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No evidence for brown adipose tissue activation after creatine supplementation in adult vegetarians

Abstract

Creatine availability in adipose tissue has been shown to have profound effects on thermogenesis and energy balance in mice. However, whether dietary creatine supplementation affects brown adipose tissue (BAT) activation in humans is unclear. In the present study, we report the results of a double-blind, randomized, placebo-controlled, cross-over trial (NCT04086381) in which 14 young, healthy, vegetarian adults, who are characterized by low creatine levels, received 20 g of creatine monohydrate per day or placebo. Participants were eligible if they met the following criteria: male or female, white, aged 18–30 years, consuming a vegetarian diet (≥6 months) and body mass index 20–25 kg m−2. BAT activation after acute cold exposure was determined by calculating standard uptake values (SUVs) acquired by [18F]fluorodeoxyglucose positron emission tomography–magnetic resonance imaging. BAT volume (−31.32 (19.32) SUV (95% confidence interval (CI) −73.06, 10.42; P = 0.129)), SUVmean (−0.34 (0.29) SUV (95% CI −0.97, 0.28; P = 0.254)) and SUVmax (−2.49 (2.64) SUV (95% CI −8.20, 3.21; P = 0.362)) following acute cold exposure were similar between placebo and creatine supplementation. No side effects of creatine supplementation were reported; one participant experienced bowel complaints during placebo, which resolved without intervention. Our data show that creatine monohydrate supplementation in young, healthy, lean, vegetarian adults does not enhance BAT activation after acute cold exposure.

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Fig. 1: Study overview.
Fig. 2: Three examples of BAT activation after acute cold exposure acquired through 18FDG PET–MRI.
Fig. 3: BAT activation.
Fig. 4: EE and substrate oxidation before and after the ingestion of a high-energy, carbohydrate-rich meal.
Fig. 5: Blood metabolites before and after the ingestion of a high-energy, carbohydrate-rich meal.

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Data availability

All other data, the MATLAB scripts to generate the data and other findings of this study are available from the corresponding author upon reasonable request. Source data are provided with this paper.

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Acknowledgements

We acknowledge the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014-02 ENERGISE). V.B.S.-H. is a recipient of an ERC starting grant (no. 759161 ‘MRS in diabetes’).

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N.J.C., W.D.v.M.-L., B.H., J.H., B.M.S., L.K. and P.S. designed the research. N.J.C., D.D. and C.A. performed the research. N.J.C., D.D., C.A., E.K.-M., Y.B., V.B.S.-H., T.v.d.W., W.D.v.M.-L., B.H., J.H. and P.S. analysed samples and data. N.J.C., J.H. and P.S. wrote the manuscript and all authors critically reviewed it. P.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the version to be published.

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Correspondence to Patrick Schrauwen.

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Peer review information Nature Metabolism thanks Kong Y. Chen, Jill Haszard and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. The primary handling editor was Christoph Schmitt.

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Extended Data Fig. 1 Flow Diagram of Study.

Flow diagram of study participants.

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Connell, N.J., Doligkeit, D., Andriessen, C. et al. No evidence for brown adipose tissue activation after creatine supplementation in adult vegetarians. Nat Metab 3, 107–117 (2021). https://doi.org/10.1038/s42255-020-00332-0

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