Obesity in adolescence or early adulthood is associated with increased risk for multiple sclerosis (MS), a new study suggests.
The study was led by Jorge Correale, MD, from the Raúl Carrera Institute for Neurological Research, Buenos Aires, Argentina. Dr. Correale suggested to Medscape Medical News that obesity appears to be an additional factor involved in the genesis of MS, an effect that may be mediated by the hormone leptin.
"We need to do more work to understand the mechanisms involved in all the different environmental/habitual factors, including body mass index. If we understand mechanisms we can propose treatment alternatives to decrease the risk to develop the disease or to prevent increase in the severity of the disease," he added.
The findings will be presented at the upcoming American Academy of Neurology (AAN) 66th Annual Meeting in Philadelphia, April 26 to May 3, 2014.
Environmental Risk Factors
For the current study, body mass index (BMI) was calculated for 210 patients with MS and 210 controls of the same age and sex who did not have MS at ages 15 and 20 years and at the time of the study.
Results showed that people who are obese (BMI > 30 kg/m2) at age 20 are twice as likely to later develop MS as people who are not obese (odds ratio, 2.1; 95% confidence interval, 1.2 - 3.7; P = .02).
The researchers also measured levels of various hormones and cytokine-producing cells, and found that BMI correlated directly with serum leptin levels, but inversely with 25(OH) vitamin D levels. In addition, leptin exerted opposite effects on regulatory and CD4+ effector T cells, promoting inflammatory responses, potentially representing a putative link between obesity and autoimmunity in MS.
"Leptin promotes inflammatory responses in the body, which could potentially explain the link between obesity and MS," Dr. Correale said.
"During the last few years we have started to understand more about different factors involved in the genesis of MS," he told Medscape Medical News. "There is a genetic predisposition, and in addition some environmental factors or habits that are thought to increase the risk of developing the disease, such as smoking, low vitamin D, and Epstein-Barr virus infection. In addition, in animal models increased amount of salt in the diet is thought to increase risk, and now it appears that obesity is an additional habit factor that can increase the risk of developing MS."
He noted that recent epidemiologic studies from Harvard and Copenhagen School of Health have also suggested that obesity is a risk factor for MS, particularly during childhood and adolescence.
Elaborating on the proposed mechanism, he pointed out that increased BMI is associated with a reduction in levels of vitamin D, which has been linked to an increased risk for MS. In addition, obesity is associated with increased production of leptin, and "in our investigation we demonstrated that in obese MS patients leptin increases the proliferation of auto-aggressive cells responsible for myelin damage."
He added: "Furthermore, leptin inhibits the actions, and reduces the number of regulatory cells that under normal conditions control auto-aggressive cells. These 2 mechanisms explain, at least in part, some of the obesity effects."
He noted that animal studies have shown that certain drugs that affect the metabolism of the glucose (metformin) and cholesterol (statins) have an inhibitory effect on leptin actions. However, statins have been tested in MS without much benefit. Another approach, simply restricting calorie intake has shown anti-inflammatory, antioxidant, and neuroprotective effects in animals, but this needs to be confirmed in humans.
However, on a cautionary note, Dr. Correale reports that leptin may have both positive and negative effects in the central nervous system. "Although leptin induces inflammatory mechanisms, it also appears to have a beneficial effect on neuronal survival and myelination. Thus, mice deficient in leptin or its receptor display reduced brain weight and immature pattern of expression of synaptic and glial proteins. Thus, a clear balance between the dichotomous actions of leptin should be achieved."
The study was supported by the Raúl Carrera Institute for Neurological Research.
American Academy of Neurology (AAN) 66th Annual Meeting, Philadelphia, April 26 to May 3, 2014. Abstract 558.
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Cite this: Obesity Linked to Increased Risk for MS - Medscape - Mar 12, 2014.