The Root Cause Medicine Podcast

The Root Cause Medicine Podcast

By Rupa Health

In each episode, we’ll meet renowned medical experts, specialists and pioneers who’ve influenced the way certain conditions and diseases are understood and treated. We focus on giving you the informat... more

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  1. Number 1: C15:0, ferroptosis, and metabolic health: What practitioners should know

    Dr. Lara Zakaria is joined by Stephanie Venn-Watson, DVM, MPH, to explore emerging research on pentadecanoic acid (C15:0), an odd-chain saturated fatty acid initially studied through research involving bottlenose dolphins. The conversation connects C15:0 with cell-membrane composition, lipid peroxidation, ferroptosis, iron metabolism, metabolic health, and steatotic liver disease. It also examines research on circulating C15:0 as a biomarker associated with cardiometabolic outcomes and early human trials of C15:0 supplementation. (Imamura 2018) (Sawh 2021) C15:0 has been proposed as a candidate essential fatty acid, however, that classification and a specific human “C15:0 deficiency syndrome” remain emerging hypotheses rather than established clinical diagnoses. Clinical TakeawaysFerroptosis is an iron-dependent form of regulated cell death. First characterized in 2012, ferroptosis involves iron-dependent lipid peroxidation and differs mechanistically from apoptosis and other forms of cell death. (Dixon 2012) Polyunsaturated fatty acids in phospholipids are particularly relevant substrates for ferroptotic lipid peroxidation. (Yang 2016)C15:0 is an odd-chain saturated fatty acid being studied for metabolic effects. Pentadecanoic acid, or C15:0, is found in dairy fat and smaller amounts in other foods. Higher circulating C15:0 has been associated with lower incidence of type 2 diabetes in prospective observational research, but these associations do not establish that C15:0 itself prevents diabetes. (Imamura 2018)Calling C15:0 an “essential fatty acid” remains an emerging scientific proposal. Experimental work has proposed C15:0 as a candidate essential fatty acid based on dietary exposure, biological activity, and associations between circulating levels and health outcomes. More research is needed before C15:0 can be treated as equivalent to the established essential fatty acids linoleic acid and alpha-linolenic acid. (Venn-Watson 2020) (Venn-Watson 2022) Metabolic hyperferritinemia is a recognized clinical framework, but it is not synonymous with ferroptosis or C15:0 deficiency. Metabolic hyperferritinemia describes elevated ferritin occurring with metabolic dysfunction. Ferritin is also an acute-phase reactant, so elevated values require evaluation in clinical context rather than being interpreted as tissue iron overload by themselves. (Valenti 2023)Human C15:0 supplementation evidence is early. Within this broader metabolic context, circulating C15:0 is an emerging biomarker of interest. In a small 12-week randomized, placebo-controlled trial in young adults with overweight or obesity, 200 mg/day oral C15:0 significantly increased circulating C15:0 concentrations. Exploratory analyses suggested that participants who achieved post-treatment circulating C15:0 concentrations above 5 µg/mL had greater reductions in ALT and AST and a greater increase in hemoglobin; these achieved-level findings were not definitive treatment effects and require replication in larger trials designed for liver and hematologic outcomes. (Robinson 2024)Diet and lifestyle remain the better-established foundation for metabolic and liver health. Dairy fat is the principal dietary source of C15:0, although circulating odd-chain fatty acids may also be influenced by endogenous production. (Weitkunat 2017) For people who avoid or tolerate little dairy, C15:0 supplementation is an emerging option that may be useful alongside high-fiber, Mediterranean-style minimally processed dietary patterns, regular exercise, metabolic-risk reduction, and appropriate evaluation and treatment of fatty liver disease or abnormal iron markers. (Chooi 2024) Guest: Stephanie Venn-Watson, DVM, MPH Stephanie Venn-Watson is a veterinary epidemiologist whose research has included comparative medicine and the health of bottlenose dolphins cared for through the U.S. Navy Marine Mammal Program. Research involving dolphins identified similarities in metabolic