Podcasts about cell metabolism

Creatine causes cancer to spread — that headline is built on a real mouse study. But what does the human data actually say? In this solo explainer, Dr. Robert Lufkin breaks down both halves of the science behind the most studied supplement on the planet.He walks through the 2021 mouse metastasis study behind the viral claim, the surprising evidence that creatine actually powers the immune cells that HUNT cancer (CD8 T cells and, per new UCLA research, dendritic cells), and what the human data — HCAs, NHANES, and the 2025 safety review — really shows. The verdict is more nuanced, and more reassuring, than the headline suggests.Chapters:00:00 — Introduction00:46 — Why This Question Exists01:32 — The Scary Half (2021 Study)02:17 — How Creatine Fuels Tumor Spread03:03 — Creatine Fights Cancer Too03:48 — UCLA June 2026 Dendritic Cells04:35 — Tumor Suppressor or Fuel?05:21 — What Human Data Shows (HCAs)06:08 — NHANES & 2025 Safety Review06:55 — The Honest Caveat07:42 — The TakeawayKey takeaways:The scary headline comes from a 2021 mouse study where dietary creatine promoted metastasis via the MPS1 → SMAD2/3 → TGF-beta pathway — in mice with established, aggressive tumors.The same metabolism fuels your immune system: creatine is essential for CD8 "killer" T cells and the dendritic cells that direct them.In a controlled human trial, creatine did NOT drive carcinogen (HCA) formation.NHANES population data links higher dietary creatine to LOWER cancer risk, and the 2025 safety review calls the human cancer-risk claim "not substantiated."Healthy adults: the human evidence does not support avoiding creatine. Active or metastatic cancer: pause and talk to your oncologist. Always choose third-party tested creatine monohydrate.Studies & sources:Zhang et al., Cell Metabolism 2021 — Creatine promotes cancer metastasis via Smad2/3Geng et al., Int. J. Mol. Sci. 2024 — The multifaceted role of creatine metabolismDi Biase et al., J. Exp. Med. 2019 — Creatine and CD8 T cell antitumor immunityKang et al., iScience 2026 (UCLA) — Creatine and dendritic cell activationPereira et al., Amino Acids 2015 — Creatine and heterocyclic aminesNHANES 2017–2020 — Dietary creatine and cancer riskAntonio et al., Frontiers in Nutrition 2025 — Common safety concerns regarding creatine

This episode is about more than food. It's about understanding why we reach for certain foods, creating a realistic off-ramp from ultra-processed eating, and giving your body a chance to reset. If you've ever felt like you're doing everything right but still struggling with weight, energy, inflammation, or cravings, this episode is for you.   Citation: Hall, Kevin D., et al. “Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.” Cell Metabolism, vol. 30, no. 1, 2019, pp. 67–77.e3. https://doi.org/10.1016/j.cmet.2019.05.008 — This is the cornerstone. Same calories, sugar, fat, fiber, and macros on both diets; people ate ~500 kcal/day more on the ultra-processed one and gained weight. It's the strongest evidence that the processing, not just the nutrients, changes intake. Why fat + sugar together hijack reward more than either alone (the “hyperpalatable” mechanism) DiFeliceantonio, Alexandra G., et al. “Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward.” Cell Metabolism, vol. 28, no. 1, 2018, pp. 33–44.e3. https://doi.org/10.1016/j.cmet.2018.05.018 McDougle, Molly, et al. “Separate Gut-Brain Circuits for Fat and Sugar Reinforcement Combine to Promote Overeating.” Cell Metabolism, vol. 36, no. 2, 2024, pp. 393–407. https://doi.org/10.1016/j.cmet.2023.12.014 — Together these support your point that engineered fat-plus-sugar foods (the Doritos idea) light up reward pathways more than natural foods, because fat and sugar run on separate gut-brain circuits that combine. Why “glycemic velocity” matters — hidden refined starches like maltodextrin Hofman, Denise L., et al. “Nutrition, Health, and Regulatory Aspects of Digestible Maltodextrins.” Critical Reviews in Food Science and Nutrition, vol. 56, no. 12, 2016, pp. https://doi.org/10.1080/10408398.2014.940415 — Supports the egg-bite/maltodextrin point: maltodextrin is a refined starch with a glycemic index around 85–110, higher than table sugar, hiding on labels as “modified food starch.” Backs your “what the calories came from” framing. Why these foods genuinely relieve stress (your central, original thesis) Ulrich-Lai, Yvonne M., et al. “Pleasurable Behaviors Reduce Stress via Brain Reward Pathways.” Proceedings of the National Academy of Sciences, vol. 107, no. 47, 2010, pp. https://doi.org/10.1073/pnas.1007740107 Tomiyama, A. Janet, et al. “Comfort Food Is Comforting to Those Most Stressed: Evidence of the Chronic Stress Response Network in High Stress Women.” Psychoneuroendocrinology, vol. 36, no. 10, 2011, pp. 1513–1519. https://doi.org/10.1016/j.psyneuen.2011.04.005 — This is the science behind “the food was doing something right.” Palatable food measurably dampens the HPA (cortisol) stress axis through reward pathways — which is exactly why pulling it without replacing the stress tool fails. Why cravings are state-dependent and rise with stress (the “urge depends on the state of your blood / stress level” claim) Adam, Tanja C., and Elissa S. Epel. “Stress, Eating and the Reward System.” Physiology & Behavior, vol. 91, no. 4, 2007, pp. 449–458. https://doi.org/10.1016/j.physbeh.2007.04.011 Darcey, Valerie L., et al. “Brain Dopamine Responses to Ultra-Processed Milkshakes Are Highly Variable and Not Significantly Related to Adiposity in Humans.” Cell Metabolism, vol. 37, no. 3, 2025, pp. 616–628. https://doi.org/10.1016/j.cmet.2025.02.002  (edited)      WHAT TO EAT FOR THE NEXT SIX WEEKS — Protein. Plant. Potato. (P³) The formula for every meal: one protein + one plant + one starch (potato, or beans and rice). Add fat — olive oil, butter, avocado, cheese, nuts. Add flavor — salt, pepper, garlic, lemon, vinegar, salsa, hot sauce, herbs. This is not the meal you dreamed of. This is the meal that sets you free. BREAKFAST Eggs + sautéed vegetables + fruit on the side Plain Greek yogurt + berries + a handful of nuts Leftover chicken or beef + potato + vegetables (last night's dinner works) LUNCH Chicken + roasted potato + green salad with olive oil and lemon Tuna + white beans + cucumber + tomato, dressed with olive oil and vinegar Beef + potato + peppers + salsa DINNER Sheet-pan chicken + potatoes + green beans Instant Pot chicken + potato + a vegetable Burger patty (no bun) + potato + salad Batch chili (beef + beans + tomato) over rice Baked fish + sweet potato + roasted broccoli Pork + beans and rice + sautéed greens THE DURESS PLATE — for when the day collapses One protein + one plant + one starch, zero cooking. Examples: • Hard-boiled eggs + apple + handful of nuts • Tuna + canned beans + cucumber, with olive oil • Pre-cooked/frozen ground beef + frozen vegetables + microwave potato • String cheese + fruit + a few nuts (in a real pinch) SIMPLE RECIPES Sheet-Pan Chicken & Potatoes (serves 4) Toss chicken thighs and quartered baby potatoes in olive oil, salt, pepper, garlic. Roast at 425°F (220°C) ~35–40 min. Add green beans for the last 15 min. Batch Chili (serves 6) Brown 2 lb ground beef with chopped onion. Add 2 cans diced tomatoes, 2 cans beans (drained), garlic, cumin, chili powder, salt. Simmer 30+ min. Freezes well — make once, eat all week. Serve over rice. Instant Pot Chicken Chicken breasts + ½ cup broth + salt, garlic, paprika. Pressure cook 10 min, natural release 5. Shred. Pairs with any potato + vegetable. The 5-Minute Tuna Bean Bowl Can of tuna + can of white beans (rinsed) + diced cucumber and tomato. Dress with olive oil, lemon or vinegar, salt, pepper. Microwave Potato, Done Right Pierce a potato, microwave 5–7 min. Split, add butter or olive oil, salt, pepper. The reliable, universal starch. Remember: Don't aim for one perfect week repeated six times. Just follow the basic protocol the best you can for six weeks. When a craving hits, run the nine-minute interrupt from Episode 14.   Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he's helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He's also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more. If you're ready to take your health seriously, this podcast is a great place to start.

Most diets fail because they never address what the food was doing for you emotionally. In this episode, Dr. Brendan McCarthy explains the stress-craving loop behind emotional eating, why ultra-processed foods feel impossible to resist, and how shame actually reinforces the cycle. You'll learn: • Why cravings feel automatic • How stress drives food urges • The “cue → urge → reward” loop • A simple 9-minute method to interrupt cravings This isn't about perfection or willpower. It's about understanding the pattern so you can finally begin to change it.   Citations:  Boswell, Rebecca G., and Hedy Kober. “Food Cue Reactivity and Craving Predict Eating and Weight Gain: A Meta-Analytic Review.” Obesity Reviews, vol. 17, no. 2, 2016, pp. 159–177. doi:10.1111/obr.12354. Use for: Food cues can trigger craving and eating even without true hunger. Berridge, Kent C., and Terry E. Robinson. “Liking, Wanting, and the Incentive-Sensitization Theory of Addiction.” American Psychologist, vol. 71, no. 8, 2016, pp. 670–679. doi:10.1037/amp0000059. Use for: “Wanting” food is not the same as true pleasure. Schultz, Wolfram, Peter Dayan, and P. Read Montague. “A Neural Substrate of Prediction and Reward.” Science, vol. 275, no. 5306, 1997, pp. 1593–1599. doi:10.1126/science.275.5306.1593. Use for: Dopamine helps encode reward prediction and learning. Wood, Wendy, and Dennis Rünger. “Psychology of Habit.” Annual Review of Psychology, vol. 67, 2016, pp. 289–314. doi:10.1146/annurev-psych-122414-033417. Use for: Habits form through repeated cue-context loops. Laborde, Sylvain, et al. “Effects of Voluntary Slow Breathing on Heart Rate and Heart Rate Variability: A Systematic Review and a Meta-Analysis.” Neuroscience & Biobehavioral Reviews, vol. 138, 2022, article 104711. doi:10.1016/j.neubiorev.2022.104711. Use for: Slow breathing supports parasympathetic regulation and stress reduction. Lieberman, Matthew D., et al. “Putting Feelings into Words: Affect Labeling Disrupts Amygdala Activity in Response to Affective Stimuli.” Psychological Science, vol. 18, no. 5, 2007, pp. 421–428. doi:10.1111/j.1467-9280.2007.01916.x. Use for: Naming emotions can reduce emotional reactivity. Gollwitzer, Peter M. “Implementation Intentions: Strong Effects of Simple Plans.” American Psychologist, vol. 54, no. 7, 1999, pp. 493–503. doi:10.1037/0003-066X.54.7.493. Use for: “If-then” plans improve behavior change under stress. Forman, Evan M., et al. “A Comparison of Acceptance- and Control-Based Strategies for Coping with Food Cravings: An Analog Study.” Behaviour Research and Therapy, vol. 45, no. 10, 2007, pp. 2372–2386. doi:10.1016/j.brat.2007.04.004. Use for: Acceptance and urge-surfing strategies help cravings pass without acting on them. Hall, Kevin D., et al. “Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.” Cell Metabolism, vol. 30, no. 1, 2019, pp. 67–77.e3. doi:10.1016/j.cmet.2019.05.008. Use for: Ultra-processed foods increase intake and reinforce overeating patterns.   Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he's helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He's also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more. If you're ready to take your health seriously, this podcast is a great place to start.

Why is it so hard to stop eating ultra-processed foods — even when you know they're hurting you? In Episode 13 of this 16-part series, Dr. Brendan McCarthy explains why the real problem is not just the food itself. The real problem is the loop: Cue or emotional state → Wanting → Bargaining → Consumption → Temporary relief → Crash/regret → Repeat. This episode explores how ultra-processed and hyper-palatable foods become attached to stress, boredom, loneliness, exhaustion, anxiety, and emotional discomfort — training the brain to seek relief through food. Key ideas from this episode: • Hunger is the body asking for nourishment • Wanting is the conditioned brain asking for the expected hit • The food is the bait. The loop is the trap. • The food breaks the feeling. It does not heal the source. • You cannot remove a counterfeit regulator without restoring real regulation. Dr. McCarthy breaks down why willpower alone often fails and why lasting change requires a physiologic off-ramp: stable meals, protein, fiber, hydration, sleep, movement, emotional regulation, cue reduction, social planning, and relapse repair. This is not about “perfect eating.” It is about building a life where food is no longer your primary regulator of stress, comfort, or identity. If you've ever felt trapped in cravings, emotional eating, binge-restrict cycles, or constant food noise, this episode is designed to help you understand the mechanism behind the loop — and how to begin leaving it.

Creatine and Microbiomes A new 2026 Cell Metabolism study explores a compelling and increasingly central idea in modern biology: the gut/brain/immune/metabolism axis is not just associative, it is mechanistic. Specifically, Dr. Lu and colleagues investigate how the gut microbiota can directly influence depressive behavior by reshaping systemic and neural metabolism. This is another in a long running list of papers describing the amazing work that bacterial commensal microbes do for us. In this case, our minds and moods. "Although peripheral-brain crosstalk regulates energy metabolism, its role in depression remains unclear. Here, we used metabolic profiling to reveal elevated fecal creatine alongside reduced plasma and cerebrospinal fluid creatine in both patients with depression and mouse depression models. Exogenous creatine produced antidepressant-like effects mediated by gut microbiota. Bifidobacterium pseudolongum was identified as a significantly reduced gut bacterial species in depression, correlating with impaired creatine absorption. Subsequent supplementation with Bifidobacterium enhanced the antidepressant effects of creatine. Mechanistically, B. pseudolongum-derived acetate promoted the creatine transporter (Slc6a8) expression in intestinal epithelial cells via histone acetylation. The Slc6a8 mediated the antidepressant-like effects of creatine. Neuronal creatine deficiency influenced energetic metabolism and neurophysiological function. In patients with depression taking antidepressants, co-administration of creatine and Bifidobacterium increased plasma creatine levels and reduced depression scores. These findings identify the Bifidobacterium-creatine combination as a promising antidepressant strategy and highlight the critical role of gut-brain energy metabolism in depression." "The brain, as an energy-intensive organ, relies on precise metabolic regulation to maintain synaptic plasticity, neurotransmitter synthesis, and stress response systems. Accumulating evidence implicates energy metabolism dysregulation as a hallmark of depression. Neuroimaging studies using positron emission tomography (PET) have identified marked glucose hypometabolism in the medial prefrontal cortex (mPFC) of patients with depression. Cerebral mitochondrial dysfunction and ATP imbalance have been mechanistically linked to depression progression. Notably, emerging studies emphasize the bidirectional interplay between peripheral metabolic signals and central energy regulation, which is fundamental to neural metabolism. Clinical observations such as fatigue, appetite dysregulation, and unexplained weight fluctuations in patients with depression further suggest systemic metabolic disturbances spanning peripheral organs and the CNS.." (Lu et. al. 2026) This is next-level medicine. Mental health can no longer be framed as a disorder of genetics, experience, or circumstance alone. This work opens a clearer window, showing how the microbiome participates as an active partner, shaping brain function through the metabolites it helps produce and deliver. Compounds like creatine are no longer just peripheral players. They become signals, fuel, structure, and information, bridging gut and brain, metabolism and behavior.... and more Enjoy, Dr. M

In this episode, Dr. Brendan McCarthy dives deep into the psychology of ultra-processed foods, compulsive eating, shame, and why so many people feel trapped in unhealthy food cycles. This conversation goes far beyond calories and willpower. Dr. McCarthy explains how ultra-processed and hyper-palatable foods are intentionally engineered to drive repeat consumption, how emotional memories and stress shape cravings, and why shame-based nutrition advice often makes the problem worse instead of better. Topics covered in this episode include: • How ultra-processed foods affect the brain • Why compulsive eating is learned — and can be unlearned • The connection between trauma, stress, and food cravings • The difference between guilt and shame • How marketing and emotional associations shape eating habits • Why “clean eating” language can be harmful • The neuroscience of cravings, dopamine, serotonin, and reward • What real freedom with food actually looks like • Why self-compassion matters in healing If you've ever felt trapped in cycles of emotional eating, binge eating, food guilt, or shame around nutrition, this episode is for you.  

Ultra-processed food makes up over half the calories Americans eat - and over 60% for kids. Here's what the research shows happens inside your body in the first 5 days after you quit. In this episode of Health Longevity Secrets, Dr. Robert Lufkin walks through the hour-by-hour timeline: the glucose spikes that disappear within 24 hours, the insulin resistance that drops 30%+ in 48 hours, the gut microbiome that reorganizes in 3 days, the blood pressure that falls 6-8 mmHg in a week, and the NIH metabolic ward data showing a 500+ calorie daily swing driven entirely by food processing - not willpower. CHAPTERS 00:00 - Introduction: Why Ultra-Processed Food Matters 00:47 - Part 1: What Happens in the First 24 Hours 01:30 - Sodium, Water Retention and the Real Reason You Lose 1-3 lbs 02:10 - Part 2: 48 Hours - Insulin Sensitivity Returns Within Days 02:45 - Gut Microbiome Shifts in 24 Hours (David et al., Nature 2014) 03:23 - Taste Receptors Recalibrate: Why Fruit Tastes Sweeter Again 03:55 - Part 3: 72 Hours - Blood Pressure Drops 6-8 mmHg 04:34 - Inflammation Falls 35-43% in One Week (CRP Data) 05:30 - Part 4: 5 Days - Kevin Hall's NIH Metabolic Ward Trial 06:58 - Part 5: The Framework - 120 Hours to Reset Your Biology KEY TAKEAWAYS Glucose stabilizes within 24 hours when fiber and food matrix are restored 3 low-carb meals can reduce post-meal insulin resistance by over 30% in a day Gut bacterial composition shifts within 24 hours of dietary change Sodium reduction lowers systolic BP 6-8 mmHg in 70-75% of people in one week CRP drops 35-43% in 7 days on a whole-food, vegetable-rich diet Kevin Hall's 2019 NIH RCT: ultra-processed diet drove 500+ extra calories/day with zero awareness STUDIES AND SOURCES Hall et al., Cell Metabolism 2019 - NIH metabolic ward UPF trial David et al., Nature 2014 - diet alters gut microbiome Shukla et al., 2019 - meal sequence and postprandial glucose American Journal of Medicine 2026 - UPF and 47% increased CV risk AHA Scientific Sessions 2023 - sodium and BP in one week Lin and Borer, PLOS ONE 2016 - ⭐ Enjoying the show? Please leave a 5-star review on Apple Podcasts — it takes 30 seconds and helps more people discover the science of health and longevity. Thank you!New episodes every Tuesday & Thursday. Subscribe so you don't miss one.Continue this conversation on Substack: https://robertlufkinmd.substack.comLies I Taught In Medical School — Free sample chapter: https://www.robertlufkinmd.com/lies/Web: https://www.robertlufkinmd.comYouTube: https://www.youtube.com/robertlufkinmdX: https://x.com/robertlufkinmdInstagram: https://www.instagram.com/robertlufkinmd/TikTok: https://www.tiktok.com/@robertlufkinLinkedIn: https://www.linkedin.com/in/robertlufkinmd/

Registered dietitian nutritionist Leyla Muedin discusses how exposure to natural daylight may improve metabolic health beyond diet and exercise, highlighting a controlled crossover study of 13 adults aged 65+ with type 2 diabetes published in Cell Metabolism. Participants spent 4.5 days in living spaces lit by either natural light through large windows or artificial light, with identical meals, sleep, activity, and screen time; after a 4-week washout they switched conditions. Natural light was associated with more hours of blood glucose in the normal range, less glucose variability, higher evening melatonin, and improved fat oxidative metabolism, suggesting effects on circadian “body clocks” and coordination between central and peripheral clocks. Muedin recommends getting morning light on the face, reducing sunglasses and high SPF use, dimming lights at night, keeping consistent sleep, and spending more time outdoors; she also notes that architecture can limit sunlight exposure.

Today, we're diving into a topic that should be getting far more attention: Cardiovascular disease in women. Heart disease is one of the leading causes of death in women—yet it's often under-addressed, oversimplified, and misunderstood in clinical practice. Most women are told: “Eat better. Take this prescription.” But that approach misses something critical. Full citation list:    •    Hall, Kevin D., et al. “Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.” Cell Metabolism, vol. 30, no. 1, 2019, pp. 67–77.e3. Supports the core causal point that ultra-processed foods drive higher intake and weight gain even under controlled feeding conditions; this is not a women-specific lipid paper, but it is the cleanest experimental anchor for why UPFs create a high-throughput metabolic environment.     •    El Khoudary, Samar R., et al. “Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement From the American Heart Association.” Circulation, vol. 142, no. 25, 2020, pp. e506–e532. Supports the midlife women's frame: across the menopause transition, LDL-C and ApoB rise, metabolic risk shifts, and cardiovascular prevention needs to become more deliberate during this window. This supports the “why I care about lipids in endocrine care” part of the episode.     •    Derby, Carol A., et al. “Lipid Changes During the Menopause Transition in Relation to Age and Weight: The Study of Women's Health Across the Nation.” American Journal of Epidemiology, vol. 169, no. 11, 2009, pp. 1352–61. Foundational SWAN paper establishing that the menopause transition itself — not just chronological aging — is associated with adverse lipid shifts in midlife women. This is the original observation that the timing argument rests on.     •    Wu, Bingjie, et al. “Trajectories of Blood Lipids Profile in Midlife Women: Does Menopause Matter?” Journal of the American Heart Association, vol. 12, no. 22, 2023, e030388. Supports the claim that LDL-C, total cholesterol, and ApoB follow distinct trajectory patterns through the menopause transition, with subgroups of women showing rising lipids in the years before the final menstrual period — useful for the timing argument that body and symptom changes can precede the obvious lab story.     •    Matthews, Karen A., et al. “Age at Menopause in Relationship to Lipid Changes and Subclinical Carotid Disease Across 20 Years: Study of Women's Health Across the Nation.” Journal of the American Heart Association, vol. 10, no. 18, 2021, e021362. Supports the point that ApoB and Apo A1 changes cluster around the final menstrual period and that adverse lipid shifts in the early postmenopausal years track with subclinical carotid disease later — connects menopausal timing to the longer cardiovascular arc rather than a one-time lab blip.     •    De Oliveira-Gomes, Diana, et al. “Apolipoprotein B: Bridging the Gap Between Evidence and Clinical Practice.” Circulation, vol. 150, no. 1, 2024, pp. 62–79. Supports the practical ApoB explanation: ApoB reflects atherogenic particle burden and outperforms LDL-C for ASCVD risk prediction in many settings, but adoption lags because clear apoB targets and triggers are still lacking in mainstream guidelines. Good support for the public-service “what the hell is ApoB anyway?” section.     •    Williamson, Laura. “The Slowly Evolving Truth About Heart Disease and Women.” American Heart Association News, 9 Feb. 2024, heart.org/en/news/2024/02/09/the-slowly-evolving-truth-about-heart-disease-and-women. Supports the broader clinical framing that women remain underrecognized or undertreated in cardiovascular care and that women's heart disease still needs better public and clinical communication. This is more public-facing than mechanistic, but useful for your opening frame. Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he's helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He's also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more. If you're ready to take your health seriously, this podcast is a great place to start.

