No authors currently receive or have received funds from commercial organizations that could directly or indirectly benefit from the question addressed by this research or its findings. PG is Director of Evidence Building and Synthesis Research Consortium that receives money to increase the number of evidence-informed decisions by intermediary organizations, including WHO and national decision makers that benefit the poor in middle and low income countries. The Centre for Evidence-based Health Care at Stellenbosch University receives a grant from the Consortium for influencing evidence-informed decisions in the sub-Saharan region, and to develop capacity of researchers to respond to requests for timely, informed systematic reviews to inform national policies. The Heart and Stroke Foundation South Africa requested this review but did not contribute in any way financially or other, to its implementation. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: CN AS MS TY PG JV. Performed the experiments: CN AS. Analyzed the data: CN AS. Contributed reagents/materials/analysis tools: CN AS MS TY PG JV. Wrote the paper: CN AS MS TY PG JV.
Some popular weight loss diets restricting carbohydrates (CHO) claim to be more effective, and have additional health benefits in preventing cardiovascular disease compared to balanced weight loss diets.
We compared the effects of low CHO and isoenergetic balanced weight loss diets in overweight and obese adults assessed in randomised controlled trials (minimum follow-up of 12 weeks), and summarised the effects on weight, as well as cardiovascular and diabetes risk. Dietary criteria were derived from existing macronutrient recommendations. We searched Medline, EMBASE and CENTRAL (19 March 2014). Analysis was stratified by outcomes at 3–6 months and 1–2 years, and participants with diabetes were analysed separately. We evaluated dietary adherence and used GRADE to assess the quality of evidence. We calculated mean differences (MD) and performed random-effects meta-analysis. Nineteen trials were included (n = 3209); 3 had adequate allocation concealment. In non-diabetic participants, our analysis showed little or no difference in mean weight loss in the two groups at 3–6 months (MD 0.74 kg, 95%CI −1.49 to 0.01 kg; I2 = 53%; n = 1745, 14 trials; moderate quality evidence) and 1–2 years (MD 0.48 kg, 95%CI −1.44 kg to 0.49 kg; I2 = 12%; n = 1025; 7 trials, moderate quality evidence). Furthermore, little or no difference was detected at 3–6 months and 1–2 years for blood pressure, LDL, HDL and total cholesterol, triglycerides and fasting blood glucose (>914 participants). In diabetic participants, findings showed a similar pattern.
Trials show weight loss in the short-term irrespective of whether the diet is low CHO or balanced. There is probably little or no difference in weight loss and changes in cardiovascular risk factors up to two years of follow-up when overweight and obese adults, with or without type 2 diabetes, are randomised to low CHO diets and isoenergetic balanced weight loss diets.
Overweight, obesity and the related burdens of cardiovascular disease (CVD), type 2 diabetes, other non-communicable diseases (NCD) and premature mortality are escalating globally
Some weight loss diets widely promoted through the media, such as the Atkins diet
We first examined evidence from existing systematic reviews. We sought any review that synthesised evidence on dietary macronutrient manipulation and cardiovascular outcomes or risk factors (last search: 3 March 2014). We found 50 reviews but these had a number of methodological constraints precluding the possibility that they could meaningfully address the question we set out to answer (see
What answering the research question requires | Why was it identified as a limitation in existing reviews? | What we did to address identified limitations in our review |
Explicit definition of treatment and control diets with complete macronutrient profile | If unclear, any effects seen on weight loss and CVD risk factors cannot be attributed to a well-defined intervention diet compared to a well-defined control diet | Used explicit cut-off ranges for macronutrients for treatment and control diets; the complete macronutrient profile of intervention diets had to be available (proportions of total energy intake) |
Recommended energy intake in treatment and control groups needs to be similar | If different, any effects seen on weight loss and CVD risk factors would be confounded by total energy intake | Only included isoenergetic diet comparisons |
Co-interventions, such as drugs given as part of the intervention, or recommendations for exercise, need to be similar in the comparison groups | If different, any effects on CVD risk factors could be confounded by co-interventions | Only included interventions with a diet component alone, or combined interventions that were similar to prevent confounding by co-interventions |
Appropriate study design for the question | Methodological heterogeneity: some reviews included both controlled and uncontrolled trials | Only included randomised controlled trials |
Meaningful and comparable follow-up in trials needs to be considered | Outcomes of trials with different follow-ups were pooled; generalised conclusions about weight loss may be skewed by early changes; or follow-up may be insufficient to detect CVD risk factor changes | Only included studies with 12 weeks or more follow-up; and outcomes were grouped by defined lengths of follow-up |
CVD: cardiovascular disease.
Note: see
Nutrition specialists have defined “recommended, balanced diets” in terms of macronutrient composition, micronutrients and dietary quality to ensure adequate nutrition, energy balance for health and weight maintenance, and prevention of NCDs in healthy populations
To further improve our understanding of these diets, we examined and summarised the main themes in the advocacy literature on low CHO diets and their supposed benefits. We identified two main
Low CHO diet, high fat variant |
Low CHO diet, high protein variant |
Balanced weight loss diet | |
Is energy explicitly restricted? | No | No |
Yes |
CHO | Extreme restriction | Moderate restriction | 45–65% of total energy |
Fat | Unrestricted fat | 25–35% of total energy | 25–35% of total energy |
Protein | Unrestricted protein | Promotes lean protein | 10–20% of total energy |
CHO | Extreme restriction of all CHO food sources | Extreme restriction of grains and starches; fruit and vegetables recommended | High fibre, unprocessed; promotion of fruit, vegetables and legumes |
Protein | Unrestricted, especially animal protein | Increased lean animal protein, protein bars and shakes | Emphasis on plant protein and lean animal protein |
Fat | Promotion of increased ‘natural’ fats, including saturated (animal) fats | Promotion of monounsaturated fats, mention of omega-3 fats | Promotion of polyunsaturated and monounsaturated fats, replacement of saturated fats with unsaturated fats, avoidance of trans fats; adequate omega-3 fats |
Is micronutrient intake addressed? | Not specifically |
Not specifically |
Not specifically |
Main | Weight loss | Weight loss | Weight loss (if energy is restricted) |
Other | “Improvement in risk factors for heart disease, hypertension and diabetes, inflammation” | “Reverses cellular inflammation”. “Cellular inflammation is what makes us gain weight, accelerate the development of chronic disease, and decrease our physical performance” | Reduces risk of obesity-related illness; Reduces risk of non-communicable diseases; Promotes nutritional adequacy |
Energy reduction is implicit as a consequence of extreme restriction of carbohydrates, the reported satiating effect of protein, and appetite suppressing effect of ketones.
Energy reduction is implicit as a consequence of extreme restriction of grains and starches and reported satiating effect of protein.
Portion guides sometimes provided.
Potential risks of inadequacies by extreme restriction of carbohydrates, including most vegetables and fruit.
Potential risks of inadequacies by restricting grains and starches.
Promoted indirectly through recommending a variety of foods from all food groups and quality food choices (including plenty of vegetables and fruit).
To compare the effects of low CHO and isoenergetic balanced weight loss diets in overweight and obese adults.
We included randomised controlled trials (RCTs) in humans published in English. Trials could be of a parallel or crossover design, however, crossover trials were only included if first period data could be extracted. We excluded trials with less than 10 participants randomised in each group.
People who are overweight or obese, have diabetes, glucose intolerance or insulin resistance, cardiovascular conditions or risk factors such as hypertension and dyslipidaemia, as defined by trial authors. We excluded pregnant and lactating women and individuals younger than 18 years.
