups. The later results no longer met the study’s rule for saying the diets worked similarly.","meaning":"A short-term improvement may not last after support ends. This follow-up does not establish permanent diabetes control from either schedule."},"populationType":"human","timelineYear":2019,"cohort":"Carter’s 12- and 24-month reports follow the same randomized cohort (ACTRN12615000383561)."},{"id":"teong","author":"Teong et al.","group":"benefits","kind":"Human randomized trial","topics":["glucose","weight","adherence"],"year":"2023","title":"Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial","doi":"10.1038/s41591-023-02287-7","pmid":"37024596","url":"https://pubmed.ncbi.nlm.nih.gov/37024596/","takeaway":"A glucose-tolerance advantage at six months was absent at eighteen.","population":"209 adults at increased diabetes risk, allocated 2:2:1. Exact arm totals not extracted from the original full text.","comparison":"3 arms: intermittent early eating, daily calorie restriction, standard-care booklet.","protocol":"Three days weekly at 30% energy needs between 08:00–12:00 followed by 20 hours without food; six months support and 12 further follow-up.","result":"Primary mixed-meal glucose comparison favored intermittent early eating at six months (P=.03), but not at eighteen months. More fatigue was reported.","limitation":"Timing and energy restriction were combined. Long-term adherence and loss of the initial difference temper the claim.","access":"Original abstract; NCT03689608. Parent trial of the Bensalem autophagy substudy.","timelineTitle":"Do blood sugar benefits from fasting last?","timelineSummary":"An advantage at six months was no longer clear at eighteen months.","explainer":{"who":"209 adults at increased risk of type 2 diabetes, divided among three groups.","compared":"One group ate very little before noon on three days a week, one cut calories daily, and one received a weight-loss booklet. Diet support lasted six months, with a further year of follow-up.","found":"The intermittent plan improved the body’s handling of a test meal more at six months than daily calorie cutting. That advantage was no longer clear at eighteen months.","meaning":"The early difference did not establish a lasting advantage. The plan changed both food timing and amount, so their individual contributions are uncertain."},"populationType":"human","timelineYear":2023,"cohort":"Bensalem is an autophagy substudy of the Teong trial (NCT03689608)."},{"id":"timet","author":"Manoogian et al.","group":"benefits","kind":"Human randomized trial","topics":["glucose","cardiovascular"],"year":"2024","title":"Time-Restricted Eating in Adults With Metabolic Syndrome : A Randomized Controlled Trial","doi":"10.7326/m24-0859","pmid":"39348690","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11929607/","takeaway":"A small HbA1c improvement accompanied a personalized eating window.","population":"122 adults with metabolic syndrome randomized, 61 per arm; 108 completed (54 each).","comparison":"2 arms: standard care plus an 8–10-hour eating window versus standard care.","protocol":"Three months; medications could continue. Personalized windows shortened habitual eating duration.","result":"HbA1c difference −0.10 percentage points (95% CI −0.19 to −0.003).","limitation":"Small effect, complete-case analysis and unadjusted co-primary tests. Primary outcome changed from fasting glucose in December 2021; authors report this preceded analysis.","access":"Full text and reporting history; NCT04057339. Historical registry versions not exhaustively audited.","timelineTitle":"Can a shorter eating window improve blood sugar?","timelineSummary":"A three-month trial found a small improvement compared with standard care alone.","explainer":{"who":"122 adults with several diabetes or heart-health risk factors; 108 completed the study.","compared":"Half added an eight- to ten-hour eating window to their usual care. The other half continued usual care alone. The comparison lasted three months.","found":"The eating-window group had a small improvement in a blood test reflecting average blood sugar.","meaning":"The effect was small, and the study did not measure whether people avoided diabetes or heart disease. Changes to the study’s main test and missing results also need consideration."},"populationType":"human","timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"early","author":"Guo et al.","group":"benefits","kind":"Human randomized trial","topics":["glucose","weight"],"year":"2024","title":"A 5:2 Intermittent Fasting Meal Replacement Diet and Glycemic Control for Adults With Diabetes: The EARLY Randomized Clinical Trial","doi":"10.1001/jamanetworkopen.2024.16786","pmid":"38904963","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11193124/","takeaway":"An intensive meal-replacement program improved early diabetes measures.","population":"405 adults with early type 2 diabetes, 135 per arm; 332 completed.","comparison":"3 arms: 5:2 meal replacement, metformin, empagliflozin. Two medication comparators; no matched dietary control.","protocol":"16 weeks plus eight-week follow-up; intervention also replaced dinners on the other five days.","result":"HbA1c fell about 1.9 versus 1.6 versus 1.5 percentage points; weight about 9.7 versus 5.5 versus 5.8 kg.","limitation":"Tests a substantial dietary package, not fasting alone. Short duration cannot establish cure or lasting superiority to medication.","access":"Full text and flow. ChiCTR2000040656. Commercial funding from Beijing MetabolicControl Technology.","timelineTitle":"How does a meal-replacement fasting plan compare with medication?","timelineSummary":"A structured food program improved early diabetes measures, but the benefit cannot be assigned to fasting alone.","explainer":{"who":"405 adults with early type 2 diabetes, 135 in each of three groups. 332 completed the study.","compared":"A sixteen-week program combining meal replacements and two low-calorie days per week was compared with two diabetes medicines. The program also changed meals on the other days.","found":"The food-program group lost more weight and had a larger fall in average blood sugar during the trial.","meaning":"This was a whole food program, not a test of fasting alone. Its short-term results do not show permanent cure or justify changing medication without clinical advice."},"populationType":"human","timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"parr","author":"Parr et al.","group":"benefits","kind":"Human randomized trial","topics":["glucose","adherence"],"year":"2026","title":"Time-restricted eating versus dietetic guidance on glycaemic outcomes in adults at risk of type 2 diabetes: a non-inferiority randomised clinical trial","doi":"10.1007/s00125-026-06762-x","pmid":"42251202","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13424568/","takeaway":"Noninferiority at four months did not persist at twelve months.","population":"247 adults at diabetes risk: 124 time restriction, 123 dietetic guidance.","comparison":"2 active programs, each with five telehealth contacts in the first three months.","protocol":"Nine-hour eating window ending by 19:00 versus individualized dietary guidance; 12 months.","result":"HbA1c difference −0.02 percentage points (95% CI −0.07 to 0.03) at four months met the 0.10 noninferiority margin. At twelve months +0.05 (−0.02 to 0.11) did not.","limitation":"Both programs produced small glycemic changes. Noninferiority at one timepoint is not superiority or durable disease prevention.","access":"Full text; NCT04762251. Public research funding.","timelineTitle":"Can an eating window work as well as dietitian advice?","timelineSummary":"An early blood sugar comparison met the study’s target. The one-year comparison did not.","explainer":{"who":"247 adults at increased diabetes risk: 124 in the eating-window group and 123 receiving individual diet advice.","compared":"One group used a nine-hour eating window ending by 7 p.m. The other worked on its diet with professional guidance. Both received five support calls early in the study.","found":"At four months, the eating window met the study’s rule for working about as well on blood sugar. At twelve months, the results were too uncertain to reach that same conclusion.","meaning":"Blood-sugar changes were small in both groups. An early comparison does not establish lasting diabetes prevention."},"populationType":"human","timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"liver","author":"Wei et al.","group":"benefits","kind":"Human randomized trial","topics":["liver","weight","glucose"],"year":"2023","title":"Effects of Time-Restricted Eating on Nonalcoholic Fatty Liver Disease: The TREATY-FLD Randomized Clinical Trial","doi":"10.1001/jamanetworkopen.2023.3513","pmid":"36930148","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10024204/","takeaway":"Liver fat improved with calorie reduction; an eating window added no clear benefit.","population":"88 adults with obesity and nonalcoholic fatty liver disease: 45 time restriction, 43 daily calorie restriction.","comparison":"2 arms with the same calorie prescription; one active dietary control.","protocol":"08:00–16:00 window versus habitual meal timing for 12 months; MRI-measured liver triglyceride was primary.","result":"At twelve months, liver fat fell 6.9 versus 7.9 percentage points; between-arm difference +1.0 (95% CI −1.6 to 3.5; P=.45).","limitation":"Changes in average liver fat do not establish universal elimination of fatty liver, fibrosis reversal or fewer liver complications.","access":"Original abstract and full text; NCT03786523 / NCT04988230.","timelineTitle":"Does an eating window help reduce liver fat?","timelineSummary":"Liver fat fell with calorie cutting. Adding an eating window did not clearly help further.","explainer":{"who":"88 adults with obesity and excess fat in the liver: 45 in the eating-window group and 43 in the other diet group.","compared":"Both groups followed calorie targets for a year. One also ate only between 8 a.m. and 4 p.m.; the other kept its usual meal timing.","found":"Liver fat fell in both groups. Scans did not show a clear extra benefit from the eating window.","meaning":"Improvement in average liver fat does not mean fasting eliminates fatty liver in everyone. The trial did not establish fewer serious liver complications."},"populationType":"human","timelineYear":2023,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"moro","author":"Moro et al.","group":"populations","kind":"Human randomized trial","topics":["muscle","weight"],"year":"2016","title":"Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males","doi":"10.1186/s12967-016-1044-0","pmid":"27737674","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5064803/","takeaway":"Lean mass was maintained in a small resistance-training trial.","population":"34 resistance-trained men, 17 per arm.","comparison":"2 meal-timing arms; both performed resistance training with matched reported energy and macronutrients.","protocol":"Eight weeks; meals at 13:00/16:00/20:00 versus 08:00/13:00/20:00.","result":"Fat mass declined more with restricted timing (P=.0448); strength and fat-free mass were maintained in both arms. Testosterone and IGF-1 decreased in the restricted arm.","limitation":"Short, small, selected male sample. Reported intake is not fully controlled feeding; findings cannot establish muscle preservation during multiday fasting.","access":"Full text, methods and results; eight-week outcome only.","timelineTitle":"Can men maintain strength while eating in a shorter window?","timelineSummary":"Strength and lean mass were maintained in a small study of men who lifted weights.","explainer":{"who":"34 men who already trained with weights, seventeen in each group.","compared":"For eight weeks, both groups lifted weights and reported similar calories and nutrients. One ate its meals in eight hours; the other spread them over a longer day.","found":"The shorter-window group lost more fat. Both groups maintained strength and lean mass, the part of body weight that is not fat.","meaning":"This small study of trained men does not tell us what happens to muscle during multiday fasting or in older, frail or untrained people."},"populationType":"human","timelineYear":2016,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"haganes","author":"Haganes et al.","group":"populations","kind":"Human randomized trial","topics":["muscle","weight","glucose"],"year":"2022","title":"Time-restricted eating and exercise training improve HbA1c and body composition in women with overweight/obesity: A randomized controlled trial","doi":"10.1016/j.cmet.2022.09.003","pmid":"36198292","url":"https://pubmed.ncbi.nlm.nih.gov/36198292/","takeaway":"Combining exercise and time restriction helped secondary outcomes, not the primary test.","population":"131 women with overweight or obesity; original arm counts not extracted.","comparison":"4 arms: 10-hour eating window, high-intensity intervals, both, or no intervention. Three comparators for the combined program.","protocol":"Seven weeks; exercise three times weekly. Primary outcome: oral-glucose-tolerance area under the curve.","result":"Primary comparisons with control were nonsignificant (P=.36, .057 and .14). Combined treatment favored some secondary fat and HbA1c measures.","limitation":"Short duration and multiple outcomes; secondary findings should not overwrite a null primary outcome.","access":"Original indexed abstract; NCT04019860.","timelineTitle":"Does combining fasting and exercise improve blood sugar?","timelineSummary":"Some measures improved, but the main blood sugar test found no clear advantage.","explainer":{"who":"131 women with overweight or obesity, divided among four groups.","compared":"For seven weeks, the groups tried a ten-hour eating window, intense exercise three times a week, both together, or neither.","found":"The combined plan improved some body-fat and blood-sugar measurements. But the main test of how the body handled a sugary drink found no clear advantage.","meaning":"A few positive measurements do not turn the main negative result into a proven benefit. Longer studies are needed to understand lasting effects."},"populationType":"human","timelineYear":2022,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"heroes","author":"Manoogian et al.","group":"populations","kind":"Human randomized trial","topics":["glucose","cardiovascular","adherence"],"year":"2022","title":"Feasibility of time-restricted eating and impacts on cardiometabolic health in 24-h shift workers: The Healthy Heroes randomized control trial","doi":"10.1016/j.cmet.2022.08.018","pmid":"36198291","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9536325/","takeaway":"An eating window was feasible for selected firefighters working 24-hour shifts.","population":"150 randomized; 137 completed, 70 time restriction and 67 standard care.","comparison":"2 arms; both received Mediterranean-diet advice, one also targeted a 10-hour window.","protocol":"12 weeks; intervention participants shortened eating from about 14.1 to 11.1 hours on average.","result":"Reported benefits included VLDL particle size and selected cardiometabolic measures in participants with elevated baseline risk.","limitation":"Subgroup and secondary results do not establish a universal benefit for shift workers. Achieved windows differed from the target.","access":"Full text and flow; NCT03533023.","timelineTitle":"Can an eating window fit around 24-hour shifts?","timelineSummary":"Selected firefighters shortened their eating windows. Some health measures improved, especially in higher-risk groups.","explainer":{"who":"150 firefighters working 24-hour shifts joined; 137 completed the study.","compared":"Both groups received Mediterranean-diet advice. One also aimed to eat within ten hours each day for twelve weeks; the other did not add that target.","found":"People in the eating-window group shortened their eating day to about eleven hours on average. Some health measurements improved, especially in people starting with higher risk.","meaning":"This suggests the plan can fit some shift schedules. It does not establish the same benefit for every shift worker, and most did not achieve the exact ten-hour target."},"populationType":"human","timelineYear":2022,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"lister","author":"Lister et al.","group":"populations","kind":"Human randomized trial","topics":["weight","safety","adherence"],"year":"2024","title":"Intermittent Energy Restriction for Adolescents With Obesity: The Fast Track to Health Randomized Clinical Trial","doi":"10.1001/jamapediatrics.2024.2869","pmid":"39186288","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11348084/","takeaway":"Intermittent restriction did not outperform continuous restriction in adolescents.","population":"141 adolescents: 71 intermittent and 70 continuous restriction; 97 completed (43 and 54).","comparison":"2 intensive multidisciplinary programs; one active dietary comparator.","protocol":"52 weeks; both began with four weeks of very-low-energy intake before differing restriction schedules.","result":"BMI z score decreased by about 0.28 in each group, without a between-group advantage.","limitation":"Substantial attrition and intensive clinical support. Does not justify unsupervised adolescent fasting; psychological monitoring was part of care.","access":"Full text and flow; ACTRN12617001630303. Related eating-behavior reports reuse this cohort.","timelineTitle":"Does intermittent calorie cutting work better for teenagers?","timelineSummary":"It did not outperform daily calorie cutting in a year-long trial with intensive clinical support.","explainer":{"who":"141 teenagers with obesity: 71 in the intermittent group and seventy in the daily-diet group. Ninety-seven completed a year.","compared":"Both groups received intensive care from a clinical team and began with the same very-low-calorie phase. They then followed different calorie-cutting schedules.","found":"Both groups had similar improvements in body size relative to age and height. The intermittent schedule did not clearly work better.","meaning":"This was closely supported adolescent care, not evidence for teenagers fasting on their own. Many participants did not finish the year."