Fasting or Calorie Restriction

• Higher response rates (90–100% tumor cell loss and radiologically complete or partial response), but no evidence of an effect on overall partial or complete response rates, among nondiabetic women with stage 2 or 3 HER-2 negative breast cancer and BMI higher than 18 eating a fasting-mimicking diet for 3 days before and during neoadjuvant chemotherapy compared to controls eating a regular diet in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects; compliance with the fasting diet ranged from 81.5% compliance for one chemotherapy cycle to 20% compliance for all cycles¹de Groot S, Lugtenberg RT et al. Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nature Communications. 2020;11(1):3083.
• No evidence of an effect on cancer-specific or all-cause mortality among nondiabetic women with early stage breast cancer fasting 13 or more hours per night compared to less than 13 hours per night in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study²Marinac CR, Nelson SH et al. Prolonged nightly fasting and breast cancer prognosis. JAMA Oncology. 2016 Aug 1;2(8):1049-55.

• Fewer reported dose reductions or delays in chemotherapy among people with gynecologic cancer receiving at least 6 cycles of chemotherapy and following a water-only fast 24 hours before and 24 hours after chemotherapy compared to nonfasting controls in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects³Riedinger CJ, Kimball KJ et al. Water only fasting and its effect on chemotherapy administration in gynecologic malignancies. Gynecologic Oncology. 2020 Dec;159(3):799-803.

• Better progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) and overall survival among people undergoing reirradiation for malignant glioma eating a calorie-restricted ketogenic diet (KD) and fasting (3 days of KD, then 3 days of fasting and then 3 days of KD) and who achieved a blood glucose level less than the median on day 6, but no evidence of an effect on survival otherwise compared to a calorie-restricted ketogenic diet alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴Voss M, Wagner M et al. ERGO2: a prospective, randomized trial of calorie-restricted ketogenic diet and fasting in addition to reirradiation for malignant glioma. International Journal of Radiation Oncology, Biology, Phyicss. 2020 Nov 15;108(4):987-995.

Fasting: strong evidence of more weight loss and less body fat among people fasting (not specific to cancer), usually for 24 hours at a time