and age-associated physiology that led investigators to study odd-chain saturated fatty acids, including C15:0 and C17:0. Her subsequent research has focused on the biological activity of C15:0 and the hypothesis that inadequate C15:0 may contribute to cellular vulnerability. Some of this research is connected with patents and commercial C15:0 products, making independent replication and larger human clinical trials particularly important when interpreting the findings. Clinician FAQ 1. What is C15:0? C15:0, or pentadecanoic acid, is a 15-carbon odd-chain saturated fatty acid. It occurs in foods including dairy fat and has historically been studied as a biomarker related to dairy-fat intake. (Imamura 2018) More recent research is examining whether C15:0 itself has biologically relevant metabolic effects. (Venn-Watson 2020) 2. Is C15:0 an essential fatty acid? Not yet by established nutritional consensus. C15:0 has been proposed as a candidate essential fatty acid, but this remains an emerging area of research. (Venn-Watson 2020) (Venn-Watson 2022) Linoleic acid and alpha-linolenic acid remain the conventionally recognized essential fatty acids in human nutrition. 3. What is ferroptosis? Ferroptosis is a regulated, iron-dependent form of cell death characterized by damaging lipid peroxidation. (Dixon 2012) The process involves interactions among cellular iron, oxidizable membrane phospholipids, and antioxidant defense systems. Ferroptosis is being investigated across metabolic, neurologic, cardiovascular, liver, and cancer biology. 4. Is high ferritin evidence that a patient is undergoing ferroptosis? No. Ferritin reflects iron storage but is also an acute-phase reactant. Elevated ferritin can occur with inflammation, liver disease, metabolic dysfunction, infection, malignancy, iron overload, and other conditions. (Valenti 2023) Ferroptosis cannot be diagnosed from serum ferritin alone. 5. What is metabolic hyperferritinemia? Metabolic hyperferritinemia describes elevated serum ferritin occurring in the context of metabolic dysfunction. A published consensus framework proposes ferritin above 300 ng/mL in men or 200 ng/mL in women together with specified metabolic criteria, while excluding or reassessing alternative explanations for hyperferritinemia. (Valenti 2023) The framework also distinguishes hyperferritinemia from confirmed tissue iron accumulation. (Liu 2024) 6. Does elevated ferritin mean a patient needs phlebotomy? Not necessarily. The metabolic hyperferritinemia consensus states that evidence supporting routine iron-depletion therapy is insufficient. (Valenti 2023) Phlebotomy should not be inferred from ferritin alone; evaluation of the cause of hyperferritinemia and, when appropriate, tissue iron burden is important. 7. What foods contain C15:0? Dairy fat is one dietary source of C15:0, and C15:0 is also present in smaller amounts in some meats, fish, and other foods. Circulating odd-chain fatty acids are not exclusively determined by dairy intake. Research also suggests that endogenous pathways involving gut-derived propionate can contribute to odd-chain fatty acid production. (Weitkunat 2017) 8. Does eating more full-fat dairy increase C15:0? Dietary dairy fat can contribute to circulating C15:0, but the health implications of increasing full-fat dairy cannot be reduced to C15:0 alone. Dairy foods contain multiple fatty acids, proteins, carbohydrates, minerals, and other components, and observational evidence differs by dairy-food type. (Imamura 2018) (Sawh 2021) Dietary recommendations should therefore consider the patient's overall diet and clinical context. 9. What has human supplementation research shown? Human evidence remains limited. One randomized trial studied 200 mg/day of C15:0 for 12 weeks in 30 young adults with overweight or obesity and found increased circulating C15:0. (Robinson 2024) A separate randomized trial evaluated 300 mg/day as an addition to an Asian-adapted Mediterranean-style diet in women with fatty liver and reported an additional reduction in LDL cholesterol and an increase in Bifidobacterium adolescentis abundance. (Chooi 2024) Neither study establishes C15:0 supplementation as treatment for metabolic disease, ferroptosis, or metabolic hyperferritinemia. 