Exposure to common chemicals, particularly a combination of multiple chemicals, was associated with an increased risk of multiple sclerosis (MS).

Investigators found that exposure to certain polyfluoroalkyl substances (PFAS) and hydroxylated polychlorinated biphenyls (OH-PCBs), chemicals widely used in industrial applications and consumer products, was associated with roughly a twofold increased risk of the disease.

“We saw that several individual substances, such as PFOS [perfluorooctane sulfonic acid] and two hydroxylated PCBs, were linked to an increased odds for MS. People with the highest concentrations of PFOS and PCBs had approximately twice as high odds of being diagnosed with MS, compared with those with the lowest concentrations,” lead investigator Kim Kultima, PhD, Department of Medical Sciences, Uppsala University, Sweden, said in a release.

The study was published online December 17 in Environment International.

Forever Chemicals 

MS is a chronic autoimmune disease affecting the central nervous system. Its onset is influenced by a complex interplay of environmental and genetic factors, with the human leukocyte antigen (HLA) complex carrying the highest genetic susceptibility.

Evidence points to a rise in the prevalence and incidence of autoimmune diseases such as MS, with endocrine-disrupting chemicals (EDCs) emerging as potential risk factors. Both PFAS and PCBs are classified as EDCs — synthetic chemicals that can interfere with hormonal and immune signaling.

Also known as “forever chemicals,” PFAS are widely used for their resistance to heat, water, and grease in products such as nonstick cookware, stain-resistant fabrics, food packaging, and firefighting foams. 

PCBs, which were banned in many countries decades ago, were historically used as insulating and cooling agents in electrical equipment and building materials. However, they are still present in the environment and food chain decades later. 

Research has linked PFAS and PCBs to dietary exposure, particularly through drinking water and fish consumption.

The investigators note that previous research has linked PFAS and PCB exposure to a range of immune-related and inflammatory conditions. However, evidence specifically examining their role in MS has been limited and inconsistent, with few large population-based studies and little attention to combined chemical exposure.

To examine the influence of chemical environmental exposure on the development of MS, the investigators analyzed blood from 1800 individuals who had recently been diagnosed with MS to investigate concentrations of these common environmental contaminants.

The study included 907 individuals with MS from the Swedish population-based Epidemiological Investigations of Multiple Sclerosis cohort and 907 randomly selected controls, matched for age (approximately 40 years), sex (about 75% female), and residential area.

Two-Fold Increased Risk 

Participants completed questionnaires detailing environmental exposures and lifestyle factors. Researchers analyzed serum samples for 24 PFAS compounds and seven HO-PCBs, selected for their environmental relevance, commercial use, and detectability using liquid chromatography-mass spectrometry.

After adjusting for age, sex, BMI, lifestyle factors, and established HLA-associated risk and protective variants, a doubling of serum 4-OH-CB187 concentrations was associated with an 8.5% increase in the odds of MS (odds ratio [OR], 1.085; 95% CI, 1.01-1.168; P = .026). 

Exposure to 3-OH-CB153 was associated with an 8.1% increase in MS odds (OR, 1.081; 95% CI, 1.029-1.137; P = 2.26×10^–3), while exposure to PFOS — a common PFAS — was associated with a 10.3% increase (OR, 1.103; 95% CI, 1.007-1.211; P = .037).

When exposure was analyzed by concentration quartiles, higher levels of PFOS, 4-OH-CB187, and 3-OH-CB153 were associated with increased odds of MS. Participants in the highest exposure quartile of 4-OH-CB187 had more than double the odds of MS compared with those in the lowest quartile (OR, 2.31; 95% CI, 1.49-3.59).

Additional analyses showed significant interaction with the HLA allele B*44:02. Although this allele is typically considered protective, each increase in PFOS exposure quartile among carriers was associated with more than a fourfold increase in MS risk.

“This indicated that there is a complex interaction between inheritance and environmental exposure linked to the odds of MS,” Kultima noted.

“We therefore think it is important to understand how environmental contaminants interact with hereditary factors, as this can provide new knowledge about the genesis of MS and could also be relevant for other diseases.”

Unclear Mechanisms 

Although the mechanisms linking these chemicals to MS risk remain unclear, both PFAS and HO-PCBs have been shown to disrupt the blood-brain barrier, potentially facilitating the entry of peripheral immune cells into the central nervous system. In addition, PFAS are thought to modulate immune function by influencing cytokine signaling, redox balance, and antigen-processing pathways. 

The observed mixture effect may reflect the simultaneous amplification of shared biological pathways, the authors wrote, noting that PFAS and HO-PCBs could contribute to MS risk through overlapping effects on immune regulation and neuroinflammation.

The investigators also outlined several study limitations. Exposure was assessed using a single serum sample collected after MS diagnosis, which they said raises the possibility of reverse causality and limits the ability to characterize long-term exposure.

They also noted that because MS likely begins years before clinical symptoms appear, measured exposures may capture only part of a more complex and prolonged disease process. 

The investigators also cautioned that because it was a case-control study, causality cannot be established. They further noted that the predominantly Swedish study population may limit the generalizability of the findings, and that analyses of interactions between chemical exposures and HLA alleles were constrained by limited statistical power, in part because HLA data were missing for about 20% of participants.

The study received support from: the Swedish Research Council, Swedish Society for Medical Research, Marianne and Marcus Wallenberg Foundation, NEURO Sweden, Region Uppsala, FORMAS Sweden, Åke Wiberg foundation, Forte Sweden, Swedish Foundation for MS Research, SciLifeLab & Wallenberg Data Driven Life Science Program, Knut and Alice Wallenberg Foundation, and the National Bioinformatics Infrastructure Sweden (NBIS) at SciLifeLab. 

Relevant financial disclosures can be found in the original study.