Today, we're diving into autoimmunity—what it actually is, why it happens, and how ultra-processed foods may be contributing to the problem. Autoimmune disease is often misunderstood. Some will tell you diet has nothing to do with it. Others claim diet is the cure. The truth is more nuanced—and that's exactly what we explore in this episode. You'll learn: What autoimmunity really is (and why it's a case of mistaken identity) How inflammation and the immune system interact The critical role of gut health and the microbiome How ultra-processed foods disrupt intestinal integrity and immune signaling Why stress and hyper-palatable foods create a harmful cycle A practical experiment you can try to see how diet impacts your own biomarkers This isn't about selling supplements or pushing extremes. It's about understanding the science so you can make informed decisions about your health. As always, this episode is backed by scientific literature. Full citations are included below, with abbreviated versions available on shorter clips. If you're dealing with autoimmune symptoms—or just want to better understand how food impacts your immune system—this episode is for you.   Full citation list: Hall KD, et al. “Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.” Cell Metabolism, 2019.     Supports the formulation argument: UPF intake increased spontaneous calorie intake and weight gain even with diets matched for presented calories, sugar, fiber, sodium, and macronutrients. This is your anchor for “hyper-palatability and formulation change physiology, not just psychology.”   Narula N, et al. “Association of Ultra-Processed Food Intake With Risk of Inflammatory Bowel Disease: Prospective Cohort Study.” BMJ, 2021.     Best human disease-level citation for the episode. Supports the claim that higher UPF intake is associated with greater IBD risk, making the gut-immune link clinically meaningful rather than purely theoretical.   Chassaing B, et al. “Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome.” Gastroenterology, 2022.     Best emulsifier paper for human translation. Supports the claim that CMC can perturb the microbiota and metabolome and may contribute to barrier-hostile gut ecology in susceptible individuals.   Daniel N, et al. “Human Intestinal Microbiome Determines Individualized Responses to Dietary Emulsifier Carboxymethylcellulose.” Cellular and Molecular Gastroenterology and Hepatology, 2024.     Useful nuance paper. Supports the point that emulsifier sensitivity is not identical across all people and that host-microbiome context matters.   Shil A, et al. “Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium Through Activation of the Sweet Taste Receptor T1R3.” Nutrients, 2020.     Best citation for the “sugar-free does not mean barrier-neutral” point. Supports direct epithelial barrier effects of common artificial sweeteners in experimental models.   Peng L, et al. “Butyrate Enhances the Intestinal Barrier by Facilitating Tight Junction Assembly via Activation of AMP-Activated Protein Kinase in Caco-2 Cell Monolayers.” Journal of Nutrition, 2009.     Classic mechanistic citation for butyrate. Supports the claim that loss of fermentable fiber and reduced butyrate production can weaken barrier function.   Kumar KP, et al. “The Interplay Between the Microbiota, Diet and T Regulatory Cells in Maintaining Intestinal Homeostasis.” Frontiers in Microbiology, 2023.     Useful for the tolerance language. Supports the argument that diet and microbial metabolites shape Treg biology and mucosal tolerance.   Haase S, et al. “Sodium Chloride Triggers Th17 Mediated Autoimmunity.” Frontiers in Immunology, 2019.     Key citation for high salt and autoimmune-prone immune skewing. Supports the claim that excess salt can promote pathogenic Th17 biology relevant to autoimmune disease.   Wilck N, et al. “Salt-Responsive Gut Commensal Modulates TH17 Axis and Disease.” Nature, 2017.     Strong bridge between salt, microbiome, and Th17 signaling. Supports the point that salt is not just a blood pressure story; it is also an immune-story.   Vitales-Noyola M, et al. “Analysis of Sodium Chloride Intake and Treg/Th17 Lymphocytes in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus.” Journal of Immunology Research, 2018.     Helpful human-facing citation for salt and immune skewing in autoimmune populations. Use cautiously, but it strengthens translation from theory to autoimmune terrain.   Phuong-Nguyen K, et al. “Advanced Glycation End-Products and Their Effects on Gut Health.” Nutrients, 2023.     Good review for the AGE section. Supports the argument that AGE-rich processed foods may worsen oxidative stress, microbiota balance, and barrier function.   Chen Y, et al. “Dietary Advanced Glycation End-Products Elicit Toxicological Effects by Disrupting Gut Microbiota and Increasing Colon Permeability in Rats.” Journal of Toxicology and Environmental Health, 2021.     Useful mechanistic support for the processing-chemistry section. Reinforces the claim that dietary AGEs can alter microbial ecology and increase permeability.   Monteiro CA, et al. “Ultra-Processed Foods: What They Are and How to Identify Them.” Public Health Nutrition, 2019.   Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he's helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He's also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more. If you're ready to take your health seriously, this podcast is a great place to start.  

A ketogenic diet put his ulcerative colitis into complete remission — off all medications, confirmed on colonoscopy. Dr. Nick Norwitz (PhD Oxford, MD Harvard) explains why evidence-based care isn't always optimal care, how keto rewires the gut and brain, and why GLP-1 drugs should catalyze lifestyle change, not replace it.CHAPTERS:0:00 - The most remarkable thing about my story is it's not unique1:14 - Welcome Nick Norwitz — Oxford PhD, Harvard MD2:02 - Ulcerative colitis, desperation, and keto remission5:34 - What medical school doesn't teach8:05 - Why evidence-based care ≠ optimal care15:53 - The carnivore-ketogenic IBD case series (10 patients)18:50 - Fiber elimination in pediatric Crohn's — 60–85% remission20:00 - Keto for depression: Ohio State trial — 69–71% reduction23:49 - Seed oils: the nuanced truth29:32 - Ketones and neurodegenerative disease32:52 - Autophagy, lateral habenula, and depression36:16 - Sonnenburg 2021: fermented foods beat fiber for inflammation37:20 - GLP-1 agonists: good tool, poor deployment43:29 - Statins slash GLP-1 by ~50% (Cell Metabolism, 2024)48:57 - ClosingREFERENCES:Carnivore-Keto for IBD (Norwitz et al., Frontiers, 2024): PMC11409203Keto for Depression (Ohio State, 2025): PMC12420795Fermented Foods vs Fiber (Sonnenburg, Cell, 2021): Stanford NewsStatins Slash GLP-1 (Cell Metabolism, 2024): pubmed/38325336Autophagy + Depression (Nature, 2025): NatureGUEST: Nick Norwitz, PhD MDHOST: Dr. Robert Lufkin MD | robertlufkinmd.com⭐ Enjoying the show? Please leave a 5-star review on Apple Podcasts — it takes 30 seconds and helps more people discover the science of health and longevity. Thank you!New episodes every Tuesday & Thursday. Subscribe so you don't miss one.Continue this conversation on Substack: https://robertlufkinmd.substack.comLies I Taught In Medical School — Free sample chapter: https://www.robertlufkinmd.com/lies/Web: https://www.robertlufkinmd.comYouTube: https://www.youtube.com/robertlufkinmdX: https://x.com/robertlufkinmdInstagram: https://www.instagram.com/robertlufkinmd/TikTok: https://www.tiktok.com/@robertlufkinLinkedIn: https://www.linkedin.com/in/robertlufkinmd/

GLP-1 medications like semaglutide and tirzepatide are everywhere right now—but are they actually solving the problem? In Episode 8 of this 16-part series on ultra-processed foods, Dr. Brendan McCarthy breaks down the truth about GLP-1 medications: how they work, why they can feel like a “miracle,” and where things go wrong when they're used without proper medical guidance. This isn't about shame. It's about understanding. GLP-1s can quiet “food noise” and help regulate appetite—but they don't fix your relationship with food, your metabolism, or the long-term patterns that lead to weight gain. Without structure, nutrition, and proper care, many patients end up with muscle loss, nutrient deficiencies, and rebound weight gain. In this episode, you'll learn: What GLP-1 medications actually do in your body Why they're not a long-term solution on their own The biggest mistakes doctors and clinics make when prescribing them How ultra-processed foods drive weight gain in the first place How to use GLP-1s the right way to create lasting change The goal isn't dependence—it's freedom. If you're currently on a GLP-1 (or considering it), this episode will change how you think about your treatment plan.   Mechanism Anchored References This episode is not anti medication. It is about putting GLP 1 therapy in its proper place. GLP 1 receptor agonists can reduce appetite pressure and alter satiety signaling. That matters. But quieter appetite is not the same as full recovery. Food quality still matters. Protein still matters. Muscle still matters. Structure still matters.   References U.S. Food and Drug Administration. WEGOVY semaglutide injection Prescribing Information. 2025. Wilding, John P H, et al. Once Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, vol. 384, no. 11, 2021, pp. 989 to 1002. Wilding, John P H, et al. Weight Regain and Cardiometabolic Effects After Withdrawal of Semaglutide The STEP 1 Trial Extension. Diabetes Obesity and Metabolism, vol. 24, no. 8, 2022, pp. 1553 to 1564. Hall, Kevin D, et al. Ultra Processed Diets Cause Excess Calorie Intake and Weight Gain An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell Metabolism, vol. 30, no. 1, 2019, pp. 67 to 77. Neeland, Ian J, et al. Changes in Lean Body Mass with Glucagon Like Peptide 1 Based Therapies and Mitigation Strategies. Diabetes Obesity and Metabolism, 2024. Wilding, John P H, et al. Impact of Semaglutide on Body Composition in Adults with Overweight or Obesity Exploratory Analysis of the STEP 1 Study. 2021. Everitt, Barry J, and Trevor W Robbins. Drug Addiction Updating Actions to Habits to Compulsions Ten Years On. Annual Review of Psychology, vol. 67, 2016, pp. 23 to 50. Monteiro, Carlos A, et al. The UN Decade of Nutrition the NOVA Food Classification and the Trouble with Ultra Processing. Public Health Nutrition, vol. 21, no. 1, 2018, pp. 5 to 17.   Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he's helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He's also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more. If you're ready to take your health seriously, this podcast is a great place to start.  

Craving junk food when you're stressed isn't a lack of discipline — it's biology. In this episode, Dr. Brendan McCarthy breaks down what ultra-processed and hyper-palatable foods actually do inside your body — from your metabolism to your hormones, your brain, and your stress response. But this isn't about guilt or shame. It's about understanding what you're up against — especially as a parent trying to make better choices in a world designed to make that difficult. You'll learn: What ultra-processed foods really are How they impact your endocrine system and metabolism Why stress makes you crave sugar and processed foods Why shame around food doesn't work (and never will) Simple, realistic ways to improve your family's eating habits This episode is about taking back control — without perfection, and without guilt.   Mechanism-Anchored References Monteiro, Carlos A., et al. “Ultra-Processed Foods: What They Are and How to Identify Them.” Public Health Nutrition, vol. 22, no. 5, 2019, pp. 936–941. Hall, Kevin D., et al. “Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.” Cell Metabolism, vol. 30, no. 1, 2019, pp. 67–77.e3. doi:10.1016/j.cmet.2019.05.008. Rush, E. Catherine, et al. “The Impact of Ultra-Processed Foods on Pediatric Health.” Nutrition Reviews, 2024. doi:10.1093/nutrit/nuae051. Ventura, Alison K., and John Worobey. “Early Influences on the Development of Food Preferences.” Current Biology, vol. 23, no. 9, 2013, pp. R401–R408. doi:10.1016/j.cub.2013.02.037. Mennella, Julie A., et al. “Preferences for Salty and Sweet Tastes Are Elevated and Related to Each Other during Childhood.” PLOS ONE, vol. 9, no. 3, 2014, e92201. doi:10.1371/journal.pone.0092201. Roberto, Christina A., et al. “Influence of Licensed Characters on Children's Taste and Snack Preferences.” Pediatrics, vol. 126, no. 1, 2010, pp. 88–93. doi:10.1542/peds.2009-3433. Swindle, Taren, et al. “Pester Power: Examining Children's Influence as an Active Component of the Family Food Environment.” Journal of Nutrition Education and Behavior, vol. 52, no. 8, 2020, pp. 801–807. doi:10.1016/j.jneb.2020.06.002. Pérez-Escamilla, Rafael, et al. “Responsive Feeding Recommendations: Harmonizing Integration into Dietary Guidelines for Infants and Young Children.” Current Developments in Nutrition, vol. 5, no. 6, 2021, nzab076. doi:10.1093/cdn/nzab076. Puhl, Rebecca M., and Chelsea A. Heuer. “Obesity Stigma: Important Considerations for Public Health.” American Journal of Public Health, vol. 100, no. 6, 2010, pp. 1019–1028. doi:10.2105/AJPH.2009.159491. World Health Organization. Set of Recommendations on the Marketing of Foods and Non-Alcoholic Beverages to Children. World Health Organization, 2010.   Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he's helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He's also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more. If you're ready to take your health seriously, this podcast is a great place to start.  

Send us Fan MailThis week, I'm taking a curious, watch-and-see approach to GLP-1 medications—things like semaglutide, Ozempic, Wegovy. We'll cover the research-backed potential benefits, the side effects, what happens after stopping, and why the conversation is about much more than just weight. No judgment, no pressure, just information, reflection, and a reminder that your choices are personal and worth considering thoughtfully.Tune in if you want to explore GLP-1 medications from a place of curiosity and clarity.Quote of the Week:“We are what we repeatedly do. Excellence, then, is not an act, but a habit.” — Will Durant Citations1.    Wilding, J. P. H., et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 384, 989–1002.2.    Rubino, D., et al. (2021). Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance. Diabetes, Obesity and Metabolism.3.    SELECT Trial Investigators (2023). Semaglutide and Cardiovascular Outcomes in Obesity. New England Journal of Medicine.4.    Drucker, D. J. (2018). Mechanisms of Action and Therapeutic Application of GLP-1. Cell Metabolism.5.    Baggio, L. L., & Drucker, D. J. (2007). Biology of Incretins. Gastroenterology.Let's go, let's get it done.Get more information at: http://projectweightloss.org

If you've ever felt hungry and wondered “What is wrong with me?”—this episode will change how you see it.Hunger isn't a lack of discipline. It's a biological signal driven by your brain, hormones, and environment.In this episode, we break down what hunger actually is and why it can feel so hard to control. You'll learn how key hormones like ghrelin, leptin, insulin, and GLP-1 regulate appetite—and why your brain is the real decision-maker.More importantly, we cover the three types of hunger:Homeostatic (true energy need) Hedonic (pleasure-driven) Conditioned (habit-based) Understanding the difference is what gives you power.We also explore how ultra-processed foods, sleep, and stress disrupt hunger signals—and what you can do to better regulate your appetite without restriction.In this episode: What hunger actually is  The hormones behind appetite  The 3 types of hunger  How processed foods impact hunger  Why sleep and stress matter This isn't about fighting your hunger—it's about understanding it so you can make more informed choices.References: Batterham RL et al. (2002). Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. Cummings DE et al. (2001). A preprandial rise in plasma ghrelin levels suggests a role in meal initiation. Diabetes. Friedman JM & Halaas JL (1998). Leptin and the regulation of body weight. Nature. Hall KD et al. (2019). Ultra-processed diets cause excess calorie intake and weight gain. Cell Metabolism. Leidy HJ et al. (2015). The role of protein in weight loss and maintenance. AJCN. Martinez Steele E et al. (2016). Ultra-processed foods in the US diet. BMJ Open. Monteiro CA et al. (2019). Ultra-processed foods: What they are and how to identify them. Public Health Nutrition. Morton GJ et al. (2006). Central nervous system control of food intake. Nature. Schwartz MW et al. (2000). Central nervous system control of food intake. Nature. Spiegel K et al. (2004). Sleep curtailment… decreased leptin and increased hunger. Annals of Internal Medicine. Volkow ND et al. (2013). Obesity and addiction: Neurobiological overlaps. Nature Reviews Neuroscience. Wang L et al. (2021). Trends in ultra-processed food consumption. JAMA. Woods SC (1991). The eating paradox. Psychological Review. Support the showGet Weekly Health Tips:  thrivehealthcoachllc.comJoin the Thrive Collective Facebook groupLet's Connect:@‌ashleythrivehealthcoach or via email: ashley@thrivehealthcoachingllc.comPodcast Produced by Virtually You!

In this episode, Vanessa breaks down the fasting mimicking diet (FMD) — including the exact calories, macros, and protein intake used in the research — and compares it to higher-protein fat loss approaches like protein-sparing modified fasting (PSMF) days.

Durante años nos han repetido que comer variado siempre es mejor, que hay que comer de todo y que esa es la base de una buena alimentación. Pero en este vídeo te explico por qué esa idea está mal planteada, cómo la variedad puede hacer que comas más y peor, y por qué una alimentación más simple, coherente y basada en alimentos densos en nutrientes puede darte más salud, más saciedad y más control.Hablamos de evolución, saciedad sensorial específica, dopamina, recompensa, control del hambre y del gran error de confundir variedad con buena nutrición.Si quieres entender por qué no necesitas una variedad absurda de comida para cubrir tus necesidades reales, este vídeo es para ti.Web: https://www.faustoalfaro.comInstagram: @faustoalfaro_X: @Faustoalfaro_Suscríbete al canal para más vídeos sobre salud, nutrición y rendimiento deportivo con criterio.#nutricion #alimentacion #salud #comidareal #dopamina #hambre #habitos #perdidadegrasa #rendimientodeportivo #nutricionsaludableReferencias:Vadiveloo M, Scott M, Quatromoni P, Jacques P. Dietary variety and its implications for obesity prevention in US adults. Circulation. 2018.Small DM, DiFeliceantonio AG. Processed foods and food reward. Science. 2019.Hall KD, Ayuketah A, Brychta R, et al. Ultra-processed diets cause excess calorie intake and weight gain. Cell Metabolism. 2019.

“工位靠窗”往往被视为职场的幸运儿专属，然而，这份“幸运”所蕴含的，远不止于舒适的工作环境。代谢领域顶级学术期刊Cell Metabolism发表的一项研究发现，与人工光相比，办公期间接触自然光能显著改善糖尿病患者的血糖控制，提高脂肪利用率，并优化生物钟功能。

Application pour EV0360 : https://hlperformance.caRéférences :Bellisle, F. (2003). Why should we study human food intake behaviour? *Nutrition, Metabolism and Cardiovascular Diseases*, *13*(4), 189–193. [https://doi.org/10.1016/S0939-4753(03)00063-7](https://doi.org/10.1016/S0939-4753(03)00063-7)Canadian Centre on Substance Use and Addiction. (2023). *Canada's guidance on alcohol and health*. CCSA. https://www.ccsa.ca/canadas-guidance-alcohol-and-healthDing, D., Nguyen, B., Nau, T., Luo, M., Del Pozo Cruz, B., Dempsey, P. C., Munn, Z., Jefferis, B. J., Sherrington, C., Calleja, E. A., Hau Chong, K., Davis, R., Francois, M. E., Tiedemann, A., Biddle, S. J. H., Okely, A., Bauman, A., Ekelund, U., Clare, P., & Owen, K. (2025). Daily steps and health outcomes in adults: A systematic review and dose-response meta-analysis. *The Lancet Public Health*, *10*(8), e668–e681. [https://doi.org/10.1016/S2468-2667(25)00164-1](https://doi.org/10.1016/S2468-2667(25)00164-1)Hall, K. D., & Guo, J. (2017). Obesity energetics: Body weight regulation and the effects of diet composition. *Gastroenterology*, *152*(7), 1718–1727. https://doi.org/10.1053/j.gastro.2017.01.052Hall, K. D., Ayuketah, A., Brychta, R., Cai, H., Cassimatis, T., Chen, K. Y., … & Walter, P. J. (2019). Ultra-processed diets cause excess calorie intake and weight gain: An inpatient randomized controlled trial. *Cell Metabolism*, *30*(1), 67–77. https://doi.org/10.1016/j.cmet.2019.05.008Hall, K. D., Sacks, G., Chandramohan, D., Chow, C. C., Wang, Y. C., Gortmaker, S. L., & Swinburn, B. A. (2012). Quantification of the effect of energy imbalance on bodyweight. *The Lancet*, *378*(9793), 826–837. [https://doi.org/10.1016/S0140-6736(11)60812-X](https://doi.org/10.1016/S0140-6736(11)60812-X)Mattes, R. D. (2014). Beverages and positive energy balance: The menace is the medium. *International Journal of Obesity*, *38*(S1), S1–S6. https://doi.org/10.1038/ijo.2014.21National Institutes of Health. (s. d.). *NIH Body Weight Planner* [Outil en ligne]. U.S. Department of Health and Human Services. https://www.niddk.nih.gov/bwpRyan, R. M., & Deci, E. L. (2000). Self-determination theory and the facilitation of intrinsic motivation, social development, and well-being. *American Psychologist*, *55*(1), 68–78. https://doi.org/10.1037/0003-066X.55.1.68Ryan, R. M., & Deci, E. L. (2017). *Self-determination theory: Basic psychological needs in motivation, development, and wellness*. Guilford Press.American College of Sports Medicine. (2022). *ACSM's guidelines for exercise testing and prescription* (11e éd.). Lippincott Williams & Wilkins. *(Position Stand original : 2009)*World Health Organization. (2020). *WHO guidelines on physical activity and sedentary behaviour*. WHO Press. https://www.who.int/publications/i/item/9789240015128

Ever feel like staying healthy today requires constant effort, planning, and discipline?You're not imagining it. Modern life is designed in ways that make health harder than it used to be. From ultra-processed foods and sedentary jobs to a culture built around convenience and constant access to calories, our environment often works against our biology.In this episode, we break down why maintaining your health today can feel like an uphill battle—and why that doesn't mean you're failing. It means you're navigating what public health researchers call an “obesogenic environment”: surroundings that make overconsumption easy and physical activity harder.You'll learn how changes in our food system, movement patterns, and daily routines have reshaped the health landscape—and most importantly, what you can do about it.In this episode:Why modern environments promote overeatingHow ultra-processed foods increase calorie intakeWhy sedentary lifestyles changed daily energy expenditureThe hidden role of convenience and “friction” in eating behaviorWhy health requires more intention todayFive practical strategies to make healthy choices easierThe goal isn't perfection—it's awareness and creating an environment that supports your health instead of working against it.You're not failing. You're navigating a system that wasn't built for human health. ReferencesBaumeister, R. F., et al. (1998). Ego depletion. Journal of Personality and Social Psychology. Ducrot, P., et al. (2017). Meal planning, diet quality and body weight. Int. Journal of Behavioral Nutrition and Physical Activity. Hall, K. D., et al. (2019). Ultra-processed diets increase calorie intake and weight gain. Cell Metabolism. Juul, F., et al. (2022). Ultra-processed food consumption and obesity in the U.S. American Journal of Clinical Nutrition. Levine, J. A. (2002). Non-exercise activity thermogenesis (NEAT). Proceedings of the Nutrition Society. Martínez Steele, E., et al. (2016). Ultra-processed foods and added sugars in the U.S. diet. BMJ Open. Matthews, C. E., et al. (2008). Sedentary behavior and health outcomes. American Journal of Epidemiology. Pontzer, H. (2015). Constrained energy expenditure model. Current Biology. Pontzer, H. (2021). Burn: New Research Blows the Lid Off How We Really Burn Calories. Swinburn, B., et al. (1999). Obesogenic environments. Preventive Medicine. Young, L. R., & Nestle, M. (2002). Expanding portion sizes. American Journal of Public Health.Support the showGet Weekly Health Tips: thrivehealthcoachllc.com Join the Thrive Collective Facebook group Let's Connect:@‌ashleythrivehealthcoach or via email: ashley@thrivehealthcoachingllc.com Podcast Produced by Virtually You!

