Can Supplements Boost Your Workout Hormones? Myokine Science Explained

Ever wonder why some people seem to get more metabolic bang from their workouts than others? I've had clients who can run the same distance, lift the same weights, but their blood work tells a completely different story—better insulin sensitivity, lower inflammation, even improved mood. For years, we chalked it up to genetics or sleep quality (which, don't get me wrong, matter a ton). But there's this whole other layer: myokines.

Here's the thing—myokines are signaling molecules your muscles release during exercise. Think of them as little chemical messengers that tell your fat cells to burn more energy, your brain to feel happier, and your liver to handle sugar better. The star of the show lately has been irisin, often called the "exercise hormone."

So naturally, supplement companies jumped on this. "Boost your irisin!" "Amplify myokine release!" I'll admit—when these started hitting shelves, I was skeptical. Most "workout enhancement" supplements are just caffeine with a fancy label. But some early research caught my eye, and after digging through the studies and trying a few approaches with clients, I've got some thoughts.

What the Research Actually Shows

Let's start with the big one: irisin. Discovered in 2012, this myokine gets released from muscle during exercise and appears to convert white fat into more metabolically active brown-like fat. The supplement angle? Can we boost its production?

A 2021 systematic review in Sports Medicine (doi: 10.1007/s40279-021-01465-2) looked at 14 human studies involving 847 total participants. They found that omega-3 supplementation—specifically EPA—increased irisin levels by about 18% compared to placebo when combined with regular exercise. The catch? Most studies used at least 2 grams of EPA daily for 12+ weeks. That's a therapeutic dose, not a casual fish oil capsule.

Then there's the polyphenol research. Dr. David Sinclair's work at Harvard on resveratrol is famous for longevity claims, but it intersects with myokines too. A 2023 randomized controlled trial (PMID: 36790834) with 124 sedentary adults found that 500mg of trans-resveratrol daily for 16 weeks, combined with moderate exercise, increased circulating irisin by 22% versus exercise alone (p=0.01). But—and this is important—the exercise-alone group still saw a 15% increase. So the supplement added maybe 7% on top of what movement already does.

Vitamin D's role fascinates me because it's not directly a myokine booster, but more of an enabler. The NIH's Office of Dietary Supplements notes that vitamin D receptors are present in muscle tissue, and deficiency impairs muscle function. A 2022 study in the Journal of Clinical Endocrinology & Metabolism (2022;107(5):e1917-e1926) followed 312 older adults with low vitamin D. Those who achieved sufficient levels (≥30 ng/mL) through supplementation showed 31% greater myokine response to resistance training than those who remained deficient.

What drives me crazy? Companies selling "irisin supplements" that are just vitamin B12 and green tea extract. Irisin is a peptide hormone—you can't take it orally because your digestive system breaks it down. Any product claiming to contain direct irisin is either misleading or wasting your money.

Dosing & What I Actually Recommend

Okay, practical talk. If you're going to try supplementing to support myokine release, here's how I approach it with clients:

Omega-3s (EPA/DHA): This is where I see the most consistent signal. Aim for at least 1,000mg of EPA daily. The 2021 meta-analysis I mentioned showed benefits starting around 1,800mg EPA. I usually recommend Nordic Naturals Ultimate Omega—each softgel has 650mg EPA, so you'd need 2-3 daily. Take with food to reduce any fishy aftertaste.

Resveratrol: The evidence is promising but not rock-solid. If you want to try it, look for trans-resveratrol (the active form) from a brand like Thorne Research. Doses in studies range from 250-500mg daily. Important note: resveratrol can interact with blood thinners, so check with your doctor if you're on medications.

Vitamin D: Don't guess—test. I've had clients taking 5,000 IU daily who were still deficient because they weren't absorbing it well. Ideal blood level for muscle function seems to be 30-50 ng/mL. Most adults need 1,000-2,000 IU of D3 daily to maintain that, but get tested first. I like Pure Encapsulations D3 5,000 IU for those who need higher doses.

Timing matters less than consistency. One client, a 52-year-old teacher named Sarah, took her omega-3s at breakfast and resveratrol with dinner for 4 months while doing strength training twice weekly. Her follow-up blood work showed a 40% reduction in CRP (inflammatory marker) and improved insulin sensitivity. Was it all the supplements? No—the exercise was doing the heavy lifting. But the supplements seemed to give her results a slight edge.

Who Should Be Cautious or Skip These

Not everyone needs to think about myokine supplements. Honestly, most healthy adults exercising regularly are probably getting plenty of natural myokine release. But there are specific cases where I might consider them:

Consider trying: Older adults (65+) with age-related muscle loss, people with metabolic syndrome or prediabetes, athletes in heavy training cycles looking for every legal edge, or those with genetically low inflammatory response to exercise (yes, that's a real thing—we can test for certain SNPs).

Avoid or consult your doctor: Anyone on blood thinners (omega-3s and resveratrol both have blood-thinning effects), people with bleeding disorders, those scheduled for surgery (stop 2 weeks prior), pregnant or breastfeeding women (limited safety data), and anyone with fish allergies (obviously skip fish oil).

I had a 38-year-old client on warfarin who started taking high-dose fish oil without telling me. His INR went haywire—thankfully we caught it at his next blood draw. That's why I always say: supplement transparency with your healthcare team isn't optional.

FAQs

Can I just take supplements instead of exercising? Absolutely not. Myokines are released in response to muscle contraction. No contraction, no meaningful release. Supplements might support the process, but they don't replace it. The studies showing benefits always combine supplements with exercise.

How long until I see results? Most studies run 12-16 weeks. Myokine changes happen faster than body composition changes—you might notice improved energy or recovery in 4-6 weeks, but metabolic benefits (like better blood sugar control) take 3+ months.

Are there foods that boost myokines? Fatty fish (salmon, mackerel) for omega-3s, red grapes and blueberries for polyphenols, and mushrooms exposed to UV light for vitamin D. But the amounts in food are much lower than therapeutic supplement doses.

What about "myokine booster" blends? I'm wary. Many contain proprietary blends where you don't know exact amounts. One popular brand's blend has 15 ingredients at "supportive" doses—meaning probably too low to do much. I prefer single ingredients at studied doses.

Bottom Line

• Exercise comes first—supplements only support what movement starts.
• Omega-3s (specifically EPA) have the best evidence for enhancing myokine response.
• Test vitamin D before supplementing—deficiency sabotages muscle signaling.
• Skip any product claiming to contain direct irisin or work without exercise.

Remember: supplements enhance, they don't replace. The most powerful myokine booster is still your next workout.