Advertisement
Journal of the Academy of Nutrition and Dietetics home
Eatright.org home
Advanced searchSave search
Research Review| Volume 121, ISSUE 8, P1551-1564.e3, August 2021

The Effect of Meal Replacement on Weight Loss According to Calorie-Restriction Type and Proportion of Energy Intake: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Open AccessPublished:June 16, 2021DOI:https://doi.org/10.1016/j.jand.2021.05.001
The Effect of Meal Replacement on Weight Loss According to Calorie-Restriction Type and Proportion of Energy Intake: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Previous ArticleInitial Development and Evaluation of the Food Processing Knowledge (FoodProK) Score: A Functional Test of Nutrition Knowledge Based on Level of Processing
Next ArticleUpdates to the Definition of Evidence-Based (Dietetics) Practice: Providing Clarity for Practice

      Abstract

      Background

      Portion control is a useful component of weight reduction interventions and meal replacement (MR) plans represent a promising strategy for portion control. Research performed with pooled data on the effect of MR plans according to various characteristics of MR interventions remains scarce.

      Objective

      Our aim was to assess the effects of MR-based diets compared with food-based diets on weight loss, according to calorie-restriction types and energy intake proportions from MR.

      Methods

      Electronic databases (Cochrane Central Register of Controlled Trials, PubMed, Embase, and Research Information Sharing Service) were searched for randomized controlled trials on weight loss results of MR-based calorie-restricted diets compared with food-based calorie-restricted diets from January 2000 to May 2020. Standardized mean differences (Hedges' g) from all study outcomes were calculated using a random-effects model. Heterogeneity was quantified by Q test and I2. Publication bias was assessed using a funnel plot and a trim and fill method. Both interventions (MR and control) were separated into very-low-energy diets and low-energy diets (LEDs). A meta-analysis of variance was conducted by dividing patient-related factors and treatment-related factors into subgroups. In multivariable meta-regressions, background variables were selected first, after which main independent variables were included.

      Results

      Twenty-two studies involving 24 interventions and 1,982 patients who were overweight or obese were included. The effect size in which MR-based LED was compared with food-based LED for weight loss was small, favoring MR (Hedges’ g = 0.261; 95% CI 0.156 to 0.365; I2 = 21.9; 95% CI 0.0 to 53.6). Diets including ≥60% of total daily energy intake from MR had a medium effect size favoring MR with regard to weight loss among the groups (Hedges’ g = 0.545; 95% CI 0.260 to 0.830; I2 = 42.7; 95% CI 0.0 to 80.8).

      Conclusions

      The effect of MR-based LED on weight loss was superior to the effect of food-based LED, and receiving ≥60% of total daily energy intake from MR had the greatest effect on weight loss.

      Keywords

      The Continuing Professional Education (CPE) quiz for this article is available for free to Academy members through the MyCDRGo app (available for iOS and Android devices) and through www.jandonline.org (click on “CPE” in the menu and then “Academy Journal CPE Articles”). Log in with your Academy of Nutrition and Dietetics or Commission on Dietetic Registration username and password, click “Journal Article Quiz” on the next page, then click the “Additional Journal CPE quizzes” button to view a list of available quizzes. Non-members may take CPE quizzes by sending a request to [email protected] There is a $45 fee per quiz (includes quiz and copy of article) for non-members. CPE quizzes are valid for 3 years after the issue date in which the articles are published.
      Research Question: Is calorie restriction with meal replacement (MR) more effective for weight loss than conventional calorie restriction? Is there a greater effect on weight loss with an increasing percentage of total daily energy intake from MR?
      Key Findings: In this systematic review and meta-analysis, the effect of an MR-based low-energy diet on weight loss was superior to the effect of food-based conventional low-energy diet (Hedges’ g = 0.261; 95% CI 0.156 to 0.365), where ≥60% of total daily energy intake from MR resulted in the greatest effect (Hedges’ g = 0.545; 95% CI 0.260 to 0.830).
      The prevalence of obesity is increasing worldwide.
      Obesity
      World Health Organization. Updated April 1, 2020. Accessed June 30, 2020.
      https://www.who.int/features/factfiles/obesity/en/
      Obesity can increase the risk of developing diabetes and several types of cancer,
      Obesity
      World Health Organization. Updated April 1, 2020. Accessed June 30, 2020.
      https://www.who.int/features/factfiles/obesity/en/
      and can increase all-cause mortality.
      • Flegal K.M.
      • Kit B.K.
      • Orpana H.
      • Graubard B.I.
      Association of all-cause mortality with overweight and obesity using standard body mass index categories: A systematic review and meta-analysis.
      JAMA. 2013; 309: 71-82https://doi.org/10.1001/jama.2012.113905
      Weight loss reduces the health risks associated with obesity.
      • Wing R.R.
      • Lang W.
      • Wadden T.A.
      • et al.
      Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes.
      Diabetes Care. 2011; 34: 1481-1486
      , 
      • Christensen R.
      • Bartels E.M.
      • Astrup A.
      • et al.
      Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: A systematic review and meta-analysis.
      Ann Rheum Dis. 2007; 66: 433-439
      , 
      • Poobalan A.
      • Aucott L.
      • Smith W.C.S.
      • et al.
      Effects of weight loss in overweight/obese individuals and long-term lipid outcomes—A systematic review.
      Obes Rev. 2004; 5: 43-50
      Among other factors, the energy imbalance caused by excessive caloric intake and/or lack of physical activity has been shown to play an important role in the occurrence of obesity,
      • Apovian C.M.
      Obesity: Definition, comorbidities, causes, and burden.
      Am J Manag Care. 2016; 22: S176-S185
      ,
      • Razina A.O.
      • Runenko S.D.
      • Achkasov E.E.
      Obesity: Current global and Russian trends.
      Vestn Ross Akad Med Nauk. 2016; 2: 154-159
      and the most common treatment for obesity is calorie restriction.
      • Johnston B.C.
      • Kanters S.
      • Bandayrel K.
      • et al.
      Comparison of weight loss among named diet programs in overweight and obese adults: A meta-analysis.
      JAMA. 2014; 312: 923-933
      , 
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      N Engl J Med. 2008; 359: 229-241
      , 
      • Hemmingsson E.
      • Johansson K.
      • Eriksson J.
      • Sundström J.
      • Neovius M.
      • Marcus C.
      Weight loss and dropout during a commercial weight-loss program including a very-low-calorie diet, a low-calorie diet, or restricted normal food: Observational cohort study.
      Am J Clin Nutr. 2012; 96: 953-961
      Calorie-restricted diets can be divided into 2 types based on the number of calories consumed per day—low-energy diets (LEDs), which are the most common and allow 1,000 to 1,500 kcal/d, and very-low-energy diets (VLED), which allow only 600 to 800 kcal/d.
      • Tsai A.G.
      • Wadden T.A.
      The evolution of very-low-calorie diets: An update and meta-analysis.
      Obesity (Silver Spring). 2006; 14: 1283-1293
      Successful calorie restriction is closely related not only to the energy density of the foods consumed, but also to behavioral strategies such as self-monitoring, planning, food purchasing and preparation, and intake control. This can eventually lead to weight loss.
      • Rolls B.J.
      What is the role of portion control in weight management?.
      Int J Obes (Lond). 2014; 38: S1-S8https://doi.org/10.1038/ijo.2014.82
      , 
      • Rolls B.J.
      • Roe L.S.
      • Meengs J.S.
      The effect of large portion sizes on energy intake is sustained for 11 days.
      Obesity. 2007; 15: 1535-1543
      , 
      • Cahayadi J.
      • Geng X.
      • Mirosa M.
      • Peng M.
      Expectancy versus experience—Comparing portion-size-effect during premeal planning and actual intake.
      Appetite. 2019; 135: 108-114
      , 
      • Gillison F.
      • Stathi A.
      • Reddy P.
      • et al.
      Processes of behavior change and weight loss in a theory-based weight loss intervention program: A test of the process model for lifestyle behavior change.
      Int J Behav Nutr Phys Act. 2015; 12: 2https://doi.org/10.1186/s12966-014-0160-6
      , 
      • Ramage S.
      • Farmer A.
      • Eccles K.A.
      • McCargar L.
      Healthy strategies for successful weight loss and weight maintenance: A systematic review.
      Appl Physiol Nutr Metab. 2014; 39: 1-20https://doi.org/10.1139/apnm-2013-0026
      Meal replacement (MR) plans are an example of behavioral strategies that help promote weight loss by eliminating choices in addition to controlling intake.
      • Heymsfield S.B.
      Meal replacements and energy balance.
      Physiol Behav. 2010; 100: 90-94
      , 
      • Heymsfield S.B.
      • Van Mierlo C.
      • Van der Knaap H.
      • Heo M.
      • Frier H.I.
      Weight management using a meal replacement strategy: Meta and pooling analysis from six studies.
      Int J Obes Relat Metab Disord. 2003; 27: 537-549
      , 
      • Ashley J.M.
      • St Jeor S.T.
      • Schrage J.P.
      • et al.
      Weight control in the physician’s office.
      Arch Intern Med. 2001; 161: 1599-1604
      MR plans, which consist of commercially available products fortified with minerals and vitamins, include total diet replacement plans to replace all daily meals and partial meal replacement plans to replace 1 or 2 meals per day.
      • Rolls B.J.
      What is the role of portion control in weight management?.
      Int J Obes (Lond). 2014; 38: S1-S8https://doi.org/10.1038/ijo.2014.82
      ,
      • Wing R.R.
      • Jeffery R.W.
      Food provision as a strategy to promote weight loss.
      Obes Res. 2001; 9: 271S-275Shttps://doi.org/10.1038/oby.2001.130
      ,
      • Ard J.D.
      • Lewis K.H.
      • Rothberg A.
      • et al.
      Effectiveness of a Total Meal Replacement Program (OPTIFAST Program) on weight loss: Results from the OPTIWIN Study.
      Obesity (Silver Spring). 2019; 27: 22-29
      The effects of MR plans on weight loss have been studied for the past 20 years.
      • Heymsfield S.B.
      • Van Mierlo C.
      • Van der Knaap H.
      • Heo M.
      • Frier H.I.
      Weight management using a meal replacement strategy: Meta and pooling analysis from six studies.
      Int J Obes Relat Metab Disord. 2003; 27: 537-549
      Previously, meta-analyses by Loveman and colleagues,
      • Loveman E.
      • Frampton G.K.
      • Shepherd J.
      • et al.
      The clinical effectiveness and cost-effectiveness of long-term weight management schemes for adults: A systematic review.
      Health Technol Assess. 2011; 15: 1-182
      Franz and colleagues,
      • Franz M.J.
      • Vanwormer J.J.
      • Lauren Crain A.
      • et al.
      Weight-loss outcomes: A systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up.
      J Am Diet Assoc. 2007; 107: 1755-1767
      and Kahleova and colleagues,
      • Kahleova H.
      • Salas-Salvadó J.
      • Rahelić D.
      • Kendall C.W.C.
      • Rembert E.
      • Sievenpiper J.L.
      Dietary patterns and cardiometabolic outcomes in diabetes: A summary of systematic reviews and meta-analyses.
      Nutrients. 2019; 11: 2209https://doi.org/10.3390/nu11092209
      showed that, as part of energy-restriction strategies, MR plans generally promote weight loss. Therefore, MR plans have been shown to be effective for weight loss as part of energy-restriction diets; however, those meta-analyses did not compare MR plans with conventional food-based diets. Other meta-analyses by Heymsfield and colleagues,
      • Heymsfield S.B.
      • Van Mierlo C.
      • Van der Knaap H.
      • Heo M.
      • Frier H.I.
      Weight management using a meal replacement strategy: Meta and pooling analysis from six studies.
      Int J Obes Relat Metab Disord. 2003; 27: 537-549
      Leslie and colleagues,
      • Leslie W.S.
      • Taylor R.
      • Harris L.
      • Lean M.E.J.
      Weight losses with low-energy formula diets in obese patients with and without type 2 diabetes: Systematic review and meta-analysis.
      Int J Obes. 2017; 41: 96-101
      and Astbury and colleagues,
      • Astbury N.M.
      • Piernas C.
      • Hartmann-Boyce J.
      • Lapworth S.
      • Aveyard P.
      • Jebb S.A.
      A systematic review and meta-analysis of the effectiveness of meal replacements for weight loss.
      Obes Rev. 2019; 20: 569-587
      suggested that MR plans lead to more effective weight loss than other weight loss methods, including alternative types of diets, with or without support and nominal intervention, at 3 months and 1 year, respectively. However, as Astbury and colleagues
      • Astbury N.M.
      • Piernas C.
      • Hartmann-Boyce J.
      • Lapworth S.
      • Aveyard P.
      • Jebb S.A.
      A systematic review and meta-analysis of the effectiveness of meal replacements for weight loss.
      Obes Rev. 2019; 20: 569-587
      reported, due to the small sample sizes for each subgroup, whether or not the characteristics of MR interventions impacted the observed effect was not assessed.
      As described, several meta-analyses examining MR plans have addressed their effects on weight loss as a part of energy-restriction diets or compared them with conventional food-based diets. An additional question may be to assess the conditions under which MR plans might be more effective. For example, it should be investigated whether there are differences in weight loss depending on patient-related factors, such as age, sex, and initial body mass index (BMI; calculated as kg/m2), or depending on treatment-related factors, such as treatment period, number of MR meals, and percentage of total daily energy intake from MR. In several clinical trials on the effect of MR plans on weight loss, no interactions were found between sex, age, and/or BMI and treatment and extent of weight lost.
      • Flechtner-Mors M.
      • Ditschuneit H.H.
      • Johnson T.D.
      • Suchard M.A.
      • Adler G.
      Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.
      Obes Res. 2000; 8: 399-402
      , 
      • Allison D.B.
      • Gadbury G.
      • Schwartz L.G.
      • et al.
      A novel soy-based meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Eur J Clin Nutr. 2003; 57: 514-522
      , 
      • Noakes M.
      • Foster P.R.
      • Keogh J.B.
      • Clifton P.M.
      Meal replacements are as effective as structured weight-loss diets for treating obesity in adults with features of metabolic syndrome.
      J Nutr. 2004; 134: 1894-1899
      , 
      • König D.
      • Zdzieblik D.
      • Deibert P.
      • Berg A.
      • Gollhofer A.
      • Büchert M.
      Internal fat and cardiometabolic risk factors following a meal-replacement regimen vs. comprehensive lifestyle changes in obese subjects.
      Nutrients. 2015; 7: 9825-9833
      Otherwise, the impact of patient-related factors has not been reported in most other clinical trials investigating the efficacy of MR plans for weight loss.
      • Guo X.
      • Xu Y.
      • He H.
      • et al.
      Effects of a meal replacement on body composition and metabolic parameters among subjects with overweight or obesity.
      J Obes. 2018; 2018: 2837367https://doi.org/10.1155/2018/2837367
      , 
      • Leader N.J.
      • Ryan L.
      • Molyneaux L.
      • Yue D.K.
      How best to use partial meal replacement in managing overweight or obese patients with poorly controlled type 2 diabetes.
      Obesity. 2013; 21: 251-253
      , 
      • Rothacker D.Q.
      • Staniszewski B.A.
      • Ellis P.K.
      Liquid meal replacement vs traditional food: A potential model for women who cannot maintain eating habit change.
      J Am Diet Assoc. 2001; 101: 345-347
      , 
      • Ahrens R.A.
      • Hower M.
      • Best A.M.
      Effects of weight reduction interventions by community pharmacists.
      J Am Pharm Assoc. 2003; 43: 583-589
      , 
      • Fisberg M.
      • de Oliveira C.L.
      • de Pádua C.I.
      • et al.
      Impact of the hypocaloric diet using food substitutes on the body weight and biochemical profile.
      Arch Latinoam Nutr. 2004; 54: 402-407
      , 
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of portion-controlled entrees enhances weight loss in women.
      Obes Res. 2004; 12: 538-546
      , 
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of packaged entrees as part of a weight-loss diet in overweight men: An 8-week randomized clinical trial.
      Diabetes Obes Metab. 2006; 8: 146-155
      , 
      • Ashley J.M.
      • Herzog H.
      • Clodfelter S.
      • Bovee V.
      • Schrage J.
      • Pritsos C.
      Nutrient adequacy during weight loss interventions: A randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group.
      Nutr J. 2007; 6: 12https://doi.org/10.1186/1475-2891-6-12
      , 
      • Rohrer J.E.
      • Takahashi P.
      Should overweight and obese primary care patients be offered a meal replacement diet?.
      Obes Res Clin Pract. 2008; 2: 263-268
      , 
      • Tsai ChH.
      • Chiu W.C.
      • Yang N.C.
      • Ouyang C.M.
      • Yen Y.H.
      A novel green tea meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Int J Food Sci Nutr. 2009; 60: 151-159
      , 
      • Smith T.J.
      • Sigrist L.D.
      • Bathalon G.P.
      • McGraw S.
      • Karl J.P.
      • Young A.J.
      Efficacy of a meal-replacement program for promoting blood lipid changes and weight and body fat loss in US Army soldiers.
      J Am Diet Assoc. 2010; 110: 268-273
      , 
      • Metzner C.E.
      • Folberth-Vögele A.
      • Bitterlich N.
      • et al.
      Effect of a conventional energy-restricted modified diet with or without meal replacement on weight loss and cardiometabolic risk profile in overweight women.
      Nutr Metab (Lond). 2011; 8: 64https://doi.org/10.1186/1743-7075-8-64
      , 
      • Khoo J.
      • Ling P.S.
      • Tan J.
      • et al.
      Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
      Int J Impot Res. 2013; 26: 61-66
      , 
      • Shikany J.M.
      • Thomas A.S.
      • Beasley T.M.
      • Lewis C.E.
      • Allison D.B.
      Randomized controlled trial of the Medifast 5 & 1 Plan for weight loss.
      Int J Obes (Lond). 2013; 37: 1571-1578
      , 
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      , 
      • Rock C.L.
      • Flatt S.W.
      • Pakiz B.
      • et al.
      Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
      Obesity. 2016; 24: 1230-1237
      , 
      • Gulati S.
      • Misra A.
      • Tiwari R.
      • Sharma M.
      • Pandey R.M.
      • Yadav C.P.
      Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.
      Br J Nutr. 2017; 117: 1531-1540
      , 
      • Kuriyan R.
      • Lokesh D.P.
      • D’Souza N.
      • et al.
      Portion controlled ready-to-eat meal replacement is associated with short term weight loss: A randomised controlled trial.
      Asia Pac J Clin Nutr. 2017; 26: 1055-1065
      , 
      • Shih C.K.
      • Chen C.M.
      • Hsiao T.J.
      • Liu C.W.
      • Li S.C.
      White sweet potato as meal replacement for overweight white-collar workers: A randomized controlled trial.
      Nutrients. 2019; 11: E165https://doi.org/10.3390/nu11010165
      , 
      • Kim J.Y.
      Effects of Very-Low-Calorie Diets using Meal replacements on Weight Reduction and Health in the Obese Premenopausal Women.
      Hanyang University, Master’s2005
      In terms of the number of MR meals per day, a characteristic of MR interventions, Guo and colleagues
      • Guo X.
      • Xu Y.
      • He H.
      • et al.
      Effects of a meal replacement on body composition and metabolic parameters among subjects with overweight or obesity.
      J Obes. 2018; 2018: 2837367https://doi.org/10.1155/2018/2837367
      reported in a clinical trial that although total diet replacement was more effective for weight loss, partial meal replacement was more beneficial as a long-term treatment when considering individual adherence to dietary regimens. In another clinical trial, Leader and colleagues
      • Leader N.J.
      • Ryan L.
      • Molyneaux L.
      • Yue D.K.
      How best to use partial meal replacement in managing overweight or obese patients with poorly controlled type 2 diabetes.
      Obesity. 2013; 21: 251-253
      showed that 2 MR meals per day are more effective than 1 MR meal per day for weight loss, regulation of blood glucose, and compliance with dietary prescriptions in patients with obesity and diabetes. However, no meta-analysis has analyzed patient-related and/or treatment-related factors in relation to the effect of MR plans on weight loss. Once these associations are known, MR plans can be applied more strategically to optimize weight loss outcomes.
      Therefore, this meta-analysis sought to investigate the effect of an MR diet on weight loss in comparison with conventional calorie-restricted diets, according to treatment-related factors, such as treatment period, number of MR meals, and percentage of total daily energy intake from MR. These findings may have the potential to inform clinical practice.

