California Pacific Medical Center, Research Institute, San Francisco, California, USA.
Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland.
J Gerontol A Biol Sci Med Sci. 2024 Feb 1;79(2). doi: 10.1093/gerona/glad217.
The relationship between amino acids, B vitamins, and their metabolites with D3-creatine (D3Cr) dilution muscle mass, a more direct measure of skeletal muscle mass, has not been investigated. We aimed to assess associations of plasma metabolites with D3Cr muscle mass, as well as muscle strength and physical performance in older men from the Osteoporotic Fractures in Men cohort study.
Out of 1 425 men (84.2 ± 4.1 years), men with the lowest D3Cr muscle mass (n = 100), slowest walking speed (n = 100), lowest grip strength (n = 100), and a random sample (n = 200) serving as a comparison group to the low groups were included. Metabolites were analyzed using liquid chromatography-tandem mass spectrometry. Metabolite differences between the low groups and random sample and their relationships with the muscle outcomes adjusted for confounders and multiple comparisons were assessed using t-test/Mann-Whitney-Wilcoxon and partial correlations, respectively.
For D3Cr muscle mass, significant biomarkers (p < .001) with ≥10% fold difference and largest partial correlations were tryptophan (Trp; r = 0.31), kynurenine (Kyn)/Trp; r = -0.27), nicotinamide (Nam)/quinolinic acid (Quin; r = 0.21), and alpha-hydroxy-5-methyl-tetrahydrofolate (hm-THF; r = -0.25). For walking speed, hm-THF, Nam/Quin, and Quin had the largest significance and fold difference, whereas valine (r = 0.17), Trp (r = 0.17), HKyn/Xant (r = -0.20), neopterin (r = -0.17), 5-methyl-THF (r = -0.20), methylated folate (r = -0.21), and thiamine (r = -0.18) had the strongest correlations. Only hm-THF was correlated with grip strength (r = -0.21) and differed between the low group and the random sample.
Future interventions focusing on how the Trp metabolic pathway or hm-THF influences D3Cr muscle mass and physical performance declines in older adults are warranted.
氨基酸、B 族维生素及其代谢物与 D3-肌酸（D3Cr）稀释肌肉量的关系，D3Cr 稀释肌肉量是肌肉质量的更直接测量指标，尚未得到研究。我们旨在评估血浆代谢物与 D3Cr 肌肉量以及肌肉力量和身体表现的关系，这些研究对象来自男性骨质疏松性骨折队列研究。
在 1425 名男性（84.2±4.1 岁）中，纳入肌肉量最低的 100 名男性、行走速度最慢的 100 名男性、握力最低的 100 名男性以及作为与低分组比较的随机样本（n=200）。使用液相色谱-串联质谱法分析代谢物。使用 t 检验/曼-惠特尼-威尔科克森检验比较低分组与随机样本的代谢物差异，并使用偏相关分析评估这些差异与肌肉结局之间的关系，这些分析均在调整混杂因素和多重比较后进行。
对于 D3Cr 肌肉量，差异有统计学意义（p<0.001）且 fold difference≥10%的显著生物标志物（r≥0.21）包括色氨酸（Trp）、犬尿氨酸（Kyn）/Trp、烟酰胺（Nam）/喹啉酸（Quin）和 alpha-羟基-5-甲基四氢叶酸（hm-THF）。对于行走速度，hm-THF、Nam/Quin 和 Quin 具有最大的意义和 fold difference，而缬氨酸（r=0.17）、Trp（r=0.17）、HKyn/Xant（r=-0.20）、新蝶呤（r=-0.17）、5-甲基-THF（r=-0.20）、甲基化叶酸（r=-0.21）和硫胺素（r=-0.18）与行走速度相关性最强。仅 hm-THF 与握力（r=-0.21）相关，且在低分组和随机样本中存在差异。
需要进一步研究针对色氨酸代谢途径或 hm-THF 如何影响老年人 D3Cr 肌肉量和身体机能下降的干预措施。
