Wide release: May 1, 2026. Not medical advice.
Nick speaks with Dr. Philip Calder, a nutritional immunologist at the University of Southampton who has spent over three decades studying how dietary fats shape immune function. Calder explains that inflammation is not simply "turned on" by omega-6s and "turned off" by omega-3s, but is a three-phase process — initiation, propagation, and resolution — each actively regulated by competing lipid mediators. The conversation covers the biochemistry of prostaglandins and resolvins, why cell membrane fatty acid composition is a key determinant of inflammatory capacity, and why the U.S. dietary pattern of high linoleic acid intake may blunt the body's ability to synthesize EPA and DHA endogenously.
TOPICS DISCUSSED:
Parenteral nutrition history: IV nutrition evolved from soybean oil alone in the 1960s to complex blends including fish oil as the biology of ω-3s became understood.
Three phases of inflammation: Initiation, propagation (driven by ω-6–derived prostaglandins and leukotrienes), and active resolution (driven by ω-3-derived resolvins and protectins).
Pro-resolving mediators: Resolution is an active biological process, not passive; EPA and DHA generate resolvins and protectins that actively terminate inflammation.
Aspirin’s ω-3 mechanism: Aspirin inhibits arachidonic acid metabolism but allows EPA/DHA to access COX-2, upregulating pro-resolution mediators — a likely underappreciated mechanism of action.
Cell membrane competition: EPA and DHA physically displace arachidonic acid in membranes, shifting the balance of mediators produced and improving resolution capacity.
Linoleic acid & EPA synthesis: High linoleic acid intake saturates shared desaturase enzymes, inhibiting the body’s conversion of ALA to EPA — meaning reducing ω-6 can raise ω-3 levels without supplementation.
Dose & timing of ω-3 incorporation: ~2g/day of EPA+DHA shifts the arachidonic acid-to-EPA ratio enough to measurably reduce prostaglandin E2 production; white blood cells reflect changes within a month.
ABOUT THE GUEST: Philip Calder, PhD is Professor of Nutritional Immunology in the Faculty of Medicine at the University of Southampton. His research focuses on how dietary fatty acids — particularly omega-3s — modulate immune responses and inflammatory processes across clinical and healthy populations.
RELATED EPISODE:
M&M 200: Dietary Fats & Seed Oils in Inflammation, Colon Cancer & Chronic Disease | Tim Yeatman & Ganesh Halade
KNOW YOURSELF:
OmegaQuant: At-home blood testing to see fatty acid profiles, including omega-3 fatty acids. Use link to see options and support M&M.
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PRACTICAL TAKEAWAYS:
Aim for 1–2g/day of EPA+DHA combined (from fatty fish, fish oil, algal oil, or krill oil) to meaningfully shift cell membrane fatty acid composition and reduce inflammatory signaling capacity.
Reducing very high linoleic acid intake — common in U.S. diets averaging 16–18g/day from seed oils — may raise your EPA levels even without adding ω-3 supplements, because both fatty acid families compete for the same conversion enzymes.
Cell membrane fatty acid composition changes are dose-dependent and reversible. Consistency matters more than any single high dose.
SUBSCRIBER CONTENT BELOW: Reference paper + episode transcript.
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