(LB01-01-24) Impact of Alternate Day Fasting (ADF) Combined With a Low-Carbohydrate Diet on Biomarkers Relevant to Immunotherapy

Objectives: The effects of alternate day fasting (ADF) and low carbohydrate dietary regimens on immune respo­nse biomarkers have not been fully characterized. This study aims to examine whether ADF combined with low carbohydrate diet exerts unique changes on biomarkers relevant to immunotherapy.

Methods: This is a secondary analysis of a single-arm clinical trial involving adults with obesity (n = 31). The six-month trial involved a three-month weight loss intervention, followed by a three-month follow-up weight maintenance period. The intervention entailed ADF (a 600-kcal “fast day” alternating with an ad-libitum “feast day”) on a low-carbohydrate diet (30% carbohydrates, 35% protein, and 35% fat). Participants received low-carbohydrate meal replacement smoothies to integrate into their dietary regimen. Serum biomarkers were measured using multiplex assay including programmed death ligand 1 (PD-L1), interleukin 1 receptor antagonist (IL1-ra), monocyte chemotactic protein 1 (MCP-1), cluster of differentiation 40 ligand (CD40-L), and interferon-γ-induced protein (IP-10). Repeated-measures ANOVA was conducted to compare the changes in biomarker levels over time. A P-value < 0.05 implied statistical significance.

Results: Body weight decreased (−5.5 ± 0.5%; P < 0.001) during the weight loss period but remained stable (P=0.57) during the weight maintenance period. Interestingly, serum PD-L1 levels significantly decreased by week 12 compared to baseline (-6.69 ± 2.15 pg/mL, P=0.005), but the change was not significant when comparing week 24 to baseline (-4.95 ± 3.79 pg/mL, P=0.203) and to week 12 (1.74 ± 2.93 pg/mL, P=0.557). Moreover, a significant change over time was observed in IL1-ra levels (P < 0.011), as serum IL1-ra significantly decreased by week 24 compared to baseline (-101.1 ± 29 pg/mL, P=0.002), but the change was not significant when comparing week 12 to baseline (-52.5 ± 34.2 pg/mL, P=0.137) and week 24 to week 12 (-48.6 ± 33.6 pg/mL, P=0.16). No significant changes over time were observed in serum MCP-1, CD40-L, or IP-10 levels.

Conclusions: These findings suggest that ADF in combination with a low-carbohydrate diet modulates circulating biomarkers relevant to immunotherapy. However, these findings must be confirmed, and their applicability to cancer populations should be explored.

Funding Sources: Nestle Health Sciences, The Ohio State University