How Fat Affects Rheumatoid Arthritis
Excess body weight increases inflammation and may affect drug effectiveness in RA.
About two-thirds of people with rheumatoid arthritis (RA) are overweight or obese, the same proportion as in the general US population. In people with RA, however, excess body fat creates special complications in addition to its well-known role in increasing risks of heart disease, stroke and other conditions.
Fat Increases Inflammation
Fat is chemically active, constantly releasing proteins that cause inflammation, which then turns up the “volume” of RA itself.
Fat cells, or adipocytes, release proteins called cytokines that, in excess, cause constant, low-grade inflammation throughout the body. “Fat, or adipose, tissue is a source of many of the same inflammatory cytokines that are produced by inflamed joint tissue in people with inflammatory arthritis,” says Jon T. Giles, MD, MPH, assistant professor of medicine at Columbia University in New York City.
The more pounds you add, the more of these proteins circulate in the body, which also seems to lead to more severe RA, says Dr. Shoenfeld, author of a 2014 Autoimmunity Reviews analysis that looked at 329 studies of obesity in autoimmune diseases.
“Fat is not a passive bystander in RA and other autoimmune diseases,” explains immunologist Yehuda Shoenfeld, MD, director of the Zabludowicz Center for Autoimmune Diseases in Tel Aviv, Israel. “When you have an excess of fat cells, it produces higher levels of inflammatory proteins that aggravate the inflammation that is already within joints.”
Shoenfeld and his co-authors detailed data showing that people with RA who are obese have more active disease, more pain and worse overall health. Inflammation-causing cytokines, which include tumor necrosis factor-alpha (TNF-alpha), interleukin-1 and interleukin-6, are already overactive in RA.
Fat May Reduce Benefit of RA Drugs
But biologics, as well as some traditional disease-modifying antirheumatic drugs (DMARDs), work less well in obese individuals with RA than in people of a healthy weight. A 2013 study, published in Arthritis Care & Research, found overweight and obese patients are as much as 50 percent less likely to have a positive outcome after 12 months of therapy with biologics that block TNF-alpha than healthy-weight patients.
“This poor response is particularly true with infliximab [Remicade],” says Eric Toussirot, MD, PhD, professor of rheumatology at the Clinical Investigation Center for Biotherapy at the University Hospital of Besançon in France. “Conversely, weight loss is related to a better clinical response.”
How fat undercuts the activity of RA drugs isn’t yet understood. “It could be that fat cells are able to produce many inflammatory proteins that can contribute and sustain the inflammatory process,” says Dr. Toussirot. “A less-studied theory is that the fat cells may fix to monoclonal antibodies such as infliximab or adalimumab [Humira] and render them non-functional.”
Fat and Joint Damage
Extra fat mass adds stress to joints, particularly weight-bearing joints, says Eric Matteson, MD, chair of the rheumatology division at the Mayo Clinic, in Rochester, Minn. Every 10 pounds of excess weight, for example, puts 40 pounds of extra pressure on knees. “If you think about all the steps you take in a day, you can see why it would lead to damage,” he says. The inflammation due to RA can cause joint erosion, and this effect can be compounded by excess body weight.
But one confusing finding about fat in RA is that several studies have found that obese people with the condition have less joint damage on x-rays than thinner people with RA, says Dr. Giles. “This may due to the action of adiponectin, an inflammatory protein produced by fat cells, that is actually found in higher levels in leaner people with RA,” he says. “Adiponectin may be harmful for inflamed joints and, as its levels tend to go down with obesity, people with more fat seem to gain a protective effect, but no studies have yet shown that weight loss is associated with more damage.”
These findings do not mean that being obese or overweight will prevent joint damage from RA. “In fact,” says Dr. Matteson, “you are still at risk for your arthritis to advance more rapidly in your weight-bearing joints simply because of the biomechanical forces that come into play.”
Updated June 2015