ReferencesJ Biol Chem 2017 292: 20481.Cell Metabolism. 2018. 27.,3 p602-615.e4March 06Proc Natl Acad Sci U S A. 2010 May 8;107(21):9626–9631Proc Natl Acad Sci U S A. 2011 May 18;108(23):9466–9471Guerra,DJ. 2026. Unpublished LecturesHoward, B. 1954.Fly Me to the Moon. Sinatrahttps://open.spotify.com/track/7FXj7Qg3YorUxdrzvrcY25?si=3104a016654d4bb9Sparks, A. "Pinetop" 1935. Every Day I Have the Blues. Count Basis and Joe Williamshttps://open.spotify.com/track/1ZVV4uUYilEdZRySfKjvpx?si=62de0af91e7648f0Kaukonen, J. 1971. Third Week in Chelsea. JAhttps://open.spotify.com/track/5t5bV1HLuULF0bX1F6MfCv?si=d65795563a324df7

Type 2 diabetes management is influenced not only by diet and medication but also by environmental factors, including the type and timing of light exposure during typical indoor workdays A Cell Metabolism study found that participants exposed to natural daylight spent more time within a healthy glucose range than those exposed to standard office lighting Daylight supports circadian alignment by strengthening communication between the brain's master clock and peripheral clocks in organs that control insulin sensitivity, glucose uptake, and energy metabolism Natural daylight also shifted how the body used energy and improved metabolic flexibility, which plays an important role in long-term insulin sensitivity and glucose regulation Simple changes like getting morning light, taking outdoor midday breaks, sitting near windows, and keeping a consistent sleep schedule can help restore circadian rhythm and support glucose stability

Are you exhausted all the time? In this solo episode, Darin breaks down why so many people feel chronically exhausted despite eating clean, exercising, and "doing everything right." He explains how modern life disrupts mitochondrial function, circadian rhythm, stress signaling, and nutrient availability, and why fatigue is not a personal failure, but a biological signal. This episode offers a grounded, practical roadmap to restoring energy by realigning your environment, habits, and daily rhythms with how the body is actually designed to function.     What You'll Learn in This Episode: Why chronic fatigue is exploding—even among healthy, active people How mitochondria do far more than "make energy" The role of circadian rhythm, light exposure, and timing in energy production Why stress, overtraining, and modern lifestyles drain cellular energy How emotional suppression and unexpressed stress affect vitality The difference between forcing energy and allowing energy Simple daily practices that support mitochondrial repair How breathwork, stillness, and social connection restore resilience Why nutrition alone isn't enough without rhythm and recovery How to realign your biology with the modern world     Timecodes 00:00:00 – Welcome to SuperLife and the intention behind this episode 00:00:32 – Sponsor: TheraSage and natural frequency-based healing 00:02:10 – Happy New Year + why this conversation matters now 00:02:37 – Are you exhausted even though you're "doing everything right"? 00:03:26 – The modern energy crisis and rising chronic fatigue 00:04:12 – Why surface-level health advice no longer works 00:04:27 – Mitochondria: more than energy factories 00:04:59 – Circadian misalignment, EMFs, and modern stressors 00:05:36 – Overtraining, stress load, and lack of recovery 00:06:00 – Fatigue as a signal, not a lack of discipline 00:06:18 – How artificial light disrupts internal clocks 00:07:25 – Discipline as alignment with natural rhythms 00:07:36 – Emotional release, primal expression, and energy recovery 00:08:47 – Why "why am I tired all the time?" is exploding online 00:09:24 – The mitochondria as environmental sensors 00:10:06 – Stress signaling, thoughts, and cellular energy flow 00:11:18 – Breathwork and slowing the nervous system 00:12:24 – Social connection and low-stress signaling 00:13:02 – Sponsor: Bite toothpaste and eliminating plastic exposure 00:15:19 – Morning sunlight and circadian priming 00:15:52 – Reducing artificial light at night 00:16:15 – Nutrients that support mitochondrial function 00:17:29 – Sleep timing, consistency, and repair 00:18:20 – Evening routines and melatonin protection 00:19:46 – Small daily steps compound into real energy 00:20:17 – Antioxidants, inflammation, and recovery 00:20:49 – Training smarter, not harder 00:21:31 – Breathwork, sauna, and recovery rituals 00:22:26 – Nutrition, protein, and polyphenols 00:24:37 – Five daily energy takeaways 00:25:24 – Energy is permitted, not forced 00:26:03 – Listening to the body and closing reflections 00:26:49 – SuperLife Patreon and community support     Join the SuperLife Community Get Darin's deeper wellness breakdowns — beyond social media restrictions: Weekly voice notes Ingredient deep dives Wellness challenges Energy + consciousness tools Community accountability Extended episodes Join for $7.49/month → https://patreon.com/darinolien     Thank You to Our Sponsors: Therasage: Go to www.therasage.com and use code DARIN at checkout for 15% off Bite Toothpaste: Go to trybite.com/DARIN20 or use code DARIN20 for 20% off your first order.     Find More from Darin Olien: Instagram: @darinolien Podcast: SuperLife Podcast Website: superlife.com Book: Fatal Conveniences     Key Takeaway "Fatigue isn't failure. It's feedback. When your environment, timing, and signals align, your biology remembers how to thrive."     Bibliography/Sources: Ames, B. N. (2006). Low micronutrient intake may accelerate the degenerative diseases of aging through allocation triage. Proceedings of the National Academy of Sciences, 103(47), 17589–17594. https://doi.org/10.1073/pnas.0608757103 Bass, J., & Takahashi, J. S. (2010). Circadian integration of metabolism and energetics. Science, 330(6009), 1349–1354. https://doi.org/10.1126/science.1195668 Gooley, J. J., Chamberlain, K., Smith, K. A., Khalsa, S. B., Rajaratnam, S. M., Van Reen, E., Zeitzer, J. M., Czeisler, C. A., & Lockley, S. W. (2011). Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. The Journal of Clinical Endocrinology & Metabolism, 96(3), E463–E472. https://doi.org/10.1210/jc.2010-2098 Kreher, J. B., & Schwartz, J. B. (2012). Overtraining syndrome: A practical guide. 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Psychosomatic Medicine, 80(2), 126–140. https://doi.org/10.1097/PSY.0000000000000544 Picard, M., McElroy, G. S., & Turnbull, D. M. (2015). Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress. Proceedings of the National Academy of Sciences, 112(48), 14920–14925. https://doi.org/10.1073/pnas.1518223112 Reiter, R. J., Rosales-Corral, S., Tan, D. X., Acuna-Castroviejo, D., Qin, L., Yang, S. F., & Xu, K. (2017). Melatonin as a mitochondria-targeted antioxidant: One of evolution's best inventions? Journal of Pineal Research, 62(1), e12394. https://doi.org/10.1111/jpi.12394 Scheer, F. A., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009). Adverse metabolic and cardiovascular consequences of circadian misalignment. Proceedings of the National Academy of Sciences, 106(11), 4453–4458. https://doi.org/10.1073/pnas.0808180106 Straub, R. H. (2017). The brain and immune system prompt energy shortage in chronic inflammation and ageing. Nature Reviews Rheumatology, 13(2), 74–79. https://doi.org/10.1038/nrrheum.2016.213 World Health Organization. (n.d.). Micronutrient deficiencies. World Health Organization. https://www.who.int/health-topics/micronutrients

Send us a textHey friends — this week, with the holidays in full swing, I wanted to bring you three research-backed strategies you can use to feel lighter — emotionally, mentally, and yes, physically — without rigidity, pressure, or perfection.This episode is all about top researched strategies, that coupled with awareness, and choosing yourself in the ways that truly matter and make a difference, particularly during the holidays. Take a listen and share the episode – even better, set up a buddy to implement the techniques with. Quotes of the Week:✨ “What most people don't realize is that food is not just calories: It's information… it communicates to every cell in the body.” — Dr. Mark Hyman✨ “Our modern lifestyle… disrupts our circadian rhythms and reduces the production of the sleep hormone melatonin.” — Satchin Panda, The Circadian CodeTake a listen — and let's move through this season with intention, clarity, and love. Citations1.    Sacks, F. M., Bray, G. A., Carey, V. J., et al. (2009). Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. Journal of the American Medical Association, 360(9), 859–873.2.    Smith, J. D., Nguyen, T., Hall, K. D., et al. (2023). Protein and fiber intake and their effects on cravings and spontaneous snacking in adults: A randomized controlled trial. Nutrients, 15(4), 812–823.3.    Sutton, E. F., et al. (2018). Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even Without Weight Loss in Men with Prediabetes. Cell Metabolism, 27(6), 1212–1221.Let's go, let's get it done. Get more information at: http://projectweightloss.org

In this solosode of The Energy Code, Dr. Mike unveils the most comprehensive update yet to BioLight's flagship supplement — BioBlue — and takes listeners deep inside the quantum bioenergetic thinking that shaped its redesign. What began as a methylene-blue-based mitochondrial catalyst has evolved into a next-generation longevity systemintegrating deuterium-depleted water, elevated NMN, taurine, and trace gold-silver resonance compounds.   Dr. Mike breaks down the science and reasoning behind each refinement: why Litewater's 10 ppm deuterium-depleted water now forms the clean matrix for all BioBlue liquids, how NMN has been increased ten-fold (10 mg → 100 mg) to meaningfully expand NAD⁺ pools and drive biogenesis, and how taurine stabilizes mitochondrial membranes and calcium signaling for endurance and resilience. He explains the subtle yet powerful tweaks — like a 50 % increase in colloidal gold and silver and a 40 % reduction in fulvic acid — that sharpen redox coherence and enhance longevity signaling.   Dr. Mike dives into: Overview of how BioBlue progressed from a simple methylene-blue solution to a full mitochondrial optimization system. Why all BioBlue liquids now utilizes Litewater for cleaner proton flow and improved ATP efficiency. Why NMN increased from 10 mg → 100 mg per dose to meaningfully raise NAD⁺ levels, drive biogenesis, and enhance DNA repair. Why the addition of Taurine – 100 mg per serving for membrane stability, calcium regulation, and long-term mitochondrial resilience. Enhanced Trace Elements – 50 % more colloidal gold & silver plus refined fulvic acid for smoother redox flow and higher photodynamic efficiency.   This episode isn't just about formulation — it's about why every molecule matters in the pursuit of mitochondrial efficiency, redox stability, and long-term cellular youthfulness. Mike also previews BioLight's upcoming new website, pre-Black-Friday event, and a soon-to-launch BioBlue Lite product line for those seeking simplicity without compromise.   Key Topics Covered Evolution of BioBlue — from the original methylene blue + NMN formula to a comprehensive mitochondrial optimization system. Integration of Deuterium-Depleted Water (Litewater, 10 ppm) — explanation of how lowering deuterium enhances ATP production, redox efficiency, and longevity potential. NMN Upgrade (10× Increase) — new 100 mg per serving dosage for boosting NAD⁺ levels, mitochondrial biogenesis, DNA repair, and energy metabolism. Addition of Taurine (100 mg per serving) — supports membrane integrity, calcium balance, ROS buffering, and cellular longevity signaling. Enhanced Colloidal Gold & Silver (50 % Increase) — improved redox stability, electron flow, and photodynamic synergy with methylene blue and red light. Refined Wu Jin Sun Fulvic Acid (−40 %) — optimizes redox balance and mineral transport while improving synergy between all active compounds. Comprehensive Mitochondrial Benefits — improved ATP efficiency, autophagy, and mitochondrial biogenesis for cleaner, more resilient energy production. New Product Lineup — introduction of BioBlue Lite and BioBlue Leuco Lite (simplified methylene blue + water versions) for accessible mitochondrial support. Key Quotes from Dr. Mike   “Deuterium-depleted water doesn't just make the mitochondria go faster—it helps them run truer, cleaner, and more efficiently.”   “We've moved BioBlue from a trace metabolic nudge to a real mitochondrial optimization protocol that supports redox cycling, biogenesis, and longevity pathways in a quantifiable way.”   “Taurine turns BioBlue from a fast-acting energy compound into a cellular longevity stack—supporting repair, recycling, and resilience.”   “By increasing colloidal gold and silver within their optimal bio-signal zones, BioBlue transforms from a chemical redox supplement into a biophysical energy transducer.”   “Each change — from Litewater to taurine — was made to help your mitochondria run longer, cleaner, and more accurately. This is longevity through bioenergetics.” Episode Timeline 00:00 – Announcements: Pre-Black Friday + new website 04:00 – The origin of BioBlue and its evolution 10:00 – Introducing the upgraded BioBlue formula 11:00 – Why BioLight partnered with Light Water 12:00 – How deuterium slows mitochondrial ATP production 17:00 – Functional benefits of deuterium-depleted water 19:00 – 10x increase in NMN for energy and repair 27:00 – Synergy between NMN and methylene blue 30:00 – Adding taurine for stability and longevity 39:00 – Increasing colloidal gold for photonic synergy 46:00 – Boosting colloidal silver for redox protection 52:00 – Why lowering fulvic acid improves coherence 56:00 – What's next: BioBlue Light + legacy pricing offer 01:02:00 – Dr. Mike's closing thoughts on mitochondrial optimization Resources & References Deuterium Depletion and Mitochondrial Efficiency Boros, L. G. Deuterium Depletion and Cellular Bioenergetics. Frontiers in Oncology (2020). Sagalevsky, V. — Light Water: The Science of Deuterium-Depleted Hydration (interview referenced in episode).   Nicotinamide Mononucleotide (NMN) & NAD⁺ Metabolism Mills, K. F. et al. Long-term administration of NMN mitigates age-associated physiological decline in mice. Cell Metabolism (2016). Yoshino, J. et al. NAD⁺ intermediates: The biology and therapeutic potential of NMN and NR. Cell Metabolism (2018).   Taurine and Longevity Pathways Wang, W. et al. Taurine deficiency as a driver of aging. Science (2023). Schaffer, S. W. et al. Physiological roles of taurine in the heart and mitochondria. Journal of Biomedical Science (2010).   Colloidal Gold & Silver in Cellular Redox Systems Li, Y. et al. Gold nanoclusters enhance mitochondrial cytochrome c oxidase activity. ACS Nano (2019). Kim, Y. S. et al. Silver nanoparticles exhibit SOD- and catalase-like activity for redox modulation. Nano Research (2020).   Fulvic & Humic Acids as Bioactive Redox Modulators   Senesi, N. Nature of humic substances and their interactions with trace metals and organics in the environment. Soil Science (1992). Wu Jin San extract — traditional Chinese “gold medicine” formulation known for enhanced mineral transport and detoxification support.     Additional Mentions PGC-1α, SIRT1/SIRT3, and Autophagy pathways in mitochondrial biogenesis and longevity. Quantum redox coupling and plasmonic resonance as mechanisms for light-driven bioenergetic optimization.  

Send us a textHave you ever wondered what happens inside your body when you don't eat for a while — when you give yourself space between meals? In this week's episode of Project Weight Loss, we explore that quiet magic with the story of Nobel Laureate Maester Yoshinori Ohsumi, whose discovery of autophagy — the body's natural process of self-cleaning and renewal — changed how we understand health, vitality, and longevity. From his humble lab in Japan to the moment he glimpsed a new world under the microscope, Ohsumi's curiosity reveals how our bodies are wired to restore themselves, especially in moments of pause.We'll talk about how autophagy connects to fasting, weight management, brain health, and aging — and why giving your body a little space to “dine in” can make such a difference. You'll hear about Ohsumi's groundbreaking experiments, his partnership with his wife and collaborator Mariko Ohsumi, and how their discoveries invite us to see self-renewal as a natural rhythm of life. I'll also link this episode to my earlier one on the Blue Zones — where long-living communities show us what it means to live in harmony with our biology. Listen in, reflect, and maybe even give your body that gentle reset it's been asking for.Quote of the Week:“We are wired for feast and famine, not feast, feast, feast.” — Dr. Jason FungListen to my related episode: The Blue Zones: The Secrets to Living Citations1.    Ohsumi, Y. (2014). Historical landmarks of autophagy research. Cell Research, 24(1), 9–23. https://doi.org/10.1038/cr.2013.1692.    Mizushima, N., & Ohsumi, Y. (2002). Autophagy: Molecular machinery for self-eating. Cell, 120(4), 639–652.3.    Kaushik, S., & Cuervo, A. M. (2018). The coming of age of chaperone-mediated autophagy. Nature Reviews Molecular Cell Biology, 19(6), 365–381.4.    Madeo, F., Zimmermann, A., Maiuri, M. C., & Kroemer, G. (2015). Essential role for autophagy in life span extension. Journal of Clinical Investigation, 125(1), 85–93.5.    Longo, V. D., & Panda, S. (2016). Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan.Cell Metabolism, 23(6), 1048–1059.6.    Fung, J. (2016). The Obesity Code: Unlocking the Secrets of Weight Loss. Greystone Books.Let's go, let's get it done. Get more information at: http://projectweightloss.org

Today, we'll examine an important debate in nutrition: whether skipping breakfast or skipping dinner is more effective for your health and metabolism. We'll unpack what the research says, how your body's internal clock affects metabolism, and why the timing of your last meal can make or break your weight loss—especially if you're on a GLP-1 medication like semaglutide, dual GIP/GLP-1 like tirzepatide, or triple agonist like retatrutide. If you want to support what we do, head over to our Partners Page. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going. https://pepties.com/partners/ Let's get into it. Circadian Rhythms and Eating Windows Our bodies are wired to follow a circadian rhythm—a 24-hour cycle that controls hormones like melatonin, cortisol, and insulin. One key thing to understand is that your body follows the rhythm of the day. When it's light out, you're naturally wired for activity—your metabolism is active, digestion works efficiently, and your body is more sensitive to insulin. As daylight fades, melatonin levels rise, signaling it's time to slow down, rest, and prepare for sleep. Here's the kicker: melatonin doesn't just make you sleepy—it also reduces insulin sensitivity. That means when you eat late at night—say at 8 or 9pm—your body doesn't handle sugar or calories as well. Instead of using that energy, you're more likely to store it as fat. So, a meal at 5pm when it's still light out? Your body's insulin response is stronger. You burn and use more of what you eat. But a meal at 9pm in the dark? Your body's gearing up for sleep, not digestion. Calories from that meal are more likely to go into fat storage. Breakfast vs. Dinner Skipping—What the Data Says Let's talk about what the research shows when it comes to skipping breakfast versus skipping dinner. Several studies have looked at early time-restricted feeding, where you eat earlier in the day, like between 8 a.m. and 4 p.m., versus eating later, where you skip breakfast and stretch meals into the evening. One of the most cited studies, published in Cell Metabolism. The study looked at men with prediabetes who followed an early time-restricted feeding schedule for five weeks. Even though they didn't lose weight, they had significant improvements in insulin sensitivity, blood pressure, and markers of oxidative stress compared to those eating over a twelve-hour window. The takeaway? Eating earlier in the day improved metabolic function even without reducing calories. Another study found that early eaters experienced lower evening hunger and better fat oxidation, meaning their bodies were burning fat more efficiently. By contrast, those eating later in the day had higher insulin and glucose levels after meals, signaling greater insulin resistance. And more broadly, research consistently shows that eating late at night, especially after seven or eight in the evening, is linked to increased body fat and higher risks of obesity and type 2 diabetes. The reason is straightforward: insulin sensitivity drops as the day goes on, so your body is less efficient at processing glucose at night, and those late calories are more likely to be stored as fat, especially around the belly. So while skipping breakfast might be easier for some people, from a metabolic standpoint, skipping dinner—or at least finishing it earlier—tends to be more beneficial. This connects directly to why fasting works for weight loss. Fasting gives your insulin a chance to drop, which signals your body to tap into stored fat for energy. Front-loading your meals earlier in the day aligns with your body's natural rhythm: insulin sensitivity is higher, digestion is more efficient, and your body has more opportunity to burn fat overnight. People who eat earlier often report feeling more energized, less hungry in the evening, and sleeping better—all key factors in long-term weight control. Now, if you're taking medications like semaglutide, tirzepatide, or retatrutide, timing becomes even more important. These drugs slow gastric emptying, which helps you feel full longer but also means that eating a large dinner late at night can lead to bloating, nausea, heartburn, and in turn, poor sleep. Digestion naturally slows down as melatonin rises and your body prepares for sleep, so combining a late meal with slower gastric emptying can make it harder for your body to rest and burn fat overnight. A good rule is to finish your last meal two to three hours before bed, ideally around five or six in the evening. This gives your body time to digest, allows insulin levels to drop, and lets you switch into fat-burning mode. What's the counter argument? Of course, it's important to remember that meal timing isn't one-size-fits-all. While the research often favors early eating, some people naturally aren't hungry in the morning, and skipping breakfast can actually be a helpful way to stick to a fasting window.  Then there are the “night owls.” Some people's circadian rhythms naturally shift later, and for them, eating later may actually align better with their biology. Forcing an early eating schedule might leave them tired, hungry, or unable to stick with it, which can actually be counterproductive for metabolic health. Research on chronotypes—the natural variations in our sleep-wake cycles—suggests that what works for a morning person might not work for someone who thrives later in the day. Practical lifestyle factors also play a role. Work schedules, family dinners, or social events can make it hard to consistently finish dinner at five or six in the evening. For some, a slightly later meal, if it's balanced and nutrient-dense, can be more sustainable over the long term than forcing an early window and ending up snacking late anyway. Finally, metabolic flexibility matters. Some people can handle a later meal without negative effects on fat storage, insulin sensitivity, or sleep, especially if the meal is lighter or focused on protein and vegetables. The bottom line is that while early eating has clear metabolic advantages for many, especially those taking weight loss medications like tirzepatide, the most important factors are consistency, total calories, and the quality of your food, not just the exact timing. So, whether you're a morning eater, a night owl, or somewhere in between, finding an approach that fits your body and lifestyle—and that you can stick to long term—is often more important than following a strict rule about skipping breakfast or dinner. Thanks for listening to The Peptide Podcast. If today's episode resonated, share it with a friend, please share this episode! Until next time, be well, and as always, have a happy, healthy week.

In this solo episode, Darin pulls back the curtain on one of the most important parts of his life:  he prepares for travel. From the supplements that keep his immune system strong to hydration hacks, adaptogenic elixirs, and EMF protection, this episode is a masterclass in staying grounded and resilient on the road. Travel doesn't have to destroy your health — it can actually elevate it. With a few intentional rituals, smart packing, and awareness, you can turn every trip into an opportunity to deepen your energy, focus, and connection to yourself. What You'll Learn 00:00:00 – Why travel is stressful and how to transform it into an empowering, health-boosting experience 00:01:00 – Darin's supplement protocol: Vitamin D3/K2, probiotics, zinc, vitamin C, and glutathione for immune defense 00:03:00 – The antioxidant power of glutathione and why it's critical for long flights and radiation exposure 00:04:30 – How CBD and terpenes support stress resilience and circadian rhythm through the endocannabinoid system 00:05:20 – Why magnesium and NAD are the unsung heroes of travel recovery and energy 00:06:30 – Darin's morning elixir recipe: cacao, guarana, ashwagandha, chaga, ginseng, and monk fruit 00:08:00 – Hydration 101: how to use a manual RO filter, mineralize your water, and ditch plastic 00:10:00 – How to build nutrient density into travel days using chlorella, spirulina, Shakeology, and Barukas 00:12:00 – Travel nutrition sovereignty: packing your own snacks, fasting, and avoiding airline food 00:14:00 – Movement anywhere: Darin's “portable gym” using bungee cords and bodyweight routines 00:16:00 – The 3-hour morning ritual: NewCalm, Healing Codes, journaling, cacao, red light therapy, and breathwork 00:20:00 – How to avoid radiation scanners, mitigate EMFs, and use WaveGuard for energy field protection 00:22:00 – Why Darin microdoses nicotine for cognitive focus and immune modulation 00:23:00 – Breathing practices for immune strength: 3–4 rounds of 40 deep breaths, Wim Hof style 00:24:00 – How to pack fruit and salads in mason jars to stay hydrated and nourished on planes 00:26:00 – Grounding after flights: barefoot on the earth, morning sunlight, and re-aligning your circadian rhythm Thank You to Our Sponsors Manna Vitality: Go to mannavitality.com/ or use code DARIN20 for 20% off your order. Fatty15: Get an additional 15% off their 90-day subscription Starter Kit by going to fatty15.com/DARIN and using code DARIN at checkout. Find More from Darin Olien: Instagram: @darinolien Podcast: SuperLife Podcast Website: superlife.com Book: Fatal Conveniences Key Takeaway “Preparation is sovereignty. When you take responsibility for your nutrition, your hydration, and your energy before you travel, you're no longer surviving the trip — you're expanding through it.” Bibliography Martineau AR et al. Vitamin D supplementation to prevent acute respiratory infections: systematic review. BMJ. 2017. Goldenberg JZ et al. Probiotics for prevention of respiratory infections. Cochrane Database. 2017. Hemilä H. Vitamin C and zinc in common cold. Nutrients. 2017. Blessing EM et al. Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics. 2015. Morris HJ et al. Spirulina and chlorella as functional foods. Nutrients. 2022. Longo VD, Panda S. Fasting, circadian rhythms, and time-restricted feeding. Cell Metabolism. 2016. Booth FW et al. Waging war on physical inactivity. J Physiol. 2017. Balmori A. Electromagnetic pollution from radiofrequency fields. Pathophysiology. 2015. Kox M et al. Voluntary activation of sympathetic nervous system and attenuation of the innate immune response. PNAS. 2014.