},"populationType":"human","timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"hallo","author":"Houston et al.","group":"populations","kind":"Human randomized trial","topics":["muscle","weight","safety"],"year":"2026","title":"Caloric restriction and time-restricted eating in older adults with overweight or obesity: The Health, Aging, and Later-Life Outcomes Pilot Study","doi":"10.1093/gerona/glag061","pmid":"41766355","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13049596/","takeaway":"An older-adult pilot addresses feasibility, not frailty prevention.","population":"90 adults aged at least 60 with overweight or obesity; nine-month retention 92%. Exact allocation per arm not extracted.","comparison":"3 arms: prescribed 20% calorie restriction in person, remotely, or an 8-hour eating window.","protocol":"Nine months; actual calorie reduction in the calorie-restriction groups was much smaller than prescribed.","result":"Within-group weight changes: −4.4, −6.7 and −1.0 kg, respectively. Some functional measures improved; lean mass fell in calorie-restriction groups.","limitation":"Pilot was not powered to rank effectiveness. Within-group changes do not establish a between-group benefit or safety in frail adults.","access":"Full text; HALLO feasibility trial. Outcomes should be interpreted as exploratory.","timelineTitle":"How practical are eating windows for older adults?","timelineSummary":"A small trial tested feasibility and function. It could not establish which diet worked best.","explainer":{"who":"Ninety adults aged sixty or older with overweight or obesity. About 92% stayed in the nine-month trial.","compared":"Three groups tried calorie cutting with in-person support, calorie cutting with remote support, or an eight-hour eating window.","found":"Weight and some movement tests changed across the groups. The calorie-cutting groups also lost some lean tissue, which includes muscle and water.","meaning":"This was a small trial designed mainly to see whether the plans were practical. It could not reliably rank them or establish that they prevent frailty."},"populationType":"human","timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"wang","author":"Wang et al.","group":"populations","kind":"Human randomized trial","topics":["cognition"],"year":"2025","title":"Effects of 15:9 time-restricted eating on cognitive function and anthropometric parameters among the elderly with mild cognitive impairment: an assessor-blinded, pilot randomized controlled trial","doi":"10.1186/s12877-025-06788-7","pmid":"41310471","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12750691/","takeaway":"A small pilot found a cognitive-test signal that needs replication.","population":"46 older adults with mild cognitive impairment, 23 per arm.","comparison":"2 arms: 15:9 time restriction versus usual eating; outcome assessor blinded.","protocol":"12 weeks; cognitive and memory tests, with anthropometric measures.","result":"MoCA between-group difference 1.70 points (95% CI 0.46 to 2.94; P=.007); some memory measures improved.","limitation":"Small, short study with multiple tests. A test-score change does not establish prevention of dementia or lasting everyday functional improvement.","access":"Full text; ChiCTR2100052766.","timelineTitle":"Could an eating window help older people with memory problems?","timelineSummary":"Some test scores improved in a small pilot. Dementia prevention was not established.","explainer":{"who":"46 older adults with mild memory or thinking problems, 23 in each group.","compared":"One group ate within nine hours each day for twelve weeks. The other continued its usual eating pattern. Researchers then compared memory and thinking tests.","found":"The eating-window group improved on a general thinking test and some memory measures.","meaning":"This is an encouraging small pilot, not proof that fasting prevents dementia. The study did not establish lasting improvements in everyday independence."},"populationType":"human","timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"mcleod","author":"McLeod et al.","group":"populations","kind":"Human randomized trial","topics":["cognition","weight"],"year":"2026","title":"Impact of a 4-week time-restricted eating (16:8) intervention on working memory and attentional control in adult women: A randomized controlled pilot","doi":"10.1016/j.actpsy.2026.107510","pmid":"42520714","url":"https://pubmed.ncbi.nlm.nih.gov/42520714/","takeaway":"Repeated cognitive tests improved in both groups, without a fasting advantage.","population":"43 healthy women: 23 time restriction, 20 control.","comparison":"2 arms: 16:8 eating versus usual behavior; one control.","protocol":"Four weeks with weekly cognitive testing.","result":"Cognitive performance improved over repeated testing in both groups, without an intervention-specific effect; BMI declined with time restriction.","limitation":"Brief, small study in healthy women; practice effects and population differences limit comparison with cognitive-impairment trials.","access":"Original indexed abstract; full-text methods and attrition not extracted.","timelineTitle":"Does a shorter eating window improve memory and focus?","timelineSummary":"Healthy women improved with repeated testing in both groups. Fasting added no clear benefit.","explainer":{"who":"43 healthy adult women: 23 in the eating-window group and twenty in the comparison group.","compared":"For four weeks, one group used an eight-hour eating window and the other kept its usual habits. Both repeated memory and attention tests weekly.","found":"Both groups improved with repeated testing. The eating window did not add a clear memory or attention benefit.","meaning":"Practice can improve test scores even when a diet has no effect. This brief study does not settle what happens in older people or those with memory disorders."},"populationType":"human","timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"chen","author":"Chen et al.","group":"populations","kind":"Human observational cohort","topics":["cardiovascular","longevity","safety"],"year":"2025","title":"Association of eating duration less than 8 h with all-cause, cardiovascular, and cancer mortality","doi":"10.1016/j.dsx.2025.103278","pmid":"40849219","url":"https://pubmed.ncbi.nlm.nih.gov/40849219/","takeaway":"Short reported eating duration was associated with cardiovascular mortality; causality is unresolved.","population":"19,831 US adults from NHANES; median follow-up 8.1 years.","comparison":"Six observed eating-duration categories, with 12–14 hours as reference; zero randomized intervention groups.","protocol":"Eating duration inferred from two dietary recalls, linked to later mortality records.","result":"Under eight hours was associated with cardiovascular mortality: adjusted HR 2.35 (95% CI 1.39–3.98). Other mortality associations were not consistently robust.","limitation":"Two recalls do not identify a sustained intentional fasting regimen. Illness, lifestyle, measurement error and reverse causation can explain associations.","access":"Original peer-reviewed abstract; not merely the earlier conference headline. Full covariate and sensitivity tables not extracted.","timelineTitle":"Are short eating windows linked to heart-related deaths?","timelineSummary":"An observational study found a link, but could not show that intentional fasting caused it.","explainer":{"who":"19,831 US adults from an existing health survey, followed through records for about eight years on average.","compared":"Researchers estimated daily eating windows from two food recalls and compared later deaths across six eating-duration groups. They did not assign anyone to fast.","found":"People reporting very short eating windows had more heart-related deaths in the analysis.","meaning":"A link is not proof that fasting caused the deaths. Illness, other habits and inaccurate food recall may explain it, and two reported days do not establish a long-term fasting routine."},"populationType":"human","timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"bauersfeld","author":"Bauersfeld et al.","group":"cancer-clinical","kind":"Human randomized crossover","topics":["cancer","safety"],"year":"2018","title":"The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study","doi":"10.1186/s12885-018-4353-2","pmid":"29699509","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5921787/","takeaway":"A small chemotherapy pilot suggests symptom benefits, with substantial attrition.","population":"50 randomized (27 fasting first, 23 usual diet first); 34 analyzed (18 and 16).","comparison":"Two sequences; each patient received fasting and normocaloric periods during different chemotherapy cycles.","protocol":"60 hours around chemotherapy: 36 before and 24 after. Juice/broth permitted up to 350 kcal/day.","result":"Quality-of-life and fatigue deterioration was smaller in some fasting comparisons, particularly the fasting-first sequence.","limitation":"16/50 not analyzed; unblinded symptoms, sequence effects and accumulated chemotherapy toxicity complicate inference. No tumor-eradication or survival test.","access":"Full text and original Figure 1. Abstract calls 34 randomized; flow diagram establishes 50 randomized and 34 analyzed. NCT01954836.","timelineTitle":"Could short fasts ease chemotherapy fatigue?","timelineSummary":"A small study suggested some symptom benefits, but many participants were not included in the final analysis.","explainer":{"who":"Fifty people with breast or ovarian cancer were assigned to treatment schedules; 34 were included in the final analysis.","compared":"Patients tried periods of very little food around chemotherapy and periods of ordinary eating, in different orders. The low-food periods lasted sixty hours and allowed juice or broth.","found":"Some comparisons suggested less fatigue and a smaller drop in quality of life during the low-food periods.","meaning":"Many participants were not in the final analysis, and the order of treatments may matter. The study did not show that fasting kills tumors or extends life."},"populationType":"human","timelineYear":2018,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"dorff","author":"Dorff et al.","group":"cancer-clinical","kind":"Human nonrandomized pilot","topics":["cancer","safety","immune"],"year":"2016","title":"Safety and feasibility of fasting in combination with platinum-based chemotherapy","doi":"10.1186/s12885-016-2370-6","pmid":"27282289","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4901417/","takeaway":"A feasibility study cannot establish anticancer effectiveness.","population":"20 selected cancer patients: 6 at 24 hours, 7 at 48 hours, 7 at 72 hours.","comparison":"3 sequential duration cohorts; zero nonfasting control groups and no randomization.","protocol":"Around two cycles of platinum chemotherapy; 72-hour schedule included 48 hours before and 24 after. Rescue intake up to 200 kcal/day permitted.","result":"Fasting-attributed toxicities were grade 2 or lower. Differences in neutropenia (P=.17) and DNA damage (P=.08) were nonsignificant.","limitation":"Excluded vulnerable patients, including those with low BMI or substantial weight loss. Small uncontrolled comparisons do not establish efficacy or general safety.","access":"Full text; NCT00936364. Includes the clinical program reported preliminarily by Cheng.","timelineTitle":"How well do selected patients tolerate fasting during chemo?","timelineSummary":"A small supervised pilot tested feasibility. It could not establish general safety or cancer-treatment benefits.","explainer":{"who":"Twenty selected cancer patients: six assigned to a 24-hour fast, seven to 48 hours and seven to 72 hours.","compared":"Researchers tried different fasting lengths around chemotherapy, allowing small rescue amounts of food when needed. There was no group receiving chemotherapy without fasting.","found":"Reported problems attributed to fasting were generally mild or moderate. Differences in blood-cell damage and low white-cell counts were not clear enough to establish protection.","meaning":"The small study mainly asked whether this could be done in selected, monitored patients. It could not establish general safety or better cancer outcomes."},"populationType":"human","timelineYear":2016,"cohort":"Cheng’s preliminary human blood findings and Dorff’s later pilot concern NCT00936364; they are not independent clinical replications."},{"id":"degroot2015","author":"de Groot et al.","group":"cancer-clinical","kind":"Human randomized trial","topics":["cancer","safety"],"year":"2015","title":"The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study","doi":"10.1186/s12885-015-1663-5","pmid":"26438237","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4595051/","takeaway":"An early breast-cancer pilot measured blood toxicity, not cancer starvation.","population":"13 women with HER2-negative stage II/III breast cancer; 7 fasting, 6 control.","comparison":"2 arms: fasting versus normal healthy-diet guidance, both with chemotherapy.","protocol":"48-hour fast, from 24 hours before until 24 hours after chemotherapy.","result":"Some red-cell and platelet measures favored fasting; nonhematological toxicity did not differ. Blood-cell DNA damage was exploratory.","limitation":"Very small pilot with multiple laboratory outcomes. Does not establish survival benefit or efficacy of fasting alone.","access":"Full text; NCT01304251. Distinct from the later DIRECT trial.","timelineTitle":"Could a short fast reduce chemotherapy side effects?","timelineSummary":"A thirteen-person breast cancer pilot found changes in some blood tests, not broad proof of protection.","explainer":{"who":"Thirteen women with a particular type of breast cancer: seven in the fasting group and six in the comparison group.","compared":"Both groups received chemotherapy. One also fasted for 48 hours around treatment; the other followed normal healthy-eating guidance.","found":"Some blood-cell measurements looked better with fasting. Other treatment side effects did not clearly improve.","meaning":"Thirteen people are too few for strong treatment claims. Changes in blood tests do not show that fasting starves cancer or helps patients live longer."},"populationType":"human","timelineYear":2015,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"cheng","author":"Cheng et al.","group":"autophagy","kind":"Animal study with human pilot","topics":["immune","cancer","longevity"],"year":"2014","title":"Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression","doi":"10.1016/j.stem.2014.04.014","pmid":"24905167","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4102383/","takeaway":"Stem-cell regeneration in mice is not a demonstrated human immune-system reset.","population":"Mice: Figure 1B legend reports n=20, 1E n=12. Human Figure 1F has 1–5 observations per timepoint and 6 per fasting-duration group for the lymphoid/myeloid ratio.","comparison":"Mouse fasting versus fed chemotherapy conditions and IGF-1/PKA perturbations; human fasting-duration cohorts without a nonfasting control.","protocol":"Repeated 48-hour fasting cycles in mice; human preliminary 24- versus 72-hour fasting around chemotherapy.","result":"Mouse findings connect IGF-1/PKA signaling with hematopoietic stem-cell protection and regeneration; human findings were preliminary lymphocyte observations.","limitation":"Species, regimen and endpoint differ from ordinary human fasting. Stem-cell markers do not establish fewer infections or rejuvenation in people.","access":"Original author-hosted PDF, Figure 1 and 2016 correction checked. Figures 2D/3G labels were corrected from MPP to HSC+MPP. Human cohort overlaps Dorff.","timelineTitle":"Can fasting help the body rebuild immune cells?","timelineSummary":"Most evidence came from mice. The small human observations did not demonstrate an immune-system reset.","explainer":{"who":"Several mouse experiments, plus very small human blood-sample comparisons during chemotherapy. Human measurements varied from one to six people per fasting group and test.","compared":"Researchers compared fasting and feeding in mice and altered growth-related signals. The human observations compared fasting durations, without a separate nonfasting group.","found":"Fasting-related changes helped protect or rebuild blood-forming cells in mice. The human observations were preliminary.","meaning":"This does not establish a three-day immune-system reset in people. Blood-cell changes are different from proving fewer infections, better cancer outcomes or a younger immune system."},"populationType":"mixed","timelineYear":2014,"cohort":"Cheng’s preliminary human blood findings and Dorff’s later pilot concern NCT00936364; they are not independent clinical replications."