Mind & Matter

• Seed Oils, Chronic Inflammation, Heart Health & Marijuana | Ganesh Halade | 266

  Send us a textHow dietary polyunsaturated fats, especially omega-6 from seed oils, influence inflammation & heart health.Topics Discussed:Polyunsaturated fatty acids (PUFAs): Omega-6 from seed oils like safflower and corn can convert to pro-inflammatory molecules, while omega-3s produce resolving ones; imbalance biases toward chronic inflammation.Inflammation regulation: Acute inflammation aids healing but requires active “on” and “off” signals from lipid mediators; chronic inflammation arises from excess omega-6, delaying resolution.Heart health & diet: High omega-6 diets worsen post-heart attack outcomes in mice by elevating pro-inflammatory lipids.Evolution & historical context: PUFAs are essential but naturally balanced in pre-industrial diets; modern processing skews ratios, contributing to diseases, as shown in early rat experiments needing minimal fats for survival.Aging & lifestyle factors: Excess omega-6 exacerbates inflammation in older mice; sleep, exercise, and balanced fats are crucial for metabolic health and enzyme function in processing lipids.Cannabis & omega-6 interaction: In mice on high omega-6 diets, CBD-rich cannabis smoke reaches the heart quickly, suppresses immune response, and weakens cardiac strain, unlike in balanced-diet controls.Genetic models: FAT-1 mice converting omega-6 to omega-3 show better healing and neuroprotection; FAT-2 mice doing the opposite exhibit liver fibrosis and metabolic issues, highlighting omega-6 excess harms.Practical Takeaways:Balance omega-6 and omega-3 intake by reducing seed oils in processed foods and increasing sources like fish or algae to support inflammation resolution and heart health.Monitor and adjust fat intake with age, as older individuals are more sensitive to omega-6 excess leading to immune dysregulation.Avoid combining high omega-6 diets with smoking, as it may impair immune and cardiac responses based on animal data.About the guest: Ganesh Halade, PhD is a cardiovascular scientist and associate professor at the University of South Florida Morsani College of Medicine.*Not medical advice.Support the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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• Evaluating Science: Clinical Trials, Epidemiology, Preclinical Studies & Mendelian Randomization | George Davey Smith | 265

  Send us a textMethods & challenges of establishing causal relationships in health research, emphasizing epidemiology, randomized trials, and genetic approaches.Topics:Epidemiology: Studies disease influences using observational designs like case-control and prospective cohorts, plus trials, to identify patterns and test hypotheses.Hierarchy of evidence critique: Rejects rigid pyramids favoring RCTs, as all studies can be biased; advocates triangulation integrating varied data types for robust conclusions.RCT strengths & weaknesses: Randomization balances confounders, but issues like poor blinding, attrition, or subversion can undermine results; large samples may yield spurious precision if biased.Confounding & reverse causation: Examples include yellow fingers and lung cancer (both from smoking) or early atherosclerosis inflating CRP-disease links; hard to fully control statistically.Nutrition epidemiology: Observational studies often overstate benefits (e.g., vitamin E for heart disease), leading to failed trials; incentives favor new findings over revisiting errors.Mendelian randomization: Uses genetic variants as proxies for exposures (e.g., ALDH2 for alcohol metabolism) to mimic randomization; reveals no heart benefits from alcohol, unlike observational data.Negative controls: Tests implausible outcomes (e.g., smoking and murder) or exposures (e.g., paternal smoking in pregnancy) to check for confounding artifacts.Evidence triangulation: Combines diverse studies with different biases (e.g., cross-cultural comparisons) for causality; applied to dismiss HDL-raising drugs despite initial promise.Practical Takeaways:Scrutinize health claims by checking for negative controls or variety in evidence sources to avoid mistaking correlation for causation.For personal decisions like alcohol intake, consider genetic studies showing risks at all levels, and aim for moderation or abstinence based on overall evidence.When evaluating supplements or diets, prioritize trials over observational data, and question media hype that ignores confounding factors.About the guest: Dr. George Davey Smith, MD, DSc is a professor of clinical epidemiology at the University of Bristol and director of the MRC Integrative Epidemiology Unit.*Not medical advice.Support the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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• Energy Metabolism & Information Processing in the Brain | Luis Felipe Barros | 264

  Send us a textIntegration of brain metabolism with neural signaling, highlighting how core metabolites regulate energy use and protect neurons.Topics Discussed:Brain energy efficiency: Brains are much more energy-efficient than computers for similar processing, relying on adaptive metabolic strategies evolved under energy scarcity.Metabolism vs. information processing: Core metabolites like glutamate bridge basic cellular energy production and neural signaling.Lactate as a signal: Produced during exercise, lactate diffuses from muscles to brain, modulating neuronal excitability and providing neuroprotection.BHB in ketosis: During fasting or ketogenic diets, beta-hydroxybutyrate displaces glucose as fuel, enhances antioxidant defenses, and activates protective potassium channels in neurons.Adenosine and sleep: Accumulates from ATP breakdown during wakefulness, triggering sleep and locally inhibiting overactive neural networks for energy conservation.Glial cells’ role: Astrocytes and oligodendrocytes handle sophisticated metabolism, release signaling molecules like lactate, and modulate synapses, and influence diseases like Alzheimer’s.Practical Takeaways:Regular exercise elevates lactate, which signals the brain to adapt metabolism and may enhance neuroprotection against stress.Intermittent fasting or ketogenic diets can induce ketosis with BHB, potentially boosting brain antioxidant defenses and preconditioning against metabolic stress.Prioritizing sleep helps clear adenosine buildup, restoring energy balance and supporting long-term neural health.About the guest: Dr. Luis Felipe Barros, MD, PhD is a Chilean neurobiologist and professor at the Universidad de Valparaíso, where he leads a lab studying brain metabolism from glucose transport to mitochondrial function.Related Episode:M&M 255 | Unlocking Energy: How Nutrition & Drugs Impact Your Mitochondria | Chris Masterjohn*Not medical advice.Support the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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• How & Why Mitochondria Make Their Own Fat | Sara Nowinski | 263

