Background Angelman syndrome (AS) patients often respond to low glycemic index therapy to manage refractory seizures. These diets significantly affect quality of life and are challenging to implement. These formulations may have benefits in AS even in the absence of biomarkers suggesting ketosis. Objectives We aimed to compare an exogenous medical food ketone formulation (KF) with placebo for the dietary management of AS. Methods This randomized, double-blind, placebo-controlled, crossover clinical trial was conducted in an academic center from 15 November, 2018 to 6 January, 2020. Thirteen participants with molecularly confirmed AS aged 4–11 y met the criteria and completed the 16-wk study. The study consisted of four 4-wk phases: a baseline phase, a blinded KF or placebo phase, a washout phase, and the crossover phase with alternate blinded KF or placebo. Primary outcomes were safety and tolerability rated by retention in the study and adherence to the formulation. Additional secondary outcomes of safety in this nonverbal population included blood chemistry, gastrointestinal health, seizure burden, cortical irritability, cognition, mobility, sleep, and developmental staging. Results Data were compared between the baseline, KF, and placebo epochs. One participant exited the trial owing to difficulty consuming the formulation. Adverse events included an increase in cholesterol in 1 subject when consuming KF and a decrease in albumin in 1 subject when consuming placebo. Stool consistency improved with KF consumption, from 6.04 ± 1.61 at baseline and 6.35 ± 1.55 during placebo to 4.54 ± 1.19 during KF (P = 0.0027). Electroencephalograph trends showed a decrease in Δ frequency power during the KF arm and event-related potentials suggested a change in the frontal memory response. Vineland-3 showed improved fine motor skills in the KF arm. Conclusions The exogenous KF appears safe. More data are needed to determine the utility of exogenous ketones as a nutritional approach in children with AS. This trial was registered at clinicaltrials.gov as NCT03644693.

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Background Studies in women of European descent showed an inverse association of dietary vitamin A (retinol and carotenoids) intake with breast cancer risks, mainly in premenopausal women. Objectives We examined whether higher compared with lower levels of dietary vitamin A are associated with reduced breast cancer risks among Black women by estrogen receptor (ER) and menopausal statuses. Methods In this pooled analysis, data were from 3564 breast cancer cases and 11,843 controls (mean ages = 56.4 and 56.3 years, respectively) in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Dietary intake was assessed by FFQs. Multivariable logistic regressions were performed to estimate ORs and 95% CIs for study-specific quintiles of total vitamin A equivalents and individual carotenoids, and a pooled OR was estimated by a random-effect model. Results We observed an inverse association of total vitamin A equivalents with ER-positive breast cancer (quintiles 5 compared with 1: pooled OR: 0.82; 95% CI: 0.67–1.00; P-trend = 0.045). The association was seen among premenopausal women (pooled OR: 0.60; 95% CI: 0.43–0.83; P-trend = 0.004), but not among postmenopausal women (pooled OR: 0.99; 95% CI: 0.77–1.28; P-trend = 0.78). Additionally, there were inverse associations of dietary β-carotene (quintiles 5 compared with 1: pooled OR: 0.70; 95% CI: 0.51–0.95; P-trend = 0.08) and lutein (pooled OR: 0.63; 95% CI: 0.45–0.87; P-trend = 0.020) with ER-positive breast cancer among premenopausal women. There was no evidence for an association of total vitamin A equivalents or individual carotenoids with ER-negative breast cancer, regardless of menopausal status. Conclusions Our findings on dietary vitamin A and breast cancer risks in Black women are consistent with observations in women of European descent and advance the literature showing an inverse association for ER-positive disease.