Higher, Possibly Damaging, Zinc Levels Seen in Blood of MS Patients

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by Vanda Pinto, PhD |

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People with multiple sclerosis (MS) have significantly higher and potentially damaging blood levels of zinc and a greater activity of the superoxide dismutase (SOD) enzyme than is evident in people without MS or similar diseases, a study reported.

SOD is an enzyme that requires zinc to function properly, including in protecting cells from a form of cellular damage called oxidative stress. In line with its protective role, the study also found that patients with higher levels of SOD activity were less likely to experience disease relapses.

The study, “Relationship between zinc-related nutritional status and the progression of multiple sclerosis,” was published in the journal Multiple Sclerosis and Related Disorders.

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Inflammation progressively damages and destroys the myelin sheath — a protective coating around nerve fibers that speeds the transmission of electrical signals — in MS, causing various disease symptoms.

Zinc levels best when in equilibrium

Previous studies have indicated that abnormal zinc levels can affect the nervous and immune systems. Zinc, “an abundant trace element in the brain,” has essential functions that include acting as a cofactor — a compound that facilitates biochemical reactions — and as a component of myelin proteins, the researchers noted.

While zinc deficiency causes brain cells to die, high levels can also be neurotoxic. Obtaining an equilibrium, or homeostasis, may be essential to improving clinical outcomes in people with MS.

A research team in Brazil aimed to assess zinc status and determine its association with MS severity. They examined blood samples collected from 49 MS patients followed at a neurology outpatient clinic in Ceara and from an equal number of controls, matched by age and sex and all without a neurological or autoimmune disease.

Most participants were women (85.7%) with a mean age of 37. Among patients, 44 had relapsing-remitting disease (RRMS), two had primary progressive MS (PPMS), and three had secondary progressive MS (SPMS). Their mean disease duration was six years, and the mean number of flares was 1.4.

Most patients (57.1%) had no functional disability according to Expanded Disability Status Scale (EDSS) scores, 30.6% had minimal or moderate disability marked by no difficulties in ambulation, and 12.3% had a moderate degree of disability, with some trouble walking and difficulty in their daily activities.

In the lab, researchers separated red blood cells (erythrocytes) from plasma, or the liquid portion of blood, and determined the mean levels of zinc in these two components.

Plasma zinc concentrations were higher in the MS group compared with the controls (94 micrograms per deciliter or mcg/dl vs. 81.5 mcg/dl) but still within the normal reference range (70-110 mcg/dl).

Mean erythrocyte zinc concentration and SOD activity were both elevated in MS patients and controls compared with the normal reference range. However, only SOD levels were higher in patients relative to controls, while mean erythrocyte zinc levels were similar between the two groups, the researchers reported.

SODs are known to protect cells from oxidative stress, which is a form of cellular damage caused by toxic reactive oxygen species (ROS). The myelin sheath is highly vulnerable to this type of damage.

“Increased antioxidant enzyme production in inflammatory MS lesions may reflect an adaptive, endogenous, compensatory defense mechanism to reduce cellular damage caused by reactive oxygen species (ROS). However, this increase may be insufficient to counteract ROS-induced cellular damage,” the team wrote.

Statistical analyses also revealed an association between erythrocyte zinc levels and SOD activity, with higher zinc levels in red blood cells predicting greater enzyme activity. Researchers also verified a strong negative correlation between SOD activity and the number of relapses, meaning that people with greater SOD activity had fewer disease exacerbations.

“Erythrocyte zinc correlates positively with SOD activity in MS group, which, in response, reduces its activity in the presence of flare-ups and consequent decompensation of the disease,” they wrote.

As a study limitation, the scientists noted that the design did not allow the determination of the relationship between zinc status and MS severity.

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