  Send us a textMitochondrial fatty acid synthesis is a little-known but essential pathway that supports energy production and metabolic health.Summary: Dr. Sara Nowinski explains how mitochondria not only burn fuels to make ATP but also synthesize their own fatty acids inside the matrix; this conserved pathway produces lipoic acid (an essential enzyme cofactor) and longer-chain fats required for proper assembly of the electron transport chain, and disrupting it impairs respiration, glucose handling, and insulin sensitivity while enhancing it appears protective against obesity and heart injury.About the guest: Sara Nowinski, PhD is an assistant professor in the Department of Metabolism and Nutritional Programming at Van Andel Institute in Grand Rapids, Michigan, where since 2021 she has led a lab focused on mitochondrial biology and the mitochondrial fatty acid synthesis (mitoFAS) pathway.Topics Discussed:Basic mitochondrial energy production: food → pyruvate/fatty acids → acetyl-CoA → TCA cycle → electron transport chain → ATPMitochondrial fatty acid synthesis (mitoFAS): a bacterial-like pathway that builds fats on an acyl carrier protein inside the matrixLipoic acid: an 8-carbon fatty acid made only by mitoFAS, covalently attached to key enzymes (e.g., pyruvate dehydrogenase); cannot be rescued by supplements for cofactor useLonger mitoFAS products (14–16 carbons) stabilize electron transport chain assembly factors, explaining why pathway loss collapses respiration even when lipoic acid is intactKnocking out mitoFAS causes embryonic lethality, insulin resistance, poor glucose homeostasis, and a rare neurodegenerative disorder (MEPAN syndrome)Overexpressing the mitochondrial acyl carrier protein protects mice from diet-induced obesity, insulin resistance, and cardiac injuryMuscle cell differentiation fails without mitoFAS, hinting at a role in tissue development and repairPractical Takeaways:Supplemental lipoic acid can act as an antioxidant but cannot replace the lipoic acid your mitochondria must make themselves for enzyme function.Severe impairment of mitochondrial fatty acid synthesis is linked to insulin resistance and metabolic disruption, suggesting mitochondrial health (beyond just biogenesis) matters for glucose control.*Not medical advice.Support the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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• Hormones & Instincts: Hunger, Aggression & Parenting Behavior | Jonny Kohl | 262

  Send us a textHow internal states like hunger and hormones shape instinctive behaviors, particularly parental careEpisode Summary: Dr. Johannes Kohl explains instinctive behaviors in mammals, emphasizing how states like hunger and hormonal cycles modulate actions such as parental care; they discuss hypothalamic circuits, hormone integration, and pregnancy-induced brain changes, highlighting the balance between motivations like feeding and nurturing offspring.About the guest: Jonny Kohl, PhD heads the State-Dependent Neural Processing Lab at the Francis Crick Institute in London.Discussion Points:Instinctive behaviors: Pre-wired actions like escaping predators or parental care enable survival without learning, yet remain modifiable by experience and internal states.Internal states: Defined as slowly changing conditions (minutes to weeks) like hunger or hormonal fluctuations that influence brain processing & behavior prioritization.Hunger regulation: Hypothalamic AGRP neurons detect caloric deficits, creating motivational discomfort relieved by food anticipation, operating on multiple timescales via neurotransmitters & peptides.Parental care: Virgin mice show variable pup-directed behaviors; hunger increases aggression, modulated by estrous cycle hormone ratios (estradiol/progesterone).Hormone-brain interactions: Steroid hormones like estradiol and progesterone diffuse into the brain, altering gene expression, neuronal excitability, and circuit plasticity over short and long timescales.Pregnancy adaptations: Late pregnancy rewires MPOA circuits via surging hormones, preparing robust maternal behavior before birth (anticipatory brain plasticity).Practical Takeaways:Recognize hunger’s impact: Mild food deprivation can heighten irritability or aggression, which can affect social interactions.Consider hormonal influences: Cyclical hormone changes affect mood and motivation; tracking cycles may help predict and manage behavioral shifts.Prioritize self-care in parenting: Sleep and nutrition deficits mimic hunger states, potentially reducing patience; ensure rest and meals to support nurturing behaviors.Question chronic hormone use: Long-term interventions like birth control or testosterone can alter brain function; weigh benefits against potential side effects.*Not medical advice.Support the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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