• More weight loss and less fat mass (6 studies) and smaller waist circumference (2 studies) among people participating in periodic fasting (intermittent energy restriction) for 12 weeks or longer compared to their usual diet, but comparable reductions to continuous energy restriction in meta-analysesstatistical analyses that combine the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵Schwingshackl L, Zähringer J et al. Impact of intermittent energy restriction on anthropometric outcomes and intermediate disease markers in patients with overweight and obesity: systematic review and meta-analyses. Critical Reviews in Food Science and Nutrition. 2021;61(8):1293-1304.
• More weight loss among overweight or obese people with diabetes or metabolic syndromea cluster of conditions that occur together, including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels participating in intermittent fasting compared to continuous energy-restricted diets in a meta-analysis of 4 RCTs⁶Wang X, Li Q, Liu Y, Jiang H, Chen W. Intermittent fasting versus continuous energy-restricted diet for patients with type 2 diabetes mellitus and metabolic syndrome for glycemic control: a systematic review and meta-analysis of randomized controlled trials. Diabetes Research and Clinical Practice. 2021 Sep;179:109003.
• Lower body weight but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on whole body fat mass among overweight or obese adults participating in 8-hour time-restricted eating (but no restrictions on eating within that time window) for 12 weeks compared to baseline, and comparable effects compared to people eating 3 structured meals per day, in a mid-sized RCT⁷Lowe DA, Wu N et al. 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. JAMA Internal Medicine. 2020 Nov 1;180(11):1491-1499.
• Higher ratio of fat-free mass to total mass among overweight or obese, nondiabetic, nonsmoking adults participating in alternate-day fasting for 24 weeks compared to controls eating 100% of calorie requirements each day in a mid-sized RCT⁸Trepanowski JF, Kroeger CM et al. Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: secondary analysis of a randomized controlled trial. Clinical Nutrition. 2018 Dec;37(6 Pt A):1871-1878.
• Lower fat mass among adults aged 30–50 with metabolic syndrome restricting eating to 69% of their normal calories 2 days a week for 8 weeks compared to controls following normal eating patterns in a small RCT⁹Guo Y, Luo S et al. Intermittent fasting improves cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. Journal of Clinical Endocrinology and Metabolism. 2021 Jan 1;106(1):64-79.
• Lower body weight and fat mass among nondiabetic, obese adults participating in time-restricted eating of 4 hours per day (eating only between 3:00 and 7:00 pm) or 6 hours (eating only between 1:00 and 7:00 pm) for 8 weeks compared to controls with no meal time restriction in a small RCT¹⁰Cienfuegos S, Gabel K et al. Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: a randomized controlled trial in adults with obesity. Cell Metabolism. 2020 Sep 1;32(3):366-378.e3.
• More weight loss and reduction in waist circumference after 4 months among people with manifest type 2 diabetes medically treated with oral hypoglycemic agents and/or insulin participating in 7 days of liquid-only fasting of 300 calories (kcal) per day and then stepwise re-introduction of solid food, followed by dietary advice compared to usual care and dietary advice only in a small RCT¹¹Li C, Sadraie B et al. Effects of a one-week fasting therapy in patients with type-2 diabetes mellitus and metabolic syndrome—a randomized controlled explorative study. Experimental and Clinical Endocrinology & Diabetes. 2017 Oct;125(9):618-624.
• More loss of fat mass, trunk fat mass, and lean mass, but comparable weight loss of about 7–8 kg (15–18 pounds) among obese, nondiabetic nonsmokers without major diseases participating in zero-calorie, alternate-day fasting for 8 weeks compared to calorie restriction in a small RCT¹²Catenacci VA, Pan Z et al. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity (Silver Spring). 2016 Sep;24(9):1874-83.
• Lower body weight and body mass index among obese people participating in any of these interventions compared to controls maintaining their previous eating and exercise habits, with more weight loss among people participating in both fasting and exercise in a small RCT:¹³Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity (Silver Spring). 2013 Jul;21(7):1370-9.
  • Fasting (controlled feeding of 25% of food energy within a 2-hour period one day alternating with unrestricted eating the next day for 4 weeks followed by 8 weeks of unrestricted eating, with guidance on healthier food choices for unrestricted eating)
  • Supervised moderate-intensity exercise program 3 times a week for 12 weeks
  • Both fasting and exercise (both 1 and 2 above)
• Lower fat mass but no evidence of an effect on fat-free mass among obese people participating in fasting (controlled feeding of 25% of food energy within a 2-hour period one day alternating with unrestricted eating the next day) for 4 weeks followed by 8 weeks of unrestricted eating, with guidance on healthier food choices for unrestricted eating, whether with supervised moderate-intensity exercise program 3 times a week or no increase in exercise, compared to controls doing neither or participating only in exercise, and the most loss of fat mass among people combining fasting and exercise, in a small RCT¹⁴Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity (Silver Spring). 2013 Jul;21(7):1370-9.
• Smaller waist circumference among obese people participating in any of these interventions compared to controls maintaining their previous eating and exercise habits, with smaller circumference among people participating in both fasting and exercise compared to the other groups, and smaller circumference among people fasting only compared to exercise only in a small RCT:¹⁵Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity (Silver Spring). 2013 Jul;21(7):1370-9.
  • Fasting (controlled feeding of 25% of food energy within a 2-hour period one day alternating with unrestricted eating the next day for 4 weeks followed by 8 weeks of unrestricted eating, with guidance on healthier food choices for unrestricted eating)
  • Supervised moderate-intensity exercise program 3 times a week for 12 weeks
  • Both controlled feeding and exercise (both 1 and 2 above)
• Lower body weight but no evidence of an effect on fat mass or lean mass among obese, nondiabetic, and nonsmoking adults participating in 8-hour time-restricted feeding (16-hour nightly fast) compared to controls following their routine dietary and physical activity habits in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial¹⁶Gabel K, Hoddy KK et al. Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: a pilot study. Nutrition and Healthy Aging. 2018 Jun 15;4(4):345-353.

Calorie restriction: strong evidence of more weight loss and less body fat among people restricting calorie intake