Send us a textThis week we're tackling a food we all know and love: flour. But is it really as harmless as it seems? Join me as I break down the surprising science of refined flour, cravings, and hormones—plus how a few small shifts can help you take back control of your weight loss journey.We'll talk about why flour is classified as an ultra-processed food, how it hijacks hunger signals, and why it can make weight loss feel harder than it should. Don't worry, I'll make it simple, light, and easy to understand—because this is about living your best life, not stressing over bread.Quote of the Week:“Your body is your home—feed it with care.” – Unknown Citations:Monteiro et al., 2019 – Ultra-processed foods: What they are and how to identify them. Public Health Nutrition.Hall et al., 2019 – Ultra-processed diets cause excess calorie intake and weight gain. Cell Metabolism.Ludwig, 2002 – The glycemic index: Physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA.Friedman, 2014 – Leptin and the regulation of body weight. American Journal of Clinical Nutrition.Volkow et al., 2013 – The addictive dimensionality of obesity. Biological Psychiatry.Slavin, 2013 – Fiber and prebiotics: Mechanisms and health benefits. Nutrients.Hu, 2011 – Globalization of diabetes: The role of diet, lifestyle, and genes. Diabetes Care.ADA, 2020 – Standards of medical care in diabetes—2020. Diabetes Care.Let's go, let's get it done. Get more information at: http://projectweightloss.org

It's In the News.. a look at the top headlines and stories in the diabetes community. This week's top stories: CRISPR modified cell transplant for type 1, risk of T1D if parent has a different type of diabetes, Metformin and the brain, oral GLP-1, and more! Find out more about Moms' Night Out  Please visit our Sponsors & Partners - they help make the show possible! Learn more about Gvoke Glucagon Gvoke HypoPen® (glucagon injection): Glucagon Injection For Very Low Blood Sugar (gvokeglucagon.com) Omnipod - Simplify Life Learn about Dexcom   Check out VIVI Cap to protect your insulin from extreme temperatures The best way to keep up with Stacey and the show is by signing up for our weekly newsletter: Sign up for our newsletter here Here's where to find us: Facebook (Group) Facebook (Page) Instagram Twitter Check out Stacey's books! Learn more about everything at our home page www.diabetes-connections.com  Reach out with questions or comments: info@diabetes-connections.com Episode transcription with links: Hello and welcome to Diabetes Connections In the News! I'm Stacey Simms and every other Friday I bring you a short episode with the top diabetes stories and headlines happening now. XX A 42-year-old man who has lived most of his life with type 1 diabetes has become the first human to receive a transplant of genetically modified insulin-producing cells. This marks the first pancreatic cell transplant in a human to sidestep the need for immunosuppressant drugs. “This is the most exciting moment of my scientific career,” says cell biologist Per-Ola Carlsson of Uppsala University in Sweden, who helped develop the procedure. The new treatment, he says, “opens the future possibility of treating not only diabetes but other autoimmune diseases.” This procedure uses the gene editing technique, CRISPR, to discourage the auto immune attack on the donor cells. Before the transplant, the participant had no measurable naturally produced insulin and was receiving daily doses of the hormone. But within four to 12 weeks following the transplant, his levels rose slightly on their own after meals—showing that the new beta cells were releasing some insulin in response to glucose. even though the new study is promising, it involved just one participant and is therefore preliminary. And longer-term monitoring is needed to confirm the therapy's safety before it can be offered to more people. She also notes that the injected cells produced only 7 percent of the insulin needed for a person to be fully independent of additional medication. The researchers supplied the recipient with insulin doses to maintain healthy blood sugar levels. While Herold thinks it's still too early to consider this approach for a cure, “these options are now here to change the disease in ways that have never been possible before,” he says. “There's tremendous hope.” https://www.scientificamerican.com/article/type-1-diabetes-patients-insulin-production-restored-with-new-cell/ XX   This one is interesting… a recent study shows that children of mothers with gestational diabetes or fathers with type 2 diabetes have higher chances of developing type 1 diabetes than kids whose parents do not have any type of diabetes. Specifically, the study found that children whose mothers had gestational diabetes during pregnancy were 94% more likely to develop type 1 diabetes compared to children of mothers without diabetes. Similarly, having a father with type 2 diabetes was linked to a 77% higher risk. The study also suggests a possible link between maternal type 2 diabetes and type 1 diabetes in children, although more data are needed to confirm whether the risk is real.   "What is interesting is that type 1 diabetes is a disease of lack of the hormone insulin while gestational diabetes and type 2 diabetes stem mostly from the body's resistance to the hormone. What may be happening is that genes, environments and behaviors that create insulin resistance may also, in some cases, trigger the immune reactions that lead to type 1 diabetes," adds Dr. Dasgupta. A 2019 meta-analysis by researchers at Soochow University in China found that gestational diabetes was linked to a 66% higher risk of type 1 diabetes in children. This new study, which includes more than twice as many studies, offers a robust synthesis of current evidence and shows the risk is even greater than previously estimated. It is also the first meta-analysis to examine the link between paternal type 2 diabetes and type 1 diabetes in offspring. "Several mechanisms may be at play. Families often share lifestyle and eating habits, which can raise the likelihood that children will be affected. But beyond that, high blood sugar levels may also cause biological changes in parents that could increase their children's risk of developing type 1 diabetes," explains Laura Rendon, co-first author of the study, who completed an MSc in experimental medicine at The Institute and, as someone living with type 1 diabetes herself, finds deep personal meaning in conducting this research. For instance, the authors suggest that high blood sugar during pregnancy may stress the fetus's insulin-producing beta cells, reducing their number at birth or making them more vulnerable to damage later in life. It may also trigger epigenetic changes—modifications to proteins and molecules attached to DNA—that increase the risk. Likewise, high blood sugar in fathers with type 2 diabetes may cause epigenetic changes in their sperm, potentially influencing their child's risk of developing type 1 diabetes. https://medicalxpress.com/news/2025-08-diabetes-children-linked-parents.html XX Can a CGM help you lose weight? The company Signos is banking on it – the just got FDA approval for their system, which uses the over the counter Dexcom Stelo. The claim here is that the system will help track how food choices, activity, stress and sleep can all affect metabolism. Signos also works in partnership with the digital nutrition counseling startup Nourish. It currently offers a quarterly subscription plan, including six CGM sensors, for $139 per month. And they tell you don't take any medical actions based on the app's output without consulting a physician. https://www.fiercebiotech.com/medtech/fda-clears-signos-over-counter-cgm-powered-weight-loss-app XX Good news for T1D1, a free mobile app that helps people calculate insulin doses, track daily data, and share insights with healthcare providers. After being pulled off the market with similar apps a few years ago, it's now back and FDA approved. Drew Mendelow created the app after his diagnosis at age 13. He came on the show last year and I'll link his story up in the show notes. Diabetes Center Berne provided the initial funding to support the T1D1 efforts to redesign the app per FDA standards.  Comerge AG , the registered manufacturer, enlisted a team of software engineers, regulatory experts, and design professionals to ensure T1D1 was FDA-ready. Dexcom graciously conducted the Human Factors study to ensure safety and accuracy.  ​ ​T1D1 is now FDA-cleared as a Class II medical device and is the first over-the-counter insulin calculator cleared for individuals aged 2 and older. T1D1 is expected to be live in the AppStore and Google Play Store by October 2025. https://diabetes-connections.com/the-fda-took-down-this-teens-free-bolus-calculator-he-needs-your-help-to-bring-it-back/ XX Metformin has been the standard treatment for type 2 diabetes for more than six decades, yet scientists still do not fully understand how it works. A team from Baylor College of Medicine, working with international collaborators, has now identified an unexpected factor in its effectiveness: the brain. Their findings reveal a brain pathway involved in metformin's glucose-lowering action, pointing to new strategies for treating diabetes with greater precision. The study was published in Science Advances. The researchers concentrated on a small protein called Rap1, located in a region of the brain known as the ventromedial hypothalamus (VMH). They discovered that metformin's ability to lower blood sugar at clinically relevant doses depends on suppressing Rap1 activity in this brain area.   “This discovery changes how we think about metformin,” Fukuda said. “It's not just working in the liver or the gut, it's also acting in the brain. We found that while the liver and intestines need high concentrations of the drug to respond, the brain reacts to much lower levels.”     https://scitechdaily.com/after-60-years-scientists-uncover-hidden-brain-pathway-behind-diabetes-drug-metformin/   XX Looks like GLP-1 pills are moving ahead. Lilly says it's version helped overweight adults with type 2 lose 10% of their body weights and lower A1C. Just two weeks ago, we were talking about how the same drug in people without diabetes had less than the stellar expected results. Orforglipron is a small-molecule pill that is easier to manufacture and package than wildly popular injectable drugs for obesity, such as Lilly's Zepbound and Novo Nordisk's NOVOb.CO rival treatment Wegovy, which are peptide mimics of the appetite-controlling GLP-1 hormone. In the 72-week study of more than 1,600 overweight or obese adults with type 2 diabetes, those who received the 36-milligram highest dose of orforglipron on average shed 10.5% of their weight, or about 23 pounds (10.43 kg), versus 2.2% for those who received a placebo, achieving the main goal of the trial. Patients on the lowest 6 mg dose of the Lilly drug lost 5.5% of their weight. https://www.usatoday.com/story/news/health/2025/08/26/lilly-glp-1-pill-weight-loss/85830686007/ XX     An intervention that combined a low-calorie Mediterranean diet and exercise led to less diabetes incidence in older adults. Men had a greater diabetes risk reduction with the intervention than women. The study was based in Spain, and the diet may not be as easy to adhere to in the U.S. Among nearly 5,000 adults with metabolic syndrome and overweight or obesity in the PREDIMED-Plus trial, those who followed this intervention had a 31% lower risk for type 2 diabetes over 6 years relative to those who received only ad libitum Mediterranean diet advice (aHR 0.69, 95% CI 0.59-0.82). the Mediterranean diet focuses on high intake of plant-based foods, moderate consumption of fish, poultry, and dairy with optional red wine, and low intake of red meats, sweets, and sugar-sweetened beverages. Common foods featured in the diet include extra-virgin olive oil, fruits, vegetables, legumes, nuts, and whole grains. However, Sharon Herring, MD, MPH, and Gina Tripicchio, PhD, MSEd, both of Temple University in Philadelphia, pointed out that this study was conducted solely in Spain, and sticking to this type of diet may be more challenging in countries like the U.S.   "Participants in the study received extra-virgin olive oil to support adherence and retention; in the United States, prices of extra-virgin olive oil have nearly doubled since 2021 due to a combination of factors including climate change, rising production costs, supply chain disruptions, and now tariffs," they noted in an accompanying editorial. "[T]he large number of dietitian contacts during the study may prove difficult to scale broadly in the United States given challenges with health care access and reimbursement for prevention services."         https://www.medpagetoday.com/primarycare/diabetes/117151 XX A group of Canadian researchers has identified an unexpected way to lower blood sugar and protect the liver: by capturing a little-known fuel produced by gut bacteria before it enters the body and causes harm. The findings, published in Cell Metabolism, could open the door to new therapies to treat metabolic diseases like type 2 diabetes and fatty liver disease. Scientists from McMaster University, Université Laval, and the University of Ottawa discovered that a molecule generated by gut microbes can cross into the bloodstream, where it drives the liver to overproduce glucose and fat. By designing a method to trap this molecule in the gut before it reaches circulation, they achieved striking improvements in blood sugar regulation and fatty liver disease in obese mice. https://scitechdaily.com/scientists-discover-a-surprising-new-way-to-fight-diabetes/ XX Dexcom, which specializes in technology for glucose biosensing, will lay off 350 workers, with nearly 200 of them in San Diego, according to the San Diego Union Tribune. The bulk of the local jobs being lost are focused on Dexcom operations and manufacturing. The Dexcom development follows cutbacks to Verily, a life sciences company that is a subsidiary of Alphabet, Google's corporate parent. Verily's work included a project with Dexcom on wearable glucose sensors. CEO Stephen Gillett, in a memo obtained by the publication, said there will be “workforce reductions across Verily.” A representative for Verily confirmed to Business Insider that “we have made the difficult decision to discontinue manufacturing medical devices and will no longer be supporting them going forward.” https://timesofsandiego.com/business/2025/08/27/report-life-sciences-firm-dexcom-lay-off-200-san-diego-workers/ XX Front office changes at Insulet. Eric Benjamin, former chief product and customer experience officer, will take the role of chief operating officer, effective immediately. Manoj Raghunandanan Mu-NOHJ Rug-a-nun-da-nun to the position of chief growth officer, leading Insulet's new growth organization. The appointments are some of CEO Ashley McEvoy's first changes since she was hired in April. The appointments come after McEvoy outlined four priorities for Insulet on an August earnings call:   enhancing the company's commercial capabilities, building Insulet's brand and direct-to-consumer capabilities, driving growth outside of the U.S. and accelerating the pace of innovation. https://www.medtechdive.com/news/insulet-eric-benjamin-manoj-raghunandanan-appointments/758668/ XX   XX Want to highlight The Children's Diabetes Foundation in Colorado – they held a medal ceremony for patients of the Barbara Davis Center who've lived with Type 1 diabetes for 50 years or more. There were 87 medal recipients in the ceremony including Dana Davis, Executive Director of the Children's Diabetes Foundation and the daughter of the founders of the Barbara Davis Center. Davis shared: "When you got Type1 diabetes in the 70s, they thought you shouldn't have children. They thought you weren't going to live past 30 or 40. It was definitely very different," Davis said.   https://www.cbsnews.com/colorado/news/barbara-davis-center-celebrates-colorado-type-1-diabetes-patients-milestone/

We all want more energy — but what if your fatigue isn't about sleep, diet, or exercise at all? In this solo episode, Darin O'Lien uncovers the invisible drains on your vitality that most people never notice. From blue light to toxic relationships, hidden mold, micro-stress loops, EMF exposure, and even unresolved trauma stored in your body, Darin reveals how your life force is being stolen — and how to take it back. You'll learn the overlooked ways your time, attention, and biology are constantly depleted — and the exact SuperLife Energy Seal Protocol Darin uses to plug those leaks, reclaim his vitality, and live fully charged.     What You'll Learn in This Episode 00:00 – Introduction & Episode Overview Darin introduces the concept of hidden energy leaks and why most fatigue isn't just about lack of sleep. 03:05 – Energy Deposits vs. Withdrawals How every interaction, choice, and environment either builds or depletes your life force. 04:33 – The Overlooked Energy Drains The most common — and invisible — ways energy slips away without your awareness. 06:58 – Blue Light & Circadian Rhythm Disruption The science of how nighttime screen use suppresses melatonin and wrecks your sleep quality. 09:06 – Ultra-Processed Foods & Energy Impact Why “dead calorie” foods cause fatigue and how to build an energy-supportive plate. 11:33 – Hydration & Water Quality Why dehydration is the #1 cause of fatigue, and the importance of filtering and mineralizing your water. 15:06 – Micro-Stress Loops & Mental Background Apps How unresolved thoughts quietly drain your energy — and how to shut them down. 17:28 – Toxic Relationships & Social Friction The measurable toll hostile interactions take on your health and recovery. 19:10 – Indoor Air Quality & Mold Exposure How unseen environmental toxins mimic chronic fatigue symptoms. 21:27 – EMF Exposure & Device Overload The overlooked stressor disrupting your sleep, nervous system, and cellular health. 23:14 – Stillness Breaks & Nature Time The proven stress-relieving effects of short nature “pills” and mindfulness pauses. 25:41 – Past Trauma & Recapitulation How unresolved experiences trap your life force — and the Toltec method to reclaim it. 30:39 – The SuperLife Energy Seal Protocol Darin's complete daily checklist to stop leaks and recharge vitality. 33:08 – Darin's Daily Rituals How he integrates energy-protective practices into his everyday life. 35:33 – Closing Thoughts Why energy isn't something you gain — it's what's left when you stop the leaks.     Thank You to Our Sponsors: Fatty15: Get an additional 15% off their 90-day subscription Starter Kit by going to fatty15.com/DARIN and using code DARIN at checkout. Therasage: Go to www.therasage.com and use code DARIN at checkout for 15% off     Find More from Darin Olien: Instagram: @darinolienPodcast: superlife.com/podcastsWebsite: superlife.comBook: Fatal Conveniences     Key Takeaway "Energy isn't something you get — it's what remains when you stop the leaks."      Bibliography · Chang AM et al. Evening use of light-emitting eReaders… PNAS, 2015. · Hall KD et al. Ultra-processed diets cause excess calorie intake… Cell Metabolism, 2019. · Ganio MS et al. Mild dehydration impairs vigilance… Br J Nutr, 2011. · McEwen BS. Allostatic load and stress physiology. Ann NY Acad Sci, 1999. · Kiecolt-Glaser JK et al. Hostile behavior slows wound healing… Arch Gen Psychiatry, 2005. · CDC/NIOSH. Health problems in damp buildings. · Satish U et al. CO₂ and decision-making. Environ Health Perspect, 2012. · WHO. Electromagnetic fields and public health. · Hunter MCR et al. Nature pill and stress relief. Front Psychol, 2019. · Levine P. Somatic experiencing and trauma discharge. PubMed, 2012. · · Somatic trauma & release: Levine P. Waking the Tiger; “Trauma creates a permanent imprint… the body can be retrained to discharge it.” (pubmed.ncbi.nlm.nih.gov) · · Recapitulation (Toltec lineage): Ruiz DM. The Four Agreements; narrative recounting as energy reclamation. (Ancestral wisdom, narrative psychology) · · Narrative therapy integration: White M. “Externalizing the problem, reclaiming identity.” (Case-based evidence, therapeutic outcomes) · · (And prior citations as listed—circadian, UPF, hydration, air, mindfulness, social, EMF, stillness—remain intact.)

Welcome to Ozempic Weightloss Unlocked, where we break down the latest science, headlines, and real world experiences around semaglutide, known by many as Ozempic and Wegovy.Here is what is new. Medical News Today reports on a fresh Cell Metabolism study in mice suggesting lean mass loss with Ozempic may be smaller than feared, about ten percent of lean mass during weight loss, with much of the change coming from organs like the liver rather than skeletal muscle. Researchers also noted some muscles maintained size while strength could still dip, underscoring the need for human trials to clarify muscle function during treatment. That is according to Medical News Today and University of Utah Health coverage of the same research.University of Utah Health explains that the liver in mice shrank by nearly half during weight loss, which can be part of healthy metabolic improvement, and that some reduction in skeletal muscle may reflect a return to baseline as body fat drops. Their message is clear. We need rigorous human studies to confirm how size and strength change in different muscles and what training and protein strategies best protect function during treatment.What about long term weight outcomes in the real world. A new analysis in the journal Advances in Therapy shows that around half of patients on semaglutide 2.4 milligrams achieved at least twenty percent weight loss at 18 to 24 months, pointing to meaningful, sustained results for many patients outside trials. That is according to Springer Nature's publication of the real world study.Stopping medication remains a pivotal issue. ScienceDaily reports on a meta analysis in BMC Medicine across 11 trials showing weight regain commonly begins about eight weeks after stopping anti obesity medications, including glucagon like peptide one drugs, and continues for several months before leveling off. The extent of regain varies by drug and by lifestyle consistency, but the pattern is widespread. One tirzepatide study found participants regained nearly half of the lost weight after switching to placebo. This highlights the importance of long term plans, whether continued medication, step down dosing, or robust nutrition, activity, sleep, and support.The pipeline is active. Fierce Biotech reports Eli Lilly's oral glucagon like peptide one candidate orforglipron achieved about twelve percent average weight loss in phase three, less than injectable rivals but with the convenience of a pill. Meanwhile, new semaglutide dosing research from Novo Nordisk's program suggests higher weekly doses like seven point two milligrams can approach or surpass twenty percent average loss at 72 weeks, adding competitive pressure and new options if approved. These developments matter for access, costs, and matching the right person to the right therapy.Beyond weight, McGill University highlights growing evidence that glucagon like peptide one medicines may also help conditions like heart and kidney disease, fatty liver disease, sleep apnea, osteoarthritis, and even addiction. Their review in eClinicalMedicine stresses both promise and open questions, including long term safety signals like gallbladder disease, mood effects, and vision risks, plus the realities of cost and access.Here are practical takeaways for listeners. First, combine medication with protein forward eating and resistance training to protect strength while losing fat. Second, plan for maintenance early, since weight regain after stopping is common. Third, talk with a clinician about the full cardiometabolic picture, including blood sugar, cholesterol, blood pressure, and fatty liver markers. Fourth, keep an eye on emerging options, including oral therapies and dose optimization, which may broaden choices.That is it for today on Ozempic Weightloss Unlocked. Thank you for tuning in, and please subscribe so you never miss an update. This has been a quiet please production, for more check out quiet please dot ai. Some great Deals https://amzn.to/49SJ3QsFor more check out http://www.quietplease.ai

