The Root Cause Medicine Podcast

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, MDDr. 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 FAQ1. 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 Moments00:01:41 Fullscript and whole-person care00:02:39 Introducing Medicine for All People00:03:09 How the book’s title and philosophy developed00:06:07 Family medicine, obstetrics, and community health00:07:18 How living conditions shaped Dr. Maker-Clark’s view of medicine00:10:00 Food as a central part of whole-person care00:11:02 Growing up with food and traditional practices00:13:19 Bringing nutrition back into clinical practice00:15:14 Culinary medicine and medical student education00:16:03 Bringing food education into Chicago public schools00:17:23 Plants, ancestral knowledge, and connection with the natural world00:20:29 Developing relationships with plants in everyday environments00:22:49 Plants and the history of medicines00:24:52 Nature, stress regulation, and belonging00:27:19 Access to nature as a health-equity issue00:31:26 Community as a medicine of connection00:35:16 Service, or seva, and connection with others00:41:31 Trust in healthcare relationships00:45:22 Rebuilding trust in the body during chronic illness00:46:39 Small practices for rebuilding self-trust00:49:21 Why dance, gratitude, and play are “medicines of spirit”00:50:36 Dance, movement, and neuroplasticity00:53:28 Dance as culture, ancestry, and expression00:54:27 Gratitude without toxic positivity00:58:22 Why adults still need play01:00:44 Different adult play personalities01:03:20 Play and social development01:05:56 Where to find Dr. Maker-Clark and her bookWant 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 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

Dr. Holly Lucille, ND, is joined by Ellie Abraham, PhD, to explain why two curcumin or Boswellia supplements may not be equivalent, even when the front of the label looks similar. The conversation covers boswellic acid standardization, AKBA, curcumin delivery systems, piperine, botanical sourcing, finished-product testing, certificates of analysis, and supply-chain controls. Research supports meaningful variation in Boswellia composition and curcumin formulations, making the specific extract and formulation relevant when interpreting product labels and published evidence. (Meins 2016) (Mimica 2022)Clinical Takeaways“Boswellic acids” describes a group of compounds. Boswellia preparations can contain different proportions of individual boswellic acids, including AKBA, KBA, and alpha- and beta-boswellic acids. Products with similar total boswellic acid claims therefore may not have identical chemical profiles. (Mannino 2016) (Meins 2016)Curcumin formulation matters. Conventional oral curcumin has low bioavailability, and formulations including phytosomes, liposomes, micelles, and piperine combinations have been studied as strategies to alter absorption. However, different formulations should not automatically be treated as interchangeable because comparative pharmacokinetic results vary. (Hegde 2023) (Fança-Berthon 2021)Standardization provides more information than an ingredient name alone. Botanical composition can vary with species, growing conditions, extraction, processing, and other supply-chain factors. Standardization and appropriate quality controls can help establish more consistent composition. (Ribnicky 2008) (Sarma 2021)Potency is only one part of quality. Botanical quality also involves identity, purity, contaminants, adulteration, and finished-product verification. Published investigations have identified labeling and authenticity concerns in both Boswellia and turmeric/curcumin products. (Meins 2016) (You 2022)Quality does not equal clinical fit. A well-characterized supplement still needs to be considered in the context of the individual patient, including the formulation, dose, supporting evidence, medication use, and potential botanical-drug interactions. (van Breemen 2008)Guest: Ellie Abraham, PhDEllie Abraham has a PhD in plant biology, with research focused on developing analytical methods for testing finished botanical products. Her background includes botanical chemistry, finished-product testing, standardization, and dietary supplement quality. In this episode, she explains how practitioners can look beyond an ingredient name to assess what a curcumin or Boswellia product is actually formulated to deliver.These five questions best match the broad topics addressed in the episode, particularly searches around Boswellia standardization, AKBA, curcumin absorption, piperine, and supplement quality. Exact search volume is not publicly available from a standard web search. These topics are also represented in published research on botanical quality and curcumin formulation.Clinician FAQ1. Are