We required the studies to provide the macronutrient goals of the diet in terms of their contribution to total energy intake, or that these goals could be calculated as proportions of total energy intake, for both the treatment and comparison arms. Treatment diets were low CHO weight loss diet plans, including a) low CHO, high fat, high protein diet (
Classifications | |||
Macronutrients | Low | Balanced | High |
Carbohydrate (% of total energy) | <45 | 45 to 65 | >65 |
Fat (% of total energy) | <25 | 25 to 35 | >35 |
Protein (% of total energy) | <10 | 10 to 20 | >20 |
*Established by drawing on macronutrient recommendations from five global institutions and governments
We excluded studies where: the treatment and control diets were not adequately defined or where the control diet was defined as ‘no dietary intervention’; diets were combined with any other interventions (e.g. exercise, pharmacological, surgical) so that the effect of diet alone could not be assessed; dietary interventions had an exclusive focus on energy restriction, i.e. no macronutrient manipulation was instituted; a substantial disparity in energy intake (>500 kilojoules) between the prescribed treatment and control diets was present; an
Total weight change (kg); body mass index (BMI) (kg/m2).
Diastolic blood pressure (DBP) and systolic blood pressure (SBP) (mmHg); serum cholesterol: low density lipoprotein (LDL), high density lipoprotein (HDL) and total (mmol/L); serum triglycerides (TG) (mmol/L).
Glycosylated haemoglobin (HbA1c) (%); fasting blood glucose (FBG) (mmol/L).
Mortality, myocardial infarction and stroke were not explicitly excluded as outcomes, but we did not expect to find randomised controlled trials with these outcomes where dietary manipulations were under study.
Electronic searches were done in
Search: 22 October 2012 | ||
No. | Query | Results |
#5 | 1312 | |
#4 | ‘randomised controlled trial’/exp OR ‘randomised controlled trial’ OR ‘randomised controlled trials’ OR ‘randomized controlled trial’/exp OR ‘randomized controlled trial’ OR ‘randomized controlled trials’/exp OR ‘randomized controlled trials’ AND [humans]/lim AND [english]/lim AND [embase]/lim AND [1-1-1966]/sd NOT [22-10-2012]/sd AND [1966-2012]/py | 249285 |
#3 | 2862 | |
#2 | ‘carbohydrate restricted diet’/exp OR ‘carbohydrate restricted diet’ OR ‘carbohydrate restricted diets’ OR ‘high fat diet’/exp OR ‘high fat diet’ OR ‘high fat diets’ OR ‘fat restricted diet’/exp OR ‘fat restricted diet’ OR ‘fat restricted diets’ OR ‘ketogenic diet’/exp OR ‘ketogenic diet’ OR ‘ketogenic diets’ AND [humans]/lim AND [english]/lim AND [embase]/lim AND [1-1-1966]/sd NOT [22-10-2012]/sd AND [1966–2012]/py | 11176 |
#1 | ‘randomized controlled trial’/exp OR ‘randomized controlled trial’ OR random*:ab,ti OR trial:ti OR allocat*:ab,ti OR factorial*:ab,ti OR placebo*:ab,ti OR assign*:ab,ti OR volunteer*:ab,ti OR ‘crossover procedure’/exp OR ‘crossover procedure’ OR ‘double-blind procedure’/exp OR ‘double-blind procedure’ OR ‘single-blind procedure’/exp OR ‘single-blind procedure’ OR (doubl* NEAR/3 blind*):ab,ti OR (singl*:ab,ti AND blind*:ab,ti) OR crossover*:ab,ti OR cross+over*:ab,ti OR (cross NEXT/1 over*):ab,ti AND [humans]/lim AND [english]/lim AND [embase]/lim AND [1-1-1966]/sd NOT [22-10-2012]/sd AND [1966–2012]/py | 879594 |
Updated search: 5 June 2013 | ||
#5 | 80 | |
#4 | ‘randomised controlled trial’/exp OR ‘randomised controlled trials’ OR ‘randomized controlled trial’/exp OR ‘randomized controlled trials’/exp AND [humans]/lim AND [english]/lim AND [embase]/lim AND [23-10-2012]/sd NOT [6-6-2013]/sd | 20424 |
#3 | 236 | |
#2 | ‘carbohydrate restricted diet’/exp OR ‘carbohydrate restricted diets’ OR ‘high fat diet’/exp OR ‘high fat diets’ OR ‘fat restricted diet’/exp OR ‘fat restricted diets’ OR ‘ketogenic diet’/exp OR ‘ketogenic diets’ AND [humans]/lim AND [english]/lim AND [embase]/lim AND [23-10-2012]/sd NOT [6-6-2013]/sd | 1005 |
#1 | ‘randomized controlled trial’/exp OR random*:ab,ti OR trial:ti OR allocat*:ab,ti OR factorial*:ab,ti OR placebo*:ab,ti OR assign*:ab,ti OR volunteer*:ab,ti OR ‘crossover procedure’/exp OR ‘double-blind procedure’/exp OR ‘single-blind procedure’/exp OR (doubl* NEAR/3 blind*):ab,ti OR (singl*:ab,ti AND blind*:ab,ti) OR crossover*:ab,ti OR cross+over*:ab,ti OR (cross NEXT/1 over*):ab,ti AND [humans]/lim AND [english]/lim AND [embase]/lim AND [23-10-2012]/sd NOT [6-6-2013]/sd | 73855 |
Updated search: 19 March 2014 | ||
#5 | #3 AND #4 | 145 |
#4 | ‘randomised controlled trial’/exp OR ‘randomised controlled trial’ OR ‘randomised controlled trials’ OR ‘randomized controlled trial’/exp OR ‘randomized controlled trial’ OR ‘randomized controlled trials’/exp OR ‘randomized controlled trials’ AND [humans]/lim AND [english]/lim AND [embase]/lim AND [7-6-2013]/sd NOT [18-3-2014]/sd | 29989 |
#3 | #1 AND #2 | 384 |
#2 | ‘carbohydrate restricted diet’/exp OR ‘carbohydrate restricted diet’ OR ‘carbohydrate restricted diets’ OR ‘high fat diet’/exp OR ‘high fat diet’ OR ‘high fat diets’ OR ‘fat restricted diet’/exp OR ‘fat restricted diet’ OR ‘fat restricted diets’ OR ‘ketogenic diet’/exp OR ‘ketogenic diet’ OR ‘ketogenic diets’ AND [humans]/lim AND [english]/lim AND [embase]/lim AND [7-6-2013]/sd NOT [18-3-2014]/sd | 1731 |
#1 | ‘randomized controlled trial’/exp OR ‘randomized controlled trial’ OR random*:ab,ti OR trial:ti OR allocat*:ab,ti OR factorial*:ab,ti OR placebo*:ab,ti OR assign*:ab,ti OR volunteer*:ab,ti OR ‘crossover procedure’/exp OR ‘crossover procedure’ OR ‘double-blind procedure’/exp OR ‘double-blind procedure’ OR ‘single-blind procedure’/exp OR ‘single-blind procedure’ OR (doubl* NEAR/3 blind*):ab,ti OR (singl*:ab,ti AND blind*:ab,ti) OR crossover*:ab,ti OR cross+over*:ab,ti OR (cross NEXT/1 over*):ab,ti AND [humans]/lim AND [english]/lim AND [embase]/lim AND [7-6-2013]/sd NOT [18-3-2014]/sd | 108635 |
Two authors (CN and AS) screened titles and abstracts of all search results and identified potentially eligible studies using the pre-specified eligibility criteria. Full text articles for these studies were obtained and assessed by the two authors simultaneously. Studies not fulfilling eligibility criteria were excluded with reasons. All discrepancies were resolved by consensus.
Two authors (CN and AS) extracted data using an electronic data extraction spreadsheet in Microsoft Excel. The main sections of the spreadsheet included information on the design, country, participants, treatment, control, diet quality, energy and nutrient composition, adherence, outcomes and results, funding, conflict of interest, and risk of bias. The extracted data were collated in tables and figures. The author of one included RCT
Outcomes were grouped into those measured between baseline and three to six months of follow-up; and between baseline and one to two years of follow-up. For trials measuring outcomes at several time points within either of these two categories, we took the values for the longest follow-up within that category (for example, where results were available at three and six months, the results at six months were used).
