#533: Making Sense of Omega-3 Supplement Trials – Prof. JoAnn Manson, MD, DrPH

When discussing cardiovascular health, few topics stir as much debate as cholesterol, particularly in relation to low-carb and ketogenic diets. Recently, there’s been significant attention given to a proposed model that suggests high LDL cholesterol may not pose the same cardiovascular risk in certain individuals, specifically those labeled as “lean mass hyper-responders.” This raises important questions: Is it possible that high cholesterol might not be dangerous for everyone? Or are we witnessing a dangerous misinterpretation of the science? In this episode, we break down the ideas behind the “lipid energy model” and explore how it has been framed in the context of low-carbohydrate and ketogenic diets. While proponents claim this model sheds light on how some people can have elevated LDL without increasing heart disease risk, critics warn that miscommunication and oversimplification of these ideas are leading many down a dangerous path. With real-world health decisions hanging in the balance, it’s crucial to carefully examine what the science truly says about cholesterol, inflammation, and heart disease. Join us as we dive into the evidence with Dr. Gary McGowan. We’ll dissect what the current research supports, what remains speculative, and how social media has amplified both the promising and problematic aspects of this model. If you’ve ever wondered about the impact of high cholesterol on heart disease risk in the context of ketogenic or low-carb diets, this episode is essential listening. Timestamps 02:27 What are the “Lean Mass Hyper Responder” phenotype and the “Lipid Energy Model” 27:29 Looking at recent publications and the “KETO Trial” 47:06 Public communication and misinterpretation 51:18 Clinical implications of diet-induced dyslipidemia 55:14 Responsibility in scientific communication 57:30 Real-world examples of poor communication or misinterpretation 01:13:27 Ethical concerns with the promotion of the model 01:25:59 Final thoughts Related Resources Go to episode page Join the Sigma email newsletter for free Subscribe to Sigma Nutrition Premium Enroll in the next cohort of our Applied Nutrition Literacy course Find Dr. McGowan at: Triage Method Instagram: @drgarymcgowan Papers discussed in this episode: Norwitz et al., 2022 – The Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate-Restricted Diets Norwitz et al., 2021 – Elevated LDL Cholesterol with a Carbohydrate-Restricted Diet: Evidence for a “Lean Mass Hyper-Responder” Phenotype KETO Trial: Budoff et al., 2024 – Carbohydrate Restriction-Induced Elevations in LDL-Cholesterol and Atherosclerosis

Fasting has gained immense popularity as a dietary approach, but what does the scientific evidence say about its health benefits? Studies have explored how fasting might influence metabolic markers, energy expenditure, and even aging. However, while fasting shows promise in some animal models, translating these effects to humans is less clear. A key part of the debate centers on whether fasting offers unique health advantages or whether its benefits stem primarily from reduced calorie intake. Time-restricted eating and intermittent fasting protocols show promise in regulating appetite and reducing energy intake, potentially leading to weight loss. But, when calories are controlled, does fasting still improve health independently? This episode explores the evidence to determine if fasting confers metabolic advantages over non-fasting diets. In addition, we’ll take a look at its impact on behavioral patterns and ask if that could play a pivotal role in promoting better health outcomes. To listen to this episode in full, subscribe to Sigma Nutrition Premium. Timestamps: [00:54] Defining fasting [03:44] Historical context and early research [08:01] Mechanisms and claims of fasting [18:15] Types of fasting protocols [22:18] Time-restricted eating and chronobiology [28:29] Energy expenditure and behavioral changes [36:53] Fasting vs. weight loss: independent benefits [41:47] Health markers and weight loss outcomes [43:37] Muscle mass concerns during fasting [47:31] Animal models vs. human studies [51:29] InterFAST study insights [01:00:37] Behavioral vs. metabolic changes [01:11:25] So what do we know? Links: Subscribe to Sigma Nutrition Premium Join the Sigma email newsletter for free Enroll in the next cohort of our Applied Nutrition Literacy course Go to the page for this episode

Body image and self-worth are deeply intertwined concepts that influence how we see ourselves and interact with the world. Many people believe that changing their physique is the key to improving their body image, but is it really that simple? This connection between appearance and self-esteem raises important questions about how we define confidence and whether our sense of worth should be tied to how we look. Our relationship with food plays a crucial role in how we view ourselves. While some see food as fuel, others attach much more significance to their eating habits, often linking dietary choices to discipline, success, or failure. But what happens when these beliefs become too rigid? Understanding how our perceptions of food and body image are shaped is essential for navigating the balance between health, happiness, and personal fulfillment. Physique change, often seen as a positive goal, can bring about unexpected psychological impacts. Pursuing a leaner or more muscular body might boost temporary feelings of confidence, but could it also reinforce negative patterns of thought? In an episode co-hosted with Dr. Eric Trexler, Danny talks with Dr. Gabrielle Fundaro in order to tackle some of these concepts and questions. Timestamps: [04:54] Start of conversation [06:40] Defining body image and self esteem [12:26] Relationship with food and weight controllability beliefs [20:38] Impact of body composition on body image [27:40] Challenges in changing body image perceptions [34:43] Influence of coaches on client body image [41:57] Screening for disordered eating [51:50] Ethical responsibilities of fitness professionals [54:53] Improving body image without physique change [61:02] Key ideas segment (premium-only) Links: Join the Sigma email newsletter for free Subscribe to Sigma Nutrition Premium Get more of Dr. Trexler’s research analysis with the MASS Research Review Related previous episodes: See episodes 484 and 367