10. Can C15:0 levels be used as a clinical treatment target? A standardized clinical target has not been established. Thresholds such as 5 μg/mL or 0.2% of total fatty acids have been proposed and explored in C15:0 research, but they should not currently be treated as universally validated diagnostic thresholds for deficiency or treatment targets. (Robinson 2024) (Venn-Watson 2024) Timestamps / Key Moments 00:00:18 Introducing C15:0, cellular aging, and ferroptosis 00:02:19 Stephanie Venn-Watson’s background and dolphin research 00:05:29 How C15:0 emerged from metabolomics research 00:10:20 Alzheimer’s disease-like pathology in dolphins 00:11:33 What C15:0 is and how fatty acids are classified 00:18:18 C15:0, membrane stability, and lipid peroxidation 00:19:25 Understanding ferroptosis 00:24:34 Metabolic hyperferritinemia and clinical patterns 00:27:37 Proposed C15:0 thresholds and metabolic research 00:30:43 Dietary sources of C15:0 00:40:19 Measuring circulating C15:0 00:45:49 Human clinical research on C15:0 Fatty acids and biological processes discussedPentadecanoic acid (C15:0)Heptadecanoic acid (C17:0)Odd-chain saturated fatty acidsSaturated fatty acidsPolyunsaturated fatty acidsLinoleic acidAlpha-linolenic acidEPADHACell-membrane lipidsLipid peroxidationFerroptosisReactive oxygen speciesMitochondrial functionIron metabolismFerritin Clinical markers and conditions discussedFerritinTransferrin saturationHemoglobinRed blood cell distribution width (RDW)ALTASTGGTLipid peroxidationLDL cholesterolGlucoseInsulinMetabolic hyperferritinemiaInsulin resistanceType 2 diabetesMetabolic syndromeMASLDMASHIron overloadCognitive decline Want to elevate your practice? This episode is sponsored by Fullscript, a comprehensive care delivery platform designed to support whole-person, integrative healthcare. Fullscript helps practitioners bring supplement dispensing, lab ordering, patient education, and care planning into a centralized workflow. The goal is not to replace clinical judgment, but to support thoughtful, individualized care and reduce unnecessary administrative steps. For more practitioner education on supplement quality, metabolic health, and clinical decision-making, visit Fullscript Academy. Disclaimer The views expressed on this podcast are those of the host and guest and do not necessarily reflect those of Fullscript or affiliated organizations. This episode is for informational and educational purposes only and is not medical advice. C15:0 research is evolving. C15:0 is not currently an established treatment for ferroptosis, metabolic hyperferritinemia, diabetes, MASLD, MASH, or neurodegenerative disease. Elevated ferritin has multiple potential causes and should be interpreted in clinical context. Patients should consult a qualified healthcare professional before changing their diet, supplements, iron intake, or treatment plan. ReferencesChooi, Y. C., Zhang, Q. A., Magkos, F., Ng, M., Michael, N., Wu, X., Brok Volchanskaya, V. S., Lai, X., Wanjaya, E. R., Elejalde, U., Goh, C. C., Yap, C. P. L., Wong, L. H., Lim, K. J., Velan, S. S., Yaligar, J., Muthiah, M. D., Chong, Y. S., Loo, E. X. L., … Eriksson, J. G. (2024). Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: The TANGO randomized controlled trial. American Journal of Clinical Nutrition, 119(3), 788–799. https://pubmed.ncbi.nlm.nih.gov/38035997/Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., Morrison, B., III, & Stockwell, B. R. (2012). Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell, 149(5), 1060–1072. https://pubmed.ncbi.nlm.nih.gov/22632970/Imamura, F., Fretts, A., Marklund, M., Ardisson Korat, A. V., Yang, W.-S., Lankinen, M., Qureshi, W., Helmer, C., Chen, T.-A., Wong, K., Bassett, J. K., Murphy, R., Tintle, N., Yu, C. I., Brouwer, I. A., Chien, K.-L., Frazier-Wood, A. C., del Gobbo, L. C., Djoussé, L., … Forouhi, N. G. (2018). Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. PLOS Medicine, 15(10), e1002670. https://pubmed.ncbi.nlm.nih.gov/30303968/Liu, W.-Y., Lian, L.-Y., Zhang, H., Chen, S.-D., Jin, X.-Z., Zhang, N., Ye, C.-H., Chen, W.-Y., Goh, G. B. B., Wang, F.-D., Miele, L., Corradini, E., Valenti, L., & Zheng, M.