Study IDs environmental factors tied globally to higher NMOSD risk
Knowing modifiable links could help prevent disease, improve outcomes
Low vitamin D levels, certain infections, and specific dietary habits may increase the risk of developing neuromyelitis optica spectrum disorder (NMOSD).
That’s according to the findings of a systematic review that analyzed data from 50 studies involving more than 21,000 people worldwide.
Certain modifiable factors, such as diets high in sugars and carbohydrates and low in protein, were associated with a greater likelihood of disease, the researchers found. Exposure to a bacterium primarily associated with intestinal inflammation, called mycobacterium avium subspecies paratuberculosis, was also consistently linked to the onset of NMOSD.
Vitamin D deficiency also was tied to higher NMOSD risk — though this was most notably a factor among Asian populations, the data showed.
Meanwhile, smoking appeared to have opposite effects across regions: Having a history of smoking was linked to lower risk in Western populations, but passive smoking was associated with higher susceptibility in Iraq.
“Knowledge of modifiable risk factors for NMOSD may be beneficial in preventing and improving disease outcomes,” the researchers wrote.
The study, “Environmental risk factors of neuromyelitis optica spectrum disorder: a systematic review,” was published in the journal Therapeutic Advances in Neurological Disorders.
A progressive autoimmune disorder, NMOSD is marked by episodes of inflammation that primarily affect the spinal cord and optic nerve, the nerve responsible for sending visual signals between the eye and the brain.
Previous studies of environmental risk factors showed conflicting results
Over the years, researchers have speculated that environmental influences, such as infections, vitamin D levels, and even diet, might contribute to the onset of NMOSD. But previous studies have yielded conflicting results, leaving the impact of these factors uncertain.
Identifying such factors “is crucial for a deeper understanding of this disease, which in turn aids in establishing prevention strategies, assessing disease risk, and enhancing clinical efficacy,” the researchers wrote.
To learn more, and to clarify the discrepancies previously found, researchers from Tehran University of Medical Sciences in Iran and the University of Southern Denmark systematically analyzed published studies from 1999 through May 2024. The work had explored factors potentially linked to NMOSD onset.
A total of 50 studies involving 21,410 people with NMOSD were used in the team’s review. Altogether, 80% of the participants — 17,080 in total — were women. The patients’ mean ages ranged from 35.8 to 58.1.
[Identifying NMOSD risk factors] is crucial for a deeper understanding of this disease, which in turn aids in establishing prevention strategies, assessing disease risk, and enhancing clinical efficacy.
About 37% of the studies were conducted in East Asia, primarily in China, Japan, and Korea, and focused largely on the effects of infections and vitamin D deficiency. Another 31% came from Asian countries outside East Asia, most notably from Iran (62%). That research covered a much broader array of environmental factors, including the impact of diet, smoking, hormonal factors, socioeconomic status, month of birth, sun exposure, and physical activity.
Approximately one-quarter of the studies came from Western countries with predominantly Caucasian populations. Those studies mainly examined the role of smoking and infections.
Altogether, the findings “indicate an environmental involvement in the onset of NMOSD,” the researchers wrote, noting that “environmental factors with seasonal variation influence the development of neurological conditions related to NMOSD.”
The studies showed a “spring-summer predominance in NMOSD onset,” which the researchers noted “might be related to a higher prevalence of viruses … and lower vitamin D levels during winter.”
Lack of vitamin D linked to disease susceptibility, especially in Asian nations
Vitamin D deficiency was among the most consistently reported risk factors. Across several studies in Asia, individuals with NMOSD had significantly lower blood vitamin D levels than healthy people who served as controls, pointing to a potential link between low vitamin D and disease susceptibility.
Infectious agents also appeared to play a role. Antibodies against bacteria subspecies paratuberculosis were detected more commonly among people with NMOSD than healthy individuals, suggesting that prior exposure to this organism may contribute to triggering the disease.
Dietary habits were another major factor. Diets high in carbohydrates and sugars and low in protein and fat were linked to a higher risk of NMOSD, while greater intake of whole grains, legumes, fruits, and vegetables had the opposite effect. Each additional 10 grams of daily sugar intake increased the odds of NMOSD by 72%, data from one study showed.
Smoking habits showed opposite trends across regions. In Western populations, smoking was associated with up to a 50% lower risk of NMOSD, whereas in Iran, passive smoking exposure was linked to a significantly higher susceptibility to the disease. One study found that passive smokers had about a 1.8 times higher likelihood of developing NMOSD, while those exposed for more than 20 years faced nearly a 2.5 times higher risk compared with nonsmokers.
A few individual studies also pointed to other potential influences. Low sunlight exposure during adolescence was linked to a nearly 18 times higher risk of developing NMOSD, whereas in adulthood, both low and moderate exposure were tied to a higher chance of disease development.
People who reported low or moderate levels of exercise during adolescence were as many as 16 times more likely to develop NMOSD than those who were more active, data showed. Those findings suggest that regular physical activity may have a protective effect.
A nearly twofold increase was seen among women using oral contraceptives, while breastfeeding appeared to lower disease risk by nearly 60%. Social and economic stressors — including divorce, unemployment, and loss of stable housing — were also associated with greater disease risk.
While “further studies are required to elucidate the findings presented in this review,” the researchers concluded that identifying triggers may help improve prevention strategies and clinical outcomes for people with NMOSD.
About the Author