},{"id":"choi","author":"Choi et al.","group":"populations","kind":"Animal study with human randomized pilot","topics":["immune","cognition"],"year":"2016","title":"A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms","doi":"10.1016/j.celrep.2016.05.009","pmid":"27239035","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4899145/","takeaway":"Promising autoimmune-disease biology, with only preliminary human evidence.","population":"60 people with relapsing-remitting multiple sclerosis, 20 per arm. Separate mouse experiments; Figure 3 used 5–6 mice/group.","comparison":"Human arms: control diet, ketogenic diet, one FMD cycle followed by Mediterranean diet. Two comparators; separate mouse diet/transfer controls.","protocol":"Human FMD lasted seven days, followed by six months Mediterranean eating; ketogenic arm lasted six months.","result":"Human quality-of-life signals accompanied mouse immune and myelin findings. Eight human relapses occurred: four control, one ketogenic, three FMD.","limitation":"Pilot was not a confirmatory relapse or disability trial. Subsequent diet confounds fasting attribution; mouse regeneration is not human cure.","access":"Original full-text human-results section and Figure 3; NCT01538355. FMD commercial interests disclosed.","timelineTitle":"Could a fasting-style diet help with multiple sclerosis?","timelineSummary":"A small human pilot found quality-of-life signals. Later diet changes make fasting’s contribution unclear.","explainer":{"who":"Sixty people with multiple sclerosis, a condition that damages nerve coverings, divided into three groups of twenty. Separate experiments used mice.","compared":"People tried usual eating, six months of a ketogenic diet, or one seven-day low-calorie diet followed by Mediterranean eating for six months.","found":"Some quality-of-life measures improved in the human diet groups. The mouse work also suggested changes in immune activity and nerve repair.","meaning":"This small human pilot did not establish a cure or reliable prevention of relapses. The later diet changes make it impossible to assign the results to the fasting-style week alone."},"populationType":"mixed","timelineYear":2016,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"goldhamer","author":"Goldhamer et al.","group":"prolonged","kind":"Human uncontrolled study","topics":["cardiovascular","safety"],"year":"2001","title":"Medically supervised water-only fasting in the treatment of hypertension","doi":"10.1067/mmt.2001.115263","pmid":"11416824","url":"https://pubmed.ncbi.nlm.nih.gov/11416824/","takeaway":"Large blood-pressure changes came from an uncontrolled residential program.","population":"174 adults with hypertension in one supervised center.","comparison":"One cohort with before/after measurements; zero separate control groups.","protocol":"About 10–11 days water-only fasting, preceded by food preparation and followed by 6–7 days low-fat, low-sodium plant-based refeeding.","result":"Average blood pressure fell approximately 37/13 mm Hg by the end of the combined program; about 90% were below 140/90.","limitation":"Cannot separate fasting, sodium reduction, weight loss, rest, medication changes and refeeding. No randomized comparison or long-term event outcome.","access":"Original abstract and author-hosted original Table 2; clinic-based study.","timelineTitle":"Can a supervised water-fasting program lower blood pressure?","timelineSummary":"Blood pressure fell in a residential program, but fasting’s effect could not be separated from other changes.","explainer":{"who":"174 adults with high blood pressure at one residential treatment center.","compared":"Everyone followed a supervised program including roughly ten to eleven days of water-only fasting, food preparation beforehand and a low-salt plant-based diet afterward. There was no comparison group.","found":"Blood pressure fell substantially by the end of the full program. About nine in ten ended below the study’s high-blood-pressure threshold.","meaning":"The result cannot separate fasting from reduced salt, rest, weight loss, medication changes or the later diet. It does not establish long-term benefit or home safety."},"populationType":"human","timelineYear":2001,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"salti","author":"Salti et al.","group":"populations","kind":"Human observational survey","topics":["glucose","safety","religious"],"year":"2004","title":"A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study","doi":"10.2337/diacare.27.10.2306","pmid":"15451892","url":"https://pubmed.ncbi.nlm.nih.gov/15451892/","takeaway":"Ramadan observations show why diabetes medication and fluid context matter.","population":"12,914 recruited; 12,243 analyzed across 13 countries: 1,070 type 1 and 11,173 type 2 diabetes.","comparison":"Observed Ramadan versus other-month histories; zero assigned intervention groups.","protocol":"Retrospective EPIDIAR survey; daytime religious fasting includes fluid abstention and changes in meals, sleep and medication.","result":"Severe hypoglycemia episodes/month were reported as 0.14 versus 0.03 in type 1, and 0.03 versus 0.004 in type 2 diabetes.","limitation":"Recall and confounding limit causal estimates. Religious daytime fasting is not equivalent to water-permitted multiday fasting or healthy-adult TRE.","access":"Original indexed abstract and recruitment/analyzed distinction; full individual-level data not reviewed.","timelineTitle":"What happens to blood sugar during Ramadan fasting?","timelineSummary":"People with diabetes reported more severe low-blood-sugar episodes during Ramadan than in other months.","explainer":{"who":"12,243 people with diabetes across thirteen countries were included in the analysis: 1,070 with type 1 and 11,173 with type 2 diabetes.","compared":"Researchers asked about eating, medicines and health during Ramadan and compared reported problems with other months. No one was randomly assigned to a diet.","found":"Severe low-blood-sugar episodes were reported more often during Ramadan than during other months.","meaning":"Ramadan changes food, drink, sleep and medication timing together. These findings in diabetes cannot be applied directly to healthy adults using a water-permitted eating window."},"populationType":"human","timelineYear":2004,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"tread","author":"Wilkinson et al.","group":"benefits","kind":"Human randomized trial","topics":["weight","adherence"],"year":"2026","title":"Time-Restricted Eating Promotes Weight Loss and Favorable Changes in Adipose in Obesity: The TREAD Randomized Control Trial","doi":"10.1002/oby.70228","pmid":"42229885","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13306140/","takeaway":"A recent trial found extra weight loss, with a reporting-history caveat.","population":"61 randomized; 52 completed, 26 per arm.","comparison":"2 arms: 10-hour eating window versus standard lifestyle counseling.","protocol":"12 weeks; behavioral support and self-monitoring.","result":"Weight changes −4.59 versus −1.68 kg; difference −2.91 kg (95% CI −4.21 to −1.60).","limitation":"Primary outcome changed from adipose catecholamine sensitivity to weight after the last participant visit; authors report the change preceded analysis. This reduces confidence in a strictly prespecified claim.","access":"Full text and linked protocol; NCT04916730. Outcome change dated July 26, 2023; final visit May 26, 2023.","timelineTitle":"Can a ten-hour eating window add to weight loss?","timelineSummary":"People lost more weight, but a late change to the trial’s main outcome makes the result less certain.","explainer":{"who":"61 adults started; 52 completed the twelve-week study, 26 in each group.","compared":"Researchers compared a ten-hour eating window with standard lifestyle advice.","found":"The eating-window group lost about 2.9 kg more weight on average.","meaning":"Researchers changed the trial’s main outcome to weight after the final participant visit, though they said analysis had not begun. That makes the finding less secure than a clearly planned test."},"populationType":"human","timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"wilhelmi","author":"Wilhelmi de Toledo et al.","group":"prolonged","kind":"Human uncontrolled study","topics":["cardiovascular","weight","safety"],"year":"2019","title":"Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects","doi":"10.1371/journal.pone.0209353","pmid":"30601864","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6314618/","takeaway":"A large supervised cohort describes experience, not comparative effectiveness.","population":"1,422 adults; duration groups in Table 1: 659, 530, 196 and 37.","comparison":"Four self-selected duration groups; zero randomized or nonfasting controls.","protocol":"Buchinger modified fasting, 200–250 kcal/day for 4–21 days, with activity and residential care.","result":"Weight, blood pressure and some metabolic markers improved; symptoms and adverse events were recorded.","limitation":"Selection, clinic setting, concurrent activities and follow-up limit causal and safety claims. Not water-only fasting; no demonstrated optimal duration.","access":"Full text. Table 1 sums to 1,422; a conflicting methods count was not used. Clinic affiliations disclosed.","timelineTitle":"What do people experience during a long modified fast?","timelineSummary":"A large supervised group reported weight and health changes. There was no nonfasting comparison group.","explainer":{"who":"1,422 adults at a supervised fasting clinic, choosing different program lengths.","compared":"People consumed small amounts of food, about 200–250 calories a day, for four to 21 days. Activity and residential care were also part of the program. There was no nonfasting group.","found":"Weight, blood pressure and some blood measurements improved. Symptoms and medical problems were recorded too.","meaning":"A large group is still not a controlled comparison. This was not water-only fasting, and the study cannot establish the best fasting length or safety outside the clinic."},"populationType":"human","timelineYear":2019,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"gabriel","author":"Gabriel et al.","group":"prolonged","kind":"Human uncontrolled secondary analysis","topics":["weight","muscle","safety"],"year":"2025","title":"Prolonged Water-Only Fasting Followed by a Whole-Plant-Food Diet Promotes Fat-Free Mass Recovery and Continued Fat Mass Loss in Adults With Overweight or Obesity","doi":"10.1002/osp4.70086","pmid":"40765844","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12322586/","takeaway":"Early lean-mass loss and later partial recovery complicate weight-loss claims.","population":"40 parent-cohort enrollees; 29 with complete DXA data analyzed.","comparison":"One repeated-measures cohort; zero independent controls.","protocol":"Median 14 days water-only fasting, six days refeeding, then approximately 45 days follow-up with a plant-based diet.","result":"Fat-free mass accounted for 74% of initial weight loss; after partial recovery, fat accounted for 67% of total loss at follow-up.","limitation":"DXA fat-free mass includes fluid and glycogen-related changes, not only muscle. Attrition and subsequent diet prevent a fasting-only interpretation.","access":"Full text and participant flow. TrueNorth clinic ownership interests disclosed.","timelineTitle":"How much weight lost during a long fast is body fat?","timelineSummary":"Early weight loss included substantial lean mass, which partly returned after eating resumed.","explainer":{"who":"Forty people enrolled in the larger program; 29 had complete body-composition scans for this analysis.","compared":"Researchers measured the same people before and after a supervised water fast, typically fourteen days, then after food returned and during later plant-based eating. There was no comparison group.","found":"Most early weight loss was measured as lean mass rather than fat. Some of that lean mass returned after eating resumed; fat accounted for more of the lasting loss.","meaning":"Lean mass includes water as well as muscle, so scan changes are not a direct measure of muscle loss. The fast and the later diet cannot be judged separately here."},"populationType":"human","timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"pfeifer","author":"Chaudhary et al.","group":"autophagy","kind":"Human and animal experiment","topics":["autophagy","muscle"],"year":"2022","title":"Intermittent fasting activates markers of autophagy in mouse liver, but not muscle from mouse or humans","doi":"10.1016/j.nut.2022.111662","pmid":"35660501","url":"https://pubmed.ncbi.nlm.nih.gov/35660501/","takeaway":"Liver and muscle markers did not respond alike.","population":"50 women in two randomized fasting protocols; mice, 8–16 per diet/fasting group.","comparison":"Human fasting at 70% versus 100% energy requirements; no nonfasting human arm. Mouse chow/high-fat diets crossed with fasting/ad-libitum conditions.","protocol":"Eight weeks; 24-hour fasts on three nonconsecutive days. Human muscle biopsies after 12 and 24 hours.","result":"Some mouse liver markers increased; muscle markers did not. Human muscle gene changes were mixed or reduced with weight loss.","limitation":"Static gene/protein measures do not quantify flux or establish onset. Mouse liver results cannot be assigned to human muscle or the whole body.","access":"Original indexed abstract; arm-specific human counts and all tissue denominators not extracted.","timelineTitle":"Does fasting change cell recycling in muscle?","timelineSummary":"Muscle and liver measurements responded differently. The findings do not establish a whole-body effect.","explainer":{"who":"Fifty women in two fasting programs, plus separate mouse experiments with eight to sixteen mice per group.","compared":"Women followed repeated 24-hour fasts with different total food amounts for eight weeks. There was no nonfasting human group. Mouse experiments compared fasting with ordinary feeding.","found":"Some recycling-related measurements rose in mouse liver, but muscle measurements in mice and people did not show the same pattern.","meaning":"A result from liver does not tell us what happens in muscle or the whole body. These gene and protein tests also do not measure the complete recycling process or locate its start time."},"populationType":"mixed","timelineYear":2022,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"pietrocola","author":"Pietrocola et al.","year":"2016","group":"autophagy","kind":"Mouse and cell experiments","populationType":"animal","topics":["cancer","autophagy","immune"],"title":"Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance","doi":"10.1016/j.ccell.2016.05.016","pmid":"27411589","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5715805/","takeaway":"In these mice, functioning tumor autophagy was needed for fasting to improve chemotherapy response.","timelineTitle":"Can cell recycling help cancer treatment work?","timelineSummary":"Fasting improved chemotherapy response in mice, but the benefit depended on cell recycling and immune cells.","population":"Mouse tumors and laboratory cells; no human fasting trial. Figure 1: at least 7 mice per group in immunocompetent comparisons, at least 5 per group in immune-deficient and Atg5-knockdown comparisons; one representative experiment of two. These are panel-specific denominators, not a total study enrollment.","comparison":"Four conditions within the principal tumor experiments: fed plus vehicle, fasted plus vehicle, fed plus chemotherapy, fasted plus chemotherapy. Comparisons repeated with functional versus impaired immunity and control versus Atg5-knockdown tumor cells. Separate experiments tested calorie-restriction-mimicking compounds.","protocol":"48-hour fasting followed by mitoxantrone or oxaliplatin in mice with palpable tumors. Tumor-growth follow-up; Figure 1 comparisons include days 27 and 31. This mouse fast caused approximately 20% reversible weight loss.","result":"Fasting improved chemotherapy-associated tumor control when tumor autophagy and T lymphocytes were functional. Atg5 knockdown or immune deficiency removed the additional benefit. Related compound experiments implicated extracellular ATP signaling and reduced regulatory T-cell suppression.","limitation":"Strong mechanistic controls in selected mouse models do not establish human efficacy, a safe fasting duration, or direct digestion of whole tumors by autophagy. A pathway required for immune-assisted treatment response is not proof that increasing it always helps.","access":"Original full text, Figure 1 caption and methods checked. Authors report randomized, blinded mouse experiments and prospective sample-size calculations. Supplementary panels have additional, distinct denominators.","explainer":{"who":"Mice with tumors and cells grown in the lab. The main mouse comparisons used at least five or seven mice per group, depending on the experiment. No people received fasting treatment.","compared":"Researchers compared usual feeding, fasting, chemotherapy, and fasting with chemotherapy. They repeated the tests after weakening either the mice’s immune response or the tumors’ ability to recycle material inside cells.","found":"Fasting helped chemotherapy slow tumor growth. That extra benefit disappeared when tumor-cell recycling or the relevant immune cells could not work properly.","meaning":"This supports a role for cell recycling in helping treatment work in some settings. It does not show that fasting alone clears cancer, or that the same effect occurs in people."