How does exercise make you lose weight? The role of Interleukin-6 (IL-6) and tocilzumab (Actemra)


We all know being overweight is bad, particularly abdominal fat or visceral fat, which surrounds our internal organs.  We also know that to lose weight, we need to diet, and exercise.

But how does exercise cause fat loss?  What is the mechanism?

A new study, published in the journal Cell Metabolism   has shown that a signalling molecule called interleukin-6 (IL-6) plays an essential role in the fat loss process.

IL-6 and Rheumatoid arthritis

Those of you who have Rheumatoid Arthritis, or other forms of inflammatory arthritis, will be familiar with IL-6, or more likely, biologic medications that block IL-6.  In some contexts, IL-6 is an inflammatory cytokine, and inhibiting IL-6 reduces inflammation and disease activity in Rheumatoid Arthritis. It’s a relatively common treatment. For me, it was the most successful medication (short of prednisone) I’d ever tried.

But I gained an incredible amount of weight.  At the time I was (and still am) barely eating and exercising regularly (albeit not as intensely or as often as I’d like).  Doctors refuse to believe my food diaries and exercise logs, because everyone knows weight gain is caused by eating too much and not moving enough.  Calories in vs calories out, right?  Simple as that!

Not in my case. I know what I eat, and I know how much exercise I do. 

Very, very frustrating. I am many things, but I am not a liar.

Now back to the study.  The scientists hypothesized that exercise-induced reductions in abdominal fat are mediated by IL-6 because its known to regulate energy metabolism, stimulates the breakdown in fats in healthy people, and is released from skeletal muscle during exercise.

To test their theory, the scientists ran a small 12 week trial where obese participants were assigned to one of four groups.  Participants were randomised and either received monthly infusions of tocilzumab (Actemra, the IL-6 blocker that treats Rheumatoid Arthritis) or a saline placebo, combined with no exercise, or a supervised 45 minute bicycle routine consisting of several 45 minute sessions per week.  Magnetic resonance imaging (MRI) was used to assess abdominal fat mass at the beginning and at the end of the study.

The people in the exercise and placebo group lost an average of 8% body mass (or 225g).  The people in the exercise and tocilzumab group not only didn’t lose any weight, they actually GAINED weight.  The effect of exercise on fat loss was completely abolished by tocilzumab, and the medication even caused them to gain more weight.  The group who received tocilzumab and did not do exercise also gained weight.

The people who received tocilzumab were unable to burn fat.  Not only that, they actually GAINED fat, without changing their diet. Tocilzumab also increased total cholesterol and LDL cholesterol in both the exercise and non-exercise groups. 

On the upside, tocilzumab did not affect improvements in cardiovascular fitness, which was the same in both groups.  So at least the exercise is still having some positive effects, despite blocking fat loss.

This was a very small study, but its was double blind, placebo controlled and peer reviewed.  It’s a high-quality study.  The study authors state the IL-6 can be both inflammatory and anti-inflammatory depending on the pathways, and chronic low-grade elevations of IL-6 are seen in patients with severe obesitytype 2 diabetes, and cardiovascular disease, therefore it is “likely that IL-6 may act differently in healthy and diseased people.”  More study needs to be done.

This is the infographic that goes along with the study. It tells the story very clearly.

IL-6 completely abolishes the fat loss effects of exercise

It’s all pretty damning.  And the next time a doctor tells me I’m lying about my weight gain, I’ll refer them to this study. And there are several others as well. A quick google shows that medicine has known for a while that IL-6 causes fat gain and prevents fat loss, just not exactly how or why.

Further googling has revealed that estrogen also inhibits IL-6, which is likely why many women on HRT gain weight.   Given that my gynecologist pumped me full of estrogen at the same time that I was taking Actemra, I had a double whammy of inhibiting IL-6.  End result?  20 kilogram weight gain that I can NOT shift.  No amount of dieting or exercise has made any difference, the weight just rose steadily, finally levelling off at 100kgs.  A full 22kg heavier than I was before I started actemra/tocilzumab and estrogen therapy.

I’m not sure how accurate this page is, but it lists all the pros and cons of IL-6.  Fascinating reading.

So where does this leave me?  Fat, unhappy but vindicated. 

What can I do about it? The way to increase IL-6 levels is through vigorous exercise, or even over exercising.  Hard to do with my lumbar spine, para-leg and RA but I will have to find a way.  Thyroid medication increases IL-6, which could be part of how being hyperthyroid causes weight loss.  Melatonin increases IL-6, which is probably why some doctors say that melatonin is contraindicated in RA…theoretically increasing IL-6 will increase RA inflammation.  I’m on an angiotensin II inhibitor for my high blood pressure, and that should also increase IL-6.  Maybe all of that will help over time.

TNF blockers are now accepted by some rheumatologists to cause weight gain, unrelated to diet and exercise, which is a break through.  It’s very offensive to give a patient a medication that causes weight gain and then harass them about that same weight gain and treat them like liars when they say they haven’t changed their diet or exercise habits. 

I gained almost 20kgs when I was on Enbrel and then Humira.  I then changed to Orencia, but still couldn’t lose weight.   Only after a year OFF all biologics did I START to lose weight. It took another year to get back to my normal weight.  It was a long, slow battle, back in 2017.  For eight months I maintained a weight between 78 and 82kgs with little effort, while not on any biologic medications. 