all Boswellia supplements the same?No. Boswellia products may differ in species, extract composition, total boswellic acid content, and concentrations of individual boswellic acids such as AKBA and KBA. A survey of commercial Boswellia supplements found substantial variation in composition and label compliance. (Meins 2016)2. What does boswellic acid standardization mean?It indicates that an extract is standardized to a stated amount of boswellic acids or, in some products, a particular constituent such as AKBA. Boswellia contains multiple boswellic acids, and their relative concentrations can vary by species and extract. (Mannino 2016) (Lauß 2024)3. Why is AKBA listed separately on some Boswellia products?AKBA, or 3-O-acetyl-11-keto-β-boswellic acid, is one individual boswellic acid that has received substantial pharmacologic research attention. Calling it out separately provides more specific compositional information than reporting total boswellic acids alone. (Ammon 2016)4. Why do curcumin supplements use phytosomes, liposomes, or piperine?Conventional oral curcumin has limited bioavailability. Phospholipid complexes, liposomal and micellar systems, and co-administration with piperine are among the approaches studied to alter its absorption and pharmacokinetics. Results vary by formulation, so an “enhanced absorption” format does not by itself establish that two products are equivalent. (Mirzaei 2017) (Heidari 2023) (Mimica 2022)5. How can practitioners assess curcumin and Boswellia supplement quality?Look beyond the ingredient name. Relevant product information may include botanical identity, extract and standardization details, branded ingredients tied to specific research, contaminant and adulteration testing, finished-product verification, and manufacturer transparency. Published studies have documented variability and authenticity concerns in commercial Boswellia and turmeric products. (Meins 2016) (You 2022)Timestamps / Key Moments00:00:36 Why familiar botanical names do not make products equivalent00:01:27 Understanding Boswellia and boswellic acid standardization00:02:05 Total boswellic acids and individual compounds00:03:47 Why the boswellic acid profile matters00:05:40 Matching botanical extracts to the supporting evidence00:06:09 Curcumin delivery methods and formulation differences00:07:12 Phospholipid-based curcumin formulations00:08:29 How piperine is used with curcumin00:10:43 Finished-product testing and label claims00:13:43 Heavy metals and synthetic curcumin concerns00:14:09 Understanding California Proposition 6500:16:40 Curcuminoid complexes and certificates of analysis00:18:18 How supply-chain controls affect botanical composition00:20:07 Why standardization matters from batch to batch00:21:05 What practitioners can look for when reviewing products00:22:40 Fullscript's approach to supplier and product quality reviewBotanicals and Compounds DiscussedBoswelliaBoswellia extractsBoswellic acidsAKBA (3-O-acetyl-11-keto-β-boswellic acid)Beta-boswellic acidTurmericCurcuminCurcuminoidsPiperinePhospholipidsQuality Methods and Documents DiscussedBotanical standardizationFinished-product testingIngredient identity verificationPotency testingHeavy-metal testingAdulteration screeningSynthetic curcumin testingCertificates of analysisBranded ingredient documentationRaw-material sourcingSupply-chain controlsExtraction methodsStability dataBatch-to-batch consistencySupplier and brand vettingWant 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 centralized system. For practitioners, Fullscript provides access to professional-grade supplements and practitioner education while incorporating quality review processes for brands and products offered through its catalog. The goal is not to replace clinical judgment, but to help practitioners make thoughtful, individualized decisions with clearer product and quality information.For more practitioner education on supplement quality and clinical decision-making, visit Fullscript Academy at academy.fullscript.com.DisclaimerThe 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. Dietary supplements may cause side effects or interact with medications. Patients should consult a qualified healthcare professional before changing their healthcare routine.ReferencesAmmon, H. P. T. (2016). Boswellic acids and their role in chronic inflammatory diseases. Advances in Experimental Medicine and Biology, 928, 291–327. https://pubmed.ncbi.nlm.nih.gov/27671822/Fança-Berthon, P., et al. (2021). Pharmacokinetics of a single dose of turmeric curcuminoids depends on formulation: Results of a human crossover study. The Journal of Nutrition, 151(7), 1802–1816. https://pubmed.ncbi.nlm.nih.gov/34363434/Hegde, M., Girisa, S., BharathwajChetty, B., Vishwa, R., & Kunnumakkara, A. B. (2023). Curcumin formulations for better bioavailability: What we learned from clinical trials thus far? ACS Omega, 8(12), 10713–10746. https://pubmed.ncbi.nlm.nih.gov/37008131/Heidari, H., Bagherniya, M., Majeed, M., Sathyapalan, T., Jamialahmadi, T., & Sahebkar, A. (2023). Curcumin-piperine co-supplementation and human health: A comprehensive review of preclinical and clinical studies. Phytotherapy Research, 37(4), 1462–1487. https://pubmed.ncbi.nlm.nih.gov/36720711/Lauß, J., Kappacher, C., Isser, O., Huck, C. W., & Rainer, M. (2024). Species-specific quantification of bioactive boswellic acids in Boswellia resin using NIR spectroscopy, HPLC and multivariate data analysis. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 316, 124384. https://pubmed.ncbi.nlm.nih.gov/38701576/Mannino, G., Occhipinti, A., & Maffei, M. E. (2016). Quantitative determination of 3-O-acetyl-11-keto-β-boswellic acid (AKBA) and other boswellic acids in Boswellia sacra and Boswellia serrata. Molecules, 21(10), 1329. https://pubmed.ncbi.nlm.nih.gov/27782055/Meins, J., Artaria, C., Riva, A., Morazzoni, P., Schubert-Zsilavecz, M., & Abdel-Tawab, M. (2016). Survey on the quality of the top-selling European and American botanical dietary supplements containing boswellic acids. Planta Medica, 82(6), 573–579. https://pubmed.ncbi.nlm.nih.gov/27054914/Mimica, B., Bučević Popović, V., Banjari, I., Jeličić Kadić, A., & Puljak, L. (2022). Methods used for enhancing the bioavailability of oral curcumin in randomized controlled trials: A meta-research study. Pharmaceuticals, 15(8), 939. https://pubmed.ncbi.nlm.nih.gov/36015087/ Mirzaei, H., Shakeri, A., Rashidi, B., Jalili, A., Banikazemi, Z., & Sahebkar, A. (2017). Phytosomal

What if metabolism and immune function aren’t separate systems, but part of one continuous conversation?In this episode of the Root Cause Medicine Podcast, Dr. Jeffrey Bland joins Kate Kresge to explore immunometabolism, the study of how immune activity and cellular metabolism influence one another. They discuss how inflammation can affect energy use across tissues, why metabolic health is about far more than weight, and how systems biology is changing the way clinicians think about chronic disease. (O'Neill 2016)Dr. Bland also introduces emerging inflammatory indices—including the Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI)—that can be derived from components of a routine CBC with differential. (Islam 2024) The conversation explores their potential role as contextual markers of inflammatory activity, while emphasizing how Journeys can help to automate CBC calculations and help create customized reports for practitioners using blood labs values, history, symptoms and more. The episode closes with a practical look at nutrition, polyphenol-rich foods, lifestyle medicine, large-scale health data, and the growing potential for personalized care.Clinical Takeaways from This EpisodeImmunometabolism connects immune signaling with cellular energy use. Immune cells alter their metabolic activity when activated, and immune-derived signals can influence the function of tissues throughout the body. (O'Neill 2016)Chronic inflammation is a systems-level process. Rather than viewing inflammation as an isolated problem within one organ, immunometabolism highlights communication among adipose tissue, the liver, brain, muscles, immune cells, and other tissues. (Burak 2024) (Juárez-Rojas 2024)A CBC may contain more information than clinicians traditionally use. SII and SIRI combine routinely measured blood-cell populations into indices being studied as markers of systemic inflammatory and immune activity. (Islam 2024) They should be interpreted in clinical context rather than used independently to diagnose disease or dictate treatment. (Mangoni 2024)Lifestyle interventions affect multiple biological systems at once. Dr. Bland discusses dietary patterns rich in diverse plant compounds alongside movement, sleep, and stress management as components of a broader approach to metabolic and immune health. (Koelman 2022)Practitioners can order Dr. Jeff Bland’s Immunometabolic Journey on Fullscript.comGuest IntroductionDr. Jeffrey Bland is a longtime leader in functional and systems-based approaches to health and one of the influential voices behind the development of functional medicine. His work focuses on translating complex biology—including immunology, metabolism, nutrition, genetics, and systems medicine—into clinically meaningful ways of thinking about health. In this conversation, he brings that systems perspective to immunometabolism and explores how clinicians may begin connecting familiar laboratory data with a deeper understanding of immune and metabolic function.FAQWhat is immunometabolism?Immunometabolism examines the two-way relationship between immune function and metabolism. Immune cells require energy