      Methods

      Eligibility Criteria

      The population, intervention, comparison, outcome and study design framework was used to formulate eligibility criteria in this study.
      Centre for Reviews and Dissemination
      Systematic Reviews: CRD’s Guidance for Undertaking Reviews in Health Care.
      University of York, 2009
      Published randomized controlled trials involved calorie-restricted diets using MR (which comprise commercially available products fortified with minerals and vitamins, including liquid formula, powdered mixes, energy bars, and prepackaged foods). Individuals aged between 18 and 65 years who were overweight or obese and without other chronic diseases (ie, no significant health conditions) were included. Only studies with weight loss interventions were included. There was no restriction in the duration of the interventions. For studies including 2 or more interventions, only those involving MR plans were included. Comparison groups included calorie-restricted diets without MR (ie, food-based diets). Studies needed to include weight-related outcomes (mean changes and standard deviation difference in weight or BMI) for estimating intervention effectiveness, otherwise they were excluded (insufficient data). The review was limited to English- or Korean-language articles. A nutritionist, a clinician, and a meta-analytical statistician collaborated on all aspects of this study.

      Search Strategy

      The meta-analysis on weight management using MR conducted by Heymsfield and colleagues
      • Heymsfield S.B.
      • Van Mierlo C.
      • Van der Knaap H.
      • Heo M.
      • Frier H.I.
      Weight management using a meal replacement strategy: Meta and pooling analysis from six studies.
      Int J Obes Relat Metab Disord. 2003; 27: 537-549
      included searches from 1960 to January 2001. Therefore, this study aimed to analyze more recent research trends regarding the effect of MR plans on weight loss by searching related studies starting from 2000. The following sources were searched for studies conducted from 2000 to May 2020: Cochrane Central Register of Controlled Trials, PubMed, Embase and Research Information Sharing Service; thesis papers were also searched. The search strategy followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines.
      • Liberati A.
      • Altman D.G.
      • Tetzlaff J.
      • et al.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration.
      PLoS Med. 2009; 6e1000100https://doi.org/10.1371/journal.pmed.1000100
      Two co-first authors (J.M., S.-Y. K.) searched the articles independently using the following search terms: ("meal replacement"[title/abstract/keywords (tiabkw)] OR "meal supplement"[tiabkw] OR "portion control"[tiabkw]) AND ("weight loss"[tiabkw] OR "weight reduction"[tiabkw] OR "obesity management"[tiabkw]). The reference lists of the included studies were screened for potentially relevant articles, and backward and forward citation searches were performed in Google Scholar for all identified trials. In the case of any discrepancy, discussions was undertaken until agreement was reached. Figure 1 (available at www.jandonline.org) shows the complete search strategy used in the electronic database Cochrane Central Register of Controlled Trials.

      Data Extraction and Quality Assessment

      Once consensus was reached regarding which articles to retain, a predefined data template was prepared; data were extracted and coded based on this template. The study characteristics (publication year, journal, study design, and location), participants (sample size, age, sex, BMI, height, and weight), intervention (duration, type of calorie-restriction, frequency of MR intake, and percentage of total daily energy intake from MR), and weight-related outcomes (mean changes and standard deviation difference in weight or BMI) were included as data. When both weight and BMI were reported in a study, the BMI was used for the analyses. The data were then cross-checked by the 2 co-first authors (J.M., S.-Y. K.). Any discrepancy was further discussed until an agreement was reached. The methodological quality of the included studies was assessed using the Cochrane’s risk of bias assessment tool 2.

      Higgins JPT, Thomas J, Chandler J, et al, eds. Cochrane Handbook for Systematic Reviews of Interventions, Version 6.0. Updated July 2019. Accessed June 30, 2020. www.training.cochrane.org/handbook

      Potential publication bias was explored using visual inspection of funnel plot asymmetry
      • Borenstein M.
      • Hedges L.V.
      • Higgins J.P.T.
      • Rothstein H.R.
      Introduction to Meta-Analysis.
      Wiley, 2009
      and the trim and fill method. Publication bias tests and funnel plots are only relevant when there are more than 10 studies; otherwise, these are underpowered for detection and tend to lead to unjustified conclusions.
      • Sterne J.A.
      • Gavaghan D.
      • Egger M.
      Publication and related bias in meta-analysis: Power of statistical tests and prevalence in the literature.
      J Clin Epidemiol. 2000; 53: 1119-1129https://doi.org/10.1016/s0895-4356(00)00242-0
      Publication bias tests were conducted according to the number of included studies. Egger test
      • Egger M.
      • Smith G.D.
      • Schneider M.
      • Minder C.
      Bias in meta-analysis detected by a simple, graphical test.
      BMJ. 1997; 315: 629-634
      and Begg and Mazumdar rank correlation
      • Begg C.B.
      • Mazumdar M.
      Operating characteristics of a rank correlation test for publication bias.
      Biometrics. 1994; 50: 1088-1101
      were applied together to provide a summary effect adjusted for publication bias.

      Computation of Effect Sizes

      Meta-analyses use statistical methods to synthesize effect sizes, and, thus, standardize the quantitative findings of all studies.
      • Lipsey M.W.
      • Wilson D.B.
      Practical Meta-Analysis. Applied Social Research Methods Series. Vol. 49.
      Sage Publications, 2001
      In this study, the effect size was based on “the standardized mean change difference (d)” between post-test and pretest measurements in 2 heterogeneous groups—the treatment and control groups.
      • Becker B.J.
      Synthesizing standardized mean-change measures.
      Br J Math Stat Psychol. 1988; 41: 257-278
      The effect size, that is, d, was calculated as follows:
      d=Ytrt−XtrtSpooled−Yctr−XctrSpooled


      where Ytrt and Xtrt are the post-test and pretest means in the treatment group, respectively; Yctr and Xctrare the post-test and pretest means in the control group, respectively; and Spooled is the within-groups standard deviation.
      Spooled=(ntrt−1)(Strt)2+(nctr−1)(Sctr)2ntrt+nctr−2


      where ntrt and nctrare the sample sizes in the treatment and control groups, respectively.
      The variance of d was calculated using the following formula:
      V(d)=ntrt+nctr(ntrt)(nctr)+d22(ntrt+nctr)


      The standard error of d is the square root of V(d). Small-sample studies show a tendency toward increased effect size. Therefore, a small-sample study correction factor (Hedges’ g) was used.
      J=1−34(Ntotal−2)−1


      The effect size, that is, g, was calculated using a correction factor (J). Then, g=JXd,V(g)=J2XV(d),andSE(g)=V(g). For this meta-analysis, the significance of the results of each study was interpreted with the following effect sizes: 0.2, small; 0.5, medium; and 0.8, large.
      • Cohen J.
      Statistical Power Analysis for the Behavioral Sciences.
      2nd ed. Routledge Academic, 1988
      Hedges’ g is a standardized mean difference. The specific effects of studies (mean differences) are also reported in Table 4 (available at www.jandonline.org) for reference.

      Data Analyses

      In this study, the primary outcome was change in BMI or weight. Heterogeneity in BMI or weight among studies was assessed using Q test and I2 with CIs. The articles were thought to be sufficiently heterogeneous, given the diversity of countries in which they were conducted and the variety of races represented across participants. If homogeneity is rejected, a random-effects model is applied. The random-effects model is more conservative and provides better estimates with wider CIs than a fixed-effects model.
      • Brockwell S.E.
      • Gordon I.R.
      A comparison of statistical methods for meta-analysis.
      Stat Med. 2001; 20: 825-840https://doi.org/10.1002/sim.650
      ,
      • Kontopantelis E.
      • Reeves D.
      Performance of statistical methods for meta-analysis when true study effects are non-normally distributed: A simulation study.
      Stat Methods Med Res. 2012; 21: 409-426https://doi.org/10.1177/0962280210392008
      Therefore, although the heterogeneity was not significant (I2 = 15.364; P = .249), the random-effects model (DerSimonian-Laird method with inverse variance weighting) was used to assess overall effect sizes; each subgroup was analyzed with Comprehensive Meta-Analysis software (version 3).

      Comprehensive Meta-Analysis [computer program]. Version 3; Biostat Inc; 2019.

