Plain English BEST OF: A Grand, Unified Theory of Why Americans Are So Unhealthy

Podcast: Plain English with Derek Thompson (The Ringer)
Date: December 16, 2025
Featured Guests: Dr. David Kessler (Former FDA Commissioner), Dr. Eric Topol (Cardiologist & Scripps Institute Director)
Host: Derek Thompson

Episode Overview

This "best of" episode tackles one of the thorniest and most important questions in American life: Why are Americans so unhealthy—particularly compared to other wealthy countries? Derek Thompson weaves together two previous interviews with Dr. David Kessler and Dr. Eric Topol to present a grand, unified theory. Their conversation builds from facts about obesity and diet to a compelling model that connects America's calorie-rich environment, the proliferation of ultra-processed foods, chronic inflammation, and the latest medical interventions.

Key Discussion Points & Insights

1. America’s Exceptional Poor Health

• U.S. has higher rates of obesity and chronic illness than other rich nations, affecting every socioeconomic, ethnic, and educational group (02:35).
• Even wealthy, insured, well-educated Americans are less healthy than their counterparts abroad.

2. The Calorie Environment: From Scarcity to Overabundance

• Kessler on Evolution & Abundance:
  • Our bodies are adapted for a world of scarcity, yet we now live in overwhelming abundance (06:32).
  • "If anything, our brains are working too well." — Dr. David Kessler (08:19)
• Historical Perspective:
  • For decades, caloric availability hovered around 3,300/day; only in the late 20th century did this shoot up to 4,000+ calories per person, per day (07:08).
• Our brains are wired to seek energy-dense foods, and we've constructed a "food circus" of easy, constant access.
  • "We put all this energy dense food, made it available, and made it socially acceptable to eat any time. So we played right into those circuits." — Dr. Kessler (09:08)

3. Ultra-Processed Foods & Metabolic Chaos

• Nova food classification: Only the most processed, “ultra-processed” (category 4) foods present real danger.
• Removing a food’s natural “structure” accelerates glucose absorption (“whoosh”), disrupting metabolic stability (10:30).

4. The Cascade: Caloric Surplus → Toxic Fat → Inflammation → Disease

• Toxic (visceral) fat:
  • Not all fat is equal—visceral (internal/organ) fat is metabolically dangerous, driving chronic disease (11:35).
• Metabolic Mechanism:
  • Chronic overconsumption leads to more visceral fat (“toxic fat”) which releases damaging acids and proteins, overtaxing the liver, pancreas, heart, and confusing immune signals (11:59, 12:23).
• Hyperinsulinemia:
  • Excess fast-absorbed sugars have resulted in a doubling of “hyperinsulinemia”: chronically high insulin levels, a root of metabolic diseases (13:26).

5. Chronic Inflammation: The Unifying Disease Driver

• Explained by Dr. Topol:
  • Chronic inflammation is to internal tissues what swelling and heat are to a banged knee: visible in injuries, but invisible and persistent in key organs (15:09, 16:31).
• Modern life bombards us with “small bangs” (rich food, lack of exercise, poor sleep, environmental toxins), leading to constant low-level inflammation (17:25).
  • "That's why it's called inflammaging." — Dr. Eric Topol (17:55)
• "It’s the underpinning, the common thread to the big three age-related diseases: cancer, atherosclerotic heart disease, and neurodegenerative diseases." — Dr. Topol (19:15)

6. Tracking and Individual Differences

• No perfect inflammation marker yet, but glucose spiking (detected by sensors) is a good proxy (23:33, 23:40).
• Individual response matters:
  • “You and I, Derek, we ate the exact same thing… We might have a very different response.” — Dr. Topol (24:31)
  • Large NIH studies are underway; personalized recommendations remain years away.

7. Exercise: The ‘Good’ Stress

• Why does exercise help if it’s also inflammatory?
  • Exercise gives the immune system “training” — a controlled stressor that ultimately improves function, unlike chronic, uncontrolled inflammation (25:31).
  • “Exercise can induce a low level inflammation, but… it gets your immune system function and your inflammation into its highest functionality.” — Dr. Topol (25:31)

