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This week’s Metabolic Classroom lecture is a deep dive into the metabolic roots of migraines—a condition that affects millions but is rarely discussed through the lens of insulin resistance and energy dysregulation.

Dr. Bikman explains that migraines are more than just headaches; they’re complex neurological events often triggered by disruptions in how the brain accesses and uses energy. When the brain becomes insulin resistant, its ability to efficiently metabolize glucose falters, increasing susceptibility to migraines due to energy shortfalls and inflammation.

Ben outlines how factors like mitochondrial dysfunction, oxidative stress, and low serotonin—often seen in people with poor metabolic health—are strongly associated with migraine onset. He highlights how common triggers such as glucose spikes, hormonal fluctuations, and inflammation are not just surface-level issues but symptoms of deeper metabolic dysfunction.

The lecture also presents a compelling case for ketogenic diets and ketone supplementation as therapeutic strategies. Drawing from both historical and modern clinical studies, Dr. Bikman shows how ketones can bypass the broken glucose pathways in the insulin-resistant brain, offering a cleaner fuel that improves cellular energy and reduces inflammation. Ultimately, the lecture emphasizes the need to address the root metabolic imbalances to reduce both the frequency and severity of migraines.

Show Notes/References:

For complete show notes and references, we invite you to become an Insider subscriber. You’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A with Ben after the lecture, ad-free podcast episodes, show notes and references, and online, live Office Hours access with Dr Bikman. It also includes Ben’s Research Review Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

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In this Metabolic Classroom lecture, Dr. Bikman explains how rare genetic forms of obesity—known as monogenic obesity—reveal deep insights into how the body stores fat and why the “calories in, calories out” model falls short.

He introduces three genetic conditions—leptin deficiency, POMC deficiency, and MC4R mutations—that disrupt appetite control and fat storage, all while keeping calorie intake the same. These disorders highlight how hormonal imbalances, especially chronically elevated insulin, play the decisive role in whether energy is stored or burned.

Ben walks through the hypothalamic POMC pathway, a brain circuit central to hunger and metabolism. Disruptions in this pathway don’t just make people feel constantly hungry; they reprogram the entire body to hoard calories as fat, even when calorie intake is strictly controlled. Animal and human studies consistently show that these conditions drive dramatic fat gain without an increase in food consumption, clearly separating energy intake from energy storage.

In all three conditions, the common endpoint is hyperinsulinemia—chronically elevated insulin levels—which drives fat storage and insulin resistance. Whether leptin is missing, POMC signals are silenced, or MC4R is defective, insulin surges as the body shifts into extreme conservation mode. This reinforces the idea that obesity is often less about willpower and more about hormonal signaling. Understanding these rare conditions sheds light on more common forms of obesity and reveals that insulin—not just calories—is the gatekeeper of fat storage.

Show Notes/References:

For complete show notes and references, we invite you to become an Insider subscriber. You’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A with Ben after the lecture, ad-free podcast episodes, show notes and references, and online, live Office Hours access with Dr Bikman. It also includes Ben’s Research Review Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

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In this Metabolic Classroom, Ben explores the fascinating metabolic effects of yerba mate, a traditional South American tea that’s gaining attention in scientific circles. Yerba mate contains a synergistic mix of bioactive compounds, including xanthines (like caffeine), chlorogenic acid, and saponins—all of which contribute to its wide-ranging health benefits. Dr. Bikman explains how this unique brew supports fat loss, improves mitochondrial efficiency, regulates appetite, and enhances insulin sensitivity.

Drawing from human and rodent studies, the lecture highlights yerba mate’s ability to increase fat oxidation, particularly when combined with exercise. It also activates AMPK, a critical energy-regulating enzyme, which promotes glucose uptake and mitochondrial biogenesis. One of the most intriguing effects of yerba mate is its stimulation of GLP-1—both directly through the gut and indirectly by modifying the gut microbiome—making it a natural, non-pharmaceutical way to enhance satiety and insulin regulation.

