Mind & Matter
Whether food, drugs or ideas, what you consume influences who you become. Learn directly from the best scientists & thinkers alive today about how your mind-body reacts to what you feed it.
The weekly M&M podcast features conversations with the most interesting scientists, thinkers, and technology entrepreneurs alive today.
Not medical advice.
At M&M, we are interested in trying to figure out how things work, not affirming our existing beliefs. We prefer consulting primary rather than secondary sources and independent rather than institutional voices. If we encounter uncomfortable truths or the evidence suggests unfashionable ideas may be valid, so be it.
As the host, my aim is to help you better understand how the body & mind work by curating & synthesizing information in a way that yields science-based insights that you can choose to use or disregard in your own life. Taking ownership of your health starts with taking ownership of your information diet.
I am motivated to connect the dots and distill general principles from what I learn, preferring to ask questions and play devil’s advocate to debating or incessantly pushing my own viewpoint.
My beliefs:
- Taking ownership of your health starts with taking ownership of your information diet.
- All knowledge is provisional and we must work hard to prevent ourselves from becoming attached to our favorite ideas & preferred conclusions.
- Wisdom comes from an iterative, trial-and-error process of learning and unlearning. Letting go of pre-conceived notions can be painful, but pain is information.
Sometimes modern discoveries teach us we must unlearn received wisdom. Other times, modern information overload & historical chauvinism cause us to forget ancient wisdom which stills applies. The framework for learning that I embody is inspired by three Ancient Greek maxims inscribed in the Temple of Apollo at Delphi:
- “Γνῶθι σεαυτόν” (Know thyself)
- “Μηδὲν ἄγαν” (Nothing in excess)
- “Ἐγγύα πάρα δ Ἄτα” (Certainty brings insanity)
Mind & Matter
Fructose Metabolism in Obesity, Dementia, Evolution | Richard Johnson | Episode 295
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Fructose survival hypothesis: how fructose metabolism in the liver triggers ATP depletion, uric acid production, oxidative stress, lipogenesis & leptin resistance.
TOPICS DISCUSSED:
- Glucose vs Fructose Metabolism: Fructose is rapidly metabolized in the liver by fructokinase without feedback, causing ATP depletion and uric acid production, unlike glucose metabolism.
- Liver Effects: Fructose induces uric acid production, NADPH oxidase activation, mitochondrial oxidative stress, and de novo lipogenesis even under caloric restriction.
- Fructose Survival Hypothesis: Fructose signaling promotes fat storage, leptin resistance, foraging behavior, and metabolic syndrome as adaptations for hibernation or starvation, including metabolic water production.
- Brain Impacts: Endogenous fructose production from glucose (polyol pathway) triggered by high glucose, salt, or stress leads to insulin resistance, mitochondrial damage, and neuroinflammation in Alzheimer’s-vulnerable regions.
- Evolutionary Context: Human uricase mutation ~12 million years ago enhanced fructose effects for fat storage during seasonal starvation but increases vulnerability today.
- Modern Triggers: Added sugars, high fructose corn syrup, salt-sugar combinations, and omega-6 fats synergize with fructose to amplify inflammation, appetite, and disease risk.
- Alzheimer’s Link: Fructose-driven brain changes mirror Alzheimer’s pathology, with high brain fructose in patients and potential for fructokinase inhibitors as therapy.
ABOUT THE GUEST: Richard Johnson MD, is a professor of medicine who has conducted clinical practice and NIH-funded research on sugar metabolism since the late 1990s. His work focuses on the role of fructose in metabolic syndrome, obesity, and related diseases.
RELATED CONTENT:
- Article | Dietary Fructose & Metabolic Health: An Evolutionary Perspective
- M&M 249: Fructose, Microglia, Anxiety & Brain Development | Justin Perry | 249
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