},"timelineYear":2016,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"buono","author":"Buono et al.","year":"2023","group":"autophagy","kind":"Mouse and cell experiments","populationType":"animal","topics":["cancer","autophagy","immune"],"title":"Fasting-Mimicking Diet Inhibits Autophagy and Synergizes with Chemotherapy to Promote T-Cell-Dependent Leukemia-Free Survival","doi":"10.3390/cancers15245870","pmid":"38136414","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10741737/","takeaway":"A fasting-style diet helped chemotherapy in mice with leukemia; reduced tumor autophagy was part of the proposed explanation.","timelineTitle":"Can a fasting-style diet help leukemia treatment?","timelineSummary":"More mice survived without leukemia when diet and chemotherapy were combined. Reduced cell recycling helped explain the result.","population":"BCR-ABL B-ALL mouse models and mouse/human leukemia cell lines; no human treatment trial. Normal-weight survival experiment: 50 mice. Obese survival experiment: 20 mice. Additional drug, immune-depletion and tissue experiments used separate groups.","comparison":"Normal-weight experiment: 4 groups: usual diet plus vehicle (10), fasting-mimicking diet plus vehicle (12), usual diet plus vincristine (14), diet plus vincristine (14). Obese experiment: the same four treatment conditions, 5 mice each, on a high-fat background diet.","protocol":"Four weekly cycles of a 3-day mouse fasting-mimicking diet and weekly vincristine, beginning one week after leukemia-cell injection. Survival followed beyond 110 days. Cell experiments used reduced glucose and serum for 24–48 hours.","result":"Over half the normal-weight combination group survived beyond 110 days without leukemia symptoms; survival exceeded vincristine alone (P<.05). Diet alone did not significantly improve median survival (25 versus 23 days), although overall survival differed. Autophagy inhibition reproduced or strengthened treatment effects; CD8-cell depletion reversed leukemia-free survival.","limitation":"Preclinical disease and treatment models; no evidence of patient cure. Small groups, no blinding and no sample-size estimation. Results support inhibition of a tumor survival pathway in this setting, not a universal rule that fasting increases autophagy and therefore kills cancer.","access":"Original full text, Figures 1–3 and methods checked. Random group assignment reported. Valter Longo disclosed equity in L-Nutra; other authors reported no competing interests.","explainer":{"who":"Two main survival experiments involved 50 normal-weight mice and 20 mice with obesity, all with leukemia. Researchers also studied mouse and human cancer cells in the lab.","compared":"Four groups received ordinary food, a fasting-style diet, chemotherapy, or both diet and chemotherapy. In the 50-mouse experiment, the groups contained 10, 12, 14 and 14 mice.","found":"More than half the normal-weight mice given both treatments survived beyond 110 days without leukemia symptoms. The combination worked better than chemotherapy alone. Reduced recycling inside cancer cells helped explain the benefit.","meaning":"This is encouraging evidence for a treatment combination in mice. It shows why “more cell recycling is always better” is too simple. No patients were treated, and researchers knew which treatment each mouse received."},"timelineYear":2023,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"gates","author":"Gates et al.","year":"2026","group":"autophagy","kind":"Laboratory preprint · not peer reviewed","populationType":"lab","publicationStatus":"preprint","topics":["cancer","autophagy"],"title":"Starvation improves epithelial fitness by selectively extruding DNA damaged cells","doi":"10.64898/2026.09.01.748489","pmid":"42817929","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13621968/","takeaway":"Nutrient deprivation made lab-grown cell layers expel damaged cells through a process distinct from ordinary autophagic digestion.","timelineTitle":"Can hungry cell layers push out damaged cells?","timelineSummary":"Lab-grown cells expelled damaged neighbors. This early finding has not been demonstrated by fasting in people.","population":"Cultured canine kidney and human airway epithelial cell lines, with additional altered-cell experiments; no human participants or whole-animal fasting intervention. Figure 1B–C: 12 biological replicates, 36 imaging fields. Nutrient-addition/removal tests: 3 replicates, 9 fields. KRas-altered cell experiment: 5 replicates, 15 fields.","comparison":"Main two-condition comparison: complete growth medium versus nutrient-poor buffer. Additional controls separately removed or restored glucose, glutamine or serum, and altered p53, ATG5, autophagy initiation or lysosomal digestion. Imaging fields are subsamples, not independent people or animals.","protocol":"Microscopy during nutrient deprivation; main time course 4 hours, with nutrient-specific tests at 2 hours. Altered-cell experiments followed 12 hours. The checked manuscript is the September 24, 2026 preprint version.","result":"Cell extrusion increased within an hour, peaked around 2 hours and returned to baseline by 4 hours in the cultured model. DNA-damaged and KRas-altered cells were preferentially expelled. ATG5/LC3 machinery contributed, but canonical lysosomal digestion was dispensable; non-expelled cells showed ordinary autophagic recycling.","limitation":"Not peer reviewed. These are culture conditions, not a human fasting clock. The authors explicitly leave fasting-induced extrusion in mice and humans unresolved and note that the body maintains glucose production. Removing altered cells from a cultured layer is not demonstrated eradication of established human cancer.","access":"Original preprint full text, Figures 1–3 and discussion checked. Indexed as a preprint, not a completed peer-reviewed clinical study. Authors declared no competing interests.","explainer":{"who":"Layers of dog kidney cells and human airway cells grown in the lab. The main time-course test used 12 separate experimental repeats, photographed in 36 areas. No people or live animals fasted.","compared":"Researchers compared cells in their usual nutrient mixture with cells deprived of nutrients. They also added nutrients back and switched off different cell processes to investigate the cause.","found":"The deprived cell layers pushed out more damaged cells. This happened in a short wave. The expelled cells used some recycling-related machinery, but were not simply digested by the usual recycling process.","meaning":"This early report has not yet been reviewed by other scientists for journal publication. It does not show that fasting removes cancer in people. Its one-to-four-hour lab observations cannot tell someone how long to fast."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"song","author":"Song et al.","year":"2026","group":"cancer-mechanisms","kind":"Mouse experiments and human tissue observations","populationType":"mixed","topics":["cancer","immune"],"title":"Intermittent Fasting Reduces Taurine Availability and Promotes Antitumor Immunity Through PERK Attenuation-Associated Paraptosis-Like Cell Death in Colorectal Cancer","doi":"10.1002/advs.78107","pmid":"42839693","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13643236/","takeaway":"Fasting reduced bowel-tumor growth in mice through nutrient-stress and immune pathways; the human component did not test fasting treatment.","timelineTitle":"Can fasting help immune cells attack bowel cancer?","timelineSummary":"Mouse tumors grew less, with changes in a nutrient and immune activity. Human tissue observations did not test a fasting treatment.","population":"Apc-mutant and implanted colorectal-tumor mouse models plus human specimens. Main intestinal-tumor comparisons: 11–15 mice per group. Human tissue/survival cohort: 85 cases; separate matched tissue cohort: 23 patients. No randomized human fasting intervention.","comparison":"Principal mouse comparison: unrestricted feeding versus two weekly fasts. Four-group immunotherapy comparisons: ordinary feeding plus control antibody, ordinary feeding plus anti-PD-1, fasting plus control antibody, fasting plus anti-PD-1. MC38: 3–6 mice/group; CT26: 6/group. Further taurine-restoration, uptake-inhibition, CD8-depletion and gene-manipulation controls tested mechanism.","protocol":"Two nonconsecutive 24-hour fasts weekly with water available. Protocols differed by mouse model; implanted-tumor interventions began after inoculation. Human work compared tissue features and survival associations, not assigned diets.","result":"Fasting reduced tumor burden and was associated with lower taurine and greater CD8 immune activity. Taurine replacement weakened the benefit; CD8 depletion impaired it. PERK reduction produced paraptosis-like stress, and combinations with anti-PD-1 improved tumor-control patterns in mice.","limitation":"Small, model-specific animal groups and observational human associations. Tumor-control findings do not establish human survival benefit. Taurine was not measured in the same human cohort used for transporter, immune-cell and survival analyses. This mechanism is neither glycogen starvation nor proof of canonical autophagic tumor clearance.","access":"Original full text published October 6, 2026; Figures 1, 2, 4 and 7, methods and limitations checked. Full supplement denominator and outcome extraction remains incomplete.","explainer":{"who":"Mice with bowel tumors, alongside separate human tissue studies. The main mouse comparison used 11–15 per group. Human analyses included an 85-case tissue set and another set of matched samples from 23 patients.","compared":"Mice ate normally or fasted twice a week. Other groups also received an immune-based cancer treatment. Researchers added back a nutrient called taurine and altered immune cells to test what mattered.","found":"Tumors grew less in fasting mice, with signs of stronger immune attack. Restoring taurine weakened some benefits. Combining fasting with the immune treatment also produced encouraging tumor-control results.","meaning":"The patient samples offered clues, but no patients were assigned fasting as a treatment. The result concerns nutrient stress and immunity; it does not prove that ketones starve cancer or that cell recycling removes tumors in people."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"hoferspermidine","year":"2024","title":"Spermidine is essential for fasting-mediated autophagy and longevity","doi":"10.1038/s41556-024-01468-x","pmid":"39117797","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11392816/","author":"Hofer et al.","group":"autophagy","kind":"Human observations and cross-species experiments","populationType":"mixed","topics":["autophagy","longevity","immune"],"timelineTitle":"A natural molecule helped connect fasting with cell recycling","timelineSummary":"Spermidine rose during fasting; experiments in cells and other organisms tested its role in recycling and longevity.","takeaway":"A plausible fasting–autophagy pathway, without a proven human longevity benefit or universal timing rule.","population":"Four human sample cohorts: 109 enrolled; 63 with available samples; 23 from a prior alternate-day-fasting group; and a new small cohort with up to 18 serum samples per time point. Separate yeast, worm, fly, mouse and human-cell experiments.","comparison":"Human before/after or 12-versus-36-hour comparisons; no single randomized human longevity trial. Mechanistic experiments used fed/fasted, gene-disruption, inhibitor and rescue controls.","protocol":"Human protocols ranged from 12/36-hour sampling to multiday modified fasting with about 200–350 kcal/day. Animal and cellular protocols differed.","result":"Fasting increased spermidine in human samples. Blocking its synthesis or downstream processing impaired fasting-associated autophagy and selected health/lifespan effects in experimental organisms.","limitation":"Human metabolite measurements are not demonstrations of whole-body autophagy timing, longer life, or cancer clearance. Cohorts reuse earlier studies; assay-specific sample counts vary.","access":"Original full text, human cohort methods and Figure 1 checked. Multiple commercial interests in autophagy, supplements and fasting services disclosed.","explainer":{"who":"Human blood samples from four groups, alongside experiments in cells, insects, worms and mice.","compared":"Researchers measured a natural molecule called spermidine during fasting, then blocked its production in laboratory experiments.","found":"Spermidine rose in human samples. In experimental organisms, blocking the pathway reduced some recycling and health effects of fasting.","meaning":"This helps explain a possible mechanism. It does not tell a person when beneficial recycling starts or prove that fasting extends human life."},"timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"bahrms","year":"2025","title":"Fasting, ketogenic, and anti-inflammatory diets in multiple sclerosis: a randomized controlled trial with 18-month follow-up","doi":"10.1186/s40795-025-01156-5","pmid":"40836308","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12366206/","author":"Bahr et al.","group":"populations","kind":"Human randomized trial","populationType":"human","topics":["cognition","immune","adherence"],"timelineTitle":"Fasting did not beat a healthy diet on the main MS outcome","timelineSummary":"An 18-month trial found no clear advantage for new brain lesions, despite some promising secondary results.","takeaway":"The primary MRI outcome did not establish an advantage for fasting or ketogenic eating.","population":"105 people with relapsing-remitting multiple sclerosis: 34 standard healthy diet, 35 fasting, 36 ketogenic diet. 81 completed.","comparison":"3 randomized arms; an active healthy-diet comparator. Existing disease-modifying treatment was permitted. MRI and disability assessors were masked.","protocol":"18 months. Fasting arm combined seven-day fasts every six months with intermittent fasting six days weekly; ketogenic arm used 20–40 g carbohydrate/day.","result":"No between-group difference in new T2 brain lesions at 18 months. Some exploratory cognition, mood and biomarker outcomes favored particular diets.","limitation":"Attrition, background treatment, low new-lesion activity and multiple exploratory outcomes limit conclusions. No proof of disease reversal.","access":"Original full text, Table 1 and primary-outcome analysis checked. NCT03508414, registered retrospectively.","explainer":{"who":"105 people with multiple sclerosis, assigned to three diets; 81 completed 18 months.","compared":"A fasting program and a ketogenic diet were each compared with a standard healthy diet.","found":"Neither showed a clear advantage for the main measure: new brain lesions. Some other measurements were encouraging.","meaning":"Secondary benefits deserve further study, but should not replace the trial’s main result or be called an MS cure."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"jamesnight","year":"2024","title":"Health impacts of a remotely delivered prolonged nightly fasting intervention in stressed adults with memory decline and obesity: A nationwide randomized controlled pilot trial","doi":"10.1017/cts.2024.651","pmid":"39790469","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11713440/","author":"James et al.","group":"populations","kind":"Human randomized pilot","populationType":"human","topics":["cognition","adherence"],"timelineTitle":"Longer overnight fasting improved sleep, but not clearly memory","timelineSummary":"A small trial separated a favorable sleep result from uncertain cognitive benefits.","takeaway":"Sleep improved relative to control; a specific cognitive advantage was not established.","population":"58 adults with obesity, stress and perceived memory decline: 28 fasting, 30 health education. 49 completed, 22 and 27 respectively.","comparison":"2 randomized groups with comparable weekly staff contact; health education was the attention control.","protocol":"Eight weeks: a 14-hour overnight fast on six nights weekly, with no calories after 20:00.","result":"Sleep-quality score improved relative to control by 2.52 points (95% CI 0.74–4.30). Stress and everyday cognition improved over time without a significant group difference.","limitation":"Pilot without a prospective power calculation; subjective outcomes, selective population and nine withdrawals. No dementia-prevention endpoint.","access":"Original full text and participant counts checked. The reported retention percentage is inconsistent with 49/58; raw counts are preserved here.","explainer":{"who":"58 adults who reported memory concerns and stress and were living with obesity.","compared":"28 tried longer overnight fasting; 30 received health education with similar staff contact.","found":"Sleep improved more with fasting. The study did not establish an extra benefit for memory or stress.","meaning":"A sleep benefit is worth investigating, but is not evidence that fasting prevents dementia."},"timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"aweer","year":"2025","title":"Wernicke's Encephalopathy Following 40 Days of Water-Only Fasting: A Case Report","doi":"10.1002/ccr3.71049","pmid":"41132629","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12541668/","author":"Aweer et al.","group":"prolonged","kind":"Human adverse-event case report","populationType":"human","topics":["safety","cognition"],"timelineTitle":"A very long water fast was followed by serious vitamin deficiency","timelineSummary":"One man developed confusion, walking problems and double vision after a 40-day fast.","takeaway":"A case illustrates a potential severe harm, without estimating how commonly it occurs.","population":"One 36-year-old man; no comparison group.","comparison":"Clinical history, examination, imaging and response to treatment; no randomized or observational control cohort.","protocol":"Presentation after a reported 40-day water-only fast; subsequent intravenous thiamine and electrolyte treatment.","result":"Wernicke’s encephalopathy was diagnosed from symptoms and MRI findings. Substantial improvement followed treatment.","limitation":"One case cannot quantify risk or determine a safe duration for others. It demonstrates why missing nutrients and refeeding require attention.","access":"Original 2025 indexed abstract checked; detailed full-text nutritional history not extracted.","explainer":{"who":"One previously reported 36-year-old man after a 40-day water-only fast.","compared":"Doctors evaluated his symptoms and scans, then followed his response to treatment.","found":"He had a serious brain disorder linked to vitamin B1 deficiency and improved after vitamin and electrolyte treatment.","meaning":"Longer fasting is not automatically better. This case shows a possible severe harm, rather than how often it happens."