Two authors (CN and AS) assessed the risk of bias in the included studies by using the Cochrane Collaboration risk of bias tool
For energy, the prescribed and reported total energy intakes (kilojoules) for each reported follow-up category in the trial were tabulated per group, as were group comparisons of mean reported energy intake reported by trial authors. For macronutrients, adherence was calculated as the difference between the reported mean and prescribed distribution of energy intake (% of total energy) from CHO, fat and protein for each follow-up category. For trials reporting dietary intake at several time points within either of the two follow-up categories, we took the values for the longest follow-up within that category. Specifically, adherence was calculated using a Mahalanobis distance equation, which can be used to measure the similarity between a set of actual conditions relative to a set of ideal conditions
The equation for the macronutrient adherence score, where TE is total energy:
Review Manager (RevMan) 5.2 was used to manage the extracted data and to conduct meta-analyses
No crossover trials met the inclusion criteria. In the case of multiple intervention groups, we selected one pair of interventions i.e. treatment and control that was most relevant to this systematic review question
Statistical heterogeneity was assessed with the Chi2 test (significance level p <0.1) and quantified with the I2 test
We assessed reporting bias with funnel plots when we had 10 or more studies per outcome, which was the case for five outcomes in non-diabetic overweight and obese adults in the early follow-up category.
The outcomes were reported as the difference in the mean change between the treatment and control groups. Because the presence of diabetes is likely to influence the effects of the diet, we stratified by trials of overweight and obese participants without and with type 2 diabetes. Heterogeneity between the included studies was anticipated due to variations in dietary plans and goals, length of follow-up and dietary methodology, and the random-effects model was therefore used for all meta-analyses. We stratified the analysis by whether the treatment group was the high fat variant or the high protein variant of low CHO diets, and pooled the estimate if there was no obvious heterogeneity.
We assessed the quality of evidence using GradePro (Grade Profiler) 3.2.2 software
We screened 3450 records and retrieved and screened 179 full-text articles, after which we included 19 RCTs (
The high fat variant of low carbohydrate diets is low in carbohydrates (<45% of total energy), high in fat (>35% of total energy) and high in protein (>20% of total energy). The high protein variant of low carbohydrate diets is low in carbohydrates (<45% of total energy), has a recommended proportion of fat (20 to 35% of total energy) and is high in protein (>20% of total energy).
There were 14 trials in people without diabetes
Two trials were only in men
First author (follow-up in weeks) | Year of publication | Country | Parallel design | No randomised | No Completed in Rx group | Dropout in Rx group | No Completed in Control group | Dropout in Control group | Gender | Age Range (yrs) | Types of Participants | Total Intervention Period in weeks |
Aude (12) |
2004 | USA | Yes | 60 | 29 | 1 | 25 | 5 | Both | 27–71 | Overweight or Obese | 12 |
De Luis (12) |
2009 | Spain | Yes | 118 | 52 | 0 | 66 | 0 | Both | NR | Overweight or Obese | 12 |
De Luis (12) |
2012 | Spain | Yes | 305 | 147 | 0 | 158 | 0 | Both | NR | Obese | 12 |
Farnsworth (16) |
2003 | UK | Yes | 66 | 28 | NR | 29 | NR | Both | 20–65 | Overweight or Obese | 16 |
Frisch (52) |
2009 | Germany | Yes | 200 | 85 | 15 | 80 | 20 | Both | 18–70 | Overweight or Obese | 52 |
Keogh (52) |
2008 | Australia | Yes | 36 | 7 | NR | 6 | NR | Both | 20–65 | Overweight or Obese | 52 |
Klemsdal (52) |
2010 | Norway | Yes | 202 | 78 | 22 | 86 | 16 | Both | 30–65 | Overweight or Obese and CVD risk | 52 |
Krauss (12) |
2006 | USA | Yes | 224 | 40 | 12 | 49 | 8 | Males | NR | Overweight or Obese with Dyslipidaemia | 12 |
Lasker (16) |
2008 | USA | Yes | 65 | 25 | 7 | 25 | 8 | Both | 40–56 | Overweight or Obese | 16 |
Layman (52) |
2009 | USA | Yes | 130 | 41 | 23 | 30 | 36 | Both | 40–57 | Overweight or Obese | 52 |
Lim (64) |
2010 | Australia | Yes | 113 | 17 | 13 | 15 | 15 | Both | 20–65 | Overweight or Obese with CVD risk | 64 |
Luscombe (16) |
2003 | Australia | Yes | 36 | 17 | 0 | 19 | 0 | Both | 20–65 | Overweight or Obese | 16 |
Sacks (104) |
2009 | USA | Yes | 811 | 168 | 33 | 169 | 35 | Both | 30–70 | Overweight or Obese | 104 |
Wycherley (52) |
2012 | Australia | Yes | 123 | 33 | 26 | 35 | 29 | Males | 20–65 | Overweight or Obese | 52 |
Guldbrand (104) |
2012 | Sweden | Yes | 61 | 30 | 0 | 31 | 0 | Both | NR | Overweight or Obese with T2DM | 104 |
Brinkworth (64) |
2004 | Australia | Yes | 66 | 19 | 14 | 19 | 14 | Both | 58–65 | Overweight or Obese with T2DM | 64 |
Krebs (104) |
2012 | New Zealand | Yes | 419 | 144 | 63 | 150 | 62 | Both | 30–78 | Overweight or Obese with T2DM | 104 |
Larsen (52) |
2011 | Australia | Yes | 108 | 48 | 9 | 45 | 6 | Both | 30–75 | Overweight or Obese and T2DM | 52 |
Parker(12) |
2002 | Australia | Yes | 66 | 26 | 6 | 28 | 6 | Both | NR | Obese with T2DM | 12 |
CVD = cardiovascular disease; No = number; NR = not reported; Rx = treatment; T2DM = type two diabetes mellitus; USA = United States of America; yrs = years.
Note: In the case of multiple intervention groups, we selected one pair of interventions i.e. treatment and control that was most relevant to this systematic review question.
First author (follow-up in weeks) | Year of publication | No. of weeks of weight loss | Prescribed energy for Rx group | Prescribed energy for Control group | Prescribed CHO for Rx group | Prescribed fat for Rx group | Prescribed protein for Rx group | Prescribed CHO for Control group | Prescribed fat for Control group | Prescribed protein for Control group |
(kJ) | (kJ) | (% of TE) | (% of TE) | (% of TE) | (% of TE) | (% of TE) | (% of TE) | |||
Aude (12) | 2004 | 12 | 5460–6720 | 5460–6720 | 28 | 39 | 33 | 55 | 30 | 15 |
De Luis (12) | 2009 | 12 | 6300 | 6330 | 38 | 36 | 26 | 52 | 27 | 20 |
De Luis (12) | 2012 | 12 | 6329 | 6300 | 38 | 36 | 26 | 53 | 27 | 20 |
Frisch (24 and 52) | 2009 | 24 | 2100 deficit | 2100 deficit | <40 | >35 | 25 | >55 | <30 | 15 |
Klemsdal (24 and 52) | 2010 | 24 | 2100 deficit | 2100 deficit | 30–35 | 35–40 | 25–30 | 55–60 | <30 | 15 |
Krauss (12) | 2006 | 5 | 4200 deficit | 4200 deficit | 26 | 45 | 29 | 54 | 30 | 16 |
Lim (24 and 64) | 2010 | 24 | 6500 | 6500 | 4 | 60 | 35 | 50 | 30 | 30 |
Sacks (24 and 104) | 2009 | 24 | 3150 deficit | 3151 deficit | 35 | 40 | 25 | 65 | 20 | 15 |
Farnsworth (16) | 2003 | 12 | 6000–6300 | 6000–6300 | 40 | 30 | 30 | 55 | 30 | 15 |
Keogh (12 and 52) | 2008 | 12 | 6000 | 6000 | 33 | 27 | 40 | 60 | 20 | 20 |
Lasker (16) | 2008 | 16 | 7100 | 7100 | 40 | 30 | 30 | 55 | 30 | 15 |
Layman (16 and 52) | 2009 | 16 | 7100–7940 | 7100–7940 | 40 | 30 | 30 | 55 | 30 | 15 |
Luscombe (16) | 2003 | 12 | 6500–8200 | 6500–8201 | 40 | 30 | 30 | 55 | 30 | 15 |
Wycherley (12 and 52) | 2012 | 52 | 7000 | 7000 | 40 | 25 | 35 | 58 | 25 | 17 |
Guldbrand (12–24) | 2012 | 12–24 | M:6696 | M:6696; | 20 | 50 | 30 | 55–60 | 30 | 10–15 |
F: 7531 | F: 7531 | |||||||||
Guldbrand (104) | 2012 | 104 | M:6696; | M:6696; | 20 | 50 | 30 | 55–60 | 30 | 10–15 |
F: 7531 | F: 7531 | |||||||||
Brinkworth (12) | 2004 | 8 | NR | NR | 40 | 30 | 30 | 55 | 30 | 15 |
Brinkworth (64) | 2004 | N/A | NR | NR | 40 | 30 | 30 | 55 | 30 | 15 |
Krebs (24 and 104) | 2012 | 12 | 2000 deficit | 2000 deficit | 40 | 30 | 30 | 55 | 30 | 15 |
Larsen (12) | 2011 | 12 | 6400/−30%E | 6400/−30%E | 40 | 30 | 30 | 55 | 30 | 15 |
Larsen (52) | 2011 | N/A | E balance | E balance | 40 | 30 | 30 | 55 | 30 | 15 |
Parker (12) | 2002 | 8 | 6720-E balance | 6721-E balance | 40 | 30 | 30 | 60 | 25 | 15 |
CHO = carbohydrate; E = energy; F = females; g = gram; kJ = kilojoule; M = males; MJ = megajoule; N/A = not applicable; No = number; NR = not reported; Rx = treatment; TE = total energy.
