Abstract
Accumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta-analysis. Four indicators, including fasting blood glucose level (weighted mean difference [WMD] = 0.13, 95% CI [0.06–0.21], p = 0.001), serum ferritin level (WMD = 63.42, 95% CI [48.12–78.73], p < 0.001), transferrin saturation coefficient level (WMD = 2.79, 95% CI [1.52–4.05], p < 0.001), and creatine kinase level (WMD = 80.29, 95% CI [32.90–127.67], p < 0.001), were significantly higher in the ALS patients, whereas the total iron-binding capacity (WMD = − 2.42, 95% CI [− 3.93, − 0.90], p = 0.002) was significantly lower in ALS patients than in the control subjects. In contrast, the other 12 candidates did not show significant differences between ALS patients and controls. Moreover, pooled hazard ratios (HR) showed significantly reduced survival (HR = 1.38, 95% CI [1.02–1.88], p = 0.039) of ALS patients with elevated serum ferritin levels. These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS. In addition, the serum ferritin level is negatively associated with the overall survival of ALS patients.
Highlights
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive paralytic disease characterized by degeneration of upper and lower motor neurons, which occurs following insidious focal weakness and spreads to most skeletal muscles, including the diaphragm [1, 2]
The serum transferrin level was significantly lower in ALS patients than in healthy controls (WMD = − 0.13, 95% confidence interval (CI) [− 0.17, − 0.08], p < 0.001) but not significantly different from that in patients with other neurological disorders (ONDs) (WMD = 0.81, 95% CI [− 1.34, 2.96], p = 0.46) (Fig. 3a)
Sensitivity analysis indicated that the findings on fasting blood glucose (FBG), ferritin, total ironbinding capacity (TIBC), transferrin saturation coefficient (TSC) and creatine kinase (CK) in the ALS patients would not be affected by any single study included, suggesting the robustness of these results
Summary
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive paralytic disease characterized by degeneration of upper and lower motor neurons, which occurs following insidious focal weakness and spreads to most skeletal muscles, including the diaphragm [1, 2]. Accumulating evidence has suggested that some indicators associated with energy homeostasis, including glucose [6,7,8], lipid [9,10,11] and protein levels [12,13,14], are aberrant in ALS patients. Abnormal iron metabolism [15,16,17] and creatinine kinase [18,19,20] have been reported in ALS patients. These studies have not reached a consensus; a systematic meta-analysis is needed to clarify the changes in biochemical indicators in ALS and make a better prognosis
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