      The study interventions, the MR-based calorie-restricted diets, were compared with the control interventions, the food-based calorie-restricted diets, after being separated into VLED and LED groups. The standardized mean change difference was calculated first as within-group change from baseline, and then as between-group difference. The shifting unit-of-analysis method was used to prevent any unit-of-analysis error.
      • Becker B.J.
      Multivariate meta-analysis.
      in: Tinsley E.A. Brown S.D. Handbook of Applied and Multivariate Statistics and Mathematical Modeling. 1st ed. Academic Press, 2000: 499-525
      ,
      • Cooper H.
      Research Synthesis and Meta-Analysis: A Step-by-Step Approach.
      5th ed. Sage, 2016
      For the overall effects, P values < .05 were considered statistically significant.
      • Wasserstein R.L.
      • Lazar N.A.
      The ASA's statement on p-values: Context, process, and purpose.
      Am Stat. 2016; 70: 129-133

      Meta-Analysis of Variance and Meta-Regression

      Meta-analysis of variance (ANOVA) and meta-regression were used to evaluate the potential clinical significance of the effects of MR diets on weight loss between groups according to the following moderators: age, sex, initial BMI, duration of treatment, frequency of MR intake, and percentage of total daily energy intake from MR. The meta-ANOVA was conducted by treating the patient-related factors as binary, and by dividing the percentage of total daily energy intake from MR, 1 of the treatment-related factors, into the following subgroups: <30%, ≥30% and <60%, and ≥60%. In a hierarchical-approach multivariable meta-regression, background variables are selected first, and the main independent variables are then included to estimate the effect of MR intake while controlling for background variables. To assess the impact of BMI and main independent variables while controlling for age and sex, they were simultaneously applied as covariates. As for the main independent variables, the percentage of total daily energy intake from MR and the frequency of MR intake were not used simultaneously because, although different from a clinical perspective, they are similar from a statistical point of view and seem to be collinear.

      Results

      Study Description

      The initial search identified 493 potential studies for inclusion. Ultimately, 22
      • Flechtner-Mors M.
      • Ditschuneit H.H.
      • Johnson T.D.
      • Suchard M.A.
      • Adler G.
      Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.
      Obes Res. 2000; 8: 399-402
      , 
      • Allison D.B.
      • Gadbury G.
      • Schwartz L.G.
      • et al.
      A novel soy-based meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Eur J Clin Nutr. 2003; 57: 514-522
      , 
      • Noakes M.
      • Foster P.R.
      • Keogh J.B.
      • Clifton P.M.
      Meal replacements are as effective as structured weight-loss diets for treating obesity in adults with features of metabolic syndrome.
      J Nutr. 2004; 134: 1894-1899
      , 
      • König D.
      • Zdzieblik D.
      • Deibert P.
      • Berg A.
      • Gollhofer A.
      • Büchert M.
      Internal fat and cardiometabolic risk factors following a meal-replacement regimen vs. comprehensive lifestyle changes in obese subjects.
      Nutrients. 2015; 7: 9825-9833
      ,
      • Rothacker D.Q.
      • Staniszewski B.A.
      • Ellis P.K.
      Liquid meal replacement vs traditional food: A potential model for women who cannot maintain eating habit change.
      J Am Diet Assoc. 2001; 101: 345-347
      , 
      • Ahrens R.A.
      • Hower M.
      • Best A.M.
      Effects of weight reduction interventions by community pharmacists.
      J Am Pharm Assoc. 2003; 43: 583-589
      , 
      • Fisberg M.
      • de Oliveira C.L.
      • de Pádua C.I.
      • et al.
      Impact of the hypocaloric diet using food substitutes on the body weight and biochemical profile.
      Arch Latinoam Nutr. 2004; 54: 402-407
      , 
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of portion-controlled entrees enhances weight loss in women.
      Obes Res. 2004; 12: 538-546
      , 
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of packaged entrees as part of a weight-loss diet in overweight men: An 8-week randomized clinical trial.
      Diabetes Obes Metab. 2006; 8: 146-155
      , 
      • Ashley J.M.
      • Herzog H.
      • Clodfelter S.
      • Bovee V.
      • Schrage J.
      • Pritsos C.
      Nutrient adequacy during weight loss interventions: A randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group.
      Nutr J. 2007; 6: 12https://doi.org/10.1186/1475-2891-6-12
      , 
      • Rohrer J.E.
      • Takahashi P.
      Should overweight and obese primary care patients be offered a meal replacement diet?.
      Obes Res Clin Pract. 2008; 2: 263-268
      , 
      • Tsai ChH.
      • Chiu W.C.
      • Yang N.C.
      • Ouyang C.M.
      • Yen Y.H.
      A novel green tea meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Int J Food Sci Nutr. 2009; 60: 151-159
      , 
      • Smith T.J.
      • Sigrist L.D.
      • Bathalon G.P.
      • McGraw S.
      • Karl J.P.
      • Young A.J.
      Efficacy of a meal-replacement program for promoting blood lipid changes and weight and body fat loss in US Army soldiers.
      J Am Diet Assoc. 2010; 110: 268-273
      , 
      • Metzner C.E.
      • Folberth-Vögele A.
      • Bitterlich N.
      • et al.
      Effect of a conventional energy-restricted modified diet with or without meal replacement on weight loss and cardiometabolic risk profile in overweight women.
      Nutr Metab (Lond). 2011; 8: 64https://doi.org/10.1186/1743-7075-8-64
      , 
      • Khoo J.
      • Ling P.S.
      • Tan J.
      • et al.
      Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
      Int J Impot Res. 2013; 26: 61-66
      , 
      • Shikany J.M.
      • Thomas A.S.
      • Beasley T.M.
      • Lewis C.E.
      • Allison D.B.
      Randomized controlled trial of the Medifast 5 & 1 Plan for weight loss.
      Int J Obes (Lond). 2013; 37: 1571-1578
      , 
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      , 
      • Rock C.L.
      • Flatt S.W.
      • Pakiz B.
      • et al.
      Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
      Obesity. 2016; 24: 1230-1237
      , 
      • Gulati S.
      • Misra A.
      • Tiwari R.
      • Sharma M.
      • Pandey R.M.
      • Yadav C.P.
      Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.
      Br J Nutr. 2017; 117: 1531-1540
      , 
      • Kuriyan R.
      • Lokesh D.P.
      • D’Souza N.
      • et al.
      Portion controlled ready-to-eat meal replacement is associated with short term weight loss: A randomised controlled trial.
      Asia Pac J Clin Nutr. 2017; 26: 1055-1065
      , 
      • Shih C.K.
      • Chen C.M.
      • Hsiao T.J.
      • Liu C.W.
      • Li S.C.
      White sweet potato as meal replacement for overweight white-collar workers: A randomized controlled trial.
      Nutrients. 2019; 11: E165https://doi.org/10.3390/nu11010165
      , 
      • Kim J.Y.
      Effects of Very-Low-Calorie Diets using Meal replacements on Weight Reduction and Health in the Obese Premenopausal Women.
      Hanyang University, Master’s2005
      met the inclusion criteria and were included in this systematic review and meta-analysis (Figure 2), which included 24 interventions and a total of 1,982 patients. Twenty-one studies,
      • Flechtner-Mors M.
      • Ditschuneit H.H.
      • Johnson T.D.
      • Suchard M.A.
      • Adler G.
      Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.
      Obes Res. 2000; 8: 399-402
      , 
      • Allison D.B.
      • Gadbury G.
      • Schwartz L.G.
      • et al.
      A novel soy-based meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Eur J Clin Nutr. 2003; 57: 514-522
      , 
      • Noakes M.
      • Foster P.R.
      • Keogh J.B.
      • Clifton P.M.
      Meal replacements are as effective as structured weight-loss diets for treating obesity in adults with features of metabolic syndrome.
      J Nutr. 2004; 134: 1894-1899
      , 
      • König D.
      • Zdzieblik D.
      • Deibert P.
      • Berg A.
      • Gollhofer A.
      • Büchert M.
      Internal fat and cardiometabolic risk factors following a meal-replacement regimen vs. comprehensive lifestyle changes in obese subjects.
      Nutrients. 2015; 7: 9825-9833
      ,
      • Rothacker D.Q.
      • Staniszewski B.A.
      • Ellis P.K.
      Liquid meal replacement vs traditional food: A potential model for women who cannot maintain eating habit change.
      J Am Diet Assoc. 2001; 101: 345-347
      , 
      • Ahrens R.A.
      • Hower M.
      • Best A.M.
      Effects of weight reduction interventions by community pharmacists.
      J Am Pharm Assoc. 2003; 43: 583-589
      , 
      • Fisberg M.
      • de Oliveira C.L.
      • de Pádua C.I.
      • et al.
      Impact of the hypocaloric diet using food substitutes on the body weight and biochemical profile.
      Arch Latinoam Nutr. 2004; 54: 402-407
      , 
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of portion-controlled entrees enhances weight loss in women.
      Obes Res. 2004; 12: 538-546
      , 
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of packaged entrees as part of a weight-loss diet in overweight men: An 8-week randomized clinical trial.
      Diabetes Obes Metab. 2006; 8: 146-155
      , 
      • Ashley J.M.
      • Herzog H.
      • Clodfelter S.
      • Bovee V.
      • Schrage J.
      • Pritsos C.
      Nutrient adequacy during weight loss interventions: A randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group.
      Nutr J. 2007; 6: 12https://doi.org/10.1186/1475-2891-6-12
      , 
      • Rohrer J.E.
      • Takahashi P.
      Should overweight and obese primary care patients be offered a meal replacement diet?.
      Obes Res Clin Pract. 2008; 2: 263-268
      , 
      • Tsai ChH.
      • Chiu W.C.
      • Yang N.C.
      • Ouyang C.M.
      • Yen Y.H.
      A novel green tea meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Int J Food Sci Nutr. 2009; 60: 151-159
      , 
      • Smith T.J.
      • Sigrist L.D.
      • Bathalon G.P.
      • McGraw S.
      • Karl J.P.
      • Young A.J.
      Efficacy of a meal-replacement program for promoting blood lipid changes and weight and body fat loss in US Army soldiers.
      J Am Diet Assoc. 2010; 110: 268-273
      , 
      • Metzner C.E.
      • Folberth-Vögele A.
      • Bitterlich N.
      • et al.
      Effect of a conventional energy-restricted modified diet with or without meal replacement on weight loss and cardiometabolic risk profile in overweight women.
      Nutr Metab (Lond). 2011; 8: 64https://doi.org/10.1186/1743-7075-8-64
      , 
      • Khoo J.
      • Ling P.S.
      • Tan J.
      • et al.
      Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
      Int J Impot Res. 2013; 26: 61-66
      , 
      • Shikany J.M.
      • Thomas A.S.
      • Beasley T.M.
      • Lewis C.E.
      • Allison D.B.
      Randomized controlled trial of the Medifast 5 & 1 Plan for weight loss.
      Int J Obes (Lond). 2013; 37: 1571-1578
      , 
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      , 
      • Rock C.L.
      • Flatt S.W.
      • Pakiz B.
      • et al.
      Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
      Obesity. 2016; 24: 1230-1237
      , 
      • Gulati S.
      • Misra A.
      • Tiwari R.
      • Sharma M.
      • Pandey R.M.
      • Yadav C.P.
      Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.
      Br J Nutr. 2017; 117: 1531-1540
      , 
      • Kuriyan R.
      • Lokesh D.P.
      • D’Souza N.
      • et al.
      Portion controlled ready-to-eat meal replacement is associated with short term weight loss: A randomised controlled trial.
      Asia Pac J Clin Nutr. 2017; 26: 1055-1065
      , 
      • Shih C.K.
      • Chen C.M.
      • Hsiao T.J.
      • Liu C.W.
      • Li S.C.
      White sweet potato as meal replacement for overweight white-collar workers: A randomized controlled trial.
      Nutrients. 2019; 11: E165https://doi.org/10.3390/nu11010165
      including 22 interventions, compared MR-based LED with food-based LED; 1 of the studies,
      • Kim J.Y.
      Effects of Very-Low-Calorie Diets using Meal replacements on Weight Reduction and Health in the Obese Premenopausal Women.
      Hanyang University, Master’s2005
      which included 2 interventions, compared MR-based VLED with food-based VLED. Only 2 studies consisted of all men, 6 consisted of all women, and 14 involved both sexes within a group. The country distribution was as follows: 853 patients from the United States (n = 10), 229 patients from Germany (n = 3), 232 patients from India (n = 2), 176 patients from Taiwan (n = 2), 118 patients from Australia (n = 2), 81 patients from the Republic of Korea (n = 2), 67 patients from Brazil (n = 1), and 46 patients from Singapore (n = 1). Table 1 summarizes the characteristics of the included studies. The calorie contents of the MRs ranged from 270 to 1,200 kcal/d.
      Figure thumbnail gr1
      Figure 2Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of the literature search and filtering of results for a systematic review and meta-analysis of the effect of meal replacement-based calorie-restricted diets on weight loss, compared with conventional calorie-restricted diets. CENTRAL = Cochrane Central Register of Controlled Trials; RISS = Research Information Sharing Service.
      Table 1Characteristics of included randomized controlled trials for the systematic review and meta-analysis of meal replacement–based, calorie-restricted diets vs conventional calorie-restricted diets
      First author, year, countryAge, yFemale, %Initial BMI
      BMI = body mass index; calculated as kg/m2.
      		Total randomized/ analyzed, nPeriod, wkType of MR
      MR = meal replacement.
      		No. of meals replacedMR, kcal/d (%)Outcome measureAdverse events (mean ± SD,
      SD = standard deviation.
      P value in intergroup)
      ←——————————————————————————————MR-based LED
      LED = low-energy diet.
      vs food-based LED————————————————————————→
      Flechtner-Mors, 2000,
      • Flechtner-Mors M.
      • Ditschuneit H.H.
      • Johnson T.D.
      • Suchard M.A.
      • Adler G.
      Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.
      Obes Res. 2000; 8: 399-402
      Germany      		45.279.033.6100/10012Liquid formula2420 (31)BW
      BW = body weight.
      		NR
      NR = not reported.
      Rothacker, 2001,
      • Rothacker D.Q.
      • Staniszewski B.A.
      • Ellis P.K.
      Liquid meal replacement vs traditional food: A potential model for women who cannot maintain eating habit change.
      J Am Diet Assoc. 2001; 101: 345-347
      United States      		36.910028.975/6152Powdered mixes plus skim milk31,320 (100)BWNone
      Ahrens, 2003,
      • Ahrens R.A.
      • Hower M.
      • Best A.M.
      Effects of weight reduction interventions by community pharmacists.
      J Am Pharm Assoc. 2003; 43: 583-589
      United States      		47.787.429.395/8812Liquid formula2220 (16)BWNR
      Allison, 2003,
      • Allison D.B.
      • Gadbury G.
      • Schwartz L.G.
      • et al.
      A novel soy-based meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Eur J Clin Nutr. 2003; 57: 514-522
      United States      		50.280.034.3100/7412Powdered mixes plus water2800 (68)BWGas/indigestion (1.59 ± NR
      P < .05 (P value in intergroup).
      ), constipation (.51 ± NR
      P < .05 (P value in intergroup).
      ), taste: abnormal (.3 ± NR
      P < .05 (P value in intergroup).
      ), lethargy (.19 ± NR
      P < .05 (P value in intergroup).
      )
      Fisberg, 2004,
      • Fisberg M.
      • de Oliveira C.L.
      • de Pádua C.I.
      • et al.
      Impact of the hypocaloric diet using food substitutes on the body weight and biochemical profile.
      Arch Latinoam Nutr. 2004; 54: 402-407
      Brazil      		36.093.6NR78/6712Liquid formula or powdered mixes plus milk2420 (30)BWTransitory elimination of flatus (n = 1)
      Hannum, 2004,
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of portion-controlled entrees enhances weight loss in women.
      Obes Res. 2004; 12: 538-546
      United States      		37.110031.660/538Prepackaged foods2733 (54)BMINR
      Noakes, 2004,
      • Noakes M.
      • Foster P.R.
      • Keogh J.B.
      • Clifton P.M.
      Meal replacements are as effective as structured weight-loss diets for treating obesity in adults with features of metabolic syndrome.
      J Nutr. 2004; 134: 1894-1899
      Australia      		48.141.832.566/4224Liquid formula and bars2430 (30)BWNR
      Hannum, 2006,
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of packaged entrees as part of a weight-loss diet in overweight men: An 8-week randomized clinical trial.
      Diabetes Obes Metab. 2006; 8: 146-155
      United States      		38.1031.460/518Prepackaged foods2733 (43.1)BMINR
      Ashley, 2007,
      • Ashley J.M.
      • Herzog H.
      • Clodfelter S.
      • Bovee V.
      • Schrage J.
      • Pritsos C.
      Nutrient adequacy during weight loss interventions: A randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group.
      Nutr J. 2007; 6: 12https://doi.org/10.1186/1475-2891-6-12
      United States      		38.210029.396/7052Liquid formula or bars2440 (37)BMINone
      Rohrer, 2008,
      • Rohrer J.E.
      • Takahashi P.
      Should overweight and obese primary care patients be offered a meal replacement diet?.
      Obes Res Clin Pract. 2008; 2: 263-268
      United States      		47.280.036.363/554Prepackaged foods3— (100)BWNR
      Tsai, 2009,
      • Tsai ChH.
      • Chiu W.C.
      • Yang N.C.
      • Ouyang C.M.
      • Yen Y.H.
      A novel green tea meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Int J Food Sci Nutr. 2009; 60: 151-159
      Taiwan      		43.285.832.4120/12012Powdered mixes plus water2.3800 (68)BWDiarrhea (.59 ± .01
      P < .05 (P value in intergroup).
      ), gas/indigestion (1.27 ± .16
      P < .05 (P value in intergroup).
      ), losing sleep (1.57 ± .73
      P < .05 (P value in intergroup).
      )
      Smith, 2010,
      • Smith T.J.
      • Sigrist L.D.
      • Bathalon G.P.
      • McGraw S.
      • Karl J.P.
      • Young A.J.
      Efficacy of a meal-replacement program for promoting blood lipid changes and weight and body fat loss in US Army soldiers.
      J Am Diet Assoc. 2010; 110: 268-273
      United States      		28.232.733.1113/11324Liquid formula or bars2380 (24)BMINR
      Metzner, 2011,
      • Metzner C.E.
      • Folberth-Vögele A.
      • Bitterlich N.
      • et al.
      Effect of a conventional energy-restricted modified diet with or without meal replacement on weight loss and cardiometabolic risk profile in overweight women.
      Nutr Metab (Lond). 2011; 8: 64https://doi.org/10.1186/1743-7075-8-64
      Germany      		49.710031.2105/8712Liquid formula, soups or bars2415 (35)BMIDiarrhea (n = 1)
      Khoo, 2013,
      • Khoo J.
      • Ling P.S.
      • Tan J.
      • et al.
      Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
      Int J Impot Res. 2013; 26: 61-66


