Comprehensive nutrient consumption estimation and metabolic profiling during ketogenic diet and relationship with myocardial glucose uptake on FDG-PET

Abstract

Aims The ketogenic diet (KD) is standard-of-care to achieve myocardial glucose suppression (MGS) for assessing inflammation using fluorine-18 fluorodeoxyglucose–positron emission tomography (FDG-PET). As KD protocols remain highly variable between centres (including estimation of nutrient intake by dietary logs for adequacy of dietary preparation), we aimed to assess the predictive utility of nutrient intake in achieving MGS. Methods and results Nineteen healthy participants underwent short-term KD, with FDG-PET performed after 1 and 3 days of KD (goal carbohydrate intake <20 g/day). Nutrient consumption was estimated from dietary logs using nutrition research software. The area under receiver operating characteristics (AUROC) of macronutrients (carbohydrate, fat, and protein intake) for predicting MGS was analysed. The association between 133 nutrients and 4 biomarkers [beta-hydroxybutyrate (BHB), non-esterified fatty acids, insulin, and glucagon] with myocardial glucose uptake was assessed using mixed effects regression with false discovery rate (FDR) correction. Median (25th–75th percentile) age was 29 (25–34) years, 47% were women, and 42% were non-white. Median (25th–75th percentile) carbohydrate intake (g) was 18.7 (13.1-30.7), 16.9 (10.4-28.7), and 21.1 (16.6-29.0) on Days 1–3. No macronutrient intake (carbohydrate, fat, or protein) predicted MGS (c-statistic 0.45, 0.53, 0.47, respectively). Of 133 nutrients and 4 biomarkers, only BHB was associated with myocardial glucose uptake after FDR correction (corrected P-value 0.003). Conclusions During highly supervised, short-term KD, approximately half of patients meet strict carbohydrate goals. Yet, in healthy volunteers, dietary review does not provide reassurance for adequacy of myocardial preparation since no clear thresholds for carbohydrate or fat intake reliably predict MGS.

A level of confidence: beta-hydroxybutyrate and myocardial glucose uptake suppression on 18F-FDG PET imaging

“…1,5 While review of dietary logs is commonly performed and could theoretically substitute as an assessment for adequate myocardial preparation, concerningly, no strong relationship has been established between estimated intake of nutrients, such as carbohydrates and fats, and MGS. 6 Recent data support a role for beta-hydroxybutyrate (BHB), a ketone produced by the liver via metabolism of fatty acids as a source of energy during insulinopenic states, in evaluating the adequacy of MGS in both healthy and clinical populations. 7,8 While more sophisticated metabolite analysis might hold similar promise, BHB importantly can be evaluated using point-of-care instruments or within one hour in major hospital laboratories, making it a clinically attractive biomarker for evaluating adequate MGS just prior to 18 F-FDG injection.…”

“…This is underscored by the fact that current protocols employing dietary review alone may not yield greater certainty. 6 Thus, the advantages of ketone measurements beyond current protocols must be defined, since BHB is an imperfect biomarker for identifying patients with adequate MGS. Finally, assessing other ketones should be considered to determine if they outperform BHB in the assessment of MGS.…”

Metabolomic Signatures of Myocardial Glucose Uptake on Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography

“…Box-Cox transformation and standardization of metabolites into z scores were performed. Linear mixed effects regression models 3 were used to assess the association between each metabolite and MGU, controlling for study visit as a fixed effect, modeling participant as a random effect, and using an independent covariance structure, where applicable. A Benjamini-Hochberg false discovery rate cutoff of 0.05 defined significance.…”