Metabolic Health Summit

Lung cancer remains the leading cause of cancer-related deaths worldwide. There are new challenges for this disease with the emergence of the Epstein-Barr virus (EBV) as a potential contributor to its pathogenesis. While EBV is well-known for its role in nasopharyngeal carcinoma and Burkitt's lymphoma, its link to lung cancer is less established but gaining attention, particularly in immune-compromised or genetically predisposed individuals, warranting the need for further investigation, and nicely summarized in this review. EBV promotes tumor progression by reprogramming host cell metabolism through viral proteins like LMP1 and LMP2A. LMP1 enhances glycolysis by upregulating glucose transporters (GLUT1) and enzymes such as hexokinase 2 (HK2), mimicking the Warburg effect, which is often a hallmark of solid tumors. This shift supports rapid cancer cell growth while producing lactate, which suppresses immune responses by impairing T and natural killer cells. Additionally, LMP2A promotes glutaminolysis, converting glutamine into anabolic intermediates that are important for cancer cell survival. LMP1 also stabilizes HIF-1α under hypoxic conditions, further promoting tumor progression by shifting metabolism toward glycolysis and creating an immunosuppressive environment. Therapeutically, targeting EBV-driven metabolic pathways offers promising opportunities. Glycolysis inhibitors like 2-deoxyglucose and PKM2 modulators, alongside glutaminase inhibitors such as CB-839, can disrupt the metabolic dependencies of EBV-positive lung cancer cells. Combining these metabolic therapies with immunotherapies, like PD-1/PD-L1 checkpoint inhibitors, enhances the immune response against EBV-infected cells. Antiviral strategies, including lytic induction therapy, can also be beneficial by reactivating latent EBV to render cancer cells more susceptible to treatment. This emerging area of research highlights the evolving relationship between EBV infection, metabolic reprogramming, and immune evasion in lung cancer. Understanding these mechanisms paves the way for novel therapies, offering the potential for better outcomes in EBV-associated lung cancer.

??Could mitochondria hold the key to understanding and treating mental illness? Dr. Ana Andreazza is revolutionizing our understanding of bipolar disorder, mood regulation, and metabolic health through groundbreaking mitochondrial research. From 3D brain organoids to mitochondrial transplants, her work is unlocking new paths to personalized medicine. In this clip, Dr. Andreazza explains how mitochondrial dysfunction in psychiatric disorders stems from nuclear and mitochondrial genes failing to work together efficiently—like putting the wrong fuel in a car. Join The Metabolic Link as Dr. Dominic D'Agostino dives into the latest discoveries in mitochondrial function and its role in mood disorders and metabolism. ?? Listen on any major podcast player or watch the full episode on YouTube: https://lnkd.in/gmyBBsf5

?? New Episode Alert! We’ve just launched a powerhouse episode of The Metabolic Link podcast, featuring a group of leading experts from our Optimizing Metabolic Health Symposium panel discussion filmed at Metabolic Health Summit! This episode is packed with cutting-edge insights on metabolism, muscle preservation, fat loss, and long-term health! The panel includes Dr. Benjamin Bikman, Dr. Richard Johnson, Dr. Jonathan Jun, Dr. Nick Norwitz, Dave Feldman, and is hosted by Dr. Dominic D'Agostino. This episode dives into some of the biggest questions in metabolism, including: ?? The real impact of GLP-1 medications — how do they affect fat, muscle, and long-term metabolic health? ?? Does long-term dieting slow metabolism? And if so, can you reverse it? ?? Can diet and fasting improve neuropathy? ?? How does yo-yo dieting impact gut bacteria? Could it make weight loss harder? ?? High-protein diets & kidney health — should we be concerned? ?? LDL cholesterol & metabolic health — does high LDL mean high risk? ? Exercise & metabolism — how does being highly active change metabolic markers? In this clip, Dr. Ben Bikman shares his evolving views on GLP-1 agonists, including his concerns about long-term use and the potential for adipocyte hyperplasia (new fat cells). He also discusses his thoughts on pairing GLP-1s with a low-carb diet. If you’re looking for science-backed insights on metabolism, insulin resistance, energy balance, and longevity, this episode is a must-listen! Watch the full episode on our Metabolic Health Summit YouTube channel or listen on any major podcast player: https://lnkd.in/geepsED9