Reasons for exclusion | Number of studies excluded |
Not a randomised controlled trial | 4 |
Duration of the intervention <12 weeks | 40 |
All three macronutrients not prescribed (or cannot be calculated as proportions of the total energy intake) | 20 |
Non-English language | 1 |
Test meal response measured | 1 |
Meal replacement | 2 |
Combined interventions were involved | 3 |
Treatment and control both low carbohydrate – not an eligible comparison | 3 |
Comparison not meaningful (carbohydrate content of treatment and controls differ <5% of TE) | 2 |
No eligible balanced carbohydrate control | 1 |
Crossover trial where first period data cannot be extracted: 1 | 1 |
Substantial disparity in energy intake between prescribed intervention diets | 13 |
Treatment diet is not low in carbohydrates | 26 |
Control diet is not within balanced macronutrient range | 4 |
Duplicate and/or complimentary | 24 |
Energy intake |
8 |
Ineligible low carbohydrate diet variant | 6 |
Less than 10 participants randomised per group | 1 |
RCT = randomised controlled trial; CHO = carbohydrate.
Risk of bias is reported in
First author | Year published | Random sequence generation Judgement | Random sequence generation Comment | Allocation concealment Judgement | Allocation concealment Comment | Performance bias Judgement | Performance bias Comment | Detection bias Judgement | Detection bias Comment | Attrition bias Judgement | Attrition |
Reporting bias Judgement | Reporting bias Comment | Other bias Judgement | Other bias Comment |
Aude |
2004 | Low risk | Block design | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Low risk | Assessors blinded | High risk | 3%/17% attrition (differential), no reasons | Low risk | Protocol not available, but prespecified and all NB outcomes addressed | High risk | Food choice advice & fibre supplements only given to Rx group |
De Luis |
2009 | Low risk | Random number list | Unclear risk | “closed envelope” | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | Low risk | No attrition | Low risk | Protocol not available, but prespecified and all NB outcomes addressed | High risk | Funding & COI NR, imbalanced baseline DBP, HDL, TG |
De Luis |
2012 | Unclear risk | NR | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | Low risk | No attrition | High risk | No prespecified outcomes, protocol not available | High risk | Funding & COI NR, imbalanced baseline SBP, HDL |
Farnsworth |
2003 | Unclear risk | NR | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | Unclear risk | 14% total attrition, attrition & reasons not provided per group | High risk | No prespecified outcomes, protocol not available | Unclear risk | Funding: possible influences |
Frisch |
2009 | Low risk | Computer generated random no. lists | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | Low risk | ITT analysis | Low risk | Prespecified and all NB outcomes addressed, protocol available | Low risk | - |
Keogh |
2008 | Unclear risk | NR | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | High risk | 36% total attrition, attrition & reasons not provided per group | Low risk | Prespecified and NB outcomes addressed, protocol available | High risk | Incomplete and suspected errors in reporting, imbalanced baseline TG |
Klemsdal |
2010 | Unclear risk | NR | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | Low risk | ITT analysis | Low risk | Prespecified and NB outcomes addressed, protocol available | Unclear risk | COI NR |
Krauss |
2006 | Low risk | Blocks of 4, 8, 12, 16, 20, 24 | Unclear risk | Sealed sequentially no. envelopes, not opaque | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | High risk | 23/14% attrition (differential), reasons not per group | High risk | Only 1 outcome prespecified, protocol not available | Unclear risk | COI NR |
Lasker |
2008 | Low risk | Block randomisation | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | High risk | 22/24% attrition, no reasons | Low risk | Protocol not available, but prespecified and all NB outcomes addressed | High risk | Funding: possible influences |
Layman |
2009 | Unclear risk | NR | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | High risk | 36/55% attrition (differential), reasons differ per group | Low risk | Protocol not available, but prespecified and all NB outcomes addressed | Unclear risk | Funding and COI reported: possible influences |
Lim |
2010 | Unclear risk | NR | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | High risk | 43/50% attrition, reasons differ per group (differential) | Low risk | Protocol not available, but prespecified and all NB outcomes addressed | Low risk | - |
Luscombe |
2003 | Unclear risk | NR | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | Low risk | No attrition | High risk | No prespecified outcomes, protocol not available | Unclear risk | COI NR; Funding: possible influences |
Sacks |
2009 | Unclear risk | NR | Low risk | Centrally | Low risk | Participants blinded | Low risk | Assessors blinded | Low risk | ITT | Low risk | Prespecified and all NB outcomes addressed, protocol available | Low risk | - |
Wycherley |
2012 | Low risk | Computer generated random no. lists | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | High risk | 44/45% attrition | Unclear risk | Protocol retrospectively registered, outcomes only specified in abstract, NB outcomes addressed | High risk | Funding: possible influence, analysis at 12 weeks only included data from 52 week completers but dropouts after 12 weeks lost less weight |
Brinkworth |
2004 | Low risk | Random no. generator | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | High risk | 42/42% attrition, reasons differ per group | Low risk | Protocol not available, but prespecified and all NB outcomes addressed | High risk | Imbalanced baseline weight, DBP, SBP glucose |
Guldbrand |
2012 | Low risk | Drawing blinded ballots | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | Low risk | No attrition | High risk | Protocol available: prespecified outcomes vague | High risk | Imbalanced baseline weight & BMI |
Krebs |
2012 | Low risk | Computer generated random no. | Low risk | Independent biostatistician | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | High risk | 30/29%, reasons differ per group (differential) | Low risk | Prespecified and NB outcomes addressed, protocol available | Low risk | - |
Larsen |
2011 | Low risk | Random block sizes | Low risk | Centrally | Unclear risk | Equal contact time but not blinded | Low risk | Assessors blinded | High risk | 16/12% attrition, reasons differ per group (differential) LOCF analysis only on some missing participants | Low risk | Prespecified and NB outcomes addressed, protocol available | Unclear risk | COI: NR |
Parker |
2002 | Unclear risk | NR | Unclear risk | NR | Unclear risk | Equal contact time but not blinded | Unclear risk | Not blinded | Unclear risk | 19/18% attrition, no reasons | High risk | No prespecified outcomes, protocol not available | High risk | COI NR; Funding: possible influences; imbalanced baseline weight & glucose |
*number of attrition per group given for longest follow-up within the categories;
BMI = body mass index; BP = blood pressures; COI = conflict of interest; DBP = diastolic blood pressure; HDL = high density lipoprotein cholesterol; ITT = intention-to-treat; LOCF: Last observation carried forward; NB = important; No = number; NR = Not reported; Rx = treatment; TG = triglycerides.