• Higher ratio of fat-free mass to total mass among nondiabetic, overweight or obese, nonsmoking adults restricting eating to 75% of calorie needs every day for 24 weeks compared to controls eating 100% of calorie needs each day in a mid-sized RCT¹⁷Trepanowski JF, Kroeger CM et al. Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: secondary analysis of a randomized controlled trial. Clinical Nutrition. 2018 Dec;37(6 Pt A):1871-1878.
• Lower body weight and trunk and total body fat among generally healthy, normal weight or overweight men and women aged 30 to 55 participating in a fasting-mimicking diet low in calories, sugars, and protein but high in unsaturated fats for 5 consecutive days per month for 3 months compared to an unrestricted diet in a mid-sized RCT¹⁸Wei M, Brandhorst S et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational Medicine. 2017 Feb 15;9(377):eaai8700.
• Lower body weight and higher percentage of lean mass, and a weak trend toward less trunk fat, among generally healthy adults with body mass index 18.5 or higher restricting eating to 34–54% of normal calories 5 days every month for 3 months compared to controls following their regular diet in a small RCT¹⁹Brandhorst S, Choi IY et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metabolism. 2015 Jul 7;22(1):86-99.
• Less body fat among healthy but overweight women aged 20-69 with a family history of breast cancer participating in severe calorie (energy) restriction 2 days a week, whether with or without restriction on protein and fat, to give overall weekly 25% energy restriction for 3 months followed by 1 month of weight maintenance compared to daily 25% daily energy restriction in a mid-sized RCT²⁰Harvie M, Wright C et al. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. British Journal of Nutrition. 2013 Oct;110(8):1534-47.
• More weight loss, loss of visceral adipose tissue and fat cell size, and lower percentage of body fat and subcutaneous abdominal adipose tissue among nonsmoking, nondiabetic, overweight people aged 25-45 who exercised less than twice a week at baseline participating in any of these treatments compared to controls following a healthy weight-maintenance diet in a small RCT:²¹Larson-Meyer DE, Heilbronn LK et al. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care. 2006 Jun;29(6):1337-44.
  • 25% calorie restriction for 6 months
  • Low-calorie diet until achieving a 15% weight reduction and then maintenance of the lower body weight for 6 months
• Substantially more weight loss and lower whole-body fat mass, visceral adipose tissue, and subcutaneous abdominal adipose tissue among overweight, nonsmoking, healthy adults without recent weight loss or eating disorder symptoms, and exercising less than twice a week at baseline, participating in a 20% calorie-restricted diet for 1 year compared to controls following a healthy lifestyle in a small RCT²²Racette SB, Weiss EP et al; Washington University School of Medicine CALERIE Group. One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2006 Sep;61(9):943-50.
• Lower weight, body mass index, and total fat mass among nondiabetic, normal weight or overweight, generally healthy people aged 50–60 restricting calories to produce a 16% energy deficit for 9 months, followed by a 20% deficit for 3 months compared to controls following a healthy lifestyle in a small RCT²³Weiss EP, Racette SB et al; Washington University School of Medicine CALERIE Group. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. American Journal of Clinical Nutrition. 2006 Nov;84(5):1033-42.
• Substantially lower body mass index and percent of body fat among people who had been on calorie restriction for an average of 6 years compared to controls eating typical American diets in a small observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study²⁴Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proceedings of the National Academy of Sciences of the USA. 2004 Apr 27;101(17):6659-63.

Exercise-induced calorie deficit: preliminary evidence of more weight loss and less body fat among overweight people exercising to create an energy deficit of about 20%

• Substantially more weight loss and lower whole-body fat mass, visceral adipose tissue, and subcutaneous abdominal adipose tissue among overweight, nonsmoking, healthy people aged 56–58 without recent weight loss or eating disorder symptoms, and exercising less than twice a week at baseline, participating in an exercise-induced 20% energy deficit for 1 year compared to controls following healthy lifestyle in a small RCT²⁵Racette SB, Weiss EP et al; Washington University School of Medicine CALERIE Group. One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2006 Sep;61(9):943-50.
• Lower weight, body mass index, and total fat mass among nondiabetic, normal weight or overweight, generally healthy people aged 50–60 creating an exercise-induced 16% energy deficit for 9 months, followed by a 20% deficit for 3 months compared to controls following a healthy lifestyle in a small RCT²⁶Weiss EP, Racette SB et al; Washington University School of Medicine CALERIE Group. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. American Journal of Clinical Nutrition. 2006 Nov;84(5):1033-42.

Both calorie restriction and exercise-induced calorie deficit: preliminary evidence of more weight loss and less body fat among overweight people exercising to create an energy deficit of about 12.5% and exercising to increase total energy expenditure by 12.5%

• More weight loss, loss of visceral adipose tissue and fat cell size, and lower percentage of body fat and subcutaneous abdominal adipose tissue among nonsmoking, nondiabetic, overweight people aged 25–45 who exercised less than twice a week at baseline restricting calories to 87.5% of normal (12.5% calorie reduction) and exercising to create a 12.5% increase in total energy expenditure for 6 months compared to controls following a healthy weight-maintenance diet in a small RCT²⁷Larson-Meyer DE, Heilbronn LK et al. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care. 2006 Jun;29(6):1337-44.

Fasting: modest and somewhat conflicting evidence of lower blood sugar (glucose) or insulin levels or lower insulin resistance among predominantly overweight or obese people fasting for several hours to 24 hours

