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. 2019 Oct 14;11(10):2442. doi: 10.3390/nu11102442

Table 2.

Changes in biomarkers of metabolic disease risk in randomized controlled weight loss trials of intermittent energy restriction (IER) compared to continuous energy restriction (CER).

Reference Participants & Interventions Measurement Conditions Glycemic Outcomes Lipid Outcomes Other Biomarker Outcomes
Harvie et al., 2011 [40] -Pre-menopausal women who were overweight or obese
-2DW; CER
-Overnight fast, at least 5 days after the last partial energy restriction day in the 2DW group
-In a subset of the 2DW group (n = 15), fasting blood samples were collected after 5 days of normal intake on the morning after a partial energy restriction day and after 2 days of normal intake
-Glucose (ND)
-Greater decrease in insulin and increase in insulin sensitivity (HOMA-IR) in the 2DW group
-Greater decreases in insulin sensitivity on the morning after a partial energy restriction day in a subset of the 2DW group
-Cholesterol (ND)
-LDL (ND)
-HDL (ND)
-TGs (ND)
-CRP (ND)
-Adiponectin (ND)
-Leptin (ND)
-Ketones (ND)
Varady et al., 2011 [47] -Adults who were overweight or obese
-ADMF; CER
12 h fasting blood samples Not assessed -Cholesterol (ND)
-LDL (ND)
-HDL (ND)
-Greater decrease in TGs in the ADMF group
Not assessed
Harvie et al., 2013 [41] -Pre-menopausal women
-2DW + Carbohydrate Restriction;
2DW + Carbohydrate restriction and ad libitum protein and fat restriction; CER
Overnight fast, at least 5 days after the weekly 2 day partial energy restriction day in the 2DW groups -Greater decrease in insulin and increase in insulin sensitivity (HOMA-IR) in the 2DW groups
-HbA1c (ND)
-Glucose (ND)
-Cholesterol (ND)
-LDL (ND)
-HDL (ND)
-TGs (ND)
-IGF-1 (ND)
-IL-6 (ND)
-TNF-α (ND)
-Ketones (ND)
-Leptin (ND)
-Adiponectin (ND)
Carter et al., 2016 [42] -Adults
with T2DM who were overweight or obese
-2DW; CER
After an overnight fast (minimum of 8 h) -HbA1c (ND) Not assessed Not assessed
Catenacci et al., 2016 [25] -Adults who were overweight or obese
-ADF; CER
After an overnight fast (minimum of 8 h) -Glucose (ND)
-Insulin (ND)
-Insulin sensitivity (HOMA-IR; ND)
-Cholesterol (ND)
-LDL (ND)
-HDL (ND)
-TGs (ND)
-Metabolic rate (ND)
-Leptin (ND)
-Ghrelin (ND)
-BDNF (ND)
Trepanowski et al., 2017 [48] -Adults who were overweight or obese
-ADMF; CER
After a 12 h fast, the morning after a “feast” day for the ADMF group -Glucose (ND)
-Insulin (ND)
-Insulin sensitivity (HOMA-IR; ND)
-Cholesterol (ND)
-Greater increase in LDL in ADMF
-HDL (ND)
-TGs (ND)
-CRP (ND)
-Homocysteine (ND)
Schübel et al., 2018 [44] Adults who were overweight or obese
-2DW; CER
Metabolic measures sampled day after fed day and an overnight fast -Fasting glucose decreased more in 2DW than CER
-Insulin (ND)
-Insulin sensitivity (HOMA-IR; ND)
-Cholesterol (ND)
-LDL (ND)
-HDL (ND)
-TGs (ND)
Not assessed
Sundfør et al., 2018 [46] -Adults who were overweight or obese
-2DW; CER
Blood samples were obtained following a minimum of a 10 h fast Glucose (ND)
HbA1c (ND)
-Cholesterol (ND)
-LDL (ND)
-HDL (ND)
-TGs (ND)
-Apo B (ND)
-CRP (ND)
-Metabolic rate (ND)
Hutchison et al., 2019 [49] -Female adults who were overweight or obese
-ADMF 70; ADMF 100; CER
Metabolic measures performed after a fed and fasted day -Greater decreases in glucose and insulin in ADMF 70 when measured after a fast day
-Insulin sensitivity (euglycemic-hyperinsulinemic clamp) increased in ADMF 70 when measured after a fed day, but changes not different than CER
-Insulin sensitivity (clamp) decreased in ADMF 70 when measured after a fasted day
-Greater decreases in fasting FFA, TC, LDL, and Tgs in ADMF 70 compared to CER, but ADMF 70 lost more weight
-Differences in changes in cholesterol and LDL remained after adjusting for weight loss
Not assessed

Abbreviations: ADF = alternate day fasting; ADMF = alternate day modified fasting; 2DW = fasting 2 days per week; CER = continuous energy restriction; ND = no difference; HOMA-IR = Homeostatic Model Assessment of Insulin Resistance; LDL = low-density lipoprotein; HDL = high-density lipoprotein; TG = triglyceride; CRP = C-reactive protein; IGF-1 = insulin-like growth factor-1; IL-6 = interleukin-6; TNF-α = Tumor Necrosis Factor alpha; HbA1c = hemoglobin A1c; BDNF = brain-derived neurotrophic factor; Apo B = apolipoprotein B; FFA = free fatty acid.