      Singapore      		40.5032.748/4612Liquid formula2640 (43)BMINone
      Shikany, 2013,
      • Shikany J.M.
      • Thomas A.S.
      • Beasley T.M.
      • Lewis C.E.
      • Allison D.B.
      Randomized controlled trial of the Medifast 5 & 1 Plan for weight loss.
      Int J Obes (Lond). 2013; 37: 1571-1578
      United States      		40.088.340.9120/10526Liquid formula and prepackaged foods31,000 (100)BMINR
      König, 2015,
      • König D.
      • Zdzieblik D.
      • Deibert P.
      • Berg A.
      • Gollhofer A.
      • Büchert M.
      Internal fat and cardiometabolic risk factors following a meal-replacement regimen vs. comprehensive lifestyle changes in obese subjects.
      Nutrients. 2015; 7: 9825-9833


      Germany      		49.057.132.750/426Powdered mixes2460 (42)BMINR
      Fuller, 2016,
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      Australia      		42.353.930.476/766Whole-grain products2NRBWGastrointestinal adverse effects (n = 2)
      Rock, 2016 (a),
      • Rock C.L.
      • Flatt S.W.
      • Pakiz B.
      • et al.
      Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
      Obesity. 2016; 24: 1230-1237
      United States      		46.458.633.1117/11612Prepackaged foods including high protein2266 (35)BMINR
      Rock, 2016 (b),
      • Rock C.L.
      • Flatt S.W.
      • Pakiz B.
      • et al.
      Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
      Obesity. 2016; 24: 1230-1237
      United States      		46.759.833.4112/11212Prepackaged foods2266 (35)BMINR
      Gulati, 2017,
      • Gulati S.
      • Misra A.
      • Tiwari R.
      • Sharma M.
      • Pandey R.M.
      • Yadav C.P.
      Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.
      Br J Nutr. 2017; 117: 1531-1540
      India      		37.557.430.4122/12212Powdered mixes2642 (43)BMINone
      Kuriyan, 2017,
      • Kuriyan R.
      • Lokesh D.P.
      • D’Souza N.
      • et al.
      Portion controlled ready-to-eat meal replacement is associated with short term weight loss: A randomised controlled trial.
      Asia Pac J Clin Nutr. 2017; 26: 1055-1065
      India      		31.010029.1110/1102—2288 (21)BMINR
      Shih, 2019,
      • Shih C.K.
      • Chen C.M.
      • Hsiao T.J.
      • Liu C.W.
      • Li S.C.
      White sweet potato as meal replacement for overweight white-collar workers: A randomized controlled trial.
      Nutrients. 2019; 11: E165https://doi.org/10.3390/nu11010165
      Taiwan      		38.151.824.860/568Powdered mixes2781.4 (58)BMINo serious adverse effects
      ←————————————————————————————MR-based VLED
      VLED = very-low-energy diet.
      vs food-based VLED—————————————————————————→
      Kim, 2005,
      • Kim J.Y.
      Effects of Very-Low-Calorie Diets using Meal replacements on Weight Reduction and Health in the Obese Premenopausal Women.
      Hanyang University, Master’s2005
      Republic of Korea      		24.410025.666/544Powdered mixes including herbal extract2270 (45)BMIConstipation (1.74 ± .10
      P < .05 (P value in intergroup).
      ), powerlessness (1.74 ± .11
      P < .05 (P value in intergroup).
      ), vomiting (1.33 ± .09
      P < .05 (P value in intergroup).
      )
      Kim, 2005,
      • Kim J.Y.
      Effects of Very-Low-Calorie Diets using Meal replacements on Weight Reduction and Health in the Obese Premenopausal Women.
      Hanyang University, Master’s2005


      Republic of Korea      		24.810027.066/544Powdered mixes2270 (45)BMIConstipation (2.22 ± .12
      P < .05 (P value in intergroup).
      ), powerlessness (2.11 ± .11
      P < .05 (P value in intergroup).
      ), anemia (2.00 ± .13
      P < .05 (P value in intergroup).
      ), vomiting (1.85 ± .16
      P < .05 (P value in intergroup).
      ), dryness of skin (1.70 ± .17
      P < .05 (P value in intergroup).
      ), headache (1.15 ± .07
      P < .05 (P value in intergroup).
      )
      a BMI = body mass index; calculated as kg/m2.
      b MR = meal replacement.
      c SD = standard deviation.
      d LED = low-energy diet.
      e BW = body weight.
      f NR = not reported.
      g VLED = very-low-energy diet.
      ∗ P < .05 (P value in intergroup).

      Risk of Bias and Publication Bias

      Quality Assessment

      Table 2 summarizes the risk of bias in the 22 articles. The assessment showed that 5 studies used adequate methods for the randomization process,
      • Allison D.B.
      • Gadbury G.
      • Schwartz L.G.
      • et al.
      A novel soy-based meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Eur J Clin Nutr. 2003; 57: 514-522
      ,
      • Khoo J.
      • Ling P.S.
      • Tan J.
      • et al.
      Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
      Int J Impot Res. 2013; 26: 61-66
      , 
      • Shikany J.M.
      • Thomas A.S.
      • Beasley T.M.
      • Lewis C.E.
      • Allison D.B.
      Randomized controlled trial of the Medifast 5 & 1 Plan for weight loss.
      Int J Obes (Lond). 2013; 37: 1571-1578
      , 
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      ,
      • Kuriyan R.
      • Lokesh D.P.
      • D’Souza N.
      • et al.
      Portion controlled ready-to-eat meal replacement is associated with short term weight loss: A randomised controlled trial.
      Asia Pac J Clin Nutr. 2017; 26: 1055-1065
      and 7 studies were rated low risk for the missing outcome data.
      • Flechtner-Mors M.
      • Ditschuneit H.H.
      • Johnson T.D.
      • Suchard M.A.
      • Adler G.
      Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.
      Obes Res. 2000; 8: 399-402
      ,
      • Tsai ChH.
      • Chiu W.C.
      • Yang N.C.
      • Ouyang C.M.
      • Yen Y.H.
      A novel green tea meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Int J Food Sci Nutr. 2009; 60: 151-159
      ,
      • Khoo J.
      • Ling P.S.
      • Tan J.
      • et al.
      Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
      Int J Impot Res. 2013; 26: 61-66
      ,
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      ,
      • Rock C.L.
      • Flatt S.W.
      • Pakiz B.
      • et al.
      Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
      Obesity. 2016; 24: 1230-1237
      ,
      • Kuriyan R.
      • Lokesh D.P.
      • D’Souza N.
      • et al.
      Portion controlled ready-to-eat meal replacement is associated with short term weight loss: A randomised controlled trial.
      Asia Pac J Clin Nutr. 2017; 26: 1055-1065
      ,
      • Shih C.K.
      • Chen C.M.
      • Hsiao T.J.
      • Liu C.W.
      • Li S.C.
      White sweet potato as meal replacement for overweight white-collar workers: A randomized controlled trial.
      Nutrients. 2019; 11: E165https://doi.org/10.3390/nu11010165
      The other domains were assessed as low risk in all studies.
      Table 2Evaluation of the risk of bias of included randomized controlled trials for systematic review and meta-analysis of meal replacement–based, calorie-restricted vs conventional calorie-restricted diets, using the Cochrane risk of bias tool

      Higgins JPT, Thomas J, Chandler J, et al, eds. Cochrane Handbook for Systematic Reviews of Interventions, Version 6.0. Updated July 2019. Accessed June 30, 2020. www.training.cochrane.org/handbook