• No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on fasting glucose levels and insulin (fasting insulin and HbA1c) among overweight or obese people with diabetes or metabolic syndromea cluster of conditions that occur together, including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels participating in intermittent fasting compared to baseline in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 4 RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²⁸Wang X, Li Q, Liu Y, Jiang H, Chen W. Intermittent fasting versus continuous energy-restricted diet for patients with type 2 diabetes mellitus and metabolic syndrome for glycemic control: a systematic review and meta-analysis of randomized controlled trials. Diabetes Research and Clinical Practice. 2021 Sep;179:109003.
• No evidence of an effect on glucose (fasting glucose or HbA1C) or insulin (fasting insulin or HOMA-IR) among overweight or obese adults restricting eating to an 8-hour time window, but no restrictions on eating within that window, for 12 weeks compared to baseline or to people eating 3 structured meals per day in a mid-sized RCT²⁹Lowe DA, Wu N et al. 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. JAMA Internal Medicine. 2020 Nov 1;180(11):1491-1499.
• Lower glucose (HbA1c) among people with elevated cardiometabolic risk working 24-hour shifts fasting 14 hours a day for 12 weeks compared to controls following normal eating patterns in a mid-sized RCT³⁰Manoogian ENC, Zadourian A et al. Feasibility of time-restricted eating and impacts on cardiometabolic health in 24-h shift workers: the Healthy Heroes randomized control trial. Cell Metabolism. 2022 Oct 4;34(10):1442-1456.e7.
• Less insulin resistance among healthy but overweight women aged 20-69 with a family history of breast cancer, and about ⅓ of whom had insulin resistance at baseline, participating in overall weekly 25% calorie (energy) restriction by severe restriction 2 days a week, whether with or without restriction on protein and fat, for 3 months followed by 1 month of weight maintenance compared to daily 25% daily energy restriction in a mid-sized RCT³¹Harvie M, Wright C et al. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. British Journal of Nutrition. 2013 Oct;110(8):1534-47.
• Lower fasting insulin levels and less insulin resistance after 6 months among generally healthy, overweight or obese, nonsmoking, nondiabetic, premenopausal women aged 30-45 participating in severe food energy restriction 2 days a week for overall 25% weekly energy restriction for 6 months compared to 25% continuous energy restriction in a mid-sized RCT³²Harvie MN, Pegington M et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. International Journal of Obesity (London). 2011 May;35(5):714-27.
• Lower fasting insulin and insulin resistance, and a very weak trend toward lower fasting glucose, among nondiabetic, obese adults participating in time-restricted eating of 4 hours per day (eating only between 3:00 and 7:00 pm) or 6 hours (eating only between 1:00 and 7:00 pm) for 8 weeks compared to controls with no meal time restriction in a small RCT³³Cienfuegos S, Gabel K et al. Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: a randomized controlled trial in adults with obesity. Cell Metabolism. 2020 Sep 1;32(3):366-378.e3.
• Better markers of insulin sensitivity (lower insulin levels and insulin resistance and higher β-cell responsiveness), especially among people with elevated insulin, but no evidence of an effect on glucose among overweight, prediabetic men participating in restricted feeding starting between 6:30 and 8:30 and finishing within 6 hours, with an 18-hour fast every day, for 5 weeks compared to controls with a 12-hour eating window and 12 hours of fasting, but all eating enough to maintain their weight, in a small RCT³⁴Sutton EF, Beyl R et al. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metabolism. 2018 Jun 5;27(6):1212-1221.e3.
• No evidence of an effect on fasting glucose, fasting insulin, and insulin resistance among metabolically healthy obese people participating in alternate-day fasting (25% and 125% of energy needs on alternate days) for 6 months compared to controls receiving no intervention beyond visiting the research center at the same frequency as intervention participants in a small RCT³⁵Trepanowski JF, Kroeger CM et al. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. JAMA Internal Medicine. 2017 Jul 1;177(7):930-938.
• Weak trendsan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward better markers of glucose (HbA1c) and insulin (HOMA-index) after 4 months among people with manifest type 2 diabetes medically treated with oral hypoglycemic agents and/or insulin participating in 7 days of liquid-only fasting of 300 calories (kcal) per day and then stepwise re-introduction of solid food, followed by dietary advice compared to usual care and dietary advice only in a small RCT³⁶Li C, Sadraie B et al. Effects of a one-week fasting therapy in patients with type-2 diabetes mellitus and metabolic syndrome—a randomized controlled explorative study. Experimental and Clinical Endocrinology & Diabetes. 2017 Oct;125(9):618-624.
• Lower fasting glucose but no evidence of an effect on insulin (fasting insulin or HOMA-IR) among obese people participating in fasting (controlled feeding of 25% of food energy within a 2-hour period one day alternating with unrestricted eating the next day) for 4 weeks followed by 8 weeks of unrestricted eating, with guidance on healthier food choices for unrestricted eating, whether with supervised moderate-intensity exercise program 3 times a week or no increase in exercise, compared to controls doing neither or participating only in exercise in a small RCT³⁷Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity (Silver Spring). 2013 Jul;21(7):1370-9.
• No evidence of an effect on measures of blood sugar and insulin resistance (fasting glucose, fasting insulin, or HOMA-IR) among obese, nondiabetic, and nonsmoking adults participating in 8-hour time-restricted feeding (16-hour nightly fast) compared to controls following their routine dietary and physical activity habits in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial³⁸Gabel K, Hoddy KK et al. Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: a pilot study. Nutrition and Healthy Aging. 2018 Jun 15;4(4):345-353.
• Better measures of blood sugar regulation (higher glucose responses and lower triacylglycerols (TAG) responses after meals, and longer glucose time to peak) among healthy, overweight or obese people participating in a zero-calorie fast for 1 day compared to eating 100% of energy needs (isoenergetic intake), with smaller responses among people eating 25% of energy needs in a small controlled trial³⁹Antoni R, Johnston KL, Collins AL, Robertson MD. Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants. British Journal of Nutrition. 2016 Mar 28;115(6):951-9.
• Lower blood sugar (HbA1c) among nondiabetic women with early stage breast cancer fasting more hours at night compared to fewer hours in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁴⁰Marinac CR, Nelson SH et al. Prolonged nightly fasting and breast cancer prognosis. JAMA Oncology. 2016 Aug 1;2(8):1049-55.