Join us for an exciting Live Q&A with Dr. Tomás Duraj, a physician-scientist with Dr. Thomas Seyfried's Lab at Boston College, specializing in cancer metabolism and ketogenic metabolic therapy! On Thursday, February 27th at 7 AM PT / 10 AM ET, Dr. Duraj will be joining Dr. Dominic D'Agostino for a Live Q&A on The Metabolic Initiative– a CME-centered platform dedicated exclusively to metabolic health and therapy. During the session, Dr. Duraj will dive into cancer metabolism and his groundbreaking research on ketogenic metabolic therapy for cancer. While a recent podcast explored the molecular mechanisms behind cancer metabolism, this live Q&A will focus on real-world applications and practical tips for implementing ketogenic metabolic therapy. It’s an opportunity to ask questions directly to Dr. Duraj and gain insights into the future of cancer treatment and metabolic oncology. Event Details: Date & Time: Thursday, February 27th at 7 AM PT / 10 AM ET Cost: FREE with a 7-day trial (cancel anytime) Recording: Available for registered participants To join, visit the link below to register. Space is limited, so be sure to secure your spot early! ?? https://lnkd.in/gdyitQ4Q

February is Heart Health Month, so let’s dive into some new research highlighting the important link between metabolic dysfunction and cardiovascular disease. A recent study published in Cardiovascular Diabetology investigated the relationship between insulin resistance (IR) and mortality in a large U.S. population. Conducted using data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018, the research compared four indices of IR: the triglyceride glucose index (TyG), metabolic score for insulin resistance (METS-IR), triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio, and the homeostatic model assessment of insulin resistance (HOMA-IR). The study analyzed 14,653 participants and found that METS-IR was the most significant predictor of both all-cause and cardiovascular mortality, particularly in individuals under 65 years old. While lower levels of METS-IR were associated with reduced mortality, higher levels increased the risk. Specifically, an inflection point was established at a METS-IR value of 41.33, beyond which mortality risk rose. The findings emphasize the importance of early identification of insulin resistance to prevent adverse health outcomes. Unlike the other indices which showed varying degrees of association with mortality, METS-IR consistently indicated significant risk across various analyses. This research supports the clinical application of METS-IR as a reliable marker for assessing insulin resistance and its potential implications for health management in the general population. As obesity rates rise, understanding and addressing insulin resistance becomes increasingly critical for improving public health outcomes. For more insights, check out the full article here: https://lnkd.in/ghFQtDxm

Can cancer be targeted at its metabolic roots? We've just released a new episode of The Metabolic Link on this topic??! This week, Dr. Dominic D'Agostino sits down with Dr. Tomás Duraj, a leading researcher in cancer metabolism, to discuss how targeting glucose and glutamine metabolism could transform cancer therapy. They explore: ? Why mitochondria play a central role in cancer development ? How the Warburg effect impacts tumor growth ? The potential of ketogenic metabolic therapy for glioblastoma ? Why combining metabolic interventions with standard care may be the future of oncology Don’t miss this fascinating deep dive into the latest research on cancer metabolism! ?? Listen on any major podcast player or watch now: https://lnkd.in/gAxh4BXB Be sure to also join Dr. Tomás Duraj in a Live Q&A on The Metabolic Initiative platform on February 27th at 7am PT/10am ET! Bring your questions about metabolic therapy for cancer. Your first 7 days are free: https://lnkd.in/gdyitQ4Q

