A link between fat molecules called ceramides and worsening disease in overweight and obese people with multiple sclerosis appears to exist, a study reports, with its findings suggesting that ceramides prompt the growth of immune cells called monocytes, which in turn spurs disease progression. These results also strengthen the likelihood that lifestyle factors, like diet and weight, can act as disease modifiers, its researchers said. High body mass index has been linked to the risk of developing MS, but for reasons that aren't clear. One idea is that weight-induced differences in lipids (fat molecules) in the blood, because they are involved in several cellular signaling processes, may affect MS and its course in people with higher BMIs. To test this hypothesis, a team led by researchers at the Advanced Science Research Center (ASRC) at The Graduate Center and at the Icahn School of Medicine at Mount Sinai analyzed 54 patients with relapsing-remitting MS (MS), ages 18 to 60, and with normal or high BMIs (27 people in each group). Participants were followed for two years. BMI is a measure of body fat based on height and weight. A normal BMI is defined as one between 18.5 and 24.9, while a person is considered overweight with a BMI of 25–29.9, and obese it is 30 or higher. Researchers took blood samples, and looked for differences between the groups in terms of both immune cells and blood lipid profiles. They then validated their findings in a separate group of 91 RRMS patients. Patients with high BMIs tended to have more monocytes than those with normal BMIs. Monocytes can travel through the blood to tissues where they develop into macrophages, immune cells with various functions that are best known for "eating" invading bacteria. Monocytes can also travel to the brain and damage nerve fibers. Overweight and obese patients also had significantly higher levels of ceramides compared with normal-weight patients, and the researchers wondered if a link might exist between the two. Through a set of experiments in cells, they discovered that ceramides cause epigenetic changes in monocytes; that is, they alter the way their genomes are "read," so they alter gene activity. Specifically, ceramide-treated cells showed a type of epigenetic change called methylation — which generally turns genes "off" — in genes that normally help prevent cells from dividing. Conceptually, these genetic changes serve to unleash monocytes, leading them to grow more (proliferate) than they otherwise might. The researchers also found more methylation on the genomes of monocytes from high-BMI patients than those from low-BMI patients, and they noted that the overweight or obese patients also tended to have greater disease activity, worse disability progression, and more brain lesions on MRI (magnetic resonance imaging) scans on follow-up. Finally, the researchers tested a mouse model of MS, giving one group of mice a standard diet and another a high-fat diet. Mice fed the high-fat diet were found to have greater disease severity, more brain lesions, and more monocytes, confirming the findings seen in MS patients. "This study gives us a much-needed view into the environmental influences that can affect and change the behavior of cells in an individual's body," Kamilah Castro, the study's first author, said in a press release. "Our findings suggest that increased levels of saturated fat as a result of dietary habits are one likely cause of the epigenetic changes that advance MS, which gives us a starting point for a potential intervention." According to the team, the findings support the concept of nutri-epigenomics: that is, the ability of food to alter the way the genetic information is interpreted by each cell, and suggest that "weight management and dietary intervention" might affect MS prognosis. One limitation was the study's small size, its researchers noted. "While we consider our results … very exciting and mechanistic, we acknowledge that the potential consideration of ceramide levels as biomarkers for disease progression in MS would require validation ... using larger cohorts with a longitudinal and/or cross-sectional design," they concluded. "It will also be important to evaluate the effectiveness of dietary intervention (with an emphasis on the reduction of specific classes of saturated fats), as potential modulator of plasma ceramide levels and possibly of disease course in MS patients."