Calorie restriction: preliminary and somewhat conflicting evidence of lower blood sugar, insulin, and insulin resistance among people restricting calorie intake

• No evidence of an effect on fasting glucose levels and insulin (fasting insulin and HbA1c) among overweight or obese people with diabetes or metabolic syndrome eating continuous energy-restricted diets compared to baseline in a meta-analysis of 4 RCTs⁴¹Wang X, Li Q, Liu Y, Jiang H, Chen W. Intermittent fasting versus continuous energy-restricted diet for patients with type 2 diabetes mellitus and metabolic syndrome for glycemic control: a systematic review and meta-analysis of randomized controlled trials. Diabetes Research and Clinical Practice. 2021 Sep;179:109003.
• Lower markers of glucose (lower plasma glucose and higher serum ketone bodies) among generally healthy adults with body mass index 18.5 or higher restricting eating to 34–54% of normal calories 5 days, but no evidence of an effect after 25 days of refeeding compared to controls following their regular diet in a small RCT⁴²Brandhorst S, Choi IY et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metabolism. 2015 Jul 7;22(1):86-99.
• More insulin sensitivity among nonsmoking, nondiabetic, overweight people aged 25–45 who exercised less than twice a week at baseline participating in either of these treatments compared to controls following a healthy weight-maintenance diet in a small RCT:⁴³Larson-Meyer DE, Heilbronn LK et al. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care. 2006 Jun;29(6):1337-44.
  • Low-calorie diet until achieving a 15% weight reduction and then maintenance of the lower body weight for 6 months
  • Weak trend toward better sensitivity among people following 25% calorie restriction for 6 months
• Better insulin sensitivity and glucose tolerance among normal weight or overweight, nondiabetic, generally healthy people aged 50-60 participating in a 16% energy deficit through calorie restriction for 9 months, followed by a 20% deficit for 3 months compared to controls following a healthy lifestyle in a small RCT⁴⁴Weiss EP, Racette SB et al; Washington University School of Medicine CALERIE Group. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. American Journal of Clinical Nutrition. 2006 Nov;84(5):1033-42.
• Substantially lower fasting glucose and fasting insulin among people who had been on calorie restriction for an average of 6 years compared to controls eating typical American diets in a small observational study⁴⁵Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proceedings of the National Academy of Sciences of the USA. 2004 Apr 27;101(17):6659-63.
• Lower markers of glucose (serum glucose and urinary ketones) and insulin among people with surgically resectable breast cancer or melanoma eating a 5-day fast-mimicking diet starting 12–15 days before surgery without any additional antitumor therapies, followed by 16–23 days of refeeding, compared to baseline in a mid-sized uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁴⁶Vernieri C, Fucà G et al. Fasting-mimicking diet is safe and reshapes metabolism and antitumor immunity in patients with cancer. Cancer Discovery. 2022 Jan;12(1):90-107.

Exercise-induced calorie deficit: preliminary evidence of better insulin sensitivity and glucose tolerance among normal weight or overweight, nondiabetic people exercising to create a 16% energy deficit

• Better insulin sensitivity and glucose tolerance among normal weight or overweight, nondiabetic, generally healthy people aged 50-60 exercising to create a 16% energy deficit for 9 months, followed by a 20% deficit for 3 months compared to controls following a healthy lifestyle in a small RCT⁴⁷Weiss EP, Racette SB et al; Washington University School of Medicine CALERIE Group. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. American Journal of Clinical Nutrition. 2006 Nov;84(5):1033-42.

Both calorie restriction and exercise-induced calorie deficit: preliminary evidence of more insulin sensitivity among nondiabetic, overweight people creating energy deficits by both restricting calories and exercising

• More insulin sensitivity among nonsmoking, nondiabetic, overweight people aged 25–45 who exercised less than twice a week at baseline restricting calories to 87.5% of normal (12.5% calorie reduction) and exercising to create a 12.5% increase in total energy expenditure for 6 months compared to controls following a healthy weight-maintenance diet in a small RCT⁴⁸Larson-Meyer DE, Heilbronn LK et al. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care. 2006 Jun;29(6):1337-44.

