Adverse gastrointestinal events were more common with high-protein diets .
Multivariable meta-regression analysis showed no significant dose response with higher protein intake .
Conclusions : Higher-protein diets  probably improve adiposity , blood pressure and triglyceride levels , but these effects are small and need to be weighed against the potential for harms
Background / Objectives : Numerous r and omised controlled trials ( RCTs ) published in first tier medical journals have evaluated the health effects of diets high in protein .
We conducted a rigorous systematic review of RCTs comparing higher- and lower-protein diets .
A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia
Context Low-carbohydrate weight reduction diets are popular despite a dearth of data on long-term efficacy and adverse effects . Contribution Community-dwelling hyperlipidemic persons were r and omly assigned to either a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet for 24 weeks . Compared to the low-fat group , patients in the low-carbohydrate group lost more weight , had a greater decrease in triglyceride levels , and had higher high-density lipoprotein cholesterol levels . Levels of low-density lipoprotein cholesterol remained stable in both groups . Side effects were more common in the low-cholesterol group but were generally mild . Caution s While the study suggests the efficacy and relative safety of the low-cholesterol diet , the high dropout rate , self-directed adherence to the diet , and relatively short observation period challenge the generalizability of the findings . The Editors As the prevalence of obesity has increased over the past 20 years ( 1 ) , the difficulties faced by overweight patients and their health care practitioners have become apparent . Fewer than 25 % of Americans who attempt to lose weight actually reduce caloric intake and increase exercise as currently recommended ( 2 ) . Persons who successfully lose weight have difficulty maintaining their weight loss ( 3 ) . Therefore , it is not surprising that consumers spend $ 33 billion yearly on weight loss products and services in search of effective therapies ( 2 ) . Because many weight loss interventions are unproven and untested , practitioners often lack information with which to recommend a certain therapy or to monitor a patient once a therapy is chosen . One approach to weight loss that has gained recognition in the face of modest supportive scientific evidence is the low-carbohydrate diet . A popular version of this diet recommends extreme restriction of carbohydrate intake to less than 20 g/d initially ( 4 ) . This level of carbohydrate restriction can induce serum and urinary ketones and weight loss ( 5 , 6 ) . However , until recently , available data on low-carbohydrate diets came from small studies of short duration , most of which were uncontrolled ( 5 , 7 - 10 ) . We examined body weight , body composition , serum lipid levels , and adverse effects over 24 weeks in hyperlipidemic persons who were r and omly assigned to follow a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet commonly used to induce weight loss and decrease serum lipid levels . Methods Participants Generally healthy persons were recruited from the community . Inclusion criteria were age 18 to 65 years , body mass index of 30 to 60 kg/m2 , desire to lose weight , elevated lipid levels ( total cholesterol level > 5.17 mmol/L [ > 200 mg/dL ] , low-density lipoprotein [ LDL ] cholesterol level > 3.36 mmol/L [ > 130 mg/dL ] , or triglyceride level > 2.26 mmol/L [ 200 mg/dL ] ) , and no serious medical condition . Exclusion criteria were use of any prescription medication in the previous 2 months ( except for oral contraceptives , estrogen therapy , and stable thyroid medication ) , pregnancy or breastfeeding , use of any weight loss diet or diet pills in the previous 6 months , and baseline ketonuria . All participants provided written informed consent , and the institutional review board of Duke University Health System approved the study . Participants received no monetary incentive . Interventions By using a computer-generated simple r and omization list , participants were allocated to receive the low-carbohydrate diet or low-fat diet . The intervention for both groups included group meetings , diet instruction , and an exercise recommendation . Group meetings took place at an outpatient research clinic twice monthly for 3 months , then monthly for 3 months . These meetings typically lasted 1 hour and consisted of diet instruction , supportive counseling , question naires , and biomedical measurements . During the study , participants selected their own menus and prepared or bought their own meals according to the guidelines presented to them . Participants were encouraged to exercise for 30 minutes at least 3 times weekly , but no formal exercise program or incentives were provided . Low-Carbohydrate Diet Using a popular diet book published by a lay press and additional h and outs , trained research staff instructed participants to restrict intake of carbohydrates to less than 20 g/d ( 4 ) . Participants were permitted unlimited amounts of animal foods ( meat , fowl , fish , and shellfish ) , unlimited eggs , 4 oz of hard cheese , 2 cups of salad vegetables ( such as lettuce , spinach , or celery ) , and 1 cup of low-carbohydrate vegetables ( such as broccoli , cauliflower , or squash ) daily . Participants were encouraged to drink 6 to 8 glasses of water daily . When participants were halfway to their goal body weight ( determined at the week 10 visit with assistance from research personnel ) , they were advised to add approximately 5 g of carbohydrates to their daily intake each week until they reached a level at which body