Some metals could directly influence the pathogenesis of multiple sclerosis (MS), according to a study published in the Journal of Proteome.

“However, the rapid progression of primary progressive MS from the onset may be driven by a combination of neurotoxicity induced by heavy metals coupled with diminished CNS antioxidative capacity associated with differential intrathecal ascorbate retention and imbalance of Mg and Cu,” the authors wrote.

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This observational study included a total of 40 patients previously diagnosed with MS, of whom the majority (n=22) had secondary progressive MS, and the remaining 18 had primary progressive MS. Moreover, 13 healthy individuals constituted the control group. The researchers took the serum and cerebrospinal fluid (CSF) samples to analyze and compare the concentration of low molecular weight metabolites, lipoproteins, glycoproteins, inflammatory markers, and metal elements.

Overall, patients with secondary progressive MS showcased higher concentrations of metabolites than those with primary progressive MS and controls. However, the primary progressive group had higher levels of neuroinflammation and neurodegeneration biomarkers, as well as metal elements, including lead, than the other 2 groups.

“These observations suggest that while secondary progressive MS is a metabolically active disease that progresses gradually over a longer period of time, the pathological insults induced in primary progressive MS are rather more intense at the beginning, causing severe disability within a relatively short period,” the authors explained. 

This phenomenon could be due to an exhaustion of the defense mechanisms against oxidative stress. For example, while a heavy metal with known neurotoxic activity, such as lead, was increased in the CSF of individuals with primary progressive MS, levels of magnesium and copper were diminished.

Although somewhat ambiguous, copper’s effects on the neurologic system are most likely protective, especially against oxidative stress. Likewise, magnesium keeps the cell membrane stable and has antioxidant activity inside the cell.

Considering the leading role of oxidative stress on the pathophysiology of MS, antioxidant drugs or supplements, such as vitamin C, vitamin D, and magnesium, could have beneficial effects on these patients.


Kwadzo P, Eichau S, Amigó N, et al. Multifaceted analysis of cerebrospinal fluid and serum from progressive multiple sclerosis patients: potential role of vitamin C and metal ion imbalance in the divergence of primary progressive multiple sclerosis and secondary progressive multiple sclerosis. J Proteome Res. Published online January 31, 2023. doi:10.1021/acs.jproteome.2c00460