It’s a common occurrence that following a challenging (or longer) workout, there’s an immediate suppression of appetite that can last several hours. This may seem strange because exercise burns energy—so shouldn’t hunger increase? In reality, appetite after exercise varies person to person, and it also depends on how intense and how long the exercise. (13–15)
Your muscles “talk” to your body
When you exercise, your muscles don’t just move you—they also send chemical messages to other organs from signaling molecules called myokines. These myokines help to coordinate how your body uses sugar (glucose) and fat, how it regulates inflammation, and sometimes how your appetite feels after exercise. (1,2)
The best-studied myokine is interleukin-6 (IL-6). During exercise, working muscle becomes a major source of IL-6 in the blood, especially when large muscle groups work steadily for longer periods (think cycling, running, rowing, fast uphill walking). (1,3)
Exercise IL-6 is not the same as chronic inflammation IL-6
IL-6 is typically identified as an “inflammation marker,” and in chronic disease states it can be elevated for long periods. But IL-6 from exercise is a short-lived signal that rises during and after exercise, and then begins to dissipate in the hours that follow. (1,2)
In exercise physiology, IL-6 is widely viewed as part of the body’s metabolic coordination system—helping the body mobilize and use fuel during and after activity. (1,2)
What type(s) of exercise raise IL-6 the most?
Human studies show IL-6 rises most with:
- Longer duration (especially sustained endurance activity) (1,3–6)
- Higher intensity or “harder” overall sessions (1,4–6,13)
- More muscle involved (legs + trunk tend to drive bigger signals than small-muscle activities) (1,3)
What IL-6 may do for metabolic health (human evidence)
Researchers have studied IL-6 in humans by two primary approaches:
A) “Direct IL-6” studies (mechanistic studies):
- In healthy adults, infusing IL-6 increased insulin-stimulated glucose disposal (a gold-standard measure of insulin sensitivity). (7)
- In another human trial, IL-6 stimulated lipolysis and increased whole-body fat oxidation acutely. (8)
Important nuance: IL-6 is not the only reason exercise improves metabolism. (9)
B) “Control IL-6” studies (causality tests):
- In abdominally obese adults, a 12-week cycling exercise program reduced visceral (deep belly) fat. However, that benefit was eliminated when IL-6 signaling was blocked with the IL-6 receptor antibody tocilizumab. (10)
- In a separate crossover study of lean and obese men, blocking IL-6 signaling reduced free-fatty-acid mobilization during rest, exercise, and recovery—consistent with impaired availability of circulating fatty acids as fuel. (11)
Why this matters: Visceral fat is strongly linked to cardiometabolic risk, and the studies suggest IL-6 signaling is one pathway by which exercise can improve fat distribution and fuel handling. (10,11)
Can IL-6 help explain appetite suppression after exercise?
Evidence does support that exercise reduces appetite, especially after vigorous work—but the mechanism is not a single molecule. (13–15)
Specifically, human evidence suggests the following:
- In boys, a high-intensity exercise bout reduced appetite ratings and the appetite change correlated inversely with IL-6. (14)
- In active young men, vigorous running/interval work produced stronger appetite suppression and appetite-hormone changes, and IL-6 is discussed as a possible contributor (along with lactate and gut hormones). (13)
- A mechanistic study found IL-6 can delay gastric emptying and reduce post-meal glucose excursions, which could contribute to fullness in some people. (12)
- However, another study involving sedentary men (normal weight and obesity) found IL-6 was not involved in appetite regulation after 60 minutes of moderate-intensity continuous exercise (~65% VO₂max). (15)
Practical takeaway: Appetite suppression post exercise is real for many people, but likely involves multiple signals like ghrelin (hunger hormone), GLP-1 and PYY (satiety hormones), sympathetic activation (“adrenaline”), lactate, temperature, and individual training status—with IL-6 involved often, but not always. (13–15)
Key points regarding IL-6
- Your muscles release myokines during exercise, and IL-6 is the most-studied of these myokines. (1,2)
- IL-6 from exercise is acute and adaptive—not the same as chronic inflammatory IL-6. (1,2)
- IL-6 rises most when larger muscles are utilized, during sustained endurance work, and higher-intensity exercise and volume. (1,3–6,13)
- Human causality data suggest IL-6 signaling contributes to visceral fat reduction with training and to fatty-acid mobilization around exercise. (10,11)
- Appetite suppression is common following vigorous exercise bouts, but typically involves multiple factors including IL-6 in several contexts.” (12–15)
Final takeaways and considerations
Regardless of the specific contributions of IL-6 from exercise, this brief review should serve to highlight the importance of increased exercise intensity for improved cardiometabolic health outcomes (e.g., improved body composition, blood pressure, glucose tolerance, and blood lipids). When appropriate (as health and tolerance allow), it may be worth considering certain ergogenic aids, which are most commonly nutritional supplements or functional foods used to enhance exercise and/or athletic performance. Exercise intensity and duration do matter and can be decisive in sustaining health and vitality.