weight was maintained . To simulate the practice of the study sponsor , the low-carbohydrate diet group also received daily nutritional supplements ( multivitamin , essential oils , diet formulation , and chromium picolinate ; for a list of the composition of these supplements , see the Appendix ) ( 6 ) . Low-Fat Diet Using a commonly available booklet and additional h and outs , a registered dietitian instructed participants in a diet consisting of less than 30 % of daily energy intake from fat , less than 10 % of daily energy intake from saturated fat , and less than 300 mg of cholesterol daily ( 11 , 12 ) . The recommended energy intake was 2.1 to 4.2 MJ ( 500 to 1000 kcal ) less than the participant 's calculated energy intake for weight maintenance ( body weight in pounds 10 ) ( 13 ) . Primary Outcome Measure Body weight and body mass index were the primary outcome measures . At each visit , participants were weighed on the same calibrated scale while wearing lightweight clothing and no shoes .  Body mass index was calculated as body weight in kilograms divided by height in meters squared . Secondary Outcome Measures Adherence Adherence to the diet was measured by self-report , food records , and , for the low-carbohydrate diet group , urinary ketone assessment . Diet Composition All participants completed a 24-hour recall of food intake at baseline and take-home food records ( 5 consecutive days , including a weekend ) that were collected at each meeting during the study . Participants were instructed on how to document food intake and were given h and outs with examples of how to complete the records . A sample of participants ( 13 in the low-carbohydrate diet group and 7 in the low-fat diet group ) who completed the study was selected for food record analysis by the research staff on the basis of adequacy of detail in their records . A registered dietitian analyzed the food records by using a nutrition software program ( Nutritionist Five , version 1.6 [ First Data Bank , Inc. , San Bruno , California ] ) . Ketonuria Restriction of dietary intake of carbohydrates to less than 40 g/d typically results in ketonuria that is detectable by dipstick analysis , which can be used to monitor adherence to the low-carbohydrate diet ( 14 , 15 ) . At each return visit , participants provided a fresh urine specimen for analysis . The following semi-quantitative scale was used to categorize ketone content : none , trace ( up to 0.9 mmol/L [ 5 mg/dL ] ) , small ( 0.9 to 6.9 mmol/L [ 5 to 40 mg/dL ] ) , moderate ( 6.9 to 13.8 mmol/L [ 40 to 80 mg/dL ] ) , large80 ( 13.8 to 27.5 mmol/L [ 80 to 160 mg/dL ] ) , and large160 ( > 27.5 mmol/L [ > 160 mg/dL ] ) . Body Composition Body composition was estimated by using bioelectric impedance ( model TBF-300A [ Tanita Corp. , Arlington Heights , Illinois ] ) at approximately the same time of day ( afternoon or evening ) at each return visit . In a subset of 33 participants , the percentage of body fat as measured by bioelectric impedance had excellent correlation with the percentage as measured by dual-energy x-ray absorptiometry ( r = 0.93 [ 95 % CI , 0.87 to 0.97 ] ) . Vital Signs Blood pressure and pulse rate were measured in the nondominant arm by using an automated digital cuff ( model HEM-725C [ Omron Corp. , Vernon Hills , Illinois ] ) after the participant had been sitting for 3 minutes . Two measurements were taken at each visit and averaged for the analysis . Serum Lipids and Lipoproteins Serum specimens for lipid measurement were obtained in the morning after at least 8 hours of fasting at the screening visit and at 8 , 16 , and 24 weeks . Other Metabolic Effects Serum tests for sodium , potassium , chloride , urea nitrogen , creatinine , calcium , phosphorus , total protein , albumin , uric acid , total bilirubin , alanine aminotransferase , aspartate aminotransferase , alkaline phosphatase , thyroid-stimulating hormone , iron , hemoglobin , leukocyte count , and platelet count were obtained at the screening visit and at 8 , 16 , and 24 weeks . The glomerular filtration rate was estimated by using an equation that included age ; sex ; race ; and serum levels of albumin , creatinine , and urea nitrogen ( Modification of Diet in Renal Disease Study equation ) ( 16 ) . Adverse Effects At all return visits , participants completed an open-ended question naire on side effects . At the 20- and 24-week visits , participants completed a checklist of the side effects that were most often mentioned during the study . Statistical Analysis Analyses were performed by using S-PLUS software , version 6.1 ( Insightful Corp. , Seattle , Washington ) , or SAS software , version 8.02 ( SAS Institute , Inc. , Cary , North Carolina ) . For categorical outcomes , groups were compared by using the chi-square test or Fisher exact test , as appropriate . For all primary and secondary continuous outcomes , linear mixed-effects models ( PROC MIXED procedure in SAS software ) that included fixed and r and om effects were used to determine expected mean values at each time point and to test hypotheses of group differences . In most body weight and
Adverse gastrointestinal events were more common with high-protein diets .
Multivariable meta-regression analysis showed no significant dose response with higher protein intake .
Conclusions : Higher-protein diets  probably improve adiposity , blood pressure and triglyceride levels , but these effects are small and need to be weighed against the potential for harms
Background / Objectives : Numerous r and omised controlled trials ( RCTs ) published in first tier medical journals have evaluated the health effects of diets high in protein .
We conducted a rigorous systematic review of RCTs comparing higher- and lower-protein diets .