-H. (2024). A population-based and clinical cohort validation of the novel consensus definition of metabolic hyperferritinemia. Journal of Clinical Endocrinology & Metabolism, 109(6), 1540–1549. https://pubmed.ncbi.nlm.nih.gov/38124275/Robinson, M. K., Lee, E., Ugalde-Nicalo, P. A., Skonieczny, J. W., Chun, L. F., Newton, K. P., & Schwimmer, J. B. (2024). Pentadecanoic acid supplementation in young adults with overweight and obesity: A randomized controlled trial. Journal of Nutrition, 154(9), 2763–2771. https://pubmed.ncbi.nlm.nih.gov/39069269/Sawh, M. C., Wallace, M., Shapiro, E., Goyal, N. P., Newton, K. P., Yu, E. L., Bross, C., Durelle, J., Knott, C., Gangoiti, J. A., Barshop, B. A., Gengatharan, J. M., Meurs, N., Schlein, A., Middleton, M. S., Sirlin, C. B., Metallo, C. M., & Schwimmer, J. B. (2021). Dairy fat intake, plasma C15:0, and plasma iso-C17:0 are inversely associated with liver fat in children. Journal of Pediatric Gastroenterology and Nutrition, 72(4), e90–e96. https://pubmed.ncbi.nlm.nih.gov/33399331/Vacher, M. C., Durrant, C. S., Rose, J., Hall, A. J., Spires-Jones, T. L., Gunn-Moore, F., & Dagleish, M. P. (2023). Alzheimer's disease-like neuropathology in three species of oceanic dolphin. European Journal of Neuroscience, 57(7), 1161–1179. https://pubmed.ncbi.nlm.nih.gov/36514861/Valenti, L., Corradini, E., Adams, L. A., Aigner, E., Alqahtani, S., Arrese, M., Bardou-Jacquet, E., Bugianesi, E., Fernandez-Real, J.-M., Girelli, D., Hagström, H., Henninger, B., Kowdley, K., Ligabue, G., McClain, D., Lainé, F., Miyanishi, K., Muckenthaler, M. U., Pagani, A., … Zoller, H. (2023). Consensus statement on the definition and classification of metabolic hyperferritinaemia. Nature Reviews Endocrinology, 19(5), 299–310. https://pubmed.ncbi.nlm.nih.gov/36805052/Venn-Watson, S., Smith, C. R., Stevenson, S., Parry, C., Daniels, R., Jensen, E., Cendejas, V., Balmer, B., Janech, M., Neely, B. A., & Wells, R. (2013). Blood-based indicators of insulin resistance and metabolic syndrome in bottlenose dolphins (Tursiops truncatus). Frontiers in Endocrinology, 4, 136. https://pubmed.ncbi.nlm.nih.gov/24130551/Venn-Watson, S., Parry, C., Baird, M., Stevenson, S., Carlin, K., Daniels, R., Smith, C. R., Jones, R., Meegan, J., Simmons, J., Gomez, F., & Jensen, E. D. (2015). Increased dietary intake of saturated fatty acid heptadecanoic acid (C17:0) associated with decreasing ferritin and alleviated metabolic syndrome in dolphins. PLOS ONE, 10(7), e0132117. https://pubmed.ncbi.nlm.nih.gov/26200116/Venn-Watson, S., Lumpkin, R., & Dennis, E. A. (2020). Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: Could it be essential? Scientific Reports, 10, 8161. https://pubmed.ncbi.nlm.nih.gov/32424181/Venn-Watson, S. K., & Butterworth, C. N. (2022). Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems. PLOS ONE, 17(5), e0268778. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0268778Venn-Watson, S. (2024). The cellular stability hypothesis: Evidence of ferroptosis and accelerated aging-associated diseases as newly identified nutritional pentadecanoic acid (C15:0) deficiency syndrome. Metabolites, 14(7), 355. https://www.mdpi.com/2218-1989/14/7/355Weitkunat, K., Schumann, S., Nickel, D., Hornemann, S., Petzke, K. J., Schulze, M. B., Pfeiffer, A. F. H., & Klaus, S. (2017). Odd-chain fatty acids as a biomarker for dietary fiber intake: A novel pathway for endogenous production from propionate. American Journal of Clinical Nutrition, 105(6), 1544–1551. https://pubmed.ncbi.nlm.nih.gov/28424190/Yang, W. S., Kim, K. J., Gaschler, M. M., Patel, M., Shchepinov, M. S., & Stockwell, B. R. (2016). Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proceedings of the National Academy of Sciences, 113(34), E4966–E4975. https://pubmed.ncbi.nlm.nih.gov/27506793/

    55min
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  2. Number 2: Medicine for All People: Food, Nature, Community, and Joy as Part of Whole-Person Care

    Dr. Geeta Maker-Clark joins the Root Cause Medicine Podcast to discuss ideas from her book, Medicine for All People: Science and Ancient Wisdom for Revolutionary Healing. Drawing from family medicine, integrative medicine, culinary medicine, community health and her own upbringing, she explores a broader view of medicine that includes food, plants, nature, community, service, trust, dance, gratitude, and play. The conversation centers on a simple idea: health is shaped not only by what happens in the clinic, but also by the environments, relationships, resources, cultural traditions, and daily practices that surround a person. Dr. Maker-Clark organizes these ideas into three areas—medicines of the earth, medicines of connection, and medicines of spirit—and discusses how practitioners