If you're anything like me, you've probably looked back and thought, “Why didn't I know this 10 years ago?” That's exactly what today's chat is about - my top five health game-changers I wish I had embraced earlier. Whether you're 25 or 75, these insights can shift the needle in how you feel, look, and thrive. From nutrition tracking without guilt to finally getting that high-quality protein in, these tips aren't about restriction - they're about empowerment. I'm opening up about what's worked, what didn't, and why strength training, ditching the processed stuff, and even allowing yourself to be hungry can be revolutionary. This one is packed with real-life examples, scientific backing, and simple steps to get started without getting overwhelmed. What we're tackling: Track your food with intention, not shame. Ditch skinny, build strong with progressive overload. Prioritize protein without obsessing. Phase out processed foods gradually. Embrace hunger and stop snacking aimlessly. Meditation App : Simply Being App Get Weekly Health Tips:  thrivehealthcoachllc.com Let's Connect:@‌ashleythrivehealthcoach or via email: ashley@thrivehealthcoachingllc.com Podcast Produced by Virtually You! Sources: Tracking Nutrition Burke, L. E., Wang, J., & Sevick, M. A. (2011). Self-monitoring in weight loss: A systematic review of the literature. Journal of the American Dietetic Association, 111(1), 92–102. https://doi.org/10.1016/j.jada.2010.10.008 Raber, M., Patterson, M., & Jia, W. (2021). A systematic review of the use of dietary self-monitoring in behavioral weight-loss interventions: Current practices and future recommendations. Public Health Nutrition, 24(17), 5885–5913. https://doi.org/10.1017/S1368980021002381 Prioritizing High-Quality Protein Holt, S. H. A., Brand Miller, J. C., Petocz, P., & Farmakalidis, E. (1995). A satiety index of common foods. European Journal of Clinical Nutrition, 49(9), 675–690. Ortinau, L. C., Culp, J. M., & Hoertel, H. A. (2014). Effects of high-protein vs. high-fat snacks on appetite control, satiety, and eating initiation in healthy women. Nutrition Journal, 13, 97. https://doi.org/10.1186/1475-2891-13-97 Dhillon, J., Craig, B. A., Leidy, H. J., Amankwaah, A. F., Jacobs, A., Jones, B. L., & Jones, J. B. (2016). The effects of increased protein intake on fullness: A meta-analysis and its limitations. Journal of the Academy of Nutrition and Dietetics, 116(6), 968–983. https://doi.org/10.1016/j.jand.2016.01.003 Zhu, R., et al. (2021). Effect of a high-protein, low-glycemic index diet on hunger and weight maintenance: Results from the PREVIEW study. Frontiers in Nutrition, 8, 649928. https://doi.org/10.3389/fnut.2021.649928 Strength Training vs. Cardio Saeidifard, F., Medina-Inojosa, J. R., West, C. P., & Lopez-Jimenez, F. (2019). The role of resistance training in the prevention and management of chronic disease. European Journal of Preventive Cardiology, 26(5), 505–515. https://doi.org/10.1177/2047487318822333 Momma, H., et al. (2022). Muscle-strengthening activities and risk of all-cause and cause-specific mortality: A systematic review and meta-analysis of cohort studies. British Journal of Sports Medicine, 56(10), 755–763. https://doi.org/10.1136/bjsports-2021-105061 Cutting Ultra-Processed Foods Monteiro, C. A., Cannon, G., Levy, R. B., Moubarac, J. C., Louzada, M. L., Rauber, F., ... & Jaime, P. C. (2019). Ultra-processed foods: What they are and how to identify them. Public Health Nutrition, 22(5), 936–941. https://doi.org/10.1017/S1368980018003762 Srour, B., et al. (2019). Ultra-processed food intake and risk of cardiovascular disease: Prospective cohort study (NutriNet-Santé). BMJ, 365, l1451. https://doi.org/10.1136/bmj.l1451 Mindful Hunger / Fasting Bruce, L. J., & Ricciardelli, L. A. (2016). A systematic review of the psychosocial correlates of intuitive eating among adult women. Appetite, 96, 454–472. https://doi.org/10.1016/j.appet.2015.10.012 Longo, V. D., & Panda, S. (2016). Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metabolism, 23(6), 1048–1059. https://doi.org/10.1016/j.cmet.2016.06.001

Send us a textHey my beautiful friends –This week's conversation was sparked by a funny little tech discovery and a box I mailed — both of which got me thinking about food in a new way. You know how people are always quick to tell you what not to eat? Well, this week we flip the script. I'm sharing thoughts from my own journey and a coach that made me laugh and think — and you'll hear why his words still stick with me to this day. We're keeping things simple, kind, and grounded in something real. I'm not handing out rules, I'm sharing a mindset and maybe even a little inspiration for your next grocery run or packed lunch. And as always, we'll close with a little heart lift — this one from Michael Pollan, who said, “Eat food. Not too much. Mostly plants.”Come hang out with me, and let's talk about what loves us back. References:1.    Zhang & Talalay, Frontiers in Nutrition, 20232.    Liu, Nutrients, 20233.    Viguiliouk et al., Obesity Reviews, 20234.    Jenkins et al., AJCN, 20245.    Estruch et al., The Lancet Diabetes & Endocrinology, 20236.    Guasch-Ferré et al., BMJ, 20237.    Yao et al., Nutrients, 20238.    Harvard Nurses' Health Study Update, 20239.    Anderson et al., AJCN, 202410.Simopoulos, Frontiers in Endocrinology, 202311.Ye et al., Nutrients, 202312.Sonnenburg et al., Cell Metabolism, 202413.Mozaffarian et al., AJCN, 202314.Mastrocola et al., Appetite, 202315.Pollan, M. (2009). In Defense of FoodLet's go, let's get it done. Get more information at: http://projectweightloss.org

This episode reveals groundbreaking research from the Journal of Cell Metabolism showing that when you eat matters as much as what you eat for hunger control and fasting success. Dr. Scott and Tommy break down a study demonstrating that consuming 45% of daily calories at breakfast versus dinner dramatically reduces hunger and appetite without changing metabolism or weight loss. Learn why your physiology works against you when eating large evening meals, making it harder to close your eating window and stick to fasts. If you struggle with late-night cravings, can't seem to end your eating window, or find yourself breaking fasts in the evening, this episode provides the meal timing strategy to align your eating with your body's natural circadian rhythm for easier, more sustainable fasting. ⁠Take the NEW FASTING PERSONA QUIZ! - The Key to Unlocking Sustainable Weight Loss With Fasting!⁠⁠ Resources and Downloads: ⁠⁠SIGN UP FOR THE DROP OF THE ULTIMATE GUIDE TO BLOOD SUGAR CONTROL⁠⁠ ⁠⁠GRAB THE OPTIMAL RANGES FOR LAB WORK HERE! - NEW RESOURCE! - December 2024⁠⁠ ⁠⁠FREE RESOURCE - DOWNLOAD THE NEW BLUEPRINT TO FASTING FOR FAT LOSS!⁠⁠ ⁠⁠SLEEP GUIDE DIRECT DOWNLOAD⁠⁠ ⁠⁠DOWNLOAD THE FASTING TRANSFORMATION JOURNAL HERE!⁠⁠ Partner Links: Get your⁠⁠ FREE BOX OF LMNT⁠⁠ hydration support for the perfect electrolyte balance for your fasting lifestyle with your first purchase⁠⁠ here!⁠⁠ Get ⁠⁠30% off a Keto-Mojo⁠⁠ blood glucose and ketone monitor (discount shown at checkout)! ⁠⁠Click here!⁠⁠ Our Community: Let's continue the conversation. Click the link below to JOIN the ⁠⁠Fasting For Life Community⁠⁠, a group of like-minded, new, and experienced fasters! The first two rules of fasting need not apply! If you enjoy the podcast, please tap the stars below and consider leaving a short review on Apple Podcasts/iTunes. It takes less than 60 seconds, and it helps bring you the best original content each week. We also enjoy reading them! Article Links: https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(22)00344-8

Join our Patreon and get access to monthly bonus episodes and more nutriton content!Can fasting really slow aging? Does calorie restriction work for humans, or just for mice and yeast? And how much protein do you actually need to age well? This week on Your Diet Sucks, we break down the evidence behind the most talked-about interventions in the longevity space, what holds up under scrutiny, what doesn't, and why you might not need a supplement stack to live longer, and enjoy life. We dig into:The actual science on calorie restriction, fasting, and supplements—and where the evidence stopsWhat inflammation, oxidative stress, and telomeres have to do with how we ageThe best-researched dietary patterns for living longer (hint: it's not sexy, but it might include red wine)Why protein becomes more important as we ageThe difference between lifespan and healthspan, and why quality of life needs to be part of the conversation

In this episode of Hema Now, Jonathan Sackier is joined by John Riches, Clinical Reader in Cancer Immunometabolism at the Barts Cancer Institute and Honorary Consultant Haemato-oncologist. They explore how metabolic shifts drive lymphoma progression, the potential of immunotherapy, and what the future holds for treating lymphoid malignancies.  Timestamps:      00:00 – Introduction  01:46 – Riches' journey into haematology  03:42 – What is T cell exhaustion?  07:06 – The key role of metabolism in lymphoma  09:33 - Richter's syndrome  13:17 – Breakthroughs in immunotherapy  20:27 – The challenges of translational research  25:39 – B cells in autoimmune diseases  28:16 – The potential of breath biopsy  32:58 – Riches' three wishes for healthcare 

Follow us on Instagram @yourdietsuckspod!This week, Kylee and Zoë take a deep dive into ultra-processed foods: what they are, where they came from, how they're designed to light up your brain's reward systems, and what role they play in athletic nutrition. We talk about everything from cereal meant to prevent sinning to the low-fat diet craze, the war-time origins of shelf-stable food, and the engineering behind the foods that are hyper-palatable.We also get into the landmark NIH study that showed just how much processing—not just calories or macros—can influence how much we eat, how full we feel, and how our bodies respond to food. This episode is about helping you understand the systems at play, so you can make choices that support your health and performance without getting caught in fear or shame about the food you eat. Because when it comes to ultra-processed foods, context matters—especially for athletes.

In this eye-opening episode of the Better Than Before Breast Cancer Podcast, host Laura Lummer dives into the powerful connection between your body's natural rhythms and the timing of your meals. Have you ever noticed how aligned you feel when you live in sync with nature's cycles? Drawing from Ayurveda—an ancient system of medicine from India—and contemporary scientific research, Laura reveals how understanding your body's internal clock, or circadian rhythm, can significantly enhance your health, especially after breast cancer.   What You'll Discover in This Episode: A gentle introduction to Ayurveda and how this 5,000-year-old wisdom emphasizes living in harmony with Earth's natural cycles. Clear, practical explanations of circadian rhythm, metabolism, hormonal balance, and their critical roles in breast cancer recovery. How Ayurvedic principles align surprisingly well with modern Western nutritional science. The profound health benefits of aligning meal timing with daylight hours, including improved sleep, reduced inflammation, and optimized metabolism. Easy strategies to shift your eating patterns gently, starting with simple steps like adjusting dinner times.   Key Studies Referenced: JAMA Oncology Study:Catherine R. Marinac, Dorothy D. Sears, Lok-Hei Lam, Shirley W. Flatt, Loki Natarajan, Ruth E. Patterson; "Prolonged Nightly Fasting and Breast Cancer Prognosis." JAMA Oncology, 2016; Read the full study here.   Cell Metabolism Study: Emily N.C. Manoogian, Satchidananda Panda et al.; "Time-restricted eating improves cardiometabolic health in overweight individuals." Cell Metabolism, 2019; Explore the study here.   Listen in to explore: How simple shifts in meal timing can powerfully support your body's natural detoxification pathways and hormonal balance. The Ayurvedic recommendations for ideal meal times and how they beautifully complement modern scientific guidelines. Ways to incorporate a loving, compassionate mindset toward food, meal timing, and your body's natural rhythm.   This episode encourages you to foster a nurturing, compassionate relationship with your body by syncing your daily habits with the earth's rhythms, creating lasting health and harmony after breast cancer.   Connect with Laura: Visit The Breast Cancer Recovery Coach for personalized metabolic health coaching, mindset transformation, and guidance specifically tailored for breast cancer survivors. Enjoyed the episode?  Subscribe, leave a review, and share with friends who could benefit from this healing wisdom!  

NADs have been a hot topic lately when it comes to conversations regarding longevity and anti-aging. Today, Courtney Van Bussem, Biomedical Engineer and COO at Longevity Launch Labs, joins us to talk about cellular health, longevity pathways, and precursors to NADs.  Courtney Van Bussem: https://www.linkedin.com/in/courtneyvanbussum Longevity Launch Labs: https://longevitylaunch.com/ Where to find 1MNA: https://www.1mna.com/

Vidcast:  https://www.instagram.com/p/DGyCI-ZOjLW/New research suggests that aspartame, a common artificial sweetener, may increase the risk of heart disease by triggering insulin spikes that lead to artery-clogging plaques—a key factor in heart attacks and strokes.The study, published in Cell Metabolism, found that mice consuming aspartame daily—equivalent to drinking three cans of diet soda—experienced persistent insulin surges. This led to chronic inflammation and the buildup of fatty plaques in their arteries, a process linked to cardiovascular disease.Researchers believe the artificial sweetness tricks the body's insulin receptors, causing a greater-than-expected insulin response. Over time, this can lead to insulin resistance, increasing the risk of type 2 diabetes and heart disease.While aspartame is FDA-approved and widely used in diet sodas, baked goods, and processed foods, experts caution that frequent consumption could have long-term health risks. Researchers plan to investigate whether these findings apply to humans, but doctors recommend limiting artificial sweetener intake, especially for those at risk of metabolic disorders.https://www.medicalnewstoday.com/articles/artificial-sweetener-triggers-insulin-spike-leading-to-blood-vessel-inflammation-in-mice#aspartame #artificialsweetner #insulin #atherosclerosis #heartattack

Introducing Blood sugar hacks to give you more energy | Glucose Goddess Jessie Inchauspé and Prof. Tim Spector from ZOE Science & Nutrition.Follow the show: ZOE Science & Nutrition Why do some people feel fine eating lots of carbs when others feel energy slumps? Is blood sugar to blame?In this episode, we learn why blood sugar varies so much between people, and the tools to manage these levels. Tim Spector and Jessie Inchauspé (aka the Glucose Goddess) will discuss the latest science around glucose control, what the cool new device on the block – the CGM – can tell us and why blood sugar levels are only one part of the picture of our health.Jessie is a bestselling author and science communicator with a community of over 5 million followers. Tim is a professor of epidemiology at King's College London and ZOE's scientific co-founder.

