Frontiers in nutrition · 2026
Association of first-month beta-hydroxybutyrate levels with subsequent ketogenic diet response in children with drug-resistant epilepsy: a prospective cohort study.
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Tan Quanzhen, Zhang Shuqian, Li Yulan, Zhang Junhong, Chang Xuting, Wu Yuan, Zhang Jie
Аннотация
BACKGROUND: Ketogenic diet therapy (KDT) is an established treatment for children with drug-resistant epilepsy (DRE), but the prognostic value of early blood beta-hydroxybutyrate (BHB) during diet stabilization remains uncertain.
METHODS: This single-center prospective cohort study enrolled children with DRE who initiated classical KDT at Peking University First Hospital between June 2023 and January 2025. First-month BHB was defined as the mean of two fasting pre-breakfast BHB measurements obtained during the final week of the first month after KDT initiation. Continuous first-month BHB was analyzed in relation to 3-month seizure reduction. An exploratory group-based analysis used a 3.0 mmol/L cutoff. The primary outcome was 3-month treatment response, defined as ≥50% seizure reduction from baseline. Later response and retention were summarized descriptively.
RESULTS: Of 40 screened children, 38 were analyzed (19 per group). Seizure type differed between groups (p = 0.028). At 3 months, response was 42.1% (8/19) in the higher-BHB group and 52.6% (10/19) in the lower-BHB group, with an absolute risk difference of -10.5 percentage points (95% CI, -38.1 to 19.6), risk ratio of 0.80 (95% CI, 0.41-1.58), and unadjusted OR of 0.65 (95% CI, 0.18-2.36). The adjusted OR was 0.64 (95% CI, 0.13-3.09; p = 0.575). Continuous BHB showed no clear monotonic association with 3-month seizure reduction (Spearman ρ = -0.105; p = 0.532). Overall treatment response was 47.4, 39.5, 26.3, and 26.3% at 3, 6, 9, and 12 months, respectively. Adverse events occurred in 13 patients (34.2%) and did not lead to KDT discontinuation.
CONCLUSION: Continuous first-month BHB showed no clear monotonic association with 3-month seizure reduction; an exploratory 3.0 mmol/L cutoff analysis similarly did not distinguish subsequent responders from non-responders. These findings describe the prognostic value of first-month BHB measured after individualized KDT titration and should not be interpreted as evidence regarding the benefit of deliberately targeting higher BHB levels.
METHODS: This single-center prospective cohort study enrolled children with DRE who initiated classical KDT at Peking University First Hospital between June 2023 and January 2025. First-month BHB was defined as the mean of two fasting pre-breakfast BHB measurements obtained during the final week of the first month after KDT initiation. Continuous first-month BHB was analyzed in relation to 3-month seizure reduction. An exploratory group-based analysis used a 3.0 mmol/L cutoff. The primary outcome was 3-month treatment response, defined as ≥50% seizure reduction from baseline. Later response and retention were summarized descriptively.
RESULTS: Of 40 screened children, 38 were analyzed (19 per group). Seizure type differed between groups (p = 0.028). At 3 months, response was 42.1% (8/19) in the higher-BHB group and 52.6% (10/19) in the lower-BHB group, with an absolute risk difference of -10.5 percentage points (95% CI, -38.1 to 19.6), risk ratio of 0.80 (95% CI, 0.41-1.58), and unadjusted OR of 0.65 (95% CI, 0.18-2.36). The adjusted OR was 0.64 (95% CI, 0.13-3.09; p = 0.575). Continuous BHB showed no clear monotonic association with 3-month seizure reduction (Spearman ρ = -0.105; p = 0.532). Overall treatment response was 47.4, 39.5, 26.3, and 26.3% at 3, 6, 9, and 12 months, respectively. Adverse events occurred in 13 patients (34.2%) and did not lead to KDT discontinuation.
CONCLUSION: Continuous first-month BHB showed no clear monotonic association with 3-month seizure reduction; an exploratory 3.0 mmol/L cutoff analysis similarly did not distinguish subsequent responders from non-responders. These findings describe the prognostic value of first-month BHB measured after individualized KDT titration and should not be interpreted as evidence regarding the benefit of deliberately targeting higher BHB levels.