Study ID | Length of follow-up (weeks) | Energy prescription in both groups in kJ | Mean reported energy intake (SD) in kJ | Group comparison of mean reported energy intake reported by trial authors | Adherence scores |
||
Low CHO diet group | Balanced diet group | Low CHO diet group | Balanced diet group | ||||
Aude 2004 | 12 | 6720 (m); 5460 (f) | – | – | NA | – | – |
Brinkworth 2004 | all | equivalent | – | – | NA | – | – |
De Luis 2009 | 12 | 6330 | 6502 (NR) | 6775 (NR) | – | – | – |
De Luis 2012 | 12 | 6300–6329 | 6598 (NR) | 6779 (NR) | – | – | – |
Farnsworth 2003 | 12 | 6000–6300 | 6300 (529) | 6500 (539) | “did not differ” | ||
16 | balance | 8000 (1058) | 8200 (1077) | “did not differ” | 5.93 | 4.00 | |
Frisch 2009 | 24 | 2100 deficit | 7316 (2621) | 7489 (2507) | p = 0.636 | 5.96 | 6.13 |
52 | 7837 (2982) | 7787 (2621) | p = 0.903 | 7.08 | 5.19 | ||
Guldbrand 2012 | 12–24 | 7531 (m); 6694 (f) | 5791 (1531) | 6498 (1787) | p = 0.065 for change | 7.87 | 8.54 |
52 | 6017 (2075) | 6619 (2075) | over all time points | ||||
104 | 5234 (1799) | 6104 (1891) | between groups | 13.89 | 9.49 | ||
Keogh 2008 | 12 | 6000 | 6242 (4576) | 6262 (3876) | “did not differ” | 6.81 | 7.15 |
52 | – | – | NA | – | – | ||
Klemsdal 2010 | All | 2100 deficit | – | – | NA | – | – |
Krauss 2006 | 12 | 4200 deficit | – | – | NA | – | – |
Krebs 2012 | 12 | 2000 deficit | 7400 (3057) | 6815 (1841) | 9.71 | 8.32 | |
52 | 7258 (2098) | 6784 (1792) | p = 0.012 | ||||
104 | 7170 (1974) | 7093 (1851) | over 104 weeks | 11.24 | 8.71 | ||
Larsen 2011 | 12 | 6400 or 30% restriction | 6449 (2652) | 6029 (2652) | p = 0.22 for “group by | 1.85 | 8.37 |
52 | balance | 6664 (3233) | 6628 (3233) | time interaction” | 4.00 | 8.09 | |
Lasker 2008 | 16 | 7100 | 6607 (1175) | 5875 (1955) | p>0.10 | 2.45 | 8.77 |
Layman 2009 | 16 | 7100 | 6730 (1659) | 6200 (1714) | p>0.05 | 3.16 | 6.93 |
52 | 7118 (1793) | 6800 (1917) | p>0.05 | 6.32 | 4.69 | ||
Lim 2010 | 12 | 6500 | 7706 (868) | 7659 (1044) | – | ||
24 | 7367 (1372) | 6449 (1668) | 11.10 | 2.77 | |||
52 | 7726 (1609) | 7124 (2287) | |||||
64 | 6841 (1348) | 6593 (1503) | 41.28 | 8.10 | |||
Luscombe 2003 | 12 | 6500 | 6358 (585) | 6663 (819) | p>0.05 | ||
16 | 8200 | 8068 (1542) | 8235 (263) | p>0.05 | 6.18 | 4.14 | |
Parker 2002 | 8 | 6720 | 6665 (771) | 6480 (977) | “not different” | ||
12 | balance | 8522 (1178 | 7497 (1645) | “not different” | 3.59 | 5.54 | |
Sacks 2009 | 24 | 3150 deficit | 6821 (2033) | 6871 (2033) | “similar between | 10.11 | 10.07 |
104 | 5935 (1793) | 6430 (2016) | groups” | 10.04 | 14.24 | ||
Wycherley 2012 | 12 | 7000 | 7134 (771) | 7189 (535) | p = 0.73 | 3.83 | 7.83 |
52 | 7629 (1085) | 7243 (739) | p = 0.09 | 7.64 | 11.55 |
–: not reported; CHO: carbohydrate; f: females, m: males; kJ: kilojoules; NA: not applicable; SD: standard deviation
Arbitrary adherence score, calculated using a Mahalanobis distance equation, represents the degree of deviation from the prescribed goals for macronutrients in the two diet groups. A lower score reflects better adherence and a higher score reflects poorer adherence.
Thirteen and eight trials reported mean CHO, fat and protein intakes at 3–6 months and 1–2 years, respectively (
The effect estimates between the two dietary variants (high fat and high protein) did not show a qualitative difference and the heterogeneity between the groups was small or not detectable, so we pooled data across the two low CHO diet variants in the analysis.
At 3–6 months, the average weight loss in trials in the low CHO group ranged from 2.65 to 10.2 kg and in the isoenergetic balanced diet group from 2.65 to 9.4 kg. At 1–2 years, the range of weight loss was 2.9 to 12.3 kg with low CHO diets and 3.5 to 10.9 kg with isoenergetic balanced diets.
The meta-analysis of the mean difference in weight loss between the low CHO and balanced diets did not demonstrate a difference at 3–6 months (−0.74 kg, 95%CI −1.49 to 0.01; 14 trials) (
Outcomes | Balanced diets | Low carbohydrate diets | No. of participants (studies) | Quality of the evidence (GRADE) |
Weight loss | Lower by 2.65 to 9.4 kg | 0.74 kg more weight lost | 1745 | ⊕⊕⊕⊝ |
(could be 1.49 lost to a gain of 0.01) | (14 studies) | moderate |
||
BMI | Lower by 1.6 to 2.4 kg/m |
0.25 kg/m |
673 | ⊕⊕⊕⊝ |
(could be 0.64 lower to 0.13 higher) | (4 studies) | moderate |
||
Diastolic | Lower by 1 to 14 mmHg | 0.08 mmHg lower diastolic blood pressure | 1362 | ⊕⊕⊝⊝ |
blood pressure | (could be 1.53 lower to 1.36 higher) | (8 studies) | low |
|
Systolic | Lower by 1 to 16 mmHg | 1.26 mmHg lower systolic blood pressure | 1057 | ⊕⊕⊕⊝ |
blood pressure | (could be 2.67 lower to 0.15 mmHg higher) | (7 studies) | moderate |
|
LDL cholesterol | From 0.03 lower to 0.82 mmol/L higher | 0.09 mmol/L higher LDL cholesterol | 1603 | ⊕⊕⊕⊝ |
(could be 0 to 0.18 mmol/L higher) | (12 studies) | moderate |
||
HDL cholesterol | From 0.1 lower to 0.08 mmol/L higher | 0.03 mmol/L higher HDL cholesterol | 1603 | ⊕⊕⊝⊝ |
(could be 0.01 lower to 0.08 mmol/L higher) | (12 studies) | low |
||
Total cholesterol | Lower by 0.07 to 0.88 mmol/L | 0.08 mmol/L higher total cholesterol | 1603 | ⊕⊕⊕⊝ |
(could be 0.02 lower to 0.17 mmol/L higher) | (12 studies) | moderate |
||
Triglycerides | From 0.49 lower to 0.01 mmol/L higher | 0.05 mmol/L lower triglycerides | 1603 | ⊕⊕⊝⊝ |
(could be 0.14 lower to 0.04 mmol/L higher) | (12 studies) | low |
CI: Confidence interval ;
Note this is the univariate average change observed between follow-up and baseline in the control group.
GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.
Downgraded by 1 for risk of bias: 8 of 14 studies did not report adequate sequence generation and 13 studies did not report adequate allocation concealment. 4 studies had high total attrition (>20%) and 2 other studies had differential attrition.
Not downgraded for inconsistency: no qualitative heterogeneity; some quantitative heterogeneity, to be expected.
Downgraded by 1 for risk of bias: 1 study did not report adequate sequence generation, none of the studies reported on allocation concealment and 1 study had high total attrition (>20%).
Downgraded by 1 for risk of bias: 5 of 8 studies did not report adequate sequence generation and 7 studies did not report adequate allocation concealment. 2 studies had high total attrition (>20%).
Downgraded by 1 for inconsistency: Mean differences were on opposite sides of the line of no difference (I2 51%).
Downgraded by 1 for risk of bias: 5 of 8 studies did not report adequate sequence generation and 7 studies did not report adequate allocation concealment. 2 studies had high total attrition (>20%).
Downgraded by 1 for risk of bias: 5 of 12 studies did not report adequate sequence generation and 11 studies did not report adequate allocation concealment. 3 studies had high total attrition (>20%) and 2 other studies had differential attrition.
Downgraded by 1 for risk of bias: 6 of 12 studies did not report adequate sequence generation and 11 studies did not report adequate allocation concealment. 3 studies had high total attrition (>20%) and 2 studies had differential attrition.
Downgraded by 1 for inconsistency: Mean differences were on opposite sides of the line of no difference (I2 63%).
Downgraded by 1 for risk of bias: 6 of 12 studies did not report adequate sequence generation and 11 studies did not report adequate allocation concealment. 3 studies had had total attrition (>20%) and 2 studies had differential attrition.
Downgraded by 1 for inconsistency: Mean differences were on opposite sides of the line of no difference (I2 72%).
Outcomes | Balanced diets | Low carbohydrate diets | No. of participants (studies) | Quality of the evidence (GRADE) |
Weight loss | Lower by 3.5 to 10.9 kg | 0.48 kilograms more weight lost | 1025 | ⊕⊕⊕⊝ |
(could 1.44 lost to a gain of 0.49 kg) | (7 studies) | moderate |
||
BMI | Lower by 1.5 kg/m |
0.40 kg/m |
200 | ⊕⊕⊝⊝ |
(at 1 year) | (could be 0.94 lower to 0.14 higher) | (1 study) | low |
|
Diastolic | Lower by 1 to 11 mmHg | 0.03 mmHg lower diastolic blood pressure | 914 | ⊕⊕⊕⊝ |
blood pressure | (could be 1.68 lower to 1.62 mmHg higher) | (6 studies) | moderate |
|
Systolic | From 10 lower to 8 mmHg higher | 2 mmHg lower systolic blood pressure | 914 | ⊕⊕⊕⊝ |
blood pressure | (could be 5 lower to 1 mmHg higher) | (6 studies) | moderate |
|
LDL cholesterol | From 0.79 lower to 0.06 mmol/L higher | 0.07 mmol/L higher LDL cholesterol | 915 | ⊕⊕⊕⊝ |
(could be 0.01 lower to 0.16 mmol/L higher) | (6 studies) | moderate |
||
HDL cholesterol | From 0.03 lower to 0.15 mmol/L higher | 0.04 mmol/L higher HDL cholesterol | 986 | ⊕⊕⊕⊝ |
(could 0.01 to 0.08 mmol/L higher) | (7 studies) | moderate |
||
Total cholesterol | From 0.76 lower 0.13 mmol/L higher | 0.06 mmol/L higher total cholesterol | 915 | ⊕⊕⊕⊝ |
(could be 0.03 lower to 0.16 mmol/L higher) | (6 studies) | moderate |
||
Triglycerides | From 0.44 lower to 0.06 mmol/L higher | 0.06 mmol/L lower triglycerides | 915 | ⊕⊕⊕⊝ |
(could be 0.14 lower to 0.03 mmol/L higher) | (6 studies) | moderate |
CI: Confidence interval;
Note this is the univariate average change observed between follow-up and baseline in the control group.
GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.
Downgraded by 1 for risk of bias: 5 of 7 studies did not report adequate sequence generation and only 1 reported adequate allocation concealment. 5 studies were judged to have a high or unclear risk of attrition bias.
Downgraded by 1 for risk of bias: the study did not report adequate allocation concealment and reasons for attrition differed between groups.
Downgraded by 1 for imprecision: difference in mean BMI change ranges from a reduction of −0.94 to an increase of 0.14 kg/m2 (approximately equivalent to 2 to 4 kilograms).
Downgraded by 1 for risk of bias: 4 of 6 studies did not report adequate sequence generation and 5 studies did not report adequate allocation concealment. 2 studies had high total attrition (>20%), 1 of which also had differential attrition.
A few studies reported change in BMI. As with weight, average BMI was lower after dieting in both diet groups, but with no difference detected at either 3–6 months across the 4 trials reporting this (
At 3–6 months, the average DBP compared to baseline in each study was reduced in both the low CHO group (range: −10 to −1 mmHg) and in those on balanced diets (range: −14 to −1 mmHg). At 1–2 years, the average drop within studies compared to baseline ranged from 9 mmHg lower to no change in DBP with low CHO and a reduction across studies with balanced diets of 11 to 1 mmHg.
The meta-analyses of the mean difference in DBP change did not demonstrate a difference between the low CHO and balanced diets at 3–6 months (95%CI −1.53 to 1.36; 8 trials) (
At 3–6 months, the average SBP in each study compared to baseline showed a drop in both the low CHO (range: −15 to −2 mmHg) and balanced diet groups (range: −16 to −1 mmHg) in all trials. At 1–2 years, average SBP decreased with low CHO (range: −10.6 to −0.9 mmHg) and either decreased or increased with balanced diets (range: −10 to 8 mmHg). The increase was observed in a small trial (n = 25) with 48% attrition when the trial ended after one year
The meta-analysis of the mean difference in SBP change showed no difference after 3–6 months (−1.26 mmHg, 95%CI −2.67 to 0.15; 7 trials) (
At 3–6 months, compared to baseline, average LDL and total cholesterol were inconsistent across trials with low CHO diets (range LDL: −0.62 to 0.3 mmol/L; total cholesterol: −0.71 to 0.1 mmol/L), while these values decreased with balanced diets in each of the 12 trials that reported these values (range LDL: −0.82 to −0.03 mmol/L; total cholesterol: −0.88 to −0.07 mmol/L). Average changes in HDL and TG from baseline varied with low CHO (range HDL: −0.07 to 0.1 mmol/L; TG: −0.64 to 0.01 mmol/L) and balanced diets (range HDL: −0.1 to 0.08 mmol/L; TG: −0.49 to 0.01 mmol/L). At 1–2 years, average lipid marker changes from baseline were inconsistent in both diet groups across trials, with variations in ranges of change that were similar to those reported at 3–6 months.