The Chief Scientific Advisor at Novo Nordisk, Lotte Bjerre Knudsen, was the key force who pushed hard to develop GLP-1 drugs for treating obesity and subsequently for Alzheimer's. She was recently recognized by the 2024 Lasker Medical Research Award, and the 2024 AAAS Bhaumik Breakthrough of the Year Award. That recognition is richly deserved, since it is unclear if the GLP-1 drug path to obesity treatment, and all of the associated benefits, would have been seen at this time without her influence. That's especially true given the mystery for why people with Type 2 diabetes (for which these drugs were used for many years) did not exhibit much in the way of weight loss. We discussed that and the future of these drugs, including their potential to prevent neurodegenerative diseases. And about dressing up in pink!The Ground Truths podcasts are also available on Apple and Spotify.Our entire conversation can also be seen by video at YouTube along with all of the Ground Truths podcasts. If you like the video format, please subscribe to this channel. Even if you prefer video, please take a look at the transcript with graphics and useful links to citations.A Video Clip below on the barriers of a woman scientist to push Novo Nordisk to develop GLP-1 for obesity. “I was always just been a nerdy little scientist who kind of found home here in this company for 35 years.”—Lotte Bjerre Knudsen, 60 MinutesTranscript with Links to audio and external referencesEric Topol (00:06):Well, hello, it's Eric Topol with Ground Truths, and I have with me a special guest. She's the Chief Science Officer of Novo Nordisk and it's Lotte Bjerre Knudsen, and we're delighted to have her. She's a recent recipient of the Lasker Award, which I think is considered like the pre-Nobel Award here in the United States. And I was involved with her in terms of researching who was the principal person who brought the GLP-1 drugs to the forefront for obesity, and it turned out to be Lotte. So welcome, Lotte.Lotte Bjerre Knudsen (00:48):Thank you very much. And also very, very happy to be here. I'm not the Chief Science Officer for Novo Nordisk, I'm the Chief Scientific Advisor of working for the Chief Science Officer of Novo Nordisk, but maybe too many people, not so different, right?From Laundry Detergents to GLP-1 DrugsEric Topol (01:06):Yes. Thank you, I actually meant to say advisor, but yes, I'm glad you cleared that up. I know from speaking to some of your colleagues, I actually spoke to Robin yesterday that you are looked to very highly, the most highly regarded person in science there, so not surprisingly. What I want to do is first talk about the glucagon-like peptide-1 (GLP-1) that got its legs back in, I guess 1984. So we're going way back. And what's also interesting is that you go way back at Novo Nordisk to 35 years in 1989. And so, there had been this work with this extraordinary hormone and neurotransmitter with a very short half-life that you knew about. But when you first started in Novo Nordisk, you weren't working on this. As I understand it, you're working on laundry detergent enzymes. How did you make this pivot from the laundry enzymes to getting into the GLP-1 world?Lotte Bjerre Knudsen (02:16):Yeah, thank you for that question. I'm from the technical University of Denmark, so I'm trained in biotechnology, and we're a small country, so not that many companies to work for. And I always had my mind set on, I wanted to work for Novo as it was called back then, and it just happened to be in the industrial enzyme part that I got my foot in first. And then I had a very interesting boss at the time. Unfortunately, he's not alive anymore, but he was both a medical doctor as well as a chemist. So he was actually put in charge of actually, let's see if we can do something new in diabetes. And then since he hired me and I had not been there that long, I simply tagged along as the youngest scientist on the team, and then suddenly I became a diabetes researcher. Around the same time, I think you remember that all of pharma was interested in obesity in the early 90s, everyone wanted to do diabetes as well as obesity, but they were separate teams and they all wanted to do small molecules, but it just happens to be so that the best idea we could find at that time was actually GLP-1, because we actually had clinical data relatively early that GLP-1 was a really good candidate as a treatment for diabetes because of the glucose sensitivity of the actions.(03:43):So you'd have efficient lowering of glucose through a dual mechanism with increasing insulin, lowering glucagon, and then it was safe because there wasn't this hypoglycemia you get from insulin. But then I had other colleagues who were working on obesity, and I was just kind of listening, right, what's going on there? And then also a colleague that I had, we had, I don't know if you remember the old Hagedorn Research Institute, but Novo actually had kind of like an academic research institute that was affiliated with us. And there was this group that were working on this glucagon tumor model that produced high levels of glucagon, GLP-1 and PYY. And these rats, they starved themselves to death. And I knew about that from 1994. So that actually inspired my thinking. So when Stephen Bloom's paper came out in January of 1996, and he was the first one to call GLP-1 a neurotransmitter, I think, but I was already way into actually screening these kind of molecules that later then became liraglutide.No One Else Thought About This [Obesity](04:54):And then I thought, why on earth should we not actually do both things at the same time? If we have an idea that can both work in diabetes in a much safer way than in insulin, and then also at the same time work in obesity. But the reality is that no one else thought about this, or if they thought about it, they didn't really think that it would a good idea. But I think I had the luxury of being in a biotech company, so everyone was working with peptides and proteins. So I don't think I got the same challenge that the other people in the other pharma's got when they all wanted small molecules.Eric Topol (05:36):Well, also just to set the foundation here, which you alluded to, there had been so many attempts to come up with a drug that would work, not just of course in diabetes where there are many classes of drugs, but moreover, to treat the condition of obesity. Actually, I was involved with one of them, Rimonabant and did the large trial, which as you know, led to having to stop the drug, discontinue it because it was associated with suicidal ideation and actual some suicide. So there had been such a long history of checkered inability to come up with a drug. But what was striking is the challenge, and this is one of the first important questions about, when you had the extended half-life of the first GLP-1 drug, that instead of having to take multiple times a day, you could actually, with liraglutide get to a point where you were starting to get to an extended half-life. This is now going back to 1997 with approval in 2010, still 14 years ago. But when you came up with this drug, because this was certainly one of your great contributions, this drug was just a step along the way in this kind of iterative process, wouldn't you say? It wasn't the long half-life and the potency that eventually got us to where we are today. Is that true?Lotte Bjerre Knudsen (07:15):Yeah, it was a stepwise process. And what's super interesting about this class of medicines is that they're actually so different. If you talk about a class of medicine where small molecules, they can be different, but they're usually more alike than they're different. And when it comes to this class with these medium-sized peptides, people tried a whole bunch of different things. So they're actually really, really different. Some are simple peptides. So the idea that I came up with was to use this fatty acid isolation principle, and that's then a subclass in the class. And then the first, once weekly, for example, was an antibody-based molecule liraglutide. So they're much, much, much larger molecule compared to the small peptides. So they're very different. And neither the simple peptides nor the really big antibody derived molecules, they don't give a lot of weight loss. So we actually get more weight loss with these kinds of molecules, which is also why you can now see that it has actually kind of inspired a whole industry to kind of try and go and make similar kinds of molecules.Eric Topol (08:27):Well, inspired a whole industry is an understatement. It's become the most extraordinary class of drugs, I think in medical history, having been a student of various, I mean obviously statins have been a major contribution, but this seems to have transcended that already. We're going to talk about more about where things are headed, but this fatty acid acetylation was a major step forward in extending the half-life of the drug, whereby today you can give semaglutide once a week. And this, I think, of course, there are many ways that you might've been able to extend the half-life, but you were starting with a hormone, a natural hormone neurotransmitter that had such an exquisitely short half-life of basically second or minutes rather than that you could give for a week. So I know there were many different ways you could have protected or extended the half-life one way or another, but this seemed to be a breakthrough of many along the chain of breakthroughs. But the question I have is when you were giving this to the diabetics, which was the precedent, that was really what these drugs were first intended, they didn't lose that much weight, and they never, still today when it's looked at for obese non-diabetics versus diabetics, there's a gap in weight loss. Why is that at the exact same dose, with the exact same peptide that the weight loss differs for people with type 2 diabetes as compared to those who have pure obesity?The Mystery of Why People With Type 2 Diabetes Don't Lose Weight Like Those With Obesity Lotte Bjerre Knudsen (10:09):Yeah, I can't give you a molecular answer to that, right. But I think the notion, I think it's the same for example with metformin, even though it gives less weight loss because that has also been tried in both people with diabetes and people without diabetes. So I think it's just for somehow people with diabetes are more resistant to weight loss. I think it's a really good question that I'm hoping maybe we could get through, for example, with proteomics and actually comparing people with diabetes and people without diabetes and looking at people who have the similar kind of weight loss. That could be really interesting. But I really don't have a good molecular answer for you, but it's just a really, really strong fact. But it also leads me to wanting to say it's interesting, because if that had been our motivation to actually say, oh, there's weight loss in diabetes, let's pursue it in people with obesity, I don't think we would've done that because the weight loss in people with diabetes wasn't that impressive. So it was very important for our chain of thought and decision early on that we actually knew that GLP-1 had these separate effects and that they could work in the brain and have a separate effect on well-known pathways in the brain. And that was more our motivation to actually continue to invest in obesity.Eric Topol (11:42):Yeah, no, I think this is when we did the research on the committee for the American Association for Advancement of Science (AAAS) award, the Mani L. Bhaumik Award, that you were recognized for the breakthrough of the year, this year. We tried to scour all the work and we actually had to hit Danish translations and all sorts of other papers they reviewed. And we learned through that process working on this committee that you were the one to be the champion of pushing this towards obesity, and it would've easily been missed because as we've been discussing, the weight loss in people with diabetes was small, but you push for it. And this was an extraordinarily important push because what it has resulted in, of course, has been spectacular. And obviously as we're going to get into much more than just obesity and obesity related conditions. But before we get to those other conditions, and as you've been known in the medical community as “the mother of GLP-1”, you were dubbed that term. The GLP-1 receptor is expressed in many parts of the body. Maybe you could just tell us about the distribution because this, I think is tied into these central nervous system effects that are not just related to the gut hormone type of axis.GLP-1 Receptors and the BrainLotte Bjerre Knudsen (13:17):So I spent a lot of time on that together with my amazing colleague, Charles Pyke, who's an histology expert because it turned out to be so very important. In general, when you're trying to make new medicines, understanding the mechanism, sometimes people say, yeah, who cares? But actually, it should matter, I think because where it becomes really important can be an understanding what they do not do. We've had to do a lot of proving the negatives for GLP-1. We went through these issues with thyroid cancer, pancreatitis, pancreas cancer. In all of that work, it was actually really important that we could show where the GLP-1 receptor was not expressed. So in the pancreas, we know that it's primarily on the insulin producing cells, and then we also have them in the intestine where they're probably involved in regulating inflammation and really creating a much healthier gut.(14:15):And then we have a lot of receptors in the brain. They're typically expressed on neurons, but they're also on astrocytes, they're also on smooth muscle cells. We have them on the heart and the sinus node. That's why there's a small increase in heart rate. We have them in the kidney, on again some smooth muscle cells that are renin positive. So there we can start thinking blood pressure and other things. So it turns out that you can go around the body and there are all of these specific GLP-1 receptor population, that you can see how they tie into the pharmacology. But obviously in physiology, they're not as important as they have turned out to be in pharmacology when we suddenly come with 24 hours a day exposure for a day or a week or for as long as the administration interval is. So, but specifically for obesity, I think it's in the vein, it's hard to, you should always be careful.(15:18):That's something I've learned to never say never. Of course, there could be a contribution from the peripheral nervous system as well to the effects in obesity. But I do think there are so many important and well described neuronal populations that have the GLP-1 receptor and which are accessible from the periphery. So just to mention, maybe one of the most, well-known is a POMC/CART neuron in the hypothalamus. They have the GLP-1 receptor, they're activated, but there also is an inhibitory tone on the AgRP and NPY neurons, and it fits very well with that. We know that people report that they feel more sated, they feel less hungry. But then there are also effects in the hindbrain and in some of the reward centers also have GLP-1 receptors. And we know that also now, we have really good actually clinical studies that show that there is a change in food choice and people can control their food intake better. So I think that fits very well with effects on the reward system. So it's a whole myriad, or maybe you could say that GLP-1 orchestrates a number of different neuronal populations to have these overall effects that reduce energy intake.Eric Topol (16:42):Yeah, it's pretty striking. It's almost like we're all walking around with GLP-1 deficiency, that if we had this present at higher levels around the clock, and of course eventually we'll see things that are well beyond obesity, how well this has an impact. Now, there was an extraordinary review in Cell Metabolism on the brain and GLP-1, and not just the brain, but the essential nervous system, the neurovascular, it's called the “GLP-1 programs and neurovascular landscape.”(17:20):And in this review, it got into the brain effects that were well beyond, I think what are generally appreciated. Not only the protection of the integrity of the blood-brain barrier, this whole neuroglial vascular unit, the myelin sheath protection, reducing inflammation within the brain, improving the glymphatic flow, which is of course critical for clearing waste and promoting cerebral vascular remodeling and more, so the brain effects here is what it seems to be. You mentioned the reward circuit, of course, but the brain effects here seem to be diverse, quite a bit of breath and extraordinary. And as we've seen in the clinic now with the work that's been done, we're seeing things about addiction, even gambling, alcohol, drugs, I mean neuropsychiatric impact, it's pretty profound. Maybe you could comment about that.On to Alzheimer's and Parkinson's DiseasesLotte Bjerre Knudsen (18:23):Yeah. I haven't read that paper yet, but I just saw it earlier. And I have been following this for about actually more than 10 years because when I was kind of over the big work of actually getting the approval for diabetes and obesity. I thought I had a little bit of capacity to actually look at Alzheimer's and Parkinson's disease because I just thought there's such an insane unmet need and what if GLP-1 could actually make a difference? And the first big paper that talked about this was actually in Nature Medicine in 2003, and it was originally, I think I should credit Nigel Greig. Greig, he's from NIH or from NIA, I can't remember, right. But he was actually the first one, I think to say if GLP-1 has all of these important effects in the pancreas and to protect cells, and there are all these GLP-1 receptors in the brain, maybe it also protects neurons.(19:25):So that was the first hypothesis. And the paper on Nature Medicine in 2003 describes how the GLP-1 receptor in the hippocampus is involved in cognition. And then we did a couple of studies in different animal models, and I was, to be honest, really confused. But then there was a new paper in Nature Medicine in 2018 that started to focus in on neuroinflammation. And by that time, I knew much more about inflammation and knew GLP-1 actually lower CRP by about 50% in the different trials. So I was really tuned into the potential importance of that in cardiovascular and kidney disease. But I was like, oh, what if that's also something that is important in the brain? Then it made more sense to me to try and build some evidence for that. So that was how we actually started looking at a hypothesis for Alzheimer's and Parkinson's.(20:21):And we now have a really large phase three study ongoing, but of course, it's a hypothesis, right? And no one has yet, I think, proven that GLP-1 has really important effects on these indications, but we are testing it in 4,000 people with Alzheimer's disease. So our hypothesis is around neuroinflammation, but defined in a way where you could say it's both peripheral inflammation and the effect it has on the vasculature, it's the effect on the blood-brain barrier. It's the astrocytes and the microglia, and there are probably also some T cells that have the GLP-1 receptor that could be important. And then couple that up also with some of the new information from neurons, because there are two papers to think in the last year that has highlighted neurons either in the hindbrain or a little bit further on. Both of them are probably hindbrain populations that actually seem to be really important in regulating both peripheral as well as central information.(21:27):So what if neurons are actually also an overlooked mechanism here, and both of these neuronal populations have the GLP-1 receptor and are accessible from the periphery, even though the child super paper in Nature doesn't mention that, but they do have the GLP-1 receptor. So there are all these different mechanisms that GLP-1 can have an impact on the broad definition maybe of neuroinflammation. And maybe the way one should start thinking about it is to say it's not an anti-inflammatory agent, but maybe it induces homeostasis in these systems. I think that could maybe be a good way to think about it, because I think saying that GLP-1 is anti-inflammatory, I think that that's wrong because that's more for agents that have a really strong effect on one particular inflammatory pathway.Eric Topol (22:22):That's a very important point you're making because I think we conceive of these drugs as anti-inflammatory agents from these more diverse actions that we've just been reviewing. But I like this restoring homeostasis. It's an interesting way to put it. This brings us, you mentioned about the Parkinson's, and when I reviewed the three randomized Parkinson's trials, they're all small, but it appears to be the first disease modifying drug ever in Parkinson's. Of course, these were done with different drugs that were older drugs. We haven't seen the ones that yet to be with semaglutide or other agents. And I wondered if you pushed, just like you did for obesity within Novo Nordisk, you pushed to go into obesity. Did you also force to push for Alzheimer's?Lotte Bjerre Knudsen (23:19):Yes. So that is also me who had to argue for that. I'm happy to do these things. I was born brave. I am happy to do these things.Eric Topol (23:31):That's wonderful. Without you, we would be way behind, and it took decades to get to this point. But look where we are now, especially with all the rigorous trials, the large clinical trials. You're into one right now of some 20,000 participants to see whether not just people with prior heart disease, but people without known heart disease to see whether or not this will have an effect. And there's so much data now, of course, already a completed trial with reduction of heart attacks and strokes. But now to extend this to people who are not such high risk, but these large trials, we keep learning more. Like for example, the reduction of inflammatory markers is occurring even before the weight loss that starts to manifest. So we learned a lot from the trials that are just even beyond some of the major primary outcomes. Would you agree about that?Lotte Bjerre Knudsen (24:34):So I'm not sure we can say that it comes before the weight loss because the energy intake reduction happens instantly. The glycemic response happens instantly. And all of these improvements will of course also have an effect to dampen inflammation. We do not have data that supports that it comes before because we haven't sampled that much in the beginning.Eric Topol (25:04):Okay.Lotte Bjerre Knudsen (25:05):I wouldn't be able to say that, and I don't think there are any, well, it's hard to keep up that the entire literature on GLP-1 these days, but I don't think anyone has actually shown that there is a separation because it's super hard to separate when things are occurring at the same time.Eric Topol (25:24):Yeah, I'm just citing the heart disease trial where in the New England Journal that point was made. But I think your point also that there was already a change in energy intake immediately is apropos for sure. Now, when we get into this new paper of yours, the proteomics, can you tell us about that because that's really exciting. We're in a high throughput proteomics era right now that we can analyze thousands of plasma proteins in any given individual. What are you learning about proteomics with the GLP-1 drug?The GLP-1 Drug Impact on ProteomicsLotte Bjerre Knudsen (26:07):Yeah, yeah. So I'm also the super excited about omics, right? Because I have worked in a wonderful organization of people who can do these large scale clinical trials, and we used to not collect a lot of samples for future use, but we've done that for some years now. So now we have this amazing collection of samples we can learn from and actually both inform the patients and the physicians, but also inform future research. So we have been doing that in our semaglutide trials, and we've just published the proteomics data from the step one and step two trials. So the phase 3a trials that supported the approval of semaglutide for the treatment of obesity. So one of them in people with obesity and one in people with obesity and diabetes, and those data are now published in Nature Medicine. [3 January 2025]. And we were learning a lot of things because you can compare the proteome effects to what has been done in the decode cohort.(27:11):So they have all these disease signature. So that's one thing that you can for sure see, and you can see a lot of things there with hints towards addiction. And then also you can take more predefined signatures also to look into what actually might be driving the cardiovascular risk. So I think there are so many things that you can learn from this, and of course it can also inform when you look at what's actually mediating the effect and probably something around inflammation is important. We have already also shown a more standard mediation analysis that shows that actually the most explainable factor for the effect on MACE [major adverse cardiovascular events] in the select trial is inflammation. It doesn't explain everything, but it actually looks like it's more important than BMI and weight loss. So that's really interesting how much we can learn from there. We're making the data are available at the summary statistic level so people can go and play with them ourselves.(28:23):And I think as we have more different kinds of medicines available in obesity, it's also a way to kind of compare how these different medicines work. And as we get more and more better at maybe also characterizing people with obesity, because I think that's a great thing that's going to happen now is there's going to be more funding for obesity research. Because I think that's what the attention that we are seeing right now is also giving. Then we can better start to understand. We always, we've been saying that people probably have different kinds of obesity, but we don't really know. So now we can actually start to understand that much better and maybe also understand how these different classes of medicines will work if we have the proteome data from different trials.Eric Topol (29:10):No, I'm absolutely fascinated about the proteomics. I call it a quiet revolution because many people don't know about it. [My recent post on this topic here.](29:18):The ability to assess thousands of proteins in each individual, and it's giving us new insights about cause and effect as you alluded to, the relationship with as you said, MACE (major adverse cardiovascular events) and the actions of this drug class. I mean, there's just so much we can learn here from the proteomics. Another thing that's fascinating about the GLP-1 is its effect on epigenetic clocks. And recently at one of the meetings it was presented, this is Steven Horvath that we had on Ground Truths not long ago. He talked about at this talk that for the first time to see that you could basically slow the epigenetic clock with a GLP-1. Is there any further information about that?Lotte Bjerre Knudsen (30:16):Yeah, no. We've never had enough of a sample size to actually be able to look at it, so unfortunately, no. But there is something else, right, because there is this group at the Stanford, Tony Wyss-Coray or something.Eric Topol (30:33):Yes, Tony Wyss-Coray.Lotte Bjerre Knudsen (30:35):Now he published a paper, is it two years ago? Where he did it using proteomics. He defined an anti-aging signature for various different organs.Lotte Bjerre Knudsen (30:46):We are in the process of trying to see if we could take those signatures and apply them on to our data.Eric Topol (30:55):Well, what's interesting is we're pretty close friends, and he, not only that paper you mentioned on organ clocks, which is a phenomenal contribution, but he has a paper coming out soon in Nature Medicine, the preprint is up, and what he showed was that the brain and the immune system was the main organ clocks that were associated with longevity. And so, it takes another step further and it's looking at 11,000 plasma proteins. So it's really interesting how this field is evolving because the omics, as you put it, whether it's proteomics, and now we're learning also about the epigenome and what brings us to the potential that this class of drugs would have an impact on health span in all people, not just those who are obese. Would you project that's going to be possible in the years ahead?Lotte Bjerre Knudsen (32:02):I don't know about health span, but because certainly there's been so many studies with metformin and there's been a lot of wonderful data showing an effect on the epigenetic clocks, but not really an effect on lifespan because that metformin is so widely used. If that was the case, it would be easy to dig those data out of different registries. But certainly a healthier aging is the most obvious one because when you have one class of medicine that actually has so many different effects. Right now we are looking at them at a one by one case, but we really should be looking at them so you are getting the benefits on the heart and the vasculature on the brain and the kidneys and the diabetes and the knees. You're getting all of that at the same time, and that certainly should lead to much, much healthier lives. And then of course, we just need to get people to eat healthier. Also, maybe we should talk a little bit about the food industry. I heard you did that in some of your podcast, right?Eric Topol (33:17):Yes. That is the big food, if you will. It's a big problem, a very big problem, and the ultra-processed foods. And so, lifestyle is not good and trying to compensate for that with a drug intervention strategy is like chasing your tail. So you're absolutely right about that. I mean, I guess what I'm getting into here is that whereas today we keep seeing the effects, whether it's the liver, the kidney, the heart, obesity, and people with diabetes. But for example, in the Alzheimer's trial, do you have to be obese to be enrolled in the Alzheimer's trial, or is it just people who are at risk for developingAlzheimer's?Lotte Bjerre Knudsen (34:01):Yeah, no, you do not have to be obese. It's a standard Alzheimer's trial.GLP-1 PillsEric Topol (34:07):So this will be one of the really important trials to get a readout in people who are not having an obesity background. Now, the future, of course, gets us to oral GLP-1 drugs, which obviously you have there at Novo Nordisk. And it seems to me once that happens, if it can simulate the effects we see with the injectables, that would be another big step forward. What do you think about that?Lotte Bjerre Knudsen (34:39):Yeah. Isn't it interesting, what we've learned is that people actually don't mind the injections, right? Also, because I think it's simple, once a week injection and the needles are so small, obviously there are people who really have needle phobia, but take those aside, it's relatively few. I would argue if you close your eyes and somebody else used this needle on you, you would not be able to feel where it was inserted, right? They're so small. So it becomes maybe a personal preference. Would you like to have once a day or maybe twice a day tablets, or are you fine with once a week injection? And I think there probably will be quite a few once they've tried it. And now so many have tried it and they actually, maybe it gives us a simple lifestyle. You don't have to do it every day, right? You can just have a weekly reminder.Eric Topol (35:46):Yeah, no, I think that's really interesting what you're bringing up. I never thought we would evolve to a point where injectables were becoming some common, and I even have some physician colleagues that are taking three different injectable drugs.Lotte Bjerre Knudsen (36:00):That's also just mentioned Richard DiMarchi, who I shared the Breakthrough Prize with, and also Svetlana Mojsov, who I was one of the other two recipients for the Lasker prize because they both been at Rockefeller, and they both have worked a lot with peptides, and they both say the same thing. They were told so many times, this is not medicines, these kinds of molecules just they're not medicines. Forget about it. It turns out people were wrong. And peptides can be medicines, and they can even be produced also in a sustainable manner with fermentation, which is not a bad way of producing medicines. And people actually don't mind. Maybe some people actually even like it because it's once a week and then it's done.Confronting BarriersEric Topol (36:58):Yeah, no, that's a very important point. And the quest for the oral, which have more issues with bioavailability versus the peptides that are having such pronounced impact is really interesting to ponder. Well, before we wrap up, it's very clear the impact you've had has been profound, not just obviously at Novo Nordisk, but for the world of advancing health and medicine. And you've mentioned some of the key other people who have made seminal contributions, but I think you stand out because when we went deep into who took this field forward into obesity and who might also wind up being credited for Alzheimer's, it was you. And as a woman in science, especially in an era that you've been at Novo now for three and a half decades, there weren't many women in science leaders. And for one to be, as you said, you're brave for the good old boys to listen to the woman in science. Tell us about that challenge. Was this ever an issue in your career? Because obviously we want to have this whole landscape change. It is in the midst of change, but it's certainly still a ways to go. So maybe you can give us insight about that.Lotte Bjerre Knudsen (38:27):Yeah. Well, it for sure was a thing. It was a very male dominated world, and in a way, it might have prevented other people from doing it. But then, as I said, I was born brave for some reason. I'm not really sure why. It actually motivated me to kind of like, yeah, I'm going to show them. I'm going to show them. So it never really got to me that people, not everyone was nice to say. There was the first 10 years of my career, I think they were quite lonely, but then I was really inspired. I was so happy to be allowed to work on this. I thought it was super fun. And I did find people who wanted to play with me. And I also have to say that the CSO back then, Mads Krogsgaard Thomsen, he always supported me. So maybe I didn't get everything I wanted, but I always got what I needed in order to progress.(39:29):So on the women's side, and I think that yes, and there's still a change to be made, and I'm actually a little bit on behalf of my generation, maybe not too proud of the change we made because we didn't do a lot of change. It was all the women coming from the arts and the culture. They were the ones who actually make the big change here like 5 or 10 years ago. So I've also started to be more open about sharing my journey and advocating for women in science. So that's why I show up in pink to some of these award sessions just to be a little bit different and to maybe also just show that you don't have to be a certain type in order to fit into a certain job. But there is still a change to be made where people should be better at listening to what a person say and what ideas they say.(40:28):And they should be mindful about not always labeling women as passionate. When people call me passionate, I say like, no, thank you. I'm actually not too happy about the mother of either, because men always are being told. They're being told that they're brave and ambitious and courageous and strategic, whereas we we're, oh, you're so passionate. No, thank you. I'm also brave and strategic and ambitious and all of that. So we simply put different vocabulary on. I don't think people don't do it on purpose. I think we need to be better at actually giving people at work the same kind of vocabulary for their contributions. And I think that would mean that we get listened to in the same way. And that would be important. And then I also have to say that science, whether it comes from men or women, doesn't really matter.(41:32):Successful science is always the work of many. And I hope that some of you will actually listen to my last speech because that's what I speak about, how it's always the work of the many. And also, how if you want to do something novel, then you actually have to do it at a time when no one else is doing it, and you should believe in your ideas. So believe in it, listen to the critique, but believe in it, and then come back with new arguments or give up if you can't come up with any new arguments, right?Eric Topol (42:05):Well, we'll definitely put a link to the Lasker Awards speech that you gave. And I just want to say that the parallels here, for example, with Kati Karikó , my friend who had the Nobel Award for mRNA, she spent three decades trying to get people to listen to her and never got a grant from the NIH or other places [our conversation here]. And it was a really tough battle. And as you already touched on Svetlana Mojsov, who did some of the seminal work at Rockefeller to isolate the portion of GLP-1, that really was the key part peptide, and it was overlooked for years. And so, it's a tough fight, but you're paving the way here. And I think the contributions you've made are just so extraordinary. And I hope that over the years we will continue to see this momentum because people like what you've done, deserve this extraordinary recognition. I'm glad to see. And the Lasker Award is really capping off some of that great recognition that is so well deserved. We've covered a lot of ground today, and I want to make sure if I missed anything that you wanted to get into before we wrap up.Lotte Bjerre Knudsen (43:30):I think we've been around all the exciting biology of GLP-1, both in diabetes, obesity, cardiovascular, kidney, potential in Alzheimer's and addiction. We'll see, we need the clinical data and we've put out a message to inspire people to do new science. There's still a lot of unmet need out there. There's a lot of diseases that don't have good treatments. Even in the diseases we've talked about there's a lot of money for diabetes. There are no disease modifying therapies for diabetes. It's not really changing the course of the disease. So there's a lot of things that needs great scientists.Eric Topol (44:17):And I guess just in finishing the discovery of this class of drugs and what it's led to, tells us something about that, there's so much more to learn that is, this has taken on perhaps the greatest obstacle in medicine, which was could you safely treat obesity and have a marked effect. Which decades, many decades were devoted to that and gotten nowhere. It's like a breakthrough in another way is that here you have an ability to triumph over such a frustrating target, just like we've seen with Alzheimer's, of course, which may actually intersect with Alzheimer's, with a graveyard of failed drugs. And the ones that it were approved so far in certain countries, like the US are so questionable as to the safety and efficacy. But it gives us an inspiration about what is natural that can be built on the basic science that can lead to with people like you who push within the right direction, give the right nudges and get the support you need, who knows what else is out there that we're going to be discovering in the years ahead. It's a broad type of lesson for us.Lotte Bjerre Knudsen (45:38):Yeah, there is another hormone that's also in phase three clinical development, right? The amylin hormone. We've had pramlintide on the market for years, but we have this long-acting version that is in phase three clinical development. That could be the same kind of story because there's also additional biology on that one.Eric Topol (45:58):Yeah, this is what grabs me Lotte, because these gut hormone, we've known about them, and there's several more out there, of course. And look what they're having. They're not just gut hormones, like you said, they're neurotransmitters and they're body-wide receptors waiting to be activated, so it's wild. It's just wild. And I'm so glad to have had this conversation with you. Now, congratulations on all that you've done, and I know the Nature Medicine paper that just came out is going to be just one of many more to come in your career. So what a joy to have the chance to visit with you, and we'll be following the work that you and your colleagues are doing with great interest.Lotte Bjerre Knudsen (46:45):And thank you very much, and thank you for your wonderful podcast. They're really great to listen to on the go. Very easy listening.*****************************************Please complete the quick poll question above.Thank you for reading, listening and subscribing to Ground Truths.If you found this podcast informative please share it!All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.Paid subscriptions are voluntary and of course appreciated. All proceeds from them go to support Scripps Research. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. I welcome all comments from paid subscribers and will do my best to respond to each of them and any questions.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio and video support at Scripps Research.Ground Truths now has subscribers in 203 countries! Get full access to Ground Truths at erictopol.substack.com/subscribe

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Send us a textIn this episode, we explore the fascinating world of circadian rhythms—your body's internal clock that impacts sleep, energy, hormones, and more. Learn what circadian rhythms are, how they function, and why they're crucial for your health. We'll dive into research-backed benefits of optimizing your sleep cycle and the adverse effects of ignoring it. Discover surprising insights about morning and evening types (chronotypes) and how light exposure, meal timing, and even exercise influence your internal clock. Plus, get a practical tip to improve your sleep tonight and download a free, customizable sleep calendar to align your schedule with your circadian rhythm. Cited Resources:•“The Circadian Code” by Dr. Satchin Panda•Study on circadian rhythms and metabolic health (Cell Metabolism, 2018)•Harvard Health on blue light and sleep disruption•Research on chronotypes and performance (Journal of Biological Rhythms, 2015)Hey Hormone Hotties:If you want to learn more about how you can work with me or what services I offer including those below- https://linktr.ee/Faithhealthfitness Interested in being a guest expert (even if you are not in business but a woman who has a story to share) fill out the application and book an appointment. Affiliated Partner for awesome products in wellness and more including the "Body balancing" slenderize for a discount using my code HAPPY24 Join me in Happy Hormones Circle. This and my email list is where I will be focusing my time and content Disclaimer: The content shared in ‘The Happy Hormones Coach' podcast (including affiliate and non affiliate products) is for informational purposes only and is not intended as medical advice, diagnosis, or treatment. Please consult with a qualified healthcare provider before making any changes to your diet, exercise, or health routine. The opinions expressed in this podcast are those of the host and guests and do not necessarily reflect the views of any healthcare organizations. The statements made regarding any of the products that I mention have not been evaluated by the Food and Drug Administration (FDA). Individual results may vary.

