1 Supplemental material Supplement 1: Search Strategy (Ovid Medline) Supplement 2: Table of included studies and references Supplement 3: List of excluded studies of interest Supplement 4: Meta-analyses of all health outcomes for change scores (Forest Plots) Supplement 5: Meta-regression analyses for all health outcomes Supplement 6: Meta-analyses of all health outcomes for end of study scores (Secondary analysis) Supplement 1: Search strategy used in Medline (OVID interface) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 diet, protein-restricted/ diet, carbohydrate-restricted/ 1 or 2 diet fads/ (carbohydrate* or protein*).ti,ab. 4 and 5 exp dietary proteins/ dietary carbohydrates/ (diet* or intake*).ti,ab. (high* or increas* or rich or low* or restrict* or decreas* or reduc*).ti,ab. (7 or 8) and 9 and 10 ((carbohydrate* or protein*) adj3 (high* or increas* or rich or low* or restrict* or decreas* or reduc*)).ti,ab. 12 and 9 3 or 6 or 11 or 13 randomized controlled trial.pt. controlled clinical trial.pt. randomized.ab. placebo.ab. clinical trials as topic.sh. randomly.ab. trial.ti. or/15-21 humans.sh. 22 and 23 14 and 24 2 Supplement 2: List of included studies and details by primary study* Primary study (references) Abete 2009 (1, 2) No of participants, losses 19 Loss to followup and dropouts: 0% Characteristics of patients obese BMI I:33.2; C:31.4 100% male 38 years Location: SPAIN Aldrich 2011 (3) 12 Loss to followup and dropouts: Obese BMI 30 17% male 50 years Location: USA Appel 2005 (4-7) Crossover trial 164 Loss to followup and dropouts: 16% hypertensive BMI 30 55% male 54 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet high protein (animal source) hypocaloric diet versus control balanced diet energy restricted Intervention diet: hypocaloric, 2088 kcal/day, 30% pro, 33% cho, 37% fat Control diet: hypocaloric, 1729 kcal/day, 19% pro, 51% cho, 33% fat Controlled moderate protein diet versus control diet Intervention diet: Hypocaloric, 1607 kcal/day, 31% pro, 41% cho, 13% fat Control diet: Hypocaloric, 1601 kcal/day, 16% pro, 56% cho, 14% fat high protein (rich in plant protein) vs high carbohydrate (similar to DASH diet); for weight maintenance for 6 weeks Intervention diet: isocaloric, 2558 kcal/day, 25% pro, 50% vegetable protein, 48% cho, 27% fat Control diet: isocaloric, 2599 kcal/day, 15% pro, 58% cho, 33% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 56 Weight, blood pressure, fglucose, finsulin, satiety 56 Weight, blood pressure, total cholesterol, HDL, LDL, TG, appetite, bloating, dry mouth, hunger, fullness 42 3 Primary study (references) Aude 2004 (8) No of participants, losses 60 Loss to followup and dropouts: 10% Characteristics of patients obese BMI I:35, C:36 52% male I:46 years, C:44 years Location: USA Baba 1999 (9) 13 Loss to followup and dropouts: 0% obese BMI I:37, C:35 100% male Location: LEBANON BallesterosPomar 2009 (10) 36 Loss to followup and dropouts: 0% Overweight, obese BMI 32 33% male Location: Spain Barnard 2004 (11,12) 64 Loss to followup and dropouts: 8% overweight , obese BMI I:32.6;C:33.6 0% male I:56 years;C:57 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet 3 phase diet with low carbohydrate (lower glycemic index) increasing to wk 5-12 vs National Cholesterol Education Program diet (normal protein), weight loss both diets Intervention diet: hypocaloric, 1300-1600 kcal/day, 33% pro, 28% cho, 39% fat Control diet: hypocaloric, 1300-1600 kcal/day, 15% pro, 55% cho, 30% fat high protein vs high carbohydrate, weight loss diets; "natural foods" Intervention diet: hypocaloric, 45% pro, 25% cho, 30% fat Control diet: hypocaloric, 12% pro, 58% cho, 30% fat Energy restricted high protein vs energy restricted usual diet Intervention diet: Hypocaloric, 1840 kcal/day, 23% pro, 42% cho, 34% fat Control diet: Hypocaloric, 1654 kcal/day, 18% pro, 55% cho, 27% fat ad libitum low fat diet (Step II National Cholesterol Education Program) versus ad libitum very low-fat vegan diet Intervention diet: ad libitum, 1424 kcal/day, 18% pro, 62%, 20% fat Control diet: ad libitum, 1408 kcal/day, 12% pro, 78% cho, 11% fat Outcomes meeting inclusion criteria Followup(days) Weight, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, satisfaction 84 Weight, BMI, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, satisfaction 28 Weight, BMI, waist circumference, total cholesterol, HDL, LDL, TG, fglucose, finsulin, C-reactive protein 112 Weight, BMI, dietary restraint, disinhibition, hunger 98 4 Primary study (references) Belobrajdic 2010 (13,14) Bowden 2007 (15) No of participants, losses 76 (from 112) Loss to followup and dropouts: 0% 108 Characteristics of patients obese BMI 33 100% male 51 years Location: AUSTRALIA obese and healthy 34% male 20 years Location: USA 108 obese and healthy 34% male 20 years Location: USA Brehm 2003 (16) 53 Loss to followup and dropouts: 21% obese BMI I:33.17; C:34.04. 0% male I:44 years; C:43 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet High protein high red meat weight loss diet versus high carbohydrate low red meat weight loss diet Intervention diet: hypocaloric, 1651 kcal/day, 33% pro, 37% cho, 30% fat Control diet: hypocaloric, 1627 kcal/day, 21% pro, 51% cho, 28% fat high protein vs AHA recommended, weight maintenance Intervention diet: isocaloric, 1222 kcal/day, 25% pro, 41% cho, 34% fat Control diet: isocaloric, 1631 kcal/day, 16% pro, 51% cho, 33% fat high protein vs AHA recommended, weight loss Intervention diet: hypocaloric, 1487 kcal/day, 27% pro, 43% cho, 31% fat Control diet: hypocaloric, 1465 kcal/day, 16% pro, 54% cho, 31% fat very low carbohydrate (high pro) ad libitum to low fat (normal pro) with energy restriction Intervention diet: ad libitum (but consumed hypocaloric, ) 1156 kcal/day, 28% pro, 15% cho, 57% fat Control diet: hypocaloric, 1245 kcal/day, 18% pro, 54% cho, 28% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, fgluc, 84 Weight, Fglucose 84 Weight, Fglucose 84 Weight, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 90 5 Primary study (references) No of participants, losses 53 Loss to followup and dropouts: 21% Characteristics of patients obese BMI I:33.17; C:34.04. 0% male I:44 years; C:43 years Location: USA Brehm 2005 (17) 50 Loss to followup and dropouts: 20% obese BMI I:32.8; C:33.5. 0% male I:45 years; C:41 years Location: USA Brinkworth 2009 (18-23) 117 Loss to followup and dropouts: 7% obese BMI 34 36% male I:51 years, C:49 years Location: AUSTRALIA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet very low carbohydrate (high pro) ad libitum to low fat (normal pro) with energy restriction Intervention diet: ad libitum (but consumed hypocaloric) 1302 kcal/day, 23% pro, 30% cho, 46% fat Control diet: hypocaloric, 1247 kcal/day, 18% pro, 29% cho, 53% fat very low carbohydrate (high pro) no energy restriction to low fat (normal pro) with energy restriction Intervention diet: ad libitum but consumed same amount of energy as control group 1288 kcal/day, 28% pro, 15% cho, 57% fat Control diet: hypocaloric, 1339 kcal/day, 18% pro, 53% cho, 29% fat very low carbohydrate, high saturated fat diet vs conventional high carbohydrate, low saturated fat diet, both weight loss Intervention diet: hypocaloric, 1578 kcal/day, 35% pro, 5% cho, 59% fat Control diet: hypocaloric, 1574 kcal/day, 24% pro, 47% cho, 28% fat Outcomes meeting inclusion criteria Followup(days) Weight, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 180 Weight, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose 60 Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, C-reactive protein, mood 56 6 Primary study (references) No of participants, losses 118 Loss to followup and dropouts: 26% Characteristics of patients obese BMI 34 I:51 years, C:49 years Location: AUSTRALIA 118 Loss to followup and dropouts: 41% obese BMI 34 Buscemi 2009 (24) 25 Loss to followup and dropouts: 20% Dansinger 2005 (25) 80 Loss to followup and dropouts: 35% overweight , obese BMI I:34.5; C:34 0% male I:38 years;C:39 years Location: ITALY obese , at least 1 cardiac risk factor BMI I:34, C:35 54% male I:51 years, C:49 years Location: USA I:51 years, C:49 years Location: AUSTRALIA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet very low carbohydrate, high saturated fat diet vs conventional high carbohydrate, low saturated fat diet, both weight loss Intervention diet: hypocaloric, 1605 kcal/day, 33% pro, 8% cho, 56% fat Control diet: hypocaloric, 1520 kcal/day, 23% pro, 45% cho, 27% fat very low carbohydrate, high saturated fat diet vs conventional high carbohydrate, low saturated fat diet, both weight loss Intervention diet: hypocaloric, 1644 kcal/day, 32% pro, 9% cho, 55% fat Control diet: hypocaloric, 1624 kcal/day, 22% pro, 46% cho, 26% fat atkins diet (very low carbohydrate) low calories versus mediterranean diet low calorie diet Intervention diet: hypocaloric, kcal/day, 25% pro, 20% cho, 55% fat Control diet: hypocaloric, kcal/day, 20% pro, 55% cho, 25% fat zone diet (high protein) vs. Weight Watchers' diet based on points (lower protein), diets for weight loss and cardiac effects Intervention diet: ad libitum (but was hypocaloric, ) 1434 kcal/day, 25% pro, 40% cho, 35% fat Control diet: hypocaloric, 1615 kcal/day, 20% pro, 47% cho, 31% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, C-reactive protein, mood 168 Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, C-reactive protein, serum creatinine, mood 365 Weight, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 60 Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, C-reactive protein, adverse events 60 7 Primary study (references) Das 2007 (26) No of participants, losses 34 Loss to followup and dropouts: 15% Characteristics of patients overweight BMI 28 24% male 35 years Location: USA De Luis 2007 (27) 90 Loss to followup and dropouts: 0% obese BMI 35.8 30% male 43 years Location: Spain De Luis 2009a (28) 193 Loss to followup and dropouts: 0% obese BMI 34.7 25% male 46 years Location: SPAIN De Luis 2009b (29) 118 Loss to followup and dropouts: 0% obese BMI 35.4 28% male 46 years Location: SPAIN Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet Energy restricted low glycemic load high protein diet vs energy restricted high glycemic load lower protein diet Intervention diet: Hypocaloric, 1900 kcal/day, 30% pro, 40% cho, 30% fat Control diet: Hypocaloric, 1960 kcal/day, 20% pro, 60% cho, 20% fat low fat (low protein) versus low carbohydrate diet (high protein) both for weight loss Intervention diet: hypocaloric, 1574 kcal/day, 26% pro, 31% cho, 43% fat Control diet: hypocaloric, 1630 kcal/day, 20% pro, 55% cho, 25% fat low carbohydrate diet (with higher protein) hypocaloric diet versus low fat diet (with higher protein) hypocaloric diet Intervention diet: hypocaloric, 1578 kcal/day, 26% pro, 31% cho, 36% fat Control diet: hypocaloric, 1628 kcal/day, 20% pro, 53% cho, 25% fat low carbohydrate diet (with higher protein) hypocaloric diet versus low fat diet (with higher protein) hypocaloric diet Intervention diet: hypocaloric, 1548 kcal/day, 26% pro, 31% cho, 36% fat Control diet: hypocaloric, 1613 kcal/day, 20% pro, 52% cho, 25% fat Outcomes meeting inclusion criteria Followup(days) Weight, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, hunger and satisfaction 365 Weight, BMI, Waist circumference, C-reactive protein 90 Weight, BMI, Waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 60 Weight, BMI, Waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 90 8 Primary study (references) Delbridge 2009 (30) Due 2004 (31-35) No of participants, losses 139 Loss to followup and dropouts: 42% 50 Loss to followup and dropouts: 8% 50 Loss to followup and dropouts: 36% Dyson 2007 (36) 13 Loss to followup and dropouts: 23% Characteristics of patients Overweight, obese BMI 39 50% male 44 years Location: Australia overweight , obese BMI I:30;C:31 24% male I:40 years; C:39 years Location: Denmark overweight , obese BMI I:30;C:31 24% male I:40 years; C:39 years Location: Denmark obese BMI 36 23% male 51 years Location: UK Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet High protein vs high carbohydrate diet Intervention diet: Isocaloric, 1589 kcal/day, 28% pro, 38% cho, 34% fat Control diet: Isocaloric, 1678 kcal/day, 22% pro, 47% cho, 30% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG 365 High carbohydrate to high protein, both ad libitum Intervention diet: ad libitum 2150 kcal/day, 24% pro, 46% cho, 30% fat Control diet: ad libitum 2580 kcal/day, 12% pro, 59% cho, 29% fat Weight, BMI, Waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, CRP, appetite, discomfort, Bone mineral density 180 high protein and high carbohydrate diet ad libitum diet counseling only Intervention diet: ad libitum 2006 kcal/day, 21% pro, 49% cho, 30% fat Control diet: ad libitum 1959 kcal/day, 14% pro, 55% cho, 31% fat Weight, BMI, Waist circumference, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 365 carbohydrate diet to <=40 g per day with lean protein sources vs healthy energy restiricted diet by Diabetes UK - in diabetes and nondiabetes nondiabetes data only used Intervention diet: ad libitum but was hypocaloric, 1289 kcal/day, 30% pro, 22% cho, 22% fat Control diet: hypocaloric, 1526 kcal/day, 19% pro, 44% cho, 35% fat Weight, BMI, HbA1C, total cholesterol, HDL, LDL, TG 90 9 Primary study (references) Farnsworth 2003 (37-39) No of participants, losses 66 Loss to followup and dropouts: 16% Characteristics of patients obese BMI I: 34(M), 35(F), C:35(M), 34(F) 25% male I: 52(M), 51(F), C:49(M), 51(F) years Location: AUSTRALIA healthy BMI I:23, C:24 100% male 26 years Location: ITALY Ferrara 2006 (40) 15 Loss to followup and dropouts: 0% Fleming 2002 (41) 56 Loss to followup and dropouts: 0% overweight , obese weight I:232 lbs;C:226 lbs 47% male 43 years Location: USA Foster 2003 (42) 63 Loss to followup and dropouts: 23%, 33%, 41% obese BMI 34 32% male 44 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet high protein versus standard protein, both energy restricted diets, 12 week weight loss then 4 wk weight maintenance Intervention diet: hypocaloric, 1505 kcal/day, 27% pro, 10% vegetable protein, 44% cho, 27% fat Control diet: hypocaloric, 1552 kcal/day, 16% pro, 57% cho, 27% fat high protein vs normal protein, weight maintenance Intervention diet: isocaloric, 2525 kcal/day, 19.5% pro, 54% cho, 26% fat Control diet: isocaloric, 2300 kcal/day, 15% pro, 59% cho, 26% fat 4 diets compared. High fat ad libitum (also high protein) compared to phase II (moderate fat diet, calorie restricted, norm protein) chosen Intervention diet: ad libitum but was hypocaloric, kcal/day, high protein Control diet: hypocaloric, 1550 kcal/day, 15% pro, 70% cho, 15% fat atkins diet vs conventional diet Intervention diet: ad libitum, high protein Control diet: hypocaloric, lower protein Outcomes meeting inclusion criteria Followup(days) Weight, BMI, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 28, 56, 84 Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG, creatinine 180 Weight, total cholesterol, HDL, LDL, TG 365 Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG 90, 180, 365 10 Primary study (references) Gardner 2007 (43) Greene 2004 (44) Hodgson 2006 (45, 46) No of participants, losses 156 Characteristics of patients obese BMI I:32, C:31 0% male I:42 years, C:40 years Location: USA 10 Loss to followup and dropouts: 0% overweight BMI 33 33% male 58 years Location: USA 11 Loss to followup and dropouts: 0% overweight BMI 33 33% male 58 years Location: USA 71 Loss to followup and dropouts: 15% hypertensive BMI 28 63% male C:60 years, I:57 years Location: AUSTRALIA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet atkins low carbohydrate (higher protein) vs LEARN ('prudent' diet. High carbohydrate, low fat, caloric restriction) Intervention diet: ad libitum (but was hypocaloric, ) 1381 kcal/day, 28% pro, 18% cho, 55% fat Control diet: hypocaloric, 1476 kcal/day, 20% pro, 49% cho, 30% fat low fat (low protein) versus ketogenic low carbohydrate diet 1 (high protein) both for weight loss Intervention diet: hypocaloric, 1500/1800 kcal/day, 30% pro, 5% cho, 65% fat Control diet: hypocaloric, 1500/1800 kcal/day, 15% pro, 55% cho, 30% fat low fat (low protein) versus ketogenic low carbohydrate diet 1 (high protein) both for weight loss Intervention diet: hypocaloric, 1500/1800 kcal/day, 30% pro, 5% cho, 65% fat Control diet: hypocaloric, 1500/1800 