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Circulating Levels of Muscle-Related Metabolites Increase in Response to a Daily Moderately High Dose of a Vitamin D3 Supplement in Women with Vitamin D Insufficiency—Secondary Analysis of a Randomized Placebo-Controlled Trial

1
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark
2
Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark
3
Department of Food Science, Aarhus University, Agro Food Park 48, 8200 Aarhus N, Denmark
4
iFOOD, Centre for Innovative Food Research, Aarhus University, 8200 Aarhus N, Denmark
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(5), 1310; https://doi.org/10.3390/nu12051310
Received: 30 March 2020 / Revised: 30 April 2020 / Accepted: 1 May 2020 / Published: 4 May 2020
Recently, we demonstrated negative effects of vitamin D supplementation on muscle strength and physical performance in women with vitamin D insufficiency. The underlying mechanism behind these findings remains unknown. In a secondary analysis of the randomized placebo-controlled trial designed to investigate cardiovascular and musculoskeletal health, we employed NMR-based metabolomics to assess the effect of a daily supplement of vitamin D3 (70 µg) or an identically administered placebo, during wintertime. We assessed the serum metabolome of 76 postmenopausal, otherwise healthy, women with vitamin D (25(OH)D) insufficiency (25(OH)D < 50 nmol/L), with mean levels of 25(OH)D of 33 ± 9 nmol/L. Compared to the placebo, vitamin D3 treatment significantly increased the levels of 25(OH)D (−5 vs. 59 nmol/L, respectively, p < 0.00001) and 1,25(OH)2D (−10 vs. 59 pmol/L, respectively, p < 0.00001), whereas parathyroid hormone (PTH) levels were reduced (0.3 vs. −0.7 pmol/L, respectively, p < 0.00001). Analysis of the serum metabolome revealed a significant increase of carnitine, choline, and urea and a tendency to increase for trimethylamine-N-oxide (TMAO) and urinary excretion of creatinine, without any effect on renal function. The increase in carnitine, choline, creatinine, and urea negatively correlated with muscle health and physical performance. Combined with previous clinical findings reporting negative effects of vitamin D on muscle strength and physical performance, this secondary analysis suggests a direct detrimental effect on skeletal muscle of moderately high daily doses of vitamin D supplements. View Full-Text
Keywords: vitamin D; secondary hyperparathyroidism; skeletal muscle; metabolomics; postmenopausal women vitamin D; secondary hyperparathyroidism; skeletal muscle; metabolomics; postmenopausal women
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MDPI and ACS Style

Bislev, L.S.; Sundekilde, U.K.; Kilic, E.; Dalsgaard, T.K.; Rejnmark, L.; Bertram, H.C. Circulating Levels of Muscle-Related Metabolites Increase in Response to a Daily Moderately High Dose of a Vitamin D3 Supplement in Women with Vitamin D Insufficiency—Secondary Analysis of a Randomized Placebo-Controlled Trial. Nutrients 2020, 12, 1310. https://doi.org/10.3390/nu12051310

AMA Style

Bislev LS, Sundekilde UK, Kilic E, Dalsgaard TK, Rejnmark L, Bertram HC. Circulating Levels of Muscle-Related Metabolites Increase in Response to a Daily Moderately High Dose of a Vitamin D3 Supplement in Women with Vitamin D Insufficiency—Secondary Analysis of a Randomized Placebo-Controlled Trial. Nutrients. 2020; 12(5):1310. https://doi.org/10.3390/nu12051310

Chicago/Turabian Style

Bislev, Lise S., Ulrik K. Sundekilde, Ece Kilic, Trine K. Dalsgaard, Lars Rejnmark, and Hanne C. Bertram 2020. "Circulating Levels of Muscle-Related Metabolites Increase in Response to a Daily Moderately High Dose of a Vitamin D3 Supplement in Women with Vitamin D Insufficiency—Secondary Analysis of a Randomized Placebo-Controlled Trial" Nutrients 12, no. 5: 1310. https://doi.org/10.3390/nu12051310

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