can think about them alongside conventional medical care. Clinical TakeawaysFood and nutrition are part of whole-person care. Dr. Maker-Clark describes food as a central part of her clinical philosophy and discusses culinary medicine as a way to combine nutrition education with practical cooking skills. Her University of Chicago culinary medicine work includes medical students, community members, and middle school students, with an emphasis on nutrition literacy, accessibility, and culturally relevant food education. (Maker-Clark 2023)Nature exposure may support stress regulation and mental well-being. The episode frames time outdoors and connection with the natural environment as accessible ways to support well-being. Research has associated nature exposure with lower perceived and physiologic stress, although study designs, settings, and outcomes vary. (Shuda 2020)Social connection deserves attention in clinical assessment. Dr. Maker-Clark emphasizes community, belonging, and service as dimensions of health. Research supports associations between loneliness and social isolation and adverse cardiovascular, brain, mental health, and inflammatory outcomes, although mechanisms and the effectiveness of specific interventions continue to be studied. (Cené 2022) (Smith 2020)Trust includes both healthcare relationships and self-trust. The conversation explores how previous negative healthcare experiences, chronic illness, and unexplained symptoms can affect trust. Dr. Maker-Clark describes rebuilding trust through relationships and small, achievable commitments rather than treating trust as something patients should simply provide.Dance combines movement, cognition, emotion, and often social interaction. Dance is presented as an accessible form of joyful movement rather than a replacement for clinical care. Research suggests dance can influence cognitive and neuroplasticity-related outcomes, particularly in older adults, although effects vary by population and intervention. (Teixeira-Machado 2019) (Hewston 2021)Gratitude and play can be viewed as practices that support well-being. Gratitude interventions have shown generally modest benefits for well-being and some psychological outcomes. (Diniz 2023) (Kerry 2023) Adult play can take many forms, including creativity, competition, collecting, storytelling, exploration, and restorative activities. (Blanche 2024) Guest: Geeta Maker-Clark, MD Dr. Geeta Maker-Clark is a family and integrative medicine physician whose work spans patient care, nutrition education, culinary medicine, and community health. In the episode, she describes early clinical work in high-risk obstetrics and underserved communities as formative in expanding her understanding of health beyond the clinic. She co-developed culinary medicine programming connected with the University of Chicago, including medical student education and community-based nutrition programs. Her book, Medicine for All People: Science and Ancient Wisdom for Revolutionary Healing, brings together themes of ancestral knowledge, scientific research, social justice, connection, and accessible approaches to well-being. Clinician FAQ 1. What does Dr. Maker-Clark mean by “medicine for all people”? She uses the phrase to describe a broader framework for health that includes conventional medicine alongside food, nature, relationships, community, cultural knowledge, and everyday practices. Accessibility and social justice are central themes in the framework. 2. What is culinary medicine? Culinary medicine combines nutrition education with practical food preparation and cooking skills. In the program discussed in the episode, medical students learn nutrition counseling and cooking skills while community and middle school programs focus on nutrition literacy, food preparation, food justice, and culturally relevant education. (Maker-Clark 2023) 3. What does research say about nature exposure and stress? Research generally supports an association between exposure to natural environments and improvements in some measures of perceived and physiological stress. Results vary across studies, and the effects depend on factors such as the population, type of nature exposure, comparison environment, and outcome measured. (Shuda 2020) 4. Why are loneliness and social connection clinically relevant? Social isolation and loneliness have been associated with poorer