kcal/day, 15% pro, 55% cho, 30% fat substitution of carbohydrate with lean red meat vs. Usual diet Intervention diet: isocaloric, 2221 kcal/day, 24% pro, 39% cho, 31% fat Control diet: isocaloric, 2006 kcal/day, 19% pro, 43% cho, 32% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG 60 Weight, waist circumference, total cholesterol, HDL, LDL, TG, creatinine 84 Weight, waist circumference, total cholesterol, HDL, LDL, TG, creatinine 84 Weight, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, HbA1C, C-reactive protein 56 11 Primary study (references) Iglay 2007 (47) No of participants, losses 50 Loss to followup and dropouts: 28% Characteristics of patients healthy BMI I:27, C:26 47% male I:61, C:62 Location: USA Jenkins 2001 (48,49) Crossover trial 20 Loss to followup and dropouts: 0% Hyperlipidemic, obese BMI 26 75% male 56 years Location: Canada Jenkins 2009 (50) 50 Loss to followup and dropouts: 16% overweight, hyperlipidemic BMI 31 44% male 57 years Location: Canada Johnston 2004 (51) 20 Loss to followup and dropouts: 20% overweight BMI 29 10% male I:40 years; C: 36 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet high to low prot, no weight loss, increase in animal proteins Intervention diet: isocaloric, 2099 kcal/day, 17% pro, 34% vegetable protein, 50% cho, 33% fat Control diet: isocaloric, 2079 kcal/day, 12% pro, 53% cho, 34% fat high vegetable protein (gluten) diet to normal diet both weight maintenance Intervention diet: isocaloric, 2764 kcal/day, 27% pro, 74% vegetable, 47% cho, 26% fat Control diet: isocaloric, 2835 kcal/day, 16% pro, 46% vegetable, 59% cho, 26% fat plant-based low carbohydrate (eco-atkins) vs high carbohydrate lacto-ovo vegetarian diet Intervention diet: hypocaloric, 1451 kcal/day, 30% pro, 27% cho, 43% fat Control diet: Hypocaloric, 1488 kcal/day, 17% pro, 58% cho, 25% fat energy and fat restricted diets: high protein vs high carbohydrate Intervention diet: hypocaloric, 1700 kcal/day, 32% pro, 40% cho, 28% fat Control diet: hypocaloric, 1700 kcal/day, 15% pro, 66% cho, 21% fat Outcomes meeting inclusion criteria Followup(days) BMI, waist circumference, total cholesterol, HDL, LDL, TG, HbA1C 98, 84 Blood pressure, total cholesterol, HDL, LDL, TG, creatinine, 30 Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, HbA1c, C-reactive protein, satiety 28 Weight, BMI, total cholesterol, HDL, LDL, TG, Fglucose, satiety 42 12 Primary study (references) Josse 2011 (52, 53) Keogh 2007 (54) Kleiner 2006 (55) No of participants, losses 90 Loss to followup and dropouts: 10% Characteristics of patients Overweight, obese BMI 32 0% male 28 years Location: Canada 44 Loss to followup and dropouts: 43% obese BMI 33 32% male 49 years Location: AUSTRALIA 44 Loss to followup and dropouts: 70% obese BMI 33 32% male 49 years Location: AUSTRALIA 20 Loss to followup and dropouts: 20% obese I:34.6;C:35.9 25% male 35 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet High protein, high dairy hypoenergetic diet vs adequate protein, medium dairy hypoenergetic diet Intervention diet: Hypocaloric, 1500 kcal/day, 28% pro, 41% cho, 31% fat Control diet: Hypocaloric, 1430 kcal/day, 18% pro, 58% cho, 24% fat high carbohydrate vs low carbohydrate diet, weight loss Intervention diet: hypocaloric, 1496 kcal/day, 36% pro, 38% cho, 25% fat Control diet: hypocaloric, 1491 kcal/day, 23% pro, 53% cho, 21% fat high carbohydrate vs low carbohydrate diet, weight loss Intervention diet: hypocaloric, 1496 kcal/day, 36% pro, 38% cho, 25% fat Control diet: hypocaloric, 1491 kcal/day, 23% pro, 53% cho, 21% fat high protein low fat diet vs. High carbohydrate low fat diet - weight loss =70 to 75% of energy needs Intervention diet: hypocaloric, 32% pro, 41% cho, 27% fat Control diet: hypocaloric, 14% pro, 59% cho, 27% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, Creactive protein, BMD 112 Weight, Waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 42, 84 Weight, Waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 365 Weight, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 56 13 Primary study (references) Labayen 2003 (56) Landers 2002 (57) Lasker 2008 (58) Layman 2005 (59) No of participants, losses 11 Loss to followup and dropouts: 0% Characteristics of patients obese BMI I:39, C:37 100% male 23-57 years Location: SPAIN 63 Loss to followup and dropouts: 63% 65 obese BMI>27 unlcear 18 to 55 years Location: USA overweight , obese BMI 33.6 38% male 47 years Location: USA 24 Loss to followup and dropouts: 0% overweight BMI 32.9 0% male 47 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet high carbohydrate to high protein (low carbohydrate), energy restricted diets Intervention diet: hypocaloric, 30% pro, 40% cho, 30% fat Control diet: hypocaloric, 15% pro, 55% cho, 30% fat Zone diet (high protein) vs. Conventional weight loss Intervention diet: ad libitum, 30% pro, 40% cho, 30% fat Control diet: hypocaloric, 20% pro, 50% cho, 30% fat high protein, low carbohydrate energy restricted diet versus high carbohydrate, low protein, low fat energy restricted diet Intervention diet: hypocaloric, 1578 kcal/day, 30% pro, 39% cho, 32% fat Control diet: hypocaloric, 1403 kcal/day, 5% pro, 61% cho, 25% fat low carbohydrate (high protein) weight loss diet vs high carbohydrate (low protein) weight loss diet Intervention diet: hypocaloric, 1448 kcal/day, 30% protein, 39% cho, 32% fat Control diet: hypocaloric, 1284 kcal/day, 18% protein, 61% cho, 24% fat Outcomes meeting inclusion criteria Followup(days) Weight 70 Weight 84 Weight, BMI, Fglucose 120 Weight, total cholesterol, HDL, LDL, TG, Finsulin 112 14 Primary study (references) No of participants, losses 24 Loss to followup and dropouts: 0% Characteristics of patients overweight BMI 32.9 0% male 47 years Location: USA Layman 2009 (60) 130 Loss to followup and dropouts: 21% overweight , obese BMI 32.6 45% male 45 years Location: USA Lean 1997 (61) 110 obese BMI I:33, C:32 0% male I:50 years, C:51 years Location: UK Leidy 2007 (62, 64) 54 Loss to followup and dropouts: 15% overweight , obese BMI 31 0% male I:46 years;C:53 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet low carbohydrate (high protein) weight loss diet vs high carbohydrate (low protein) weight loss diet Intervention diet: hypocaloric, 1323 kcal/day, 31% protein, 38% cho, 31% fat Control diet: hypocaloric, 1348 kcal/day, 17% pro, 60% cho, 24% fat high protein, low carbohydrate energy restricted diet versus high carbohydrate, low protein, low fat energy restricted diet Intervention diet: hypocaloric, 1607 kcal/day, 29% pro, 38% cho, 32% fat Control diet: hypocaloric, 1481 kcal/day, 18% pro, 59% cho, 26% fat low carbohydrate (high protein) vs high carbohydrate (low protein), weight loss Intervention diet: hypocaloric, 1197 kcal/day, 30% pro, 35% cho, 35% fat Control diet: hypocaloric, 1198 kcal/day, 21% pro, 58% cho, 21% fat high protein to normal protein, weight loss 750 kcal deficit Intervention diet: hypocaloric, 1540 kcal/day, 30% pro, 45% cho, 25% fat Control diet: hypocaloric, 1500 kcal/day, 18% pro, 57% cho, 22% fat Outcomes meeting inclusion criteria Followup(days) Weight, total cholesterol, HDL, LDL, TG, Finsulin 112 Weight, HDL, LDL, TG 120 Weight, BMI, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG (30 weight only), 90, 120 (weight only), 180 Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, creatinine, appetite, arousal-sleep, pleasure, hunger, desire to eat, fullness, BMD 84, (63 hunger, desire to eat, fullness ) 15 Primary study (references) Lopez-Jiminez 2010 (65) LuscombeMarsh 2005 (66, 67) No of participants, losses 55 Loss to followup and dropouts: 0% 73 Loss to followup and dropouts: 22% Characteristics of patients Metabolic syndrome BMI 34.5 obese BMI 34 36% male 50 years Location: AUSTRALIA Mahon 2007 (68, 69) 61 Loss to followup and dropouts: 11% obese hyperlipidemic C:28.4; I:30.1 0% male between 50 and 80 yrs Location: USA Maki 2007 (70) 86 Loss to followup and dropouts: 19% overweight , obese BMI 32 33% male 50 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet Low carbohydrate, relatively high protein enriched with mono- or polyunsaturated oils vs standard diet for diabetic patients Low fat high protein vs high fat standard protein, both weight loss for 12 wks, then 4 wks maintenance Intervention diet: hypocaloric, 1472 kcal/day, 34% pro, 35% cho, 29% fat Control diet: hypocaloric, 1426 kcal/day, 18% pro, 35% cho, 45% fat weight loss diets: beef moderate protein vs. Lactoovo vegetarian lower protein Intervention diet: hypocaloric, 1114 kcal/day, 24% pro, 100% vegetable protein, 46% cho, 30% fat Control diet: hypocaloric, 1158 kcal/day, 17% pro, 59% cho, 24% fat low carbohydrate, low glycemic ad libitum diet compared to nutritionally balanced lower fat diet energy restricted Intervention diet: ad libitum 1343 kcal/day, 26% protein, 32% cho, 42% fat Control diet: hypocaloric, 1500 kcal/day, 19% pro, 46% cho, 37% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, waist circumference, total cholesterol, HDL, LDL, TG, Fglucose, Finsultin, C reactive protein Weight, total cholesterol, HDL, LDL, TG, adverse events 180 Weight, BMI, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, Creactive protein, BMD 63 Weight, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 84 28 (weight only) and 56 (weight, Fglucose, Finsulin), 84 16 Primary study (references) Mamo 2005 (71) No of participants, losses 20 Loss to followup and dropouts: 0% McAuley 2005 (72) 62 Loss to followup and dropouts: 8% McMillanPrice 2006 (73) 129 Loss to followup and dropouts: 9% Characteristics of patients hyperlipidemic BMI 32 60% male I:55 years, C:41 years Location: AUSTRALIA obese BMI I:35, C:37 0% male I:47 years, C:45 years Location: New Zealand obese BMI - high glycemic groups: 31; low glycemic groups I:32, C:31 24% male high glycemic groups I:31, C:32 years; low glycemic groups I:35, C:30 years Location: AUSTRALIA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet high protein vs low protein, weight maintenance Intervention diet: isocaloric, 24% pro, 43% cho, 30% fat Control diet: isocaloric, 17% pro, 52% cho, 27% fat zone (high protein) vs. Healthy eating, non diabetci (high carbohydrate, high fibre) diets. For 8 weeks weight loss + 16 weeks maintenance Intervention diet: ad libitum (but was hypocaloric, ) 1353 kcal/day, 28% pro, 34% cho, 35% fat Control diet: ad libitum (but was hypocaloric, ) 1372 kcal/day, 21% pro, 49% cho, 24% fat high carbohydrate to high protein (with high GI), reduced fat, weight loss Intervention diet: hypocaloric, 1400-1900 kcal/day, 28% pro, 42% cho, 27% fat Control diet: hypocaloric, 1400-1900 kcal/day, 18% pro, 60% cho, 19% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, total cholesterol, HDL, LDL, TG, Finsulin 42 Weight, BMI, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, Creactive protein 56 Weight, waist circumference, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, C-reactive protein 84 17 Primary study (references) No of participants, losses 129 Loss to followup and dropouts: 11% Meckling 2004 (74) 40 Loss to followup and dropouts: 23% Meckling 2007 (75) 60 Loss to followup and dropouts: 40% Characteristics of patients obese BMI - high glycemic groups: 31; low glycemic groups I:32, C:31 24% male high glycemic groups I:31, C:32 years; low glycemic groups I:35, C:30 years Location: AUSTRALIA overweight BMI 32 71% male I:41 years; C:43 years Location: Canada obese BMI I: 31, C:29 0% male I:45 years, C:47 years, I(with exercise):37 years, C(with intervention):41 years Location: CANADA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet high carbohydrate to high protein (with low GI), reduced fat, weight loss Intervention diet: hypocaloric, 1400-1900 kcal/day, 26% pro, 40% cho, 29% fat Control diet: hypocaloric, 1400-1900 kcal/day, 19% pro, 56% cho, 22% fat low carbohydrate (high protein) versus low fat (lower protein) both weight loss Intervention diet: hypocaloric, 1534 kcal/day, 26% pro, 15% cho, 56% fat Control diet: hypocaloric, 1451 kcal/day, 20% pro, 62% cho, 18% fat control to high protein, weight loss Intervention diet: hypocaloric, 1383 kcal/day, 24% pro, 37% cho, 39% fat Control diet: hypocaloric, 1391 kcal/day, 16% pro, 50% cho, 34% fat Outcomes meeting inclusion criteria Followup(days) Weight, waist circumference, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, C-reactive protein 84 Weight, BMI, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, adverse effects 70 Weight, BMI, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, Creactive protein 84 18 Primary study (references) Moran 2003 (76, 77) No of participants, losses 60 Loss to followup and dropouts: 17% 45 Loss to followup and dropouts: 0% 45 Loss to followup and dropouts: 37% Characteristics of patients obese BMI I: 31, C:29 0% male I:45 years, C:47 years, I(with exercise):37 years, C(with intervention):41 years Location: CANADA Obese, polycystic ovary syndrome BMI 38 0% male 33 years Location: AUSTRALIA obese, polycystic ovary syndrome BMI 38 0% male 33 years Location: AUSTRALIA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet high protein with exercise vs low protein with exercise, weight loss Intervention diet: hypocaloric, 1217 kcal/day, 37% pro, 36% cho, 26% fat Control diet: hypocaloric, 1260 kcal/day, 18% pro, 50% cho, 29% fat high protein vs low protein for weight loss, 12 week weight loss, 4 week maintenance Intervention diet: hypocaloric, 1494 kcal/day, 27% pro, 43% cho, 28% fat Control diet: hypocaloric, 1514 kcal/day, 16% pro, 57% cho, 27% fat high protein vs low protein for weight loss, 12 week weight loss, 4 week maintenance, entered as 12 weeks Intervention diet: hypocaloric, 1494 kcal/day, 27% pro, 43% cho, 28% fat Control diet: hypocaloric, 1514 kcal/day, 16% pro, 57% cho, 27% fat Outcomes meeting inclusion criteria Followup(days) Weight, waist circumference, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, C-reactive protein 84 Weight 112 BMI, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, depression 84 19 Primary study (references) Morgan 2008 (78, 79) No of participants, losses 118 Loss to followup and dropouts: 28% Characteristics of patients Overweight and obese BMI 31 30% male 40 years Location: United Kingdom obese BMI 37 27% male C:52 years, I:53 years Location: ITALY Muzio 2007 (80) 100 Loss to followup and dropouts: 0% NickolsRichardson 2005 (81) 28 Loss to followup and dropouts: 0% overweight BMI I:31.1, C:30.3 100% I:39 years; C:40 years Location: USA Noakes 2005 (82) 119 Loss to followup and dropouts: 16% obese BMI I:32, C:33 0% male I:50 years, C:49 years Location: AUSTRALIA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet Atkins diet (low carbohydrate) vs usual diet Intervention diet: 1630 kcal/day, 26% pro, 18% cho, 56% fat Control diet: Isocaloric, 1596 kcal/day, 20% pro, 39% cho, 40% fat high carbohydrate to low carbohydrate-high proteinhigh monounsaturated fat for weight loss Intervention diet: hypocaloric, 1490 kcal/day, 19% pro, 25% vegetable protein, 48% cho, 33% fat Control diet: hypocaloric, 1456 kcal/day, 13% pro, 60% vegetable, 65% cho, 22% fat low carbohydrate/high protein diet (Atkins diet with changing carbohydrate over time) ad libitum vs high carbohydrate/low fat diet energy restricted Intervention diet: ad libitum (but consumed hypocaloric, ) 1420 kcal/day, 26% pro, 12% cho, 61% fat Control diet: hypocaloric, 1395 kcal/day, 18% pro, 60% cho, 22% fat high protein, low saturated fat vs high carbohydrate, low saturated fat, both weight loss, 12 weeks Intervention diet: hypocaloric, 1268 kcal/day, 31% pro, 44% cho, 22% fat Control diet: hypocaloric, 1247 kcal/day, 18% pro, 61% cho, 20% fat Outcomes meeting inclusion criteria Followup(days) Weight, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose 180 Weight, BMI, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 150 Weight, BMI, cognitive eating, hunger 42 Weight, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, C-reactive protein 84 20 Primary study (references) Noakes 2006 (83) No of participants, losses 55 Loss to followup and dropouts: 0.19% Characteristics of patients obese BMI 33 16% male I: 48 years, C: 46 years Location: AUSTRALIA Phillips 2008 (84) 28 Loss to followup and dropouts: 29% obese BMI 34 25 % male I:33 years, C:38 years Location: USA Rouse 1986 (85-87) Crossover trial 40 Loss to followup and dropouts: 3% Sacks 1984 (88) Crossover trial 23 Loss to followup and