8. Hope & Novel Treatments: GLP-1 Agonists

• Old advice (“eat less, exercise more”) failed at scale; biology and addiction override willpower (26:53, 27:10).
• GLP-1 Mediated Drugs (Ozempic, Wegovy, etc.):
  • Delay gastric emptying (food stays in the stomach longer, increasing fullness).
  • Remarkable effect: Not only do people eat less, but they change what they eat—less ultra-processed food; more fruits and vegetables.
    • “When I went on these GLP1 drugs, I didn't want to put anything else in my stomach... So I started for the first time eating vegetables.” — Dr. Kessler (29:43)
  • Affect dopamine and reward circuits; may even curb other compulsive behaviors (gambling, smoking) (30:26, 30:44).
  • Dr. Topol: “We're only at the beginning of the gut hormone story... this has turned out to be one of the most extraordinary anti-inflammatory mediators that we have ever seen. They make statins look weak.” (30:44, 31:14)

9. The Future: Gut Hormones & Microbiome Support

• Dramatic growth anticipated in gut hormone-based treatments (triple agonists, much broader prescriptions, pills instead of injections), potentially recommended for non-obese, non-diabetic patients as an anti-inflammatory (“standard part of medicine in the years ahead”) (33:10, 34:59).
• Manipulating the gut microbiome (via pre/probiotics) might offer another path.
  • "This is just early stuff; people don't realize how big this gut hormone and gut microbiome story is to unfold." — Dr. Topol (34:59)

Notable Quotes & Memorable Moments

• "It's not that there's something wrong with our brains. If anything, our brains are working too well." — Dr. David Kessler [08:19]
• "We live in a food circus." — Dr. Kessler [08:39]
• "[Ultra-processed foods] are rapidly absorbed in the GI tract. They are, in essence, creating metabolic chaos." — Dr. Kessler [10:30]
• "Toxic fat... is causal in those chronic diseases." — Dr. Kessler [11:35]
• "That's why it's called inflammaging." — Dr. Eric Topol [17:55]
• "It's the common thread to the big three age-related diseases: cancer, atherosclerotic heart disease, and neurodegenerative diseases." — Dr. Topol [19:15]
• "Exercise can induce a low level inflammation, but… it gets your immune system function and your inflammation into its highest functionality." — Dr. Topol [25:31]
• “When I went on these GLP1 drugs, I didn't want to put anything else in my stomach... So I started for the first time eating vegetables.” — Dr. Kessler [29:43]
• "They make statins look weak." — Dr. Topol on anti-inflammatory power of GLP-1 drugs [31:14]
• "This is just early stuff; people don't realize how big this gut hormone and gut microbiome story is to unfold." — Dr. Topol [34:59]

Major Segment Timestamps

• [02:35] – U.S. health disadvantage, problem statement
• [04:43] – David Kessler’s personal weight struggle
• [06:32] – Evolutionary roots: scarcity to abundance
• [07:08] – Historical calorie availability
• [08:39] – The ‘food circus’ of modern America
• [09:23] – The Nova food classification and ultra-processed foods
• [11:35] – “Toxic fat,” subcutaneous vs. visceral fat
• [13:26] – Hyperinsulinemia and metabolic disruption
• [15:09] – Chronic inflammation: what it is and why it matters
• [17:55] – Inflammaging and age-related disease
• [23:33] – Lack of inflammation biomarkers; using glucose as proxy
• [24:31] – Individual differences in metabolism
• [25:31] – The paradox and benefits of exercise
• [26:53] – Failures of “eat less, exercise more”
• [28:10] – Introduction to GLP-1s (Ozempic, Wegovy, etc.)
• [29:43] – How GLP-1s change not just “how much” but “what” we eat
• [30:44] – GLP-1s and the gut-brain-immune connection; future possibilities
• [33:10] – The future of broad prescription for gut hormone agonists
• [34:59] – The importance and untapped potential of the gut microbiome

Closing Analogy & Takeaway

• Derek Thompson closes with the metaphor of the human body as a car:
  The modern food environment is like jamming the gas pedal with a brick, propelling us into overeating and inflammation. GLP-1s act as a brake, slowing gastric emptying, dulling food noise, and returning us to balance.

Conclusion

This episode constructs a persuasive, multi-part theory connecting societal, biological, and technological factors behind America's health crisis. Rooted in an evolutionary mismatch and turbocharged by profit-driven food innovation, Americans are beset by a cascade: caloric abundance → visceral fat → chronic inflammation → chronic disease. While built environment and biology have made self-control supremely difficult, new advances—especially GLP-1 drugs and gut hormone manipulation—hold revolutionary promise not just for weight loss, but for preventing and undoing the chronic inflammation underlying America’s epidemic of disease.

“They turn down the volume of the food noise and return us to our regularly scheduled thoughts… They remind the body that the brake pedal exists.” — Derek Thompson [36:34]