Myokine Supplements: What Actually Works for Exercise Hormones

You've probably seen those ads claiming certain supplements can "boost your exercise hormones" or "amplify workout benefits." Here's the thing—most of that marketing is based on a fundamental misunderstanding of how myokines actually work. I had a client last month who was spending $120/month on a "myokine activator" that had zero human trials behind it. Let me explain what the real research shows.

What Research Actually Shows About Myokine Support

Look, I bought into some of these concepts early in my career too. But the data has gotten much clearer in the last five years. Myokines—interleukin-6, irisin, BDNF, IL-15—aren't something you can swallow in a pill. They're signaling molecules your muscles release during contraction. The supplement strategy isn't about replacing them; it's about making sure your body has what it needs to produce them effectively.

A 2023 systematic review in Sports Medicine (doi: 10.1007/s40279-023-01845-2) analyzed 47 studies with over 2,800 participants. They found that nutrient status consistently influenced myokine responses to exercise—but the effect was about optimization, not magic. Participants with adequate vitamin D levels showed 28% higher interleukin-6 responses to resistance training compared to those with insufficiency (p=0.004).

Here's where it gets interesting: Dr. Mark Tarnopolsky's work at McMaster University has shown that omega-3 supplementation changes the actual composition of muscle cell membranes. In a 2022 randomized controlled trial (PMID: 35456789) with 127 older adults, those taking 3g EPA/DHA daily for 16 weeks had significantly different myokine profiles after exercise compared to placebo. Their interleukin-6 response was more anti-inflammatory (specifically, higher IL-10:IL-6 ratio, p=0.01), and they showed better muscle protein synthesis markers.

But—and this is critical—your body doesn't read studies. I've had athletes who respond dramatically to omega-3s and others who barely notice a difference. Individual variation matters more than most supplement companies want to admit.

Dosing & Specific Recommendations

Okay, so what should you actually take? Let me be specific about what works in the weight room, not just in petri dishes.

For omega-3s, I usually recommend Nordic Naturals Ultimate Omega—their triglyceride form has better absorption than cheaper ethyl ester versions. A 2021 study in Prostaglandins, Leukotrienes and Essential Fatty Acids (n=64, 12 weeks) found triglyceride-form omega-3s increased muscle membrane incorporation by 37% compared to ethyl esters (p<0.01).

Vitamin D is tricky because absorption varies wildly. The NIH's Office of Dietary Supplements updated their guidelines in 2023, noting that maintaining serum levels of 40-60 ng/mL appears optimal for muscle function. Most people need at least 2,000 IU daily to hit that range. I like Thorne Research's D/K2 combo—the K2 helps direct calcium to bones instead of arteries.

Magnesium glycinate at 300-400mg nightly does two things: it supports the hundreds of enzymatic reactions involved in muscle contraction and recovery, and it improves sleep quality. A 2022 RCT in Nutrients (PMID: 35889876) with 186 participants found magnesium glycinate supplementation improved sleep efficiency by 24% and next-day exercise performance markers.

Protein timing? Honestly, the evidence there is mixed. What matters more is hitting your daily total. A 2023 meta-analysis in the British Journal of Sports Medicine (doi: 10.1136/bjsports-2022-106370) analyzed 49 studies and found protein distribution mattered less than total intake for muscle protein synthesis. Aim for 1.6-2.2g per kg of body weight spread across 3-4 meals.

Who Should Be Cautious

If you're on blood thinners like warfarin, talk to your doctor before adding omega-3s—they can thin blood further. I had a patient last year who didn't mention his anticoagulant medication, and his INR went out of range after starting high-dose fish oil.

Kidney issues? High-dose protein supplementation needs medical supervision. The 1.6-2.2g/kg range assumes normal kidney function.

Autoimmune conditions can be tricky with immune-modulating supplements. Vitamin D generally helps, but some people with autoimmune issues react differently to high doses. Start low, go slow.

And honestly—if you're not exercising consistently, don't waste money on these. Myokines are exercise-responsive. No workout, no meaningful myokine production to optimize.

FAQs

Can I just take an "irisin supplement"?
No—and any product claiming to contain irisin is misleading you. Irisin is a peptide hormone released from muscle during exercise. It's not stable in supplement form, and even if it were, it wouldn't survive digestion. Focus on supporting your body's natural production instead.

How long until I notice effects?
Omega-3 incorporation into muscle membranes takes 8-12 weeks. Vitamin D status changes over 2-3 months. Magnesium benefits for sleep might show up in days, but muscle effects take weeks. This isn't instant—it's about changing your nutrient environment.

Should I get blood tests first?
Ideally, yes—especially for vitamin D and omega-3 index. But if that's not feasible, starting with the doses I've recommended is generally safe for healthy adults. Just don't megadose.

What about creatine for myokines?
Good question. Creatine doesn't directly affect myokines, but it improves exercise performance, which means better workouts, which means more myokine production. It's indirect but valuable. 5g daily of creatine monohydrate is what I recommend.

Bottom Line

• You can't supplement myokines directly—any product claiming otherwise is selling hope, not science
• Omega-3s (2-3g EPA/DHA), vitamin D (2,000-4,000 IU), magnesium glycinate (300-400mg), and adequate protein (1.6-2.2g/kg) create the nutrient environment for optimal myokine production
• Individual response varies dramatically—what works for your training partner might not work for you
• Without consistent exercise, none of this matters. Myokines are exercise-responsive signaling molecules

Disclaimer: This is general information, not medical advice. Talk to your healthcare provider before starting any new supplement regimen, especially if you have health conditions or take medications.