dropouts: 22% healthy weight I:70kg;C:67kg 49% male I:40 years;C:41 years Location: USA vegans weight 63 kg 39% male 32 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet very low carbohydrate diet (high protein) vs low sat fat/high unsaturated fat diet - both energy restricted Intervention diet: hypocaloric, 1479 kcal/day, 33% pro, 9% cho, 55% fat Control diet: hypocaloric, 1432 kcal/day, 23% pro, 48% cho, 27% fat low carbohydrate (high protein according to Atkins' diet) vs low fat (American Heart Association) 750 kcal decrease; diets were 6 weeks (4 week weight loss, 2 maintenance) Intervention diet: ad libitum (but was hypocaloric, ) 1855 kcal/day, 32% pro, 5% cho, 22% fat Control diet: hypocaloric, 1755 kcal/day, 21% pro, 58% cho, 23%fat omnivore diet weight maintenance versus lacto-ovovegetarian diet weight maintenance Intervention diet: ad libitum 2193 kcal/day, 16% pro, 41% cho, 40% fat Control diet: ad libitum 2174 kcal/day, 12% pro, 27% cho, 39% fat high protein vs low protein foods added to vegan diets of below average protein Intervention diet: isocaloric, 1879 kcal/day, 25% pro, 56% cho, 19% fat Control diet: isocaloric, 1589 kcal/day, 16% pro, 60% cho, 24% fat Outcomes meeting inclusion criteria Followup(days) Weight, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin 56 Fglucose, Finsulin 28 Weight, blood pressure 56 Weight, blood pressure 56 21 Primary study (references) Sacks 2009 (89) No of participants, losses 405 Loss to followup and dropouts: 17% Schweiger 1986 (90) 18 Loss to followup and dropouts: 0% Seshadri 2004 (91, 92) 132 randomised (45 nondiabetic) Stamets 2004 (93) 35 Loss to followup and dropouts: 26% Stoernell 2008 (94) 28 Loss to followup and dropouts: 18% Characteristics of patients Overweight, obese BMI 33 37% male 51 years Location: USA healthy BMI I:22.6; C:21.9 0% male I:24 years; C:22 years Location: Germany severe obesity I:44;C:42 69% male I:53 years;C:52 years Location: USA Obese, polycystic ovary syndrome BMI I:38, C:37 0% male I:29 years, C:26 years Location: USA hypertriglyceremi a, diabetes BMI I:34.5;C:29.6 48% male I:57 years; C: 48 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet Low fat, average protein to high fat, high protein diet Intervention diet: hypocaloric, 1624 kcal/day, 23% pro, 43% cho, 34% fat Control diet: hypocaloric, 1636 kcal/day, 18% pro, 58% cho, 26% fat mixed protein (higher protein) to vegetarian diet Intervention diet: hypocaloric, 923 kcal/day, 20% pro, 48% cho, 30% fat Control diet: hypocaloric, 1142 kcal/day, 12% pro, 62% cho, 23%fat low carbohydrate, no restriction to fat intake Intervention diet: ad libitum 1343 kcal/day, 25% pro, 31% cho, 44% fat Control diet: hypocaloric, 1590 kcal/day, 16% pro, 51% cho, 32% fat high protein vs high carbohydrate (normal protein), diets were 1000kcal below needs. Fat similar Intervention diet: hypocaloric, 30% pro, 40% cho, 30% fat Control diet: hypocaloric, 15% pro, 55% cho, 30% fat Atkins (low carbohydrate not energy restricted) vs. Low fat (energy restricted) Intervention diet: hypocaloric, 25% pro, 20% cho, 55% fat Control diet: hypocaloric, 20% pro, 48% cho, 33% fat Outcomes meeting inclusion criteria Followup(days) Weight, waist circumference, satiety, quality of life, adverse events 180 Weight, global mood 42 TG, HbA1C, Fglucose, Finsulin 180 Weight, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, 28 Weight, waist circumference, total cholesterol, HDL, LDL, TG, Creactive protein, satiety 56 22 Primary study (references) Te Morenga 2011 (95) No of participants, losses 83 Loss to followup and dropouts: 11% Characteristics of patients Overweight, obese BMI 34 0% male 42 years Location: New Zealand Thorpe 2008 (96) 71 Loss to followup and dropouts: 20% obese BMI I: 31, C: 32 0% male I: 45 years, C: 46 years Location: USA Volek 2003 (97) Crossover trial 10 Loss to followup and dropouts: 0% healthy BMI 22 0% male 26 years Location: USA Volek 2004 (98-101) Crossover trial 15 Loss to followup and dropouts: 0% overweight , obese BMI 34 100% male 33 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet Moderately high protein energy restricted diet vs high fibre relatively high carbohydrate energy restricted diet Intervention diet: Hypocaloric, 1556 kcal/day, 28% pro, 40% cho, 32% fat Control diet: Hypocaloric, 1428 kcal/day, 22% pro, 51% cho, 27% fat 4 months of weight loss diet then 8 months of weight maintenance Intervention diet: hypocaloric, 1409 kcal/day, 28% pro, 42% cho, 33% fat Control diet: hypocaloric, 1409 kcal/day, 17% pro, 57% cho, 29% fat very low carbohydrate diet (low carbohydrate bars and shakes were provided) vs low fat diet - not weight loss Intervention diet: isocaloric, 1911 kcal/day, 29% pro, 10% cho, 60% fat Control diet: isocaloric, 1576 kcal/day, 17% pro, 62% cho, 19% fat very low carbohydrate ketogenic diet weight loss diet (low carbohydrate bars and shakes were provided) vs low fat weight loss diet Intervention diet: hypocaloric, 1855 kcal/day, 28% pro, 8% cho, 50% fat Control diet: hypocaloric, 1562 kcal/day, 20% pro, 56% cho, 23% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, waist circumference, blood pressure, total cholesterol, HDL, LDL, TG, hunger/preoccupation with food 56 BMI, Bone mineral density 120 Weight, total cholesterol, HDL, LDL, TG 28 Weight 50 23 Primary study (references) No of participants, losses Crossover trial 13 Loss to followup and dropouts: 0% Characteristics of patients overweight , obese BMI 30 0% male 34 years Location: USA Volek 2009 (102, 103) 40 Loss to followup and dropouts: 0% overweight BMI I:34; C:32 50% male I: 33 years, C: 37 years Location: USA Wolfe 1991 (104, 105) Crossover trial 10 Loss to followup and dropouts: 0% hyperlipidaemic weight 64 kg 40% male 50 years Location: CANADA Wolfe 1992 (106, 107) Crossover trial 5 Loss to followup and dropouts: 0% hyperlipidaemic 40% male 48 years Location: CANADA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet very low carbohydrate ketogenic diet weight loss diet (low carbohydrate bars and shakes were provided) vs low fat weight loss diet Intervention diet: hypocaloric, 1288 kcal/day, 28% pro, 9% cho, 63% fat Control diet: hypocaloric, 1243 kcal/day, 19% pro, 59% cho, 21% fat very low carbohydrate ketogenic vs low fat diet - no energy restrictions Intervention diet: adlibitum (but was hypocaloric, ) 1504 kcal/day, 28% pro, 12% cho, 59% fat Control diet: adlibitum (but was hypocaloric, ) 1478 kcal/day, 20% pro, 56% cho, 24% fat high protein vs low protein(substituting meat and dairy protein with carb) weight maintenance Intervention diet: isocaloric, 1909 kcal/day, 23% pro, 23%vegetable protein, 53% cho, 24% fat Control diet: isocaloric, 2011 kcal/day, 11% pro, 70% vegetable, 65% cho, 24% fat weight maintenance high versus low protein Intervention diet: isocaloric, 2409 kcal/day, 26% pro, 19% vegetable protein, 19% cho, 25% fat Control diet: isocaloric, 1808 kcal/day, 10% pro, 92% vegetable, 65% cho, 25% fat Outcomes meeting inclusion criteria Followup(days) Weight 30 Weight, BMI, total cholesterol, HDL, LDL, TG, Fglucose, Finsulin, CRP 84 Weight, total cholesterol, HDL, LDL, TG 35 Weight, total cholesterol, HDL, LDL, TG 35 24 Primary study (references) Wolfe 1999 (108, 109) Yancy 2004 (110, 111) No of participants, losses Crossover trial 10 Loss to followup and dropouts: 0% 120 Loss to followup and dropouts: 26% Characteristics of patients Healthy Weight 65 kg 20% male 28 years Location: CANADA Obese, hyperlipidemic BMI I:35, C:34 26% male I:44 years, C:46 years Location: USA Description of diets included in analyses (as per authors’ description) and actual intake reported for each diet high protein (substitution of mixed carbohydrates with low-fat, high protein foods) to low protein diet; not for weight loss; crossover design Intervention diet: isocaloric, 2178 kcal/day, 22% pro, 30% vegetable protein, 43% cho, 35% fat Control diet: isocaloric, 2155 kcal/day, 12% pro, 60% vegetable, 53% cho, 35% fat very low carbohydrate (with increasing carbohydrate to weight maintenance weekk 10 + mutivitamin and nutritional supplement) vs low fat low calorie diet Intervention diet: ad libitum (but was hypocaloric, ) 1461 kcal/day, 26% pro, 8% cho, 68% fat Control diet: hypocaloric, 1502 kcal/day, 19% pro, 52% cho, 29% fat Outcomes meeting inclusion criteria Followup(days) Weight, BMI, total cholesterol, HDL, LDL, TG, satiety 28 Weight, BMI, blood pressure, total cholesterol, HDL, LDL, TG, creatinine, adverse effects 168 Abbreviations: I, intervention group; C: control group; pro, protein: cho, carbohydrate; BMI, body mass index; Finsulin, fasting serum insulin; Fglucose, fasting serum glucose; HDL, high density lipoproteins; LDL, low density lipoproteins; TG, triglycerides; 25 References to included studies NOTE: references ordered by study and articles that were published about each study; *indicates primary article for study Note: we highlighted new references from the updated search for the peer reviewers only. Abete 2009 1. 2. Abete I, Parra D, Martinez JA. Legume-, fish-, or high-protein-based hypocaloric diets: effects on weight loss and mitochondrial oxidation in obese men. Journal of Medicinal Food 2009;12(1):100-8. Abete I, Parra D, De Morentin BM, Martinez JA. Effects of two energy-restricted diets differing in the carbohydrate/protein ratio on weight loss and oxidative changes of obese men. International Journal of Food Sciences and Nutrition.2009;60(SUPPL.3):1-13. Aldrich 2011 3. Aldrich ND, Reicks MM, Sibley SD, Redmon JB, Thomas W, Raatz SK. Varying protein source and quantity do not significantly improve weight loss, fat loss, or satiety in reduced energy diets among midlife adults. Nutrition Research 2011;31(2):104-112. Appel 2005 4. 5. 6. 7. Appel LJ, Sacks FM, Carey VJ, Obarzanek E, Swain JF, Miller ER III, et al. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA 2005;294(19):2455-64. Beasley JM, Ange BA, Anderson CA, Miller ER III, Erlinger TP, Holbrook JT, et al. Associations between macronutrient intake and self-reported appetite and fasting levels of appetite hormones: results from the Optimal Macronutrient Intake Trial to Prevent Heart Disease. American Journal of Epidemiology 2009;169(7):893-900. Furtado JD, Campos H, Appel LJ, Miller ER, Laranjo N, Carey VJ, et al. Effect of protein, unsaturated fat, and carbohydrate intakes on plasma apolipoprotein B and VLDL and LDL containing apolipoprotein C-III: results from the OmniHeart Trial. American Journal of Clinical Nutrition 2008;87(6):1623-30. Swain JF, McCarron PB, Hamilton EF, Sacks FM, Appel LJ, Swain Janis F, et al. Characteristics of the diet patterns tested in the optimal macronutrient intake trial to prevent heart disease (OmniHeart): options for a heart-healthy diet. Journal of the American Dietetic Association 2008;108(2):257-65. Aude 2004 8. Aude YW, Agatston AS, Lopez-Jimenez F, Lieberman EH, Marie Almon, Hansen M, et al. The national cholesterol education program diet vs a diet lower in carbohydrates and higher in protein and monounsaturated fat: a randomized trial. Archives of Internal Medicine 2004;164(19):2141-6. Baba 1999 9. Baba NH, Sawaya S, Torbay N, Habbal Z, Azar S, Hashim SA, et al. High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects. International Journal of Obesity & Related Metabolic Disorders: Journal of the International Association for the Study of Obesity 1999;23(11):1202-6. Ballesteros-Pomar 2010 10. Ballesteros-Pomar MD, Calleja-Fernandez AR, Vidal-Casariego A, Urioste-Fondo AM, Cano-Rodriguez I. Effectiveness of energy-restricted diets with different protein:carbohydrate ratios: the relationship to insulin sensitivity. Public Health Nutrition 2010;13(12):2119-26. Barnard 2004 11. Barnard ND, Scialli AR, Turner-McGreivy G, Lanou AJ. Acceptability of a low-fat vegan diet compares favorably to a Step II Diet in a randomized, controlled trial. Journal of Cardiopulmonary Rehabilitation 2004;24:229-235. 12. Turner-McGrievy GM, Barnard ND, Scialli AR, Lanou AJ, Turner-McGrievy Gabrielle M, Barnard Neal D, et al. Effects of a low-fat vegan diet and a Step II diet on macro- and micronutrient intakes in overweight postmenopausal women. Nutrition 2004;20(9):738-46. 26 Belobrajdic 2010 13. Belobrajdic DP, Frystyk J, Jeyaratnaganthan N, Espelund U, Flyvbjerg A, Clifton PM, et al. Moderate energy restriction-induced weight loss affects circulating IGF levels independent of dietary composition. European Journal of Endocrinology 2010 162;Supplement (6):1075-1082. 14. Benassi-Evans B, Clifton PM, Noakes M, Keogh JB, Fenech M. High protein-high red meat versus high carbohydrate weight loss diets do not differ in effect on genome stability and cell death in lymphocytes of overweight men. Mutagenesis 2009;24(3):271-7. Bowden 2007 15. Bowden RG, Lanning BA, Doyle EI, Slonaker B, Johnston HM, Scanes G, et al. Systemic glucose level changes with a carbohydrate-restricted and higher protein diet combined with exercise. Journal of American College Health 2007;56(2):147-52. Brehm 2003 16. Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. Journal of Clinical Endocrinology and Metabolism 2003;88(4):1617-23. Brehm 2005 17. Brehm BJ, Spang SE, Lattin BL, Seeley RJ, Daniels SR, D'Alessio DA, et al. The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets. Journal of Clinical Endocrinology & Metabolism 2005;90(3):1475-82. Brinkworth 2009 18. Brinkworth GD, Noakes M, Buckley JD, Keogh JB, Clifton PM. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Am J Clin Nutr 2009;90:23-32. 19. Keogh JB, Brinkworth GD, Noakes M, Belobrajdic DP, Buckley JD, Clifton PM. Effects of weight loss from a very-low-carbohydrate diet on endothelial function and markers of cardiovascular disease risk in subjects with abdominal obesity. Am J Clin Nutr 2008;87:567-76. 20. Tay J, Brinkworth GD, Noakes M, Keogh J, Clifton PM. Metabolic effects of weight loss on a very-lowcarbohydrate diet compared with an isocaloric high-carbohydrate diet in abdominally obese subjects. J Am Coll Cardiol 2008;51(1):59-67. 21. Brinkworth GD, Buckley JD, Noakes M, Clifton PM. Renal Function Following Long-Term Weight Loss in Individuals with Abdominal Obesity on a Very-Low-Carbohydrate Diet vs High-Carbohydrate Diet. Journal of the American Dietetic Association 2010;110(4):633-638. 22. Brinkworth GD, Buckley JD, Noakes M, Clifton PM, Wilson CJ. Long-term effects of a very low-carbohydrate diet and a low-fat diet on mood and cognitive function. Archives of Internal Medicine 2009;169(20):18731880. 23. Halyburton AK, Brinkworth GD, Wilson CJ, Noakes M, Buckley JD, Keogh JB, et al. Low- and high-carbohydrate weight-loss diets have similar effects on mood but not cognitive performance. The American journal of clinical nutrition 2007;86(3):580-7. Buscemi 2009 24. Buscemi S, Verga S, Tranchina MR, Cottone S, Cerasola G. Effects of hypocaloric very-low-carbohydrate diet vs.Mediterranean diet on endothelial function in obese women. European Journal of Clinical Investigation.39(5)()(pp 339-347), 2009.Date of Publication: May 2009. 2009;(5):339-47. Dansinger 2005 25. Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ, Dansinger Michael L, et al. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial.[see comment]. JAMA 2005;293(1):43-53. Das 2007 27 26. Das SK, Gilhooly CH, Golden JK, Pittas AG, Fuss PJ, Cheatham RA, et al. Long-term effects of 2 energyrestricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial. The American journal of clinical nutrition 2007;85(4):1023-30. de Luis 2007 27. de Luis DA, Aller R, Izaola O, Gonzalez Sagrado M, Bellioo D, Conde R, et al. Effects of a low-fat versus a lowcarbohydrate diet on adipocytokines in obese adults. Hormone Research 2007;67(6):296-300. de Luis 2009a 28. de Luis DA, Gonzalez SM, Aller R, Izaola O, Conde R. Influence of Trp64Arg polymorphism of beta 3adrenoreceptor gene on insulin resistance, adipocytokines and weight loss secondary to two hypocaloric diets. Annals of Nutrition & Metabolism 2009;54(2):104-10. de Luis 2009b 29. de Luis DA, Sagrado MG, Conde R, Aller R, Izaola O. The effects of two different hypocaloric diets on glucagonlike peptide 1 in obese adults, relation with insulin response after weight loss. Journal of Diabetes and its Complications 2009;23(4);239-243. Delbridge 2009 30. Delbridge EA, Prendergast LA, Pritchard JE, Proietto J. One-year weight maintenance after significant weight loss in healthy overweight and obese subjects: Does diet composition matter? American Journal of Clinical Nutrition.90 (5) (pp 1203-1214) 2009;01. Due 2004 31. Due A, Toubro S, Skov AR, Astrup A. Effect of normal-fat diets, either medium or high in protein, on body weight in overweight subjects: a randomised 1-year trial. International Journal of Obesity & Related Metabolic Disorders: Journal of the International Association for the Study of Obesity 2004;28(10):1283-90. 