The Metabolic Link

Dr. Paul Reynolds has spent his career studying what he calls “two heads of the same beast”: inflammation and glycation — two interlocking processes that may help explain why so many chronic diseases are connected, even when they are treated as separate conditions.
Dr. Reynolds is a professor and research scientist at Brigham Young University whose NIH-funded research program studies inflammation, lung biology, glycation, and the AGE/RAGE receptor system that links metabolic and environmental stressors to disease throughout the body.
In this episode, Dr. Reynolds traces the glycation cascade from early sugar-protein reactions to advanced glycation end-products, or AGEs, and explains how the RAGE receptor can act as a self-perpetuating accelerant for inflammation. He also breaks down why the brain may be uniquely vulnerable to glucose dysregulation, how diesel exhaust and tobacco smoke can create AGE-like structures that bind the same inflammatory receptors, and how the glyoxalase defense system helps neutralize damage before it becomes permanent.
Questions Answered in This Episode:
Can breathing polluted air trigger some of the same inflammatory pathways as excess sugar exposure?
Is browned food a real glycation concern, or is the bigger issue what happens inside the body when glucose stays elevated?
Why is the brain especially vulnerable to glucose dysregulation?
How does fasting help the body reduce glycation and inflammatory burden?
What do people need to understand about sugar substitutes like allulose and xylitol when it comes to glycation?
How should we approach kids’ nutrition if glycation and inflammation can begin early in life?
Is glycation damage reversible, and where does the body draw the line?
This conversation offers a mechanistic map connecting cardiovascular disease, neurodegeneration, metabolic dysfunction, environmental exposures, and visible aging back to two upstream processes many patients never hear named in a clinical visit.
Find the Meet Consumption and Cognitive Health paper here.
Sign up for his upcoming Q&A on The Metabolic Initiative here.
Find Dr. Reynolds online:
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Special thanks to the sponsors of this episode:
✅ Toups and Co – Get 15% off your first order with code METABOLIC here.
✅ Fatty15 – Get 15% off a 90-day Starter Kit with code METABOLICLINK here
✅ ZocDoc - Find and instantly book a top-rated doctor here
In every episode of The Metabolic Link, we'll uncover the very latest research on metabolic health and therapy. If you like this episode, please share it, subscribe, follow, and leave us a comment or review on whichever platform you use to tune in!

You can find us on all your major podcast players here and full episodes are also up on our Metabolic Health Summit YouTube channel!

Find us on social: 
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Please keep in mind: The Metabolic Link does not provide medical or health advice, but rather general information that does not serve as a substitute for a licensed healthcare professional. Never delay in seeking medical advice from an appropriately licensed medical provider for any health condition that you may have.

In people with severe depression and cognitive decline, brain glucose metabolism has been shown in some studies to decline measurably. Ketone metabolism, by contrast, appears relatively preserved. That single observation is reshaping how researchers think about psychiatric illness.
In this episode, Dominic D'Agostino sits down with Bret Scher, a cardiologist who pivoted to metabolic psychiatry and now leads clinical education and content for Metabolic Mind at the Baszucki Group. Dr. Scher brings a rare dual perspective: deep training in conventional cardiology paired with three years embedded in the research and clinical practice exploring metabolic approaches in psychiatry.
The conversation covers brain energy dysfunction as a potential unifying mechanism across psychiatric disorders, the preserved ketone metabolism documented in work by researchers like Stephen Cunnane, the recently published Delphi consensus paper on metabolic psychiatry, why four-week randomized trials may be inadequate for nutritional interventions, and the case for future diagnostic categories like metabolic depression and metabolic bipolar disorder.
Questions Answered in This Episode:
Are we underestimating brain energy dysfunction as a potential unifying mechanism across psychiatric disorders?
What are the two biggest clinical mistakes patients make when starting ketogenic therapy for mental illness?
Should ketogenic therapy ever be positioned as a first-line intervention for psychiatric disorders?
What is the single biggest bottleneck preventing wider clinical adoption of ketogenic therapy?
What has been the most unexpected challenge in moving metabolic psychiatry into the mainstream?
What does precision, personalized, prescriptive ketone metabolic therapy actually look like in clinical practice?
This conversation reframes psychiatric illness as a question of brain energy alongside neurotransmitter signaling and other biological mechanisms, with implications for how the next decade of research and clinical training will unfold.
Join the Live Q&A with Dr. Bret Scher. Bring your questions directly to Dr. Scher on May 29 at 10:00 a.m. Pacific / 1:00 p.m. Eastern. Register here.
Where to Find Dr. Bret Scher Online:
Metabolic Mind
Coalition for Metabolic Health
Special thanks to the sponsors of this episode:
✅ Toups and Co – Get 15% off your first order with code METABOLIC here.
✅ iRestore – Get a huge discount on the Elite and the Illumina bundle with the code LINK here.
✅ MudWtr – Get up to 43% off + free shipping and a free rechargeable frother with code METABOLICLINK here.
In every episode of The Metabolic Link, we'll uncover the very latest research on metabolic health and therapy. If you like this episode, please share it, subscribe, follow, and leave us a comment or review on whichever platform you use to tune in!