Dr. Bikman also discusses the underappreciated role of bitter taste receptors in the body—not just on the tongue, but also in fat cells and the gut. Yerba mate interacts with these receptors to influence hormone release (like CCK and PYY) and to promote thermogenesis in brown and beige fat, offering yet another pathway for metabolic support. Finally, he shares unpublished findings from his lab showing yerba mate’s impact on hepatic redox balance, adding to its reputation as a powerful metabolic ally.

Ben’s favorite yerba mate and fiber supplement: https://ufeelgreat.com/usa/en/c/1BA884

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In this Metabolic Classroom lecture, Ben explores the concept of anabolic resistance—the body’s reduced ability to build and maintain muscle in response to stimuli like protein intake and resistance training.

This phenomenon, often associated with aging, also affects individuals with obesity or a sedentary lifestyle. Because muscle health is directly tied to longevity, strength, insulin sensitivity, and independence, understanding and reversing anabolic resistance is critical for long-term metabolic health.

Dr. Bikman explains the key drivers of anabolic resistance: reduced anabolic hormone levels, impaired amino acid delivery, inflammation, and cellular changes such as insulin resistance and intramuscular lipid buildup. He emphasizes the central role of the mTOR signaling pathway in muscle protein synthesis, and how factors like age, obesity, and inactivity blunt this response—even when adequate nutrients and exercise are present.

The lecture ends with practical strategies to overcome anabolic resistance, including resistance training, high-leucine animal protein intake, creatine, omega-3s, vitamin D3, and even peptides. Ben stresses that building muscle isn’t just about looking good—it’s about preventing frailty, insulin resistance, and loss of independence. Resistance training is non-negotiable, and diet alone will never be enough to restore optimal muscle health.

Show Notes/References:

For complete show notes and references, we invite you to become an Insider subscriber. You’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A with Ben after the lecture, ad-free podcast episodes, show notes and references, and online, live Office Hours access with Dr Bikman. It also includes Ben’s Research Review Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

Ben’s favorite yerba maté and fiber supplement: https://ufeelgreat.com/usa/en/c/1BA884

Ben’s favorite meal-replacement shake: https://gethlth.com (discount: BEN10)

Ben’s favorite allulose source: https://rxsugar.com (discount: BEN20)

Ben’s favorite health check-up for women: https://choosejoi.co/drben15 (discount: DRBEN15)

Ben’s favorite health check-up for men: https://blokes.co/drben15 (discount: DRBEN15)

Other products Ben likes: https://www.amazon.com/shop/benbikmanphd

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In this episode of the Metabolic Classroom, Dr. Ben Bikman explores a surprising and controversial dietary trend: the “sugar diet.”

Despite its name, this diet isn’t built around candy and soda. Instead, it promotes a very high intake of simple carbohydrates—primarily from natural sources like fruit, honey, and juices—while restricting both protein and fat to below 10% of total calories. This unusual approach has been gaining popularity, especially among lean, athletic men, some of whom report improved energy, body composition, and insulin sensitivity.

Ben traces the diet's philosophical roots back to the 1930s rice diet used for managing kidney and heart disease, noting how both rely heavily on low-protein, high-carbohydrate intake. He reviews studies in both animals and humans showing that the key metabolic shifts—such as increased mitochondrial uncoupling, fat loss, and improved glucose control—may not be due to the sugar itself, but rather to the restriction of protein. This triggers a spike in FGF21, a liver hormone that enhances energy expenditure and metabolic health.

The lecture also examines the limitations of this approach. Dr. Bikman points out that the diet appears to work only under very specific conditions: in metabolically healthy individuals, especially men, with high physical activity levels. For others, particularly those prone to insulin resistance, food addiction, or poor satiety control, such a high-sugar diet could be problematic. He emphasizes that, as with all dietary interventions, context matters.

Ultimately, this lecture doesn’t promote the sugar diet but uses it as a lens to highlight the underestimated power of protein restriction in driving hormonal and mitochondrial adaptations. Dr. Bikman urges caution and encourages further exploration of how individual physiology responds to dietary extremes.