32. Due A, Toubro S, Stender S, Skov AR, Astrup A, Due A, et al. The effect of diets high in protein or carbohydrate on inflammatory markers in overweight subjects. Diabetes, Obesity & Metabolism 2005;7(3):223-9. 33. Skov AR, Haulrik N, Toubro S, Molgaard C, Astrup A. Effect of protein intake on bone mineralization during weight loss: a 6-month trial. Obesity Research 2002;10(6):432-438. 34. Skov AR, Toubro S, Bulow J, Krabbe K, Parving HH, Astrup A, et al. Changes in renal function during weight loss induced by high vs low-protein low-fat diets in overweight subjects. International Journal of Obesity & Related Metabolic Disorders: Journal of the International Association for the Study of Obesity 1999;23(11):1170-7. 35. Skov AR, Toubro S, Ronn B, Holm L, Astrup A, Skov AR, et al. Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity. International Journal of Obesity & Related Metabolic Disorders: Journal of the International Association for the Study of Obesity 1999;23(5):528-36. Dyson 2007 36. Dyson PA, Beatty S, Matthews DR, Dyson PA, Beatty S, Matthews DR. A low-carbohydrate diet is more effective in reducing body weight than healthy eating in both diabetic and non-diabetic subjects. Diabetic Medicine 2007;24(12):1430-5. Farnsworth 2003 37. Farnsworth E, Luscombe ND, Noakes M, Wittert G, Argyiou E, Clifton PM, et al. Effect of a high-protein, energy-restricted diet on body composition, glycemic control, and lipid concentrations in overweight and obese hyperinsulinemic men and women. American Journal of Clinical Nutrition 2003;78(1):31-9. 38. Luscombe ND, Clifton PM, Noakes M, Farnsworth E, Wittert G, Luscombe ND, et al. Effect of a high-protein, energy-restricted diet on weight loss and energy expenditure after weight stabilization in hyperinsulinemic subjects. International Journal of Obesity & Related Metabolic Disorders: Journal of the International Association for the Study of Obesity 2003;27(5):582-90. 39. Luscombe ND, Noakes M, Wittert G, Farnsworth E, Argyiou E, Clifton PM. Effect of a high protein, energy restricted diet on body composition, insulin sensitivity and lipid levels in hyperinsulinemic subjects (abstract). Atherosclerosis 2002;3(2). Ferrara 2006 28 40. Ferrara LA, Innelli P, Palmieri V, Limauro S, De Luca G. Effects of different dietary protein intakes on body composition and vascular reactivity. European Journal of Clinical Nutrition 2006;60(5):643-9. Fleming 2002 41. Fleming RM. The effect of high-, moderate-, and low-fat diets on weight loss and cardiovascular disease risk factors. Preventive Cardiology.5(3)()(pp 110-118), 2002.Date of Publication: Jun 2002. 2002;(3):110-8. Foster 2003 42. Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, et al. A randomized trial of a lowcarbohydrate diet for obesity. New England Journal of Medicine 2003;348(21):2082-90. Gardner 2007 43. Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA 2007;297(9):969-77. Greene 2004 44. Greene PJ, Devecis J, Willett WC. Effects of low-fat vs ultra-low-carbohydrate weight-loss diets: A 12-week pilot feeding study. Journal of Parenteral and Enteral Nutrition 2004;28(1):S13-4. Hodgson 2006 45. Hodgson JM, Burke V, Beilin LJ, Puddey IB, Hodgson Jonathan M, Burke Valerie, et al. Partial substitution of carbohydrate intake with protein intake from lean red meat lowers blood pressure in hypertensive persons. American Journal of Clinical Nutrition 2006;83(4):780-7. 46. Hodgson JM, Ward NC, Burke V, Beilin LJ, Puddey IB, Hodgson Jonathan M, et al. Increased lean red meat intake does not elevate markers of oxidative stress and inflammation in humans. Journal of Nutrition 2007;137(2):363-7. Iglay 2007 47. 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Annals of Internal Medicine 2004;140(10):769-77. 34 Supplement 3: List of excluded studies of interest and primary reason for exclusion Note: articles of studies which were included but did not provide additional data were excluded. Excluded study Reason Abete 2008 Less than 5% difference in protein between diets Andreenko 1978 Awaiting translation Aston 2008 Less than 5% difference in protein between diets Bopp 2008 Co-intervention could not be separated Borghi 2002 Co-intervention could not be separated Chan 2008 Less than 5% difference in protein between diets Dale 2009 Less than 5% difference in protein between diets DeLuis 2009 Awaiting translation DeLuis 2009 (Horm Met Res) Same study as DeLuis Ann Nut Metab with no additional data Dewell 2008 Less than 5% difference in protein between diets Dussol 2008 Less than 5% difference in protein between diets Erkkila 2008 Less than 5% difference in protein between diets Gordon 2008 Liquid supplements Greany 2008 Less than 5% difference in protein between diets Harrrington 2004 Co-intervention could not be separated Hays 2004 Less than 5% difference in protein between diets Hursel 2009 Cannot separate out participants Jacobs 2009 Less than 5% difference in protein between diets Kavanagh 2009 Cannot separate out participants Kirk 2009 Less than 5% difference in protein between diets Krauss 2006 First phase data not available Larsen 2010 Less than 5% difference in protein between diets Lejeune 2005 Protein packet supplements Lim 2009 Less than 5% difference in protein between diets Martin 2006 Awaiting reply from author Raeini-Sarjaz 2001 No reply from author Sacks 1983 Less than 5% difference in protein between diets Sagara 2004 No reply from author Seshadri 2004 More than 20% participants requiring dietary restrictions Shai 2008 Less than 5% difference in protein between diets Tsai 2005 More than 20% participants requiring dietary restrictions Verrillo 1985 Less than 5% difference in protein between diets Vollmer 2008 Less than 5% difference in protein between diets Westerterp-Pantenga 2009 Less than 28 days duration Wycherley 2009 Subgroup of Brinkworth 2009 AJCN with no additional data 35 Supplement 4: Meta-analyses of all health outcomes for change scores (SD: Standard deviation; IV: inverse variance method; Std: Standard; CI: confidence intervals) Weight loss Higher protein Study or Subgroup Mean SD Total Abete 2009 -8.5 1.1 9 Aldrich 2011 -5.9 1.45 6 Aude 2004 -6.2 1.8 22 Baba 1999 -8.3 1.9 7 Ballesteros-Pomar 2010 -9 5.53 18 Belobrajdic 2010 -9.3 3.62 34 Brehm 2003 -8.5 4.7 22 Brehm 2005 -6.69 2.2 20 Brinkworth 2009 -13.1 12.1 57 Dansinger 2005 -3.8 3.6 40 Das 2007 -7.8 5 14 Delbridge 2009 3 7.13 42 Due 2004 -6.2 5.6 23 Dyson 2007 -5.8 3.1 6 Foster 2003 -7.2 7.2 33 Greene 2004 -10.5 5.5 7 Greene 2004 -9.1 4.1 7 Jenkins 2009 -3.9 2 25 Keogh 2007 -4.6 5.9 8 Labayen 2003 -9.2 3.7 6 Landers 2002 -4.44 3.21 12 Lasker 2008 -9.1 4.5 25 Layman 2009 -8.2 3.6 52 Lean 1997 -5.4 5.1 53 Leidy 2007 -8.1 1.83 21 Mahon 2007 -6.6 2.7 14 Maki 2007 -4.9 3.2 42 McMillan-Price 2006 -5.3 2.83 32 McMillan-Price 2006b -4.4 2.83 33 Morgan 2009 -6 6.4 57 Noakes 2005 -7.6 2.9 52 Rouse 1986 0.8 0.2 19 Sacks 2009 -5.8 9.9 201 Stamets 2004 -3.7 1.9 13 Stoernell 2008 -1.7 1.5 10 Te Morenga 2011 -4.5 2.4 37 Volek 2003 -1.2 0.8 5 Volek 2004 -3.2 0.5 7 Volek 2004 -8.1 0.7 8 Yancy 2004 -12 6.9 59 Lower protein diets Std. Mean Difference Mean SD Total Weight IV, Random, 95% CI -4.7 2.9 10 1.8% -1.62 [-2.69, -0.55] -5.3 1.86 6 1.6% -0.33 [-1.48, 0.81] -3.4 2 23 2.6% -1.44 [-2.11, -0.78] -6 1.5 6 1.5% -1.24 [-2.47, -0.01] -7.2 4.2 18 2.6% -0.36 [-1.02, 0.30] -8.1 3.31 42 3.2% -0.34 [-0.80, 0.11] -3.9 4.5 20 2.7% -0.98 [-1.62, -0.34] -4.79 2.6 20 2.7% -0.77 [-1.42, -0.13] -11.6 12.5 61 3.4% -0.12 [-0.48, 0.24] -3.5 3.8 40 3.2% -0.08 [-0.52, 0.36] -8 4.1 15 2.5% 0.04 [-0.69, 0.77] 4.3 8.85 40 3.2% -0.16 [-0.59, 0.27] -4.3 4.2 18 2.7% -0.37 [-0.99, 0.25] -2.8 1.6 4 1.3% -1.03 [-2.42, 0.36] -4.4 7.8 30 3.0% -0.37 [-0.87, 0.13] -7.7 1.9 3 1.3% -0.52 [-1.90, 0.86] -7.7 2.2 4 1.5% -0.36 [-1.60, 0.89] -4.2 1.5 25 2.9% 0.17 [-0.39, 0.72] -5.5 2.7 5 1.7% 0.17 [-0.95, 1.29] -4.8 2.5 5 1.3% -1.25 [-2.60, 0.11] -5.4 2.75 21 2.5% 0.32 [-0.39, 1.03] -6.9 4 25 2.9% -0.51 [-1.07, 0.06] -7 3.6 51 3.3% -0.33 [-0.72, 0.06] -4.2 4.5 57 3.3% -0.25 [-0.62, 0.13] -9.5 5 25 2.8% 0.35 [-0.23, 0.94] -5.6 1.8 14 2.4% -0.42 [-1.17, 0.33] -2.5 3.2 42 3.2% -0.74 [-1.19, -0.30] -3.7 2.83 32 3.0% -0.56 [-1.06, -0.06] -4.8 2.83 32 3.1% 0.14 [-0.35, 0.63] 0.6 2.2 61 3.3% -1.39 [-1.79, -0.99] -6.9 3.5 48 3.3% -0.22 [-0.61, 0.18] -0.25 0.35 20 1.8% 3.58 [2.54, 4.63] -5.6 12.1 204 3.7% -0.02 [-0.21, 0.18] -4.4 1.5 13 2.4% 0.40 [-0.38, 1.17] -0.7 1.2 13 2.2% -0.72 [-1.58, 0.13] -3.3 2.7 37 3.1% -0.46 [-0.93, -0.00] -0.8 1 5 1.4% -0.40 [-1.66, 0.86] -2.9 0.7 6 1.7% -0.47 [-1.58, 0.65] -4.4 0.6 7 0.5% -5.31 [-7.75, -2.88] -6.5 7.4 60 3.4% -0.76 [-1.14, -0.39] Std. Mean Difference IV, Random, 95% CI Total (95% CI) 1158 1168 100.0% -0.36 [-0.56, -0.17] Heterogeneity: Tau² = 0.25; Chi² = 167.76, df = 39 (P < 0.00001); I² = 77% -4 -2 0 2 4 Test for overall effect: Z = 3.71 (P = 0.0002) Favours higher Favours lower 35 36 Change in Body Mass Index Higher protein diets Lower protein diets Mean SD Total Mean SD Abete 2009 -3.1 0.53 9 -1.5 0.94 Baba 1999 Study or Subgroup Std. Mean Difference Total Weight IV, Random, 95% CI 10 2.3% -1.97 [-3.12, -0.83] -2.7 0.5 7 -2 0.5 6 2.0% -1.30 [-2.55, -0.06] Belobrajdic 2010 -3 1.16 34 -2.5 1.23 42 8.3% -0.41 [-0.87, 0.04] Brinkworth 2009 -5.2 3.4 33 -4.1 2.4 36 8.0% -0.37 [-0.85, 0.10] Dansinger 2005 -1.3 1.2 40 -1.2 1.3 40 8.7% -0.08 [-0.52, 0.36] Delbridge 2009 1 2.59 42 1.4 3.16 40 8.8% -0.14 [-0.57, 0.30] Due 2004 -2.2 2.1 23 -1.5 2 18 5.9% -0.33 [-0.96, 0.29] Dyson 2007 -2.2 1.2 6 -1.1 0.7 4 1.7% -0.95 [-2.33, 0.42] Gardner 2007 -1.6 0.98 77 -0.99 1 79 11.1% -0.61 [-0.93, -0.29] Johnston 2004 -1.5 0.6 9 -1.8 0.6 7 2.9% 0.47 [-0.53, 1.48] Lasker 2008 -3.1 1.5 25 -2.4 1.5 25 6.6% -0.46 [-1.02, 0.10] Lean 1997 -2.6 2 40 -2.2 1.8 42 8.7% -0.21 [-0.64, 0.23] Leidy 2007 -3 0.46 21 -3.4 1.5 25 6.3% 0.34 [-0.24, 0.93] -2.5 1.1 14 -2.1 0.7 14 4.5% -0.42 [-1.17, 0.33] -2.53 3.1 23 -0.98 1.54 22 6.1% -0.62 [-1.22, -0.02] -1.7 0.9 37 -1.2 0.9 37 8.2% -0.55 [-1.01, -0.09] 447 100.0% -0.37 [-0.56, -0.19] Mahon 2007 Seshadri 2005 Te Morenga 2011 Total (95% CI) 440 Heterogeneity: Tau² = 0.06; Chi² = 25.71, df = 15 (P = 0.04); I² = 42% Std. Mean Difference IV, Random, 95% CI -2 -1 0 1 2 Favours higher protein Favours lower protein Test for overall effect: Z = 3.91 (P < 0.0001) Change in waist circumference Study or Subgroup Abete 2009 Higher protein diets Lower protein diets Mean SD Total Mean SD Std. Mean Difference -10.6 2.7 9 -6.4 3.3 10 4.0% Total Weight IV, Random, 95% CI -3 3.5 40 -3.5 4.2 40 7.6% 0.13 [-0.31, 0.57] Delbridge 2009 -0.8 6.48 42 0.92 9.49 40 7.7% -0.21 [-0.64, 0.22] Due 2004 -8.4 4.9 23 -1.8 3.7 18 5.8% -1.47 [-2.17, -0.76] Greene 2004 -9.7 12.1 7 -6.6 7.1 4 3.1% -0.26 [-1.50, 0.97] Greene 2004 -10.9 12.1 7 -6.6 6.2 3 2.7% -0.36 [-1.72, 1.01] -4 4.5 8 -7 1.6 5 3.3% 0.75 [-0.42, 1.92] Lean 1997 -6.5 5 40 -5.7 4.8 41 7.7% -0.16 [-0.60, 0.27] Maki 2007 -4.3 4.3 37 -2.8 3.2 42 7.6% -0.40 [-0.84, 0.05] McMillan-Price 2006 -6.3 3.39 32 -4.3 3.96 32 7.2% -0.54 [-1.04, -0.04] McMillan-Price 2006b -5 3.96 33 -5.6 3.96 32 7.3% 0.15 [-0.34, 0.64] Morgan 2009 -8.1 7.4 57 -0.8 3.8 61 8.0% -1.25 [-1.64, -0.85] Sacks 2009 -0.05 [-0.24, 0.15] -6.2 12.8 201 -5.6 11.4 204 9.2% Stamets 2004 -5 5 13 -1 6 13 5.2% -0.70 [-1.50, 0.09] Stoernell 2008 -10.1 5 23 -4.2 6.2 23 6.3% -1.03 [-1.65, -0.41] -5.4 2.7 37 -4.7 3.3 37 7.5% -0.23 [-0.69, 0.23] 605 100.0% -0.43 [-0.69, -0.16] Te Morenga 2011 Total (95% CI) 609 Heterogeneity: Tau² = 0.19; Chi² = 60.83, df = 15 (P < 0.00001); I² = 75% Test for overall effect: Z = 3.18 (P = 0.001) IV, Random, 95% CI -1.32 [-2.34, -0.31] Dansinger 2005 Keogh 2007 Std. Mean Difference -4 -2 0 2 4 Favours higher protein Favours lower protein 36 37 Change in systolic blood pressure Higher protein diets Lower protein diets Mean SD Total Mean SD Abete 2009 -13.3 14.7 9 -3 5.8 Aldrich 2011 -8.7 9.55 6 -2.2 12.5 Appel 2005 -9.5 8.8 82 -8.2 9.1 Brinkworth 2009 -13.8 14.4 33 -14.6 12 Dansinger 2005 -4.1 14 40 -4.8 Delbridge 2009 1.9 18.1 42 Foster 2003 -1.9 14.7 Gardner 2007 -6.8 8 Lean 1997 -0.3 Leidy 2007 -5 Maki 2007 Morgan 2009 Study or Subgroup Stamets 2004 Std. Mean Difference Total Weight 10 IV, Random, 95% CI 1.4% -0.90 [-1.86, 0.06] 6 1.0% -0.54 [-1.70, 0.62] 82 14.0% -0.14 [-0.45, 0.16] 36 5.9% 0.06 [-0.41, 0.53] 13 40 6.8% 0.05 [-0.39, 0.49] 7.5 14.5 40 6.9% -0.34 [-0.77, 0.10] 33 3.6 19.5 30 5.3% -0.32 [-0.81, 0.18] 77 -3.6 6.9 79 13.0% -0.43 [-0.74, -0.11] 17.3 36 -1.1 16.7 38 6.3% 0.05 [-0.41, 0.50] 9.17 21 -3 10 25 3.9% -0.20 [-0.79, 0.38] -0.6 13 42 -1.2 14.9 42 7.2% 0.04 [-0.39, 0.47] -7.2 11.6 57 -2.8 11.8 61 9.9% -0.37 [-0.74, -0.01] -4 13 13 -3 13 13 2.2% -0.07 [-0.84, 0.69] Te Morenga 2011 -5.4 9 37 -1.7 8.1 37 6.2% -0.43 [-0.89, 0.03] Yancy 2004 -9.6 14 59 -7.5 15.7 60 10.1% -0.14 [-0.50, 0.22] 599 100.0% -0.21 [-0.32, -0.09] Total (95% CI) 587 Heterogeneity: Tau² = 0.00; Chi² = 11.84, df = 14 (P = 0.62); I² = 0% Std. Mean Difference IV, Random, 95% CI -4 -2 0 2 4 Favours higher protein Favours lower protein Test for overall effect: Z = 3.56 (P = 0.0004) Change in diastolic blood pressure Higher protein diets Lower protein diets Mean SD Total Mean SD -5 10.4 9 -5.5 7.2 Aldrich 2011 -4.3 5.14 6 3.8 10.3 Appel 2005 -5.2 3.9 82 -4.1 3.9 Brinkworth 2009 -6.3 9.2 33 -7.9 9.6 36 5.9% 0.17 [-0.31, 0.64] Dansinger 2005 -4.8 7.6 40 -3.1 7.4 40 6.8% -0.22 [-0.66, 0.22] 0.00 [-0.43, 0.43] Study or Subgroup Abete 2009 Delbridge 2009 Std. Mean Difference Total Weight 10 IV, Random, 95% CI 1.6% 0.05 [-0.85, 0.95] 6 0.9% -0.92 [-2.14, 0.30] 82 13.6% -0.28 [-0.59, 0.03] 3.7 14.3 42 3.7 12 40 7.0% Foster 2003 -4.6 11.6 33 -5.2 13.3 30 5.4% 0.05 [-0.45, 0.54] Gardner 2007 -2.9 6.2 77 -1.4 4.4 79 13.0% -0.28 [-0.59, 0.04] Lean 1997 -2.3 11.2 36 -2.7 11.4 38 6.4% 0.04 [-0.42, 0.49] Leidy 2007 -4 4.58 21 -6 10 25 3.9% 0.25 [-0.34, 0.83] Maki 2007 -3.3 11.7 42 -0.6 9.1 42 7.1% -0.26 [-0.68, 0.17] Morgan 2009 -4.9 8.1 57 -1.6 7.4 61 9.8% -0.42 [-0.79, -0.06] Stamets 2004 0 18 13 0 11 13 2.3% 0.00 [-0.77, 0.77] -4.7 6 37 -0.9 6.6 37 6.1% -0.60 [-1.06, -0.13] -6 7.9 59 -5.2 8.9 60 10.1% -0.09 [-0.45, 0.27] 599 100.0% -0.18 [-0.29, -0.06] Te Morenga 2011 Yancy 2004 Total (95% CI) 587 Heterogeneity: Tau² = 0.00; Chi² = 14.27, df = 14 (P = 0.43); I² = 2% Test for overall effect: Z = 3.01 (P = 0.003) Std. Mean Difference IV, Random, 95% CI -4 -2 0 2 4 Favours higher protein Favours lower protein 37 38 Change in total cholesterol Higher protein Lower protein diets Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI Abete 2009 -0.41 Appel 2005 -0.51 Aude 2004 -0.31 Baba 1999 -1.27 Brinkworth 2009 0.7 Dansinger 2005 -0.48 Das 2007 -0.3 Delbridge 2009 0.54 Dyson 2007 0.2 Foster 2003 0.01 Lean 1997 -0.12 Leidy 2007 -0.83 Mahon 2007 -0.59 Maki 2007 -0.32 McMillan-Price 2006 0.24 McMillan-Price 2006b -0.05 Morgan 2009 -0.3 Noakes 2005 -0.48 Stamets 2004 -0.7 Te Morenga 2011 -0.6 Yancy 2004 -0.21 Total (95% CI) 0.61 0.42 0.76 1.16 1.1 0.65 0.48 0.84 0.6 0.66 0.9 0.71 0.93 0.44 0.56 0.56 0.8 0.7 1.19 0.54 0.8 9 82 22 7 33 40 14 42 6 33 37 21 14 39 32 33 57 52 13 37 59 682 -0.32 -0.32 -0.34 -0.86 0.1 -0.38 0 0.36 -0.1 -0.28 -0.34 -0.75 -1.14 -0.21 0.05 -0.18 -0.5 -0.33 -0.47 -0.5 -0.35 0.5 0.39 0.45 0.1 0.6 0.67 0.41 1.08 0.2 0.52 0.7 0.65 1.71 0.59 0.56 0.56 0.18 0.6 0.39 0.6 1.4 10 82 23 6 36 40 15 40 4 30 40 25 14 38 32 32 61 48 13 37 60 2.3% 7.7% 4.2% 1.6% 5.3% 5.8% 3.0% 5.9% 1.2% 5.1% 5.7% 4.3% 3.0% 5.7% 5.2% 5.2% 6.9% 6.4% 2.9% 5.6% 6.9% -0.16 [-1.06, 0.75] -0.47 [-0.78, -0.16] 0.05 [-0.54, 0.63] -0.44 [-1.55, 0.67] 0.68 [0.19, 1.16] -0.15 [-0.59, 0.29] -0.66 [-1.41, 0.10] 0.18 [-0.25, 0.62] 0.55 [-0.75, 1.86] 0.48 [-0.02, 0.98] 0.27 [-0.18, 0.72] -0.12 [-0.70, 0.46] 0.39 [-0.36, 1.14] -0.21 [-0.66, 0.24] 0.34 [-0.16, 0.83] 0.23 [-0.26, 0.72] 0.35 [-0.02, 0.71] -0.23 [-0.62, 0.17] -0.25 [-1.02, 0.52] -0.17 [-0.63, 0.28] 0.12 [-0.24, 0.48] 686 100.0% 0.04 [-0.11, 0.20] Heterogeneity: Tau² = 0.05; Chi² = 37.09, df = 20 (P = 0.01); I² = 46% Test for overall effect: Z = 0.57 (P = 0.57) Std. Mean Difference IV, Random, 95% CI -2 -1 Favours