Stage-Dependent Metabolic Responses to Oral Nutritional Supplementation in Cancer Cachexia: A Single-Arm Pilot Study.

The 8-week ONS intervention demonstrated feasibility with high adherence and excellent tolerability in cancer cachexia patients undergoing chemotherapy.

• Adherence rate was 82%.
• Tolerability was described as excellent with no ONS-related adverse events.
• A total of 10 patients participated (median age 65 years, range 42–76).
• Primary cancer types included cholangiocarcinoma (n=4), colorectal (n=4), and gallbladder cancer (n=2).
• Study was conducted at Chungnam National University Hospital, Daejeon, Republic of Korea between January 2023 and October 2023.

Hand-grip strength and walking speed were slightly improved in the overall cohort after 8 weeks of ONS intervention.

• Hand-grip strength improvement was statistically significant (p=0.014, Wilcoxon signed-rank test).
• Walking speed improvement was statistically significant (p=0.021, Wilcoxon signed-rank test).
• These improvements were observed in the overall cohort of 10 patients.
• Body composition, quality of life, and gut microbiome showed no significant changes.

Metabolomics identified 10 metabolites, predominantly fatty acids, with significant differential responses between severe and non-severe cachexia groups following ONS.

• 10 metabolites with significant between-group differential responses were identified (p<0.05, Mann-Whitney U test).
• The predominant metabolites identified were fatty acids.
• Fatty acid metabolism emerged as the predominant discriminatory pathway between groups.
• Assessment was performed at baseline and after 8 weeks using serum metabolomics.

Non-severe cachexia patients showed reductions in circulating fatty acids following ONS, whereas severe cachexia patients demonstrated increases.

• Reductions in circulating fatty acids in non-severe cachexia were interpreted as consistent with attenuated lipolysis and reduced endogenous fat mobilization.
• Increases in circulating fatty acids in severe cachexia patients suggested limited metabolic responsiveness to nutritional intervention.
• These stage-dependent metabolic responses indicate differential effects of ONS depending on cachexia severity.
• Patients were stratified into severe and non-severe cachexia groups for this analysis.

Certain fatty acids were identified as candidate biomarkers for cancer cachexia that warrant further validation in larger cohorts.

• Fatty acids were identified as candidate biomarkers based on their differential responses between cachexia severity groups.
• The authors suggest these metabolic alterations might precede clinically detectable changes.
• The findings potentially provide a rationale for early nutritional intervention in cancer cachexia.
• Further validation in larger cohorts was recommended by the authors.

Body composition, quality of life, and gut microbiome composition showed no significant changes following the 8-week ONS intervention.

• Secondary outcomes assessed included body composition, physical performance, biochemical markers, quality of life, plasma GDF-15 levels, serum metabolomics, and gut microbiome composition.
• Multi-omics profiling including gut microbiome assessment was performed at baseline and after 8 weeks.
• The lack of significant changes in gut microbiome was noted despite the ONS intervention.
• No significant changes in body composition were observed across the overall cohort.