Editor's Pick
Journal: Nutrients 2025;17(16):
PMID: 40871713
Many different diets recommend varying amounts of carbohydrates, fats, and proteins for weight loss and heart health. However, there is ongoing debate about which macronutrient balance is most effective for reducing body weight and improving cardiovascular risk. Because individual studies often compare only two diets at a time, it can be difficult for healthcare professionals and the public to know which approach is most beneficial overall. This systematic review and network meta-analysis of randomised controlled trials aimed to compare multiple dietary macronutrient patterns at the same time to determine how different macronutrient ratios influence body weight and cardiovascular risk factors in adults.
The results showed that certain lower-carbohydrate diets, particularly the very low carbohydrate–low protein (VLCLP) diet, resulted in greater short-term weight loss compared to the moderate fat–low protein reference diet (up to -4.10 kg). Several lower-carbohydrate or higher-protein dietary groups also showed greater reductions in triglycerides. However, differences between most macronutrient ratios were modest, and there was little to no difference between dietary groups for effects on blood glucose, blood pressure, cholesterol (with some variations in high-density lipoprotein).
In conclusion, the VLCLP dietary group may be the most appropriate for weight loss, while the moderate carbohydrate–low protein group performed best for reducing triglycerides. For control of blood sugar, blood pressure, and cholesterol levels, there is little to no difference between macronutrient dietary groups. Diet quality, sustainability, and individual preferences remain important considerations. Healthcare professionals can use this evidence to support personalised dietary recommendations rather than promoting one universal macronutrient distribution.
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• Different dietary macronutrient combinations lead to varying outcomes for managing weight and reducing risk factors associated with cardiovascular disease.
• VLCLP, MCHP and VLCHP dietary types were all significantly associated with greater reductions in body weight compared to the MFLP group.
• MCLP, VLCHP, VLCLP and MFHP were all significantly associated with greater reductions in triglycerides compared to the MFLP group.
• This study therefore supports the need for personalised dietary advice, to meet the diverse needs of individual health and lifestyle requirements. Healthcare practitioners may want to assess the relative effects of different macronutrient profiles depending on their patient weight and cardiovascular markers.
Introduction
The aim of this systematic network meta-analysis was to compare the relative effectiveness of diets with a range of different macronutrient ratios for reducing body weight and cardiovascular risk factors.
Methods
• 66 randomised controlled trials (RCTs) were included with study durations of between 1-96 weeks with a total of N=3745 adult participants completing the studies.
• 8 macronutrient dietary groups were analysed based on energy intake ratios for proteins, fats and carbohydrates: very low carbohydrate-low protein (VLCLP), very low carbohydrate-high protein (VLCHP), moderate carbohydrate-high protein (MCHP), moderate carbohydrate-low protein (MCLP), moderate fat-low protein (MFLP), moderate fat-high protein (MFHP), very low fat-low protein (VLFLP), very low fat-high protein (VLFHP).
• Results were reported for their relative effectiveness compared to the MFLP diet group (control), considered the most typical in usual daily life.
• Outcome measures: body weight (BW), blood pressure (systolic and diastolic), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and blood glucose.
• Sub-groups were analysed for intervention durations of <6 or >6 months. Potential influencing factors considered: physical activity, energy intake, country of study, sample size, intervention duration, funding source and year of publication.
Results
• Compared to a MFLP diet the most significant reductions in BW were found in the following groups; VLCLP, mean difference (MD) -4.10kg, MCHP, MD -1.51kg, and VLCHP, MD -1.35kg (95% credible interval (CrI)). All other dietary types were found to have little or no positive effect on weight loss.
• The greatest reductions in blood glucose were found in the MCLP and VLCLP groups, however, results were not clinically significant.
• The VLCHP was best for lowering systolic BP and the MFHP most effective for reducing diastolic BP, however, findings did not reach clinical significance.
• Cholesterol results showed the MFHP and VLFLP were best for lowering all types of cholesterol, however, results were not statistically significant. The MCLP performed best for lowering triglycerides (95% CrI).
