Here are the resources that Ben references during the episode:
Study #1 - https://care.diabetesjournals.org/content/25/2/364.short
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Caffeine, Insulin & Metabolism

Welcome to The Metabolic Classroom, a nutrition&nbsp;and lifestyle podcast focused on metabolism, which is how our bodies use energy, and the truth behind why we get sick and fat. Every week, Dr. Ben Bikman shares valuable insights that you can apply in your own life and share with friends and loved ones. The Metabolic Classroom is brought to you by InsulinIQ.com. Hosted on Acast. See acast.com/privacy for more information.

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In this episode of The Metabolic Classroom, Dr. Bikman explores the history, science, and benefits of ketones, focusing on exogenous ketones.
Ben highlights the significant benefits of ketones for brain health. He disputes the common belief that glucose is the brain’s preferred fuel, citing research by Dr. George Cahill that indicates the brain relies heavily on ketones during fasting.
The classroom also addresses the evolution and advantages of exogenous ketones. Early forms of exogenous ketones, like ketone salts, had limitations such as mineral imbalance and poor taste. Advances led to the development of ketone esters and bioidentical BHB, which are more effective and palatable. Exogenous ketones can help control appetite, reduce inflammation, and improve exercise performance. Despite initial concerns about their potential to be converted back into fat, Professor Bikman clarifies that this is not a risk, as the liver cannot reverse ketone production into fat.
Overall, Dr. Bikman emphasizes that while ketones themselves offer numerous metabolic benefits, the primary advantage of a ketogenic state is maintaining low insulin levels, which supports fat burning and overall metabolic health. He encourages the use of exogenous ketones to enhance these benefits, particularly for managing cravings, improving physical performance, and supporting cognitive function.
00:01 - Introduction to Ketones 01:58 - Types of Ketones - Explanation of the three main types of ketones: acetoacetate, acetone, and beta-hydroxybutyrate. 02:58 - Ketones and Blood Acidity - Discussion on how ketones can affect blood acidity and the distinction between ketosis and ketoacidosis. 04:04 - Insulin's Role in Ketone Production - How insulin levels determine whether the body produces fat or ketones from acetyl-CoA. 07:23 - Benefits of Low Insulin Levels - Overview of the metabolic benefits of low insulin levels, including improved fat burning and metabolic health. 08:19 - Ketones and Brain Health - The positive effects of ketones on brain function and cognitive health, debunking the myth that glucose is the brain's preferred fuel. 13:33 - Ketones and Physical Performance - Evidence that ketones improve physical performance and energy efficiency in muscle cells. 17:31 - Anti-inflammatory Effects of Ketones - Ketones’ role in inhibiting inflammation and their benefits for inflammatory disorders.
Studies Referenced:
Alzheimer’s and Parkinson’s (Cunnane et al., 2016): https://alzres.biomedcentral.com/articles/10.1186/s13195-021-00783-x
Ketones Elicit Distinct Alterations in Adipose Mitochondrial Bioenergetics: https://pubmed.ncbi.nlm.nih.gov/32872407/
Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice: https://pubmed.ncbi.nlm.nih.gov/28877458/
The Effects of Ketogenic Diet on Insulin Sensitivity and Weight Loss, Which Came First: The Chicken or the Egg?: https://pubmed.ncbi.nlm.nih.gov/37513538/ 
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Exogenous Ketones with Dr. Ben Bikman