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"xieglycogen","year":"2021","title":"Glycogen metabolism is dispensable for tumour progression in clear cell renal cell carcinoma","doi":"10.1038/s42255-021-00367-x","pmid":"33758423","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7995639/","author":"Xie et al.","group":"cancer-mechanisms","kind":"Cells, mice and human tissue","populationType":"mixed","topics":["cancer"],"timelineTitle":"Do kidney tumors always need stored sugar?","timelineSummary":"Removing the ability to make or use glycogen did not stop these kidney-cancer models growing.","takeaway":"Glycogen dependence was absent in the tested kidney-cancer models.","population":"Human kidney-cancer cell lines; 20 matched human tumor/normal-tissue pairs; public data from 428 tumors and 66 normal samples. Mouse experiments used 7 tumor pairs for GYS1 deletion and 10 pairs for PYGB/PYGL deletion.","comparison":"Control and gene-deleted tumors grew on opposite flanks of each mouse. Cell experiments compared intact versus impaired glycogen synthesis/breakdown across glucose and oxygen conditions; drug and vehicle controls were also used.","protocol":"Genetic disruption, metabolic tracing, culture-growth assays and mouse tumor follow-up. No human fasting intervention.","result":"Blocking glycogen synthesis or breakdown did not substantially impair growth in these models, despite abundant tumor glycogen.","limitation":"Established kidney-cancer models cannot represent every cancer or disease stage. Absence of dependence here does not invalidate positive findings elsewhere.","access":"Original full text, methods and Figure 4 checked; matched tumor pairs are not independent treatment participants.","explainer":{"who":"Kidney-cancer cells, human tissue samples and mice. The two main mouse tests compared seven and ten pairs of tumors.","compared":"Researchers disabled either sugar storage or release from storage and compared the altered tumors with control tumors in the same mice.","found":"The tumors kept growing despite the changes to glycogen, the stored form of sugar.","meaning":"Some tumors can cope without glycogen. This directly challenges a claim that every cancer cell needs it to survive."},"timelineYear":2021,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"chenglycogen","year":"2020","title":"GYS1 induces glycogen accumulation and promotes tumor progression via the NF-κB pathway in Clear Cell Renal Carcinoma","doi":"10.7150/thno.46825","pmid":"32802186","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7415807/","author":"Chen et al.","group":"cancer-mechanisms","kind":"Cells, mice and human tissue","populationType":"mixed","topics":["cancer"],"timelineTitle":"A sugar-storage protein helped some kidney tumors grow","timelineSummary":"Reducing GYS1 slowed laboratory tumors, but the protein’s signaling role complicates the fuel explanation.","takeaway":"Targeting a glycogen-related protein showed promise without proving glycogen starvation.","population":"306 surgical kidney-cancer cases; separate molecular analyses included 24 paired samples and 12 protein-analysis pairs. Mouse methods describe five animals in the experimental groups, without a fully reconciled total across experiments.","comparison":"High versus low tissue expression; GYS1 overexpression or silencing versus vector/scrambled controls in cells and mice. Additional sunitinib combination comparisons.","protocol":"Observational tissue follow-up and gene manipulation; mouse tumors assessed over four weeks. No dietary treatment in patients.","result":"Higher GYS1 tracked worse prognosis. Manipulating it changed tumor growth and NF-κB signaling; silencing increased drug sensitivity in cells.","limitation":"The authors explicitly did not establish that tumor growth depended on glycogen as fuel. Different models and gene effects may explain disagreement with Xie’s study.","access":"Original full text, human cohort, mouse methods and stated limitations checked. Mouse allocation wording remains ambiguous.","explainer":{"who":"Tissue records from 306 people with kidney cancer, plus cells and mice. Patients were not assigned fasting.","compared":"Researchers raised or lowered a protein involved in storing sugar, then compared growth with control cells and tumors.","found":"Lowering the protein slowed growth in these experiments. Higher levels in patient tumors were associated with worse outcomes.","meaning":"The protein also affects growth signals. This does not show that fasting empties tumors of glycogen or kills them."},"timelineYear":2020,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"zhuogys1","year":"2026","title":"Glycogen synthase 1 promotes breast cancer progression by promoting IκBα ubiquitination and degradation independent of its canonical enzyme function","doi":"10.1186/s12964-026-02728-z","pmid":"41709237","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13020142/","author":"Zhuo et al.","group":"cancer-mechanisms","kind":"Mouse and cell experiments","populationType":"animal","topics":["cancer"],"timelineTitle":"A cancer protein mattered for more than storing sugar","timelineSummary":"Removing GYS1 slowed breast-cancer growth, while other ways of lowering glycogen did not.","takeaway":"A glycogen-related protein’s growth effect was separable from its sugar-storage function.","population":"Mouse and human breast-cancer cell lines. Tumor-growth comparison: 5 mice per group; lung-metastasis comparison: 4 per group. Cell-assay denominators vary by panel.","comparison":"GYS1 deletion versus control; separate deletion of GBE1/GYG1 and drug inhibition of glycogen synthesis; rescue experiments and signaling controls.","protocol":"Gene manipulation and mouse tumor experiments; lung-metastasis assessment at 21 days. No patient fasting trial.","result":"GYS1 deletion reduced growth and migration. Other glycogen-lowering interventions did not reproduce this. Experiments implicated a scaffolding role in NF-κB signaling.","limitation":"Small, model-specific experiments. A result from deleting a protein cannot automatically be attributed to depletion of its metabolic product.","access":"Original 2026 full text, Figures 1–4 and methods checked. Laboratory subsamples are not human participants.","explainer":{"who":"Breast-cancer cells and mice, including five mice in each main tumor-growth group.","compared":"Researchers removed a sugar-storage protein, then tested other ways to reduce stored sugar.","found":"Removing the protein slowed cancer growth. Lowering glycogen through the other methods did not have the same effect.","meaning":"The protein’s separate signaling job mattered. A protein linked to glycogen is not, by itself, proof that cancer depends on glycogen for fuel."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"kaluba","year":"2025","title":"An alternative route for β-hydroxybutyrate metabolism supports cytosolic acetyl-CoA synthesis in cancer cells","doi":"10.1038/s42255-025-01366-y","pmid":"40921754","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12552118/","author":"Kaluba et al.","group":"cancer-mechanisms","kind":"Mouse and cell experiments","populationType":"animal","topics":["cancer"],"timelineTitle":"Some cancers used ketones to build new cells","timelineSummary":"Tracing experiments found a route from ketones to the building materials needed for tumor growth.","takeaway":"Ketones can support tumor metabolism, including through an alternative synthesis pathway.","population":"Cancer cell lines and male mice. Pancreatic tumors implanted in the pancreas: five genotype groups of 8, 7, 7, 8 and 8 mice. Tracing experiments used 3 mice per knockout comparison.","comparison":"Control versus disrupted ketone-processing genes; normal versus restricted calories in melanoma experiments. Cell tests varied glucose, fats and ketone availability.","protocol":"Isotope tracing, gene deletion and tumor-growth experiments. Main culture work used 5 mM β-hydroxybutyrate; mouse tracing lasted 6.5 hours.","result":"Ketone carbon supplied cytosolic acetyl-CoA and lipids. Disrupting ketone-processing routes reduced growth in selected pancreatic and calorie-restricted melanoma models.","limitation":"A mechanistic demonstration, not a patient diet trial. It establishes capability in tested tumors, not that every ketogenic diet worsens cancer.","access":"Original full text, main Figures 1–4 and panel-specific mouse counts checked.","explainer":{"who":"Cancer cells and mice with pancreatic tumors or melanoma. One pancreatic experiment used five groups totaling 38 mice.","compared":"Researchers tracked labeled ketones and disabled different ways tumors could process them.","found":"Some tumors used ketones to make material for new cells. Blocking that processing hindered growth.","meaning":"Switching the body toward ketones does not guarantee that a tumor loses its fuel supply."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"jiangbhb","year":"2025","title":"β-Hydroxybutyrate promotes cancer metastasis through β-hydroxybutyrylation-dependent stabilization of Snail","doi":"10.1038/s41467-025-61541-3","pmid":"40675949","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12271565/","author":"Jiang et al.","group":"cancer-mechanisms","kind":"Human observations and animal experiments","populationType":"mixed","topics":["cancer"],"timelineTitle":"A ketone helped pancreatic cancer spread in mice","timelineSummary":"The effect involved a growth-related protein; patient observations did not establish a diet effect.","takeaway":"β-hydroxybutyrate promoted metastasis in these pancreatic-cancer models.","population":"Human serum analyses included 68 pancreatic-cancer cases; separate tissue analyses included 50. Main mouse metastasis panels used 5 animals per group; cell assays commonly used 3 biological samples.","comparison":"BHB versus vehicle, with genetic and drug controls affecting Snail and CBP. Patient analyses compared ketone levels and disease characteristics observationally.","protocol":"Metabolic profiling, cell-migration assays and mouse metastasis experiments; no randomized human fasting or ketogenic diet.","result":"BHB stabilized the Snail protein and increased metastasis in tested models. Interfering with that pathway reduced the effect and improved gemcitabine combinations.","limitation":"Patient associations can reflect the disease itself. Animal supplementation and engineered tumors do not establish the effect of fasting on patient survival.","access":"Original full text, Figures 1, 2 and 6 and animal methods checked. Panel denominators should not be added as unique study enrollment.","explainer":{"who":"People’s blood and tissue samples, cancer cells, and mice. Main mouse comparisons used five animals per group.","compared":"Researchers added a ketone and tested ways to block its effects on a protein involved in cancer spread.","found":"The ketone helped pancreatic-cancer cells spread in the tested models.","meaning":"Ketones can have effects beyond providing energy. This finding warrants caution, but does not show that fasting causes cancer to spread in people."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"mashinchian","year":"2025","title":"β-Hydroxybutyrate promotes chemoresistance and proliferation in breast cancer cells","doi":"10.1016/j.bbrep.2025.102217","pmid":"40917722","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12409806/","author":"Mashinchian et al.","group":"cancer-mechanisms","kind":"Laboratory cell experiments","populationType":"lab","topics":["cancer"],"timelineTitle":"A ketone made some breast-cancer cells harder to treat","timelineSummary":"Cells exposed to BHB became more resistant to one chemotherapy drug in laboratory cultures.","takeaway":"Ketone exposure increased resistance to fluorouracil in two cell models.","population":"Human MCF7 and canine CF41.Mg cancer cell lines, grown in flat cultures and three-dimensional clusters. Main viability assays report three independent experiments; no people or live-animal treatment.","comparison":"Untreated cells, BHB exposure, fluorouracil alone, and BHB before or after fluorouracil, under different glucose conditions.","protocol":"Cell viability, migration and cluster-size measurements, principally over 48–72 hours.","result":"BHB pretreatment increased viability relative to fluorouracil alone and enlarged three-dimensional clusters in both cell lines.","limitation":"Two cell lines and one drug cannot establish clinical resistance or the effect of a ketogenic diet. Replicate reporting differs by assay.","access":"Original full text and figure captions checked; culture repeats are not patient numbers.","explainer":{"who":"One human and one dog cancer-cell line grown in the laboratory. No patients took part.","compared":"Cells received chemotherapy with or without prior exposure to the ketone BHB.","found":"More cells survived treatment after BHB exposure in these experiments.","meaning":"This is another reason to test ketones by cancer and treatment type. It cannot predict what will happen to a person who fasts."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"wangketones","year":"2026","title":"Conditional dependency of oncogenic KRAS in driving ketone body catabolism and pancreatic cancer growth","doi":"10.1016/j.jbc.2026.113332","pmid":"42447995","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13519632/","author":"Wang et al.","group":"cancer-mechanisms","kind":"Cells, mice and human tissue","populationType":"mixed","topics":["cancer"],"timelineTitle":"Pancreatic tumors could switch on ketone use","timelineSummary":"A cancer mutation and additional signals together helped cells turn ketones into usable energy.","takeaway":"Ketone use depended on both tumor genetics and the surrounding signals.","population":"Human pancreatic-cancer cell lines, mouse tumors and human tissue observations. Main mouse experiment: 3 engineered-cell groups, 5 animals each. Human cohort denominator not independently extracted.","comparison":"Control, restored normal OXCT1 and a modified OXCT1 protein; cell tests combined BHB with or without IGF1 and altered KRAS/SUCLA2 signaling.","protocol":"Cell experiments included 2 mM BHB for 48 hours. Mouse tumors harvested at day 21.","result":"Cooperating signals increased ketone breakdown, acetyl-CoA, ATP and tumor growth. KRAS mutation alone was insufficient.","limitation":"Preclinical mechanism; human tissue trends require validation. No patient fasting intervention or survival comparison.","access":"Original 2026 full text, tumor-growth figure and animal methods checked. An antibody-supplier equity interest was disclosed.","explainer":{"who":"Pancreatic-cancer cells and mice; the main growth test used three groups of five mice.","compared":"Researchers changed the machinery and signals that let cancer cells process ketones.","found":"Under particular conditions, cells used ketones to support energy production and growth.","meaning":"Cancer fuel use can adapt. A ketone-rich environment is not automatically a starvation environment for cancer."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"zengbladder","year":"2026","title":"Ketogenic Diet and β-Hydroxybutyrate Suppress Bladder Cancer Growth and Enhance Anti-PD-L1 Immunotherapy Efficacy","doi":"10.1111/cas.70447","pmid":"42274090","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13394661/","author":"Zeng et al.","group":"cancer-mechanisms","kind":"Mouse and cell experiments","populationType":"animal","topics":["cancer","immune"],"timelineTitle":"Ketones helped bladder-cancer treatment in mice","timelineSummary":"A ketogenic diet or BHB slowed tumors and strengthened an immune-based treatment in this model.","takeaway":"Ketogenic interventions improved tumor control in a specific bladder-cancer model.","population":"Mouse MB49 tumors and bladder-cancer cell lines. Initial diet comparison: 6 mice per group. Combination-experiment animal totals were not clearly specified in the checked Figure 7 caption.","comparison":"Normal versus ketogenic diet. Separate comparisons added BHB, anti-PD-L1 treatment, or their combinations, with normal-diet/control-treatment comparators.","protocol":"Diet began four days after tumor implantation; initial growth measurements covered two weeks. Additional cell and immune experiments investigated mechanism.","result":"Diet and BHB reduced tumor growth, increased tumor-cell stress, and enhanced anti-PD-L1-associated control and immune-cell activity.","limitation":"Small animal experiments; no human treatment or survival trial. Benefits need not arise from simple sugar starvation.","access":"Original 2026 full text, Figures 1 and 7 and methods checked. Unresolved combination-group denominators are retained explicitly.","explainer":{"who":"Mice with bladder tumors and cancer cells in the lab. The first diet comparison used six mice per group.","compared":"Researchers tested ordinary food, a ketogenic diet, added ketones, and combinations with an immune-based cancer treatment.","found":"Tumors grew less, and the treatment combinations produced encouraging results.","meaning":"This is positive laboratory evidence worth following. It does not establish a cancer treatment for people or a universal ketone effect."