Research Summary: An adverse lipid profile and increased levels of adiposity significantly predict clinical course after a first demyelinating event

An increasing emphasis is being placed on how lifestyle modifications can be used to manage multiple sclerosis (MS).  It is well known that everyone benefits from having a healthy diet and undertaking regular exercise.  These findings are being supported in people with MS with studies showing that there are positive impacts on both overall health and MS related symptoms.

However, the impacts of an unhealthy diet or lower exercise levels (specifically increased weight and bad fat levels in the blood) are not well known in people with MS.  Body mass index (BMI) is a way of measuring the amount of body fat on an individual.  The BMI values can be used to classify whether a person is in a healthy weight range, overweight or obese.  It has previously been shown that a higher BMI during childhood and adolescence increases the risk of developing MS.

In this study (a collaboration between the Menzies Institute for Medical Research, the Murdoch Childrens Research Institute and The University of Queensland), 190 people were monitored from disease onset to 5 years.  Across this time, their BMI, as well as hip and waist circumference were recorded.  Blood samples were also taken to measure the levels of different types of lipids (fats).  Using this information, they asked the following questions and found the following answers:

Do serum lipid levels, BMI or waist/hip circumference measures predict conversion to MS?

No.  They looked at these different factors and checked to see whether there was any association between them and the transition from the first demyelinating event to multiple sclerosis.  By doing this, they found that no association existed.

Do serum lipid levels, BMI or waist/hip circumference measures associate with relapses?

Yes.  They found that triglyceride levels did correspond to an increased risk of relapses.  Individuals with triglyceride levels that would rank them as a high-risk for cardiovascular disease had double the risk of relapses.  Similarly, an increased BMI (as well as hip circumference) was also associated with a higher number of relapses.  In fact, the higher the BMI, the greater the number of relapses.

Do serum lipid levels, BMI or waist/hip circumference measures associate with progression?

Yes. It was found that BMI (as well as waist/hip circumference) at onset was associated with disease progression.  People who were obese or overweight at the beginning of the study had a 60% greater risk of having a 0.5 increase in EDSS after 5 years.  This was also reflected in the levels of certain fats.  Non-High Density Lipoprotein (Non-HDL) levels and the total cholesterol to HDL ratio were both found to associate with a greater 5 year change in EDSS.

So what does this mean?

While many studies have shown that making positive changes to lifestyle can lead to benefits, I think this research indicates that a higher BMI (e.g. being overweight/obese) and adverse fat levels can actually result in multiple sclerosis progression.  In this way, it provides further support to the use of diet and exercise as part of a multiple sclerosis management plan.

In my opinion, it would now be interesting to see what happens to disease progression in people with MS who may have been overweight at disease onset, but then initiated these lifestyle changes.  As an example, for the people who showed an increased relapse rate or EDSS at 5 years, what would happen to them now if they could reduce their BMI and levels of bad fats in their blood?  Hopefully this is the next stage of the research, as it would provide really strong evidence to highlight the benefits of such an approach.

As well as this, I think the researchers will now try and establish why these factors have these effects.  Currently, it is still unknown, however, the authors did suggest that it could be directly through fat metabolism pathways, side-effects of reduced exercise levels/activity or potentially through interaction with Vitamin D.  We will keep you updated on any further progress in this area, as we know that it’s of huge interest to many people in the MS community.

The abstract for this study can be read in full here, while a second summary of the same study can be read on the MS Research Australia website here.

2 Responses

  1. Nigel Wadham

    Amazing research assessment, the factor that is important was overlooked.
    Is there a connection between the BMI & Lipid Levels and MS full stop!
    Is there any indication the diet has effects in the Lifetime/period before symptoms and the dx process?
    Is there a need for diet, lifestyle, and stresses modifications in the general population?
    I ponder WHY this line of thought only comes after a dx and not before.

    Reply
  2. Nigel Wadham

    Dr. Angelique Corthals, a forensic anthropologist and professor at the John Jay College of Criminal Justice in New York, suggests instead that MS is caused by faulty lipid metabolism.

    Researcher contends multiple sclerosis is not a disease of the immune system

    An article forthcoming in the December 2011 issue of The Quarterly Review of Biology argues that multiple sclerosis, long viewed as primarily an autoimmune disease, is not actually a disease of the immune system. Dr. Angelique Corthals, a forensic anthropologist and professor at the John Jay College of Criminal Justice in New York, suggests instead that MS is caused by faulty lipid metabolism, in many ways more similar to coronary atherosclerosis (hardening of the arteries) than to other autoimmune diseases.