In this episode of The Metabolic Classroom, Dr. Ben Bikman challenges the traditional view that saturated fats are the primary cause of atherosclerotic plaques and heart disease. He asserts that while plaques, or atheromas, in coronary arteries are composed partly of fats and foam cells, the exact process of plaque formation remains speculative. Dr. Bikman emphasizes that anyone claiming to know the definitive cause of plaque formation is likely overstating their knowledge. Foam cells, which are fat-laden macrophages, play a critical role in plaque development and are consistently present at the sites of these plaques.
Dr. Bikman explains that inflammation is a significant factor in atherosclerosis, and C-reactive protein (CRP), a marker of inflammation, is a better predictor of heart disease than LDL cholesterol. He describes how macrophages engulf oxidized LDL cholesterol, turning into foam cells and secreting pro-inflammatory proteins like CRP. This process is driven by the presence of oxidized lipids, particularly those derived from omega-6 polyunsaturated fats such as linoleic acid, which are prevalent in modern diets due to the widespread use of vegetable oils.
Ben highlights several studies to support his argument. A notable study from 1979 by Brown and Goldstein showed that macrophages only consume LDL cholesterol when it is oxidized, not in its native form. Another study from 1998 found that oxidized LDL containing specific bioactive lipids, nine and 13 HODE, is particularly problematic. These oxidized lipids are derived from linoleic acid, not from saturated or monounsaturated fats. Moreover, historical dietary studies, such as the Minnesota Coronary Experiment and the Sydney Diet Heart Study, revealed that participants consuming more polyunsaturated fats had higher mortality rates than those consuming saturated fats.
To conclude, Dr. Bikman argues that the traditional belief that saturated fat causes heart disease is flawed. He points out that recent studies, including a correlational study published in the British Medical Journal, show that refined grains, not saturated fats, are more strongly linked to heart disease and overall mortality. He suggests that the real dietary culprit is the overconsumption of omega-6 polyunsaturated fats, particularly linoleic acid, found in processed foods. This shift in perspective underscores the importance of reevaluating dietary guidelines and focusing on the types of fats consumed.
#HeartHealth #SaturatedFat #Atherosclerosis #Inflammation #InsulinResistance #LDLCholesterol #OxidizedLDL #FoamCells #Macrophages #BenBikman #MetabolicHealth #CholesterolMyths #LinoleicAcid #PolyunsaturatedFats #DietaryFats #CardiovascularResearch
Studies referenced:
Binding Site on Macrophages that Mediates Uptake in Degradation by Brown and Goldstein (1979): https://academic.oup.com/clinchem/article/46/6/829/5641219 
Oxidized LDL Regulates Macrophage Gene Expression (1998): You can find more details on this study in resources like ScienceDirect and Cell Journal (you may need specific access or subscriptions to retrieve full texts).
Strong Increase in Hydroxy Fatty Acids Derived from Linoleic Acid in Human Low-Density Lipoproteins of Atherosclerotic Patients (1998): https://www.sciencegate.app/document/10.1016/s0009-3084(97)00095-9 
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Heart Health: Fat Matters

This episode of The Metabolic Classroom is sponsored by RxSugar. Use this link to get 20% off: https://rxsugar.com/discount/BEN20
02:10 - Overview of Uric Acid: Explanation of what uric acid is and its origins from purine metabolism. 03:16 - Uric Acid and Hyperuricemia: Discussion on uric acid production, excretion, and the condition of hyperuricemia. 05:09 - Gout and Uric Acid Crystallization: How high uric acid levels lead to gout and kidney stones. 07:08 - Importance of Uric Acid in Metabolism: Why uric acid is important, its clinical relevance, and its connection to insulin resistance. 09:14 - Uric Acid and Inflammation: How uric acid causes systemic inflammation and contributes to insulin resistance. 12:27 - Sources of Uric Acid, Purines and Fructose: Detailed breakdown of purine and fructose metabolism leading to uric acid production. 16:31 - Fructose Metabolism and Uric Acid: The role of the liver in metabolizing fructose and its link to uric acid production. 22:47 - Pharmacological and Nutritional Interventions: Treatments like allopurinol and the benefits of allulose in reducing uric acid. 30:34 - Ketogenic Diet and Uric Acid: The effects of the ketogenic diet on uric acid levels and insulin sensitivity.
Summary:
In this episode of The Metabolic Classroom, Professor Bikman discusses the significance of uric acid, particularly its impact on insulin resistance. Uric acid, a byproduct of purine metabolism, is usually expelled through the kidneys. When production exceeds excretion, it leads to hyperuricemia, causing gout, kidney stones, and inflammation linked to insulin resistance.
Dr. Bikman explains that excessive uric acid activates inflammation pathways, producing ceramides that disrupt insulin signaling, leading to insulin resistance. He highlights the connection between fructose consumption and uric acid production, noting that unregulated fructose metabolism in the liver increases uric acid levels. This rise in fructose intake, rather than purine-rich foods, contributes to gout and metabolic issues.
To address this, Dr. Bikman discusses pharmacological interventions like allopurinol, which lowers uric acid levels but may have side effects. He also mentions allulose, a rare sugar that shows promise in reducing uric acid by enhancing its excretion. Despite potentially increasing uric acid, the ketogenic diet is noted for reducing inflammation and improving insulin sensitivity due to ketones.
Dr. Bikman concludes by emphasizing the importance of understanding uric acid's role in metabolic health and encourages further research and practical dietary interventions to manage uric acid levels, integrating pharmacological, nutritional, and lifestyle approaches to improve overall metabolic health.
Studies referenced in this episode:
https://pubmed.ncbi.nlm.nih.gov/24769205/
https://www.sciencedirect.com/science/article/abs/pii/S1933171115006063?via=ihub 
https://www.metabolismjournal.com/article/S0026-0495(65)80039-7/abstract 
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Uric Acid with Dr. Ben Bikman