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"bahrami","year":"2024","title":"Fasting mimicking diet during neo-adjuvant chemotherapy in breast cancer patients: a randomized controlled trial study","doi":"10.3389/fnut.2024.1483707","pmid":"39703333","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11656309/","author":"Bahrami et al.","group":"cancer-clinical","kind":"Human randomized trial","populationType":"human","topics":["cancer","safety"],"timelineTitle":"A fasting-style diet showed promise during breast chemotherapy","timelineSummary":"A 44-person trial found better tumor response and some fewer severe side effects, with important caveats.","takeaway":"A small trial reported favorable response and toxicity results for a combined diet-and-supplement program.","population":"44 people with HER2-negative breast cancer, 22 per arm; diabetes excluded.","comparison":"2 arms: chemotherapy plus modified FMD and 2 g omega-3, versus chemotherapy with regular diet. One usual-diet control; no omega-3-only arm.","protocol":"Eight three-week chemotherapy cycles. Full methods describe four dietary days per cycle: about 1,100 kcal on day 1 and 500 on days 2–4.","result":"Table 5: high pathological response in 16/22 versus 9/22; imaging response in 15/22 versus 8/22. Severe vomiting: 3/22 versus 12/22; severe neutropenia: 5/22 versus 10/22. No survival endpoint established.","limitation":"Small single-center trial, multiple outcomes, and omega-3 cointervention. Table 5 gives P=.03 for response comparisons while prose gives .01; neither should be silently substituted.","access":"Original full text, randomization, intervention and Tables 2 and 5 checked. Registry IRCT20171227038099N1; reporting discrepancies retained.","explainer":{"who":"44 people receiving chemotherapy for breast cancer, randomly divided into two groups of 22.","compared":"One group added a low-calorie diet around treatment and omega-3 supplements. The other continued its regular diet.","found":"More people in the diet group had a strong tumor response, and some severe side effects were less frequent.","meaning":"Encouraging, but small and not a survival study. The supplements and reporting inconsistencies make the result harder to interpret."},"timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"ligoriosurvival","year":"2024","title":"Adding fasting-mimicking diet to first-line carboplatin-based chemotherapy is associated with better overall survival in advanced triple-negative breast cancer patients: A subanalysis of the NCT03340935 trial","doi":"10.1002/ijc.34701","pmid":"37615485","url":"https://pubmed.ncbi.nlm.nih.gov/37615485/","author":"Ligorio et al.","group":"cancer-clinical","kind":"Human nonrandomized comparison","populationType":"human","topics":["cancer"],"timelineTitle":"Longer survival was observed in a small fasting-diet group","timelineSummary":"Fourteen women receiving diet plus chemotherapy lived longer than a separate comparison group; selection could explain part of the difference.","takeaway":"A favorable survival association requires confirmation in a randomized trial.","population":"14 advanced triple-negative breast-cancer patients from NCT03340935; 76 consecutive patients treated outside that diet group.","comparison":"2 nonrandomized cohorts: cyclic FMD plus carboplatin-gemcitabine versus carboplatin-based chemotherapy alone. Statistical adjustment and matching do not recreate randomization.","protocol":"Trial-cohort subanalysis with overall-survival follow-up. Companion to the broader Vernieri cohort, not an independent replication.","result":"Median survival 30.3 versus 17.2 months; adjusted hazard ratio 0.40 (95% CI 0.19–0.86).","limitation":"Only 14 diet participants, treatment/selection differences and residual confounding. Association does not establish that fasting caused longer survival.","access":"Original indexed abstract checked; full-text allocation history and detailed baseline balance not extracted.","explainer":{"who":"14 people receiving a fasting-style diet with chemotherapy, compared with 76 other people receiving chemotherapy.","compared":"The groups were selected through different care pathways, rather than assigned randomly.","found":"Survival was longer in the diet group, including after statistical adjustments.","meaning":"This is a meaningful positive signal, but differences between the patients could contribute. A randomized survival trial is needed."},"timelineYear":2024,"cohort":"Ligorio’s 14-patient survival comparison is a subanalysis of NCT03340935, the broader trial reported by Vernieri; these are overlapping publications."},{"id":"breakfast","year":"2025","title":"Early downmodulation of tumor glycolysis predicts response to fasting-mimicking diet in triple-negative breast cancer patients","doi":"10.1016/j.cmet.2024.11.004","pmid":"39694040","url":"https://pubmed.ncbi.nlm.nih.gov/39694040/","author":"Ligorio et al.","group":"cancer-clinical","kind":"Human phase II study","populationType":"human","topics":["cancer"],"timelineTitle":"A fasting-style diet was tested before breast-cancer surgery","timelineSummary":"Thirty patients received the diet with chemotherapy; tumor changes were promising but the abstract provides no usual-diet comparison.","takeaway":"BREAKFAST provides a clinical and mechanistic signal, with comparator limits.","population":"30 early-stage triple-negative breast-cancer patients in the BREAKFAST trial, NCT04248998.","comparison":"Registry specifies 2 randomized experimental arms: chemotherapy plus FMD, with or without metformin. Both received FMD; no chemotherapy-only diet control. Published arm-specific numbers are not supplied in the checked abstract.","protocol":"Five-day severely calorie-restricted cycles every three weeks. Tumor response was primary; longer-term outcomes and tumor molecular analyses were also reported.","result":"Authors report favorable pathological complete response and longer-term outcomes. Responding tumors showed early reductions in glycolysis-related activity. Exact response numerator not extracted from the checked source.","limitation":"Small cohort; no estimated benefit over a matched standard-diet arm established here. A molecular predictor does not prove glycogen depletion or a ketone-starvation mechanism.","access":"Original indexed abstract and NCT04248998 registry checked. Full article, response counts and historical registry amendments remain incompletely extracted.","explainer":{"who":"30 people with early triple-negative breast cancer receiving chemotherapy before surgery.","compared":"The registered groups both received chemotherapy and the fasting-style diet; one also received metformin. There was no usual-diet group.","found":"They reported encouraging responses. Tumors that responded showed early changes in how they processed sugar.","meaning":"The available summary cannot tell us how much benefit the diet added. Chemotherapy was also being given, and complete study details still need checking."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"gabriellymphoma","year":"2024","title":"Prolonged water-only fasting in the management of low-grade follicular lymphoma: a case series","doi":"10.1186/s13256-024-04609-w","pmid":"38956708","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11221076/","author":"Gabriel et al.","group":"cancer-clinical","kind":"Human case series","populationType":"human","topics":["cancer","safety"],"timelineTitle":"Lymphoma improved in three reported fasting cases","timelineSummary":"Scans improved after prolonged fasting and dietary changes, but three cases cannot establish the cause.","takeaway":"Positive case observations support investigation, not a demonstrated lymphoma treatment.","population":"3 adults aged 49, 50 and 56 with low-to-intermediate-grade follicular lymphoma. No control group.","comparison":"Before-and-after clinical observations. Fasting was combined with refeeding and a whole-plant-food diet; prior disease and treatment histories differed.","protocol":"Supervised prolonged fasts, including 18- and 21-day periods, with some repeated interventions and subsequent oncology follow-up.","result":"Lymph-node size and imaging activity decreased. One patient developed potassium of 2.9 mmol/L and received vegetable broth during the final fasting days.","limitation":"Follicular lymphoma can fluctuate or regress during observation. Three selected cases, combined interventions and no control cannot establish efficacy, safety rates or a cancer-clearing mechanism.","access":"Original full text and case histories checked. The first case’s broth means the entire reported fast was not strictly water-only.","explainer":{"who":"Three people with a type of lymphoma that can grow slowly and sometimes change during observation.","compared":"Doctors compared scans before and after prolonged fasting and a plant-food diet. There was no comparison group.","found":"Their scans improved. One person developed low potassium and needed broth during the fast.","meaning":"These cases deserve study, but cannot tell us whether fasting caused the improvement or how safe it would be for others."},"timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"swift","year":"2026","title":"A feasibility randomised controlled trial of water-only fasting prior to CAPOX chemotherapy for stage 2/3 colorectal cancer","doi":"10.1186/s40814-026-01848-0","pmid":"42237427","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13449517/","author":"Herbert et al.","group":"cancer-clinical","kind":"Human randomized feasibility trial","populationType":"human","topics":["cancer","adherence","safety"],"timelineTitle":"Could people fast before bowel-cancer chemotherapy?","timelineSummary":"Most of the six fasting participants followed the plan; the trial was too small to establish treatment benefits.","takeaway":"A 2026 feasibility report supports further testing, not an efficacy conclusion.","population":"79 screened, 44 eligible, 12 randomized: 6 fasting and 6 control. Five fasting participants remained for cycles 2 and 3.","comparison":"2 arms: 36-hour water-only fasting before CAPOX versus standard dietary advice. Concealed online randomization; laboratory analyses masked.","protocol":"Fasting before the first three chemotherapy cycles. Primary outcomes concerned recruitment, retention, adherence and acceptability.","result":"All six followed the first-cycle fast; five continued and adhered in later cycles. Recruitment was difficult, and some viewed fasting as an additional burden.","limitation":"Twelve participants cannot establish tumor control, survival benefit or reliable toxicity differences. Pandemic disruption affected recruitment.","access":"Original 2026 full text, randomization and Table 4 checked. ISRCTN17994717.","explainer":{"who":"12 people receiving bowel-cancer chemotherapy, randomly split into groups of six.","compared":"A 36-hour fast before treatment was compared with usual dietary advice.","found":"Most fasting participants could follow the plan, but recruiting enough people was difficult.","meaning":"The study tested whether a larger trial could work. It was too small to show that fasting improves cancer outcomes."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"briata","year":"2026","title":"Time-Restricted Eating and Metformin in Invasive Breast Cancer or DCIS: A Randomized, Phase IIb, Presurgical Trial. Preliminary Safety Analysis","doi":"10.1158/1940-6207.capr-25-0104","pmid":"41165048","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12770929/","author":"Briata et al.","group":"cancer-clinical","kind":"Human trial interim safety report","populationType":"human","topics":["cancer","safety"],"timelineTitle":"An early breast-cancer trial checked safety first","timelineSummary":"Fourteen patients tried nightly fasting with metformin; cancer-effectiveness results were not reported.","takeaway":"This publication reports early safety, not proof of cancer prevention or treatment.","population":"First 14 participants completing the experimental arm of an ongoing randomized presurgical breast-cancer/DCIS trial.","comparison":"Parent trial has two arms: at least 16-hour nightly fasting, nutrition counseling and metformin with glucose monitoring, versus monitoring alone. This interim analysis reports the treated group only.","protocol":"Four to six weeks before surgery, with gradual metformin introduction and monitoring for dose-limiting toxicity.","result":"No dose-limiting toxicity or toxicity-related discontinuation in these 14. Eight experienced at least one adverse event; tumor-proliferation efficacy results were not supplied.","limitation":"Combination intervention, small selected sample and interim analysis. Absence of severe events here does not establish broad safety or efficacy.","access":"Original full text and interim safety methods checked; indexed journal year 2026, first online publication 2025.","explainer":{"who":"The first 14 patients in the treatment group of a larger breast-cancer study.","compared":"They tried nightly fasting with metformin and monitoring before surgery. This report focused on their side effects.","found":"No side effect met the study’s definition of a dose-limiting problem, although milder symptoms occurred.","meaning":"This supports continuing the trial. It does not yet show that the combination slows cancer."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"yeary","year":"2026","title":"Intermittent fasting versus continuous calorie energy reduction in prostate cancer patients on active surveillance","doi":"10.1093/tbm/ibag069","pmid":"42816069","url":"https://pubmed.ncbi.nlm.nih.gov/42816069/","author":"Yeary et al.","group":"cancer-clinical","kind":"Human randomized pilot","populationType":"human","topics":["cancer","weight","adherence"],"timelineTitle":"Two diets helped men under prostate-cancer surveillance lose weight","timelineSummary":"Both 5:2 fasting and daily calorie reduction worked in a 20-person pilot; cancer progression was not established.","takeaway":"Weight-loss feasibility in cancer patients is different from an anticancer effect.","population":"20 men with prostate cancer on active surveillance; 10 per arm, all retained through six months. 95% White; mean age about 66.","comparison":"2 active arms: 5:2 intermittent restriction versus continuous calorie restriction. No usual-diet control.","protocol":"Two 600-kcal days weekly in the intermittent arm; supported weight-loss programs with three- and six-month assessments.","result":"Six-month weight change from baseline: −7.50% with intermittent restriction and −5.79% with continuous restriction. These within-arm results do not establish between-arm superiority.","limitation":"Small feasibility study. Exploratory metabolic and immune changes do not establish reduced prostate-cancer progression.","access":"Original 2026 indexed abstract checked. NCT05764330; full-text comparative effect estimates not extracted.","explainer":{"who":"20 men whose prostate cancer was being monitored, with ten randomly assigned to each diet.","compared":"Eating much less on two days a week was compared with reducing calories every day.","found":"Both groups lost weight and all participants stayed in the study for six months.","meaning":"The trial shows these programs can be practical. It does not show that either diet slowed the cancer."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"fit","year":"2024","title":"Integration of a fasting-mimicking diet programme in primary care for type 2 diabetes reduces the need for medication and improves glycaemic control: a 12-month randomised controlled trial","doi":"10.1007/s00125-024-06137-0","pmid":"38546821","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11153305/","author":"van den Burg et al.","group":"benefits","kind":"Human randomized trial","populationType":"human","topics":["glucose","weight","safety"],"timelineTitle":"Monthly low-calorie cycles reduced diabetes medication needs","timelineSummary":"A 100-person trial found better glucose management after a year of supervised fasting-style diet cycles.","takeaway":"Periodic FMD improved diabetes management compared with usual care in a selected population.","population":"100 adults with type 2 diabetes and BMI at least 27: 51 FMD, 49 control. Eight and ten, respectively, were lost to follow-up.","comparison":"2 arms: usual primary care plus monthly FMD versus usual care alone. Participants used diet and/or metformin, not a broad mix of diabetes medicines at baseline.","protocol":"Five-day FMD cycles monthly for 12 months, with clinical medication management. Outcome assessors were masked.","result":"Adjusted differences favored FMD: HbA1c −0.3 percentage points (95% CI −0.6 to approximately 0), weight −3.6 kg (−5.2 to −2.1), and lower medication-effect score. Improved glycemic management: 53% versus 8%.","limitation":"No equally intensive calorie-restriction comparator; cannot isolate fasting from weight loss and support. Results do not generalize automatically to insulin-treated patients.","access":"Original full text and participant flow checked. NCT03811587. L-Nutra co-funded the study; related MRI and cost reports concern this same trial.","explainer":{"who":"100 people with type 2 diabetes managed with diet or metformin.","compared":"51 added a five-day low-calorie diet each month; 49 continued usual care.","found":"After a year, the diet group needed less medication on average and had modestly better blood-sugar control and weight loss.","meaning":"Useful evidence for a supervised program in this group. It does not show a cure or prove an advantage over other supported weight-loss diets."