cardiovascular and brain health and with some inflammatory markers. However, loneliness and objective social isolation are distinct concepts, and evidence does not establish that every health effect attributed to social disconnection operates through inflammation. (Cené 2022) (Smith 2020) 5. Can dance support brain health? Dance combines physical movement with rhythm, learning, coordination, and sometimes social interaction. Systematic reviews have reported changes in cognitive and neuroplasticity-related outcomes, particularly among middle-aged and older adults. The magnitude of benefit and the cognitive domains affected vary across studies. (Teixeira-Machado 2019) (Hewston 2021) (Fong Yan 2024) 6. Does practicing gratitude improve mental health? Gratitude interventions have been associated with small improvements in well-being and, in some studies, psychological symptoms. Results are heterogeneous, and gratitude should be viewed as a supportive practice rather than a substitute for appropriate mental healthcare. (Diniz 2023) (Kerry 2023) Timestamps / Key Moments 00:01:41 Fullscript and whole-person care 00:02:39 Introducing Medicine for All People 00:03:09 How the book’s title and philosophy developed 00:06:07 Family medicine, obstetrics, and community health 00:07:18 How living conditions shaped Dr. Maker-Clark’s view of medicine 00:10:00 Food as a central part of whole-person care 00:11:02 Growing up with food and traditional practices 00:13:19 Bringing nutrition back into clinical practice 00:15:14 Culinary medicine and medical student education 00:16:03 Bringing food education into Chicago public schools 00:17:23 Plants, ancestral knowledge, and connection with the natural world 00:20:29 Developing relationships with plants in everyday environments 00:22:49 Plants and the history of medicines 00:24:52 Nature, stress regulation, and belonging 00:27:19 Access to nature as a health-equity issue 00:31:26 Community as a medicine of connection 00:35:16 Service, or seva, and connection with others 00:41:31 Trust in healthcare relationships 00:45:22 Rebuilding trust in the body during chronic illness 00:46:39 Small practices for rebuilding self-trust 00:49:21 Why dance, gratitude, and play are “medicines of spirit” 00:50:36 Dance, movement, and neuroplasticity 00:53:28 Dance as culture, ancestry, and expression 00:54:27 Gratitude without toxic positivity 00:58:22 Why adults still need play 01:00:44 Different adult play personalities 01:03:20 Play and social development 01:05:56 Where to find Dr. Maker-Clark and her book Want to elevate your practice? This episode is sponsored by Fullscript, a comprehensive care delivery platform designed to support whole-person, integrative healthcare. Fullscript allows clinicians to streamline supplement dispensing, lab ordering, and patient education in one free, centralized system—helping reduce administrative burden while supporting clinical decision-making. For practitioners, Fullscript offers access to professional-grade supplements, evidence-informed protocols, and lab integrations that can support more efficient planning and follow-up. For patients, it provides a clear, organized way to receive recommendations, manage refills, and stay engaged in their care. The goal is not to replace clinical judgment, but to make it easier for clinicians to focus on what matters most: thoughtful, individualized patient care. Disclaimer The views expressed on this podcast are those of the host and guest and do not necessarily reflect those of Fullscript or affiliated organizations. This episode is for informational and educational purposes only and is not medical advice. Practices discussed in the episode should not replace individualized medical assessment or treatment. Patients should consult a qualified healthcare professional before making changes to their healthcare routine. ReferencesMaker-Clark G, McHugh A, Shireman H, et al. Empowering Future Physicians and Communities on Chicago’s South Side through a 3-Arm Culinary Medicine Program. Nutrients. 2023;15(19):4212.Shuda Q, Bougoulias ME, Kass R. Effect of nature exposure on perceived and physiologic stress: A systematic review. Complement Ther Med. 2020;53:102514.Smith KJ, Gavey S, Riddell NE, Kontari P, Victor C. The association between loneliness, social isolation and inflammation: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2020;112:519–541.Cené CW, Beckie TM, Sims M, et al. Effects of Objective and Perceived Social Isolation on Cardiovascular and Brain Health: A Scientific Statement From the American Heart Association. J Am Heart Assoc. 