    Framing MS as a metabolic disorder helps to explain many puzzling aspects of the disease, particularly why it strikes women more than men and why cases are on the rise worldwide, Corthals says. She believes this new framework could help guide researchers toward new treatments and ultimately a cure for the disease.

    Multiple sclerosis affects at least 1.3 million people worldwide. Its main characteristic is inflammation followed by scarring of tissue called myelin, which insulates nerve tissue in the brain and spinal cord. Over time, this scarring can lead to profound neurological damage. Medical researchers have theorized that a runaway immune system is at fault, but no one has been able to fully explain what triggers the onset of the disease. Genes, diet, pathogens, and vitamin D deficiency have all been linked to MS, but evidence for these risk factors is inconsistent and even contradictory, frustrating researchers in their search for effective treatment.

    “Each time a genetic risk factor has shown a significant increase in MS risk in one population, it has been found to be unimportant in another,” Corthals said. “Pathogens like Epstein-Barr virus have been implicated, but there’s no explanation for why genetically similar populations with similar pathogen loads have drastically different rates of disease. The search for MS triggers in the context of autoimmunity simply hasn’t led to any unifying conclusions about the etiology of the disease.”

    However, understanding MS as metabolic rather than an autoimmune begins to bring the disease and its causes into focus.

    THE LIPID HYPOTHESIS

    Corthals believes that the primary cause of MS can be traced to transcription factors in cell nuclei that control the uptake, breakdown, and release of lipids (fats and similar compounds) throughout the body. Disruption of these proteins, known as peroxisome proliferator-activated receptors (PPARs), causes a toxic byproduct of “bad” cholesterol called oxidized LDL to form plaques on the affected tissue. The accumulation of plaque in turn triggers an immune response, which ultimately leads to scarring. This is essentially the same mechanism involved in atherosclerosis, in which PPAR failure causes plaque accumulation, immune response, and scarring in coronary arteries.

    “When lipid metabolism fails in the arteries, you get atherosclerosis,” Corthals explains. “When it happens in the central nervous system, you get MS. But the underlying etiology is the same.”

    A major risk factor for disruption of lipid homeostasis is having high LDL cholesterol. So if PPARs are at the root of MS, it would explain why cases of the disease have been on the rise in recent decades. “In general people around the world are increasing their intake of sugars and animal fats, which often leads to high LDL cholesterol,” Corthals said. “So we would expect to see higher rates of disease related to lipid metabolism—like heart disease and, in this case, MS.” This also explains why statin drugs, which are used to treat high cholesterol, have shown promise as an MS treatment.

    The lipid hypothesis also sheds light on the link between MS and vitamin D deficiency. Vitamin D helps to lower LDL cholesterol, so it makes sense that a lack of vitamin D increases the likelihood of the disease—especially in the context of a diet high in fats and carbohydrates.

    Corthals’s framework also explains why MS is more prevalent in women.

    “Men and women metabolize fats differently,” Corthals said. “In men, PPAR problems are more likely to occur in vascular tissue, which is why atherosclerosis is more prevalent in men. But women metabolize fat differently in relation to their reproductive role. Disruption of lipid metabolism in women is more likely to affect the production of myelin and the central nervous system. In this way, MS is to women what atherosclerosis is to men, while excluding neither sex from developing the other disease.”

    In addition to high cholesterol, there are several other risk factors for reduced PPAR function, including pathogens like Epstein-Barr virus, trauma that requires massive cell repair, and certain genetic profiles. In many cases, Corthals says, having just one of these risk factors isn’t enough to trigger a collapse of lipid metabolism. But more than one risk factor could cause problems. For example, a genetically weakened PPAR system on its own might not cause disease, but combining that with a pathogen or with a poor diet can cause disease. This helps to explain why different MS triggers seem to be important for some people and populations but not others.

    “In the context of autoimmunity, the various risk factors for MS are frustratingly incoherent,” Corthals said. “But in the context of lipid metabolism, they make perfect sense.”

    Much more research is necessary to fully understand the role of PPARs in MS, but Corthals hopes that this new understanding of the disease could eventually lead to new treatments and prevention measures.

    “This new framework makes a cure for MS closer than ever,” Corthals said.

    ###

    Angelique Corthals, “Multiple Sclerosis (MS) is not a disease of the immune system,” The Quarterly Review of Biology 86:4 (December 2011).

    http://www.eurekalert.org/pub_releases/2011-12/uocp-rcm122211.php?utm_source=twitterfeed&utm_medium=twitter

    also some links to papers that support the theory;

    http://www.thisisms.com/forum/suggestions-f3/topic15207.html

    ORIGINAL PAPER

    http://www.jstor.org/stable/10.1086/662453?seq=1#page_scan_tab_contents

    Reply

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