Abnormal Serum Iron-Status Indicator Changes in Amyotrophic Lateral Sclerosis (ALS) Patients: A Meta-Analysis

Abstract

Background: In recent years, the role of iron metabolism in amyotrophic lateral sclerosis (ALS) attracts more and more attention, and some studies have focused on the link between abnormal serum iron indicators and ALS. However, there are still big conflicts and inconsistency among different studies. To study the possible relationship between ALS and disturbed iron metabolism, we conducted this meta-analysis to conclude characteristics of abnormal serum iron-status indicator changes in ALS patients. Methods: We searched and screened main databases, including the PubMed, Embase, and Cochrane Library, to find studies related to the association between iron metabolism and ALS. The Revman 5.3 software was used to conduct meta-analysis. Results: Eleven studies were finally included in our analysis, composed of 1,599 ALS patients and 1,255 controls in total. The results showed that the ferritin level was much higher in ALS patients compared with controls (MD = 70.48, 95% CI [51.41, 89.55], p < 0.00001), and the transferrin level was decreased in ALS patients compared with controls (SMD = -0.28, 95% CI [-0.38, -0.18], p < 0.00001), while there was no statistical difference in iron levels (SMD = 0.48, 95% CI [-0.07, 1.03], p = 0.09) between ALS patients and controls. Conclusions: Our research finds unusual changes in several indicators representing iron status, which suggest possible iron metabolism abnormalities in ALS patients. That may provide evidence for the link between iron metabolism and the pathogenesis of ALS.

Keywords: amyotrophic lateral sclerosis; ferritin; iron; iron metabolism; transferrin.

Figure 1

Specific process of research selection.

Figure 2

The result showed that ferritin was higher in ALS patients, no matter in the male subgroup (MD = 54.94, 95% CI [41.21, 68.67], p < 0.00001) or female subgroup (MD = 50.23, 95% CI [38.59, 61.86], p < 0.00001). The result in total showed the same result (MD = 70.48, 95% CI [51.41, 89.55], p < 0.00001).

Figure 3

The result showed that there was no statistical difference of iron level both in the male subgroup (SMD = 0.06, 95% CI [−0.09, 0.20], p = 0.43) and in the female subgroup (SMD = −0.05, 95% CI [−0.12, 0.22], p = 0.56). The result in the total sample group showed the same (SMD = 0.48, 95% CI [−0.07, 1.03], p = 0.09).

Figure 4

The result showed in the male subgroup (SMD = −0.28, 95% CI [−0.43, −0.13], p = 0.0002) and female subgroup (SMD = −0.34, 95% CI [−0.52, −0.16], p = 0.0002) that the transferrin level was lower in ALS patients, and the results in total showed the same (SMD = −0.28, 95% CI [−0.38, −0.18], p < 0.00001).

Figure 5

Publication bias assessment of the studies included iron level as one indicator. SE, standard error.

Figure 6

Publication bias assessment of the studies included transferrin level as one indicator.

Figure 7

Publication bias assessment of the studies included ferritin level as one indicator.