      First author, yearRandomization processDeviations from intended interventionsMissing outcome dataMeasurement of the outcomeSelection of the reported resultOverall bias
      Flechtner-Mors, 2000
      • Flechtner-Mors M.
      • Ditschuneit H.H.
      • Johnson T.D.
      • Suchard M.A.
      • Adler G.
      Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.
      Obes Res. 2000; 8: 399-402
      		Some concernsLowLowLowLowSome concerns
      Rothacker, 2001
      • Rothacker D.Q.
      • Staniszewski B.A.
      • Ellis P.K.
      Liquid meal replacement vs traditional food: A potential model for women who cannot maintain eating habit change.
      J Am Diet Assoc. 2001; 101: 345-347
      		Some concernsLowHighLowLowHigh
      Ahrens, 2003
      • Ahrens R.A.
      • Hower M.
      • Best A.M.
      Effects of weight reduction interventions by community pharmacists.
      J Am Pharm Assoc. 2003; 43: 583-589
      		Some concernsLowHighLowLowHigh
      Allison, 2003
      • Allison D.B.
      • Gadbury G.
      • Schwartz L.G.
      • et al.
      A novel soy-based meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Eur J Clin Nutr. 2003; 57: 514-522
      		LowLowHighLowLowHigh
      Fisberg, 2004
      • Fisberg M.
      • de Oliveira C.L.
      • de Pádua C.I.
      • et al.
      Impact of the hypocaloric diet using food substitutes on the body weight and biochemical profile.
      Arch Latinoam Nutr. 2004; 54: 402-407
      		Some concernsLowHighLowLowHigh
      Hannum, 2004
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of portion-controlled entrees enhances weight loss in women.
      Obes Res. 2004; 12: 538-546
      		Some concernsLowHighLowLowHigh
      Noakes, 2004
      • Noakes M.
      • Foster P.R.
      • Keogh J.B.
      • Clifton P.M.
      Meal replacements are as effective as structured weight-loss diets for treating obesity in adults with features of metabolic syndrome.
      J Nutr. 2004; 134: 1894-1899
      		Some concernsLowHighLowLowHigh
      Hannum, 2006
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of packaged entrees as part of a weight-loss diet in overweight men: An 8-week randomized clinical trial.
      Diabetes Obes Metab. 2006; 8: 146-155
      		Some concernsLowHighLowLowHigh
      Ashley, 2007
      • Ashley J.M.
      • Herzog H.
      • Clodfelter S.
      • Bovee V.
      • Schrage J.
      • Pritsos C.
      Nutrient adequacy during weight loss interventions: A randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group.
      Nutr J. 2007; 6: 12https://doi.org/10.1186/1475-2891-6-12
      		Some concernsLowHighLowLowHigh
      Rohrer, 2008
      • Rohrer J.E.
      • Takahashi P.
      Should overweight and obese primary care patients be offered a meal replacement diet?.
      Obes Res Clin Pract. 2008; 2: 263-268
      		Some concernsLowHighLowLowHigh
      Tsai, 2009
      • Tsai ChH.
      • Chiu W.C.
      • Yang N.C.
      • Ouyang C.M.
      • Yen Y.H.
      A novel green tea meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Int J Food Sci Nutr. 2009; 60: 151-159
      		Some concernsLowLowLowLowSome concerns
      Smith, 2010
      • Smith T.J.
      • Sigrist L.D.
      • Bathalon G.P.
      • McGraw S.
      • Karl J.P.
      • Young A.J.
      Efficacy of a meal-replacement program for promoting blood lipid changes and weight and body fat loss in US Army soldiers.
      J Am Diet Assoc. 2010; 110: 268-273
      		Some concernsLowHighLowLowHigh
      Metzner, 2011
      • Metzner C.E.
      • Folberth-Vögele A.
      • Bitterlich N.
      • et al.
      Effect of a conventional energy-restricted modified diet with or without meal replacement on weight loss and cardiometabolic risk profile in overweight women.
      Nutr Metab (Lond). 2011; 8: 64https://doi.org/10.1186/1743-7075-8-64
      		Some concernsLowHighLowLowHigh
      Khoo, 2013
      • Khoo J.
      • Ling P.S.
      • Tan J.
      • et al.
      Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
      Int J Impot Res. 2013; 26: 61-66
      		LowLowLowLowLowLow
      Shikany, 2013
      • Shikany J.M.
      • Thomas A.S.
      • Beasley T.M.
      • Lewis C.E.
      • Allison D.B.
      Randomized controlled trial of the Medifast 5 & 1 Plan for weight loss.
      Int J Obes (Lond). 2013; 37: 1571-1578
      		LowLowHighLowLowHigh
      König, 2015
      • König D.
      • Zdzieblik D.
      • Deibert P.
      • Berg A.
      • Gollhofer A.
      • Büchert M.
      Internal fat and cardiometabolic risk factors following a meal-replacement regimen vs. comprehensive lifestyle changes in obese subjects.
      Nutrients. 2015; 7: 9825-9833
      		Some concernsLowHighLowLowHigh
      Fuller, 2016
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      		LowLowLowLowLowLow
      Rock, 2016
      • Rock C.L.
      • Flatt S.W.
      • Pakiz B.
      • et al.
      Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
      Obesity. 2016; 24: 1230-1237
      		Some concernsLowLowLowLowSome concerns
      Gulati, 2017
      • Gulati S.
      • Misra A.
      • Tiwari R.
      • Sharma M.
      • Pandey R.M.
      • Yadav C.P.
      Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.
      Br J Nutr. 2017; 117: 1531-1540
      		Some concernsLowHighLowLowHigh
      Kuriyan, 2017
      • Kuriyan R.
      • Lokesh D.P.
      • D’Souza N.
      • et al.
      Portion controlled ready-to-eat meal replacement is associated with short term weight loss: A randomised controlled trial.
      Asia Pac J Clin Nutr. 2017; 26: 1055-1065
      		LowLowLowLowLowLow
      Shih, 2019
      • Shih C.K.
      • Chen C.M.
      • Hsiao T.J.
      • Liu C.W.
      • Li S.C.
      White sweet potato as meal replacement for overweight white-collar workers: A randomized controlled trial.
      Nutrients. 2019; 11: E165https://doi.org/10.3390/nu11010165
      		Some concernsLowLowLowLowSome concerns
      Kim, 2005
      • Kim J.Y.
      Effects of Very-Low-Calorie Diets using Meal replacements on Weight Reduction and Health in the Obese Premenopausal Women.
      Hanyang University, Master’s2005
      		Some concernsLowHighLowLowHigh

      Publication Bias

      Publication bias was assessed by visual inspection of a funnel plot with trim and fill,
      • Borenstein M.
      • Hedges L.V.
      • Higgins J.P.T.
      • Rothstein H.R.
      Introduction to Meta-Analysis.
      Wiley, 2009
      Egger test,
      • Egger M.
      • Smith G.D.
      • Schneider M.
      • Minder C.
      Bias in meta-analysis detected by a simple, graphical test.
      BMJ. 1997; 315: 629-634
      and Begg and Mazumdar rank correlation.
      • Begg C.B.
      • Mazumdar M.
      Operating characteristics of a rank correlation test for publication bias.
      Biometrics. 1994; 50: 1088-1101
      A symmetrical distribution of funnel plot data reflects no publication bias.
      • Borenstein M.
      • Hedges L.V.
      • Higgins J.P.T.
      • Rothstein H.R.
      Introduction to Meta-Analysis.
      Wiley, 2009
      No evidence of publication bias was found, as shown in Figure 3. Moreover, no significant publication bias was found on the Egger test (P = .909) or on Begg and Mazumdar rank correlation (P = 1.000).
      Figure thumbnail gr2
      Figure 3Funnel plot of the effect size on change in body weight or body mass index between meal replacement-based calorie restriction and conventional calorie restriction groups.

      Main Findings

      Effects on Weight Loss by Calorie-Restriction Diet Type

      To estimate an overall effectiveness based on “shifting unit of analysis,”
      • Cooper H.
      Research Synthesis and Meta-Analysis: A Step-by-Step Approach.
      5th ed. Sage, 2016
      an effect size per study was calculated to consider the study as a unit of analysis. The overall effect size of MR diet on weight loss was small compared with conventional diets (Hedges’ g = 0.255; 95% CI 0.154 to 0.356; I2 = 15.4; 95% CI 0.0 to 48.3). Results of a meta-ANOVA analysis indicated that the effect size of MR-based LED vs food-based LED was small (Hedges’ g = 0.261; 95% CI 0.156 to 0.365; I2 = 21.9; 95% CI 0.0 to 53.6). However, the effect size of MR-based VLED vs food-based VLED (Hedges’ g = 0.166; 95% CI –0.235 to 0.567; I2 = 0) was not statistically significant (Table 3), and there was no significant difference between the LED and the VLED groups (Q = .202, degrees of freedom = 1; P = .653).
      Table 3Effect size of meal replacement diets vs conventional diets on weight loss according to calorie-restriction type
      GroupnEffect SizeTest of Heterogeneity
      Hedges’ g95% CI
      Point estimateStandard errorLower limitUpper limitQ valuedf (Q value)P valueI2 (CI)
      LED
      LED = low energy diet.
      		220.2610.0530.1560.36526.87521.17521.9 (0.0 to 53.6)
      VLED
      VLED = very-low-energy diet.
      		20.1660.205–0.2350.5670.0631.8030
      Overall240.2550.0520.1540.35627.17523.24915.4 (0.0 to 48.3)
      (Title: The effect of meal replacement on weight loss according to calorie-restriction type and proportion of energy intake: a systematic review and meta-analysis of randomized controlled trials)
      a LED = low energy diet.
      b VLED = very-low-energy diet.

      Effects of MR-Based LED Compared with Food-Based LED on Weight Loss According to Percentage of Total Daily Energy Intake from MR

      Figure 4 depicts the Hedges’ g values and the forest plots for MR-based LED compared with food-based LED. To examine whether the overall effects of MR-based LED differed according to the percentage of total daily energy intake from MR, 3 subgroups (<30%, ≥30% and <60%, and ≥60%) were created according to caloric intake percentage. The meta-ANOVA test showed that in those receiving ≥60% calories from MR, the effect size was medium and had the greatest effect size on weight loss (Hedges’ g = 0.545; 95% CI 0.260 to 0.830; I2 = 42.7; 95% CI 0.0 to 80.8); this was followed by the group receiving ≥30% and <60% (Hedges’ g = 0.232; 95% CI 0.114 to 0.350; I2 = 0). The group with <30% calories from MR was not statistically different (Hedges’ g = 0.055; 95% CI –0.206 to 0.316; I2 = 0); there was a significant difference between groups (Q = 9.226; degrees of freedom = 2; P = .010). In addition, to highlight the clinical significance, the results were separated by BMI and body weight to summarize unstandardized effect sizes, such as mean difference (Table 4; available at www.jandonline.org), and the results of additional meta-ANOVAs that examined whether each factor moderated the effect size of weight loss are presented in Table 5 (available at www.jandonline.org).
      Figure thumbnail gr3
      Figure 4Forest plot of effect size on change in body weight (BW) or body mass index (BMI) between meal replacement (MR)-based and conventional low-energy diets.

      Meta-Regression

      This multiple meta-regression model analyzed and selected independent variables using a step-by-step approach and a hierarchical regression analysis. Table 6 summarizes the results of the meta-regression. The results of the meta-regression demonstrated that the percentage of total daily energy intake from MR and the frequency of MR intake were significant moderators (Z = 2.39; P = .017 and Z = 3.15; P = .002, respectively), and none of the other factors, including age, sex, initial BMI, and treatment duration, were significant. Figure 5 depicts the results of the meta-regression on the percentage of total daily energy intake from MR (model 5).
      Table 6Multiple meta-regression analysis using the hierarchical regression analysis approach, for the impact of patient- and treatment-related moderators of meal replacement–based, calorie-restricted vs conventional calorie-restricted diets on weight loss
      VariableModel
      123456
      Intercept0.28–0.23–0.60–0.550.17–0.38
      Patient-related moderators
      Age0.010.010.010.010.01
      Sex (percentage of females)0.000.000.000.000.00
      Initial BMI
      BMI = body mass index.
      		0.010.01–0.01–0.02
      Treatment-related moderators
      Period, wk0.000.000.00
       % of caloric intake from MR
      MR = meal replacement.
      		0.01
      P < .05.
       Frequency of MR intake0.47
      P < .01.
      Statistics for current model
      Q value01.732.142.128.7213.45
      df
      df = degrees of freedom.
      		023455
      a BMI = body mass index.
      b MR = meal replacement.
      c df = degrees of freedom.
      ∗ P < .05.
      ∗∗ P < .01.
      Figure thumbnail gr4
      Figure 5Regression of Hedges’ g for meal replacement-based low-energy vs conventional low-energy diets according to the percentage of total daily energy intake from meal replacement (model 5).

      Adverse Events and Safety

      Among the 22 studies, 11 reported information on adverse events (Table 1). Five of them reported no serious adverse events,
      • Rothacker D.Q.
      • Staniszewski B.A.
      • Ellis P.K.
      Liquid meal replacement vs traditional food: A potential model for women who cannot maintain eating habit change.
      J Am Diet Assoc. 2001; 101: 345-347
      ,
      • Ashley J.M.
      • Herzog H.
      • Clodfelter S.
      • Bovee V.
      • Schrage J.
      • Pritsos C.
      Nutrient adequacy during weight loss interventions: A randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group.
      Nutr J. 2007; 6: 12https://doi.org/10.1186/1475-2891-6-12
      ,
      • Khoo J.
      • Ling P.S.
      • Tan J.
      • et al.
      Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
      Int J Impot Res. 2013; 26: 61-66
      ,
      • Gulati S.
      • Misra A.
      • Tiwari R.
      • Sharma M.
      • Pandey R.M.
      • Yadav C.P.
      Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.
      Br J Nutr. 2017; 117: 1531-1540
      ,
      • Shih C.K.
      • Chen C.M.
      • Hsiao T.J.
      • Liu C.W.
      • Li S.C.
      White sweet potato as meal replacement for overweight white-collar workers: A randomized controlled trial.
      Nutrients. 2019; 11: E165https://doi.org/10.3390/nu11010165
      and 6 reported mild adverse events.
      • Allison D.B.
      • Gadbury G.
      • Schwartz L.G.
      • et al.
      A novel soy-based meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Eur J Clin Nutr. 2003; 57: 514-522
      ,
      • Fisberg M.
      • de Oliveira C.L.
      • de Pádua C.I.
      • et al.
      Impact of the hypocaloric diet using food substitutes on the body weight and biochemical profile.
      Arch Latinoam Nutr. 2004; 54: 402-407
      ,
      • Tsai ChH.
      • Chiu W.C.
      • Yang N.C.
      • Ouyang C.M.
      • Yen Y.H.
      A novel green tea meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Int J Food Sci Nutr. 2009; 60: 151-159
      ,
      • Metzner C.E.
      • Folberth-Vögele A.
      • Bitterlich N.
      • et al.
      Effect of a conventional energy-restricted modified diet with or without meal replacement on weight loss and cardiometabolic risk profile in overweight women.
      Nutr Metab (Lond). 2011; 8: 64https://doi.org/10.1186/1743-7075-8-64
      ,
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      ,
      • Kim J.Y.
      Effects of Very-Low-Calorie Diets using Meal replacements on Weight Reduction and Health in the Obese Premenopausal Women.
      Hanyang University, Master’s2005
      The remaining 11 studies did not report any results for adverse events. The mild adverse events cited included constipation, diarrhea, gastrointestinal symptoms, lethargy, abnormal taste, transitory elimination of flatus, and sleep loss; in the MR-based VLED groups only, the mild adverse events were anemia, constipation, skin dryness, lack of strength, and vomiting.

      Discussion

      To the best of the authors’ knowledge, this is the first systematic review and meta-analysis to analyze the effects of MR diets on weight loss compared with conventional food-based diets; the analysis was performed according to the characteristics of the MR plan, including the type of calorie-restriction MR plan and percentage of total daily energy intake from MR.
      The results demonstrate that the effect size of MR-based LED on weight loss was small compared with that of food-based LED (Hedges’ g = 0.261); however, compared with food-based VLED, the effect of MR-based VLED on weight loss remained unclear (Hedges’ g = 0.166). The sample size from the studies was too small to allow a subgroup analysis to be performed on the effects of MR-based VLED vs food-based VLED on weight loss. In general, VLEDs are only recommended for short-term use when rapid weight loss is required clinically for treating obesity.