Metabolic hormones

Good evidence of lower levels of insulin-like growth factor-1 (IGF-1)—higher levels are linked to higher risk of cancer and worse outcomes—among people fasting or restricting calories by more than 30% but not among people restricting calories by 30% or less

• Lower levels of insulin-like growth factor-1 (IGF-1) among adults fasting or restricting calories to 50% or less of normal required calories (daily energy intake), but not among people restricting calories to eat more than 50% of required calories, compared to controls in meta-analysesstatistical analyses that combine the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 11 RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴⁹Rahmani J, Kord Varkaneh H et al. The influence of fasting and energy restricting diets on IGF-1 levels in humans: a systematic review and meta-analysis. Ageing Research Reviews. 2019 Aug;53:100910.
• Lower IGF-1 levels among generally healthy, normal weight or overweight men and women aged 30‒55 participating in a fast-mimicking diet low in calories, sugars, and protein but high in unsaturated fats for 5 consecutive days per month for 3 months, and still evident 3 months after completing the intervention, compared to an unrestricted diet in a mid-sized RCT⁵⁰Wei M, Brandhorst S et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational Medicine. 2017 Feb 15;9(377):eaai8700.
• Lower markers of IGF-1 and higher insulin-like growth factor binding protein-1 (IGFBP-1)) among generally healthy adults with body mass index 18.5 or higher restricting eating to 34–54% of normal calories for 5 days, but no evidence of an effect after 25 days of refeeding compared to controls following their regular diet in a small RCT⁵¹Brandhorst S, Choi IY et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metabolism. 2015 Jul 7;22(1):86-99.
• No evidence of an effect on levels of IGF-1 and the ratio of IGF-1 to insulin-like growth factor binding protein-3 (IGFBP-3) among sedentary, nonobese people aged 50–60 either restricting calories to 20% of normal or exercising to increase calorie expenditure by 20%, but lower levels and ratios among people restricting protein, for one year compared to controls following a healthy lifestyle in a small RCT⁵²Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. 2008 Oct;7(5):681-7.
• No evidence of an effect on IGF-1, IGFBP-3, and IGF-1:IGFBP-3 ratio among people aged 50–65 restricting calories to about 30% of normal eating but maintaining adequate nutrition for 6 years compared to controls eating a typical Western diet in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁵³Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. 2008 Oct;7(5):681-7.
• Lower markers of IGF-1 among people with surgically resectable breast cancer or melanoma eating a 5-day fast-mimicking diet starting 12–15 days before surgery while maintaining standard of care, prescribed antitumor therapy followed by 16–23 days of refeeding, compared to baseline in a mid-sized uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁵⁴Vernieri C, Fucà G et al. Fasting-mimicking diet is safe and reshapes metabolism and antitumor immunity in patients with cancer. Cancer Discovery. 2022 Jan;12(1):90-107.
• 30% lower IGF-1 levels at 24 hours, 33% lower at 48 hours, and 8% lower at 72 hours of fasting among people with cancer eating 200 kcal or less per 24-hour period for 24 or 48 hours before platinum-based chemotherapy without concurrent radiation or 48 hours before and 24 hours after chemotherapy compared to baseline in a small uncontrolled trial⁵⁵Dorff TB, Groshen S et al. Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer. 2016 Jun 10;16:360.

Preliminary evidence of lower total and free IGF-1 among people restricting protein intake

• Lower total and free IGF-1 among sedentary, nonobese people aged 50–60 restricting protein compared to a healthy lifestyle for one year in a small RCT⁵⁶Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. 2008 Oct;7(5):681-7.

Weak evidence of higher adiponectin levels among people fasting but no evidence of an effect from restricting calories

• No evidence of an effect on adiponectina hormone and signaling protein involved in regulating glucose levels and fatty acid breakdown levels among nondiabetic, overweight or obese, nonsmoking adults restricting eating to 75% of calorie needs every day for 24 weeks compared to controls eating 100% of calorie needs each day in a mid-sized RCT⁵⁷Trepanowski JF, Kroeger CM et al. Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: secondary analysis of a randomized controlled trial. Clinical Nutrition. 2018 Dec;37(6 Pt A):1871-1878.
• 30% higher adiponectin levels among obese adults fasting every other day for 4 weeks followed by 4 weeks of self-selected eating compared to 2 weeks of baseline values in a small uncontrolled trial⁵⁸Bhutani S, Klempel MC, Berger RA, Varady KA. Improvements in coronary heart disease risk indicators by alternate-day fasting involve adipose tissue modulations. Obesity (Silver Spring). 2010 Nov;18(11):2152-9.
• Higher plasma adiponectin levels among healthy, borderline overweight young men participating in 20 hours of fasting every second day for 15 days compared to baseline in a small uncontrolled trial⁵⁹Halberg N, Henriksen M et al. Effect of intermittent fasting and refeeding on insulin action in healthy men. Journal of Applied Physiology (1985). 2005 Dec;99(6):2128-36.

Preliminary evidence of lower serum T3 levels and energy intake but no evidence of an effect on serum total T4, free T4, reverse T3, and TSH levels among healthy adults participating in long-term calorie restriction

• Lower serum T3 levels and energy intake but no evidence of an effect on serum total T4, free T4, reverse T3, and TSH levels among lean and weight-stable healthy adults participating in long-term (3 to 15 years) calorie restriction compared to age- and sex matched sedentary or body fat-matched exercising subjects eating Western diets in a small observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁶⁰Fontana L, Klein S, Holloszy JO, Premachandra BN. Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones. Journal of Clinical Endocrinology and Metabolism. 2006 Aug;91(8):3232-5.