},"timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"reset","year":"2024","title":"Effects of 3 months of 10-h per-day time-restricted eating and 3 months of follow-up on bodyweight and cardiometabolic health in Danish individuals at high risk of type 2 diabetes: the RESET single-centre, parallel, superiority, open-label, randomised controlled trial","doi":"10.1016/s2666-7568(24)00028-x","pmid":"38588687","url":"https://pubmed.ncbi.nlm.nih.gov/38588687/","author":"Quist et al.","group":"benefits","kind":"Human randomized trial","populationType":"human","topics":["weight","glucose","adherence"],"timelineTitle":"A ten-hour eating window did not clearly improve weight loss","timelineSummary":"The main comparison in this 100-person trial found little added benefit, including after follow-up.","takeaway":"The RESET trial did not establish a clinically important weight advantage.","population":"100 adults at high diabetes risk, 50 per group; 46 in each completed the three-month intervention.","comparison":"2 arms: self-selected ten-hour eating window between 06:00 and 20:00 versus habitual living.","protocol":"Three months of intervention followed by three months of follow-up. External randomization; open-label behavior, masked statistical outcome assessment.","result":"Weight difference at three months: −0.8 kg (95% CI −1.7 to 0.2; P=.099). At six months: −0.2 kg (−1.6 to 1.2). A favorable completer analysis did not persist.","limitation":"Specific population and schedule. A nonsignificant result does not exclude every possible benefit, but does not support a strong weight-loss promise.","access":"Original indexed abstract checked; NCT03854656. Full-text extraction incomplete.","explainer":{"who":"100 middle-aged or older adults at high risk of type 2 diabetes.","compared":"Half limited eating to ten hours daily; half kept their usual schedule.","found":"The main analysis did not show a clear weight advantage after three months, or after the later follow-up.","meaning":"A shorter eating window is not guaranteed to produce meaningful extra weight loss."},"timelineYear":2024,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"karahanautophagy","year":"2025","title":"Effects of Intermittent Fasting on Liver Steatosis and Fibrosis, Serum FGF-21 and Autophagy Markers in Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized Controlled Trial","doi":"10.3390/life15050696","pmid":"40430125","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12113254/","author":"Ozlu Karahan et al.","group":"autophagy","kind":"Human randomized trial","populationType":"human","topics":["autophagy","liver","weight"],"timelineTitle":"A liver study measured a cell-recycling marker","timelineSummary":"A blood protein changed after eight weeks; this did not reveal when autophagy started or how much recycling occurred.","takeaway":"A marker change is weaker evidence than direct measurement of autophagic flux.","population":"48 adults with metabolic fatty liver disease: 26 energy-plus-time restriction, 22 energy restriction alone.","comparison":"2 active dietary arms with similar prescribed calorie content; one also used an eight-hour eating window. Sealed-envelope assignment; laboratory/imaging assessors masked.","protocol":"Eight weeks, with blood markers and liver imaging before and after. Serum ATG-5 and Beclin-1 measured by immunoassay.","result":"ATG-5 increased within the time-restricted group; Beclin-1 did not change significantly. Liver-fat measures improved in both arms, with a larger change in the timing arm.","limitation":"No direct flux assay, tissue measurement or hourly sampling. A within-arm significant result is not itself evidence of a significant between-arm difference; no cancer outcome.","access":"Original full text, assignment, group counts and marker results checked. Short duration and multiple outcomes limit interpretation.","explainer":{"who":"48 adults with fatty liver disease, divided into groups of 26 and 22.","compared":"Both groups reduced calories; one also ate within eight hours each day.","found":"A blood protein associated with cell recycling increased in the timing group after eight weeks.","meaning":"Measuring that protein is not the same as watching recycling happen. This cannot establish a fasting countdown or show cancer removal."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"luoketones","year":"2025","title":"Ketone bodies and cancer risk in the general population: The prevention of renal and vascular end-stage disease (PREVEND) study","doi":"10.1111/eci.70100","pmid":"40947948","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12434450/","author":"Luo et al.","group":"cancer-clinical","kind":"Human observational cohort","populationType":"human","topics":["cancer"],"timelineTitle":"Do people with higher ketones develop less cancer?","timelineSummary":"A large observational study did not establish a protective relationship or test a fasting diet.","takeaway":"Blood ketone associations are not equivalent to the effects of changing diet.","population":"6,079 PREVEND participants; 828 developed cancer over a median 13.4 years.","comparison":"Observed ketone concentrations and subsequent cancer incidence; no assigned intervention or randomized control group.","protocol":"Baseline circulating ketones measured by magnetic resonance spectroscopy; statistical adjustment for demographic, metabolic and inflammatory factors.","result":"Higher ketones initially tracked greater risk. The association weakened after adjustment and was no longer statistically significant after including inflammation: HR 1.09 per doubling (95% CI 0.97–1.23).","limitation":"Confounding, underlying illness and a baseline measurement limit causal interpretation. It proves neither benefit nor harm from ketogenic diets or fasting.","access":"Original full text and adjusted models checked; the indexed record did not contain an abstract.","explainer":{"who":"More than 6,000 adults followed for roughly 13 years; 828 developed cancer.","compared":"Researchers compared cancer rates at different blood-ketone levels. They did not assign diets.","found":"Higher ketones were initially linked with more cancer, but the relationship became uncertain after accounting for other factors.","meaning":"This cannot tell us whether deliberately raising ketones changes cancer risk."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"pietrocolablood","pmid":"28059587","group":"autophagy","populationType":"mixed","topics":["autophagy"],"year":"2017","title":"Metabolic effects of fasting on human and mouse blood in vivo.","author":"Pietrocola et al.","doi":"10.1080/15548627.2016.1271513","url":"https://pubmed.ncbi.nlm.nih.gov/28059587/","kind":"Human/mouse fasting physiology and blood-cell assay study","timelineTitle":"Blood-cell recycling depended on how it was measured","timelineSummary":"Small human experiments detected a fasting response with a special laboratory test, without establishing a universal clock.","takeaway":"Different cells and tests give different answers. This does not establish when whole-body autophagy starts, peaks or stops.","population":"Healthy volunteers and mice; Figure 5 shows four volunteers per condition for paired 48-hour blood comparison and four for 24-hour ex vivo flux assays; mouse panels use three or five animals per condition.","comparison":"Fed versus fasting; isolated cells tested with and without a degradation inhibitor.","protocol":"Mice fasted 48 hours; humans up to four days.","result":"Direct blood-cell measurements at 48 hours did not clearly detect increased human autophagy. After 24-hour fasting, an ex vivo assay blocking degradation detected increased flux; responses differed by cell type and species.","limitation":"Small assay-specific samples and processing outside the body; no universal start, peak or stop time follows. Human four-day fasting and mouse 48-hour starvation are not physiologically equivalent.","access":"Original indexed abstract and original Figure 5–6 captions checked; full methods unavailable through checked repository routes.","explainer":{"who":"Healthy volunteers and mice. The key human tests used four volunteers per condition.","compared":"Researchers compared blood cells before and after fasting, including a test that temporarily blocked the recycling process outside the body.","found":"The special test detected increased recycling after a 24-hour fast. A direct blood-cell measurement at 48 hours did not clearly show it.","meaning":"Different cells and tests give different answers. This does not establish when whole-body autophagy starts, peaks or stops."},"timelineYear":2017,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"yangketochemo","pmid":"35425930","group":"cancer-mechanisms","populationType":"animal","topics":["cancer"],"year":"2022","title":"Ketogenic diet and chemotherapy combine to disrupt pancreatic cancer metabolism and growth.","author":"Yang et al.","doi":"10.1016/j.medj.2021.12.008","url":"https://pubmed.ncbi.nlm.nih.gov/35425930/","kind":"Controlled mouse pancreatic-cancer experiments","timelineTitle":"Ketogenic food helped chemotherapy in mice, even as tumors burned ketones","timelineSummary":"The diet alone did not extend survival; the combination with chemotherapy did.","takeaway":"A promising combination can work through mechanisms other than starving cancer of all usable fuel. Patient benefit still needs clinical testing.","population":"KPC pancreatic-cancer mouse models. Diet-only survival: 14 mice per arm. Pooled diet-plus-chemotherapy comparison: 31 standard-diet and 35 ketogenic-diet mice; separate spontaneous-tumor comparison: 5 versus 4.","comparison":"Standard versus ketogenic diet, with and without chemotherapy; separate immune-deficient experiments.","protocol":"Sixteen-hour fast before diet allocation; gemcitabine, nab-paclitaxel and cisplatin on days 4 and 7. Metabolic tracer experiments used separate assay-specific samples.","result":"Tumors burned more ketones on ketogenic diet. Diet alone did not slow growth or extend survival; combined with chemotherapy it increased the average survival gain from 5.8 to 16 days in the pooled mouse experiments.","limitation":"Mouse results do not establish patient survival benefit. The proposed combination worked despite ketone utilization, not because all tumor cells were unable to use ketones; patent/commercial interests were disclosed.","access":"Original results, animal methods and main figure denominators checked; all supplements and independent review not completed.","explainer":{"who":"Mice with pancreatic tumors: 28 in the diet-only survival comparison and 66 in the main chemotherapy comparison.","compared":"Standard food and ketogenic food, tested with and without chemotherapy.","found":"Tumors used ketones as fuel. Diet alone did not help survival, but adding it to chemotherapy increased the survival gain in these models.","meaning":"A promising combination can work through mechanisms other than starving cancer of all usable fuel. Patient benefit still needs clinical testing."},"timelineYear":2022,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"liupersisters","pmid":"36863257","group":"cancer-mechanisms","populationType":"mixed","topics":["cancer","autophagy"],"year":"2023","title":"Fasting-mimicking diet synergizes with ferroptosis against quiescent, chemotherapy-resistant cells.","author":"Liu et al.","doi":"10.1016/j.ebiom.2023.104496","url":"https://pubmed.ncbi.nlm.nih.gov/36863257/","kind":"Cell and animal colorectal-cancer experiments","timelineTitle":"Slower-growing cancer cells could still survive treatment","timelineSummary":"Fasting-like conditions left some bowel-cancer cells dormant; an experimental drug combination increased killing.","takeaway":"Autophagy can be involved in a successful combination without fasting alone clearing the cancer. This was laboratory evidence, not a patient treatment trial.","population":"Colorectal-cancer cells, patient-derived cells/organoids and several mouse models. Main survival comparison: 7 usual-diet and 8 FMD mice; chemotherapy factorial experiment: 5 mice per arm. Further drug combinations used 5–7 mice per arm.","comparison":"Usual diet, FMD, chemotherapy and combination; separate ferroptosis-inducing drugs, autophagy/ferroptosis inhibitors and cell-state controls.","protocol":"Two FMD cycles in the first model; each four-day cycle supplied 50% of normal intake on day one and 10% on days two to four. Cell and drug protocols differed.","result":"FMD slowed growth, but surviving colorectal-cancer cells could enter a resting, drug-tolerant state. Adding ferroptosis-inducing drugs increased killing, with autophagy implicated by reporter/inhibitor experiments.","limitation":"Preclinical, small model-specific groups and experimental drugs; lower proliferation is not complete cancer elimination. Cell-state and inhibitor results do not establish a human fasting duration or clinical treatment.","access":"Original full methods, results and Figures 1–8 checked; supplementary methods and independent review not completed.","explainer":{"who":"Bowel-cancer cells, patient-derived samples and mice. The first survival comparison used 15 mice; later groups generally used five to seven.","compared":"Usual feeding, fasting-mimicking food, chemotherapy and combinations with experimental cell-killing drugs.","found":"Growth slowed, but some cells entered a resting, drug-tolerant state. Adding drugs that trigger iron-related cell death increased killing, with recycling pathways involved.","meaning":"Autophagy can be involved in a successful combination without fasting alone clearing the cancer. This was laboratory evidence, not a patient treatment trial."},"timelineYear":2023,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"lungoxct","pmid":"37223533","group":"cancer-mechanisms","populationType":"mixed","topics":["cancer"],"year":"2023","title":"OXCT1 regulates NF-κB signaling pathway through β-hydroxybutyrate-mediated ketone body homeostasis in lung cancer.","author":"Lu et al.","doi":"10.1016/j.gendis.2022.04.020","url":"https://pubmed.ncbi.nlm.nih.gov/37223533/","kind":"Cell experiments, mouse xenografts and human tissue observations","timelineTitle":"Ketones helped these stressed lung-cancer cells grow","timelineSummary":"Blocking a ketone-processing enzyme reduced growth in laboratory and mouse experiments.","takeaway":"Some cancers can use ketones. This does not tell us that every ketogenic diet harms patients, but it contradicts a universal starvation claim.","population":"Lung-cancer lines including H1299; 13 paired human tumors/adjacent tissues; mouse group sizes not specified in main report","comparison":"Serum-starved cells with/without ketones; OXCT1 knockdown versus control in cells and grafts","protocol":"Beta-hydroxybutyrate 1 or 5 mM in growth assays; pathway knockdown and rescue experiments","result":"Ketones rescued growth of serum-starved lung-cancer cells. Blocking ketone-use enzyme OXCT1 reduced growth and altered NF-kB signaling; high expression was associated with worse survival in human data.","limitation":"No patient dietary trial; main figure states three independent experiments, not three patients per treatment. Supplementary animal counts were not verified.","access":"Full article text checked, including methods and reported results; independent duplicate review and all supplements not completed.","explainer":{"who":"Lung-cancer cell lines, mice and 13 paired human tumor and nearby-tissue samples.","compared":"Cells with and without added ketones, and cells with normal or reduced ability to process them.","found":"Ketones restored growth under nutrient stress. Disabling the processing enzyme reduced cell and mouse-tumor growth.","meaning":"Some cancers can use ketones. This does not tell us that every ketogenic diet harms patients, but it contradicts a universal starvation claim."},"timelineYear":2023,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"interfastfollow","pmid":"39748228","group":"benefits","populationType":"human","topics":["weight","glucose","adherence"],"year":"2025","title":"Sustained weight reduction following 12 weeks of intermittent fasting intervention in people with insulin-treated type 2 diabetes-Two-year follow-up of the randomised controlled InterFast-2 trial.","author":"Azhar et al.","doi":"10.1111/dom.16158","url":"https://pubmed.ncbi.nlm.nih.gov/39748228/","kind":"Two-year observational follow-up of randomized trial","timelineTitle":"Some weight loss lasted two years; the glucose advantage did not clearly last","timelineSummary":"Follow-up separated a lasting weight difference from uncertain diabetes benefits.","takeaway":"Weight and diabetes control are different outcomes. Missing participants and self-chosen eating after the trial make long-term effects less certain.","population":"46 originally randomized: 22 fasting, 24 control; 39 returned: 17 and 22","comparison":"Original randomized groups; continued fasting after twelve weeks was self-selected","protocol":"INTERFAST-2: three days weekly at up to 500 kcal before noon, with insulin-adjustment protocol","result":"At two years, weight change was −4.2 versus −0.4 kg (P=.021). HbA1c, insulin dose and the composite outcome did not differ significantly. Ten of 17 fasting-group returnees continued at least occasionally.","limitation":"Attrition and unregulated post-trial behavior limit causal durability claims. This is follow-up of PMID 36508320, not a new trial; absence of reported severe hypoglycemia in this small follow-up does not establish general safety.","access":"Full article text checked, including methods and reported results; independent duplicate review and all supplements not completed.","explainer":{"who":"39 returning participants from a 46-person trial in insulin-treated type 2 diabetes: 17 originally assigned to fasting and 22 to usual eating.","compared":"The original groups two years after a twelve-week supervised fasting program.","found":"Weight fell about 4.2 kg versus 0.4 kg. Long-term blood-sugar and insulin-dose differences were not statistically clear.","meaning":"Weight and diabetes control are different outcomes. Missing participants and self-chosen eating after the trial make long-term effects less certain."