      Logue J. Management of Obesity: A National Clinical Guideline. NHS Quality Improvement Scotland. Published February 2010. Accessed June 30, 2020. https://www.sign.ac.uk/assets/sign115.pdf

      , 
      • Jensen M.D.
      • Ryan D.H.
      • Apovian C.M.
      • et al.
      2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society.
      J Am Coll Cardiol. 2014; 63: 2985-3023
      , 
      National Institute for Health and Care Excellence
      Obesity: Identification, Assessment and Management of Overweight and Obesity in Children, Young People and Adults.
      National Institute for Health and Care Excellence, 2014
      Parretti and colleagues
      • Parretti H.M.
      • Jebb S.A.
      • Johns D.J.
      • Lewis A.L.
      • Christian-Brown A.M.
      • Aveyard P.
      Clinical effectiveness of very-low-energy diets in the management of weight loss: A systematic review and meta-analysis of randomized controlled trials.
      Obes Rev. 2016; 17: 225-234
      reported that VLED with behavioral programs compared with behavioral programs alone resulted in an average reduction of 3.9 kg (95% CI –6.7 to –1.1) at 1 year, with few notable adverse effects. This shows the potential of long-term VLED use as a weight loss plan. However, Bailey and colleagues
      • Bailey B.W.
      • Jacobsen D.J.
      • Donnelly J.E.
      Weight loss and maintenance outcomes using moderate and severe caloric restriction in an outpatient setting.
      Dis Manag. 2008; 11: 176-180
      and Riecke and colleagues
      • Riecke B.F.
      • Christensen R.
      • Christensen P.
      • et al.
      Comparing two low-energy diets for the treatment of knee osteoarthritis symptoms in obese patients: A pragmatic randomized clinical trial.
      Osteoarthritis Cartilage. 2010; 18: 746-754
      reported no significant difference between VLED and LED, and Bailey and colleagues suggested that LED is an efficacious, safe, and less burdensome diet compared with VLED. In view of these findings, the lack of research on the effect of MR-based VLED on weight loss may reflect the lack of preference for VLED in the context of long-term interventions.
      A meta-ANOVA and meta-regression were conducted to examine the association between factors of interest and weight loss. First, in terms of the proportion of energy intake per day from MR, the results indicated that ≥60% of total daily energy intake from MR had the greatest effect size for weight loss (Hedges’ g = 0.545), and that ≥30% and <60% had small effect size (Hedges’ g = 0.232). However, when <30% of calories were consumed from MR, this was not statistically significant. There was also a significant difference between groups. In a similar context, when comparing the effects based on the frequency of MR intake, the results revealed that different meal frequency options had different effect sizes for weight loss; the findings also suggested that replacing 3 meals per day had a medium effect size (Hedges’ g = 0.544), whereas simply replacing 2 meals daily had a small effect size (Hedges’ g = 0.177). In the meta-regression, the last 2 variables, that is, percentage of total daily energy intake from MR and frequency of MR intake, were not used simultaneously; this is because they are similar from a statistical perspective, despite being different from the clinical one, as mentioned previously. The meta-regression also showed that only 2 factors—percentage of total daily energy intake from MR and frequency of MR intake per day—had significant effects for weight loss; this finding is similar to those of previous studies (by Guo and colleagues
      • Guo X.
      • Xu Y.
      • He H.
      • et al.
      Effects of a meal replacement on body composition and metabolic parameters among subjects with overweight or obesity.
      J Obes. 2018; 2018: 2837367https://doi.org/10.1155/2018/2837367
      and Leader and colleagues
      • Leader N.J.
      • Ryan L.
      • Molyneaux L.
      • Yue D.K.
      How best to use partial meal replacement in managing overweight or obese patients with poorly controlled type 2 diabetes.
      Obesity. 2013; 21: 251-253
      ) comparing the effect of MR plans according to MR intake frequency on weight loss. As reported by Guo and colleagues,
      • Guo X.
      • Xu Y.
      • He H.
      • et al.
      Effects of a meal replacement on body composition and metabolic parameters among subjects with overweight or obesity.
      J Obes. 2018; 2018: 2837367https://doi.org/10.1155/2018/2837367
      dietary compliance can vary, depending on the frequency of MR intake regardless of the effect; as MR products are generally not provided for free, these factors must be considered when attempting MR plans for weight loss. The dropout rate increases otherwise. Yackobovitch-Gavan and colleagues
      • Yackobovitch-Gavan M.
      • Steinberg D.M.
      • Endevelt R.
      • Benyamini Y.
      Factors associated with dropout in a group weight-loss programme: A longitudinal investigation.
      J Hum Nutr Diet. 2015; 28: 33-40
      reported that poor weight loss during the first 2 weeks of the program was the strongest predictor of dropout. In conjunction, these results show that replacing 3 meals with MR per day, at least at the beginning of MR plans, will help patients lose weight successfully by increasing initial weight loss and motivation. Reporting the weight loss benefits of the number of meals from MR per day can help patients select a more efficient MR plan.
      When comparing the effects according to duration of treatment, Table 5 (available at www.jandonline.org) shows that plans implemented for 3 or more months and fewer than 6 months were slightly effective (Hedges’ g = 0.292), whereas the others were not significantly effective. At the same time, there was no statistically significant difference between the groups. In many studies,
      • Flechtner-Mors M.
      • Ditschuneit H.H.
      • Johnson T.D.
      • Suchard M.A.
      • Adler G.
      Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.
      Obes Res. 2000; 8: 399-402
      ,
      • König D.
      • Zdzieblik D.
      • Deibert P.
      • Berg A.
      • Gollhofer A.
      • Büchert M.
      Internal fat and cardiometabolic risk factors following a meal-replacement regimen vs. comprehensive lifestyle changes in obese subjects.
      Nutrients. 2015; 7: 9825-9833
      ,
      • Ahrens R.A.
      • Hower M.
      • Best A.M.
      Effects of weight reduction interventions by community pharmacists.
      J Am Pharm Assoc. 2003; 43: 583-589
      ,
      • Fisberg M.
      • de Oliveira C.L.
      • de Pádua C.I.
      • et al.
      Impact of the hypocaloric diet using food substitutes on the body weight and biochemical profile.
      Arch Latinoam Nutr. 2004; 54: 402-407
      intervention periods for weight loss and weight maintenance were different. Because this study compared randomized controlled trials that performed the same intervention for weight loss, excluding the maintenance period after losing weight, the average treatment period lasted approximately 4 months; there were only 3 studies that assessed plans for 6 or more months (a 26-week study and two 52-week studies). Results revealed that MR-based LED for fewer than 3 months or 6 or more months was not substantially more effective than food-based LED. As it is difficult to maintain calorie-restriction diets for a long time, it can be assumed that short-term, calorie-restricted diets can be controlled by a conventional diet without MR. However, MR interventions for 6 or more months may have decreased dietary adherence as they can become monotonous.
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of packaged entrees as part of a weight-loss diet in overweight men: An 8-week randomized clinical trial.
      Diabetes Obes Metab. 2006; 8: 146-155
      Eleven of the 22 studies reported adverse events, 5 reported no serious adverse events, and 6 documented mild adverse events. The mild adverse events included constipation, diarrhea, gastrointestinal symptoms, lethargy, abnormal taste, transitory elimination of flatus, and decreased sleep. In previous studies on adverse effects of LED, Christensen and colleagues
      • Christensen P.
      • Bliddal H.
      • Riecke B.F.
      • Leeds A.R.
      • Astrup A.
      • Christensen R.
      Comparison of a low-energy diet and a very low-energy diet in sedentary obese individuals: A pragmatic randomized controlled trial.
      Clin Obes. 2011; 1: 31-40
      reported that mild adverse events, such as abdominal and intestinal symptoms, musculoskeletal symptoms, central nervous system and psychiatric symptoms, skin and subcutaneous symptoms, and miscellaneous symptoms, lasted for 8 weeks on average, and a 1-year-long study by Moreno and colleagues
      • Moreno B.
      • Bellido D.
      • Sajoux I.
      • et al.
      Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity.
      Endocrine. 2014; 47: 793-805
      reported constipation, nausea (only for the first 4 months), and hyperuricemia (only for the first 15 days). It is difficult to assess the incidence of adverse events of MR-based diets compared with that of food-based diets, and the relationship is unclear. However, MR meals that can nutritionally enhance the diet are advantageous in terms of nutrient intake (including proteins, essential amino acids, dietary fiber, and vitamins) compared with conventional diets with similar calories.
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      ,
      • Gulati S.
      • Misra A.
      • Tiwari R.
      • Sharma M.
      • Pandey R.M.
      • Yadav C.P.
      Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.
      Br J Nutr. 2017; 117: 1531-1540
      Nevertheless, other foods without protein and/or dietary fiber, such as milk and cereal, are also used for MR plans; these may help limit caloric intake. However, nutritional adequacy cannot be ensured when consumed over a long time.
      • Keogh J.B.
      • Clifton P.M.
      The role of meal replacements in obesity treatment.
      Obes Rev. 2005; 6: 229-234
      MRs are fortified with minerals and vitamins of which conventional diets may not ensure an adequate intake, and MR plans are useful for weight loss.
      • Heymsfield S.B.
      Meal replacements and energy balance.
      Physiol Behav. 2010; 100: 90-94
      , 
      • Heymsfield S.B.
      • Van Mierlo C.
      • Van der Knaap H.
      • Heo M.
      • Frier H.I.
      Weight management using a meal replacement strategy: Meta and pooling analysis from six studies.
      Int J Obes Relat Metab Disord. 2003; 27: 537-549
      , 
      • Ashley J.M.
      • St Jeor S.T.
      • Schrage J.P.
      • et al.
      Weight control in the physician’s office.
      Arch Intern Med. 2001; 161: 1599-1604
      , 
      • Wing R.R.
      • Jeffery R.W.
      Food provision as a strategy to promote weight loss.
      Obes Res. 2001; 9: 271S-275Shttps://doi.org/10.1038/oby.2001.130
      , 
      • Ard J.D.
      • Lewis K.H.
      • Rothberg A.
      • et al.
      Effectiveness of a Total Meal Replacement Program (OPTIFAST Program) on weight loss: Results from the OPTIWIN Study.
      Obesity (Silver Spring). 2019; 27: 22-29
      ,
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of packaged entrees as part of a weight-loss diet in overweight men: An 8-week randomized clinical trial.
      Diabetes Obes Metab. 2006; 8: 146-155
      As weight loss in patients with obesity often requires calorie restriction, MR plans help ensure effective calorie-restricted diets by restricting the types of foods consumed, as well as by executing excellent portion control. This study sought to provide evidence for an effective percentage of total daily energy intake from MR by analyzing the effect of MR characteristics on weight loss. These findings may be helpful in designing more effective MR diet plans for weight loss by considering the frequency of MR intake and the percentage of total daily energy intake from MR.
      There are some limitations to this study. First, as mentioned earlier, the number of included studies that explored the effect of MR-based VLED on weight loss was small. Further studies are needed to address this limitation. Second, because the studies consisting of only men or only women were limited and few studies reported results by separating sexes, the effect of MR-based calorie-restricted diets on weight loss was not analyzed according to sex. However, Miller and colleagues
      • Miller W.C.
      • Koceja D.M.
      • Hamilton E.J.
      A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention.
      Int J Obes. 1997; 21: 941-947
      reported no sex differences in terms of the effectiveness of each intervention in a meta-analysis that compared the effect of diet and/or exercise on weight loss. Third, the effect of MR plans on weight loss according to the nutritional components of MR was not analyzed. More effective MR characteristics for weight loss may be identified if studies on the benefits of MR plans are re-analyzed by systematic reviews and meta-analyses according to their components.
      • Tobias D.K.
      • Chen Mu
      • Manson J.E.
      • Ludwig D.S.
      • Willett W.
      • Hu F.B.
      Effect of low-fat vs. other diet interventions on long-term weight change in adults: A systematic review and meta-analysis.
      Lancet Diabetes Endocrinol. 2015; 3: 968-979
      ,
      • Imamura F.
      • Micha R.
      • Wu J.H.
      • et al.
      Effects of saturated fat, polyunsaturated fat, monounsaturated fat, and carbohydrate on glucose-insulin homeostasis: A systematic review and meta-analysis of randomised controlled feeding trials.
      PLoS Med. 2016; 13e1002087https://doi.org/10.1371/journal.pmed.1002087
      Fourth, meta-regression provides great advantages for investigating intervention effects, while controlling for other factors such as sex, age, and patient status of disease. However, meta-regression is usually underpowered to detect anything but massive associations. Meta-ANOVA could be a better choice for finding and interpreting the clinical meaning. Researchers should consider these merits and drawbacks together when conducting meta-regression analyses. Lastly, this systematic review study has not been registered, despite research registration being recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards.
      • Straus S.
      • Moher D.
      Registering systematic reviews.
      CMAJ. 2010; 182: 13-14

      Conclusions

      According to this systematic review and meta-analysis, the effect of MR-based LED on weight loss was superior to that of food-based LED. In addition, the findings suggest that at least 30%, and preferably 30% to 60%, of total daily energy intake should be derived from MR for optimal weight loss.

      Acknowledgements

      We would like to thank Editage (www.editage.co.kr) for English-language editing.

      Author Contributions

      J. Min and S.-Y. Kim reviewed literature and wrote the manuscript as equally contributing authors with support from Y.-B. Park and Y.-Woo Lim. I.-S. Shin verified the analytical methods. All authors discussed the results and approved the final manuscript.

