A recent study published in Cell Reports Medicine explored the factors governing the success of long- and short-term weight loss interventions.
Many obese individuals attempt to lose weight. However, it remains challenging to maintain weight loss, as reports indicate that 30% to 50% of the weight is regained within a year. This may stem from the lack of sustained adherence to the diet that caused weight loss. Obesity and overnutrition can cause low inflammation, leading to metabolic dysfunction that may influence an individual’s response to weight loss interventions.
The study and findings
In the present study, researchers performed a secondary analysis using data from a dietary weight loss intervention study to examine the effects of dietary and non-dietary factors on weight loss. The diet intervention examining the factors interacting with treatment success (DIETFITS) study comprised 609 individuals randomized to a healthy low-fat (HLF) or -carbohydrate (HLC) diet for one year.
Participants were sampled at baseline, six months, and one year when data on dietary intake, clinical markers, protein biomarkers, respiratory quotient, and body composition were collected. There were no differences in dietary calories between HLC and HLF groups at the specified time points. Most participants lost weight in the first six months relative to baseline, with the HLC group losing more weight in the first six months and regaining more in the next six months.
Since most dietary changes were evident in the first six months, the team examined the impact of dietary restriction during this period (henceforth, short-term intervention) by determining caloric restriction and dietary adherence. In receiver operating characteristic (ROC) analysis, they observed that dietary adherence was more significant than caloric restriction in differentiating the two groups.
Moreover, they identified 24, 38, and 18 nutrients associated with weight loss in HLF, HLC, and both groups, respectively. In the HLC group, vitamins K and E and the vitamin C-to-iron ratio correlated with more successful weight loss. Since HLC participants reduced dietary carbohydrates, calories from fat increased.
A higher percentage of mono-unsaturated fatty acids (MUFAs) relative to saturated fatty acids (SFAs) was associated with more weight loss in HLC participants. In the HLF group, unrefined carbohydrates significantly correlated with weight loss. The authors observed a significant decrease in RQ measured at six months relative to baseline in HLC participants, due to an increase in dietary fat, with a significant association between RQ reduction and the amount of weight lost.
Contrastingly, there were no significant changes in RQ in the HLF group. Although most participants (399) exhibited weight loss in the first six months, some of these (118) continued to lose weight in the next six months (long-term intervention, weight quadrant 3 [Wq3]), while others (Wq1) did not. These two subsets of participants did not differ in dietary adherence or caloric restriction.
Notably, more individuals in the HLF group achieved long-term weight loss. Further, targeted proteomics was performed to explore differentially expressed proteins between Wq1 and Wq3 groups, focusing on baseline samples for biomarkers than can predict the success of the long-term intervention.
Several proteins associated with weight loss were identified. For instance, HLC individuals were more likely to lose more weight in one year if they exhibited lower baseline levels of tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B), dickkopf-related protein 1 (DKK1), alpha-L-iduronidase (IDUA), and interleukin (IL)-16.
HLC individuals with higher levels of these proteins were highly enriched in the Wq1 group, and those with lower levels were enriched in the Wq3 group. Unlike in the HLC group, TNFRSF13B was significantly elevated in the HLF-Wq3 group, suggesting a different role in HLF- and HLF-induced weight loss.
Longitudinal stool samples were available from 49 participants (12 from Wq3 and 38 from Wq1). Principal component analysis revealed that the success of long-term weight loss was better distinguished by microbiota composition than dietary intervention (HLF or HLC); intriguingly, this microbial difference between Wq1 and Wq3 was also evident at baseline.
Most participants showed weight loss in the first six months (short-term), with HLC participants exhibiting marginally better success. In the long term (12 months), HLF participants regained much less weight. However, there were no weight-loss differences between groups by the end of one year. Dietary adherence and quality but not caloric restriction correlated with weight loss. An increased intake of vitamins C, E, and K (in HLC participants) and fiber and whole grains (in the HLF group) was associated with higher weight loss.
Minimal dietary differences were observed between participants who succeeded in the long term (Wq3) and those who did not (Wq1). Gut microbiota and proteomic signatures significantly differed between Wq1 and Wq3 groups at baseline. Identifying common or unique dietary, metabolic, and molecular factors offers a roadmap for personalized weight-loss interventions.