In this episode of The Metabolic Classroom, Professor Ben Bikman, an expert in metabolic research, discusses the debate surrounding saturated fat and its impact on insulin resistance.
Dr. Bikman addresses misconceptions about saturated fat perpetuated by proponents of plant-based diets, who often blame meat-based saturated fats for insulin resistance. He refers to his own 2011 research, highlighting the role of toll-like receptor four (TLR4) activation in inducing inflammation and insulin resistance, particularly stimulated by saturated fats.
Acknowledging limitations in his earlier work, Dr. Bikman transitions to discussing fat digestion and absorption, setting the stage for studies on the impact of dietary saturated fat on metabolic outcomes. He cites a study by Volk et al. (2014) contradicting the direct link between dietary saturated fat intake and plasma saturated fat levels. Further, he discusses research challenging the low-fat emphasis of diets like DASH, including a study by Chiu et al. (2016) showing comparable blood pressure reduction with a high-fat version.
The lecture also covers a meta-analysis by Choi et al. (2020) supporting the benefits of ketogenic diets high in saturated fat for glycemic control and insulin resistance.
Dr. Bikman emphasizes the importance of considering context, suggesting that saturated fat consumption without excessive carbohydrate intake may not necessarily lead to insulin resistance. However, he acknowledges studies indicating potential concerns with high saturated fat intake in hypercaloric, high-carb diets, advocating for balanced macronutrient consumption.
00:01 - Introduction of the topic of saturated fat and insulin resistance, highlighting common misconceptions and his expertise in the field. 02:33 - Role of TLR4: Research on toll-like receptor four (TLR4) activation and its connection to inflammation and ceramide synthesis, leading to insulin resistance. 07:05 - Fat Digestion Primer: Explanation of fat digestion in the small intestine, emphasizing the formation of chylomicrons for fat transport into the bloodstream. 11:55 - Study by Volk et al. (2014): Key study that challenges the idea of dietary saturated fat directly increasing plasma saturated fat levels, despite high consumption. 16:41 - High-Fat DASH Diet Study: Research comparing a high-fat version of the DASH diet to the standard low-fat version, highlighting similar blood pressure reduction but improved lipid profiles with the high-fat diet. 19:46 - Meta-analysis by Choi et al. (2020): Demonstrating the benefits of ketogenic diets, typically high in saturated fat, in improving glycemic control and insulin resistance. 21:40 - Historical Trends: The paradox of decreasing saturated fat consumption over time while insulin resistance rates have increased, suggesting a more complex relationship. 25:58 - Overfeeding Studies: Studies showing that overconsumption of carbohydrates, particularly refined sugars and starches, can increase liver fat and saturated fat production, contributing to insulin resistance. 27:09 - Study by Luukkonen et al. (2018): Study indicating that in a hypercaloric, high-carb diet, high saturated fat intake may worsen insulin resistance compared to high unsaturated fat intake. 28:06 - Conclusion: The need for nuanced understanding, context, and critical appraisal of research findings regarding the relationship between saturated fat, carbohydrate intake, and insulin resistance.
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#InsulinResistance #SaturatedFat #MetabolicHealth #NutritionScience #HealthEducation #DietaryMyths #CellBiology #ResearchInsights #FatDigestion #KetogenicDiet #CardiometabolicHealth #DASHDiet #Inflammation #MedicalResearch #HealthDebunked  Hosted on Acast. See acast.com/privacy for more information.