higher 0 1 2 Favours lower 38 39 Change in high density lipoprotein Higher protein lower protein diet Std. Mean Difference Study or SubgroupMean SD Total Mean SD Total Weight IV, Random, 95% CI Abete 2009 -0.24 Appel 2005 -0.07 Aude 2004 -0.03 Baba 1999 -0.12 Brinkworth 2009 0.3 Dansinger 2005 0.05 Das 2007 0.16 Delbridge 2009 0.18 Dyson 2007 0.08 Foster 2003 0.22 Gardner 2007 -0.01 Greene 2004 0 Greene 2004 -0.03 Johnston 2004 -0.2 Lean 1997 0.05 Leidy 2007 -0.23 Mahon 2007 -0.05 Maki 2007 -0.01 McMillan-Price 2006 0.07 McMillan-Price 2006 0.05 Morgan 2009 -0.1 Noakes 2005 -0.09 Stamets 2004 0.18 Te Morenga 2011 -0.1 Yancy 2004 0.14 Total (95% CI) 0.41 0.12 0.24 0.13 0.4 0.2 0.13 0.26 0.17 0.27 0.2 0.2 0.2 0.2 0.02 0.12 0.28 0.2 0.23 0.23 0.1 0.1 0.8 0.12 0.31 9 82 22 7 33 40 14 42 6 33 77 7 7 9 34 21 14 39 33 32 57 52 13 37 59 779 -0.21 -0.04 -0.1 0.09 0.07 0.01 0.19 0.16 0.06 0.04 -0.1 -0.07 -0.07 -0.3 -0.02 -0.16 -0.31 -0.05 0.03 0.08 -0.2 -0.09 -0.08 -0.1 -0.04 0.41 0.13 0.16 0.13 0.4 0.05 0.23 0.19 0.23 0.19 0.2 0.1 0.1 0.3 0.2 0.26 0.44 0.1 0.23 0.23 0.04 0.1 0.13 0.18 0.29 10 82 23 6 36 40 15 40 4 30 79 3 4 7 37 25 14 38 32 32 61 48 13 37 60 2.6% 5.9% 4.1% 1.6% 4.7% 5.0% 3.3% 5.0% 1.6% 4.5% 5.8% 1.4% 1.7% 2.3% 4.8% 4.1% 3.2% 4.9% 4.7% 4.7% 5.3% 5.3% 3.1% 4.9% 5.5% -0.07 [-0.97, 0.83] -0.24 [-0.55, 0.07] 0.34 [-0.25, 0.93] -1.50 [-2.79, -0.21] 0.57 [0.09, 1.05] 0.27 [-0.17, 0.71] -0.15 [-0.88, 0.57] 0.09 [-0.35, 0.52] 0.09 [-1.17, 1.36] 0.76 [0.24, 1.27] 0.45 [0.13, 0.77] 0.35 [-1.02, 1.72] 0.21 [-1.02, 1.44] 0.38 [-0.62, 1.38] 0.48 [0.00, 0.95] -0.33 [-0.91, 0.25] 0.68 [-0.08, 1.45] 0.25 [-0.20, 0.70] 0.17 [-0.32, 0.66] -0.13 [-0.62, 0.36] 1.32 [0.92, 1.72] 0.00 [-0.39, 0.39] 0.44 [-0.34, 1.22] 0.00 [-0.46, 0.46] 0.60 [0.23, 0.96] 776 100.0% 0.25 [0.07, 0.44] Heterogeneity: Tau² = 0.13; Chi² = 68.17, df = 24 (P < 0.00001); I² = 65% Test for overall effect: Z = 2.71 (P = 0.007) Std. Mean Difference IV, Random, 95% CI -2 -1 Favours lower 0 1 2 Favours higher 39 40 Change in low density lipoprotein Higher protein lower protein diet Std. Mean Difference Study or SubgroupMean SD Total Mean SD Total Weight IV, Random, 95% CI Abete 2009 -0.14 Appel 2005 -0.37 Aude 2004 -0.1 Baba 1999 -0.55 Brinkworth 2009 0.6 Dansinger 2005 0.25 Delbridge 2009 0.33 Dyson 2007 0.16 Foster 2003 0.02 Gardner 2007 0.06 Greene 2004 -0.34 Greene 2004 -0.36 Jenkins 2009 -0.9 Johnston 2004 -0.3 Lean 1997 0.03 Leidy 2007 -0.47 Mahon 2007 -0.44 Maki 2007 -0.18 McMillan-Price 2006 0.26 McMillan-Price 2006 -0.04 Morgan 2009 -0.2 Noakes 2005 -0.26 Stamets 2004 0.34 Te Morenga 2011 -0.4 Yancy 2004 0.04 0.13 0.39 0.71 0.94 1.1 0.7 0.58 0.42 0.71 0.6 0.6 0.7 0.62 0.4 0.8 0.59 0.7 0.4 0.57 0.57 0.1 0.6 0.5 0.42 0.97 Total (95% CI) 9 82 22 7 33 40 42 6 33 77 7 7 25 9 34 21 14 39 32 33 57 52 13 37 59 -0.09 -0.3 -0.17 -0.56 0.1 0.31 -1.4 -0.17 -0.18 0.19 -0.52 -0.52 -0.5 -0.4 -0.17 -0.57 -0.52 -0.09 0.04 -0.17 -0.1 -0.19 0.3 -0.3 -0.19 0.2 0.36 0.4 0.34 0.6 0.6 9.49 0.21 0.5 0.5 0.5 0.5 0.57 0.6 0.6 0.52 1.29 0.5 0.57 0.57 0.08 0.6 0.4 0.48 1.1 790 10 82 23 6 36 40 40 4 30 79 4 3 25 7 37 25 14 38 32 32 61 48 13 37 60 2.4% 6.1% 4.0% 1.8% 4.7% 5.0% 5.1% 1.3% 4.6% 6.0% 1.5% 1.3% 4.0% 2.1% 4.8% 4.0% 3.1% 5.0% 4.6% 4.6% 5.4% 5.4% 2.9% 4.9% 5.7% -0.28 [-1.19, 0.63] -0.19 [-0.49, 0.12] 0.12 [-0.46, 0.71] 0.01 [-1.08, 1.10] 0.56 [0.08, 1.05] -0.09 [-0.53, 0.35] 0.26 [-0.18, 0.69] 0.84 [-0.51, 2.19] 0.32 [-0.18, 0.82] -0.23 [-0.55, 0.08] 0.29 [-0.95, 1.53] 0.22 [-1.14, 1.58] -0.66 [-1.23, -0.09] 0.19 [-0.80, 1.18] 0.28 [-0.19, 0.75] 0.18 [-0.40, 0.76] 0.07 [-0.67, 0.82] -0.20 [-0.64, 0.25] 0.38 [-0.11, 0.88] 0.23 [-0.26, 0.71] -1.10 [-1.49, -0.71] -0.12 [-0.51, 0.28] 0.09 [-0.68, 0.85] -0.22 [-0.68, 0.24] 0.22 [-0.14, 0.58] 786 100.0% -0.00 [-0.17, 0.16] Heterogeneity: Tau² = 0.09; Chi² = 57.95, df = 24 (P = 0.0001); I² = 59% Test for overall effect: Z = 0.04 (P = 0.97) Std. Mean Difference IV, Random, 95% CI -2 -1 Favours higher 0 1 2 Favours lower Change in C-reactive protein Higher protein lower protein diet Std. Mean Difference Study or SubgroupMean SD Total Mean SD Total Weight IV, Random, 95% CI Brinkworth 2009 -1.3 1.1 Dansinger 2005 -0.22 1.9 Mahon 2007 0 1.5 McMillan-Price 2006 -0.01 2.26 McMillan-Price 2006 -0.8 2.26 Noakes 2005 -1.7 2.9 Total (95% CI) 31 -1.4 40 -0.04 14 -0.6 33 -1.1 32 -0.8 52 -0.8 202 1.8 1.2 4 2.26 2.26 2.1 30 40 14 32 32 48 16.2% 19.5% 8.8% 16.6% 16.8% 22.2% 0.07 [-0.44, 0.57] -0.11 [-0.55, 0.33] 0.19 [-0.55, 0.94] 0.48 [-0.02, 0.97] 0.00 [-0.49, 0.49] -0.35 [-0.75, 0.04] 196 100.0% 0.01 [-0.23, 0.25] Heterogeneity: Tau² = 0.03; Chi² = 7.17, df = 5 (P = 0.21); I² = 30% Test for overall effect: Z = 0.06 (P = 0.95) Std. Mean Difference IV, Random, 95% CI -4 -2 Favours higher 0 2 Favours lower 4 40 41 Change in HbA1c Higher protein Lower protein diet Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI Dyson 2007 Iglay 2007 Seshadri 2005 Subtotal (95% CI) -0.2 0.2 0 0 -0.17 0.58 6 17 23 46 -0.2 0 -0.16 0.2 0 0.4 4 56.8% 15 22 43.2% 41 100.0% Mean Difference IV, Random, 95% CI 0.00 [-0.25, 0.25] Not estimable -0.01 [-0.30, 0.28] -0.00 [-0.19, 0.19] Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 1 (P = 0.96); I² = 0% Test for overall effect: Z = 0.04 (P = 0.96) -0.5 -0.25 Favours higher 0 0.25 0.5 Favours lower Change in fasting blood glucose Higher protein diet Lower protein diet Mean SD Total Mean SD Abete 2009 -0.24 0.51 9 -0.17 0.35 Baba 1999 -0.44 0.31 7 -0.04 -0.3 0.34 34 -0.2 Bowden 2007 -0.29 0.27 15 Bowden 2007 -0.28 0.52 Brinkworth 2009 -0.3 Dansinger 2005 Study or Subgroup Std. Mean Difference Total Weight IV, Random, 95% CI 10 2.4% -0.15 [-1.06, 0.75] 0.38 6 1.4% -1.08 [-2.28, 0.12] 0.76 42 7.3% -0.16 [-0.62, 0.29] 0.04 0.88 34 4.6% -0.43 [-1.05, 0.18] 7 -0.08 0.65 38 2.9% -0.31 [-1.12, 0.50] 0.1 33 -0.3 0.6 36 6.9% 0.00 [-0.47, 0.47] -0.5 1.6 40 -0.3 1.3 40 7.6% -0.14 [-0.57, 0.30] Gardner 2007 0 0.4 77 0 0.5 79 11.1% 0.00 [-0.31, 0.31] Johnston 2004 0 0.7 9 -0.2 0.6 7 2.0% 0.29 [-0.71, 1.28] Lasker 2008 -0.28 0.65 25 -0.52 0.6 25 5.4% 0.38 [-0.18, 0.94] Leidy 2007 -0.04 0.5 21 -0.39 0.28 25 4.7% 0.87 [0.26, 1.48] Maki 2007 -0.2 0.4 39 0 0.4 39 7.3% -0.50 [-0.95, -0.04] McMillan-Price 2006 -0.05 0.57 32 0.04 0.57 32 6.5% -0.16 [-0.65, 0.33] McMillan-Price 2006 0.02 0.57 33 -0.06 0.57 32 6.6% 0.14 [-0.35, 0.63] Morgan 2009 -0.2 0.5 57 -0.1 0.5 61 9.6% -0.20 [-0.56, 0.16] Noakes 2005 -0.21 0.4 52 -0.25 0.5 48 8.7% 0.09 [-0.30, 0.48] Seshadri 2005 0.08 0.8 23 0.09 0.1 22 5.0% -0.02 [-0.60, 0.57] 576 100.0% -0.05 [-0.20, 0.10] Belobrajdic 2010 Total (95% CI) 513 Heterogeneity: Tau² = 0.03; Chi² = 22.38, df = 16 (P = 0.13); I² = 29% Test for overall effect: Z = 0.70 (P = 0.49) Std. Mean Difference IV, Random, 95% CI -4 -2 0 2 4 Favours higher protein Favours lower protein 41 42 Change in triglycerides Higher protein lower protein diet Std. Mean Difference Study or SubgroupMean SD Total Mean SD Total Weight IV, Random, 95% CI Abete 2009 -0.05 Appel 2005 -0.19 Aude 2004 -0.47 Baba 1999 -1.24 Brinkworth 2009 -0.58 Dansinger 2005 -0.61 Delbridge 2009 0.13 Dyson 2007 -0.1 Foster 2003 -0.42 Gardner 2007 -0.59 Greene 2004 -1.05 Greene 2004 -0.64 Jenkins 2009 -0.6 Johnston 2004 -0.2 Lean 1997 -0.25 Leidy 2007 -0.25 Mahon 2007 -0.26 Maki 2007 -0.28 McMillan-Price 2006 -0.19 McMillan-Price 2006 -0.18 Morgan 2009 -0.6 Noakes 2005 -0.3 Seshadri 2005 -0.52 Stamets 2004 -0.33 Te Morenga 2011 -0.3 Yancy 2004 -0.84 0.47 0.47 1.14 1.15 0.6 1.2 0.97 0.4 0.35 0.8 0.33 0.6 0.59 0.3 0.5 0.52 0.56 0.4 0.4 0.4 0.1 0.7 1 1 0.36 1.9 Total (95% CI) 9 82 22 7 33 40 42 6 33 77 7 7 25 9 34 21 14 39 33 32 57 52 23 13 37 59 -0.03 0 -0.17 -0.85 -0.22 -0.1 0.3 -0.1 0.02 -0.19 -0.78 -0.78 -0.4 0.1 -0.27 -0.14 -0.11 -0.13 -0.05 -0.14 -0.1 -0.11 0.05 -0.23 -0.2 -0.31 0.63 0.45 0.52 0.75 0.7 0.4 0.7 0.4 0.58 0.6 0.6 0.7 0.47 0.5 0.5 0.45 0.78 0.5 0.4 0.4 0.1 0.4 0.5 0.6 0.33 1.1 813 10 82 23 6 36 40 40 4 30 79 3 4 25 7 39 25 14 38 32 32 61 48 22 13 37 60 3.2% 4.7% 4.0% 2.7% 4.3% 4.4% 4.4% 2.4% 4.2% 4.6% 2.2% 2.5% 4.1% 2.9% 4.3% 4.0% 3.6% 4.4% 4.3% 4.3% 3.6% 4.5% 4.0% 3.6% 4.3% 4.6% -0.03 [-0.93, 0.87] -0.41 [-0.72, -0.10] -0.34 [-0.92, 0.25] -0.37 [-1.47, 0.74] -0.54 [-1.03, -0.06] -0.56 [-1.01, -0.12] -0.20 [-0.63, 0.24] 0.00 [-1.27, 1.27] -0.92 [-1.44, -0.40] -0.56 [-0.88, -0.24] -0.59 [-1.98, 0.80] 0.20 [-1.03, 1.43] -0.37 [-0.93, 0.19] -0.71 [-1.74, 0.32] 0.04 [-0.42, 0.50] -0.22 [-0.81, 0.36] -0.21 [-0.96, 0.53] -0.33 [-0.78, 0.12] -0.35 [-0.84, 0.14] -0.10 [-0.59, 0.39] -4.97 [-5.71, -4.23] -0.33 [-0.72, 0.07] -0.70 [-1.31, -0.10] -0.12 [-0.89, 0.65] -0.29 [-0.74, 0.17] -0.34 [-0.70, 0.02] 810 100.0% -0.51 [-0.78, -0.24] Heterogeneity: Tau² = 0.39; Chi² = 162.19, df = 25 (P < 0.00001); I² = 85% Test for overall effect: Z = 3.69 (P = 0.0002) Std. Mean Difference IV, Random, 95% CI -2 -1 Favours higher 0 1 2 Favours lower Change in fasting blood insulin Higher protein Lower protein diets Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI Abete 2009 -36 Baba 1999 -120.8 Brinkworth 2009 -23.6 Dansinger 2005 -49.3 Das 2007 -18 Gardner 2007 -20.8 Maki 2007 -2.8 McMillan-Price 2006 -17.1 McMillan-Price 2006b -10.4 Noakes 2005 -1.9 Seshadri 2005 -64.2 Total (95% CI) 24.1 55.6 23.9 83.3 14.5 27.1 47.9 39.6 39.1 25 135.6 9 7 33 40 14 77 39 32 33 52 23 359 -7.7 48.1 -97.9 76.4 -22.9 20.8 -12.5 41.7 -14 11.3 -13.2 32.6 6.3 47.9 -8.1 39 -13.3 39 -11.1 43.1 76.4 262.5 10 6 36 40 15 79 39 32 32 48 22 3.2% 2.4% 10.2% 11.1% 5.0% 17.5% 11.2% 9.6% 9.8% 13.2% 7.0% -0.70 [-1.63, 0.24] -0.32 [-1.42, 0.78] -0.03 [-0.50, 0.44] -0.55 [-1.00, -0.11] -0.30 [-1.03, 0.43] -0.25 [-0.57, 0.06] -0.19 [-0.63, 0.26] -0.23 [-0.72, 0.27] 0.07 [-0.41, 0.56] 0.26 [-0.13, 0.66] -0.67 [-1.27, -0.06] 359 100.0% -0.20 [-0.37, -0.03] Heterogeneity: Tau² = 0.02; Chi² = 13.00, df = 10 (P = 0.22); I² = 23% Test for overall effect: Z = 2.26 (P = 0.02) Std. Mean Difference IV, Random, 95% CI -2 -1 Favours higher 0 1 Favours lower 2 42 43 Change bone mineral density Higher protein lower protein diet Mean Difference Study or SubgroupMean SD Total Mean SD Total Weight IV, Random, 95% CI 2.14.1 total body Due 2004 1.17 0.05 25 1.17 0.05 Mahon 2007 1.126 0.0935 14 1.107 0.0973 Thorpe 2008 2.1 2.5 28 1.7 2.5 Thorpe 2008 1.5 2.3 36 1.1 1.9 Subtotal (95% CI) 103 25 86.6% 14 13.3% 31 0.0% 35 0.1% 105 100.0% Mean Difference IV, Random, 95% CI 0.00 [-0.03, 0.03] 0.02 [-0.05, 0.09] 0.40 [-0.88, 1.68] 0.40 [-0.58, 1.38] 0.00 [-0.02, 0.03] Heterogeneity: Tau² = 0.00; Chi² = 1.24, df = 3 (P = 0.74); I² = 0% Test for overall effect: Z = 0.23 (P = 0.82) 2.14.2 lumbar spine Due 2004 Thorpe 2008 Thorpe 2008 Subtotal (95% CI) 1.04 2.4 1.3 0.1 4.2 2.9 25 28 36 89 1.01 0.6 0.5 0.15 1.9 1.7 25 31 35 91 50.8% 19.2% 30.0% 100.0% 0.03 [-0.04, 0.10] 1.80 [0.11, 3.49] 0.80 [-0.30, 1.90] 0.60 [-0.34, 1.54] Heterogeneity: Tau² = 0.45; Chi² = 6.04, df = 2 (P = 0.05); I² = 67% Test for overall effect: Z = 1.25 (P = 0.21) 2.14.3 hip Thorpe 2008 Thorpe 2008 Subtotal (95% CI) -0.2 -0.2 2.5 2.2 36 28 64 -0.7 -0.9 2.1 1.7 35 47.0% 31 53.0% 66 100.0% 0.50 [-0.57, 1.57] 0.70 [-0.31, 1.71] 0.61 [-0.13, 1.34] Heterogeneity: Tau² = 0.00; Chi² = 0.07, df = 1 (P = 0.79); I² = 0% Test for overall effect: Z = 1.61 (P = 0.11) -2 -1 Favours lower 0 1 2 Favours higher Change in creatinine (umol/L) Higher protein Study or Subgroup Mean Greene 2004 Greene 2004 Leidy 2007 Total (95% CI) Lower protein diet Mean Difference SD Total Mean -6.2 17.7 -2.7 9.4 1.8 4.1 7 7 21 35 Mean Difference IV, Random, 95% CI SD Total Weight IV, Random, 95% CI -9.7 10.7 -9.7 12.4 -4.4 8.8 3 4.2% 3.50 [-14.35, 21.35] 4 6.8% 7.00 [-7.01, 21.01] 25 89.0% 6.20 [2.33, 10.07] 32 100.0% 6.14 [2.49, 9.79] Heterogeneity: Tau² = 0.00; Chi² = 0.10, df = 2 (P = 0.95); I² = 0% Test for overall effect: Z = 3.30 (P = 0.0010) -100 -50 Favours lower 0 50 100 Favours higher Satiety Higher protein Study or Subgroup Mean SD Total Aldrich 2011 61 14.6969 6 Aude 2004 4.2 0.9 29 Jenkins 2009 1.5 1.5 25 Johnston 2004 5 0.5 9 Nickols-Richardson 2005-3.2 2.4 13 Sacks 2009 64.1 18.9 164 Wolfe 1999 6.1 1.3 5 Lower protein diets Std. Mean Difference Mean SD Total Weight IV, Random, 95% CI 58 14.6969 6 6.1% 0.19 [-0.95, 1.32] 3.6 1.2 25 18.0% 0.56 [0.02, 1.11] 0.8 1.5 25 17.4% 0.46 [-0.10, 1.02] 4.22 1.1 7 7.0% 0.91 [-0.15, 1.96] -5.9 3.8 15 11.2% 0.81 [0.03, 1.59] 63.5 20.4 164 35.5% 0.03 [-0.19, 0.25] 5.4 0.0000001 5 4.8% 0.69 [-0.61, 1.99] Total (95% CI) 251 247 100.0% Heterogeneity: Tau² = 0.05; Chi² = 9.52, df = 6 (P = 0.15); I² = 37% Test for overall effect: Z = 2.53 (P = 0.01) Std. Mean Difference IV, Random, 95% CI 0.39 [0.09, 0.69] -4 -2 Favours lower 0 2 4 Favours higher 43 44 Supplement 5: Meta-regression results by outcome (primary and full adjusted models) Note: any changes from the last analysis are highlighted in yellow for the peer reviewer Note for all models: † Protein is difference in % of total energy intake between intervention and control diet. ‡ Difference in total energy intake between intervention and control diet. § Percent male > 0% versus 0% male (since studies with 0% male were over-represented). ¶ Carbohydrates is difference in % of total energy intake between intervention and control diet. Models for mean difference in body weight. (N=2,542 participants; 34 studies) Primary Model 95% C.I. Intercept Beta Coefficient 7.904 * Protein † Full Adjusted Model 95% C.I. 2.816, 12.992 * Beta Coefficient 8.383 * 0.054 -0.069, 0.177 0.082 -0.058, 0.222 Duration of diet intervention, days Energy, 100 kcals ‡ 0.0009 -0.003, 0.005 0.001 -0.003, 0.005 -0.467* -0.877, -0.057 * -0.393 -0.903, 0.117 Body mass index, kg/m2 -0.309* -0.474, -0.144 * -0.282* -0.458, -0.106 * Age, years -0.001 -0.079, 0.077 % male § -0.670 -1.875, 0.535 Carbohydrates, % of energy intake ¶ 0.023 -0.015, 0.061 2.465, 14.301 * Models for mean difference in body mass index. (N=1,176 participants; 15 studies) Primary Model 95% C.I. Intercept Beta Coefficient 2.611 Protein † Full Adjusted Model 95% C.I. -0.837, 6.059 Beta Coefficient 5.360 * 0.014 -0.041, 0.069 0.069 * 0.015, 0.123 * Duration of diet intervention, days Energy, 100 kcals ‡ -0.0003 -0.003, 0.003 0.0004 -0.002, 0.003 -0.173 -0.370, 0.025 -0.304 * -0.468, -0.140 * Body mass index, kg/m2 -0.097 -0.202, 0.008 -0.110 * -0.198, -0.022 * Age, years -0.029 -0.060, 0.002 % male § -0.399 -0.860, 0.062 Carbohydrates, % of energy intake ¶ 0.054 * 0.025, 0.083 * 1.703, 9.017 * 44 45 Models for mean difference in waist circumference. (N=1,413 participants; 14 studies) Primary Model 95% C.I. Intercept Beta Coefficient -19.735 Protein † Full Adjusted Model 95% C.I. -52.5, 13.0 Beta Coefficient -21.5 0.378 -0.390, 1.146 0.619 -0.422, 1.660 Duration of diet intervention, days Energy, 100 kcals ‡ 0.0003 -0.009, 0.010 -0.0001 -0.012, 0.012 -0.866 -2.373, 0.641 -0.728 -2.627, 1.171 Body mass index, kg/m2 0.45 -0.503, 1.403 0.456 -0.710, 1.622 Age, years 0.123 -0.277, 0.523 % male § -2.064 -7.068, 2.940 Carbohydrates, % of energy intake ¶ 0.154 -0.185, 0.493 -59.4, 16.4 Models for mean difference in systolic blood pressure. (N=1,259 participants; 13 studies) Primary Model 95% C.I. Intercept Beta Coefficient 0.318 Protein † Duration of diet intervention, days Energy, 100 kcals ‡ Full Adjusted Model 95% C.I. -42.0, 42.654 Beta Coefficient -10.6 0.121 -0.796, 1.038 -0.805 -1.995, 0.385 0.004 -0.018, 0.026 0.005 -0.020, 0.030 -1.152 -2.579, 0.275 -0.115 -1.793, 1.563 -0.139 -1.329, 1.051 -0.326 -1.567, 0.915 Age, years 0.573 * 0.089, 1.057 * % male § -2.22 -6.022, 1.582 Carbohydrates, % of energy intake ¶ -0.077 -0.249, 0.095 Body mass index, kg/m 2 -57.4, 36.2 45 46 Models for mean difference in diastolic blood pressure. (N=1,259 participants; 13 studies) Primary Model 95% C.I. Intercept Beta Coefficient -15.9 Protein † Full Adjusted Model 95% C.I. -43.9, 12.1 Beta Coefficient -16.5 0.602 -0.022, 1.226 0.331 -0.561, 1.223 Duration of diet intervention, days Energy, 100 kcals ‡ 0.005 -0.009, 0.019 0.006 -0.012, 0.024 -0.470 -1.456, 0.516 -0.205 -1.405, 0.995 Body mass index, kg/m2 0.279 -0.499, 1.057 0.175 -0.656, 1.006 Age, years 0.149 -0.192, 0.490 % male § -0.966 -3.651, 1.719 Carbohydrates, % of energy intake ¶ -0.033 -0.145, 0.079 -46.7, 13.7 Models for mean difference in total cholesterol. (N=1,686 participants; 19 studies) Primary Model 95% C.I. Intercept Beta Coefficient -0.999 Protein † Duration of diet intervention, days Energy, 100 kcals ‡ Full Adjusted Model 95% C.I. -2.367, 0.369 Beta Coefficient -0.780 -0.009 -0.040, 0.022 -0.015 -0.048, 0.018 0.001 -0.0001, 0.002 0.0005 -0.001, 0.002 0.026 -0.066, 0.118 0.004 -0.110, 0.118 0.030 -0.011, 0.071 0.028 -0.013, 0.069 Age, years -0.005 -0.021, 0.011 % male § -0.003 -0.260, 0.254 Carbohydrates, % of energy intake ¶ -0.009 -0.021, 0.003 Body mass index, kg/m 2 -2.416, 0.857 46 47 Models for mean difference in HDL-cholesterol. (N=1,715 participants; 22 studies) Primary Model Full Adjusted Model 95% C.I. Beta Coefficient 95% C.I. Intercept Beta Coefficien t -0.074 -0.533, 0.385 -0.158 -0.534, 0.218 Protein † -0.0004 -0.010, 0.009 -0.007 * -0.013, -0.001 * Duration of diet intervention, days Energy, 100 kcals ‡ 0.0001 -0.0002, 0.0005 0.0001 -0.0002, 0.0003 -0.011 -0.046, 0.024 -0.006 -0.031, 0.019 Body mass index, kg/m2 0.003 -0.011, 0.017 0.003 -0.007, 0.013 Age, years 0.0008 -0.003, 0.005 % male § 0.010 -0.029, 0.049 Carbohydrates, % of energy intake ¶ -0.005 * -0.007, -0.003 * Models for mean difference in LDL-cholesterol. (N=1,765 participants; 23 studies) Primary Model 95% C.I. Full Adjusted Model Intercept Beta Coefficient -1.386 * Beta Coefficient -1.372 95% C.I. Protein † 0.014 -2.591, -0.181 * -0.006, 0.034 0.016 -0.009, 0.041 Duration of diet intervention, days Energy, 100 kcals ‡ 0.001 * 0.001, 0.003 * 0.001 -0.0001, 0.002 -0.009 -0.054, 0.036 -0.017 -0.076, 0.042 Body mass index, kg/m2 0.036 * 0.001, 0.071 * 0.041 -0.0001, 0.081 Age, years -0.004 -0.016, 0.008 % male § 0.007 -0.146, 0.160 Carbohydrates, % of energy intake ¶ 0.002 -0.006, 0.010 -2.781, 0.037 47 48 Models for mean difference in Triglycerides. (N=1,897 participants; 24 studies) Primary Model 95% C.I. Intercept Beta Coefficient 0.194 Protein † Full Adjusted Model 95% C.I. -0.939, 1.327 Beta Coefficient 0.319 0.009 -0.020, 0.038 0.021 -0.012, 0.054 Duration of diet intervention, days Energy, 100 kcals ‡ 0.0001 -0.001, 0.001 0.0004 -0.001, 0.001 0.023 -0.067, 0.113 0.012 -0.086, 0.110 Body mass index, kg/m2 -0.016 -0.049, 0.017 -0.014 -0.047, 0.019 Age, years -0.0008 -0.013, 0.011 % male § -0.078 -0.286, 0.130 Carbohydrates, % of energy intake ¶ 0.007 -0.003, 0.017 -0.896, 1.534 Models for mean difference in C-reactive protein. (N=398 participants; 6 studies) Primary Model 95% C.I. Intercept Beta Coefficient 1.759 Protein † Duration of diet intervention, days Energy, 100 kcals ‡ Full Adjusted Model 95% C.I. -3.431, 6.950 Beta Coefficient -31.0 -0.171 -0.675, 0.333 0.363 -0.424, 1.151 -0.0002 -0.008, 0.008 -0.028 -0.067, 0.010 0.547 -1.332, 2.426 3.522 -1.034, 8.078 Age, years 0.347 -0.139, 0.832 % male § 9.889 -3.042, 22.820 -74.6, -12.5 2 Body mass index, kg/m †† Carbohydrates, % of energy intake ¶ ‡‡ †† BMI is not included in any of the models since BMI is not an a priori predictor of CRP. ‡‡ Carbohydrate intake is not included in any of the models due to colinearity with trial duration (R=-0.95). 48 49 Models for mean difference in fasting blood glucose. (N=1,433 participants; 17 studies) Primary Model 95% C.I. Intercept Beta Coefficient 0.393 Protein † Full Adjusted Model 95% C.I. -0.575, 1.361 Beta Coefficient 0.058 0.018 -0.004, 0.040 0.014 -0.006, 0.034 Duration of diet intervention, days Energy, 100 kcals ‡ 0.0005 -0.0001, 0.001 0.0011 * 0.0001, 0.002 * 0.012 -0.059, 0.083 0.025 -0.046, 0.096 Body mass index, kg/m2 -0.019 -0.050, 0.012 -0.0095 -0.045, 0.026 Age, years -0.001 -0.011, 0.009 % male § -0.211 * -0.419, -0.003 * Carbohydrates, % of energy intake ¶ 0.007 -0.005, 0.019 -0.891, 1.007 Models for mean difference in fasting serum insulin. (N=1,002 participants; 10 studies) Primary Model 95% C.I. Intercept Beta Coefficient 48.4 Protein † Duration of diet intervention, days Energy, 100 kcals ‡ Full Adjusted Model 95% C.I. -121.0, 217.8 Beta Coefficient 315.5 3.114 -2.785, 9.013 -2.274 -15.7, 11.1 -0.004 -0.086, 0.078 0.021 -0.226, 0.268 -1.502 -12.164, 9.160 3.695 -15.533, 22.923 -2.644 -7.434, 2.146 -6.657 -17.351, 4.037 Age, years -0.170 -4.431, 4.092 % male § -40.47 -137.8, 56.9 Carbohydrates, % of energy intake ¶ 1.015 -4.190, 6.220 Body mass index, kg/m 2 -106.7, 737.7 49 50 Supplement 6: Meta-analyses of all health outcomes for end of study scores (secondary analysis) (SD: Standard deviation; IV: inverse variance method; Std: Standard, CI: confidence intervals) Weight Study or Subgroup 7.2.1 at 1 month Appel 2005 Baba 1999 Farnsworth 2003 Farnsworth 2003 Johnston 2004 Lean 1997 Luscombe-Marsh 2005men Luscombe-Marsh 2005women Mamo 2005 Nickols-Richardson 2005 Wolfe 1991 Wolfe 1992 Wolfe 1999 Subtotal (95% CI) Higher protein diets Mean SD Total 86 104.9 102.7 86.4 78.28 82 95.1 86.6 88.7 78.2 62.4 78 65 18.2 16.9 13.8 10.1 27.4 14.6 10.4 10.8 3.6 15.9 18.7 2 12.6 80 7 7 21 9 53 12 15 10 13 5 3 5 132 Lower protein diets Mean SD Total Weight Std. Mean Difference IV, Random, 95% CI 86.3 99.5 104 84.7 81.2 81.7 106 86 93.3 75.6 66.2 87 65 18.2 12.2 12.7 10.1 18.6 16.6 14.1 9.5 5.5 15.4 15.1 21.2 15.8 81 6 7 21 7 57 13 17 10 15 5 2 5 131 8.4% 0.7% 0.0% 0.0% 0.8% 0.0% 0.0% 0.0% 0.9% 1.4% 0.5% 0.2% 0.5% 13.5% -0.02 [-0.33, 0.29] 0.34 [-0.77, 1.44] -0.09 [-1.14, 0.96] 0.17 [-0.44, 0.77] -0.11 [-1.10, 0.87] 0.02 [-0.35, 0.39] -0.85 [-1.67, -0.02] 0.06 [-0.64, 0.75] -0.95 [-1.88, -0.01] 0.16 [-0.58, 0.91] -0.20 [-1.45, 1.04] -0.53 [-2.46, 1.40] 0.00 [-1.24, 1.24] -0.06 [-0.31, 0.18] 86 90.7 78.8 88.8 101 82.7 80 90.5 103 83.7 70.3 93.7 85.5 85 62.6 88.5 6.3246 13.8 8.22 17.1 11.1 10.5 15.3 20.64 14.1 9.9 9 14.5 12 11.8 9.9 14.9 20 47 10 96 7 21 31 7 13 17 14 31 16 21 9 37 292 2.1% 0.0% 1.0% 10.1% 0.0% 0.0% 3.1% 0.8% 0.0% 0.0% 1.4% 3.1% 1.6% 2.3% 0.9% 3.8% 30.3% -0.25 [-0.88, 0.37] -0.27 [-0.66, 0.13] 0.07 [-0.80, 0.95] -0.05 [-0.33, 0.24] -0.19 [-1.24, 0.86] 0.16 [-0.44, 0.77] 0.10 [-0.41, 0.61] 0.68 [-0.34, 1.71] -0.86 [-1.69, -0.04] 0.08 [-0.61, 0.78] 0.43 [-0.32, 1.18] -0.41 [-0.92, 0.09] -0.10 [-0.80, 0.61] -0.44 [-1.03, 0.15] 0.04 [-0.89, 0.96] -0.21 [-0.67, 0.24] -0.09 [-0.25, 0.07] 78.5 83.5 92 88.5 91.1 87.5 92.9 99 81.1 73.1 85.9 80.2 74.5 101 82.3 76.9 76.6 89.2 11.9262 13.5 12.9615 8.9443 18 10.1 29.1 10.8 10.5 9.7 12.1 16.6 10.5 15.9 9.9 7.5 15 13.9 18 29 42 20 43 66 4 7 21 12 12 57 25 13 17 8 11 20 348 1.9% 3.1% 3.9% 0.0% 4.7% 6.1% 0.5% 0.7% 2.2% 1.2% 1.2% 0.0% 2.4% 1.2% 1.7% 0.9% 1.3% 2.1% 35.0% 0.14 [-0.51, 0.79] -0.09 [-0.60, 0.42] 0.23 [-0.23, 0.68] -0.53 [-1.15, 0.08] -0.20 [-0.62, 0.21] 0.19 [-0.17, 0.56] -0.30 [-1.57, 0.98] -0.25 [-1.30, 0.80] 0.13 [-0.48, 0.73] 0.26 [-0.54, 1.07] -0.25 [-1.05, 0.56] -0.01 [-0.39, 0.36] 0.00 [-0.58, 0.58] -0.77 [-1.59, 0.05] 0.10 [-0.59, 0.79] 0.21 [-0.72, 1.14] 0.18 [-0.61, 0.98] -0.21 [-0.83, 0.41] 0.01 [-0.14, 0.16] 89 74.7 79.6 93.31 88.5 11.1803 13 16.6 20.59 15 20 8 57 27 37 149 2.1% 0.8% 5.7% 2.9% 3.6% 15.1% -0.51 [-1.13, 0.10] -0.40 [-1.43, 0.63] -0.02 [-0.39, 0.36] -0.05 [-0.58, 0.48] -0.40 [-0.87, 0.07] -0.20 [-0.44, 0.03] 83 89.5 18 16.4 36 38 74 3.6% 2.6% 6.1% -0.20 [-0.67, 0.28] 0.08 [-0.48, 0.64] -0.08 [-0.44, 0.28] 994 100.0% -0.07 [-0.16, 0.02] Std. Mean Difference IV, Random, 95% CI Heterogeneity: Tau² = 0.00; Chi² = 4.67, df = 7 (P = 0.70); I² = 0% Test for overall effect: Z = 0.51 (P = 0.61) 7.2.3 at 2 months Brehm 2005 Brinkworth 2009 Buscemi 2009 de Luis 2009a Farnsworth 2003 Farnsworth 2003 Hodgson 2006 Kleiner 2006 Luscombe-Marsh 2005men Luscombe-Marsh 2005women Mahon 2007 McAuley 2005 Meckling 2004 Noakes 2006 Sacks 1984 Te Morenga 2011 Subtotal (95% CI) 84 87 79.6 88 98.5 84.4 81.5 102.2 91.6 84.6 74.4 87.8 84 80 63 85.3 8.9443 13.9 12.02 17.6 13 10.1 14.3 11.7 11.1 11.2 9.6 13.7 17.04 10.6 10.2 14.7 20 52 10 97 7 21 29 9 12 15 14 30 15 24 9 37 294 Heterogeneity: Tau² = 0.00; Chi² = 8.30, df = 10 (P = 0.60); I² = 0% Test for overall effect: Z = 1.07 (P = 0.28) 7.2.5 at 3 months Ballesteros-Pomar 2010 Barnard 2004 Belobrajdic 2010 Brehm 2003 de Luis 2007 de Luis 2009b Dyson 2007 Farnsworth 2003 Farnsworth 2003 Layman 2005 Layman 2005 Lean 1997 Leidy 2007 Luscombe-Marsh 2005men Luscombe-Marsh 2005women Meckling 2007 Meckling 2007 Volek 2009 Subtotal (95% CI) 80.3 82.3 95 83.5 87.7 90.4 85.3 96 82.5 76.3 82.4 80 74.5 90 83.4 79.5 79.2 86.4 13.2423 12 13.4112 9.3808 15.3 19.7 18.8 11.6 10.8 13.5 15.2 14.6 15.12 11.1 11.6 14.2 12.4 12 18 30 34 22 47 52 6 7 21 12 12 53 21 12 15 10 14 20 331 Heterogeneity: Tau² = 0.00; Chi² = 8.91, df = 15 (P = 0.88); I² = 0% Test for overall effect: Z = 0.10 (P = 0.92) 7.2.7 at 6 months Brehm 2003 Ferrara 2006 Lean 1997 Lopez-Jimenez 2010 Morgan 2009 Subtotal (95% CI) 83 70 79.3 92.21 83.2 11.726 8 15.3 20.43 10.6 22 7 53 28 33 143 Heterogeneity: Tau² = 0.00; Chi² = 3.02, df = 4 (P = 0.55); I² = 0% Test for overall effect: Z = 1.73 (P = 0.08) 7.2.9 more than 6 months Brinkworth 2009 Fleming 2002 Subtotal (95% CI) 79.5 90.9 17.2337 17.3 33 18 51 Heterogeneity: Tau² = 0.00; Chi² = 0.55, df = 1 (P = 0.46); I² = 0% Test for overall effect: Z = 0.43 (P = 0.66) Total (95% CI) 951 Heterogeneity: Tau² = 0.00; Chi² = 27.83, df = 41 (P = 0.94); I² = 0% Test for overall effect: Z = 1.50 (P = 0.13) Test for subgroup differences: Chi² = 2.37, df = 4 (P = 0.67), I² = 0% -2 -1 Favours higher protein 0 1 2 Favours lower protein 50 51 Body Mass Index Study or Subgroup 7.4.1 at 1 month Baba 1999 Mamo 2005 Nickols-Richardson 2005 Subtotal (95% CI) Higher protein diets Lower protein diets Std. Mean Difference Mean SD Total Mean SD Total Weight IV, Random, 95% CI 34.1 31.2 29.3 4.8 1.2 4.6 7 10 13 30 32.6 31.6 29 2 1.6 5.3 Std. Mean Difference IV, Random, 95% CI 6 10 15 31 1.0% 1.6% 2.2% 4.7% 0.37 [-0.74, 1.47] -0.27 [-1.15, 0.61] 0.06 [-0.68, 0.80] 0.02 [-0.49, 0.52] 10 47 96 14 31 16 37 204 1.5% 0.0% 15.1% 2.1% 4.6% 2.4% 5.8% 31.5% 0.10 [-0.80, 1.00] -0.18 [-0.57, 0.22] 0.13 [-0.15, 0.42] 0.38 [-0.37, 1.13] -0.53 [-1.04, -0.02] 0.02 [-0.69, 0.72] -0.26 [-0.72, 0.20] -0.05 [-0.31, 0.21] 18 29 42 43 66 4 18 25 8 11 31 35 20 350 2.8% 4.6% 5.8% 7.0% 9.1% 0.7% 2.8% 3.6% 1.3% 1.9% 4.6% 5.6% 3.0% 52.9% -0.07 [-0.72, 0.58] -0.07 [-0.58, 0.44] 0.35 [-0.11, 0.80] -0.05 [-0.47, 0.36] -0.06 [-0.42, 0.30] -0.42 [-1.70, 0.87] 0.33 [-0.33, 0.98] 0.17 [-0.42, 0.75] 0.55 [-0.40, 1.50] 0.10 [-0.69, 0.89] -0.13 [-0.64, 0.38] -0.12 [-0.58, 0.35] -0.49 [-1.12, 0.14] -0.00 [-0.15, 0.15] 43 8 27 35 0.0% 1.2% 4.3% 5.4% -0.19 [-0.61, 0.23] -0.04 [-1.06, 0.97] -0.25 [-0.79, 0.28] -0.21 [-0.68, 0.26] 36 5.4% -0.20 [-0.68, 0.27] 36 5.4% -0.20 [-0.68, 0.27] Heterogeneity: Tau² = 0.00; Chi² = 0.81, df = 2 (P = 0.67); I² = 0% Test for overall effect: Z = 0.06 (P = 0.95) 7.4.3 at 2 months Abete 2009 Brinkworth 2009 de Luis 2009a Mahon 2007 McAuley 2005 Meckling 2004 Te Morenga 2011 Subtotal (95% CI) 30.1 30.9 34.5 27.6 32.4 30.1 31.3 1.9 3.8 7.3 3.4 4.8 6.2 4.5 9 52 97 14 30 15 37 202 29.8 31.6 33.6 26.3 35.2 30 32.5 3.4 4 5.9 3.2 5.6 3.6 4.7 Heterogeneity: Tau² = 0.03; Chi² = 7.19, df = 5 (P = 0.21); I² = 31% Test for overall effect: Z = 0.40 (P = 0.69) 7.4.5 at 3 months Ballesteros-Pomar 2010 29.4556 2.9246 Barnard 2004 31.2 3.5 Belobrajdic 2010 30.4 3.4986 de Luis 2007 34.1 5.6 de Luis 2009b 33.9 6.6 Dyson 2007 31.5 7.4 Iglay 2007 26.8 3.81 Leidy 2007 27.7 4.12 Meckling 2007 29.5 4.1 Meckling 2007 28.8 4.9 Thorpe 2008 29.1 3.6 Thorpe 2008 29.7 4.5 Volek 2009 30 4.3 Subtotal (95% CI) 18 29.6611 2.7789 30 31.5 5.3 34 29.1 3.8884 47 34.4 5.9 52 34.3 6.9 6 36.2 13.6 18 25.6 3.39 21 27.1 3 10 27.6 1.7 14 28.3 4.4 28 29.6 3.9 36 30.2 3.8 20 32.1 4.1 334 Heterogeneity: Tau² = 0.00; Chi² = 8.32, df = 12 (P = 0.76); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 7.4.7 at 6 months Brinkworth 2009 Ferrara 2006 Lopez-Jimenez 2010 Subtotal (95% CI) 28.9 22.8 31.88 3.4 2.4 6.65 45 7 28 35 29.6 22.9 33.48 3.9 1.9 5.67 Heterogeneity: Tau² = 0.00; Chi² = 0.13, df = 1 (P = 0.72); I² = 0% Test for overall effect: Z = 0.87 (P = 0.38) 7.4.9 more than 6 months Brinkworth 2009 28.4 3.45 Subtotal (95% CI) 33 29.2 4.2 33 Heterogeneity: Not applicable Test for overall effect: Z = 0.85 (P = 0.40) Total (95% CI) 634 656 100.0% Heterogeneity: Tau² = 0.00; Chi² = 17.72, df = 24 (P = 0.82); I² = 0% Test for overall effect: Z = 0.55 (P = 0.59) Test for subgroup differences: Chi² = 1.28, df = 4 (P = 0.86), I² = 0% -0.03 [-0.14, 0.08] -2 -1 Favours higher 0 1 Favours lower 2 51 52 Waist circumference Higher protein Lower protein diets Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI 7.26.1 at 1 month Subtotal (95% CI) 0 0 Not estimable Heterogeneity: Not applicable Test for overall effect: Not applicable 7.26.3 at 2 months Abete 2009 97.6 6.6 9 98 6.5 10 3.8% Buscemi 2009 94 15.81 10 97 6.32 10 3.9% de Luis 2009a 102.5 14 97 103.1 15.5 96 20.6% McAuley 2005 100.3 9.6 30 104 10.9 31 9.9% Te Morenga 2011 88.3 10.4 37 92.5 11.4 37 11.4% Subtotal (95% CI) 183 184 49.6% Heterogeneity: Tau² = 0.00; Chi² = 2.21, df = 4 (P = 0.70); I² = 0% Test for overall effect: Z = 1.64 (P = 0.10) 7.26.5 at 3 months Ballesteros-Pomar 201098.3 9.3517 18 95.43898.3509 de Luis 2007 103.9 14.8 47 105 15.5 de Luis 2009b 105.8 13.4 52 100 13.9 Iglay 2007 83.5 11.6 16 83.5 12.4 Subtotal (95% CI) 133 18 6.5% 43 13.2% 66 15.4% 17 6.1% 144 41.2% Std. Mean Difference IV, Random, 95% CI -0.06 [-0.96, 0.84] -0.24 [-1.12, 0.64] -0.04 [-0.32, 0.24] -0.36 [-0.86, 0.15] -0.38 [-0.84, 0.08] -0.17 [-0.38, 0.03] 0.32 [-0.34, 0.97] -0.07 [-0.49, 0.34] 0.42 [0.05, 0.79] 0.00 [-0.68, 0.68] 0.19 [-0.08, 0.45] Heterogeneity: Tau² = 0.01; Chi² = 3.50, df = 3 (P = 0.32); I² = 14% Test for overall effect: Z = 1.40 (P = 0.16) 7.26.7 at 6 months Lopez-Jimenez 2010 101.6 14.04 Subtotal (95% CI) 28 106.33 13.46 28 27 27 9.2% 9.2% -0.34 [-0.87, 0.19] -0.34 [-0.87, 0.19] Heterogeneity: Not applicable Test for overall effect: Z = 1.25 (P = 0.21) 7.26.9 more than 6 months Subtotal (95% CI) Heterogeneity: Not applicable Test for overall effect: Not applicable Total (95% CI) 0 344 0 355 100.0% Heterogeneity: Tau² = 0.02; Chi² = 12.21, df = 9 (P = 0.20); I² = 26% Test for overall effect: Z = 0.57 (P = 0.57) Test for subgroup differences: Chi² = 5.61, df = 2 (P = 0.06), I² = 64.3% Not estimable -0.05 [-0.24, 0.13] -1 -0.5 0 0.5 1 Favours higher Favours lower 52 53 Systolic blood pressure Higher protein Lower protein diets Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI 7.6.1 at 1 month Jenkins 2001 Keogh 2007 Subtotal (95% CI) 117 110 9.5 14.4 10 13 10 118 115 9.5 13.9 10 12 10 2.3% 0.0% 2.3% -0.10 [-0.98, 0.78] -0.34 [-1.13, 0.45] -0.10 [-0.98, 0.78] 10 2.2% 20 4.2% 47 0.0% 10 2.0% 96 11.9% 31 5.5% 7 1.8% 30 5.7% 16 3.3% 20 4.1% 9 2.1% 37 6.7% 286 49.5% 0.07 [-0.83, 0.97] -0.13 [-0.75, 0.49] -0.09 [-0.49, 0.31] -0.95 [-1.89, -0.01] -0.13 [-0.41, 0.15] -0.66 [-1.18, -0.14] -0.57 [-1.58, 0.44] 0.00 [-0.51, 0.51] 0.56 [-0.16, 1.28] -0.11 [-0.73, 0.52] 0.06 [-0.87, 0.98] -0.07 [-0.53, 0.39] -0.15 [-0.34, 0.04] Std. Mean Difference IV, Random, 95% CI Heterogeneity: Not applicable Test for overall effect: Z = 0.23 (P = 0.82) 7.6.3 at 2 months Abete 2009 Brehm 2005 Brinkworth 2009 Buscemi 2009 de Luis 2009a Hodgson 2006 Kleiner 2006 McAuley 2005 Meckling 2004 Rouse 1986 Sacks 1984 Te Morenga 2011 Subtotal (95% CI) 115 114 122 117 122.8 131.8 114 122 114.6 118.7 108.8 121 3.1 17 12 9.49 26.6 12.8 6 14 6.97 13.6 13.5 15 9 114.5 8.6 20 116 12.5 51 123 10 10 125 6.32 97 125.5 12.8 29 140 11.9 9 119 10.58 29 122 13 15 110 8.8 19 120 10.3 9 108 13.7 37 122 13 283 Heterogeneity: Tau² = 0.02; Chi² = 11.77, df = 10 (P = 0.30); I² = 15% Test for overall effect: Z = 1.54 (P = 0.12) 7.6.5 at 3 months Brehm 2003 de Luis 2009b Keogh 2007 Leidy 2007 Meckling 2007 Meckling 2007 Subtotal (95% CI) 112 124 111 104 127 119 11.1 13 14.4 9.17 17 13 22 52 13 21 14 10 97 116 126 118 110 122 118 9 16 17.3 45 10 12 20 0.0% 66 9.1% 12 0.0% 25 4.7% 11 2.7% 8 2.1% 110 18.5% -0.39 [-1.00, 0.23] -0.13 [-0.50, 0.23] -0.43 [-1.22, 0.37] -0.17 [-0.76, 0.41] 0.34 [-0.46, 1.13] 0.08 [-0.85, 1.01] -0.07 [-0.34, 0.21] Heterogeneity: Tau² = 0.00; Chi² = 1.34, df = 3 (P = 0.72); I² = 0% Test for overall effect: Z = 0.49 (P = 0.62) 7.6.7 at 6 months Brehm 2003 114 13.23 Brinkworth 2009 120.8 11.5 Ferrara 2006 111.6 5 Sacks 2009 119 12 Subtotal (95% CI) 22 45 7 201 230 113 10.78 125 15.8 113 9 116 12 20 4.4% 43 0.0% 8 1.8% 201 15.9% 229 22.0% 0.08 [-0.52, 0.69] -0.30 [-0.72, 0.12] -0.18 [-1.19, 0.84] 0.25 [0.05, 0.45] 0.22 [0.04, 0.40] Heterogeneity: Tau² = 0.00; Chi² = 0.88, df = 2 (P = 0.65); I² = 0% Test for overall effect: Z = 2.35 (P = 0.02) 7.6.9 more than 6 months Brinkworth 2009 118.9 11.49 Keogh 2007 115 14.1 Subtotal (95% CI) 33 8 41 121 130 17.4 8.9 36 5 41 6.4% 1.2% 7.6% -0.14 [-0.61, 0.33] -1.12 [-2.35, 0.11] -0.46 [-1.36, 0.44] Heterogeneity: Tau² = 