While there are many popular, safe, and evidence-based supplements and foods known to support exercise and athletic performance, such as creatine, caffeine, beta-alanine, and dietary nitrate for example, more recent research highlights the benefits of supplements like Alpha GPC and phosphatidylserine for their effects on neuromuscular signaling and stress responses to exercise. BioSpec Nutritionals recently developed an acetylcholine support formula, Neuro-Strength, to support memory, focus and mental clarity that may also double as an ergogenic aid when appropriately dosed.* For additional details: https://biospecnutritionals.com/product/neuro-strength/
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
References
- Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88(4):1379-1406. doi:10.1152/physrev.90100.2007.
- Pedersen BK. Muscle as an endocrine organ: IL-6 and other myokines. Appl Physiol Nutr Metab. 2009;34(3):365-370.
- Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Klarlund Pedersen B. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol. 2000;529(Pt 1):237-242. doi:10.1111/j.1469-7793.2000.00237.x.
- Helge JW, Stallknecht B, Pedersen BK, Galbo H, Kiens B, Richter EA. The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle. J Physiol. 2003;546(Pt 1):299-305. doi:10.1113/jphysiol.2002.030437.
- MacDonald C, Wojtaszewski J, Klarlund Pedersen B, Kiens B, Richter EA. Interleukin-6 release from human skeletal muscle during exercise: relation to AMPK activity. J Appl Physiol. 2003;95(6):2273-2277. doi:10.1152/japplphysiol.00242.2003.
- Pedersen BK, Steensberg A, Fischer C, et al. The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proc Nutr Soc. 2004;63(2):263-267. doi:10.1079/PNS2004338.
- Carey AL, Steinberg GR, Macaulay SL, et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMPK. Diabetes. 2006;55(10):2688-2697. doi:10.2337/db05-1404.
- van Hall G, Steensberg A, Sacchetti M, et al. Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab. 2003;88(7):3005-3010. doi:10.1210/jc.2002-021687.
- Hiscock N, Fischer CP, Sacchetti M, et al. Recombinant human interleukin-6 infusion during low-intensity exercise does not enhance whole body lipolysis or fat oxidation in humans. Am J Physiol Endocrinol Metab. 2005;289:E2-E7. doi:10.1152/ajpendo.00274.2004.
- Wedell-Neergaard AS, Lehrskov LL, Christensen RH, et al. Exercise-induced changes in visceral adipose tissue mass are regulated by IL-6 signaling: a randomized controlled trial. Cell Metab. 2019;29(4):844-855.e3. doi:10.1016/j.cmet.2018.12.007.
- Trinh B, Peletier M, Simonsen C, et al. Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men. Cell Rep Med. 2021;2(9):100396. doi:10.1016/j.xcrm.2021.100396.
- Lehrskov LL, Christensen RH, Theodorakis MJ, et al. Interleukin-6 delays gastric emptying in humans with direct effects on glycemic control. Cell Metab. 2018;27(6):1201-1211.e3. doi:10.1016/j.cmet.2018.04.018.
- Islam H, Townsend LK, McKie GL, et al. Potential involvement of lactate and interleukin-6 in the appetite-regulatory hormonal response to an acute exercise bout. J Appl Physiol (1985). 2017;123(5). doi:10.1152/japplphysiol.00218.2017.
- Hunschede S, Kubant R, Akilen R, Thomas S, Anderson GH. Decreased appetite after high-intensity exercise correlates with increased plasma interleukin-6 in normal-weight and overweight/obese boys. Curr Dev Nutr. 2017.
- Bornath DPD, et al. Interleukin-6 is not involved in appetite regulation following moderate-intensity exercise in males with normal weight and obesity. Obesity (Silver Spring). 2023. doi:10.1002/oby.23841.