2022.Teixeira-Machado L, Arida RM, de Jesus Mari J. Dance for neuroplasticity: A descriptive systematic review. Neurosci Biobehav Rev. 2019;96:232–240.Hewston P, Kennedy CC, Borhan S, et al. Effects of dance on cognitive function in older adults: a systematic review and meta-analysis. Age Ageing. 2021;50(4):1084–1092.Fong Yan A, Nicholson LL, Ward RE, et al. The Effectiveness of Dance Interventions on Psychological and Cognitive Health Outcomes Compared with Other Forms of Physical Activity: A Systematic Review with Meta-analysis. Sports Med. 2024.Diniz G, Korkes L, Tristão LS, et al. The effects of gratitude interventions: a systematic review and meta-analysis. Einstein (São Paulo). 2023.Kerry N, Chhabra R, Clifton JDW. Being Thankful for What You Have: A Systematic Review of Evidence for the Effect of Gratitude on Life Satisfaction. Psychol Res Behav Manag. 2023;16:4799–4816.Blanche EI, Chang MC, Parham LD. Experiences of Adult Play. Am J Occup Ther. 2024;78(4).

    1h 7min
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  3. Number 3: One Hidden Immune Trigger Everyone Misses: A Complex Autoimmune Case Study

    What happens when a patient with multiple autoimmune conditions has already addressed the obvious contributors—but continues to experience flares? In this Root Cause Medicine Podcast case study, Dr. Kate Kreske sits down with clinical nutritionist and IFM-certified practitioner Robyn Puglia to explore a complex case involving polyautoimmunity and persistent immune dysregulation. The patient had already worked with multiple practitioners and undergone extensive evaluation, including assessments related to gut health, food reactivity, mold, and stress. Yet something was still being missed. Robyn explains how additional testing shifted her attention away from the gut and toward an unexpected area: the respiratory tract. She walks through how those findings changed her clinical thinking, why complex cases sometimes require practitioners to reconsider their assumptions, and what happened when the care plan was adjusted based on this new information. The conversation offers an important reminder for practitioners: deeper testing can sometimes provide useful clues, but results need to be interpreted within the broader clinical picture rather than treated as a diagnosis on their own. Key TakeawaysHow Robyn approaches highly complex patients who have already addressed many common contributorsWhy gut health should not automatically be assumed to be the primary driver of every autoimmune presentationHow testing identified a respiratory microbial pattern that had not been clinically obviousWhy laboratory findings are most useful when interpreted alongside symptoms, history, prior testing, and the overall clinical pictureHow unexpected findings can change clinical decision-making in complex casesWhy an individual case can illustrate clinical reasoning without establishing that the same testing or intervention will produce similar outcomes in other patients Episode Highlights When the obvious answers have already been explored Robyn describes her practice as serving patients at the “zebra” or even “unicorn” stage—people who have often seen multiple experienced practitioners and already addressed common areas such as nutrition, metabolic health, circadian rhythms, stress, and gut health. Looking beyond the gut in autoimmunity The featured patient had four autoimmune conditions and continued experiencing immune dysregulation and flares despite significant previous investigation and improvement. Rather than assuming the gastrointestinal tract remained the primary contributor, Robyn expanded the investigation. An unexpected respiratory finding Testing suggested a respiratory tract microbial pattern despite the absence of obvious respiratory symptoms. This finding shifted Robyn's clinical hypothesis and became an important part of how she approached the case. Practitioner TakeawayWhen a complex patient has already addressed the most plausible contributors but continues to experience symptoms, repeating the same investigation may not provide the missing answer. Consider stepping back and asking whether another system, exposure, infection, or