You can find us on all your major podcast players here and full episodes are also up on our Metabolic Health Summit YouTube channel!

Find us on social: 
Instagram
Facebook
YouTube
LinkedIn
Please keep in mind: The Metabolic Link does not provide medical or health advice, but rather general information that does not serve as a substitute for a licensed healthcare professional. Never delay in seeking medical advice from an appropriately licensed medical provider for any health condition that you may have.

A gene mutation that reduces ketone production in the fasted state is associated with sudden infant death in modern populations. But in the ancestral context where it evolved alongside an omega-3-rich diet, it may have been part of what kept infants alive.
Dr. Gideon Mailer and Nicola Hale join The Metabolic Link to present their hypothesis that the CPT1A L479 Arctic variant is not anti-ketogenic but pro-metabolic flexibility, conserving glucose by upregulating ketosis at the fed-state threshold. Their work explains why SIDS rates are dramatically elevated in modern Inuit communities no longer eating the ancestral Inuit diet, and how omega-3 fatty acids counteract the downregulation the mutation produces.
The clinical picture extends beyond infancy. Modern carriers of the variant show lower triglycerides, lower VLDL, slightly higher HDL, and a "healthy obesity" phenotype with favorable fat distribution. But the health advantages seen in traditional Inuit populations disappear with Western diet adoption, as cardiovascular disease and diabetes rates rise to match the general population.
Questions Answered in This Episode:
How is the mutation associated with SIDS, and why is there a detrimental effect in modern populations?
How prevalent is the CPT1A Arctic variant in the U.S. population, and does partial Inuit ancestry carry metabolic consequences?
How do omega-3 fatty acids physically upregulate CPT1A activity and concentration within cell membranes?
What metabolic markers distinguish carriers of the L479 variant from non-carriers?
What happens to cardiovascular disease rates in Inuit populations that adopt Western diets?
What should people take away from the Arctic variant story for their own metabolic health?
A sobering case study in what happens when ancestral genetic adaptations collide with modern dietary environments, and what can be recovered when they are realigned.
Special thanks to the sponsors of this episode:
✅ Toups and Co – Get 15% off your first order with code METABOLIC here.
✅ Fatty15 – Get 15% off a 90-day Starter Kit with code METABOLICLINK here
✅ ZocDoc - Find and instantly book a top-rated doctor here
In every episode of The Metabolic Link, we'll uncover the very latest research on metabolic health and therapy. If you like this episode, please share it, subscribe, follow, and leave us a comment or review on whichever platform you use to tune in!

You can find us on all your major podcast players here and full episodes are also up on our Metabolic Health Summit YouTube channel!

Find us on social: 
Instagram
Facebook
YouTube
LinkedIn
Please keep in mind: The Metabolic Link does not provide medical or health advice, but rather general information that does not serve as a substitute for a licensed healthcare professional. Never delay in seeking medical advice from an appropriately licensed medical provider for any health condition that you may have.