},"cohort":"Two-year follow-up of INTERFAST-2 (PMID 36508320), also reported in PMIDs 39267053 and 41527226; these are not independent trials.","timelineYear":2025},{"id":"ohmasld","pmid":"40543603","group":"benefits","populationType":"human","topics":["liver","weight"],"year":"2025","title":"Efficacy and safety of time-restricted eating in metabolic dysfunction-associated steatotic liver disease.","author":"Oh et al.","doi":"10.1016/j.jhep.2025.06.005","url":"https://pubmed.ncbi.nlm.nih.gov/40543603/","kind":"Randomized three-arm fatty-liver trial","timelineTitle":"A shorter eating window reduced liver fat about as much as calorie cutting","timelineSummary":"A larger trial found benefit compared with usual care, with similar results from daily calorie restriction.","takeaway":"Timed eating can be one workable strategy. This does not show it is uniquely effective or prevents long-term liver complications.","population":"337 randomized; 333 analyzed: 113 usual care, 110 calorie restriction, 110 time restriction","comparison":"Usual care versus daily calorie restriction versus time restriction","protocol":"16 weeks; NCT05579158","result":"Liver fat fell about 25.8% relatively with timing restriction versus 0.7% with usual care; calorie restriction produced a similar 24.7% decrease.","limitation":"Stronger sample for a surrogate endpoint; timing did not outperform calorie restriction. Relative fat reduction is not a 25.8-percentage-point absolute change or proven cirrhosis prevention.","access":"Original indexed abstract checked; full-text details not independently verified.","explainer":{"who":"337 adults were randomized; 333 were analyzed: 113 usual care, 110 calorie restriction and 110 time-restricted eating.","compared":"Sixteen weeks of a shorter eating window, daily calorie restriction or usual care.","found":"Reported relative liver-fat reductions were about 26% with timed eating and 25% with calorie restriction, versus little change with usual care.","meaning":"Timed eating can be one workable strategy. This does not show it is uniquely effective or prevents long-term liver complications."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"bonhamshift","pmid":"40554393","group":"benefits","populationType":"human","topics":["weight","glucose","adherence"],"year":"2025","title":"Intermittent fasting for weight loss in night shift workers: a three-arm, superiority randomised clinical trial.","author":"Bonham et al.","doi":"10.1016/j.ebiom.2025.105803","url":"https://pubmed.ncbi.nlm.nih.gov/40554393/","kind":"Randomized three-arm superiority trial","timelineTitle":"For night workers, fasting did not clearly beat daily calorie cutting","timelineSummary":"All three programs helped some participants lose weight, with no clear advantage on the main comparisons.","takeaway":"The best schedule may depend on what a person can maintain. Secondary results should not replace the trial’s main comparison.","population":"250 night-shift workers: 85 continuous restriction, 83 fasting on days off/day shifts, 82 fasting on night shifts; 170 completed","comparison":"Continuous restriction versus two modified 5:2 schedules","protocol":"24 weeks; restricted days about 2,100 kJ","result":"Neither intermittent schedule outperformed continuous restriction for weight or insulin resistance; one schedule improved cholesterol more.","limitation":"32% attrition and wide weight-effect intervals; completer improvements do not establish superiority. Same parent trial as qualitative PMID 40437584.","access":"Original indexed abstract checked; full-text details not independently verified.","explainer":{"who":"250 night-shift workers: 85 assigned to daily calorie restriction, 83 to fasting on day shifts and 82 to fasting on night shifts; 170 completed.","compared":"Three supported eating programs over 24 weeks.","found":"Fasting was not significantly better for the main weight and insulin-resistance outcomes. One schedule improved a cholesterol measure.","meaning":"The best schedule may depend on what a person can maintain. Secondary results should not replace the trial’s main comparison."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"mutoketones","pmid":"40578956","group":"cancer-mechanisms","populationType":"lab","topics":["cancer"],"year":"2025","title":"Ketone Bodies Inhibit Growth of Hepatoblastoma and Rhabdoid Tumor of the Kidney Cells.","author":"Muto-Fujita et al.","doi":"10.21873/anticanres.17673","url":"https://pubmed.ncbi.nlm.nih.gov/40578956/","kind":"Pediatric-cancer cell-line experiment","timelineTitle":"Ketones could not replace glucose for these childhood-cancer cells","timelineSummary":"Three cell lines failed to keep growing in glucose-free conditions when ketones were supplied.","takeaway":"This supports glucose dependence in particular cells. Fasting in a person does not create a glucose-free bloodstream, and other cancers respond differently.","population":"Huh6 liver-tumor cells, G401/WT-CLS1 kidney-tumor cells, fibroblast reference","comparison":"Normal versus glucose-free media, with/without ketones","protocol":"Cell growth, ATP and ketone-enzyme assays","result":"Ketones did not rescue growth in glucose-free media; ATP response differed by tumor line.","limitation":"Positive support for poor ketone rescue in these specific cells, not clinical pediatric diet efficacy. Fasting does not make human blood glucose-free; title and conclusion exceed what was tested.","access":"Original indexed abstract checked; full-text details not independently verified.","explainer":{"who":"Three laboratory cell lines representing liver and kidney tumors found in children; no children received a diet intervention.","compared":"Cells grown with different glucose and ketone conditions.","found":"Ketones did not rescue growth when glucose was absent in these models.","meaning":"This supports glucose dependence in particular cells. Fasting in a person does not create a glucose-free bloodstream, and other cancers respond differently."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"xuefmd","pmid":"40711668","group":"cancer-clinical","populationType":"human","topics":["cancer","safety"],"year":"2025","title":"The feasibility and safety of fasting-mimicking diet in breast cancer patients with chemotherapy in China.","author":"Xue et al.","doi":"10.1007/s10549-025-07756-w","url":"https://pubmed.ncbi.nlm.nih.gov/40711668/","kind":"Single-arm breast-cancer feasibility pilot","timelineTitle":"A fasting-like diet during chemotherapy was feasible, but symptoms mattered","timelineSummary":"A small study recorded severe symptoms during some diet cycles and did not test whether cancer outcomes improved.","takeaway":"Cycles are not people, and feasibility is not proof of safety for everyone or better cancer survival.","population":"95 screened, 30 enrolled, 27 completed; 84 FMD cycles. Later body-composition samples fell to 19.","comparison":"Single arm; historical adverse-event assumptions for sample-size calculation, not a concurrent control.","protocol":"Three five-day recipe-based FMD cycles before/on chemotherapy, with 21-day final washout.","result":"Five grade III-or-higher self-reported events were recorded over 84 cycles, including fatigue, dizziness, constipation, abdominal pain and leg weakness. Some metabolic/body-composition measures changed; no cancer efficacy was established.","limitation":"Events per cycle are not the proportion of patients harmed. No concurrent control and concurrent chemotherapy limit safety attribution; repeated cycles are not independent participants.","access":"Original methods, results, safety denominator and body-composition sample counts checked; independent review not completed.","explainer":{"who":"30 women receiving breast-cancer chemotherapy; 27 completed the study, across 84 diet cycles.","compared":"Three five-day diet cycles, without a concurrent comparison group.","found":"Five severe symptom events were reported across the 84 cycles. Some blood and body measurements changed.","meaning":"Cycles are not people, and feasibility is not proof of safety for everyone or better cancer survival."},"timelineYear":2025,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"ketocompsurvival","pmid":"41405605","group":"cancer-clinical","populationType":"human","topics":["cancer","adherence"],"year":"2026","title":"Survival outcomes of rectal and head and neck cancer patients receiving radio(chemo)therapy with a ketogenic diet. A post-hoc analysis from the KETOCOMP trial.","author":"Klement et al.","doi":"10.1007/s00066-025-02499-5","url":"https://pubmed.ncbi.nlm.nih.gov/41405605/","kind":"Long-term post-hoc KETOCOMP cohort analysis","timelineTitle":"Longer follow-up did not show a clear cancer-survival benefit","timelineSummary":"Patients who chose ketogenic food during radiation were followed for about six years.","takeaway":"The study cannot rule out a modest effect, but it does not establish longer survival from ketogenic eating.","population":"81 patients: 35 ketogenic, 46 standard diet; rectal/head-neck cohorts","comparison":"Nonrandomized diet groups during radio/chemotherapy","protocol":"Median follow-up about 71 months rectal and 77 months head/neck","result":"No significant overall, progression-free or locoregional recurrence-free survival benefit in either cancer cohort, including exploratory matched analyses.","limitation":"Important longer follow-up of existing KETOCOMP participants, not a new randomized trial. Borderline recurrence/skin-toxicity trends cannot establish efficacy or broad safety.","access":"Original indexed abstract checked; full-text details not independently verified.","explainer":{"who":"81 people with rectal or head-and-neck cancer: 35 followed ketogenic food and 46 a standard diet.","compared":"Two nonrandomized diet groups receiving radiation, sometimes with chemotherapy.","found":"None of the reported survival comparisons showed a statistically clear advantage, including exploratory matched comparisons.","meaning":"The study cannot rule out a modest effect, but it does not establish longer survival from ketogenic eating."},"cohort":"Long-term KETOCOMP follow-up; overlaps earlier rectal/head-and-neck reports including PMIDs 34233255 and 35499696.","timelineYear":2026},{"id":"wangthyroid","pmid":"41973605","group":"cancer-mechanisms","populationType":"animal","topics":["cancer","autophagy"],"year":"2026","title":"Preliminary study on ketone body metabolism in anaplastic thyroid cancer.","author":"Wang et al.","doi":"10.1530/etj-25-0305","url":"https://pubmed.ncbi.nlm.nih.gov/41973605/","kind":"Thyroid-cancer cell and mouse experiment","timelineTitle":"A ketone slowed thyroid-cancer growth, with cell recycling involved","timelineSummary":"The experiments showed growth arrest, without a clear increase in programmed cell death.","takeaway":"This is evidence for a possible anticancer pathway. Slower growth is different from eliminating tumors, and no patient benefit was tested.","population":"Two thyroid-cancer cell lines, generally three experimental replicates. Mouse methods report ten nude mice allocated five per diet; two tumor-line models are displayed, so the total across models is not unambiguously reconciled.","comparison":"Acetoacetate dose series with/without chloroquine; ketogenic versus standard diet in mice.","protocol":"Cell treatments 2.5–12.5 mM acetoacetate, with 50 μM chloroquine in combination groups; mouse tumors followed four weeks.","result":"Acetoacetate slowed proliferation and arrested the cell cycle without a clear increase in apoptosis. Ketogenic diet reduced mouse tumor growth. Autophagy markers changed and chloroquine weakened the cell effects.","limitation":"Marker/inhibitor evidence supports a pathway hypothesis but is not proof of complete autophagic cancer-cell clearance. No human trial; drug off-target effects, doses and ambiguous total animal count limit inference.","access":"Original methods, results and figure captions checked; supplementary materials and independent review not completed.","explainer":{"who":"Two thyroid-cancer cell lines and mice; the reported diet comparison used five mice per group.","compared":"Ketone treatment with and without a recycling-blocking drug; ketogenic versus standard food in mice.","found":"Growth slowed and recycling markers changed. Blocking recycling weakened the cell effects, but the study did not show a clear increase in apoptosis.","meaning":"This is evidence for a possible anticancer pathway. Slower growth is different from eliminating tumors, and no patient benefit was tested."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"dantasketo","pmid":"42192131","group":"cancer-clinical","populationType":"human","topics":["cancer","immune","safety"],"year":"2026","title":"Very low-carbohydrate ketogenic diet in treatment-naïve women with endometrial cancer and overweight: a randomized feasibility study.","author":"Dantas et al.","doi":"10.1038/s41467-026-73519-w","url":"https://pubmed.ncbi.nlm.nih.gov/42192131/","kind":"Randomized feasibility trial","timelineTitle":"A small cancer trial found immune changes, not proven tumor control","timelineSummary":"Ketogenic meals before surgery changed blood markers and immune-cell measurements in endometrial cancer.","takeaway":"This was a feasibility study. It did not establish cancer shrinkage or longer survival, and the extra tissue controls weaken causal interpretation.","population":"775 screened, 19 randomized 2:1; 15 completed: 9 ketogenic and 6 standard diet. RNA analysis used 5 versus 3; immune-cell histology used 7 versus 17, including additional nonrandomized controls.","comparison":"Two randomized diets with weekly counseling; twelve extra standard-diet tissue cases were added for histology.","protocol":"Three to four weeks before surgery; provided ketogenic meals intended to meet energy needs, standard-diet arm not provided meals. NCT03285152.","result":"Diet adherence was high and no grade 3–4 adverse events were reported. Weight, glucose and insulin fell, LDL rose, and exploratory tumor immune-cell markers changed.","limitation":"Feasibility, not tumor-response or survival trial. Small sample, attrition, short duration, tissue-sampling differences and added nonrandomized histology controls limit immune findings.","access":"Original full text, participant flow in prose, diet methods and Figures 1–3 checked; supplement-level allocation counts not fully reconciled.","explainer":{"who":"19 women were randomized; 15 completed: nine ketogenic and six standard diet. Extra nonrandomized tissue samples were used for one analysis.","compared":"Three to four weeks of provided ketogenic meals or usual food, both with weekly nutrition counseling.","found":"Glucose and insulin fell, LDL cholesterol rose, and selected tumor immune-cell measurements changed. No severe diet-related events were reported.","meaning":"This was a feasibility study. It did not establish cancer shrinkage or longer survival, and the extra tissue controls weaken causal interpretation."},"timelineYear":2026,"cohort":"No linked companion report identified in this selected library; this is not an exhaustive cohort-overlap audit."},{"id":"leaner","pmid":"42754908","group":"prolonged","populationType":"human","topics":["weight","adherence","safety"],"year":"2026","title":"Machine learning identifies microbiome and clinical predictors of sustained weight loss following prolonged fasting.","author":"Kaufhold et al.","doi":"10.1186/s13073-026-01765-0","url":"https://pubmed.ncbi.nlm.nih.gov/42754908/","kind":"Randomized waitlist-controlled trial with prediction analyses","timelineTitle":"A five-day modified fast left some weight change, while many blood changes faded","timelineSummary":"A small controlled study followed healthy adults for twelve weeks after fasting.","takeaway":"This adds evidence beyond intermittent fasting. It was not water-only fasting and did not show superiority to a regular calorie-restricted diet.","population":"38 healthy adults, initially 19 immediate fasting and 19 waitlist; all later underwent the intervention. External prediction datasets reuse previously published cohorts.","comparison":"Randomized waitlist control; no active calorie-restriction comparator.","protocol":"Five days with 200–250 kcal/day from vegetable juice/broth, then refeeding; twelve-week follow-up. LEANER, NCT04452916.","result":"Resting energy expenditure fell about 62 kcal/day during fasting. Some weight/fat reduction remained at twelve weeks, while many metabolic changes reverted. Eighty-three percent reported mild transient adverse events.","limitation":"Small exploratory trial with no predetermined power calculation; post-fast diet was incompletely documented. It does not establish superiority to ordinary calorie restriction or validate a clinical prediction service.","access":"Original methods, results and Figure 1 checked; all supplements and independent review not completed.","explainer":{"who":"38 healthy adults: 19 started immediately and 19 waited before receiving the same program.","compared":"Five days with small amounts of vegetable juice and broth, compared with a waiting period.","found":"Some weight and fat reduction remained at twelve weeks. Many metabolic changes returned toward baseline; 83% reported mild, temporary symptoms.","meaning":"This adds evidence beyond intermittent fasting. It was not water-only fasting and did not show superiority to a regular calorie-restricted diet."},"cohort":"LEANER is NCT04452916. Its external prediction analyses reuse Maifeld, Bahr, GENESIS and OralFast participants; they are not four new fasting trials.","timelineYear":2026}]}