Association of blood lipids with onset and prognosis of amyotrophic lateral sclerosis: results from the ALS Swabia registry

Abstract

Background To date, the role of blood lipid levels and their association with the onset and prognosis of ALS is controversial. We explored these associations in a large, population-based case–control study. Methods Between October 2010 and June 2014, 336 ALS patients (mean age 65.7 ± 10.7; 57.7% male) and 487 sex- and age-matched controls from the same geographic region were recruited within the ALS registry in Southwest Germany. Triglycerides and cholesterol (high-density lipoprotein (HDL), low-density lipoprotein (LDL), total) were measured. The ALS cohort was followed up for vital status. Conditional logistic regression models were applied to calculate odds ratio (OR) for risk of ALS associated with serum lipid concentrations. In ALS patients only, survival models were used to appraise the prognostic value. Results High concentration of total cholesterol (OR 1.60, 95% confidence interval (CI) 1.03–2.49, top vs. bottom quartile), but not HDL, LDL, LDL–HDL ratio, or triglycerides, was positively associated with the risk of ALS. During the median follow-up time of 88.9 months, 291 deaths occurred among 336 ALS patients. In the adjusted survival analysis, higher HDL (HR 1.72, 95% CI 1.19–2.50) and LDL cholesterol levels (HR 1.58, 95% CI 1.11–2.26) were associated with higher mortality in ALS patients. In contrast, higher triglyceride levels were associated with lower mortality (HR 0.68, 95% CI 0.48–0.96). Conclusion The results highlight the importance to distinguish cholesterol from triglycerides when considering the prognostic role of lipid metabolism in ALS. It further strengthens the rationale for a triglyceride-rich diet, while the negative impact of cholesterol must be further explored.

Trimetazidine Improves Mitochondrial Dysfunction in SOD1G93A Cellular Models of Amyotrophic Lateral Sclerosis through Autophagy Activation

“…Since we were unable to evaluate Complex IV activity using Seahorse technology, we performed a spectrophotometric analysis of the functional activity of Complex IV in both PSCs and PCCs and did not detect any specific damage in this complex, in accordance with Scaricamazza et al, 2020 (Figure S2a,b) [14]. Moreover, we previously observed the failure of mitochondrial activity of Complex I and Complexes II/III in isolated mitochondria from spinal cord and skeletal muscles of SOD1 G93A mice, and we showed that chronic administration of TMZ restores these dysfunctions [16]. In this study, we observed that TMZ treatment has a comparable impact on both PSCs and PCCs, restoring the diminished activity of Complex I and Complexes II/III (Figure 3a,b).…”

Abnormal energy metabolism in ALS: a key player?

“…Third, a large population-based case-control study showed that higher cholesterol levels, but not HDL-c or LDL-c, were positively associated with the ALS risk. Furthermore, higher HDL-c and LDL-c levels were associated with higher mortality in ALS patients in the adjusted survival analysis [38]. High HDL-c levels were linked with either an increased [33,39,40] or a decreased [41] risk of ALS.…”

“…However, the beneficial effect was no longer significant when adjusted for BMI, indicating that higher triglycerides may be partially explained by the association with higher BMI [38].…”

“…Concerning triglycerides, the results are more consistent. Hypertriglyceridemia was found in ALS patients and was associated with prolonged survival [29,38,42]. However, the beneficial effect was no longer significant when adjusted for BMI, indicating that higher triglycerides may be partially explained by the association with higher BMI [38].…”

“…Concerning triglycerides, the results are more consistent. Hypertriglyceridemia was found in ALS patients and was associated with prolonged survival [29,38,42].…”