In a 12-week clinical trial at The Ohio State University, every woman with PCOS who completed the intervention experienced a change in her menstrual status. One participant, who had never had a period in her life, began menstruating within a week. Another saw spotting after five years of amenorrhea while taking only a ketone supplement without adopting a ketogenic diet. These are among the earliest controlled findings linking ketogenic interventions directly to reproductive hormone restoration.
Dr. Madison Kackley is an Assistant Professor of Kinesiology at The Ohio State University and Director of the SHE Is Laboratory. Her work focuses on how hormonal fluctuations shape metabolic flexibility and resilience in women across the lifespan.
In this episode, she explains why a single fasting glucose or insulin measurement is misleading without knowing where a woman is in her cycle, how the luteal phase creates a state of increased energy expenditure and insulin resistance that conventional carb-loading advice may worsen, and why perimenopausal women who jump into intermittent fasting and high-intensity exercise without prior fat adaptation can end up in a high-cortisol catabolic spiral. She also introduces the Renew study, which examines ketone supplementation alongside group exercise for postpartum depression, a condition she frames as an energy-availability problem rather than a purely psychological one.
Questions Answered in This Episode:
What will we look back on in ten years and realize we got fundamentally wrong about women's health?
Why are women more susceptible to dementia than men, and what does it have to do with reproductive energy?
Why might long-term hormonal birth control contribute to infertility, metabolic syndrome, and type 2 diabetes?
Why can women in perimenopause feel exhausted and still not be able to sleep?
Should weaning be understood as its own distinct hormonal event, separate from postpartum?
For clinicians, researchers, and women navigating these transitions, this conversation previews the evidence-based framework that female metabolic health has been waiting for.
Special thanks to the sponsors of this episode:
✅ Toups and Co – Get 15% off your first order with code METABOLIC here.
✅ iRestore – Get a huge discount on the Elite and the Illumina bundle with the code LINK here.
✅ MudWtr – Get up to 43% off + free shipping and a free rechargeable frother with code METABOLICLINK here.
In every episode of The Metabolic Link, we'll uncover the very latest research on metabolic health and therapy. If you like this episode, please share it, subscribe, follow, and leave us a comment or review on whichever platform you use to tune in!

You can find us on all your major podcast players here and full episodes are also up on our Metabolic Health Summit YouTube channel!

Find us on social: 
Instagram
Facebook
YouTube
LinkedIn
Please keep in mind: The Metabolic Link does not provide medical or health advice, but rather general information that does not serve as a substitute for a licensed healthcare professional. Never delay in seeking medical advice from an appropriately licensed medical provider for any health condition that you may have.

A veteran walks into the clinic with a persistent migraine. Four minutes of vagal nerve stimulation later, the migraine is gone. This is not a one-off result. It is what Dr. Michael Hoffman has been observing for over seven years in the VA hospital system, using non-invasive devices he considers severely underutilized.

Dr. Hoffman is a stroke and cognitive-behavioral neurologist who trained at Columbia University, spent 14 years in the VA system, and has evaluated an estimated 10,000 stroke patients across his career. He now practices at the University of Central Florida, where he integrates ketogenic nutrition, advanced imaging, vagal nerve stimulation, and hyperbaric oxygen into his neurological care.

In this episode, Dr. Hoffman walks through what he calls the "five brain fitness rules," the specific, measurable lifestyle prescriptions he gives every patient, and explains why standard cognitive screening tools like the MoCA and Mini Mental miss the most dramatic behavioral syndromes caused by brain injury.

He also discusses why PET scans and diffusion tensor imaging should be used far more often, and why post-TBI hormonal evaluation is critical but routinely overlooked.
Questions Answered in This Episode:
What are the five brain fitness rules every neurological patient should follow?
Why do standard cognitive tests fail to detect some of the most severe brain injury syndromes?
How is vagal nerve stimulation treating migraines, and why is it so underutilized outside the VA?
What clinical changes would most improve neurological care today?
Does the evidence support hyperbaric oxygen therapy for traumatic brain injury?
Could fungal infections contribute to some long-standing Alzheimer's diagnoses?
What is the surprising decade when your brain's cognitive function peaks?
Dr. Hoffman makes a case that the gap between what we know about the brain and what we do in clinical practice has never been wider, and that closing it starts with giving clinicians the time and tools to actually examine their patients.
Learn more about Dr. Hoffman on his website here.
Special thanks to the sponsors of this episode:
✅ Fatty15 – Get 15% off a 90-day Starter Kit with code METABOLICLINK here
✅ Troscriptions – Get 10% off your first order with code METABOLICLINK here
✅ ZocDoc - Find and instantly book a top-rated doctor here
✅ MudWtr – Get up to 43% off + free shipping and a free rechargeable frother with code METABOLICLINK here

In every episode of The Metabolic Link, we'll uncover the very latest research on metabolic health and therapy. If you like this episode, please share it, subscribe, follow, and leave us a comment or review on whichever platform you use to tune in!

You can find us on all your major podcast players here and full episodes are also up on our Metabolic Health Summit YouTube channel!

Find us on social: 
Instagram
Facebook
YouTube
LinkedIn
Please keep in mind: The Metabolic Link does not provide medical or health advice, but rather general information that does not serve as a substitute for a licensed healthcare professional. Never delay in seeking medical advice from an appropriately licensed medical provider for any health condition that you may have.