To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.

The effect of a “normal” ( n = 8) and “high” ( n = 6) protein intake (1 and 2.5 g ⋅ kg⁻¹⋅ day⁻¹, respectively) and of exercise on plasma amino acid (AA) concentrations, insulin, and glucagon concentrations was followed throughout a continuous 24-h period in adult male subjects at energy balance after six days on a standardized diet and exercise program. Subjects were fasting from 2100 on day 6 to 1200 on day 7 and then fed 10 identical meals hourly until 2100. Physical exercise was performed (46% maximal oxygen uptake) between 0830 and 1000 (fasting) and in a fed state (1600–1730) on each day. The normal-protein group showed fasting plasma AA concentrations that were higher ( P < 0.05) than those for the high-protein group, except for leucine, methionine, and tyrosine. Glutamine, glycine, alanine, taurine, and threonine concentrations were distinctly higher (∼30% or greater) throughout the 24-h period in subjects consuming the normal- vs. the high-protein diets. Exercise appeared to increase, although not profoundly, the plasma concentrations of amino acids except for glutamate, histidine, ornithine, and tryptophan. The profound diet-related differences in plasma AA concentrations are only partially explained by differences in the renal clearance of the amino acids. We speculate on the possible metabolic basis for these findings.

The present work investigated serum vitamin D (25(OH)D) status in relation to bone and muscle qualities and functions in 19 female soccer players (13–16 years) resident at northern latitude with very low sun exposure (∼32–36 h/month) during winter season (late January to early March). Serum 25(OH)D, parathyroid hormone and bone turnover markers osteocalcin (OC) and beta carboxy‐terminal collagen cross‐links (β‐Ctx), as well as body composition and muscle performance were examined. Hormones were tested using routine laboratory methods. Fat mass, lean mass, and bone mineral density in whole body, as well as femur and lumbar spine were evaluated with dual‐energy X‐ray absorptiometry. Muscle performance was assessed through isokinetic knee extension and flexion, countermovement jump, and sprint running. 25(OH)D was low (50.5 ± 12.8 nmol l⁻¹), whereas the values of bone turnover markers were markedly high (OC: 59.4 ± 18.6 µg l⁻¹; β‐Ctx: 1075 ± 408 ng l⁻¹). All bone and muscle measurements were normal or above normal. 25(OH)D was not significantly correlated with most of the parameters of bone and muscle quality or function, except the knee extension time to peak torque (r = −0.50, p = .03). In conclusion, the level of vitamin D is markedly low in adolescent female soccer players during the winter in Sweden. However, vitamin D levels did not significantly correlate with measures of bone and muscle except a moderate correlation in time to peak torque in the knee extensors. The practical implication of low vitamin D levels in young growing female athletes remains unclear.