risk factors
Menstruation Onset, Pregnancies and Breastfeeding Habits Don’t Influence MS Risk, Study Suggests
A woman’s age at her first menstruation, or becoming pregnant and breastfeeding does not substantially influence the long-term risk of multiple sclerosis (MS) or the risk of increased disability, a study of a large number of patients with clinically isolated syndrome…
The amount of zinc, iron, and other minerals a person has in his or her diet is not associated with the risk of developing multiple sclerosis (MS), according to a study. The study, “Total intake of different minerals and the risk of multiple sclerosis,” was published…
Body mass index (BMI), but not the age at which people start puberty, could increase the risk of multiple sclerosis (MS), a study suggests. The study, “Effect of age at puberty on risk of multiple sclerosis: A mendelian randomization study,” was published in the journal …
Sex, age, disability level, and current disease-modifying therapy use are linked to how multiple sclerosis (MS) patients weigh the potential benefits and safety risks of treatments, new research from two teams funded by the National Multiple Sclerosis Society shows. These studies shed light on how…
#ACTRIMS2019 – Bacterial Epsilon Toxin Found in MS Patients Triggers MS Disease Features in Rodents
The levels of epsilon toxin are increased in multiple sclerosis (MS) patients, and its presence in laboratory rodents replicated some aspects of disease activity, according to data presented at the 4th Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum. The researchers suggested that the epsilon…
Low income and education levels are linked to a higher risk of physical disability and disease progression in patients with multiple sclerosis (MS), study says. The study with that finding, “Socioeconomic status and disability progression in multiple sclerosis,” was published in the journal Neurology. “This study is the…
Early-life use of antibiotics disrupts gut microbiota in a rat model of multiple sclerosis (MS) and provokes nervous system autoimmunity, ultimately aggravating disease severity, new research shows. Results also indicate early-life antibiotic use may have unfavorable consequences on regulation of the immune system. The research article, “…
People with multiple sclerosis may be twice as likely to develop deep-vein blood clots, a condition known as venous thromboembolism, than healthy people do, a study reports. But data linking the two is limited, and its researchers say further work is needed to understand if MS is directly related to…
“Oh no, not again.” My mind races and time slows as I crumble to the floor. Every downward movement is magnified, and so too is the pain of my twisted left foot and leg. They have become the resting place for my slumping body. My fuzzy and confused mind…
The herbicide linuron, commonly used with other herbicides, insecticides and fungicides to control the growth of grass and weeds, may be an important environmental risk factor in the development of neurological diseases that include multiple sclerosis, researchers suggest. Used in the U.S. and other countries — but recently…
Each Major Risk Factor (Like Genes, Smoking and Obesity) Can Affect Disease Course, Study Finds
Risk factors often associated with multiple sclerosis (MS), such as genetic background, obesity and smoking, contribute independently to the disease’s variability and may be an early influence on progression, a study reported. The retrospective study, “Multiple sclerosis risk factors contribute to onset heterogeneity,” was published in the journal …
The U.S. Food and Drug Administration (FDA) has issued a safety alert, warning about a rare but life-threatening risk of stroke and artery rupture in patients with relapsing forms of multiple sclerosis (MS) being treated with Lemtrada (alemtuzumab). Since Lemtrada’s approval in 2014 to treat relapsing MS, 13…
Diabetes, hypertension, and active smoking correlate with more brain shrinkage in multiple sclerosis (MS) patients, a new study shows. The study, “Assessing the burden of vascular risk factors on brain atrophy in multiple sclerosis: A case- control MRI study” was published in the journal Multiple Sclerosis and Related Disorders.
Researchers at Yale uncovered a way that high-salt diets may trigger inflammation and possibly contribute to the development of autoimmune diseases such as multiple sclerosis (MS). Their study, “Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity,” was recently published in the journal Nature…
Bacteria that reside in human gut may trigger autoimmune reactions by producing human-like proteins that mimic a naturally occurring and crucial cell protein. Researchers at Queen’s University Belfast in Ireland report that patients with autoimmune disorders — such as multiple sclerosis (MS), rheumatoid arthritis, and ulcerative colitis — have…
Children exposed to certain air pollutants in urban areas or some household chemicals are at higher risk of developing multiple sclerosis (MS) during childhood or adolescence, two new research studies suggest. The studies “Urban air quality and associations with pediatric multiple sclerosis” and…
An international consortium studying more than 68,000 people, about half of them multiple sclerosis (MS) patients, found rare genetic variations that account for up to 5 percent of the heritable MS risk, a study reports. The newly discovered mutations were associated with either an increased…
Environmental changes, such as high temperatures and alterations in salt types and concentrations, trigger structural changes to myelin that may increase the risk of multiple sclerosis (MS), according to a new study. The research, “Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions,” was…