A leader for conducting rigorous randomized trials of humans along with animal models for understanding nutrition and metabolism, Dr. Kevin Hall is a Senior Investigator at the National Institutes of Health, and Section Chief of the Integrative Physiology Section, NIDDK. In this podcast, we reviewed his prolific body of research a recent publications. The timing of optimizing our diet and nutrition seems apropos, now that we're in in the midst of the holiday season!Below is a video snippet of our conversation on his ultra-processed food randomized trial.Full videos of all Ground Truths podcasts can be seen on YouTube here. The current one is here. If you like the YouTube format, please subscribe! The audios are also available on Apple and Spotify.Note: I'll be doing a Ground Truths Live Chat on December 11th at 12 N EST, 9 AM PST, so please mark your calendar and join!Transcript with links to publications and audioEric Topol (00:05):Well, hello. This is Eric Topol with Ground Truths, and I'm really delighted to have with me today, Dr. Kevin Hall from the NIH. I think everybody knows that nutrition is so important and Kevin is a leader in doing rigorous randomized trials, which is not like what we usually see with large epidemiologic studies of nutrition that rely on food diaries and the memory of participants. So Kevin, it's really terrific to have you here.Kevin Hall (00:34):Thanks so much for the invitation.Ultra-Processed FoodsEric Topol (00:36):Yeah. Well, you've been prolific and certainly one of the leaders in nutrition science who I look to. And what I thought we could do is go through some of your seminal papers. There are many, but I picked a few and I thought we'd first go back to the one that you published in Cell Metabolism. This is ultra-processed diets cause excessive caloric intake and weight gain. (Main results in graph below.) So maybe you can take us through the principle findings from that trial.Kevin Hall (01:10):Yeah, sure. So that was a really interesting study because it's the first randomized control trial that's investigated the role of ultra-processed foods in potentially causing obesity. So we've got, as you mentioned, lots and lots of epidemiological data that have made these associations between people who consume diets that are very high in ultra-processed foods as having greater risk for obesity. But those trials are not demonstrating causation. I mean, they suggest a strong link. And in fact, the idea of ultra-processed foods is kind of a new idea. It's really sort of appeared on the nutrition science stage probably most prominently in the past 10 years or so. And I first learned about this idea of ultra-processed foods, which is really kind of antithetical to the way most nutrition scientists think about foods. We often think about foods as nutrient delivery vehicles, and we kind of view foods as being the fraction of carbohydrates versus fats in them or how much sodium or fiber is in the foods.Kevin Hall (02:17):And along came this group in Brazil who introduced this new way of classifying foods that completely ignores the nutrient composition and says what we should be doing is classifying foods based on the extent and purpose of processing of foods. And so, they categorize these four different categories. And in the fourth category of this so-called NOVA classification scheme (see graphic below) , they identified something called ultra-processed foods. There's a long formal definition and it's evolved a little bit over the years and continues to evolve. But the basic ideas that these are foods that are manufactured by industries that contain a lot of purified ingredients made from relatively cheap agricultural commodity products that basically undergo a variety of processes and include additives and ingredients that are not typically found in home kitchens, but are typically exclusively in manufactured products to create the wide variety of mostly packaged goods that we see in our supermarkets.Kevin Hall (03:22):And so, I was really skeptical that there was much more about the effects of these foods. Other than that they typically have high amounts of sugar and saturated fat and salt, and they're pretty low in fiber. And so, the purpose of this study was to say, okay, well if there's something more about the foods themselves that is causing people to overconsume calories and gain weight and eventually get obesity, then we should do a study that's trying to test for two diets that are matched for these various nutrients of concern. So they should be matched for the macronutrients, they should be matched for the sugar content, the fat, the sodium, the fiber, and people should just be allowed to eat whatever they want and they shouldn't be trying to change their weight in any way. And so, the way that we did this was, as you mentioned, we can't just ask people to report what they're eating.Kevin Hall (04:19):So what we did was we admitted these folks to the NIH Clinical Center and to our metabolic ward, and it's a very artificial environment, but it's an environment that we can control very carefully. And so, what we basically did is take control over their food environment and we gave them three meals a day and snacks, and basically for a two-week period, they had access to meals that were more than 80% of calories coming from ultra-processed foods. And then in random order, they either received that diet first and give them simple instructions, eat as much as little as you want. We're going to measure lots of stuff. You shouldn't be trying to change your weight or weight that gave them a diet that had no calories from ultra-processed foods. In fact, 80% from minimally processed foods. But again, both of these two sort of food environments were matched for these nutrients that we typically think of as playing a major role in how many calories people choose to eat.Kevin Hall (05:13):And so, the basic idea was, okay, well let's measure what these folks eat. We gave them more than double the calories that they would require to maintain their weight, and what they didn't know was that in the basement of the clinical center where the metabolic kitchen is, we had all of our really talented nutrition staff measuring the leftovers to see what it was that they didn't eat. So we knew exactly what we provided to them and all the foods had to be in our nutrition database and when we compute what they actually ate by difference, so we have a very precise estimate about not only what foods they chose to ate, but also how many calories they chose to eat, as well as the nutrient composition.And the main upshot of all that was that when these folks were exposed to this highly ultra-processed food environment, they spontaneously chose to eat about 500 calories per day more over the two-week period they were in that environment then when the same folks were in the environment that had no ultra-processed foods, but just minimally processed foods. They not surprisingly gained weight during the ultra-processed food environment and lost weight and lost body fat during the minimally processed food environment. And because those diets were overall matched for these different nutrients, it didn't seem to be that those were the things that were driving this big effect. So I think there's a couple of big take homes here. One is that the food environment really does have a profound effect on just the biology of how our food intake is controlled at least over relatively short periods of time, like the two-week periods that we were looking at. And secondly, that there's something about ultra-processed foods that seem to be driving this excess calorie intake that we now know has been linked with increased risk of obesity, and now we're starting to put some of the causal pieces together that really there might be something in this ultra-processed food environment that's driving the increased rates of obesity that we've seen over the past many decades.Eric Topol (07:18):Yeah, I mean I think the epidemiologic studies that make the link between ultra-processed foods and higher risk of cancer, cardiovascular disease, type 2 diabetes, neurodegenerative disease. They're pretty darn strong and they're backed up by this very rigorous study. Now you mentioned it short term, do you have any reason to think that adding 500 calories a day by eating these bad foods, which by the way in the American diet is about 60% or more of the average American diet, do you have any inkling that it would change after a few weeks?Kevin Hall (07:54):Well, I don't know about after a few weeks, but I think that one of the things that we do know about body weight regulation and how it changes in body weight impact both metabolism, how many calories were burning as well as our appetite. We would expect some degree of moderation of that effect eventually settling in at a new steady state, that's probably going to take months and years to achieve. And so the question is, I certainly don't believe that it would be a 500 calorie a day difference indefinitely. The question is when would that difference converge and how much weight would've been gained or lost when people eventually reached that new plateau? And so, that's I think a really interesting question. Some folks have suggested that maybe if you extrapolated the lines a little bit, you could predict when those two curves might eventually converge. That's an interesting thought experiment, but I think we do need some longer studies to investigate how persistent are these effects. Can that fully explain the rise in average body weight and obesity rates that have occurred over the past several decades? Those are open questions.Eric Topol (09:03):Yeah. Well, I mean, I had the chance to interview Chris van Tulleken who wrote the book, Ultra-Processed People and I think you might remember in the book he talked about how he went on an ultra-processed diet and gained some 20, 30 pounds in a short time in a month. And his brother, his identical twin brother gained 50, 60 pounds, and so it doesn't look good. Do you look at all the labels and avoid all this junk and ultra-processed food now or are you still thinking that maybe it's not as bad as it looks?Kevin Hall (09:38):Well, I mean I think that I certainly learned a lot from our studies, and we are continuing to follow this up to try to figure out what are the mechanisms by which this happen. But at the same time, I don't think we can throw out everything else we know about nutrition science. So just because we match these various nutrients in this particular study, I think one of the dangers here is that as you mentioned, there's 60% of the food environment in the US and Great Britain and other places consist of these foods, and so they're unavoidable to some extent, right? Unless you're one of these privileged folks who have your backyard garden and your personal chef who can make all of your foods, I'm certainly not one of those people, but for the vast majority of us, we're going to have to incorporate some degree of ultra-processed foods in our day-to-day diet.Kevin Hall (10:24):The way I sort of view it is, we really need to understand the mechanisms and before we understand the mechanisms, we have to make good choices based on what we already know about nutrition science, that we should avoid the foods that have a lot of sugar in them. We should avoid foods that have a lot of saturated fat and sodium. We should try to choose products that contain lots of whole grains and legumes and fruits and vegetables and things like that. And there's some of those, even in the ultra-processed food category. I pretty regularly consume a microwavable ready meal for lunch. It tends to be pretty high in whole grains and legumes and low in saturated fat and sugar and things like that. But to engineer a food that can heat up properly in a microwave in four minutes has some ultra-processing technology involved there. I would be pretty skeptical that that's going to cause me to have really poor health consequences as compared to if I had the means to eat homemade French fries every day in tallow. But that's the kind of comparison that we have to think about.Eric Topol (11:36):But I think what you're touching on and maybe inadvertently is in that NOVA class four, the bad ultra-processed foods, there's a long, long list of course, and some of those may be worse than others, and we haven't seen an individual ranking of these constituents. So as you're alluding to what's in that microwave lunch probably could be much less concerning than what's in these packaged snacks that are eaten widely. But I would certainly agree that we don't know everything about this, but your study is one of the most quoted studies ever in the ultra-processed food world. Now, let me move on to another trial that was really important. This was published in Nature Medicine and it's about a plant-based diet, which is of course a very interesting diet, low-fat versus an animal-based ketogenic diet. Also looking at energy intake. Can you take us through that trial?Plant-Based, Low Fat Diet vs Animal-Based, Low Carbohydrate Ketogenic DietKevin Hall (12:33):Sure. So it's actually interesting to consider that trial in the context of the trial we just talked about because both of these diets that we tested in this trial were relatively low in ultra-processed foods, and so both of them contained more than a kilogram of non-starchy vegetables as a base for designing these, again, two different food environments. Very similar overall study design where people again were exposed to either diets that were vegan plant-based diet that was really high in starches and was designed to kind of cause big insulin increases in the blood after eating the meals. And the other diet had very, very few carbohydrates of less than 10% in total, and we built on that kind of non-starchy vegetable base, a lot of animal-based products to kind of get a pretty high amount of fat and having very low carbohydrates. Both diets in this case, like I mentioned, were pretty low in ultra-processed foods, but what we were really interested in here was testing this idea that has come to prominence recently, that high carbohydrate diets that lead to really large glucose excursions after meals that cause very high insulin levels after meals are particularly obesogenic and should cause you to be hungrier than compared to a diet that doesn't lead to those large swings in glucose and insulin and the prototypical case being one that's very low in carbohydrate and might increase the level of ketones that are floating around in your blood, which are hypothesized to be an appetite suppressant. Same sort of design, these minimally processed diets that one was very high in carbs and causes large swings in insulin and the other that's very low in carbs and causes increases in ketones.Kevin Hall (14:22):We ask people, again, while you're in one food environment or the other, don't be trying to gain weight or lose weight, eat as much or as little as you'd like, and we're going to basically measure a lot of things. They again, don't know what the primary outcome of the study is. We're measuring their leftovers afterwards. And so, the surprise in this particular case was that the diet that caused the big swings in glucose and insulin did not lead to more calorie consumption. In fact, it led to about 700 calories per day less than when the same people were exposed to the ketogenic diet. Interestingly, both food environments caused people to lose weight, so it wasn't that we didn't see the effect of people over consuming calories on either diet, so they were reading fewer calories in general than they were when they came in, right. They're probably eating a pretty ultra-processed food diet when they came in. We put them on these two diets that varied very much in terms of the macronutrients that they were eating, but both were pretty minimally processed. They lost weight. They ended up losing more body fat on the very low-fat high carb diet than the ketogenic diet, but actually more weight on the ketogenic diet than the low-fat diet. So there's a little bit of a dissociation between body fat loss and weight loss in this study, which was kind of interesting.Eric Topol (15:49):Interesting. Yeah, I thought that was a fascinating trial because plant-based diet, they both have their kind of camps, you know.Kevin Hall (15:57):Right. No, exactly.Immune System Signatures for Vegan vs Ketogenic DietsEric Topol (15:58):There are people who aren't giving up on ketogenic diet. Of course, there's some risks and some benefits and there's a lot of interest of course with the plant-based diet. So it was really interesting and potentially the additive effects of plant-based with avoidance or lowering of ultra-processed food. Now, the more recent trial that you did also was very interesting, and of course I'm only selecting ones that I think are particularly, there are a lot of trials you've done, but this one is more recent in this year where you looked at vegan versus ketogenic diets for the immune signature, immune response, which is really important. It's underplayed as its effect, and so maybe you can take us through that one.[Link to a recent Nature feature on this topic, citing Dr. Hall's work]Kevin Hall (16:43):Yeah, so just to be clear, it's actually the same study, the one that we just talked about. This is a secondary sort of analysis from a collaboration we had with some folks at NIAID here at the NIH to try to evaluate immune systems signatures in these same folks who wonder what these two changes in their food environment. One is vegan, high carbohydrate low-fat diet and the other, the animal-based ketogenic diet. And again, it was pretty interesting to me that we were able to see really substantial changes in how the immune system was responding. First of all, both diets again seem to have improved immune function, both adaptive and innate immune function as compared to their baseline measurements when they came into the study. So when they're reading their habitual diet, whatever that is typically high in ultra-processed foods, they switched to both of these diets.Kevin Hall (17:39):We saw market changes in their immune system even compared to baseline. But when we then went and compared the two diets, they were actually divergent also, in other words, the vegan diet seemed to stimulate the innate immune system and the ketogenic diet seemed to stimulate the adaptive immune system. So these are the innate immune system can be thought of. Again, I'm not an immunologist. My understanding is that this is the first line defense against pathogens. It happens very quickly and then obviously the adaptive immune system then adapts to a specific pathogen over time. And so, this ability of our diet to change the immune system is intriguing and how much of that has to do with influencing the gut microbiota, which obviously the gut plays a huge role in steering our immune system in one direction versus another. I think those are some really intriguing mechanistic questions that are really good fodder for future research.Eric Topol (18:42):Yeah, I think it may have implications for treatment of autoimmune diseases. You may want to comment about that.Kevin Hall (18:51):Yeah, it's fascinating to think about that the idea that you could change your diet and manipulate your microbiota and manipulate your gut function in a way to influence your immune system to steer you away from a response that may actually be causing your body damage in your typical diet. It's a fascinating area of science and we're really interested to follow that up. I mean, it kind of supports these more anecdotal reports of people with lupus, for example, who've reported that when they try to clean up their diet for a period of time and eliminate certain foods and eliminate perhaps even ultra-processed food products, that they feel so much better that their symptoms alleviate at least for some period of time. Obviously, it doesn't take the place of the therapeutics that they need to take, but yeah, we're really interested in following this up to see what this interaction might be.Eric Topol (19:46):Yeah, it's fascinating. It also gets to the fact that certain people have interesting responses. For example, those with epilepsy can respond very well to a ketogenic diet. There's also been diet proposed for cancer. In fact, I think there's some even ongoing trials for cancer of specific diets. Any comments about that?Kevin Hall (20:10):Yeah, again, it's a really fascinating area. I mean, I think we kind of underappreciate and view diet in this lens of weight loss, which is not surprising because that's kind of where it's been popularized. But I think the role of nutrition and how you can manipulate your diet and still you can have a very healthy version of a ketogenic diet. You can have a very healthy version of a low-fat, high carb diet and how they can be used in individual cases to kind of manipulate factors that might be of concern. So for example, if you're concerned about blood glucose levels, clearly a ketogenic diet is moderating those glucose levels over time, reducing insulin levels, and that might have some positive downstream consequences and there's some potential downsides. Your apoB levels might go up. So, you have to kind of tune these things to the problems and the situations that individuals may face. And similarly, if you have issues with blood glucose control, maybe a high carbohydrate diet might not be for you, but if that's not an issue and you want to reduce apoB levels, it seems like that is a relatively effective way to do that, although it does tend to increase fasting triglyceride levels.Kevin Hall (21:27):So again, there's all of these things to consider, and then when you open the door beyond traditional metabolic health markers to things like inflammation and autoimmune disease as well as some of these other things like moderating how cancer therapeutics might work inside the body. I think it's a really fascinating and interesting area to pursue.Eric Topol (21:55):No question about it. And that also brings in the dimension of the gut microbiome, which obviously your diet has a big influence, and it has an influence on your brain, brain-gut axis, and the immune system. It's all very intricate, a lot of feedback loops and interactions that are not so easy to dissect, right?Kevin Hall (22:16):Absolutely. Yeah, especially in humans. That's why we rely on our basic science colleagues to kind of figure out these individual steps in these chains. And of course, we do need human experiments and carefully controlled experiments to see how much of that really translates to humans, so we need this close sort of translational partnership.On the Pathogenesis of Obesity, Calories In and Calories OutEric Topol (22:35):Yeah. Now, you've also written with colleagues, other experts in the field about understanding the mechanisms of pathogenesis of obesity and papers that we'll link to. We're going to link to everything for what we've been discussing about calories in, calories out, and that's been the longstanding adage about this. Can you enlighten us, what is really driving obesity and calories story?Kevin Hall (23:05):Well, I co-organized a meeting for the Royal Society, I guess about a year and a half ago, and we got together all these experts from around the world, and the basic message is that we have lots of competing theories about what is driving obesity. There's a few things that we all agree on. One is that there is a genetic component. That adiposity in a given environment is somewhere between 40% to 70% heritable, so our genes play a huge role. It seems like there's certain genes that can play a major role. Like if you have a mutation in leptin, for example, or the leptin receptor, then this can have a monogenic cause of obesity, but that's very, very rare. What seems to be the case is that it's a highly polygenic disease with individual gene variants contributing a very, very small amount to increased adiposity. But our genes have not changed that much as obesity prevalence has increased over the past 50 years. And so, something in the environment has been driving that, and that's where the real debates sort of starts, right?Kevin Hall (24:14):I happen to be in the camp that thinks that the food environment is probably one of the major drivers and our food have changed substantially, and we're trying to better understand, for example, how ultra-processed foods which have risen kind of in parallel with the increased prevalence of obesity. What is it about ultra-processed foods that tend to drive us to overconsume calories? Other folks focus maybe more on what signals from the body have been altered by the foods that we're eating. They might say that the adipose tissue because of excess insulin secretion for example, is basically driven into a storage mode and that sends downstream signals that are eventually sensed by the brain to change our appetite and things like that. There's a lot of debate about that, but again, I think that these are complementary hypotheses that are important to sort out for sure and important to design experiments to try to figure out what is more likely. But there is a lot of agreement on the idea that there's something in our environment has changed.Kevin Hall (25:17):I think there's even maybe a little bit less agreement of exactly what that is. I think that there's probably a little bit more emphasis on the food environment as opposed to there are other folks who think increased pollution might be driving some of this, especially endocrine disrupting chemicals that have increased in prevalence. I think that's a viable hypothesis. I think we have to try to rank order what we think are the most likely and largest contributors. They could all be contributing to some extent and maybe more so in some people rather than others, but our goal is to try to, maybe that's a little simple minded, but let's take the what I think is the most important thing and let's figure out the mechanisms of that most important thing and we'll, number one, determine if it is the most important thing. In my case, I think something about ultra-processed foods that are driving much of what we're seeing. If we could better understand that, then we could both advise consumers to avoid certain kinds of foods because of certain mechanisms and still be able to consume some degree of ultra-processed foods. They are convenient and tasty and relatively inexpensive and don't require a lot of skill and equipment to prepare. But then if we focus on the true bad guys in that category because we really understand the mechanisms, then I think that would be a major step forward. But that's just my hypothesis.Eric Topol (26:43):Well, I'm with you actually. Everything I've read, everything I've reviewed on ultra-processed food is highly incriminating, and I also get frustrated that nothing is getting done about it, at least in this country. But on the other hand, it doesn't have to be either or, right? It could be both these, the glycemic index story also playing a role. Now, when you think about this and you're trying to sort out calories in and calories out, and let's say it's one of your classic experiments where you have isocaloric proteins and fat and carbohydrate exactly nailed in the different diets you're examining. Is it really about calories or is it really about what is comprising the calorie?Kevin Hall (27:29):Yeah, so I think this is the amazing thing, even in our ultra-processed food study, if we asked the question across those people, did the people who ate more calories even in the ultra-processed diet, did they gain more weight? The answer is yes.Kevin Hall (27:44):There's a very strong linear correlation between calorie intake and weight change. I tend to think that I started my career in this space focusing more on the metabolism side of the equation, how the body's using the calories and how much does energy expenditure change when you vary the proportion of carbs versus fat, for example. The effect size is there, they might be there, but they're really tiny of the order of a hundred calories per day. What really struck me is that when we just kind of changed people's food environments, the magnitude of the effects are like we mentioned, 500 to 700 calories per day differences. So I think that the real trick is to figure out how is it that the brain is regulating our body weight in some way that we are beginning to understand from a molecular perspective? What I think is less well understood is, how is that food intake control system altered by the food environment that we find ourselves in?The Brain and GLP-1 DrugsKevin Hall (28:42):There are a few studies now in mice that are beginning to look at how pathways in the brain that have been believed to be related to reward and not necessarily homeostatic control of food intake. They talk to the regions of the brain that are related to homeostatic control of food intake, and it's a reciprocal sort of feedback loop there, and we're beginning to understand that. And I think if we get more details about what it is in our foods that are modulating that system, then we'll have a better understanding of what's really driving obesity and is it different in different people? Are there subcategories of obesity where certain aspects of the food environment are more important than others, and that might be completely flipped in another person. I don't know the answer to that question yet, but it seems like there are certain common factors that might be driving overall changes in obesity prevalence and how they impact this reward versus homeostatic control systems in the brain, I think are really fascinating questions.Eric Topol (29:43):And I think we're getting much more insight about this circuit of the reward in the brain with the food intake, things like optogenetics, many ways that we're getting at this. And so, it's fascinating. Now, that gets me to the miracle drug class GLP-1, which obviously has a big interaction with obesity, but of course much more than that. And you've written about this as well regarding this topic of sarcopenic obesity whereby you lose a lot of weight, but do you lose muscle mass or as you referred to earlier, you lose body fat and maybe not so much muscle mass. Can you comment about your views about the GLP-1 family of drugs and also about this concern of muscle mass loss?Kevin Hall (30:34):Yeah, so I think it's a really fascinating question, and we've been trying to develop mathematical models about how our body composition changes with weight gain and weight loss for decades now. And this has been a long topic, one of the things that many people may not realize is that people with obesity don't just have elevated adiposity, they also have elevated muscle mass and lean tissue mass overall. So when folks with obesity lose weight, and this was initially a pretty big concern with bariatric surgery, which has been the grandfather of ways that people have lost a lot of weight. The question has been is there a real concern about people losing too much weight and thereby becoming what you call sarcopenic? They have too little muscle mass and then they have difficulties moving around. And of course, there are probably some people like that, but I think what people need to realize is that folks with obesity tend to start with much higher amounts of lean tissue mass as well as adiposity, and they start off with about 50% of your fat-free mass, and the non-fat component of your body is skeletal muscle.Kevin Hall (31:45):So you're already starting off with quite a lot. And so, the question then is when you lose a lot of weight with the GLP-1 receptor agonist or with bariatric surgery, how much of that weight loss is coming from fat-free mass and skeletal muscle versus fat mass? And so, we've been trying to simulate that using what we've known about bariatric surgery and what we've known about just intentional weight loss or weight gain over the years. And one of the things that we found was that our sort of expectations for what's expected for the loss of fat-free mass with these different drugs as well as bariatric surgery, for the most part, they match our expectations. In other words, the expected amount of fat loss and fat free mass loss. The one outlier interestingly, was the semaglutide study, and in that case, they lost more fat-free mass than would be expected.Kevin Hall (32:44):Now, again, that's just raising a little bit of a flag that for whatever reason, from a body composition perspective, it's about a hundred people underwent these repeated DEXA scans in that study sponsored by Novo Nordisk. So it's not a huge number of people, but it's enough to really get a good estimate about the proportion of weight loss. Whether or not that has functional consequences, I think is the open question. There's not a lot of reports of people losing weight with semaglutide saying, you know what? I'm really having trouble actually physically moving around. I feel like I've lost a lot of strength. In fact, it seems to be the opposite, right, that the quality of the muscle there seems to be improved. They seem to have more physical mobility because they've lost so much more weight, that weight had been inhibiting their physical movement in the past.Kevin Hall (33:38):So it's something to keep an eye on. It's an open question whether or not we need additional therapies in certain categories of patients, whether that be pharmacological, there are drugs that are interesting that tend to increase muscle mass. There's also other things that we know increase muscle mass, right? Resistance exercise training, increase this muscle mass. And so, if you're really concerned about this, I certainly, I'm not a physician, but I think it's something to consider that if you go on one of these drugs, you might want to think about increasing your resistance exercise training, maybe increasing the protein content of your diet, which then can support that muscle building. But I think it's a really interesting open question about what the consequences of this might be in certain patient populations, especially over longer periods of time.Dietary Protein, Resistance Exercise, DEXA ScansEric Topol (34:30):Yeah, you've just emphasized some really key points here. Firstly, that resistance exercise is good for you anyway. And get on one of these drugs, why don't you amp it up or get it going? The second is about the protein diet, which it'd be interesting to get your thoughts on that, but we generally have too low of a protein diet, but then there are some who are advocating very high protein diets like one gram per pound, not just one gram per kilogram. And there have been studies to suggest that that very high protein diet could be harmful, but amping up the protein diet, that would be a countering thing. But the other thing you mentioned is a DEXA scan, which can be obtained very inexpensively, and because there's a variability in this muscle mass loss if it's occurring, I wonder if that's a prudent thing or if you just empirically would just do the things that you mentioned. Do you have any thoughts about that?Kevin Hall (35:32):Yeah, that's really a clinical question that I don't deal with on a day-to-day basis. And yeah, I think there's probably better people suited to that. DEXA scans, they're relatively inexpensive, but they're not readily accessible to everyone. I certainly wouldn't want to scare people away from using drugs that are now known to be very effective for weight loss and pretty darn safe as far as we can tell, just because they don't have access to a DEXA scanner or something like that.Eric Topol (36:00):Sure. No, that makes a lot of sense. I mean, the only reason I thought it might be useful is if you're concerned about this and you want to track, for example, how much is that resistant training doing?Kevin Hall (36:13):But I think for people who have the means to do that, sure. I can't see any harm in it for sure.Continuous Glucose Sensors?Eric Topol (36:19):Yeah. That gets me to another metric that you've written about, which is continuous glucose tracking. As you know, this is getting used, I think much more routinely in type one insulin diabetics and people with type 2 that are taking insulin or difficult to manage. And now in recent months there have been consumer approved that is no prescription needed, just go to the drugstore and pick up your continuous glucose sensor. And you've written about that as well. Can you summarize your thoughts on it?Kevin Hall (36:57):Yeah, sure. I mean, yeah, first of all, these tools have been amazing for people with diabetes and who obviously are diagnosed as having a relative inability to regulate their glucose levels. And so, these are critical tools for people in that population. I think the question is are they useful for people who don't have diabetes and is having this one metric and where you target all this energy into this one thing that you can now measure, is that really a viable way to kind of modulate your lifestyle and your diet? And how reliable are these CGM measurements anyway? In other words, do they give the same response to the same meal on repeated occasions? Does one monitor give the same response as another monitor? And those are the kinds of experiments that we've done. Again, secondary analysis, these trials that we talked about before, we have people wearing continuous glucose monitors all the time and we know exactly what they ate.Kevin Hall (37:59):And so, in a previous publication several years ago, we basically had two different monitors. One basically is on the arm, which is the manufacturer's recommendation, the other is on the abdomen, which is the manufacturer's recommendation. They're wearing them simultaneously. And we decided just to compare what were the responses to the same meals in simultaneous measurements. And they were correlated with each other thankfully, but they weren't as well predictive as you might expect. In other words, one device might give a very high glucose reading to consuming one meal and the other might barely budge, whereas the reverse might happen for a different meal. And so, we asked the question, if we were to rank the glucose spikes by one meal, so we have all these meals, let's rank them according to the glucose spikes of one device. Let's do the simultaneous measurements with the other device.Kevin Hall (38:53):Do we get a different set of rankings? And again, they're related to each other, but they're not overlapping. They're somewhat discordant. And so, then the question becomes, okay, well if I was basically using this one metric to kind of make my food decisions by one device, I actually start making different decisions compared to if I happen to have been wearing a different device. So what does this really mean? And I think this sort of foundational research on how much of a difference you would need to make a meaningful assessment about, yeah, this is actionable from a lifestyle perspective, even if that is the one metric that you're interested in. That sort of foundational research I don't think has really been done yet. More recently, we asked the question, okay, let's ignore the two different devices. Let's stick to the one where we put it on our arm, and let's ask the question.Kevin Hall (39:43):We've got repeated meals and we've got them in this very highly regimented and controlled environment, so we know exactly what people ate previously. We know the timing of the meals, we know when they did their exercise, we know how much they were moving around, how well they slept the night before. All of these factors we could kind of control. And the question that we asked in that study was, do people respond similarly to the same meal on repeated occasions? Is that better than when you actually give them very different meals? But they match overall for macronutrient content, for example. And the answer to that was surprisingly no. We had as much variability in the glucose response to the same person consuming the same meal on two occasions as a whole bunch of different meals. Which suggests again, that there's enough variability that it makes it difficult to then recommend on for just two repeats of a meal that this is going to be a meal that's going to cause your blood glucose to be moderate or blood glucose to be very high. You're going to have to potentially do this on many, many different occasions to kind of figure out what's the reliable response of these measurements. And again, that foundational research is typically not done. And I think if we're really going to use this metric as something that is going to change our lifestyles and make us choose some meals other than others, then I think we need that foundational research. And all we know now is that two repeats of the same meal is not going to do it.Eric Topol (41:21):Well, were you using the current biosensors of 2024 or were you using ones from years ago on that?Kevin Hall (41:27):No, we were using ones from several years ago when these studies were completed. But interestingly, the variability in the venous measurements to meal tests is also very, very different. So it's probably not the devices per se that are highly variable. It's that we don't really know on average how to predict these glucose responses unless there's huge differences in the glycemic load. So glycemic load is a very old concept that when you have very big differences in glycemic load, yeah, you can on average predict that one kind of meal is going to give rise to a much larger glucose excursion than another. But typically these kind of comparisons are now being made within a particular person. And we're comparing meals that might have quite similar glycemic loads with the claim that there's something specific about that person that causes them to have a much bigger glucose spike than another person. And that we can assess that with a couple different meals.Eric Topol (42:31):But also, we know that the spikes or the glucose regulation, it's very much affected by so many things like stress, like sleep, like exercise. And so, it wouldn't be at all surprising that if you had the exact same food, but all these other factors were modulated that it might not have the same response. But the other thing, just to get your comment on. Multiple groups, particularly starting in Israel, the Weizmann Institute, Eran Segal and his colleagues, and many subsequent have shown that if you give the exact same amount of that food, the exact same time to a person, they eat the exact same amount. Their glucose response is highly heterogeneous and variable between people. Do you think that that's true? That in fact that our metabolism varies considerably and that the glucose in some will spike with certain food and some won't.Kevin Hall (43:29):Well, of course that's been known for a long time that there's varying degrees of glucose tolerance. Just oral glucose tolerance tests that we've been doing for decades and decades we know is actually diagnostic, that we use variability in that response as diagnostic of type 2 diabetes.Eric Topol (43:49):I'm talking about within healthy people.Kevin Hall (43:53):But again, it's not too surprising that varying people. I mean, first of all, we have a huge increase in pre-diabetes, right? So there's various degrees of glucose tolerance that are being observed. But yeah, that is important physiology. I think the question then is within a given person, what kind of advice do we give to somebody about their lifestyle that is going to modulate those glucose responses? And if that's the only thing that you look at, then it seems like what ends up happening, even in the trials that use continuous glucose monitors, well big surprise, they end up recommending low carbohydrate diets, right? So that's the precision sort of nutrition advice because if that's the main metric that's being used, then of course we've all known for a very long time that lower carbohydrate diets lead to a moderated glucose response compared to higher carbohydrate diets. I think the real question is when you kind of ask the issue of if you normalize for glycemic load of these different diets, and there are some people that respond very differently to the same glycemic load meal compared to another person, is that consistent number one within that person?Kevin Hall (45:05):And our data suggests that you're going to have to repeat that same test multiple times to kind of get a consistent response and be able to make a sensible recommendation about that person should eat that meal in the future or not eat that meal in the future. And then second, what are you missing when that becomes your only metric, right? If you're very narrowly focused on that, then you're going to drive everybody to consume a very low carbohydrate diet. And as we know, that might be great for a huge number of people, but there are those that actually have some deleterious effects of that kind of diet. And if you're not measuring those other things or not considering those other things and put so much emphasis on the glucose side of the equation, I worry that there could be people that are being negatively impacted. Not to mention what if that one occasion, they ate their favorite food and they happen to get this huge glucose spike and they never eat it again, their life is worse. It might've been a complete aberration.Eric Topol (46:05):I think your practical impact point, it's excellent. And I think one of the, I don't know if you agree, Kevin, but one of the missing links here is we see these glucose spikes in healthy people, not just pre-diabetic, but people with no evidence of glucose dysregulation. And we don't know, they could be up to 180, 200, they could be prolonged. We don't know if the health significance of that, and I guess someday we'll learn about it. Right?Kevin Hall (46:36):Well, I mean that's the one nice thing is that now that we have these devices to measure these things, we can start to make these correlations. We can start to do real science to say, what a lot of people now presume is the case that these spikes can't be good for you. They must lead to increased risk of diabetes. It's certainly a plausible hypothesis, but that's what it is. We actually need good data to actually analyze that. And at least that's now on the table.Eric Topol (47:04):I think you're absolutely right on that. Well, Kevin, this has been a fun discussion. You've been just a great leader in nutrition science. I hope you'll keep up your momentum because it's pretty profound and I think we touched on a lot of the uncertainties. Is there anything that I didn't ask you that you wish I did?Kevin Hall (47:23):I mean, we could go on for hours, I'm sure, Eric, but this has been a fascinating conversation. I really appreciate your interest. Thank you.Eric Topol (47:30):Alright, well keep up the great stuff. We'll be following all your work in the years ahead, and thanks for joining us on Ground Truths today.**************************************Footnote, Stay Tuned: Julia Belluz and Kevin Hall have a book coming out next September titled “WHY WE EAT? Thank you for reading, listening and subscribing to Ground Truths.If you found this fun and informative please share it!All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.Paid subscriptions are voluntary. All proceeds from them go to support Scripps Research. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. I welcome all comments from paid subscribers and will do my best to respond to them and any questions.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio and video support at Scripps Research.Note on Mass Exodus from X/twitter:Many of you have abandoned the X platform for reasons that I fully understand. While I intend to continue to post there because of its reach to the biomedical community, I will post anything material here in the Notes section of Ground Truths on a daily basis and cover important topics in the newsletter/analyses. You can also find my posts at Bluesky: @erictopol.bsky.social, which is emerging as an outstanding platform for sharing life science. Get full access to Ground Truths at erictopol.substack.com/subscribe

Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode:  Olink tools and softwareOlink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/  UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies  Research articlesThe support of human genetic evidence for approved drug indicationsMatthew R Nelson et al,  Nature Genetics 2015https://www.nature.com/articles/ng.3314 Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populationsM. Austin Argentieri et al,  Nature Medicine 2024https://www.nature.com/articles/s41591-024-03164-7 Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systemsLudger J.E. Goeminne et al, Cell Metabolism 2024, in presshttps://www.sciencedirect.com/science/article/abs/pii/S1550413124004017?via%3Dihub Plasma proteomic associations with genetics and health in the UK BiobankBenjamin B. Sun et, Nature 2023https://www.nature.com/articles/s41586-023-06592-6 Rare variant associations with plasma protein levels in the UK BiobankRyan S. Dhindsa; Nature 2023https://www.nature.com/articles/s41586-023-06547-x Disease prediction with multi-omics and biomarkers empowers case–control genetic discoveries in the UK BiobankManik Garg, Nature Genetics, 2024https://www.nature.com/articles/s41588-024-01898-1 China Kadoorie Biobank: https://www.ckbiobank.org/publicationsPublications: https://www.ckbiobank.org/publications Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm  Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...  Google Podcasts: https://podcasts.google.com/feed/aHR0...   Amazon Music: https://music.amazon.com/podcasts/d97...   Podcast Addict:

Episode 179: Impact of intermittent fasting Impact on T2DMFuture Dr. Carlisle explains the physiology of fasting and how it can help revert type 2 diabetes. Dr. Arreaza adds details on how to do intermittent fasting. Written by Cameron Carlisle, MSIV, Ross University School of Medicine. Comments and edits by Hector Arreaza, MD, FAAFP.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.What is type 2 Diabetes Mellitus (T2DM)?-Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and impaired glucose regulation. -This impaired regulation can lead to hyperglycemia, contributing to complications in a myriad of organs: heart, kidneys, eyes, nerves, etc. (target organs). According to the CDC, more than 38 million Americans have T2DM (about 1/10 people). -Multiple mechanisms are believed to contribute to insulin resistance in obese patients with T2DM, such as increased lipid deposition throughout the body and systemic inflammation.What is Intermittent Fasting (IF)? Intermittent fasting (IF) has recently gained popularity as a dietary approach for health benefits, but it has been around for thousands of years. IF is an eating pattern that alternates between eating and fasting (no calories consumed) over a specific period of time. When you are fasting, you are allowed and encouraged to keep drinking water and non-caloric drinks, like coffee, tea, and even homemade bone broth.-According to the International Food Information Council Foundation (IFIC), 10% of Americans engage in IF daily. -According to Mark Mattson, a neuroscientist and IF expert for over 25 years, a mechanism called “metabolic switching” is seen with IF. This is when your body runs out of glucose and starts burning fat (i.e., fatty oxidation). These metabolic changes can help protect your organs and reduce the risk of chronic conditions, like T2DM. Common IF methods: Time-restricted eating: Most common method, involves eating within a specific time frame (e.g., the 16:8, 18:6, 12:12 method is also common.  [16:8 means you have 16 hours of fasting and 8 hours of eating.]Alternate-day fasting: Alternating between fasting days and normal eating days.  [Find more info in The Complete Guide to Fasting, by Jason Fung, who is a nephrologist, he explains that alternate-day is basically eating every other day, which would give 36 hours of fasting, but if you are a beginner you can try a 24 hours fasting, in short, not eating breakfast any day of the week and having lunch 4 days a week, and dinner every night.]5:2 diet (aka periodic fasting): Maintaining a normal diet for 5 days, with 2 days (usually non-consecutive) of caloric restriction (25% of normal caloric intake; e.g., 500 calorie meal). IF is strongly believed to improve metabolic health in individuals with T2DM by reducing insulin resistance via increasing insulin sensitivity, promoting weight loss (patients with obesity and DM… AKA patients with diabesity), and enhancing lipolysis via fat oxidation.While fasting, the body goes through several phases that affect how energy is metabolized. Between 0 and 4 hours after eating, the body enters a feeding state, using glucose as its main energy source. After fasting for 12-16 hours, the body enters ketosis and starts to use fat for energy. Within 24-36 hours, autophagy begins, a process that recycles damaged cells and allows for cellular repair. This process can have great benefits for people with T2DM, such as improved insulin sensitivity and glucose regulation. Pathophysiology of Implementing IF in T2DM. -IF is thought to increase insulin sensitivity by decreasing fatty tissue in the body (i.e., visceral adipose tissue), which is correlated to insulin resistance. Insulin resistance is defined as higher than normal circulating insulin levels needed for a glucose lower response, which is thought to be the culprit for the generation of T2DM. It means you need high levels of insulin to keep glucose normal. -Obesity is an important risk factor for T2DM. Visceral adipose tissue functions as an organ via the secretion of adipokines (cytokines or cellular messengers produced by adipose tissue): leptin and adiponectin. Leptin: proinflammatory, leading to chronic inflammation. Patients with higher BMI levels and increased insulin resistance were found to have increased leptin levels.[Leptin is a good hormone at normal levels, but there is leptin resistance] Adiponectin: anti-inflammatory and antidiabetic effects. Higher adiponectin levels result in decreased hepatic gluconeogenesis, enhanced glucose absorption, and enhanced skeletal muscle and hepatic fatty acid oxidation. Levels drop as visceral fat increases. -Dr. López-Jaramillo, a Colombian endocrinologist and researcher, and colleagues published a review in 2014 examining the imbalance in the levels of leptin and adiponectin in individuals with metabolic syndrome. This imbalance (increase in leptin and decrease in adiponectin) is linked to obesity and insulin resistance, which has been shown to increase the risk of T2DM. It has been shown that IF has resulted in the reduction of leptin levels and increased levels of adiponectin, which leads to decreased insulin resistance and increased insulin sensitivity. -IF allows pancreatic beta-cells to rest by not having to secrete insulin constantly. This allows the beta-cells of the pancreas to improve in function over time. In addition, IF has been shown to lead to noticeable weight loss and loss in body fat, both of which play an important contribution in managing T2DM. Research demonstrates that this weight loss increases insulin sensitivity and decreases the need for insulin therapy, making IF a powerful approach for improving metabolic health. AMP-Activated Protein Kinase (AMPK) and Its Role in IF and T2DM Recent research has highlighted an important enzyme seen in IF, AMP-activated protein kinase (AMPK), which plays a vital role as an important energy sensor in cells. It is activated when cellular energy levels are low, such as during IF. A 2020 research study in Nature Reviews Endocrinology explains that activation of AMPK aids in suppressing gluconeogenesis and stimulates fatty acid oxidation, leading to optimal energy balance and reduction of visceral adipose tissue accumulation, a major contributor to insulin resistance and T2DM progression. AMPK is upregulated during fasting, which enhances glucose metabolism and reduces insulin resistance. This is imperative in managing T2DM, as it counters the effects of insulin resistance associated with T2DM.Exercise, which also promotes AMPK activation, complements IF and can promote a synergistic effect in improving insulin sensitivity and promoting fat burning, New Research Findings on IF and T2DM -The EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study is a randomized clinical trial published in JAMA Network Open (2024). Findings In this randomized clinical trial study found that a time-restricted eating window significantly improved fasting glucose levels and HbA1c levels in individuals with T2DM. The study examined the effect of a 16-week 5:2 meal replacement (5:2 MR) fasting plan that consisted of five days of normal eating and 2 days, nonconsecutive of restricted diet (500-600 calories). This group was examined alongside a group of patients who took metformin 0.5 g BID and empagliflozin 10 mg QD. The study wanted to investigate the changes in HbA1c in Chinese adults with early T2DM.-The study was a randomized clinical trial of 405 adults, and a study showed that the 5:2 MR approach led to better glycemic control at 16 weeks compared to the counter treatments with metformin and empagliflozin. The 5:2 MR group had the greatest reduction in HbA1c (-1.9%), followed by metformin (-1.6%), and empagliflozin (-1.5%). The 5:2 MR plan also revealed the greatest weight loss (-9.7 kg), followed by empagliflozin (-5.8 kg), and metformin (-5.5 kg). -This research suggests IF, such as 5:2 MR, can be a powerful tool in the management of T2DM and improving metabolic health. This study can potentially open doors for healthcare providers to provide the 5:2 MR approach for individuals as an effective initial lifestyle intervention. However, follow-up studies are needed to assess the effectiveness and durability of the 5:2 MR.Safety and Risks of IF in T2DM. -IF when combined with glucose-lowering medications (e.g., insulin, sulfonylureas, GLP-1 agonists) can increase the risk of hypoglycemia. Also, prolonged fasting can lead to nutrient deficiencies if not planned carefully. Patients should be counseled on maintaining a balanced, nutritious diet during non-fasting days. -IF is not suitable for everyone. Children under the age of 18 should not try IF due to needing proper calories for adequate development and proper growth. Also, it is recommended that pregnant or breastfeeding women do not undergo IF. It is advised that people with eating disorders should not try IF. -Individuals with certain medical conditions, such as kidney stones or gastroesophageal disease should speak with their doctor before trying IF. Also, patients on insulin or other glucose-lowering medications should adjust their dose and talk with their healthcare providers to prevent hypoglycemia during fasting. It is recommended that each person speak with their doctor to discuss the safety and risks of IF and see if it would benefit the individual before starting IF. -Many studies have explored the benefits of IF at the micro level revealing its cellular benefits and on a macro level of the body as a whole. However, more research is needed to confirm the long-term effects of IF on glycemic control and its sustainability as a therapeutic approach for T2DM. Conclusion:-IF shows potential for improving glycemic control, promoting weight loss, and enhancing metabolic health in individuals with T2DM. Despite its benefits, IF may present with risks, such as hypoglycemia, nutrition deficiencies, or dehydration in certain patients. Therefore, it may not be suitable for all individuals. It's important to monitor patients who engage in IF, especially for patients with T2DM. Patients should follow up with their doctor for individualized IF plans in patients with T2DM. ______________This week we thank Hector Arreaza and Cameron Carlisle. Audio editing by Adrianne Silva.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:Albosta, Michael, and Jesse Bakke. “Intermittent Fasting: Is There a Role in the Treatment of Diabetes? A Review of the Literature and Guide for Primary Care Physicians - Clinical Diabetes and Endocrinology.” BioMed Central, BioMed Central, 3 Feb. 2021, doi.org/10.1186/s40842-020-00116-1.Blumberg, Jack, et al. “Intermittent Fasting: Consider the Risks of Disordered Eating for Your Patient - Clinical Diabetes and Endocrinology.” BioMed Central, BioMed Central, 21 Oct. 2023, https://clindiabetesendo.biomedcentral.com/articles/10.1186/s40842-023-00152-7.De Cabo, Rafael, and Mark P. Mattson. “Effects of intermittent fasting on health, aging, and disease.” New England Journal of Medicine, vol. 381, no. 26, 26 Dec. 2019, pp. 2541–2551, https://doi.org/10.1056/nejmra1905136.Guo, Lixin, et al. “A 5:2 intermittent fasting meal replacement diet and glycemic control for adults with diabetes.” JAMA Network Open, vol. 7, no. 6, 21 June 2024, https://doi.org/10.1001/jamanetworkopen.2024.16786.Herz, Daniel, et al. “Efficacy of Fasting in Type 1 and Type 2 Diabetes Mellitus: A Narrative Review.” Nutrients, U.S. National Library of Medicine, 10 Aug. 2023, www.ncbi.nlm.nih.gov/pmc/articles/PMC10459496/. Herzig, S., & Shaw, R. J. (2018). AMPK: Guardian of metabolism and mitochondrial homeostasis. Nature Reviews Molecular Cell Biology, 19(2), 121-135.Longo, V. D., & Mattson, M. P. (2014). Fasting: Molecular mechanisms and clinical applications. Cell Metabolism, 19(2), 181-192. https://doi.org/10.1016/j.cmet.2013.12.008López-Jaramillo P, Gómez-Arbeláez D, López-López J, et al. The role of leptin/adiponectin ratio in metabolic syndrome and diabetes. Hormone Molecular Biology and Clinical Investigation. 2014;18(1):37–45.Mattson, Mark P., et al. “Impact of intermittent fasting on health and disease processes.” Ageing Research Reviews, vol. 39, Oct. 2017, pp. 46–58, https://doi.org/10.1016/j.arr.2016.10.005. Patikorn, Chanthawat, et al. “Intermittent fasting and obesity-related health outcomes.” JAMA Network Open, vol. 4, no. 12, 17 Dec. 2021, https://doi.org/10.1001/jamanetworkopen.2021.39558.Sharma, Suresh K, et al. “Effect of Intermittent Fasting on Glycaemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” TouchREVIEWS in Endocrinology, U.S. National Library of Medicine, May 2023, www.ncbi.nlm.nih.gov/pmc/articles/PMC10258621/#:~:text=In%20IF%2C%20eating%20habits%20are,the%20risk%20of%20developing%20T2DM.Xiaoyu, Wen, et al. “The effects of different intermittent fasting regimens in people with type 2 diabetes: A network meta-analysis.” Frontiers in Nutrition, vol. 11, 25 Jan. 2024, https://doi.org/10.3389/fnut.2024.1325894. Theme song, Works All The Time by Dominik Schwarzer, YouTube ID: CUBDNERZU8HXUHBS, purchased from https://www.premiumbeat.com/.

Why do some people feel fine eating lots of carbs when others feel energy slumps? Is blood sugar to blame? In this episode, we learn why blood sugar varies so much between people, and the tools to manage these levels.  Tim Spector and Jessie Inchauspé (aka the Glucose Goddess) will discuss the latest science around glucose control, what the cool new device on the block – the CGM – can tell us and why blood sugar levels are only one part of the picture of our health. Jessie is a bestselling author and science communicator with a community of over 5 million followers. Tim is a professor of epidemiology at King's College London and ZOE's scientific co-founder.