Even if the scales appear stuck and the pounds are not dropping, adopting healthy habits still improves some heart health markers.
Study: Population screening of adults identifies novel genetic variants associated with celiac disease. Image credit: Rostislav_Sedlacek/Shutterstock.com
In a recent article published in the European Journal of Preventive Cardiology, researchers investigated how people respond to long-term lifestyle interventions targeting weight loss and how different levels of weight change affect their cardiometabolic health.
Background
Weight loss is widely recognized for its benefits in reducing the risk of cardiometabolic conditions, including type 2 diabetes, cardiovascular disease, hypertension, and mortality.
A minimum weight loss of 5% has been linked to favorable changes in key health indicators such as body fat, waist circumference, high-density lipoprotein (HDL) cholesterol, and blood pressure.
However, maintaining weight loss is challenging. Studies show that a substantial portion of lost weight is often regained within one and five years. Individuals also vary significantly in their response to lifestyle-based weight loss interventions, likely due to behavioral, metabolic, and genetic differences.
Many people experience initial success in the early months, followed by weight regain or stabilization, a trend often influenced by metabolic slowdown, hormonal shifts, and relapse into old habits. Given this variability, more personalized approaches to weight loss may be needed.
About the study
This study aimed to quantify improvements in cardiometabolic markers relative to modest weight loss and examine differences across categories of weight loss success.
Additionally, the researchers sought to identify baseline biological predictors of weight loss outcomes. To do so, they pooled data from three major long-term lifestyle weight loss trials, which varied in dietary and behavioral strategies but shared similar patterns in weight trajectory and health improvements.
Participants were grouped into three categories based on the weight they lost during the trials: The first group contained those who lost more than 5% of their total body weight (weight loss successful), those who lost between 0% and 5% (weight loss moderate), and no loss or gain (weight loss resistant).
Each participant underwent multiple assessments throughout the trials, including anthropometrics, blood pressure, and fasting blood biomarkers. In two trials, participants underwent magnetic resonance imaging to assess visceral adipose tissue and liver fat. Outcome measures were recorded at baseline, six months, and the end of the intervention (18 or 24 months).
A sub-study was conducted using baseline samples to explore predictors of weight loss success, including deoxyribonucleic acid (DNA) methylation, proteomics, and metabolomics. Two predictive modeling approaches were applied. Cross-trial-wide association studies and elastic net regression.
Statistical analyses included chi-square, analysis of variance (ANOVA), paired t-tests, and multivariable regressions, adjusting for outliers and correcting for multiple comparisons using the False Discovery Rate (FDR). Linear or spline regression models were applied depending on model fit.
Key findings
At baseline, weight loss resistant individuals were generally younger, more likely to be female, and had lower waist circumference, liver enzyme levels, and intra-hepatic fat (IHF). However, after adjusting for the trial, body mass index (BMI), age, and sex, these differences were non-significant primarily.
Predictive modeling using pre-intervention DNA methylation, proteomics, and metabolomics data failed to predict weight loss accurately. The models using omics data, DNA methylation, proteomics, and metabolomics generally showed weak predictive performance, with only 12 specific DNA methylation regions showing moderate predictive accuracy in subset analyses. However, these findings are exploratory and not yet ready for clinical use.
Long-term health benefits varied by weight loss category. Weight loss resistant individuals showed some improvements in HDL cholesterol and fat distribution, including reduced visceral fat and leptin, but increases in total cholesterol and fasting glucose.
Weight loss moderate participants showed broader improvements, including blood pressure, triglycerides, liver fat, and insulin. Weight loss successful individuals had the most significant health improvements across nearly all biomarkers.
Significant changes were observed in HDL, blood pressure, insulin resistance, triglycerides, leptin, and IHF for each kilogram of weight loss. After adjusting for trials and demographics, these effects remained robust, with no sex-specific interactions detected.
Conclusions
This study pooled data from three long-term lifestyle intervention trials and found that although only one-third achieved successful long-term weight loss, even weight loss resistant individuals experienced health benefits.
Sustained weight loss, even as little as one kilogram, led to meaningful improvements in cardiometabolic markers, including ectopic fat reduction, blood lipids, liver enzymes, and glycemic control.
Significantly, the study’s methods, including comprehensive sensitivity analysis, meta-analysis, and subgroup checks, strengthen the reliability of these findings.
Omics-based predictors such as DNA methylation showed promise, though predictive accuracy was limited, and current results are only preliminary.
Key strengths include high adherence across trials, comprehensive analyses, and robust sensitivity checks. Limitations include the study's being about 89% male, which limits how broadly these findings can be generalized to women, limited female representation, and lack of intervention-specific stratification.
Importantly, those who did not lose weight also experienced health benefits, emphasizing weight loss-independent benefits of lifestyle changes. However, some risk markers in the groups worsened, so the health effects of lifestyle changes without weight loss may be mixed and should be interpreted cautiously.
The study highlights the critical role of lifestyle in cardiovascular prevention and offers evidence-based guidance for clinicians advising patients.
Future research should include larger, more diverse samples, particularly women, and further explore omics markers to personalize weight loss strategies. Emphasizing healthy behaviors remains essential, even when weight loss is not achieved.
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Journal reference:
- Individual response to lifestyle interventions: a pooled analysis of three long-term weight loss trials. Meir, A.Y., Tsaban, G., Rinott, E., Zelicha, H., Schwarzfuchs, D., Gepner, Y., Rudich, A., Shelef, I., Blüher, M., Stumvoll, M., Ceglarek, U., Isermann, B., Klöting, N., Keller, M., Kovacs, P., Qi, L., Wang, D.D., Liang, L., Hu, F.B., Stampfer, M.J., Shai, I. European Journal of Preventive Cardiology (2025). DOI: 10.1093/eurjpc/zwaf308 https://www.nature.com/articles/s41598-025-04421-6