• No substantial differences were found when adjusting for sub-groups or potential influencing factors.
Conclusion
Different diets performed best for different outcome measures. The VLCLP was best for weight loss and the MCLP best for reducing triglycerides. There were no significant differences between groups for the control of blood pressure, blood glucose or cholesterol levels,
• Dietary guidelines for various countries are most closely aligned with the MFLP diet, as it provides a balanced nutrient profile for general population health. However, this macronutrient dietary type was not found to be the most effective for either blood pressure control or weight management.
• High protein diets may improve insulin and blood glucose levels but have a negative impact on renal and cardiovascular health.
• Dietary advice needs to be personalised to meet an individual’s lifestyle and health needs.
• 2/66 trials were in normal weight adults and 62/66 were in adults with overweight or obesity. Further research is therefore needed in normal weight populations for dietary advice to be generalised for cardiovascular benefits and weight maintenance advice.
• Further research is also needed into optimal macronutrient ratios for reducing blood glucose and blood pressure.
• Heterogeneity between studies may provide only partial comparisons and inconsistent evidence. Further research is therefore needed
This network meta-analysis aimed to assess the relative efficacy of macronutrient dietary groups with varying carbohydrate, fat, and protein ratios on weight control and cardiovascular risk factors improvement in adults. We searched PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Web of Science Core Collection, and ClinicalTrials.gov from inception to 30 November 2024, as well as reference lists of related systematic reviews. Eligible randomized controlled trials (RCTs) were included. Literature screening, data extraction, and risk of bias assessment were conducted independently by two reviewers. The changes in body weight, blood glucose, systolic blood pressure, diastolic blood pressure, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, and total cholesterol were the study outcomes. Utilizing a Bayesian framework, a series of random-effects network meta-analyses were conducted to estimate mean difference (MD) with 95% credible interval (CrI) and determine the relative effectiveness of the macronutrient dietary groups. The quality of evidence for each pair of dietary groups was assessed based on the online tool called confidence in network meta-analysis (CINeMA). This study initially identified 14,988 studies and ultimately included 66 eligible RCTs involving 4301 participants in the analysis. The very low carbohydrate-low protein (VLCLP, MD -4.10 kg, 95% CrI -6.70 to -1.54), the moderate carbohydrate-high protein (MCHP, MD -1.51 kg, 95% CrI -2.90 to -0.20), the very low carbohydrate-high protein (VLCHP, MD -1.35 kg, 95% CrI -2.52 to -0.26) dietary groups might lead to weight loss compared with the moderate fat-low protein (MFLP) dietary group. Among the dietary groups relative to the MFLP dietary group, the moderate carbohydrate-low protein (MCLP, MD 0.09 mmol/L, 95% CrI 0.02 to 0.16) and VLCHP (MD 0.16 mmol/L, 95% CrI 0.08 to 0.24) dietary groups were less effective in lowering HDL cholesterol, and the VLCHP (MD 0.50 mmol/L, 95% CrI 0.26 to 0.75) dietary group was less effective in lowering LDL cholesterol. In terms of triglyceride reduction, the MCLP (MD -0.33 mmol/L, 95% CrI -0.44 to -0.22), VLCHP (MD -0.31 mmol/L, 95% CrI -0.42 to -0.18), VLCLP (MD -0.14 mmol/L, 95% CrI -0.25 to -0.02), and moderate fat-high protein (MFHP, MD -0.13 mmol/L, 95% CrI -0.21 to -0.06) dietary groups were more efficacious than the MFLP dietary group, while any pair of dietary group interventions showed minimal to no difference in the effects on blood glucose, blood pressure, and total cholesterol. High or moderate certainty evidence reveals that the VLCLP dietary group is the most appropriate for weight loss, while the MCLP dietary group is best for reducing triglycerides. For control of blood glucose, blood pressure, and cholesterol levels, there is little to no difference between macronutrient dietary groups. Additionally, future studies in normal-weight populations are needed to verify the applicability of our findings.
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