contributor deserves evaluation. At the same time, avoid allowing a single specialized test result to become the new explanation for the entire case. Use testing to inform clinical reasoning alongside the patient's history, symptoms, conventional evaluation, and other relevant findings. Want to elevate your practice? This episode is sponsored by Fullscript, a comprehensive care delivery platform designed to support whole-person, integrative healthcare. Fullscript allows clinicians to streamline supplement dispensing, lab ordering, and patient education in one free, centralized system—helping reduce administrative burden while supporting clinical decision-making. For practitioners, Fullscript offers access to professional-grade supplements, evidence-informed protocols, and lab integrations that can support more efficient planning and follow-up. For patients, it provides a clear, organized way to receive recommendations, manage refills, and stay engaged in their care. The goal is not to replace clinical judgment, but to make it easier for clinicians to focus on what matters most: thoughtful, individualized patient care. DisclaimerThe views expressed on this podcast are those of the hosts and the guests, and they don't necessarily reflect the views of FullScript or any affiliated organizations. This podcast is for informational and educational purposes only, and it's not intended to be medical advice. For your safety, always check with your healthcare provider before making any changes to your healthcare routine.

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  4. Number 4: The Top Causes of Mental Health with Brendan Vermeire: Episode Rerun

    In this episode, Brendan Vermeire talks about mental health, from depression, anxiety, and neuroinflammation to dementia and Alzheimer's. They dive into: 1. Debunking the classic psychiatric narrative 2. Inflammation and mental health symptoms 3. The role of neuroplasticity in mental health 4. How does the microbiome affect mental health? 5. The Mental M.A.P. Brendan is a mental and metabolic health researcher, functional medicine educator, board-certified holistic practitioner, personal trainer, writer, speaker, and host of The Holistic Savage podcast. He is also the owner and founder of the Metabolic Solutions Institute for Functional Health and Fitness Practitioners and the Metabolic Solutions Research & Education Foundation, a not-for-profit foundation dedicated to "changing the way the world views mental health" through advancing the science of mental health dysfunction.

    57min
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  5. Number 5: 10 New Oxidative Stress & Gut Health Biomarkers to Know

    In this episode of the Root Cause Medicine Podcast, Dr. Kate Kresge welcomes back Dr. Cheryl Burdette—naturopathic physician, educator, and founder of Precision Point Diagnostics—for a deep dive into one of the most evidence-backed biomarker bundles in functional medicine: the Gut, Oxidation & Stress panel. Dr. Burdette explains how ten underutilized but highly predictive biomarkers—including anti-LPS antibodies, zonulin, 8OHdG, F2-isoprostanes, glutathione, and more—can give clinicians a full-body snapshot of inflammation, leaky gut, immune dysregulation, and oxidative stress. She discusses how each marker ties into chronic conditions from cardiovascular disease to autoimmunity to neuroinflammation—and exactly how to intervene when these labs are out of range. This is a must-listen masterclass for any practitioner working with chronic illness, mystery symptoms, or “normal” labs that don’t tell the whole story. You’ll Hear Them Discuss: - Why LPS antibodies are one of the most predictive markers in medicine today - How oxidative stress contributes to cardiovascular disease, autoimmunity, and brain fog - What 8OHdG, zonulin, secretory IgA, and glutathione tell us about barrier integrity - The surprising links between gut dysfunction and GLP-1, mood, and immune balance - Case studies showing biomarker-guided interventions that worked - How to boost glutathione (and what forms work best) - When to re-test and what lab shifts to look for - Advanced testing for food sensitivity: IgG subclasses, complement, and tolerance vs. reactivity - Natural GLP-1 agonists, bitters, fiber, and bile as part of metabolic healing

    59min
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