This Drug May Sabotage Your New Exercise Program

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biologic drug side effects

One of the more interesting things I've observed in the past few decades is medicine's money-fueled focus on biologics. These aren't the orthobiologics like your own stem cells or platelets that you may see me writing about, but are artificially created drugs that block inflammation. While these drugs can be lifesavers for some patients, they can also have serious, life-threatening side effects. Now new research shows a new side effect: blocking weight loss. 

Biologic Immunosuppressants

This drug class has the name "biologics" because the drugs here are derived from living cells. In fact, a more precise definition is "biological medications are developed from blood, proteins, viruses, and living organisms and are used to prevent, treat, and cure human disease." You can recognize the drug class easily because the chemical name often has the ending "umab" or just "mab." For example, tocilizumab is the drug we'll be discussing this morning. 

These drugs have been huge moneymakers for pharma for last two decades. What concerns me as a doctor is that they all seriously suppress the immune system and, as such, have severe and even life-threatening side effects. That may have been a reasonable gamble when they were used to treat serious disease, but all too often these days, they're being used to treat less and less serious diseases. 

How real are these side effects? One of my attorney friends died due to these side effects. He was an otherwise healthy elderly man who was on a biologic to treat chronic disease, got pneumonia, and, because of the immune-suppression caused by the biologic, never left the hospital. So these serious side effects are quite real. 

What Is IL-6?

Interleukin 6 (IL-6) is a protein secreted into the bloodstream via cells and muscles. IL-6 can create a pro-inflammatory response through immune cells such as macrophages or monocytes. However, it can also create an anti-inflammatory response via the muscles and is particularly elevated during exercise as muscles contract. In those who are sedentary and obese (a condition associated with inflammation), pro-inflammatory IL-6 (as a cytokine, or cell-signaling protein) can be chronically elevated.

A new study suggests that in those who exercise regularly, however, anti-inflammatory IL-6 (as a myokine, or muscle-signaling protein) released during muscle contraction actually works to break down fat by a process called lipolysis, which utilizes stored triglycerides as an energy source. Let’s take a look at the study.

Exercise Ineffective at Reducing Belly Fat when Drug Blocks IL-6 Release

Tocilizumab (Acetmra) is an immunosuppressant and is most commonly injected every few weeks to treat moderate to severe rheumatoid arthritis. It decreases arthritic pain and inflammation by blocking the inflammatory IL-6 protein. Exercise is known to reduce abdominal fat, and researchers hypothesized that this occurs via lipolysis due to the release of IL-6 during muscle contraction and that blocking IL-6 release would negate these belly-burning efforts.

The new study was a randomized controlled trial in which obese participants were randomly assigned to either a standard-dosage tocilizumab group (IL-6 blocked) or a saline placebo group (IL-6 not blocked). Exercise consisted of high-intensity cycling throughout a three-month period. The results? Those who exercised in the placebo group experienced a reduction in belly fat; in those who exercised in the tocilizumab group, belly fat was unchanged. Researchers concluded that the release of IL-6 was indeed a key mechanism in the ability of exercise to reduce abdominal fat and that blocking the IL-6 protein receptor (in this case via the drug tocilizumab) stopped exercise from reducing abdominal fat and, in addition, increased cholesterol.

What does this mean? If you’re taking an IL-6–blocking drug, such as tocilizumab, and you are exercising regularly in an attempt to decrease your belly fat, you probably aren’t having much luck.

What other drugs are anti-IL6? Another one that's approved right now is Sylvant (siltuximab) with many more on the way, including olokizumab, elsilimomab, and sirukumab. So this is an emerging drug class. 

If I’m Taking an IL-6–Blocking Drug, Should I Just Stop Exercising?

First, you might talk with your physician and see if there is an alternative to an IL-6–blocking drug for your condition, especially since obesity is associated with metabolic disorders and the featured study also associated this drug with an increase in cholesterol, which over time could lead to cardiovascular conditions. If the benefits of the drug are determined to outweigh these risks, while you might not get that trim waistline you’re hoping for (keeping in mind, the study only looked at those with obese bellies), there are other highly beneficial outcomes to exercise. Let me review a few:

The Complex Dance of Healthy Inflammation

Modern medicine's view of inflammation is that it's all bad. This is a short-sighted view not supported by the science. As you can see here, you need the inflammatory IL-6 molecule to help initiate not only fat loss but also likely muscle repair itself. So short-term inflammation with exercise is not only good, it's essential. This is why, as a doctor, when I see more and more patients using these biologic drugs for less serious diseases because this is a way for pharma to expand profits, I get really concerned. 

The upshot? These biologic drugs are serious medicines with serious side effects. However, some of the less serious side effects can teach us about the complex interactions between inflammation and health. Meaning, short bursts of inflammation are how we heal and maintain our bodies, so using a thermonuclear approach to suppressing inflammation (like these heavy-handed biologic drugs) will have negative consequences as well as positive ones. 

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Chris Centeno, MD

Regenexx Founder

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications.
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