Appetite hormones

Modest evidence of lower levels of leptin, a hormone that helps regulate energy balance by inhibiting hunger, among overweight or obese people fasting or restricting calories

• Lower leptin levels among nondiabetic, overweight or obese, nonsmoking adults either restricting eating to 75% of calorie needs every day or alternating between 25% of energy needs and 125% on alternating days for 24 weeks compared to controls eating 100% of calorie needs each day in a mid-sized RCT⁶¹Trepanowski JF, Kroeger CM et al. Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: secondary analysis of a randomized controlled trial. Clinical Nutrition. 2018 Dec;37(6 Pt A):1871-1878.
• Comparable reductions in leptin after 6 months among generally healthy, overweight or obese, nonsmoking, nondiabetic, premenopausal women aged 30-45 fasting (severely restricting calories) 2 days a week for overall 25% weekly energy restriction for 6 months compared to 25% continuous energy restriction in a mid-sized RCT⁶²Harvie MN, Pegington M et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. International Journal of Obesity (London). 2011 May;35(5):714-27.
• 21% lower serum leptin and 23% lower resistin levels among obese adults fasting every other day for 4 weeks followed by 4 weeks of self-selected eating compared to 2 weeks of baseline values in a small uncontrolled trial⁶³Bhutani S, Klempel MC, Berger RA, Varady KA. Improvements in coronary heart disease risk indicators by alternate-day fasting involve adipose tissue modulations. Obesity (Silver Spring). 2010 Nov;18(11):2152-9.
• Lower serum leptin levels on restricted eating days among obese non-smoking adults with moderate asthma and without use of systemic corticosteroids or hypoglycemics for at least 6 weeks participating in 20% lower calorie intake alternating with unrestricted eating every other day for 8 weeks compared to baseline in a small uncontrolled trial⁶⁴Johnson JB, Summer W et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radical Biology and Medicine. 2007 Mar 1;42(5):665-74.

No evidence of an effect on levels of the “hunger hormone” ghrelin among nonobese, nondiabetic adults fasting every other day in a small study

• No evidence of an effect on levels of ghrelin among nonobese, nondiabetic adults aged 23-53 fasting every other day for 22 days compared to baseline in a small uncontrolled trial⁶⁵Heilbronn LK, Smith SR, Martin CK, Anton SD, Ravussin E. Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. American Journal of Clinical Nutrition. 2005 Jan;81(1):69-73.

Sex hormones

Preliminary evidence of comparable reductions in free androgen index among generally healthy, overweight or obese women achieving overall 25% weekly calorie restriction either by fasting or restricting daily calories

• Comparable reductions in free androgen index after 6 months among generally healthy, overweight or obese, nonsmoking, nondiabetic, premenopausal women aged 30-45 participating in severe food energy restriction 2 days a week for overall 25% weekly energy restriction for 6 months compared to 25% continuous energy restriction in a mid-sized RCT⁶⁶Harvie MN, Pegington M et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. International Journal of Obesity (London). 2011 May;35(5):714-27.

Fasting: no evidence of an effect on markers of inflammation among overweight or obese people fasting in several small studies

• No evidence of an effect on markers of inflammation (TNF-ɑ or IL-6) among nondiabetic, obese adults participating in time-restricted eating of 4 hours per day (eating only between 3:00 and 7:00 pm) or 6 hours (eating only between 1:00 and 7:00 pm) for 8 weeks compared to controls with no meal time restriction in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁶⁷Cienfuegos S, Gabel K et al. Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: a randomized controlled trial in adults with obesity. Cell Metabolism. 2020 Sep 1;32(3):366-378.e3.
• No evidence of an effect on markers of inflammation (hs-CRP, IL-6, or cortisol) among overweight, prediabetic men participating in restricted feeding starting between 6:30 and 8:30 and finishing within 6 hours, with an 18-hour fast every day for 5 weeks compared to controls with a 12-hour eating window and 12 hours of fasting, but all eating enough to maintain their weight, in a small RCT⁶⁸Sutton EF, Beyl R et al. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metabolism. 2018 Jun 5;27(6):1212-1221.e3.
• No evidence of effects on markers of inflammation (C-reactive protein) among metabolically healthy obese people participating in alternate-day fasting (25% and 125% of energy needs on alternate days) for 6 months compared to controls receiving no intervention beyond visiting the research center at the same frequency as intervention participants in a small RCT⁶⁹Trepanowski JF, Kroeger CM et al. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. JAMA Internal Medicine. 2017 Jul 1;177(7):930-938.
• No evidence of an effect on a marker of inflammation (CRP) among obese people participating in fasting (controlled feeding of 25% of food energy within a 2-hour period one day alternating with unrestricted eating the next day) for 4 weeks followed by 8 weeks of unrestricted eating, with guidance on healthier food choices for unrestricted eating, whether with supervised moderate-intensity exercise program 3 times a week or no increase in exercise, compared to controls doing neither in a small RCT⁷⁰Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity (Silver Spring). 2013 Jul;21(7):1370-9.