      Supplementary Materials

      Figure thumbnail fx1
      Figure 1Example of the database search strategy implemented in the Cochrane Central Register of Controlled Trials for systematic review and meta-analysis of the effect of meal replacement-based calorie-restricted diets on weight loss, compared with conventional calorie-restricted diets.
      Table 4Between-group differences in body mass index or body weight of meal replacement-based low-energy diets compared with conventional low-energy diets
      Study% of calorie intake from MR
      MR = meal replacement.
      		nBMI
      BMI = body mass index; calculated as kg/m2.
      difference in means (Trt
      Trt = treatment group.
      – Ctrl
      Ctrl = control group.
      )      		BW
      BW = body weight.
      difference in means (Trt – Ctrl)
      BMISE
      SE = standard error.
      		P valueBWSEP value
      Proportion of calorie intake from MR: ≥60%
      Shikany, 2013
      • Shikany J.M.
      • Thomas A.S.
      • Beasley T.M.
      • Lewis C.E.
      • Allison D.B.
      Randomized controlled trial of the Medifast 5 & 1 Plan for weight loss.
      Int J Obes (Lond). 2013; 37: 1571-1578
      		1001051.200.51.019———
      Tsai, 2009
      • Tsai ChH.
      • Chiu W.C.
      • Yang N.C.
      • Ouyang C.M.
      • Yen Y.H.
      A novel green tea meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Int J Food Sci Nutr. 2009; 60: 151-159
      		68120———6.002.19.006
      Allison, 2003
      • Allison D.B.
      • Gadbury G.
      • Schwartz L.G.
      • et al.
      A novel soy-based meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
      Eur J Clin Nutr. 2003; 57: 514-522
      		6874———4.100.93.000
      Rohrer, 2008
      • Rohrer J.E.
      • Takahashi P.
      Should overweight and obese primary care patients be offered a meal replacement diet?.
      Obes Res Clin Pract. 2008; 2: 263-268
      		8055———0.600.67.368
      Proportion of calorie intake from MR: ≥30% and <60%
      Gulati, 2017
      • Gulati S.
      • Misra A.
      • Tiwari R.
      • Sharma M.
      • Pandey R.M.
      • Yadav C.P.
      Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.
      Br J Nutr. 2017; 117: 1531-1540
      		431221.600.71.025———
      Rock, 2016 (b)
      • Rock C.L.
      • Flatt S.W.
      • Pakiz B.
      • et al.
      Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
      Obesity. 2016; 24: 1230-1237
      		351120.800.69.248———
      Hannum, 2006
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of packaged entrees as part of a weight-loss diet in overweight men: An 8-week randomized clinical trial.
      Diabetes Obes Metab. 2006; 8: 146-155
      		43510.700.91.440———
      Rock, 2016 (a)
      • Rock C.L.
      • Flatt S.W.
      • Pakiz B.
      • et al.
      Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
      Obesity. 2016; 24: 1230-1237
      		351160.700.69.313———
      König, 2015
      • König D.
      • Zdzieblik D.
      • Deibert P.
      • Berg A.
      • Gollhofer A.
      • Büchert M.
      Internal fat and cardiometabolic risk factors following a meal-replacement regimen vs. comprehensive lifestyle changes in obese subjects.
      Nutrients. 2015; 7: 9825-9833
      		42420.600.73.409———
      Khoo, 2013
      • Khoo J.
      • Ling P.S.
      • Tan J.
      • et al.
      Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
      Int J Impot Res. 2013; 26: 61-66
      		43460.590.93.526———
      Shih, 2019
      • Shih C.K.
      • Chen C.M.
      • Hsiao T.J.
      • Liu C.W.
      • Li S.C.
      White sweet potato as meal replacement for overweight white-collar workers: A randomized controlled trial.
      Nutrients. 2019; 11: E165https://doi.org/10.3390/nu11010165
      		58560.580.28.038———
      Hannum, 2004
      • Hannum S.M.
      • Carson L.A.
      • Evans E.M.
      • et al.
      Use of portion-controlled entrees enhances weight loss in women.
      Obes Res. 2004; 12: 538-546
      		54530.500.94.595———
      Metzner, 2011
      • Metzner C.E.
      • Folberth-Vögele A.
      • Bitterlich N.
      • et al.
      Effect of a conventional energy-restricted modified diet with or without meal replacement on weight loss and cardiometabolic risk profile in overweight women.
      Nutr Metab (Lond). 2011; 8: 64https://doi.org/10.1186/1743-7075-8-64
      		35870.400.48.406———
      Ashley, 2007
      • Ashley J.M.
      • Herzog H.
      • Clodfelter S.
      • Bovee V.
      • Schrage J.
      • Pritsos C.
      Nutrient adequacy during weight loss interventions: A randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group.
      Nutr J. 2007; 6: 12https://doi.org/10.1186/1475-2891-6-12
      		3770–0.700.59.232———
      Flechtner-Mors, 2000
      • Flechtner-Mors M.
      • Ditschuneit H.H.
      • Johnson T.D.
      • Suchard M.A.
      • Adler G.
      Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.
      Obes Res. 2000; 8: 399-402
      		31100———5.802.49.020
      Rothacker, 2001
      • Rothacker D.Q.
      • Staniszewski B.A.
      • Ellis P.K.
      Liquid meal replacement vs traditional food: A potential model for women who cannot maintain eating habit change.
      J Am Diet Assoc. 2001; 101: 345-347
      		5561———5.002.07.016
      Fisberg, 2004
      • Fisberg M.
      • de Oliveira C.L.
      • de Pádua C.I.
      • et al.
      Impact of the hypocaloric diet using food substitutes on the body weight and biochemical profile.
      Arch Latinoam Nutr. 2004; 54: 402-407
      		3067———3.323.06.277
      Ahrens, 2003
      • Ahrens R.A.
      • Hower M.
      • Best A.M.
      Effects of weight reduction interventions by community pharmacists.
      J Am Pharm Assoc. 2003; 43: 583-589
      		3388———0.602.26.791
      Noakes, 2004
      • Noakes M.
      • Foster P.R.
      • Keogh J.B.
      • Clifton P.M.
      Meal replacements are as effective as structured weight-loss diets for treating obesity in adults with features of metabolic syndrome.
      J Nutr. 2004; 134: 1894-1899
      		3042.00———-0.201.85.914
      Proportion of calorie intake from MR: <30%
      Kuriyan, 2017
      • Kuriyan R.
      • Lokesh D.P.
      • D’Souza N.
      • et al.
      Portion controlled ready-to-eat meal replacement is associated with short term weight loss: A randomised controlled trial.
      Asia Pac J Clin Nutr. 2017; 26: 1055-1065
      		211100.200.48.678———
      Smith, 2010
      • Smith T.J.
      • Sigrist L.D.
      • Bathalon G.P.
      • McGraw S.
      • Karl J.P.
      • Young A.J.
      Efficacy of a meal-replacement program for promoting blood lipid changes and weight and body fat loss in US Army soldiers.
      J Am Diet Assoc. 2010; 110: 268-273
      		241130.100.56.858———
      Proportion of calorie intake from MR: NR
      NR = not reported.
      Fuller, 2016
      • Fuller N.R.
      • Fong M.
      • Gerofi J.
      • et al.
      A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
      Clin Obes. 2016; 6: 108-116
      		NR76———0.110.52.832
      Meta
      Fixed—1,7660.5220.153.0011.2360.347.000
      Random—1,7660.5220.153.0012.3420.822.004
      Q value——9.7812.00.63527.658.00.001
      a MR = meal replacement.
      b BMI = body mass index; calculated as kg/m2.
      c Trt = treatment group.
      d Ctrl = control group.
      e BW = body weight.
      f SE = standard error.
      g NR = not reported.
      Table 5Meta-ANOVA
      ANOVA = analysis of variance.
      for the impact of moderators of meal replacement–based, calorie-restricted vs conventional calorie-restricted diets on weight loss
      ModeratornEffect SizeTest of Heterogeneity
      Hedges’ g95% CI
      Point estimateStandard errorLower limitUpper limitQ valuedf
      df = degrees of freedom.
      (Q value)      		P valueI2 (95% CI)
      Age.1581.691
      <45 y130.2430.0720.1010.38414.15112.29115.2 (0.0 to 54.2)
      ≥45 y90.2880.0880.1150.46012.5468.12836.2 (0.0 to 70.7)
      Initial BMI
      BMI = body mass index; calculated as kg/m2.
      		1.0562.590
      <3050.1550.117–0.0750.3858.1724.08551.1 (0.0 to 82.0)
      ≥30160.2930.0650.1660.42017.04415.31612.0 (0.0 to 49.3)
      Period.5492.760
      <3 mo70.1950.109–0.0180.4082.3576.8840 (0.0 to 25.7)
      ≥3 mo, <6 mo120.2920.0730.1480.43616.04211.14031.4 (0.0 to 65.4)
      ≥6 mo30.2550.154–0.0460.5567.6202.02273.8 (12.2 to 92.2)
      Frequency of intake of MRs
      MR = meal replacement. ∗∗ p < 0.01.
      		10.4341.001∗∗
      2 meals/d170.1770.0540.0710.28411.19116.7980 (0.0 to 30.1)
      3 meals/d50.5440.1000.3490.7395.2504.26323.8 (0.0 to 68.9)
      a ANOVA = analysis of variance.
      b df = degrees of freedom.
      c BMI = body mass index; calculated as kg/m2.
      d MR = meal replacement. ∗∗ p < 0.01.