0.25; Chi² = 2.12, df = 1 (P = 0.15); I² = 53% Test for overall effect: Z = 1.00 (P = 0.32) Total (95% CI) 661 676 100.0% Heterogeneity: Tau² = 0.02; Chi² = 26.29, df = 20 (P = 0.16); I² = 24% Test for overall effect: Z = 0.96 (P = 0.33) Test for subgroup differences: Chi² = 9.16, df = 4 (P = 0.06), I² = 56.3% -0.07 [-0.21, 0.07] -2 -1 Favours higher 0 1 Favours lower 2 53 54 Diastolic blood pressure Study 7.8.1 at 1 month Jenkins 2001 Keogh 2007 Subtotal (95% CI) Higher protein Lower protein diets Std. Mean Difference Mean SD Total Mean SD Total Weight IV, Random, 95% CI 76 68 6.3 7.2 10 13 10 77 72 6.3 3.5 72.5 74 70 84 81.9 77.9 69 80 72.9 73.2 71.3 79 8.5 8.9 9 6.32 7.7 7.4 7.94 9 10 10.7 8.6 10 10 12 10 1.8% 0.0% 1.8% -0.15 [-1.03, 0.73] -0.67 [-1.48, 0.14] -0.15 [-1.03, 0.73] 10 1.6% 20 3.6% 47 0.0% 10 1.8% 96 13.8% 31 5.2% 7 1.5% 30 5.0% 16 2.8% 20 3.5% 9 1.7% 37 6.1% 286 46.5% 0.69 [-0.24, 1.62] -0.10 [-0.72, 0.52] -0.26 [-0.66, 0.13] 0.12 [-0.76, 1.00] -0.14 [-0.42, 0.14] -0.04 [-0.54, 0.47] 0.00 [-0.99, 0.99] -0.49 [-1.01, 0.03] -0.11 [-0.82, 0.59] -0.24 [-0.87, 0.39] 0.06 [-0.86, 0.99] -0.44 [-0.90, 0.02] -0.16 [-0.32, 0.01] Std. Mean Difference IV, Random, 95% CI Heterogeneity: Not applicable Test for overall effect: Z = 0.34 (P = 0.73) 7.8.3 at 2 months Abete 2009 Brehm 2005 Brinkworth 2009 Buscemi 2009 de Luis 2009a Hodgson 2006 Kleiner 2006 McAuley 2005 Meckling 2004 Rouse 1986 Sacks 1984 Te Morenga 2011 Subtotal (95% CI) 78.3 7.5 73 10.7 67 13 85 9.49 80 17.7 77.6 9 69 9 76 7 71.6 12.39 70.9 8.2 71.9 9.3 75 8 9 20 51 10 97 29 9 29 15 19 9 37 283 Heterogeneity: Tau² = 0.00; Chi² = 7.18, df = 10 (P = 0.71); I² = 0% Test for overall effect: Z = 1.88 (P = 0.06) 7.8.5 at 3 months Brehm 2003 de Luis 2009b Keogh 2007 Leidy 2007 Meckling 2007 Meckling 2007 Subtotal (95% CI) 72 81.1 67 66 78 72 9.7 7.4 7.2 4.58 10 7 22 52 13 21 14 10 97 75 79.2 70 65 77 75 8 12.8 6.9 10 9 14 20 0.0% 66 9.2% 12 0.0% 25 4.0% 11 2.3% 8 1.6% 110 17.1% -0.33 [-0.94, 0.28] 0.18 [-0.19, 0.54] -0.41 [-1.21, 0.38] 0.12 [-0.46, 0.70] 0.10 [-0.69, 0.89] -0.27 [-1.20, 0.67] 0.12 [-0.16, 0.39] Heterogeneity: Tau² = 0.00; Chi² = 0.75, df = 3 (P = 0.86); I² = 0% Test for overall effect: Z = 0.83 (P = 0.41) 7.8.7 at 6 months Brehm 2003 Brinkworth 2009 Ferrara 2006 Sacks 2009 Subtotal (95% CI) 74 10.46 69 11.7 70 7 119 12 22 45 7 201 230 74 72.3 73.1 116 7.24 9.01 7 12 20 3.7% 43 0.0% 8 1.4% 201 22.5% 229 27.6% 0.00 [-0.61, 0.61] -0.31 [-0.73, 0.11] -0.42 [-1.45, 0.61] 0.25 [0.05, 0.45] 0.20 [0.00, 0.40] Heterogeneity: Tau² = 0.00; Chi² = 2.04, df = 2 (P = 0.36); I² = 2% Test for overall effect: Z = 2.00 (P = 0.05) 7.8.9 more than 6 months Brinkworth 2009 Keogh 2007 Subtotal (95% CI) 66 11.49 68 8.5 33 8 41 69.2 74 10.2 6.7 36 5 41 5.8% 1.1% 6.9% -0.29 [-0.77, 0.18] -0.71 [-1.87, 0.46] -0.35 [-0.79, 0.09] Heterogeneity: Tau² = 0.00; Chi² = 0.42, df = 1 (P = 0.52); I² = 0% Test for overall effect: Z = 1.57 (P = 0.12) Total (95% CI) 661 676 100.0% Heterogeneity: Tau² = 0.01; Chi² = 21.98, df = 20 (P = 0.34); I² = 9% Test for overall effect: Z = 0.49 (P = 0.63) Test for subgroup differences: Chi² = 10.73, df = 4 (P = 0.03), I² = 62.7% -0.03 [-0.15, 0.09] -1 -0.5 Favours higher 0 0.5 1 Favours lower 54 55 Total cholesterol Higher protein Lower protein diets Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI 7.10.1 at 1 month Baba 1999 3.37 0.81 7 3.48 0.82 6 1.5% -0.13 [-1.22, 0.97] Farnsworth 2003 4.66 0.5 7 4.39 10.1 7 0.0% 0.04 [-1.01, 1.08] Farnsworth 2003 4.84 1.1 21 5.34 1 21 0.0% -0.47 [-1.08, 0.15] Jenkins 2001 5.85 0.7 10 6.06 0.7 10 2.0% -0.29 [-1.17, 0.59] Johnston 2004 4.52 0.7 9 4.36 0.4 7 1.7% 0.26 [-0.74, 1.25] Keogh 2007 4.52 3 13 4.78 4.8 12 0.0% -0.06 [-0.85, 0.72] Mamo 2005 5.1 0.2 10 5.7 0.4 10 1.5% -1.82 [-2.90, -0.74] Volek 2003 5.34 0.89 5 4.35 0.88 5 1.1% 1.01 [-0.35, 2.37] Wolfe 1991 5.34 0.85 5 6.5 0.58 5 0.9% -1.44 [-2.92, 0.04] Wolfe 1992 7.1 1.4 3 7.8 0.3 2 0.6% -0.44 [-2.33, 1.44] Wolfe 1999 3.8 0.6 5 4.1 0.3 5 1.2% -0.57 [-1.85, 0.71] Subtotal (95% CI) 54 50 10.4% -0.42 [-1.03, 0.20] Heterogeneity: Tau² = 0.40; Chi² = 14.69, df = 7 (P = 0.04); I² = 52% Test for overall effect: Z = 1.32 (P = 0.19) 7.10.3 at 2 months Abete 2009 4.31 1.01 9 4.47 0.68 10 Brehm 2005 5.01 0.82 20 4.67 1.01 20 Brinkworth 2009 5.1 1.2 52 4.8 0.7 47 Buscemi 2009 4.71 0.98 10 5.15 1.23 10 de Luis 2009a 4.82 1.02 97 5.11 0.86 96 Farnsworth 2003 4.91 0.9 21 5.26 0.9 21 Farnsworth 2003 4.7 0.6 7 4.59 0.9 7 Hodgson 2006 4.9 0.8 29 4.9 0.8 31 Kleiner 2006 5.36 0.62 9 4.62 0.66 7 Mahon 2007 5.64 1.37 14 6.21 1.09 14 McAuley 2005 5 0.8 30 5.3 0.9 31 Meckling 2004 6 1.1 15 4.29 1.03 16 Noakes 2006 5.68 1.4 24 5.27 1.2 21 Stoernell 2008 4.47 0.45 10 4.73 1.19 13 Te Morenga 2011 4.7 0.9 37 4.7 0.7 37 Subtotal (95% CI) 304 306 Heterogeneity: Tau² = 0.14; Chi² = 28.84, df = 11 (P = 0.002); I² = 62% Test for overall effect: Z = 0.39 (P = 0.69) 1.9% 2.8% 0.0% 2.0% 4.4% 0.0% 0.0% 3.3% 1.5% 2.4% 3.3% 2.1% 3.0% 2.1% 3.6% 32.3% -0.18 [-1.08, 0.72] 0.36 [-0.26, 0.99] 0.30 [-0.10, 0.70] -0.38 [-1.27, 0.51] -0.31 [-0.59, -0.02] -0.38 [-0.99, 0.23] 0.13 [-0.91, 1.18] 0.00 [-0.51, 0.51] 1.10 [0.02, 2.18] -0.45 [-1.20, 0.30] -0.35 [-0.85, 0.16] 1.56 [0.75, 2.38] 0.31 [-0.28, 0.90] -0.26 [-1.09, 0.56] 0.00 [-0.46, 0.46] 0.06 [-0.23, 0.34] 2.7% 0.0% 4.0% 1.2% 0.0% 0.0% 2.7% 3.3% 0.0% 2.2% 2.2% 2.9% 3.2% 2.0% 1.7% 2.3% 3.9% 2.8% 37.1% -0.46 [-1.13, 0.20] 0.35 [-0.26, 0.96] 0.27 [-0.10, 0.63] 0.24 [-1.03, 1.51] -0.36 [-0.97, 0.25] 0.15 [-0.90, 1.20] 0.29 [-0.37, 0.96] 0.00 [-0.51, 0.51] -0.06 [-0.85, 0.72] 0.47 [-0.34, 1.28] 0.23 [-0.57, 1.04] -0.73 [-1.33, -0.12] 0.28 [-0.25, 0.81] 1.06 [0.21, 1.91] -0.82 [-1.79, 0.16] -0.88 [-1.66, -0.09] -0.26 [-0.66, 0.13] 0.06 [-0.56, 0.67] -0.02 [-0.27, 0.23] 20 43 23 8 27 201 279 2.8% 0.0% 3.0% 1.6% 3.2% 4.7% 15.3% 0.74 [0.11, 1.36] 0.50 [0.07, 0.92] -0.46 [-1.05, 0.12] -0.32 [-1.34, 0.71] 0.24 [-0.29, 0.77] 0.31 [0.12, 0.51] 0.17 [-0.19, 0.53] 36 5 41 3.5% 1.4% 4.9% 0.42 [-0.06, 0.90] -0.34 [-1.47, 0.79] 0.22 [-0.45, 0.88] Total (95% CI) 985 991 100.0% Heterogeneity: Tau² = 0.13; Chi² = 96.76, df = 40 (P < 0.00001); I² = 59% Test for overall effect: Z = 0.00 (P = 1.00) Test for subgroup differences: Chi² = 3.11, df = 4 (P = 0.54), I² = 0% 0.00 [-0.16, 0.16] 7.10.5 at 3 months Ballesteros-Pomar 2010 4.45 1.11 18 4.94 0.95 18 Brehm 2003 4.8 0.68 22 4.56 0.68 20 de Luis 2009b 5.04 0.8 52 4.77 1.14 66 Dyson 2007 5.7 1.2 6 5.4 1 4 Farnsworth 2003 4.92 1 21 5.31 1.1 21 Farnsworth 2003 4.69 0.69 7 4.55 1 7 Iglay 2007 4.97 0.88 18 4.71 0.85 17 Josse 2011a 4.39 0.13 30 4.39 0.11 30 Keogh 2007 4.59 3.1 13 4.82 3.8 12 Layman 2005 5.35 1 12 4.91 0.8 12 Layman 2005 4.8 0.8 12 4.63 0.6 12 Leidy 2007 4.09 0.59 21 4.55 0.65 25 Luscombe-Marsh 2005 5.2 1.1 26 4.9 1 30 Meckling 2007 4.5 0.8 14 3.28 1.42 11 Meckling 2007 3.13 1.09 10 6.36 5.56 8 Moran 2003 4.87 0.9 14 5.56 0.6 14 Noakes 2005 5.26 1.1 52 5.54 1 48 Volek 2009 5.08 0.9 20 5.03 0.88 20 Subtotal (95% CI) 305 315 Heterogeneity: Tau² = 0.11; Chi² = 28.29, df = 13 (P = 0.008); I² = 54% Test for overall effect: Z = 0.18 (P = 0.85) 7.10.7 at 6 months Brehm 2003 5.31 0.82 22 4.73 0.72 Brinkworth 2009 5.37 1.19 45 4.85 0.84 Due 2004 4.6 0.8 23 5 0.9 Ferrara 2006 3.23 1.1 7 3.57 0.92 Lopez-Jimenez 2010 4.88 0.74 28 4.71 0.65 Sacks 2009 5.15 0.91 201 4.86 0.93 Subtotal (95% CI) 281 Heterogeneity: Tau² = 0.09; Chi² = 9.55, df = 4 (P = 0.05); I² = 58% Test for overall effect: Z = 0.92 (P = 0.36) 7.10.9 more than 6 months Brinkworth 2009 6 1.15 33 5.5 1.2 Keogh 2007 4.62 0.7 8 4.94 1.1 Subtotal (95% CI) 41 Heterogeneity: Tau² = 0.10; Chi² = 1.49, df = 1 (P = 0.22); I² = 33% Test for overall effect: Z = 0.64 (P = 0.52) Std. Mean Difference IV, Random, 95% CI -2 -1 0 1 2 Favours higher protein Favours lower protein 55 56 HDL cholesterol Higher protein Lower protein diets Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI 7.10.1 at 1 month Baba 1999 3.37 0.81 7 3.48 0.82 6 1.5% -0.13 [-1.22, 0.97] Farnsworth 2003 4.66 0.5 7 4.39 10.1 7 0.0% 0.04 [-1.01, 1.08] Farnsworth 2003 4.84 1.1 21 5.34 1 21 0.0% -0.47 [-1.08, 0.15] Jenkins 2001 5.85 0.7 10 6.06 0.7 10 2.0% -0.29 [-1.17, 0.59] Johnston 2004 4.52 0.7 9 4.36 0.4 7 1.7% 0.26 [-0.74, 1.25] Keogh 2007 4.52 3 13 4.78 4.8 12 0.0% -0.06 [-0.85, 0.72] Mamo 2005 5.1 0.2 10 5.7 0.4 10 1.5% -1.82 [-2.90, -0.74] Volek 2003 5.34 0.89 5 4.35 0.88 5 1.1% 1.01 [-0.35, 2.37] Wolfe 1991 5.34 0.85 5 6.5 0.58 5 0.9% -1.44 [-2.92, 0.04] Wolfe 1992 7.1 1.4 3 7.8 0.3 2 0.6% -0.44 [-2.33, 1.44] Wolfe 1999 3.8 0.6 5 4.1 0.3 5 1.2% -0.57 [-1.85, 0.71] Subtotal (95% CI) 54 50 10.4% -0.42 [-1.03, 0.20] Heterogeneity: Tau² = 0.40; Chi² = 14.69, df = 7 (P = 0.04); I² = 52% Test for overall effect: Z = 1.32 (P = 0.19) 7.10.3 at 2 months Abete 2009 4.31 1.01 9 4.47 0.68 10 Brehm 2005 5.01 0.82 20 4.67 1.01 20 Brinkworth 2009 5.1 1.2 52 4.8 0.7 47 Buscemi 2009 4.71 0.98 10 5.15 1.23 10 de Luis 2009a 4.82 1.02 97 5.11 0.86 96 Farnsworth 2003 4.91 0.9 21 5.26 0.9 21 Farnsworth 2003 4.7 0.6 7 4.59 0.9 7 Hodgson 2006 4.9 0.8 29 4.9 0.8 31 Kleiner 2006 5.36 0.62 9 4.62 0.66 7 Mahon 2007 5.64 1.37 14 6.21 1.09 14 McAuley 2005 5 0.8 30 5.3 0.9 31 Meckling 2004 6 1.1 15 4.29 1.03 16 Noakes 2006 5.68 1.4 24 5.27 1.2 21 Stoernell 2008 4.47 0.45 10 4.73 1.19 13 Te Morenga 2011 4.7 0.9 37 4.7 0.7 37 Subtotal (95% CI) 304 306 Heterogeneity: Tau² = 0.14; Chi² = 28.84, df = 11 (P = 0.002); I² = 62% Test for overall effect: Z = 0.39 (P = 0.69) 1.9% 2.8% 0.0% 2.0% 4.4% 0.0% 0.0% 3.3% 1.5% 2.4% 3.3% 2.1% 3.0% 2.1% 3.6% 32.3% -0.18 [-1.08, 0.72] 0.36 [-0.26, 0.99] 0.30 [-0.10, 0.70] -0.38 [-1.27, 0.51] -0.31 [-0.59, -0.02] -0.38 [-0.99, 0.23] 0.13 [-0.91, 1.18] 0.00 [-0.51, 0.51] 1.10 [0.02, 2.18] -0.45 [-1.20, 0.30] -0.35 [-0.85, 0.16] 1.56 [0.75, 2.38] 0.31 [-0.28, 0.90] -0.26 [-1.09, 0.56] 0.00 [-0.46, 0.46] 0.06 [-0.23, 0.34] 2.7% 0.0% 4.0% 1.2% 0.0% 0.0% 2.7% 3.3% 0.0% 2.2% 2.2% 2.9% 3.2% 2.0% 1.7% 2.3% 3.9% 2.8% 37.1% -0.46 [-1.13, 0.20] 0.35 [-0.26, 0.96] 0.27 [-0.10, 0.63] 0.24 [-1.03, 1.51] -0.36 [-0.97, 0.25] 0.15 [-0.90, 1.20] 0.29 [-0.37, 0.96] 0.00 [-0.51, 0.51] -0.06 [-0.85, 0.72] 0.47 [-0.34, 1.28] 0.23 [-0.57, 1.04] -0.73 [-1.33, -0.12] 0.28 [-0.25, 0.81] 1.06 [0.21, 1.91] -0.82 [-1.79, 0.16] -0.88 [-1.66, -0.09] -0.26 [-0.66, 0.13] 0.06 [-0.56, 0.67] -0.02 [-0.27, 0.23] 20 43 23 8 27 201 279 2.8% 0.0% 3.0% 1.6% 3.2% 4.7% 15.3% 0.74 [0.11, 1.36] 0.50 [0.07, 0.92] -0.46 [-1.05, 0.12] -0.32 [-1.34, 0.71] 0.24 [-0.29, 0.77] 0.31 [0.12, 0.51] 0.17 [-0.19, 0.53] 36 5 41 3.5% 1.4% 4.9% 0.42 [-0.06, 0.90] -0.34 [-1.47, 0.79] 0.22 [-0.45, 0.88] Total (95% CI) 985 991 100.0% Heterogeneity: Tau² = 0.13; Chi² = 96.76, df = 40 (P < 0.00001); I² = 59% Test for overall effect: Z = 0.00 (P = 1.00) Test for subgroup differences: Chi² = 3.11, df = 4 (P = 0.54), I² = 0% 0.00 [-0.16, 0.16] 7.10.5 at 3 months Ballesteros-Pomar 2010 4.45 1.11 18 4.94 0.95 18 Brehm 2003 4.8 0.68 22 4.56 0.68 20 de Luis 2009b 5.04 0.8 52 4.77 1.14 66 Dyson 2007 5.7 1.2 6 5.4 1 4 Farnsworth 2003 4.92 1 21 5.31 1.1 21 Farnsworth 2003 4.69 0.69 7 4.55 1 7 Iglay 2007 4.97 0.88 18 4.71 0.85 17 Josse 2011a 4.39 0.13 30 4.39 0.11 30 Keogh 2007 4.59 3.1 13 4.82 3.8 12 Layman 2005 5.35 1 12 4.91 0.8 12 Layman 2005 4.8 0.8 12 4.63 0.6 12 Leidy 2007 4.09 0.59 21 4.55 0.65 25 Luscombe-Marsh 2005 5.2 1.1 26 4.9 1 30 Meckling 2007 4.5 0.8 14 3.28 1.42 11 Meckling 2007 3.13 1.09 10 6.36 5.56 8 Moran 2003 4.87 0.9 14 5.56 0.6 14 Noakes 2005 5.26 1.1 52 5.54 1 48 Volek 2009 5.08 0.9 20 5.03 0.88 20 Subtotal (95% CI) 305 315 Heterogeneity: Tau² = 0.11; Chi² = 28.29, df = 13 (P = 0.008); I² = 54% Test for overall effect: Z = 0.18 (P = 0.85) 7.10.7 at 6 months Brehm 2003 5.31 0.82 22 4.73 0.72 Brinkworth 2009 5.37 1.19 45 4.85 0.84 Due 2004 4.6 0.8 23 5 0.9 Ferrara 2006 3.23 1.1 7 3.57 0.92 Lopez-Jimenez 2010 4.88 0.74 28 4.71 0.65 Sacks 2009 5.15 0.91 201 4.86 0.93 Subtotal (95% CI) 281 Heterogeneity: Tau² = 0.09; Chi² = 9.55, df = 4 (P = 0.05); I² = 58% Test for overall effect: Z = 0.92 (P = 0.36) 7.10.9 more than 6 months Brinkworth 2009 6 1.15 33 5.5 1.2 Keogh 2007 4.62 0.7 8 4.94 1.1 Subtotal (95% CI) 41 Heterogeneity: Tau² = 0.10; Chi² = 1.49, df = 1 (P = 0.22); I² = 33% Test for overall effect: Z = 0.64 (P = 0.52) Std. Mean Difference IV, Random, 95% CI -2 -1 0 1 2 Favours higher protein Favours lower protein 56 57 LDL cholesterol Higher protein diet lower protein diet Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI 7.14.2 at 1 month Baba 1999 2.03 0.7 7 1.88 0.7 6 1.2% 0.20 [-0.89, 1.29] Farnsworth 2003 3.32 1 21 3.59 1 21 0.0% -0.26 [-0.87, 0.34] Farnsworth 2003 3.1 0.4 7 2.89 0.7 7 0.0% 0.34 [-0.71, 1.40] Jenkins 2001 3.86 0.6 10 3.64 0.6 10 1.7% 0.35 [-0.53, 1.24] Keogh 2007 2.86 2.7 13 3.01 4.6 12 0.0% -0.04 [-0.82, 0.75] Mamo 2005 3.1 0.2 10 3.5 0.4 10 1.5% -1.21 [-2.18, -0.24] Volek 2003 3.37 0.62 5 2.96 0.67 5 1.0% 0.57 [-0.71, 1.85] Wolfe 1991 4.22 0.88 5 5.08 0.57 5 0.9% -1.05 [-2.42, 0.33] Wolfe 1992 5.5 0.6 3 5.2 0.4 2 0.5% 0.40 [-1.47, 2.27] Wolfe 1999 2.4 0.3 5 2.6 0.3 5 1.0% -0.60 [-1.89, 0.68] Subtotal (95% CI) 45 43 7.8% -0.22 [-0.79, 0.36] Heterogeneity: Tau² = 0.23; Chi² = 9.80, df = 6 (P = 0.13); I² = 39% Test for overall effect: Z = 0.74 (P = 0.46) 7.14.4 at 2 months Abete 2009 2.98 0.89 9 2.79 0.61 10 Brehm 2005 3.36 0.8 20 2.87 0.9 20 Brinkworth 2009 3.1 1.1 52 2.9 0.6 47 Buscemi 2009 3.03 0.9 10 3.26 1.1 10 de Luis 2009a 2.79 0.9 97 3.06 1.2 96 Farnsworth 2003 3.09 0.4 7 2.93 0.9 7 Farnsworth 2003 3.26 0.8 21 3.47 0.9 21 Hodgson 2006 3 0.7 29 2.7 0.8 31 Kleiner 2006 3.5 0.6 9 2.87 1 7 Mahon 2007 3.62 1 14 3.65 0.85 14 McAuley 2005 3.3 0.7 30 3.6 0.9 31 Meckling 2004 4.4 1 15 2.92 0.9 16 Noakes 2006 3.89 1.4 24 3.54 1.1 21 Stoernell 2008 2.83 0.45 10 2.88 1.1 13 Te Morenga 2011 3 0.8 37 2.9 0.6 37 Subtotal (95% CI) 304 306 Heterogeneity: Tau² = 0.13; Chi² = 26.85, df = 11 (P = 0.005); I² = 59% Test for overall effect: Z = 1.35 (P = 0.18) 1.6% 2.5% 0.0% 1.7% 4.4% 0.0% 0.0% 3.1% 1.4% 2.1% 3.1% 1.9% 2.7% 1.9% 3.4% 30.0% 0.24 [-0.66, 1.15] 0.56 [-0.07, 1.20] 0.22 [-0.17, 0.62] -0.22 [-1.10, 0.66] -0.25 [-0.54, 0.03] 0.22 [-0.84, 1.27] -0.24 [-0.85, 0.37] 0.39 [-0.12, 0.90] 0.75 [-0.28, 1.78] -0.03 [-0.77, 0.71] -0.37 [-0.87, 0.14] 1.52 [0.71, 2.33] 0.27 [-0.32, 0.86] -0.05 [-0.88, 0.77] 0.14 [-0.32, 0.60] 0.19 [-0.09, 0.47] 2.5% 0.0% 3.9% 1.0% 1.3% 2.7% 2.4% 3.1% 0.0% 1.9% 1.9% 3.2% 2.6% 3.0% 1.8% 1.5% 2.0% 3.8% 2.6% 41.2% -0.25 [-0.90, 0.41] 0.32 [-0.29, 0.93] 0.19 [-0.18, 0.55] 0.18 [-1.09, 1.45] 0.19 [-0.86, 1.24] 0.24 [-0.36, 0.85] 0.30 [-0.37, 0.97] -0.19 [-0.69, 0.32] -0.03 [-0.82, 0.75] 0.68 [-0.15, 1.51] 0.30 [-0.50, 1.11] 0.79 [0.30, 1.28] -0.94 [-1.56, -0.33] 0.39 [-0.14, 0.93] 0.93 [0.10, 1.77] -0.73 [-1.70, 0.24] -0.86 [-1.64, -0.08] -0.20 [-0.59, 0.19] 0.29 [-0.33, 0.92] 0.08 [-0.16, 0.33] 20 43 23 27 37 201 308 2.6% 0.0% 2.8% 3.0% 3.3% 4.8% 16.6% 0.59 [-0.03, 1.21] 0.46 [0.03, 0.88] -0.33 [-0.91, 0.25] 0.29 [-0.25, 0.82] 0.01 [-0.46, 0.48] 0.27 [0.07, 0.47] 0.19 [-0.04, 0.42] 36 5 41 3.3% 1.2% 4.5% 0.34 [-0.14, 0.81] -0.36 [-1.48, 0.77] 0.19 [-0.37, 0.74] Total (95% CI) 1071 1071 100.0% Heterogeneity: Tau² = 0.10; Chi² = 88.29, df = 42 (P < 0.0001); I² = 52% Test for overall effect: Z = 1.48 (P = 0.14) Test for subgroup differences: Chi² = 2.01, df = 4 (P = 0.73), I² = 0% 0.11 [-0.03, 0.25] 7.14.5 at 3 months Ballesteros-Pomar 2010 2.64 0.91 18 2.93 1.36 18 Brehm 2003 2.92 0.6 22 2.71 0.7 20 de Luis 2009b 2.97 0.8 52 2.81 0.9 66 Dyson 2007 3.6 1 6 3.4 0.95 4 Farnsworth 2003 3.05 0.5 7 2.9 0.9 7 Farnsworth 2003 3.76 0.7 21 3.53 1.1 21 Iglay 2007 3.1 0.8 18 2.87 0.7 17 Josse 2011a 2.51 0.12 30 2.53 0.09 30 Keogh 2007 2.88 2.9 13 2.98 3.4 12 Layman 2005 3.54 0.8 12 3.07 0.5 12 Layman 2005 3.11 0.7 12 2.93 0.4 12 Layman 2009 3.61 0.58 41 3.08 0.77 30 Leidy 2007 2 0.5 21 2.48 0.5 25 Luscombe-Marsh 2005 3.5 1 26 3.1 1 30 Meckling 2007 3.36 0.8 14 2.4 1.2 11 Meckling 2007 1.97 1 10 4.91 5.7 8 Moran 2003 3.23 0.79 14 3.81 0.49 14 Noakes 2005 3.53 0.9 52 3.71 0.9 48 Volek 2009 3.5 0.8 20 3.26 0.8 20 Subtotal (95% CI) 374 373 Heterogeneity: Tau² = 0.15; Chi² = 40.02, df = 16 (P = 0.0008); I² = 60% Test for overall effect: Z = 0.65 (P = 0.52) 7.14.7 at 6 months Brehm 2003 3.21 0.7 22 2.79 0.7 Brinkworth 2009 3.19 0.94 45 2.8 0.74 Due 2004 2.8 0.9 23 3.1 0.9 Lopez-Jimenez 2010 3.21 0.6 28 3.04 0.57 Morgan 2009 3.56 0.76 33 3.55 0.73 Sacks 2009 3.21 0.8 201 3 0.75 Subtotal (95% CI) 307 Heterogeneity: Tau² = 0.02; Chi² = 5.81, df = 4 (P = 0.21); I² = 31% Test for overall effect: Z = 