Show Notes/References:

For complete show notes and references, we invite you to become an Insider subscriber. You’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A with Ben after the lecture, ad-free podcast episodes, show notes and references, and online, live Office Hours access with Dr Bikman. It also includes Ben’s Research Review Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

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In this lecture, Ben challenges the conventional insulin-centric model of type 1 diabetes by introducing the “bi-hormonal hypothesis” proposed by Dr. Roger Unger.

While insulin deficiency is a defining feature of T1DM, Dr. Bikman emphasizes the overlooked role of glucagon in driving hyperglycemia, ketone production, and muscle wasting. In normal physiology, insulin from beta cells locally suppresses glucagon from alpha cells. But in type 1 diabetes, this local regulation is lost, allowing glucagon to run unchecked—even when blood glucose is high.

Ben explains how injected insulin, although lifesaving, can’t mimic the precise intra-islet insulin levels needed to suppress glucagon secretion. This mismatch helps explain why blood sugar control can remain elusive despite appropriate insulin use. Excess glucagon ramps up liver glucose output and ketogenesis, creating a more complex hormonal storm than insulin alone can calm.

The lecture also explores new therapeutic strategies—including glucagon receptor blockers and GLP-1 agonists—that may help suppress glucagon more effectively. Dr. Bikman urges a shift in perspective: instead of seeing diabetes as just a disease of insulin, it’s time to recognize its bi-hormonal nature and tailor treatment accordingly.

For complete show notes and references, we invite you to become an Insider subscriber. You’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A with Ben after the lecture, ad-free podcast episodes, show notes and references, online Office Hours access, Ben’s Research Review Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

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This Metabolic Classroom lecture explores the often misunderstood world of nitrates and nitrites—compounds historically feared due to their association with processed meats.

Dr. Bikman presents a balanced examination of their biological role, historical use, and potential risks and benefits. While concerns remain over their conversion into carcinogenic nitrosamines (mainly in animal studies), the real-world human data is inconsistent and largely correlational. In fact, vegetables are the largest dietary source of nitrates—not processed meats.

Far from being mere preservatives, nitrates and nitrites play a key role in converting to nitric oxide in the body, which supports vascular health, mitochondrial function, and even insulin sensitivity. Human and animal studies suggest nitrates can improve mitochondrial efficiency, promote blood flow, and enhance insulin signaling via cyclic GMP and PKG pathways. They may also encourage the browning of fat tissue, supporting metabolic flexibility.

Despite the correlation-based cancer fears often cited in media and observational studies, Dr. Bikman emphasizes the importance of context, dose, and confounding variables. He argues that nitrates and nitrites are bioactive compounds with legitimate metabolic benefits—far from the health villains they’re often made out to be.

Show Notes/References:

For complete show notes and references, we invite you to become an Insider subscriber. You’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A with Ben after the lecture, ad-free podcast episodes, show notes and references, online Office Hours access, Ben’s Research Review Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

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This Metabolic Classroom lecture with Dr. Bikman explores how the loss of estradiol during menopause affects five key metabolic systems: the brain, muscles, mitochondria, fat tissue, and inflammation.

Each of these systems relies on estradiol for optimal function, and its decline contributes to increased risk for cognitive impairment, muscle loss, reduced mitochondrial function, increased visceral fat, and systemic inflammation.

Ketones—particularly beta-hydroxybutyrate (BHB)—can provide a partial compensatory effect in each system. In the brain, BHB supports glucose metabolism, reduces neuroinflammation, and enhances neuroplasticity. In muscles, ketones reduce protein degradation and improve mitochondrial function. At the mitochondrial level, BHB promotes mitochondrial biogenesis and helps reduce oxidative stress through NRF2 activation.

The lecture also outlines how ketones affect fat tissue by promoting mitochondrial uncoupling and upregulating thermogenic genes like UCP1. Additionally, BHB helps reduce inflammation by inhibiting the NLRP3 inflammasome. A final section reviews exogenous ketone strategies—salts, esters, acids, and MCTs—as potential tools to support women through menopause-related metabolic changes.

Show Notes/References:

For complete show notes and references, we invite you to become an Insider subscriber. You’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A with Ben after the lecture, ad-free podcast episodes, show notes and references, online Office Hours access, Ben’s Research Review Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

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