And then the hysterectomy, HRT and Actemra.  I logged my weight gain on my Fitbit app, because it was fast – more than 1kg a week, and all this while I was living on fruit and vegetable purees, at the worst of my Eosinophilic Esophagitis restrictive diet.  The graph is steep, and steady.  Inexorable. 

It has been about a year since I stopped actemra.  My estrogen levels are falling into a normal range.  When my body chemistry changes, weight loss might be possible. When? I have no idea. The only way to accelerate that process is to exercise. Hard.  Intensely.  A simple walking program won’t do it.  It needs to be sustained, intense exercise. Preferably intervals (HIIT). 

I’ll work on that. I am a qualified personal trainer, though obviously I don’t work as one. I remember enough of my studies to know how to program a workout routine for myself. 

Today I started with a walk job/shuffle.  Because my left leg is partially paralysed and my left side on the whole is far weaker than my right, running looks pretty ridiculous. But it is HARD work and it takes a lot of energy to move my body mass.  Therefore, I burn a lot of calories. 

And honestly? While its not fun per se, it does feel good.  I have always enjoyed exercise and have exercised in some form all of my life. Which makes it particularly offensive when doctors look at my large, soft body and assume I have spent my life sitting on the couch eating chocolates and chips.

I’ll have to build up strength and stamina slowly, and if I have to taper prednisone exercising at the intensity required, might not be possible.  Sometimes there is truly NOTHING you can do about your weight/bodyfat percentage.

At least studies like this one make the battle a little easier, in that it forces doctors, rheumatologists, to accept that not every obese patient got that way by over eating and under exercising. There IS more to it than calories in/calories out, especially where biologic medications are part of the picture. And its NOT ok to fat shame patients for weight gain that is entirely outside of their control, and wholy caused by the prescribed medication.


    • OMG yes! Prednisone is the worst! But at least doctors acknowledge it. Its high time they realised prednisone is not the only thing we have stacked against us in the weight stakes. Thanks Rochelle x

    • I’m sorry to hear it Rick, weight gain is not pleasant for anyone :(. I do appreciate the validation though. May I ask, were you able to lose the pounds? And if so, did it take effort, or did it happen naturally as the effects of actemra waned? I’m guessing you moved from Actemra to another biologic, and many of them also cause weight gain. It’s so difficult. And if a med takes my pain down from a constant 8 to a 4-5, then is the weight worth it? Honestly, to me, no. But to most people who don’t have my history, probably it is. Hope you’re doing OK. I’m rarely on facebook anymore these days. Best to you, Rick xx

  1. Thanks for this article! I have been trying to lose weight for 8 months and literally thought I had lost my mind because I kept gaining. It’s the Actemra and was given no warning from my doctor. 6 days of working out per week (high intensity) didn’t do it. I just lost five pounds doing a Whole30, but I’m pretty sure I’ll blink and be up 10.

    • YES! This week when I saw my rheum he finally admitted that they realise that actemra can cause “significant” weight gain in some patients, but they do not understand why. And they cannot predict who will have this side effect. I also gained weight with TNF blockers, but only 10kg, not 25kg! Congratulations on the 5 pound loss…every bit counts! I’m not able to exercise as often or as intensely as I need, but even an 800 calorie or less a day diet hasn’t moved the weight. I lots 9kgs with saxenda, but only for the first month. then the weight loss stalled there too. Its incredibly frustrating and depressing. Your diet and your exercise IS making you healthier and fitter…I try to focus on that. But its hard, I hate the way I look and theres nothing I can do. Let me know how you’re doing? I don’t want to bring you down, maybe we can keep in touch and all support eachother if we find something that helps. You’re totally not crazy…this stuff messed up your fat metabolism.

  2. My Dr. wants me to start Actemra next week and I have cirrhosis of liver and I’m type 2 diabetic I am supposed to lose weight for my health in your opinion should I do the infusion I’m scared to try this medicine

    • I’m so sorry for the slow reply, no doubt you’ve made your decision by now. It’s always fraught. Biologics seem to have a long list of very serious side effects, and we just don’t know if we’ll be the unlucky one. On the other hand, they can be life changing and give us our lives back. I found actemra to be very effective. I started running again within 3 weeks of starting, but i was doing the injections, not the infusions. One thing I have to mention, is that actemra caused extreme weight gain for me. 25 kgs that over 3 years later after stopping it I am still unable to lose. It doesnt’ happen to everyone, but when it happens, the weight comes on and it won’t come off. My rheum finally admitted its a known side effect now but they cannot predict who will be affected. If you’re taking it and you find yourself gaining weight, I’d consider stopping it. The weight gain has cause me more harm than anything else, so I wish I’d never touched it. And because my rheum denied that it was the culprit, I took it for many months. but please…I don’t mean to scare you off, I just wish someone had of told me. If you gained weight with TNF blockers, you might be in the same boat, only worse. I hope you’re doing well, please write back and let me know how you’re doing?

  3. I put on 15kg almost overnight on Toc. I cannot shift it. I am now on Baricitinib which still blocks il6.

    That’s bad enough, but to have the implications that you are a liar thrown into the mix has left me so angry and grieving for my my body.

    Thank you for the validation of my experience.


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