Saturated Fat with Dr. Ben Bikman

This episode of the Metabolic Classroom is sponsored by Redmond Real Salt. Use code BEN15 to get 15% off of their products: https://redmond.life
Summary: In this lecture, Professor Ben Bikman explores the cardiometabolic effects of salt intake, detailing its role in electrolyte balance, fluid regulation, nerve function, muscle contractions, acid-base balance, and nutrient absorption. He explains the renin-angiotensin-aldosterone system (RAAS) and its response to low blood pressure or sodium levels, leading to sodium retention and water reabsorption in the kidneys. Dr. Bikman discusses how insulin influences salt handling by stimulating sodium reabsorption and increasing aldosterone production. He warns against the unintended consequences of salt restriction, such as elevated insulin levels and resistance, exacerbating metabolic syndrome and cardiovascular risk.
Shifting focus to fat cells, Dr. Bikman explains how aldosterone and angiotensin II affect fat cell growth and differentiation, promoting lipogenesis, inflammation, and fibrosis. He suggests salt restriction may contribute to obesity and insulin resistance. Discussing potential anti-obesity effects, he mentions angiotensin receptor blockers inhibiting angiotensin II signaling in fat cells.
Dr. Bikman stresses the complex interplay between salt, insulin, and fat cell biology, cautioning against oversimplified dietary recommendations. He encourages critical thinking about salt intake's impact on metabolic health and body composition, advocating for deeper understanding and knowledge sharing to improve health outcomes.
01:52: Importance of Salt in the Body - Overview of the essential role of salt, particularly sodium, in electrolyte balance, fluid regulation, nerve function, muscle contractions, acid-base balance, and nutrient absorption.
06:00: Biochemical Pathways of Salt Regulation - Detailed explanation of the RAAS cascade, involving renin, angiotensinogen, angiotensin-converting enzyme, angiotensin I and II, and aldosterone. Discussion of the physiological effects of angiotensin II, including vasoconstriction, thirst stimulation, and stimulation of aldosterone production.
09:48: Interaction Between Salt Regulation and Insulin - Exploration of the interaction between salt regulation pathways and insulin, including insulin's direct effect on sodium reabsorption in the kidneys and its modulation of the RAAS. Explanation of how salt restriction can lead to increased insulin levels and insulin resistance.
13:44: Consequences of Salt Restriction - Discussion of the negative health consequences of salt restriction, including increased insulin resistance and metabolic syndrome. Reference to studies showing the association between salt restriction and adverse metabolic outcomes.
17:58: Hypertension and Cardiovascular Health - Summary of the relationship between salt restriction, hypertension, and cardiovascular disease. Mention of anti-hypertensive medications targeting the RAAS, such as ACE inhibitors and angiotensin receptor blockers.
20:59: Metabolic Effects on Fat Cells - Transition to discussing the metabolic effects of salt-regulating pathways on fat cells. Explanation of how aldosterone and angiotensin II promote fat cell growth, differentiation, lipogenesis, inflammation, and fibrosis.
27:53: Conclusion and Takeaways - Recap of the lecture's key points, emphasizing the complex interplay between salt intake, insulin, and fat cell biology. Call to action for critical thinking about dietary recommendations and sharing of knowledge for informed decision-making.
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Caffeine, Insulin & Metabolism

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