High vitamin D levels predict better cognitive function, while smoking is associated with worse long-term cognitive disability in patients with clinically isolated syndrome (CIS), a study suggests. Data from the study was presented by Marianna Cortese, MD, PhD, from the Department of Nutrition, Harvard T.H. Chan…
Smoking and low levels of vitamin D can worsen prognosis for people with clinically isolated syndrome (CIS), researchers who developed a model for predicting long-term disability progression report. Their study, “Predicting the course of CIS patients adding…
A person’s genes influence the development of multiple sclerosis (MS), but so does the environment — both that in which an MS patient lives, and that which a patient creates through diet and other lifestyle choices, researchers said in a Thursday session at the 34th congress of the European…
Treatment of multiple sclerosis (MS) patients with rituximab does not increase breast cancer risk in women, and is not associated with a higher risk for malignant cancer of any type in men or women, when compared to Gilenya (fingolimod) or Tysabri (natalizumab), according to a nationwide study in…
The rate of kidney deterioration as a result of bladder dysfunction due to multiple sclerosis (MS) is low, affecting only 3 percent of the patients, a single tertiary center study shows. However, kidney deterioration is a slow process and detected only after 60 months of follow-up, highlighting the need for…
Smoking may increase multiple sclerosis (MS) disease activity, quicken disability progression, and speed the transition from relapsing to secondary progressive MS (SPMS) by as much as eight years, according to an MS Society review study. The review data shows that, although the U.K.’s National Institute for Health…
People who eat a healthy diet that includes foods such as vegetables, fish, eggs, poultry, and legumes may have a reduced risk of multiple sclerosis (MS), a study suggests. The study, “A healthy dietary pattern associates with a lower risk of a first clinical diagnosis of central nervous system…
Smoking increases the relapse rate in patients with relapsing-remitting multiple sclerosis being treated with Tysabri , an observational study suggests. Multiple sclerosis is a multifactorial disease associated with both genetic and environmental risk factors. Smoking, in particular, has been linked to numerous aspects of MS, including its development and progression. In a previous study, the research team looked at how smoking influences the relapse rate in RRMS patients being treated with interferon beta. From more than 800 patients, they found that smoking one pack per day (about 20 cigarettes) essentially interfered with the positive effect of the IFN-beta treatment and increased the relapse rate by 27%. The researchers then questioned whether the same was true for other treatments. Tysabri, developed by Biogen, is a monoclonal antibody that targets the alpha-4 integrin protein. By interfering with this molecule, the therapy prevents white blood cells from moving into the central nervous system, suppressing the immune reaction that contributes to MS symptoms. In the study, 355 Tysabri-treated RRMS patients from the Danish Multiple Sclerosis Centre were assessed. To gather information on smoking habits and body mass index, the patients filled out a 100-question survey. Data was collected between the start of the treatment and a two-year follow-up visit. Results showed that smoking one pack of cigarettes per day increases the relapse rate by 38% in RRMS patients on Tysabri. This increase in relapse rate takes into account both sex and age at the start of treatment, since age can affect the relapse rate. For example, an increase in age by one year raises the number of relapses by 2%. The researchers also looked at the relationship between smoking and the presence of two immune-related alleles: HLA-DRB1*15:01 and HLA-A*02:01. Previous studies showed that HLADRB1*15:01 is associated with an increased risk of developing MS, while HLA-A*02:01 is linked to a decreased risk. Although previous studies reported a link between smoking and these two alleles in MS patients, the current study did not find an association between smoking and carrying either of these alleles. Based on the results, the researchers concluded that smoking significantly increases the relapse rate in RRMS patients receiving Tysabri. According to the team, the results "add important information that hopefully will sharpen the focus on the overall harmful effects of smoking in MS patients."
Vitamin D3 insufficiency increases multiple sclerosis (MS) susceptibility in a gene and sex-dependent manner, a mouse study suggests. The study with that finding, “Sex-Specific Gene-by-Vitamin D Interactions Regulate Susceptibility to Central Nervous System Autoimmunity,” by researchers at the University of Vermont, was published in the journal Frontiers in…
A genetic variant close to a gene called interferon regulatory factor 6 (IRF6) may help to predict those multiple sclerosis (MS) patients most at risk of liver injury while using interferon-beta therapies, a study reports. The study, “Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis” was published…
Evaluating the local differences in iron accumulation in the deep gray matter of the brain using a special magnetic resonance imaging (MRI) technique, may help identify multiple sclerosis (MS) patients at greater risk for disease progression and disability, a study reports. The study “Brain Iron by Using Quantitative MRI…
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