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Comparison of Exogenous Ketone Administration Versus Dietary Carbohydrate Restriction on Myocardial Glucose Suppression: A Crossover Clinical Trial.

Publication ,  Journal Article
Selvaraj, S; Margulies, KB; Dugyala, S; Schubert, E; Tierney, A; Arany, Z; Pryma, DA; Shah, SH; Rame, JE; Kelly, DP; Bravo, PE
Published in: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
May 2022

The ketogenic diet (KD) is the standard of care to achieve myocardial glucose suppression (MGS) for assessing inflammation using 18F-FDG PET. However, failure to suppress physiologic glucose uptake remains a significant diagnostic barrier. Although extending the duration of KD may be effective, exogenously delivered ketones may provide a convenient, reliable, and same-day alternative. The aims of our study were to determine whether exogenous ketone administration is noninferior to the KD to achieve MGS and whether serum β-hydroxybutyrate (BHB) levels can predict MGS. Methods: KEETO-CROSS (Ketogenic Endogenous versus Exogenous Therapies for myoCaRdial glucOse SuppresSion) is a crossover, noninferiority trial of the KD (endogenous ketosis) versus ketone ester ([KE] exogenous ketosis) drink. Twenty healthy participants were enrolled into 3 arms: weight-based KE drink, 24-h KD, and 72-h KD (n = 18 completed all arms). The primary outcome was achievement of complete MGS on PET (noninferiority margin 5%). The area under receiver-operating-characteristics (AUROC) of endogenous BHB levels (analyzed in a laboratory and by point-of-care device) for predicting MGS was analyzed in 37 scans completed on the KD. Results: The mean age was 30 ± 7 y, 50% were women, and 45% were nonwhite. The median achieved BHB levels (mmol/L) were 3.82 (25th-75th percentile, 2.55-4.97) (KE drink), 0.77 (25th-75th percentile, 0.58-1.02) (25th-75th percentile, 24-h KD), and 1.30 (25th-75th percentile, 0.80-2.24) (72-h KD). The primary outcome was achieved in 44% (KE drink), 78% (24-h KD), and 83% (72-h KD) of participants (noninferiority P = 0.97 and 0.98 for KE vs. 24-h and 72-h KD). Endogenous BHB levels robustly predicted MGS (AUROC, 0.88; 95% CI 0.71, 1.00). A BHB of 0.58 or more correctly classified 92% of scans. A point-of-care device provided comparable predictive value. Conclusion: In healthy volunteers, KE was inferior to KD for achieving MGS. Serum BHB is a highly predictive biomarker for MGS and can be clinically implemented upstream of 18F-FDG PET, with rapid facilitation by point-of-care testing, to reduce false-positive scans.

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Published In

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

DOI

EISSN

1535-5667

ISSN

0161-5505

Publication Date

May 2022

Volume

63

Issue

5

Start / End Page

770 / 776

Related Subject Headings

  • Young Adult
  • Nuclear Medicine & Medical Imaging
  • Male
  • Ketosis
  • Ketones
  • Humans
  • Glucose
  • Fluorodeoxyglucose F18
  • Female
  • Dietary Carbohydrates
 

Citation

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Selvaraj, S., Margulies, K. B., Dugyala, S., Schubert, E., Tierney, A., Arany, Z., … Bravo, P. E. (2022). Comparison of Exogenous Ketone Administration Versus Dietary Carbohydrate Restriction on Myocardial Glucose Suppression: A Crossover Clinical Trial. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 63(5), 770–776. https://doi.org/10.2967/jnumed.121.262734
Selvaraj, Senthil, Kenneth B. Margulies, Supritha Dugyala, Erin Schubert, Ann Tierney, Zoltan Arany, Daniel A. Pryma, et al. “Comparison of Exogenous Ketone Administration Versus Dietary Carbohydrate Restriction on Myocardial Glucose Suppression: A Crossover Clinical Trial.Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine 63, no. 5 (May 2022): 770–76. https://doi.org/10.2967/jnumed.121.262734.
Selvaraj S, Margulies KB, Dugyala S, Schubert E, Tierney A, Arany Z, et al. Comparison of Exogenous Ketone Administration Versus Dietary Carbohydrate Restriction on Myocardial Glucose Suppression: A Crossover Clinical Trial. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2022 May;63(5):770–6.
Selvaraj, Senthil, et al. “Comparison of Exogenous Ketone Administration Versus Dietary Carbohydrate Restriction on Myocardial Glucose Suppression: A Crossover Clinical Trial.Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, vol. 63, no. 5, May 2022, pp. 770–76. Epmc, doi:10.2967/jnumed.121.262734.
Selvaraj S, Margulies KB, Dugyala S, Schubert E, Tierney A, Arany Z, Pryma DA, Shah SH, Rame JE, Kelly DP, Bravo PE. Comparison of Exogenous Ketone Administration Versus Dietary Carbohydrate Restriction on Myocardial Glucose Suppression: A Crossover Clinical Trial. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2022 May;63(5):770–776.

Published In

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

DOI

EISSN

1535-5667

ISSN

0161-5505

Publication Date

May 2022

Volume

63

Issue

5

Start / End Page

770 / 776

Related Subject Headings

  • Young Adult
  • Nuclear Medicine & Medical Imaging
  • Male
  • Ketosis
  • Ketones
  • Humans
  • Glucose
  • Fluorodeoxyglucose F18
  • Female
  • Dietary Carbohydrates