Human genetic variants in the circadian clock gene PERIOD3 (PER3), specifically the P415A and H417R variants, are shedding new light on the biological mechanisms behind winter depression, also known as seasonal affective disorder (SAD). A recent study in Nature Metabolism investigates how genetic and environmental factors, such as shortened day length, interact to influence seasonal mood changes. The research used male mice genetically engineered to carry these human PER3 variants. Under winter-like photoperiods (4 hours of light and 20 hours of darkness), these mice exhibited significant depression-like behaviors, including increased despair and stress susceptibility. These behaviors were linked to disruptions in adrenal gland function, where the PER3 variants heightened sensitivity to ACTH (a hormone that stimulates corticosterone synthesis). This caused an overproduction of corticosterone, a glucocorticoid hormone important for stress responses. The excessive corticosterone levels had downstream effects on the brain, particularly in the dorsal raphe nucleus (DRN), a key region involved in mood regulation. Elevated glucocorticoid signaling suppressed the transcription of Tph2, the gene encoding an enzyme necessary for serotonin synthesis. The resulting serotonin deficiency was identified as a central driver of the observed depression-like behaviors. Importantly, the study found these effects were reversible. Light therapy, commonly used to treat SAD, and pharmacological treatments, such as serotonin reuptake inhibitors, successfully mitigated the behavioral changes in mice. Genetic interventions to restore Tph2 expression in the DRN also rescued the mood-related phenotypes. These findings establish a direct link between PER3 variants, adrenal gland dysfunction, and seasonal mood traits. This research highlights a novel pathway by which seasonal changes in day length influence mood, emphasizing the importance of glucocorticoid signaling in this process. Beyond understanding SAD, these findings could have larger implications for addressing mood disorders with seasonal patterns, offering potential targets for personalized treatments. Read the full paper here: https://lnkd.in/g45hqPGk

???New episode??! This week, we've just released Dr. Dominic D'Agostino's interview with Dr. Ian Lake on The Metabolic Link podcast! Diagnosed with type 1 diabetes at 36, Dr. Lake turned to a ketogenic diet for life-changing results. He shares his powerful journey, discusses insulin optimization, and as a physician, reveals how he helps others thrive with Type 1 diabetes through education and retreats. Whether you’re managing type 1 or exploring low-carb living, this episode is packed with the science on metabolic therapy and actionable insights. ?? Watch the full episode on YouTube or listen now on your favorite podcast player (link in bio): https://lnkd.in/gtMJZY6x

The study titled "The combined treatment with ketogenic diet and metformin slows tumor growth in two mouse models of triple-negative breast cancer" investigates a therapeutic approach targeting the metabolic vulnerabilities of hypoxic tumors, particularly those in triple-negative breast cancer (TNBC). These tumors are often resistant to conventional therapies due to their reliance on glucose-driven glycolysis, a survival adaptation to their poorly vascularized and oxygen-deprived microenvironments. Researchers used two TNBC mouse models: an orthotopic injection model using FVB mice and PyMT transgenic mice that spontaneously develop mammary tumors. Animals were divided into four treatment groups: control, ketogenic diet (K), metformin (M), and a combination of ketogenic diet with metformin (KM). Tumor growth rates, latency, overall survival, and glucose dependency were measured in vivo and further validated in vitro under simulated hypoxic conditions. Compared to the other groups, the combination of the ketogenic diet and metformin (KM) reduced tumor burden by 66%, slowed tumor growth by 38%, and extended tumor latency (the time to detectable tumor growth) by 36%. The combined treatment also extended median survival by 31 days, which translates to approximately three years in human terms. These effects were attributed to the significant reduction in systemic glucose levels achieved by the combination therapy, which deprives hypoxic tumor cells of their primary energy source. In vitro studies supported this mechanism, demonstrating that hypoxic TNBC cells depend on abnormally high glucose levels for survival, unlike normoxic cells. This research demonstrates the potential of combining a ketogenic diet and metformin to target glycolytic tumors like TNBC. By exploiting a metabolic vulnerability, this strategy could complement existing treatments and improve outcomes, not only for TNBC but for a range of cancers that are glycolytic. The findings highlight a promising direction for future cancer therapies, emphasizing the role of systemic glucose control in mitigating tumor progression. Read full paper: https://lnkd.in/giv_tm9B

We've just released a new episode of The Metabolic Link! At Metabolic Health Summit 2024, Chad Vanags stood before a room of clinicians, researchers, and innovators to share a perspective that’s often overlooked but deeply needed—that of the patient. Diagnosed with stage 4 lung cancer in July 2022 and given just 6 to 12 months to live, Chad instead shifted his focus on becoming metabolically, physically, and mentally elite. His presentation offers a powerful reminder of how patient voices can drive innovation, challenge assumptions, and inspire change in the field of metabolic health. In this episode of The Metabolic Link, Chad recounts his journey and the critical insights he’s uncovered about self-directed neuroplasticity, nutrition, and what it means to truly advocate for yourself. His story is a testament to the importance of integrating patient experiences into research and clinical practice. ?? Listen now and discover how Chad’s journey is paving the way for a more inclusive and innovative approach to metabolic health: https://lnkd.in/g4D7T_Fv