The meta-analyses of the mean differences in blood lipids between the low CHO and balanced diets were small in both follow-up categories, with narrow confidence intervals suggesting little or no difference in effect between the two diets (
From baseline to 3–6 months, average FBG decreased with low CHO (range −0.47 to −0.06 mmol/L) and balanced diets (range −0.52 to −0.1 mmol/L), and at 1–2 years average changes were variable with low CHO (range: −0.71 to 0.17 mmol/L) and balanced diets (range: of −0.4 to 0.06 mmol/L). The meta-analysis showed no difference between low CHO and balanced diets in FBG change at either 3–6 months (0.05 mmol/l, 95%CI −0.05 to 0.15; 10 trials; Figure S2O in
Average weight loss was evident at 3–6 months with low CHO (range: 2.79 to 5.5 kg) and isoenergetic balanced diets (range: 3.08 to 5.4 kg), and similarly with both diets at 1–2 years (range low CHO diets: 2 to 3.9 kg; range balanced diets: 2.1 to 6 kg) in all trials. The meta-analysis of the mean difference in weight loss between the low CHO and balanced diets did not demonstrate a difference at 3–6 months (0.82 kg, 95%CI −1.25 to 2.90; 5 trials) (
Outcomes | Balanced diets | Low carbohydrate diets | No. of participants (studies) | Quality of the evidence (GRADE) |
Weight loss | Lower by 3.08 to 5.4 kg | 0.82 kg less weight lost | 599 | ⊕⊕⊝⊝ |
(could be 1.25 lost to a gain of 2.9 kg) | (5 studies) | low |
||
HbA1c | Lower by 0.3 to 0.51% | 0.19% higher HbA1c | 599 | ⊕⊕⊕⊝ |
(could be 0 to 0.39% higher) | (5 studies) | moderate |
||
Diastolic | From 3 lower to 1.63 mmHg higher | 0.77 mmHg higher diastolic blood pressure | 545 | ⊕⊕⊕⊝ |
blood pressure | (could be 1.77 lower to 3.3 mmHg higher) | (4 studies) | moderate |
|
Systolic | Lower by 0.06 to 8 mmHg | 0.61 mmHg higher systolic blood pressure | 545 | ⊕⊕⊝⊝ |
blood pressure | (could be 3.14 lower to 4.36 mmHg higher) | (4 studies) | low |
|
LDL cholesterol | From 0.11 lower to 0.09 mmol/L higher | 0.06 mmol/L higher LDL cholesterol | 599 | ⊕⊕⊕⊝ |
(could be 0.11 lower to 0.23 mmHg higher) | (5 studies) | moderate |
||
HDL cholesterol | From 0.01 lower to 0.03 mmol/L higher | 0.01 lower HDL cholesterol | 599 | ⊕⊕⊕⊝ |
(could be 0.05 lower to 0.04 mmol/L higher) | (5 studies) | moderate |
||
Total cholesterol | Lower by 0.01 to 0.31 mmol/L | 0.04 mmol/L higher total cholesterol | 599 | ⊕⊕⊕⊝ |
(could be 0.21 lower to 0.3 mmol/L higher) | (5 studies) | moderate |
||
Triglycerides | From 0 to 0.45 mmol/L lower | 0.20 mmol/L lower triglycerides | 252 | ⊕⊕⊝⊝ |
(could be 0.45 lower to 0.05 mmol/L higher) | (4 studies) | low |
Note this is the univariate average change observed between follow-up and baseline in the control group.
GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.
Downgraded by 1 for risk of bias: 1 of 5 studies did not report adequate sequence generation and 3 of 5 studies did not report adequate allocation concealment. 1 study had high total attrition (>20%) and 2 studies had differential attrition.
Downgraded by 1 for imprecision: difference in mean weight loss ranges from a loss of 1.25 to a gain of 2.9 kilograms.
Downgraded by 1 for risk of bias: 1 out of 5 studies did not report adequate sequence generation and 3 out of 5 studies did not report allocation concealment. 1 study had high total attrition and 2 studies had differential attrition.
Downgraded by 1 for risk of bias: 2 of 4 studies did not report adequate allocation concealment. 1 study had high total attrition (>20%) and 2 studies had differential attrition.
Downgraded by 1 for imprecision: difference in mean systolic blood pressure ranges from a reduction of 3.14 to an increase of 4.36 mmHg.
Downgraded for risk of bias: 1 of 4 studies did not report adequate sequence generation and 2 studies did not report adequate allocation concealment. 2 studies had differential attrition.
Downgraded by 1 for imprecision: confidence interval range is 0.5 mmol/L.
Outcomes | Balanced diets | Low carbohydrate diets | No. of participants (studies) | Quality of the evidence (GRADE) |
Weight loss | Lower by 2.1 to 6 kg | 0.91 kg less weight lost | 492 | ⊕⊕⊝⊝ |
(could be 2.08 lost to a gain of 3.89) | (4 studies) | low |
||
HbA1c | From 0.28% lower to 0.4% higher | 0.01% higher HbA1c | 492 | ⊕⊕⊕⊝ |
(could be 0.28 lower to 0.3 higher) | (4 studies) | moderate |
||
Diastolic | From 6 lower to 2.5 mmHg higher | 0.09 mmHg higher diastolic blood pressure | 492 | ⊕⊕⊕⊝ |
blood pressure | (could be 1.95 lower to 2.13 higher) | (4 studies) | moderate |
|
Systolic | From 11 lower to 3.7 mmHg higher | 0.31 mmHg higher systolic blood pressure | 492 | ⊕⊕⊕⊝ |
blood pressure | (could be 3.1 lower to 3.72 higher) | (4 studies) | moderate |
|
LDL cholesterol | From 0.3 lower to 0.04 mmol/L higher | 0.10 mmol/L higher LDL cholesterol | 492 | ⊕⊕⊕⊝ |
(could be 0.06 lower to 0.27 higher) | (4 studies) | moderate |
||
HDL cholesterol | Higher by 0.02 to 0.19 mmol/L | No difference in HDL cholesterol | 492 | ⊕⊕⊕⊝ |
(could be 0.09 lower to 0.08 higher) | (4 studies) | moderate |
||
Total cholesterol | From 0.3 lower to 0.35 mmol/L higher | 0.10 mmol/L higher total cholesterol | 492 | ⊕⊕⊕⊝ |
(could be 0.12 lower to 0.31 mmol/L higher) | (4 studies) | moderate |
||
Triglycerides | Lower by 0.1 to 0.3 mmol/L | 0.08 mmol/L lower triglycerides | 198 | ⊕⊕⊝⊝ |
(could be 0.49 lower to 0.26 higher) | (3 studies) | low |
CI: Confidence interval;
Note this is the univariate average change observed between follow-up and baseline in the control group.
GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.
Downgraded by 1 for risk of bias: 2 of 4 studies did not report adequate allocation concealment. 1 study had high total attrition (>20%) and 2 studies had differential attrition.
Downgraded by 1 for imprecision: The 95% confidence interval includes both a loss of 2.08 kg and a gain of 3.89 kg.
Downgraded by 1 for risk of bias: 2 of 4 studies did not report adequate allocation concealment, 2 studies had high total attrition (>20%), 2 studies had differential attrition.
Downgraded by 1 for risk of bias: 1 of 3 studies did not report adequate allocation concealment. 2 studies had high total attrition (>20%), 2 studies had differential attrition.
Downgraded by 1 for imprecision: confidence interval range is about 0.7 mmol/L.
A single trial found no difference in BMI change between the low CHO (high fat variant) and balanced diets at 3–6 months (Figures S3A and S3B in
At 3–6 months, compared to baseline, changes in average HbA1c varied across studies with low CHO diets (range: −0.54 to 0%), and decreased in each study with balanced diets (range: −0.51 to −0.3%). At 1–2 years, average HbA1c changes from baseline were inconsistent in both diet groups across trials (range low CHO: −0.23 to 0.1%; balanced: −0.28 to 0.4%).
The meta-analyses of the mean difference in HbA1c change did not demonstrate a difference between the low CHO and balanced diets at 3–6 months (0.19%, 95%CI −0.0 to 0.39; 5 trials) (
Similarly, no mean difference in FBG change between low CHO and balanced diets was detected by meta-analysis of 2 studies at 3–6 months (Figure S3E in
Average changes in DBP from baseline varied at 3–6 months with low CHO (range: −4 to 2.24 mmHg) and balanced diets (range: −3 to 1.63 mmHg) and also at 1–2 years (range low CHO: −5 to 0.21 mmHg; balanced: −6 to 2.5 mmHg).
The meta-analyses of the mean difference in DBP change did not demonstrate a difference between the low CHO and balanced diets at 3–6 months (95%CI −1.77 to 3.30; 4 trials) (
The average SBP in each study compared to baseline showed a drop in both the low CHO (range: −9 to −1 mmHg) and balanced diets (range: −8 to −0.06 mmHg) at 3–6 months, with varied changes at 1–2 years (range low CHO: −9 to 2.2 mmHg; balanced: −11 to 3.7 mmHg).
