Urolithin A: The Human Data on ‘Anti-Aging’ (Mitophagy, Inflammation, Muscle — What Actually Changes)

In this Energy Code Deep Dive, Dr. Mike Belkowski and moderator Don Bailey break down a 2024 systematic review, “Targeting Aging With Urolithin A in Humans," that focuses on human supplementation studies, not “eat pomegranate and hope.” 

You’ll learn what Urolithin A is (and why your gut bacteria can make results wildly inconsistent), why it’s tied to “geroprotection,” and what the clinical evidence actually supports so far: dose-dependent anti-inflammatory signals, changes in mitochondrial/autophagy gene markers, and some improvements in strength/endurance — with a reality check on what didn’t move (ATP max, broad physical function, microbiome composition, body comp, cardiovascular markers in short windows).

Bottom line: promising, practical, but still early.

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Article Discussed in Episode:

Targeting aging with urolithin A in humans: A systematic review

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Key Quotes From Dr. Mike & Don:

• “It’s like giving two people the same coffee beans, but one of them doesn’t own a coffee grinder!”

• "It may be improving the ‘quality control and efficiency settings’ more than raw peak horsepower.“

• “So it’s like tuning the car so it runs smoother; not necessarily making the top speed higher.”

• "It’s not a ‘lose 20 pounds and become a triathlete’ pill.”

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• Urolithin A is a gut-derived metabolite from ellagic acid foods (pomegranate, walnuts, berries), but many people don’t convert well. So food intake ≠ reliable levels.

• Supplementation “skips the gut lottery” and produces higher, more consistent plasma levels than food sources.

• The systematic review included 5 human studies / 250 healthy participants with 10–1000 mg/day for 28 days to 4 months.

• Biggest consistent theme: dose-dependent anti-inflammatory effects (some markers improve more at 1000 mg/day over 4 months).

• Mitochondria story is nuanced: it may improve gene expression signatures related to mitochondrial activity, autophagy, and fatty-acid oxidation—more “quality control” than peak power.

• What it didn’t reliably do: increase maximal ATP production, consistently boost biogenesis/dynamics markers, change gut microbiota composition, or meaningfully affect body metrics/cardiovascular outcomes in short trials.

• Muscle outcomes: some gains in specific strength/endurance measures (e.g., torque metrics; certain fatigue tests), but not universal (e.g., handgrip and broad function didn’t consistently improve).

• Safety in these studies looked clean (no serious adverse events attributed), but the overall conclusion remains: promising—but the human aging evidence is still young and needs longer/larger trials.

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0:27 — Welcome + urolithin A is trending + episode topic

0:45 — Don’s moderator frame: “does it work / worth it?”

1:04 — Paper ID (2024 systematic review; human supplementation)

1:25 — What urolithin A is + “gut lottery”

2:02 — Why supplement (higher/consistent levels vs food)

2:24 — Why it matters: mitophagy / healthier aging angle

3:05 — What’s included (5 studies, 250 people; 10–1000 mg; 28d–4mo)

3:34 — What improved (inflammation signals, gene markers, some strength/endurance)

4:06 — What didn’t (max ATP, microbiome, broad health/body metrics)

7:02 — Dosing/PK basics (peak ~6h; half-life ~17–22h; plateau ~7d)

7:40 — Safety summary

8:06 — Practical take + “promising but early” conclusion

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