      References

        • Obesity
        World Health Organization. Updated April 1, 2020. Accessed June 30, 2020.
        https://www.who.int/features/factfiles/obesity/en/
        View in Article
        • Flegal K.M.
        • Kit B.K.
        • Orpana H.
        • Graubard B.I.
        Association of all-cause mortality with overweight and obesity using standard body mass index categories: A systematic review and meta-analysis.
        JAMA. 2013; 309: 71-82https://doi.org/10.1001/jama.2012.113905
        View in Article
        • Wing R.R.
        • Lang W.
        • Wadden T.A.
        • et al.
        Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes.
        Diabetes Care. 2011; 34: 1481-1486
        View in Article
        • Christensen R.
        • Bartels E.M.
        • Astrup A.
        • et al.
        Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: A systematic review and meta-analysis.
        Ann Rheum Dis. 2007; 66: 433-439
        View in Article
        • Poobalan A.
        • Aucott L.
        • Smith W.C.S.
        • et al.
        Effects of weight loss in overweight/obese individuals and long-term lipid outcomes—A systematic review.
        Obes Rev. 2004; 5: 43-50
        View in Article
        • Apovian C.M.
        Obesity: Definition, comorbidities, causes, and burden.
        Am J Manag Care. 2016; 22: S176-S185
        View in Article
        • Razina A.O.
        • Runenko S.D.
        • Achkasov E.E.
        Obesity: Current global and Russian trends.
        Vestn Ross Akad Med Nauk. 2016; 2: 154-159
        View in Article
        • Johnston B.C.
        • Kanters S.
        • Bandayrel K.
        • et al.
        Comparison of weight loss among named diet programs in overweight and obese adults: A meta-analysis.
        JAMA. 2014; 312: 923-933
        View in Article
        • Shai I.
        • Schwarzfuchs D.
        • Henkin Y.
        • et al.
        Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
        N Engl J Med. 2008; 359: 229-241
        View in Article
        • Hemmingsson E.
        • Johansson K.
        • Eriksson J.
        • Sundström J.
        • Neovius M.
        • Marcus C.
        Weight loss and dropout during a commercial weight-loss program including a very-low-calorie diet, a low-calorie diet, or restricted normal food: Observational cohort study.
        Am J Clin Nutr. 2012; 96: 953-961
        View in Article
        • Tsai A.G.
        • Wadden T.A.
        The evolution of very-low-calorie diets: An update and meta-analysis.
        Obesity (Silver Spring). 2006; 14: 1283-1293
        View in Article
        • Rolls B.J.
        What is the role of portion control in weight management?.
        Int J Obes (Lond). 2014; 38: S1-S8https://doi.org/10.1038/ijo.2014.82
        View in Article
        • Rolls B.J.
        • Roe L.S.
        • Meengs J.S.
        The effect of large portion sizes on energy intake is sustained for 11 days.
        Obesity. 2007; 15: 1535-1543
        View in Article
        • Cahayadi J.
        • Geng X.
        • Mirosa M.
        • Peng M.
        Expectancy versus experience—Comparing portion-size-effect during premeal planning and actual intake.
        Appetite. 2019; 135: 108-114
        View in Article
        • Gillison F.
        • Stathi A.
        • Reddy P.
        • et al.
        Processes of behavior change and weight loss in a theory-based weight loss intervention program: A test of the process model for lifestyle behavior change.
        Int J Behav Nutr Phys Act. 2015; 12: 2https://doi.org/10.1186/s12966-014-0160-6
        View in Article
        • Ramage S.
        • Farmer A.
        • Eccles K.A.
        • McCargar L.
        Healthy strategies for successful weight loss and weight maintenance: A systematic review.
        Appl Physiol Nutr Metab. 2014; 39: 1-20https://doi.org/10.1139/apnm-2013-0026
        View in Article
        • Heymsfield S.B.
        Meal replacements and energy balance.
        Physiol Behav. 2010; 100: 90-94
        View in Article
        • Heymsfield S.B.
        • Van Mierlo C.
        • Van der Knaap H.
        • Heo M.
        • Frier H.I.
        Weight management using a meal replacement strategy: Meta and pooling analysis from six studies.
        Int J Obes Relat Metab Disord. 2003; 27: 537-549
        View in Article
        • Ashley J.M.
        • St Jeor S.T.
        • Schrage J.P.
        • et al.
        Weight control in the physician’s office.
        Arch Intern Med. 2001; 161: 1599-1604
        View in Article
        • Wing R.R.
        • Jeffery R.W.
        Food provision as a strategy to promote weight loss.
        Obes Res. 2001; 9: 271S-275Shttps://doi.org/10.1038/oby.2001.130
        View in Article
        • Ard J.D.
        • Lewis K.H.
        • Rothberg A.
        • et al.
        Effectiveness of a Total Meal Replacement Program (OPTIFAST Program) on weight loss: Results from the OPTIWIN Study.
        Obesity (Silver Spring). 2019; 27: 22-29
        View in Article
        • Loveman E.
        • Frampton G.K.
        • Shepherd J.
        • et al.
        The clinical effectiveness and cost-effectiveness of long-term weight management schemes for adults: A systematic review.
        Health Technol Assess. 2011; 15: 1-182
        View in Article
        • Franz M.J.
        • Vanwormer J.J.
        • Lauren Crain A.
        • et al.
        Weight-loss outcomes: A systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up.
        J Am Diet Assoc. 2007; 107: 1755-1767
        View in Article
        • Kahleova H.
        • Salas-Salvadó J.
        • Rahelić D.
        • Kendall C.W.C.
        • Rembert E.
        • Sievenpiper J.L.
        Dietary patterns and cardiometabolic outcomes in diabetes: A summary of systematic reviews and meta-analyses.
        Nutrients. 2019; 11: 2209https://doi.org/10.3390/nu11092209
        View in Article
        • Leslie W.S.
        • Taylor R.
        • Harris L.
        • Lean M.E.J.
        Weight losses with low-energy formula diets in obese patients with and without type 2 diabetes: Systematic review and meta-analysis.
        Int J Obes. 2017; 41: 96-101
        View in Article
        • Astbury N.M.
        • Piernas C.
        • Hartmann-Boyce J.
        • Lapworth S.
        • Aveyard P.
        • Jebb S.A.
        A systematic review and meta-analysis of the effectiveness of meal replacements for weight loss.
        Obes Rev. 2019; 20: 569-587
        View in Article
        • Flechtner-Mors M.
        • Ditschuneit H.H.
        • Johnson T.D.
        • Suchard M.A.
        • Adler G.
        Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.
        Obes Res. 2000; 8: 399-402
        View in Article
        • Allison D.B.
        • Gadbury G.
        • Schwartz L.G.
        • et al.
        A novel soy-based meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
        Eur J Clin Nutr. 2003; 57: 514-522
        View in Article
        • Noakes M.
        • Foster P.R.
        • Keogh J.B.
        • Clifton P.M.
        Meal replacements are as effective as structured weight-loss diets for treating obesity in adults with features of metabolic syndrome.
        J Nutr. 2004; 134: 1894-1899
        View in Article
        • König D.
        • Zdzieblik D.
        • Deibert P.
        • Berg A.
        • Gollhofer A.
        • Büchert M.
        Internal fat and cardiometabolic risk factors following a meal-replacement regimen vs. comprehensive lifestyle changes in obese subjects.
        Nutrients. 2015; 7: 9825-9833
        View in Article
        • Guo X.
        • Xu Y.
        • He H.
        • et al.
        Effects of a meal replacement on body composition and metabolic parameters among subjects with overweight or obesity.
        J Obes. 2018; 2018: 2837367https://doi.org/10.1155/2018/2837367
        View in Article
        • Leader N.J.
        • Ryan L.
        • Molyneaux L.
        • Yue D.K.
        How best to use partial meal replacement in managing overweight or obese patients with poorly controlled type 2 diabetes.
        Obesity. 2013; 21: 251-253
        View in Article
        • Rothacker D.Q.
        • Staniszewski B.A.
        • Ellis P.K.
        Liquid meal replacement vs traditional food: A potential model for women who cannot maintain eating habit change.
        J Am Diet Assoc. 2001; 101: 345-347
        View in Article
        • Ahrens R.A.
        • Hower M.
        • Best A.M.
        Effects of weight reduction interventions by community pharmacists.
        J Am Pharm Assoc. 2003; 43: 583-589
        View in Article
        • Fisberg M.
        • de Oliveira C.L.
        • de Pádua C.I.
        • et al.
        Impact of the hypocaloric diet using food substitutes on the body weight and biochemical profile.
        Arch Latinoam Nutr. 2004; 54: 402-407
        View in Article
        • Hannum S.M.
        • Carson L.A.
        • Evans E.M.
        • et al.
        Use of portion-controlled entrees enhances weight loss in women.
        Obes Res. 2004; 12: 538-546
        View in Article
        • Hannum S.M.
        • Carson L.A.
        • Evans E.M.
        • et al.
        Use of packaged entrees as part of a weight-loss diet in overweight men: An 8-week randomized clinical trial.
        Diabetes Obes Metab. 2006; 8: 146-155
        View in Article
        • Ashley J.M.
        • Herzog H.
        • Clodfelter S.
        • Bovee V.
        • Schrage J.
        • Pritsos C.
        Nutrient adequacy during weight loss interventions: A randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group.
        Nutr J. 2007; 6: 12https://doi.org/10.1186/1475-2891-6-12
        View in Article
        • Rohrer J.E.
        • Takahashi P.
        Should overweight and obese primary care patients be offered a meal replacement diet?.
        Obes Res Clin Pract. 2008; 2: 263-268
        View in Article
        • Tsai ChH.
        • Chiu W.C.
        • Yang N.C.
        • Ouyang C.M.
        • Yen Y.H.
        A novel green tea meal replacement formula for weight loss among obese individuals: A randomized controlled clinical trial.
        Int J Food Sci Nutr. 2009; 60: 151-159
        View in Article
        • Smith T.J.
        • Sigrist L.D.
        • Bathalon G.P.
        • McGraw S.
        • Karl J.P.
        • Young A.J.
        Efficacy of a meal-replacement program for promoting blood lipid changes and weight and body fat loss in US Army soldiers.
        J Am Diet Assoc. 2010; 110: 268-273
        View in Article
        • Metzner C.E.
        • Folberth-Vögele A.
        • Bitterlich N.
        • et al.
        Effect of a conventional energy-restricted modified diet with or without meal replacement on weight loss and cardiometabolic risk profile in overweight women.
        Nutr Metab (Lond). 2011; 8: 64https://doi.org/10.1186/1743-7075-8-64
        View in Article
        • Khoo J.
        • Ling P.S.
        • Tan J.
        • et al.
        Comparing the effects of meal replacements with reduced-fat diet on weight, sexual and endothelial function, testosterone and quality of life in obese Asian men.
        Int J Impot Res. 2013; 26: 61-66
        View in Article
        • Shikany J.M.
        • Thomas A.S.
        • Beasley T.M.
        • Lewis C.E.
        • Allison D.B.
        Randomized controlled trial of the Medifast 5 & 1 Plan for weight loss.
        Int J Obes (Lond). 2013; 37: 1571-1578
        View in Article
        • Fuller N.R.
        • Fong M.
        • Gerofi J.
        • et al.
        A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
        Clin Obes. 2016; 6: 108-116
        View in Article
        • Rock C.L.
        • Flatt S.W.
        • Pakiz B.
        • et al.
        Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.
        Obesity. 2016; 24: 1230-1237
        View in Article
        • Gulati S.
        • Misra A.
        • Tiwari R.
        • Sharma M.
        • Pandey R.M.
        • Yadav C.P.
        Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.
        Br J Nutr. 2017; 117: 1531-1540
        View in Article
        • Kuriyan R.
        • Lokesh D.P.
        • D’Souza N.
        • et al.
        Portion controlled ready-to-eat meal replacement is associated with short term weight loss: A randomised controlled trial.
        Asia Pac J Clin Nutr. 2017; 26: 1055-1065
        View in Article
        • Shih C.K.
        • Chen C.M.
        • Hsiao T.J.
        • Liu C.W.
        • Li S.C.
        White sweet potato as meal replacement for overweight white-collar workers: A randomized controlled trial.
        Nutrients. 2019; 11: E165https://doi.org/10.3390/nu11010165
        View in Article
        • Kim J.Y.
        Effects of Very-Low-Calorie Diets using Meal replacements on Weight Reduction and Health in the Obese Premenopausal Women.
        Hanyang University, Master’s2005
        View in Article
        • Centre for Reviews and Dissemination
        Systematic Reviews: CRD’s Guidance for Undertaking Reviews in Health Care.
        University of York, 2009
        View in Article
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration.
        PLoS Med. 2009; 6e1000100https://doi.org/10.1371/journal.pmed.1000100
        View in Article

      53. Higgins JPT, Thomas J, Chandler J, et al, eds. Cochrane Handbook for Systematic Reviews of Interventions, Version 6.0. Updated July 2019. Accessed June 30, 2020. www.training.cochrane.org/handbook

        View in Article
        • Borenstein M.
        • Hedges L.V.
        • Higgins J.P.T.
        • Rothstein H.R.
        Introduction to Meta-Analysis.
        Wiley, 2009
        View in Article
        • Sterne J.A.
        • Gavaghan D.
        • Egger M.
        Publication and related bias in meta-analysis: Power of statistical tests and prevalence in the literature.
        J Clin Epidemiol. 2000; 53: 1119-1129https://doi.org/10.1016/s0895-4356(00)00242-0
        View in Article
        • Egger M.
        • Smith G.D.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        View in Article
        • Begg C.B.
        • Mazumdar M.
        Operating characteristics of a rank correlation test for publication bias.
        Biometrics. 1994; 50: 1088-1101
        View in Article
        • Lipsey M.W.
        • Wilson D.B.
        Practical Meta-Analysis. Applied Social Research Methods Series. Vol. 49.
        Sage Publications, 2001
        View in Article
        • Becker B.J.
        Synthesizing standardized mean-change measures.
        Br J Math Stat Psychol. 1988; 41: 257-278
        View in Article
        • Cohen J.
        Statistical Power Analysis for the Behavioral Sciences.
        2nd ed. Routledge Academic, 1988
        View in Article
        • Brockwell S.E.
        • Gordon I.R.
        A comparison of statistical methods for meta-analysis.
        Stat Med. 2001; 20: 825-840https://doi.org/10.1002/sim.650
        View in Article
        • Kontopantelis E.
        • Reeves D.
        Performance of statistical methods for meta-analysis when true study effects are non-normally distributed: A simulation study.
        Stat Methods Med Res. 2012; 21: 409-426https://doi.org/10.1177/0962280210392008
        View in Article

      63. Comprehensive Meta-Analysis [computer program]. Version 3; Biostat Inc; 2019.

        View in Article
        • Becker B.J.
        Multivariate meta-analysis.
        in: Tinsley E.A. Brown S.D. Handbook of Applied and Multivariate Statistics and Mathematical Modeling. 1st ed. Academic Press, 2000: 499-525
        View in Article
        • Cooper H.
        Research Synthesis and Meta-Analysis: A Step-by-Step Approach.
        5th ed. Sage, 2016
        View in Article
        • Wasserstein R.L.
        • Lazar N.A.
        The ASA's statement on p-values: Context, process, and purpose.
        Am Stat. 2016; 70: 129-133
        View in Article

      67. Logue J. Management of Obesity: A National Clinical Guideline. NHS Quality Improvement Scotland. Published February 2010. Accessed June 30, 2020. https://www.sign.ac.uk/assets/sign115.pdf

        View in Article
        • Jensen M.D.
        • Ryan D.H.
        • Apovian C.M.
        • et al.
        2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society.
        J Am Coll Cardiol. 2014; 63: 2985-3023
        View in Article
        • National Institute for Health and Care Excellence
        Obesity: Identification, Assessment and Management of Overweight and Obesity in Children, Young People and Adults.
        National Institute for Health and Care Excellence, 2014
        View in Article
        • Parretti H.M.
        • Jebb S.A.
        • Johns D.J.
        • Lewis A.L.
        • Christian-Brown A.M.
        • Aveyard P.
        Clinical effectiveness of very-low-energy diets in the management of weight loss: A systematic review and meta-analysis of randomized controlled trials.
        Obes Rev. 2016; 17: 225-234
        View in Article
        • Bailey B.W.
        • Jacobsen D.J.
        • Donnelly J.E.
        Weight loss and maintenance outcomes using moderate and severe caloric restriction in an outpatient setting.
        Dis Manag. 2008; 11: 176-180
        View in Article
        • Riecke B.F.
        • Christensen R.
        • Christensen P.
        • et al.
        Comparing two low-energy diets for the treatment of knee osteoarthritis symptoms in obese patients: A pragmatic randomized clinical trial.
        Osteoarthritis Cartilage. 2010; 18: 746-754
        View in Article
        • Yackobovitch-Gavan M.
        • Steinberg D.M.
        • Endevelt R.
        • Benyamini Y.
        Factors associated with dropout in a group weight-loss programme: A longitudinal investigation.
        J Hum Nutr Diet. 2015; 28: 33-40
        View in Article
        • Christensen P.
        • Bliddal H.
        • Riecke B.F.
        • Leeds A.R.
        • Astrup A.
        • Christensen R.
        Comparison of a low-energy diet and a very low-energy diet in sedentary obese individuals: A pragmatic randomized controlled trial.
        Clin Obes. 2011; 1: 31-40
        View in Article
        • Moreno B.
        • Bellido D.
        • Sajoux I.
        • et al.
        Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity.
        Endocrine. 2014; 47: 793-805
        View in Article
        • Keogh J.B.
        • Clifton P.M.
        The role of meal replacements in obesity treatment.
        Obes Rev. 2005; 6: 229-234
        View in Article
        • Miller W.C.
        • Koceja D.M.
        • Hamilton E.J.
        A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention.
        Int J Obes. 1997; 21: 941-947
        View in Article
        • Tobias D.K.
        • Chen Mu
        • Manson J.E.
        • Ludwig D.S.
        • Willett W.
        • Hu F.B.
        Effect of low-fat vs. other diet interventions on long-term weight change in adults: A systematic review and meta-analysis.
        Lancet Diabetes Endocrinol. 2015; 3: 968-979
        View in Article
        • Imamura F.
        • Micha R.
        • Wu J.H.
        • et al.
        Effects of saturated fat, polyunsaturated fat, monounsaturated fat, and carbohydrate on glucose-insulin homeostasis: A systematic review and meta-analysis of randomised controlled feeding trials.
        PLoS Med. 2016; 13e1002087https://doi.org/10.1371/journal.pmed.1002087
        View in Article
        • Straus S.
        • Moher D.
        Registering systematic reviews.
        CMAJ. 2010; 182: 13-14
        View in Article

      Biography

      J. Min is a researcher, Nubebe Mibyeong Research Institute, Seoul, South Korea.
      S.-Y. Kim is a clinician, Nubebe Korean Medical Clinic (Bundang), Seongnam, South Korea.
      I.-S. Shin is a professor, Department of Transdisciplinary Security, Dongguk University, Seoul, South Korea.
      Y.-B. Park is a research director, Nubebe Mibyeong Research Institute, Seoul, South Korea.
      Y.-Woo Lim is a representative, Nubebe Mibyeong Research Institute, Seoul, South Korea.

      Article info

      Publication history

      Published online: June 16, 2021
      Accepted: May 3, 2021
      Received: July 22, 2020

      Footnotes

      Supplementary materials: Figure 1 and Tables 4 and 5 are available at www.jandonline.org

      STATEMENT OF POTENTIAL CONFLICT OF INTEREST No potential conflict of interest was reported by the authors.

      FUNDING/SUPPORT There is no funding to disclose.

      Identification

      DOI: https://doi.org/10.1016/j.jand.2021.05.001

      Copyright

      © 2021 by the Academy of Nutrition and Dietetics.

      User license

      Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0) |
      How you can reuse Information Icon
      Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)

      Permitted

      For non-commercial purposes:

      • Read, print & download
      • Redistribute or republish the final article
      • Text & data mine
      • Translate the article (private use only, not for distribution)
      • Reuse portions or extracts from the article in other works

      Not Permitted

      • Sell or re-use for commercial purposes
      • Distribute translations or adaptations of the article

      Elsevier's open access license policy

      ScienceDirect

      Access this article on ScienceDirect
      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties. The content on this site is intended for healthcare professionals.


      RELX