Calorie restriction: preliminary and conflicting evidence of lower markers of inflammation among people restricting calories

• No evidence of an effect on markers of inflammation (TNF-ɑ, IL-6 or resistin) among nondiabetic, overweight or obese, nonsmoking adults restricting eating to 75% of calorie needs every day for 24 weeks compared to controls eating 100% of calorie needs each day in a mid-sized RCT⁷¹Trepanowski JF, Kroeger CM et al. Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: secondary analysis of a randomized controlled trial. Clinical Nutrition. 2018 Dec;37(6 Pt A):1871-1878.
• Fewer inflammatory cytokines but no effect on inflammatory markers (IL-6 or TNF-α) among adults aged 30–50 with metabolic syndromea cluster of conditions that occur together, including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels restricting eating to 69% of their normal calories 2 days a week for 8 weeks compared to controls following normal eating patterns in a small RCT⁷²Guo Y, Luo S et al. Intermittent fasting improves cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. Journal of Clinical Endocrinology and Metabolism. 2021 Jan 1;106(1):64-79.
• A lower marker of inflammation (CRP) among generally healthy adults with body mass index 18.5 or higher and eleveated CRP levels restricting eating to 34–54% of normal calories 5 days every month for 3 months compared to controls following their regular diet in a small RCT⁷³Brandhorst S, Choi IY et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metabolism. 2015 Jul 7;22(1):86-99.
• Lower levels of markers of inflammation (C-reactive protein, TNF-ɑ, and TGF-beta(1)) among people aged between 41-65 restricting calories for an average of 6.5 years compared to controls eating Western diets in a small observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁷⁴Meyer TE, Kovács SJ et al. Long-term caloric restriction ameliorates the decline in diastolic function in humans. Journal of the American College of Cardiology. 2006 Jan 17;47(2):398-402.
• A substantially lower marker of inflammation (high-sensitivity CRP) among people participating in calorie restriction for an average of 6 years compared to controls eating typical American diets in a small observational study⁷⁵Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proceedings of the National Academy of Sciences of the USA. 2004 Apr 27;101(17):6659-63.
• Lower inflammatory markers (serum tumor necrosis factor-α and brain-derived neurotrophic factor) among obese non-smoking adults with moderate asthma and without use of systemic corticosteroids or hypoglycemics for at least 6 weeks participating in 20% lower calorie intake alternating with unrestricted eating every other day for 8 weeks compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁷⁶Johnson JB, Summer W et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radical Biology and Medicine. 2007 Mar 1;42(5):665-74.

• Less oxidative stress among adults aged 30–50 with metabolic syndromea cluster of conditions that occur together, including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels restricting eating to 69% of their normal calories 2 days a week for 8 weeks compared to controls following normal eating patterns in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁷⁷Guo Y, Luo S et al. Intermittent fasting improves cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. Journal of Clinical Endocrinology and Metabolism. 2021 Jan 1;106(1):64-79.
• A lower marker of oxidative stress to lipids (8-isoprostane) among nondiabetic, obese adults participating in time-restricted eating of 4 hours per day (eating only between 3:00 and 7:00 pm) or 6 hours (eating only between 1:00 and 7:00 pm) for 8 weeks compared to controls with no meal time restriction in a small RCT⁷⁸Cienfuegos S, Gabel K et al. Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: a randomized controlled trial in adults with obesity. Cell Metabolism. 2020 Sep 1;32(3):366-378.e3.
• A lower marker of oxidative stress (8-isoprostane) among overweight, prediabetic men experiencing restricted feeding starting between 6:30 and 8:30 and finishing within 6 hours, with an 18-hour fast every day for 5 weeks compared to controls with a 12-hour eating window and 12 hours of fasting, but all eating enough to maintain their weight, in a small RCT⁷⁹Sutton EF, Beyl R et al. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metabolism. 2018 Jun 5;27(6):1212-1221.e3.

• Changes in the gut microbiota linked to fewer cardiometabolic risk factors plus higher production of short-chain fatty acids among adults aged 30–50 with metabolic syndrome restricting eating to 69% of their normal calories 2 days a week for 8 weeks compared to controls following normal eating patterns in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁸⁰Guo Y, Luo S et al. Intermittent fasting improves cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. Journal of Clinical Endocrinology and Metabolism. 2021 Jan 1;106(1):64-79.

• A higher marker of adult tissue and organ regeneration (mesenchymal stem/progenitor cells) among generally healthy adults with body mass index 18.5 or higher restricting eating to 34–54% of normal calories 5 days every month for 3 months compared to controls following their regular diet in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁸¹Brandhorst S, Choi IY et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metabolism. 2015 Jul 7;22(1):86-99.