Some suggest that, since individual lifts or short-duration efforts don’t rely heavily on glycogen, carb intake might not be critical for strength athletes. If glycogen depletion isn’t a pressing issue, could athletes thrive on lower-carb diets without sacrificing performance? Or could there be overlooked benefits to having greater carbohydrate availablily in those sessions? In strength sports and resistance training, do carbohydrates play an important role or not? Are carbohydrates really necessary for resistance training? How does training volume, intensity and goals impact the carbohydrate requirement? In this episode, Dr. Cliff Harvey and Dr. Eric Helms offer their perspectives on this interesting and practically important issue. Timestamps: [00:03:40] Do carbohydrates have a role in resistance training? [00:12:23] Do individuals respond differently? [00:18:25] Recent research insights [00:35:08] Carbohydrate “sensing” and performance [00:47:17] How to think about carbohydrate needs [00:54:06] Changing views on nutrient timing [01:06:37] Ketogenic diets and muscle gain [01:22:02] Dietary patterns and health – Are macronutrients that important? [01:31:42] Key ideas segment (Premium-only) Links: Subscribe to Premium for study notes and transcript Receive the email newsletter for free Join the waitlist for our Applied Nutrition Literacy course Sports Nutrition Association Get more of Dr. Helm’s research analysis with the MASS Research Review SigmaNutrition.com

Omega-3 fatty acids are often viewed as beneficial or, at worst, neutral supplements when it comes to supporting cardiovascular health, lowering triglycerides, and offering anti-inflammatory effects. Much of the focus in recent years has centered on understanding how significant these benefits are, particularly for heart health, with many studies highlighting the potential for omega-3s to play a positive role in reducing cardiovascular risk. However, an emerging concern has complicated the conversation around omega-3 supplementation. Several large trials, including the REDUCE-IT and STRENGTH trials, have suggested that omega-3 supplementation might be linked to an increased risk of atrial fibrillation (AF), a common cardiac arrhythmia characterized by an irregular and often rapid heart rate. These findings have sparked debate over whether omega-3s could contribute to this potentially serious heart condition, leaving clinicians and health-conscious individuals uncertain about the safety of these supplements. However, not all the research supports this elevated risk. This discrepancy raises important questions about how we interpret the data from various studies, the design of those trials, and whether other factors might be influencing these results. Understanding this issue in depth is crucial for making informed decisions about omega-3 supplementation and its potential risks and benefits. In this episode we walk through the studies and the key points to consider. Timestamps: 00:30 Updates on Alan’s upcoming study 05:06 Atrial Fibrillation and Omega-3 14:52 RCTs and AFib: Key Studies 29:14 Meta-Analyses and Dose-Response 46:46 Practical Implications and Recommendations 53:53 Key Ideas Segment (Premium-only) Links: Join the Sigma email newsletter for free Subscribe to Sigma Nutrition Premium Go to episode page

This is an “ask me anything” (AMA) episode with Dr. Stephan Guyenet, an expert in obesity neuroscience and eating behavior. This episode was originally published on Sigma Nutrition Premium. If you’re interested in subscribing to Sigma Nutrition Premium, then check all the details here. Questions Answered: [04.27] If we surgically remove adipose tissue, do leptin levels suddenly drop? How would this impact hunger over time? [06.56] How does chronic energy restriction (or following a crash diet) affect long-term appetite regulation? [13.21] How do anorexia and pronounced obesity defy the rules of metabolic compensation? [24.12] Why do some SDRIs (serotonin–dopamine reuptake inhibitors) reduce hunger/appetite? [28.02] Can an algorithm really decipher someone’s “ideal weight? [33.08] Could the “brain microbiome” impact appetite regulation and/or obesity? [35.34] In our current environment, are the only efficacious interventions drugs and bariatric surgery? [46.01] What should we make of claims by Gary Taubes about insulinogenic foods? [52.37] Is there a maximum duration someone should spend in fat loss (or weight gain) phases? [53.43] Why do some people struggle to gain weight? Links: Join our newsletter Subscribe to Premium View our recommended resources

Questions Answered in This Episode [02:28] Caffeine metabolism and individual variation. [14:47] High-sodium electrolyte supplements & recreational trainees. [32:55] Is a “too low” BMI a problem? [41:38] Are claims about vegan diets being nutritionally insufficient overblown? [51:33] Familial hypercholesterolemia & further lipid-lowering [58:05] Menopause, resistenace training and progressive overload [01:11:56] Does body weight matter if someone has healthy behaviours? This episode is one of our Premium-exclusive AMA (ask me anything) episodes, where we answer questions submitted by Premium subscribers. To listen to the full episode, you’ll need to be a Premium subscriber and access the episode on the private Premium feed. Otherwise, you can hear the first question on the public feed of the podcast. Links: Subscribe to Premium Enroll in our course, Applied Nutrition Literacy Learn more about Sigma Nutrition