The meta-analysis of the mean difference in SBP change showed no difference after 3–6 months (95%CI −3.14 to 4.36; 4 trials) (
At 3–6 months, blood lipids (LDL, HDL, total cholesterol, TG) showed variable changes from baseline in both low CHO and balanced diets. Overall, changes from baseline were inconsistent between the diet groups and for both follow-up categories. The changes on meta-analysis were small suggesting little or no difference in effect between the two diets (
This review, including 19 RCTs with 3209 participants showed there is probably little or no difference in changes in weight and cardiovascular and diabetes risk factors with low CHO weight loss diets compared to isoenergetic balanced weight loss diets. This was in both overweight and obese adults without diabetes and those with diabetes, with follow-up for up to two years. When reported, energy intake was similar in the diet groups being compared, but participants did not adhere fully to the prescribed macronutrient goals for both diets in most trials.
Participants lost weight in both groups, with similar before and after average loss after 3–6 months, and 1–2 years of follow-up. There was little or no difference in weight loss and change in BMI between the low CHO and balanced weight loss diets in the two follow-up periods. The similar reported mean energy intakes in the low CHO and balanced diet groups and the corresponding similar average weight loss in the diet groups supports the fundamental physiologic principle of energy balance, namely that a sustained energy deficit results in weight loss regardless of macronutrient composition of the diet
Norms for defining “stable weight” are gaining less than or equal to 2 kg and losing less than 2 kg
Weight loss improves markers of cardiovascular risk
When considering blood lipid changes, a weight loss of 5 kg to 8 kg is reported to result in LDL cholesterol reduction of approximately 0.13 mmol/L and an increase in HDL cholesterol of between 0.05 to 0.08 mmol/L
The primary reason for the moderate grade of evidence in most outcomes at 3–6 months and 1–2 years is the risk of selection, performance and attrition bias in most included trials. For serum triglycerides, inconsistency (as discussed above) in effects resulted in further downgrading to low quality indicative of less confidence in the findings. Similarly, for DBP at 3–6 months, inconsistency in the mean differences across the different trials resulted in further downgrading to low quality evidence. This inconsistency could not be explained by the different variants of the low CHO diet. Most of the inconsistency can be ascribed to two trials
Both low CHO diets and balanced weight loss diets showed similar weight loss on average after 3–6 months and after 1–2 years. Meta-analysis and quality of evidence indicate that in overweight and obese adults with type 2 diabetes there may be little or no difference in weight loss after 3–6 months and 1–2 years. The earlier discussion of the long-term effects of dieting on weight loss is also applicable in this population.
Weight loss is associated with improvements in glycaemia in overweight and obese adults with type 2 diabetes. According to the 2013 AHA/ACC/TOS Guideline, 2% to 5% weight loss achieved with one to four years of lifestyle intervention results in modest reductions in FBG and lowering of HbA1c by 0.2% to 0.3%
Effects on DBP with low CHO and balanced diets were variable in most trials, showing both reductions and increases. Both the low CHO and balanced weight loss diets demonstrated reductions in average SBP in all trials after 3–6 months, but effects were variable with both diets after 1–2 years. Based on both the meta-analyses and the quality of the evidence, there is probably little or no difference in DBP change between the two diets and there may be little or no difference in SBP change after 3–6 months. After 1–2 years, there is probably little or no difference in changes in both DBP and SBP.
Effects on blood lipids with low CHO and balanced diets were variable between included trials, as was seen in the non-diabetic population. Considering the meta-analyses and the quality of the evidence, there is probably little or no difference in changes in LDL, HDL and total cholesterol after 3–6 months and 1–2 years when comparing the two diets. There may be little or no difference in changes in TG concentrations after 3–6 months and 1–2 years.
As in the non-diabetic overweight and obese population, the presence of risk of selection, performance and attrition bias in most included trials were the primary reasons for the moderate grade of evidence in most outcomes in the diabetic population. For weight loss at 3–6 months and 1–2 years follow-up, imprecision of the effect estimates resulted in further downgrading to low quality evidence. Similarly, the evidence for triglycerides for both follow-up categories and for SBP at 3–6 months was downgraded due to imprecision of the effect estimates. These imprecise estimates possibly relate to the smaller samples in the diabetes population.
Assessment of adherence to energy prescriptions across the 19 trials was problematic due to the different methods used to express prescriptions and the lack of reported energy intake data in some trials. The dietary intake methodology used also varied between the included trials, with trials using food records/diaries, single or multiple 24 hour recalls, food frequency questionnaires or combinations of these methods.
From the calculated adherence scores it was clear that strict adherence to prescribed macronutrient goals failed with both diets in most trials and generally declined with longer follow-up. This diminished adherence after the first few months has been well documented in weight loss trials
The findings of our review need to be interpreted in light of the presence of risk of bias or lack of power or both in many of the included trials, the possibility that adherence to dietary macronutrient goals were not optimal and that there was inter-trial variation in quantity (and type) of fat consumed. The interpretation of many weight loss trials is limited by a lack of blinded ascertainment of the outcome, small samples, large loss to follow-up, potentially limited generalisability and a lack of data on adherence to assigned diets
Our results show that the weight loss in overweight and obese subjects with or without diabetes on isoenergetic low CHO or balanced weight loss diets was similar at 3–6 months and at 1–2 years. Thus, the weight loss is the result of a reduction in total dietary energy intake rather than manipulation of macronutrient contribution. It follows that when considering dietary strategies for weight loss, less emphasis should be placed on an ‘ideal’ macronutrient composition and more emphasis on reduction in total energy intake, as well as improvement of behavioural adherence to reduced energy intake. This will go a long way to ensure that weight loss is achieved and maintained to gain health benefits. Guidance on macronutrient composition to meet nutritional requirements and prevent disease
The small size and short duration of weight loss trials often account for their lack of definitive evidence of the effectiveness of dietary interventions on CVD risk. By contrast sound observational data, population-level interventions and “natural experiments” in whole populations have demonstrated a reduction in population risk with adoption of recommended, balanced dietary strategies to lower cardiovascular risk. For example, over the past three decades, levels of population cardiovascular risk factors have declined in Finland, with the greatest change being dietary behaviour (reduction in total and saturated fat and increased vegetables and fruit intake). These declines explain most of the observed decline in CHD mortality in the Finnish middle-aged population over this period
Our systematic review did not address macronutrient quality of the diets, specifically the quality of CHO and fat, which along with total macronutrient quantities and proportions, explains the effects of diet on cardiovascular risk
Any dietary guidelines for health should be sustainable in the long-term, specifically in terms of ease of adherence, availability and affordability of foods, as well as social and cultural acceptability. Bearing this in mind, the dietary approach for weight management should be one that is nutritionally sound, not harmful and feasible to maintain over time. Such diets can be tailored to the needs of individuals on the basis of each individual's complete health and risk profile, for example existing lipid abnormalities and comorbidities, as well as food preferences, socioeconomic circumstances and personal and cultural preferences, thereby improving the chances of longer term success. Suitably qualified healthcare professionals should guide the tailoring of dietary advice for individuals. Monitoring and follow-up by a healthcare professional during a dietary weight loss intervention is known to positively affect outcomes
Three prominent electronic databases were searched and two authors carried out the various steps in the review (screening and selecting, extracting, risk of bias assessment, analysing, collation and interpretation). Although we planned not to include non-English randomised controlled trials, we did not come across any potentially eligible studies that we needed to exclude based on language.
Trials show weight loss in the short-term irrespective of whether the diet is low CHO or balanced in terms of its macronutrient composition. There is probably little or no difference in weight loss and changes in cardiovascular risk factors up to two years of follow-up when overweight and obese adults, with or without type 2 diabetes, are randomised to low CHO diets and isoenergetic balanced weight loss diets.
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We acknowledge Elizabeth Pienaar for searching EMBASE.