1.59 (P = 0.11) 7.14.9 more than 6 months Brinkworth 2009 3.8 1.15 33 3.4 1.2 Keogh 2007 2.69 0.8 8 3.01 0.9 Subtotal (95% CI) 41 Heterogeneity: Tau² = 0.04; Chi² = 1.22, df = 1 (P = 0.27); I² = 18% Test for overall effect: Z = 0.66 (P = 0.51) Std. Mean Difference IV, Random, 95% CI -2 -1 0 1 2 Favours lower protein Favours higher protein 57 58 Triglycerides Higher protein diet lower protein diet Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI 7.16.1 at 1 month Baba 1999 1.08 0.6 7 1.06 0.4 6 1.6% 0.04 [-1.05, 1.13] Farnsworth 2003 1.36 0.4 7 1.33 0.4 7 0.0% 0.07 [-0.98, 1.12] Farnsworth 2003 1.37 0.5 21 1.69 0.5 21 0.0% -0.63 [-1.25, -0.01] Jenkins 2001 2.07 0.7 10 2.79 1.1 10 1.9% -0.75 [-1.66, 0.17] Keogh 2007 1.2 2.1 13 1.13 1.8 12 0.0% 0.03 [-0.75, 0.82] Mamo 2005 1.4 0.4 10 2.2 0.3 10 1.5% -2.17 [-3.32, -1.01] Volek 2003 0.6 0.14 5 0.82 0.28 5 1.3% -0.90 [-2.24, 0.44] Wolfe 1991 1.62 0.23 5 2.44 0.56 5 1.0% -1.73 [-3.31, -0.15] Wolfe 1992 1.5 0.6 3 2.65 0.6 2 0.5% -1.39 [-3.99, 1.20] Wolfe 1999 0.69 0.1 5 0.95 0.2 5 1.1% -1.49 [-2.98, 0.01] Subtotal (95% CI) 45 43 8.9% -1.10 [-1.71, -0.49] Heterogeneity: Tau² = 0.22; Chi² = 8.99, df = 6 (P = 0.17); I² = 33% Test for overall effect: Z = 3.53 (P = 0.0004) 7.16.3 at 2 months Abete 2009 0.96 0.48 9 1.11 0.56 10 Brehm 2005 0.89 0.2 20 1.46 0.5 20 Brinkworth 2009 1.1 0.4 52 1.5 0.9 47 Buscemi 2009 0.88 0.2 10 1.11 0.4 10 de Luis 2009a 1.19 0.5 97 1.34 0.5 96 Farnsworth 2003 1.43 0.5 21 1.66 0.5 21 Farnsworth 2003 1.56 0.7 7 1.52 0.7 7 Hodgson 2006 1.35 0.76 29 1.31 1.16 31 Kleiner 2006 1.73 1.4 9 1.56 0.9 7 Mahon 2007 1.17 0.5 14 1.95 1 14 McAuley 2005 1.23 0.43 30 1.46 0.51 31 Meckling 2004 1.08 0.7 15 1.13 0.5 16 Noakes 2006 1.16 0.5 24 1.29 0.5 21 Stoernell 2008 1.33 0.61 10 2.08 1.52 13 Te Morenga 2011 1.2 0.5 37 1.2 0.5 37 Subtotal (95% CI) 304 306 Heterogeneity: Tau² = 0.07; Chi² = 19.24, df = 11 (P = 0.06); I² = 43% Test for overall effect: Z = 3.09 (P = 0.002) 2.0% 2.4% 0.0% 2.0% 3.4% 0.0% 0.0% 2.9% 1.8% 2.2% 2.9% 2.4% 2.7% 2.1% 3.0% 29.6% 7.16.5 at 3 months Ballesteros-Pomar 2010 1.02 0.42 18 1.37 0.68 18 2.5% Brehm 2003 1.04 0.5 22 1.15 0.3 20 0.0% de Luis 2009b 1.42 0.5 52 1.1 0.4 66 3.2% Dyson 2007 1.5 1.1 6 1.3 0.6 4 1.4% Farnsworth 2003 1.31 0.5 7 1.62 0.7 7 1.7% Farnsworth 2003 1.34 0.5 21 1.67 0.6 21 2.6% Iglay 2007 1.08 0.3 18 1.2 0.5 17 2.5% Josse 2011a 0.81 0.06 30 1.09 0.11 30 2.3% Keogh 2007 1.06 1.8 13 1.11 2.1 12 0.0% Layman 2005 1.12 0.4 12 1.38 0.6 12 2.2% Layman 2005 0.98 0.6 12 0.91 0.5 12 2.2% Layman 2009 1.37 0.58 41 1.09 0.38 30 2.9% Leidy 2007 0.96 0.6 21 1.24 0.5 25 2.7% Luscombe-Marsh 2005 1.4 0.7 26 1.7 1 30 2.8% Meckling 2007 1.22 0.3 14 0.98 0.3 11 2.1% Meckling 2007 1.59 0.6 10 2.05 1.2 8 1.9% Moran 2003 1.33 0.64 14 1.42 0.52 14 2.3% Noakes 2005 1.07 0.4 52 1.35 0.7 48 3.1% Volek 2009 1.17 0.5 20 1.71 0.4 20 2.5% Subtotal (95% CI) 374 373 40.7% Heterogeneity: Tau² = 0.60; Chi² = 109.07, df = 16 (P < 0.00001); I² = 85% Test for overall effect: Z = 1.77 (P = 0.08) 7.16.7 at 6 months Brehm 2003 1.29 0.8 22 1.25 0.6 20 Brinkworth 2009 0.96 0.35 45 1.43 0.96 43 Due 2004 1.2 0.5 23 1.5 0.6 23 Ferrara 2006 0.57 0.4 7 0.49 0.3 8 Lopez-Jimenez 2010 1.45 0.5 28 1.5 0.67 27 Morgan 2009 1.01 0.33 33 1.38 0.65 37 Sacks 2009 1.29 0.8 201 1.31 0.82 201 Subtotal (95% CI) 314 316 Heterogeneity: Tau² = 0.05; Chi² = 9.03, df = 5 (P = 0.11); I² = 45% Test for overall effect: Z = 1.44 (P = 0.15) -0.27 [-1.18, 0.63] -1.47 [-2.17, -0.76] -0.58 [-0.98, -0.18] -0.70 [-1.61, 0.21] -0.30 [-0.58, -0.02] -0.45 [-1.06, 0.16] 0.05 [-0.99, 1.10] 0.04 [-0.47, 0.55] 0.13 [-0.86, 1.12] -0.96 [-1.75, -0.17] -0.48 [-0.99, 0.03] -0.08 [-0.79, 0.62] -0.26 [-0.84, 0.33] -0.59 [-1.44, 0.25] 0.00 [-0.46, 0.46] -0.37 [-0.60, -0.13] -0.61 [-1.28, 0.06] -0.26 [-0.87, 0.35] 0.71 [0.34, 1.09] 0.19 [-1.08, 1.46] -0.48 [-1.55, 0.59] -0.59 [-1.21, 0.03] -0.29 [-0.95, 0.38] -3.12 [-3.89, -2.35] -0.02 [-0.81, 0.76] -0.49 [-1.31, 0.32] 0.12 [-0.68, 0.92] 0.55 [0.07, 1.03] -0.50 [-1.09, 0.09] -0.34 [-0.87, 0.19] 0.77 [-0.05, 1.60] -0.48 [-1.43, 0.47] -0.15 [-0.89, 0.59] -0.49 [-0.89, -0.09] -1.17 [-1.84, -0.49] -0.37 [-0.78, 0.04] 2.6% 0.0% 2.7% 1.8% 2.8% 2.9% 3.5% 16.3% 0.06 [-0.55, 0.66] -0.65 [-1.08, -0.22] -0.53 [-1.12, 0.06] 0.22 [-0.80, 1.23] -0.08 [-0.61, 0.45] -0.70 [-1.18, -0.21] -0.02 [-0.22, 0.17] -0.20 [-0.47, 0.07] 2.9% 1.5% 4.5% -0.52 [-1.00, -0.04] -0.64 [-1.79, 0.52] -0.54 [-0.98, -0.09] Total (95% CI) 1078 1079 100.0% Heterogeneity: Tau² = 0.25; Chi² = 161.94, df = 43 (P < 0.00001); I² = 73% Test for overall effect: Z = 4.39 (P < 0.0001) Test for subgroup differences: Chi² = 7.59, df = 4 (P = 0.11), I² = 47.3% -0.42 [-0.61, -0.23] 7.16.9 more than 6 months Brinkworth 2009 1.09 0.63 33 1.58 1.14 Keogh 2007 1.07 0.2 8 1.34 0.6 Subtotal (95% CI) 41 Heterogeneity: Tau² = 0.00; Chi² = 0.03, df = 1 (P = 0.86); I² = 0% Test for overall effect: Z = 2.37 (P = 0.02) 36 5 41 Std. Mean Difference IV, Random, 95% CI -4 -2 0 2 4 Favours higher protein Favours lower protein 58 59 Fasting blood glucose Higher protein lower protein diet Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI 7.18.1 at 1 month Baba 1999 5 0.2 7 5.1 0.4 6 1.0% -0.30 [-1.40, 0.80] Farnsworth 2003 5.3 0.5 28 5.3 0.5 29 0.0% 0.00 [-0.52, 0.52] Keogh 2007 5.44 1.6 13 5.5 1.8 12 0.0% -0.03 [-0.82, 0.75] Phillips 2008 5 0.4 10 5 0.3 10 1.5% 0.00 [-0.88, 0.88] Subtotal (95% CI) 17 16 2.4% -0.12 [-0.80, 0.57] Heterogeneity: Tau² = 0.00; Chi² = 0.18, df = 1 (P = 0.67); I² = 0% Test for overall effect: Z = 0.34 (P = 0.74) 7.18.3 at 2 months Abete 2009 4.79 0.26 9 4.99 0.32 10 Brinkworth 2009 5.5 0.5 52 5.4 0.5 47 Buscemi 2009 5.1 0.7 10 5.2 0.7 10 de Luis 2009a 5.3 0.8 97 5.1 0.7 96 Farnsworth 2003 5.6 0.5 28 5.2 5 29 Hodgson 2006 5.1 0.8 29 4.7 0.6 31 Kleiner 2006 6.1 2 9 5.9 0.9 7 Luscombe-Marsh 2005 5.4 0.5 27 5.5 0.7 30 McAuley 2005 5 0.6 30 4.8 0.4 31 Meckling 2004 5.8 2.1 15 4.9 0.7 16 Noakes 2006 5.3 0.5 24 5.2 0.5 21 Subtotal (95% CI) 223 222 Heterogeneity: Tau² = 0.00; Chi² = 6.83, df = 7 (P = 0.45); I² = 0% Test for overall effect: Z = 2.86 (P = 0.004) 1.3% 0.0% 1.5% 7.9% 0.0% 3.6% 1.2% 0.0% 3.7% 2.1% 2.9% 24.1% 7.18.5 at 3 months Ballesteros-Pomar 2010 4.46 0.44 18 4.47 0.53 18 2.4% Belobrajdic 2010 5.6 0.5831 34 5.6 0.6481 42 4.4% Bowden 2007 4.9 0.4 7 4.8 0.5 38 1.7% Bowden 2007 4.8 0.3 15 5 0.4 34 2.7% Brehm 2003 5.2 0.7 22 5 0.6 20 0.0% de Luis 2009b 5.1 0.67 52 5.2 0.8 66 5.9% Farnsworth 2003 5.4 0.3 28 5.2 0.5 29 3.5% Josse 2011a 4.9 0.1 30 4.9 0.1 30 3.7% Keogh 2007 5.52 1.5 13 5.48 1.7 12 0.0% Leidy 2007 4.8 0.3 21 4.9 0.6 25 3.0% Luscombe-Marsh 2005 5.4 0.5 27 5.5 0.6 30 3.5% Meckling 2007 5.7 0.6 14 5.1 0.5 11 1.5% Meckling 2007 5 0.9 10 4.8 0.3 8 1.3% Moran 2003 5.42 0.5 14 5.31 0.64 14 2.0% Noakes 2005 5.93 4.4 52 5.83 4.3 48 5.4% Volek 2009 4.9 0.4 20 5.2 0.5 20 2.5% Subtotal (95% CI) 342 413 43.5% Heterogeneity: Tau² = 0.03; Chi² = 17.82, df = 13 (P = 0.16); I² = 27% Test for overall effect: Z = 0.15 (P = 0.88) 7.18.7 at 6 months Brehm 2003 5 0.54 22 4.9 0.5 20 Brinkworth 2009 5.49 0.48 45 5.38 0.49 43 Due 2004 4.9 0.5 23 5.1 0.8 23 Ferrara 2006 4.4 0.4 7 4.9 0.5 8 Lopez-Jimenez 2010 5.56 0.77 28 5.47 0.61 27 Morgan 2009 5.3 0.61 33 5.18 0.51 37 Sacks 2009 5.01 0.66 201 4.95 0.61 201 Subtotal (95% CI) 314 316 Heterogeneity: Tau² = 0.01; Chi² = 5.94, df = 5 (P = 0.31); I² = 16% Test for overall effect: Z = 0.48 (P = 0.63) -0.65 [-1.58, 0.28] 0.20 [-0.20, 0.59] -0.14 [-1.01, 0.74] 0.26 [-0.02, 0.55] 0.11 [-0.41, 0.63] 0.56 [0.04, 1.08] 0.12 [-0.87, 1.11] -0.16 [-0.68, 0.36] 0.39 [-0.12, 0.90] 0.57 [-0.15, 1.29] 0.20 [-0.39, 0.78] 0.27 [0.09, 0.46] -0.02 [-0.67, 0.63] 0.00 [-0.45, 0.45] 0.20 [-0.61, 1.01] -0.53 [-1.14, 0.09] 0.30 [-0.31, 0.91] -0.13 [-0.50, 0.23] 0.48 [-0.05, 1.00] 0.00 [-0.51, 0.51] 0.02 [-0.76, 0.81] -0.20 [-0.78, 0.38] -0.18 [-0.70, 0.34] 1.04 [0.19, 1.89] 0.27 [-0.66, 1.21] 0.19 [-0.56, 0.93] 0.02 [-0.37, 0.42] -0.65 [-1.29, -0.01] -0.01 [-0.19, 0.16] 2.8% 0.0% 3.0% 1.0% 3.5% 4.1% 10.8% 25.1% 0.19 [-0.42, 0.80] 0.22 [-0.19, 0.64] -0.29 [-0.88, 0.29] -1.03 [-2.13, 0.07] 0.13 [-0.40, 0.66] 0.21 [-0.26, 0.68] 0.09 [-0.10, 0.29] 0.05 [-0.15, 0.25] 4.1% 0.8% 4.9% 0.17 [-0.30, 0.64] -0.85 [-2.03, 0.34] -0.19 [-1.14, 0.76] Total (95% CI) 937 1008 100.0% Heterogeneity: Tau² = 0.02; Chi² = 39.55, df = 31 (P = 0.14); I² = 22% Test for overall effect: Z = 1.13 (P = 0.26) Test for subgroup differences: Chi² = 5.82, df = 4 (P = 0.21), I² = 31.3% 0.06 [-0.05, 0.17] 7.18.9 more than 6 months Brinkworth 2009 5.4 0.57 33 5.3 0.6 36 Keogh 2007 5.19 0.4 8 5.5 0.2 5 Subtotal (95% CI) 41 41 Heterogeneity: Tau² = 0.30; Chi² = 2.43, df = 1 (P = 0.12); I² = 59% Test for overall effect: Z = 0.39 (P = 0.70) Std. Mean Difference IV, Random, 95% CI -1 -0.5 0 0.5 1 Favours higher protein Favours lower protein 59 60 Fasting blood insulin Higher protein lower protein diet Std. Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI 7.18.1 at 1 month Baba 1999 5 0.2 7 5.1 0.4 6 1.0% -0.30 [-1.40, 0.80] Farnsworth 2003 5.3 0.5 28 5.3 0.5 29 0.0% 0.00 [-0.52, 0.52] Keogh 2007 5.44 1.6 13 5.5 1.8 12 0.0% -0.03 [-0.82, 0.75] Phillips 2008 5 0.4 10 5 0.3 10 1.5% 0.00 [-0.88, 0.88] Subtotal (95% CI) 17 16 2.4% -0.12 [-0.80, 0.57] Heterogeneity: Tau² = 0.00; Chi² = 0.18, df = 1 (P = 0.67); I² = 0% Test for overall effect: Z = 0.34 (P = 0.74) 7.18.3 at 2 months Abete 2009 4.79 0.26 9 4.99 0.32 10 Brinkworth 2009 5.5 0.5 52 5.4 0.5 47 Buscemi 2009 5.1 0.7 10 5.2 0.7 10 de Luis 2009a 5.3 0.8 97 5.1 0.7 96 Farnsworth 2003 5.6 0.5 28 5.2 5 29 Hodgson 2006 5.1 0.8 29 4.7 0.6 31 Kleiner 2006 6.1 2 9 5.9 0.9 7 Luscombe-Marsh 2005 5.4 0.5 27 5.5 0.7 30 McAuley 2005 5 0.6 30 4.8 0.4 31 Meckling 2004 5.8 2.1 15 4.9 0.7 16 Noakes 2006 5.3 0.5 24 5.2 0.5 21 Subtotal (95% CI) 223 222 Heterogeneity: Tau² = 0.00; Chi² = 6.83, df = 7 (P = 0.45); I² = 0% Test for overall effect: Z = 2.86 (P = 0.004) 1.3% 0.0% 1.5% 7.9% 0.0% 3.6% 1.2% 0.0% 3.7% 2.1% 2.9% 24.1% 7.18.5 at 3 months Ballesteros-Pomar 2010 4.46 0.44 18 4.47 0.53 18 2.4% Belobrajdic 2010 5.6 0.5831 34 5.6 0.6481 42 4.4% Bowden 2007 4.9 0.4 7 4.8 0.5 38 1.7% Bowden 2007 4.8 0.3 15 5 0.4 34 2.7% Brehm 2003 5.2 0.7 22 5 0.6 20 0.0% de Luis 2009b 5.1 0.67 52 5.2 0.8 66 5.9% Farnsworth 2003 5.4 0.3 28 5.2 0.5 29 3.5% Josse 2011a 4.9 0.1 30 4.9 0.1 30 3.7% Keogh 2007 5.52 1.5 13 5.48 1.7 12 0.0% Leidy 2007 4.8 0.3 21 4.9 0.6 25 3.0% Luscombe-Marsh 2005 5.4 0.5 27 5.5 0.6 30 3.5% Meckling 2007 5.7 0.6 14 5.1 0.5 11 1.5% Meckling 2007 5 0.9 10 4.8 0.3 8 1.3% Moran 2003 5.42 0.5 14 5.31 0.64 14 2.0% Noakes 2005 5.93 4.4 52 5.83 4.3 48 5.4% Volek 2009 4.9 0.4 20 5.2 0.5 20 2.5% Subtotal (95% CI) 342 413 43.5% Heterogeneity: Tau² = 0.03; Chi² = 17.82, df = 13 (P = 0.16); I² = 27% Test for overall effect: Z = 0.15 (P = 0.88) 7.18.7 at 6 months Brehm 2003 5 0.54 22 4.9 0.5 20 Brinkworth 2009 5.49 0.48 45 5.38 0.49 43 Due 2004 4.9 0.5 23 5.1 0.8 23 Ferrara 2006 4.4 0.4 7 4.9 0.5 8 Lopez-Jimenez 2010 5.56 0.77 28 5.47 0.61 27 Morgan 2009 5.3 0.61 33 5.18 0.51 37 Sacks 2009 5.01 0.66 201 4.95 0.61 201 Subtotal (95% CI) 314 316 Heterogeneity: Tau² = 0.01; Chi² = 5.94, df = 5 (P = 0.31); I² = 16% Test for overall effect: Z = 0.48 (P = 0.63) -0.65 [-1.58, 0.28] 0.20 [-0.20, 0.59] -0.14 [-1.01, 0.74] 0.26 [-0.02, 0.55] 0.11 [-0.41, 0.63] 0.56 [0.04, 1.08] 0.12 [-0.87, 1.11] -0.16 [-0.68, 0.36] 0.39 [-0.12, 0.90] 0.57 [-0.15, 1.29] 0.20 [-0.39, 0.78] 0.27 [0.09, 0.46] -0.02 [-0.67, 0.63] 0.00 [-0.45, 0.45] 0.20 [-0.61, 1.01] -0.53 [-1.14, 0.09] 0.30 [-0.31, 0.91] -0.13 [-0.50, 0.23] 0.48 [-0.05, 1.00] 0.00 [-0.51, 0.51] 0.02 [-0.76, 0.81] -0.20 [-0.78, 0.38] -0.18 [-0.70, 0.34] 1.04 [0.19, 1.89] 0.27 [-0.66, 1.21] 0.19 [-0.56, 0.93] 0.02 [-0.37, 0.42] -0.65 [-1.29, -0.01] -0.01 [-0.19, 0.16] 2.8% 0.0% 3.0% 1.0% 3.5% 4.1% 10.8% 25.1% 0.19 [-0.42, 0.80] 0.22 [-0.19, 0.64] -0.29 [-0.88, 0.29] -1.03 [-2.13, 0.07] 0.13 [-0.40, 0.66] 0.21 [-0.26, 0.68] 0.09 [-0.10, 0.29] 0.05 [-0.15, 0.25] 4.1% 0.8% 4.9% 0.17 [-0.30, 0.64] -0.85 [-2.03, 0.34] -0.19 [-1.14, 0.76] Total (95% CI) 937 1008 100.0% Heterogeneity: Tau² = 0.02; Chi² = 39.55, df = 31 (P = 0.14); I² = 22% Test for overall effect: Z = 1.13 (P = 0.26) Test for subgroup differences: Chi² = 5.82, df = 4 (P = 0.21), I² = 31.3% 0.06 [-0.05, 0.17] 7.18.9 more than 6 months Brinkworth 2009 5.4 0.57 33 5.3 0.6 36 Keogh 2007 5.19 0.4 8 5.5 0.2 5 Subtotal (95% CI) 41 41 Heterogeneity: Tau² = 0.30; Chi² = 2.43, df = 1 (P = 0.12); I² = 59% Test for overall effect: Z = 0.39 (P = 0.70) Std. Mean Difference IV, Random, 95% CI -1 -0.5 Favours higher 0 0.5 1 Favours lower 60 61 C-reactive protein Higher protein diets Study or Subgroup Mean SD Lower protein diets Total Mean SD Std. Mean Difference Total Weight IV, Random, 95% CI Std. Mean Difference IV, Random, 95% CI 7.21.1 at 1 month Baba 1999 142.4 38.9 7 190.3 50.7 6 2.6% Farnsworth 2003 87.5 40.3 28 86.8 48.6 29 0.0% 0.02 [-0.50, 0.53] Mamo 2005 57.6 6.9 10 75.7 21.5 10 2.9% -1.09 [-2.04, -0.13] 10 33.66906 15.10791 27 10 26 3.0% 8.4% 0.00 [-0.88, 0.88] -0.64 [-1.37, 0.09] Phillips 2008 Subtotal (95% CI) 33.66906475 14.86811 -1.00 [-2.18, 0.19] Heterogeneity: Tau² = 0.16; Chi² = 3.23, df = 2 (P = 0.20); I² = 38% Test for overall effect: Z = 1.73 (P = 0.08) 7.21.3 at 2 months Abete 2009 53.5 28.5 9 60.4 34 10 3.0% -0.21 [-1.11, 0.69] 97 8 20 131 12 20 2.9% -3.27 [-4.24, -2.29] 47.9 34.7 52 54.2 21.5 47 0.0% -0.21 [-0.61, 0.18] 84 37.5 97 103.5 50.7 96 3.7% -0.44 [-0.72, -0.15] Farnsworth 2003 93.8 51.4 28 74.3 33.3 29 0.0% 0.45 [-0.08, 0.97] Hodgson 2006 82.6 86.8 29 51.4 31.3 31 3.5% 0.48 [-0.04, 0.99] Keogh 2007 66.2 152.1 13 46.7 74.3 12 0.0% 0.16 [-0.63, 0.94] Kleiner 2006 208.4 243.8 9 136.1 113.9 7 2.8% 0.34 [-0.65, 1.34] 63.2 25.7 27 69.5 36.1 30 0.0% -0.20 [-0.72, 0.32] McAuley 2005 46.5 10.6 30 63.9 10.6 31 3.4% -1.62 [-2.20, -1.04] Meckling 2004 117.4 51.4 15 140.3 41.7 16 3.2% -0.48 [-1.19, 0.24] 56.3 34 24 233 54.9 18.8 21 232 3.4% 25.8% 0.05 [-0.54, 0.63] -0.61 [-1.27, 0.04] Brehm 2005 Brinkworth 2009 de Luis 2009a Luscombe-Marsh 2005 Noakes 2006 Subtotal (95% CI) Heterogeneity: Tau² = 0.76; Chi² = 65.51, df = 7 (P < 0.00001); I² = 89% Test for overall effect: Z = 1.84 (P = 0.07) 7.21.5 at 3 months Ballesteros-Pomar 2010 76.4 58.9 18 71.1 47 18 3.3% 0.10 [-0.56, 0.75] Brehm 2003 80.6 38.9 22 125.7 77.8 20 0.0% -0.73 [-1.36, -0.10] Buscemi 2009 125 13.9 10 104.2 13.9 10 2.8% 1.43 [0.43, 2.44] de Luis 2009b 106.3 41.7 52 79.9 34 66 3.6% 0.70 [0.32, 1.07] 72.9 25.7 28 72.2 22.2 29 3.5% 0.03 [-0.49, 0.55] Farnsworth 2003 Josse 2011a 44 6 30 59 7 30 3.3% -2.27 [-2.93, -1.61] Keogh 2007 55.4 128.5 13 62.2 130.6 12 0.0% -0.05 [-0.84, 0.73] Layman 2005 138.5 27.4 12 133.4 29.8 12 3.1% 0.17 [-0.63, 0.97] Layman 2005 125.5 37.4 12 141.3 32.2 12 3.1% -0.44 [-1.25, 0.37] Luscombe-Marsh 2005 63.9 29.2 27 77.1 81.3 30 3.5% -0.21 [-0.73, 0.31] Meckling 2007 102.1 34.7 14 116 46.5 11 3.1% -0.33 [-1.13, 0.46] Meckling 2007 110.4 31.9 10 130.6 49.3 8 2.9% -0.48 [-1.42, 0.47] Moran 2003 115.3 62.5 14 88.9 52.1 14 3.2% 0.45 [-0.31, 1.20] Noakes 2005 50.7 25 52 58.3 57.6 48 3.6% -0.17 [-0.57, 0.22] 54 57 20 299 57 9 20 308 3.3% 42.2% -0.07 [-0.69, 0.55] -0.10 [-0.52, 0.33] Volek 2009 Subtotal (95% CI) Heterogeneity: Tau² = 0.48; Chi² = 72.52, df = 12 (P < 0.00001); I² = 83% Test for overall effect: Z = 0.44 (P = 0.66) 7.21.7 at 6 months Brehm 2003 100 45.8 22 127.8 65.3 20 3.4% -0.49 [-1.10, 0.13] Brinkworth 2009 42.9 24.2 45 51.7 23.9 43 0.0% -0.36 [-0.78, 0.06] Due 2004 47.4 22.5 23 47.4 33.2 23 3.4% 0.00 [-0.58, 0.58] Lopez-Jimenez 2010 48.3 30.8 28 61.3 32.8 27 3.4% -0.40 [-0.94, 0.13] Morgan 2009 54.8 32.4 33 75.9 45 37 3.5% -0.53 [-1.01, -0.05] Sacks 2009 Subtotal (95% CI) 22.6 4.4 201 307 17.6 3.4 201 308 3.7% 17.4% 1.27 [1.05, 1.48] -0.01 [-0.95, 0.92] Heterogeneity: Tau² = 1.07; Chi² = 88.24, df = 4 (P < 0.00001); I² = 95% Test for overall effect: Z = 0.03 (P = 0.98) 7.21.9 more than 6 months Brinkworth 2009 33.3 19.9 33 45.1 20.8 36 3.5% -0.57 [-1.06, -0.09] Keogh 2007 Subtotal (95% CI) 50.6 29.2 8 41 36.3 7.6 5 41 2.6% 6.1% 0.56 [-0.59, 1.71] -0.13 [-1.21, 0.95] 915 100.0% -0.26 [-0.59, 0.07] Heterogeneity: Tau² = 0.44; Chi² = 3.19, df = 1 (P = 0.07); I² = 69% Test for overall effect: Z = 0.24 (P = 0.81) Total (95% CI) 907 Heterogeneity: Tau² = 0.75; Chi² = 317.04, df = 30 (P < 0.00001); I² = 91% Test for overall effect: Z = 1.54 (P = 0.12) -4 -2 0 2 4 Favours higher protein Favours lower protein Test for subgroup differences: Chi² = 3.07, df = 4 (P = 0.55), I² = 0% 61