In the world of combat sports, optimizing performance extends beyond physical training and nutrition—sleep plays a critical role. Maladaptive sleep behaviors, such as inconsistent sleep schedules and inadequate sleep duration, can significantly impair an athlete’s performance by reducing cognitive function, reaction time, and recovery ability. Understanding these impacts is crucial for athletes and coaches seeking to enhance performance through more effective sleep strategies. One of the key challenges combat sports athletes face is managing the effects of shift work and irregular event timings, which often conflict with typical training schedules. What are some strategies to mitigate these challenges, such as adjusting sleep schedules in advance? And what are the implications of jet lag for athletes traveling to major competitions? While technology offers valuable tools for tracking sleep, there are potential drawbacks, including reliance on inaccurate data or the psychological effects of constant monitoring. By educating athletes and coaches on best practices for sleep, they can make informed adjustments to training regimens, ultimately enhancing overall performance. In this episode, sleep scientist Dr. Ian Dunican discusses his work related to understanding and improving sleep behaviors in combat sports athletes. Timestamps: 01:43 Introduction to the Episode 04:38 Discussion on Recent Research Paper 09:52 Sleep Behaviors in Athletes 13:11 Questionnaire and Study Findings 20:38 Common Sleep Disorders in Athletes 33:23 Impact of Training Schedules on Sleep 34:25 Practical Tips for Better Sleep 41:17 Phases of Training and Their Importance 42:31 Understanding Chronotypes and Sleep Habits 45:19 Wearable Devices and Sleep Tracking 53:05 Practical Advice for Coaches and Athletes 59:03 Travel, Jet Lag, and Sleep for Athletes Links: Enroll in the next cohort of our Applied Nutrition Literacy course Go to episode page (with links to studies in this episode) Dr. Dunican's course (20% off with code MELIUS20) Learn more about Sigma Nutrition Subscribe to Premium

To many, meta-analyses are seen as a research tool that is often regarded as the pinnacle of evidence in nutrition science. But is this accurate? What exactly makes a meta-analysis reliable or flawed? How can we distinguish between a well-conducted study and one that might mislead even the most well-intentioned reader? In this episode, through three concrete examples, we explore the fundamental principles of meta-analyses, focusing on key aspects such as study selection, heterogeneity, and effect sizes. We discuss how these elements can significantly impact the conclusions drawn from a meta-analysis and what you should look out for when interpreting their results. Whether you’re a nutrition professional, a researcher, or simply someone interested in the science behind dietary guidelines, this discussion will help you navigate the often murky waters of meta-analytic research. Timestamps: 05:14 Understanding Meta-Analyses 12:11 Example 1: Dairy Consumption and Health 39:06 Example 2: Meta-Analysis on Carbohydrate Intake 54:59 Example 3: Meta-Analysis on Intermittent Fasting 01:02:44 Challenges in Meta-Analysis of Intermittent Fasting 01:13:56 Key Ideas Segment (Premium-only) Links: Enroll in the next cohort of our Applied Nutrition Literacy course Meta-analyses discussed in the episode: Example 1: Dairy Consumption and Health Example 2: Meta-Analysis on Carbohydrate Intake Example 3: Meta-Analysis on Intermittent Fasting Subscribe to Sigma Nutrition Premium

The debate between animal-based and plant-based meat alternatives (PBMAs) has garnered significant attention, especially concerning their impact on cardiovascular health. As PBMAs become increasingly popular, questions about their nutritional profiles and long-term health implications have emerged. Are these alternatives genuinely healthier than traditional meat, or do their highly processed nature and high sodium content undermine potential benefits? This discussion is crucial as dietary choices increasingly influence public health policies and consumer behaviors. Dr. Matthew Nagra’s recent review in the Canadian Journal of Cardiology sheds light on these issues by analyzing the nutritional differences between PBMAs and meat. The review highlights the potential cardiovascular benefits of PBMAs, such as lower levels of saturated fat and cholesterol, alongside higher fiber content. However, the review also points out the significant variability in PBMAs’ nutritional content, raising questions about standardization and consumer guidance. Understanding these differences is key to making informed dietary decisions and shaping future food industry practices. With growing consumer interest and public health implications, several pertinent questions arise: How do different PBMAs compare in their nutritional impact? What role does food processing play in their health outcomes? How can consumers make the best choices given the variability in PBMAs? In our discussion, Dr. Nagra will cover all these details, providing a comprehensive look at the current state of PBMAs and their role in a healthy diet. Timestamps: 01:59 Introducing Dr. Matthew Nagra 10:48 Nutritional Profiles of Plant-Based Meat Alternatives 14:39 Cardiovascular Risk Factors and Review Findings 21:17 Public Perception and Criticisms 25:10 Practical Advice for Choosing Plant-Based Meat Alternatives 34:29 Future Research Directions 43:51 Key Ideas Segment (Premium-only)   Links: Subscribe to Sigma Nutrition Premium Go to episode page Receive our free weekly email: the Sigma Synopsis Enroll in the next cohort of our Applied Nutrition Literacy course