to perform their functions, and changes in their metabolic state can influence inflammatory signaling and communication with other tissues. (O'Neill 2016)What are SII and SIRI?SII and SIRI are calculated indices derived from blood-cell counts commonly included in a CBC with differential. They have been studied across several clinical populations as markers associated with systemic inflammatory and immune activity, but they are nonspecific and should be interpreted alongside the broader clinical picture. (Islam 2024)Can SII or SIRI diagnose chronic inflammation?No single index can establish the cause or clinical significance of inflammation on its own. These measures may provide additional context, but symptoms, medical history, other laboratory findings, medications, acute illness, and underlying conditions can all influence blood-cell counts. (Mangoni 2024)Why does mitochondrial function come up in a discussion about immunity?Immune activation changes cellular energy demands. Because mitochondria and other metabolic pathways help determine how cells generate and use energy, cellular metabolism is closely connected with immune-cell behavior. (O'Neill 2016)How can practitioners order a CBC with SIRI and SII calculations included?Ordering a CBC and other biomarkers included in the Immuno-Metabolic Journey from Dr. Jeff Bland allows for automatic calculation of SIRI and SII, as well as recommending next steps for clinicians depending on findings. Timestamps02:22 — What immunometabolism meansWhy immune function and metabolism can no longer be viewed as separate biological systems.06:15 — From “angry fat” to systems biologyHow communication between immune cells and adipose tissue helped shape modern thinking about immunometabolism.09:31 — Immunometabolism and root-cause thinkingLooking upstream from organ dysfunction toward the processes that may be influencing it.17:23 — Metabolism is more than weightCellular energy production, mitochondria, inflammation, and why metabolic function affects the entire body.22:01 — What a routine CBC may revealMoving beyond gross abnormalities to explore patterns within the CBC with differential.23:20 — Introducing SII and SIRIHow researchers combine neutrophils, lymphocytes, platelets, and monocytes into inflammatory indices.34:06 — Translating biomarkers into whole-person careNutrition, polyphenols, movement, sleep, and stress management enter the conversation.39:27 — Why food complexity mattersDr. Bland uses buckwheat to illustrate the diversity of plant polyphenols.46:38 — Big data and personalized medicineHow large health datasets may help researchers identify more individualized biological patterns.54:43 — Owning your healthDr. Bland closes with a message about agency, personalization, and creating healthier patterns over time.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 hosts and guests and don’t necessarily reflect those of Fullscript or any affiliated organizations. This podcast is for informational and educational purposes only and is not intended to be medical advice. For your safety, always check with your doctor or healthcare provider before making changes to your health routine.CitationsBurak, M. F., Stanley, T. L., Lawson, E. A., Campbell, S. L., Lynch, L., Hasty, A. H., Domingos, A. I., Dixit, V. D., Hotamışlıgil, G. S., Sheedy, F. J., Dixon, A. E., Brinkley, T. E., Hill, J. A., Donath, M. Y., & Grinspoon, S. K. (2024). Adiposity, immunity, and inflammation: Interrelationships in health and disease—A report from the 24th Annual Harvard Nutrition Obesity Symposium, June 2023. The American Journal of Clinical Nutrition, 120(1), 257–268. https://www.sciencedirect.com/science/article/abs/pii/S0002916524004556Islam, M. M., Osoydan Satici, M., & Eroglu, S. E. (2024). Unraveling the clinical significance and prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and delta neutrophil index: An extensive literature review. Turkish Journal of Emergency Medicine, 24(1), 8–19. https://pubmed.ncbi.nlm.nih.gov/38343523/Juárez-Rojas, J. G., Reyes-Barrera, J., & Medina-Urrutia, A. X. (2024). Adipose tissue immunometabolism: Unveiling the intersection of metabolic and immune regulation. Revista de Investigación Clínica, 76(2), 65–79. https://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0034-83762024000200001Koelman, L., Egea Rodrigues, C., & Aleksandrova, K. (2022). Effects of dietary patterns on biomarkers of inflammation and immune responses: A systematic review and meta-analysis of randomized controlled trials. Advances in Nutrition, 13(1), 101–115. https://pmc.ncbi.nlm.nih.gov/articles/PMC8803482/Mangoni, A. A., & Zinellu, A. (2024). The diagnostic role of the systemic inflammation index in patients with immunological diseases: A systematic review and meta-analysis. Clinical and Experimental Medicine, 24(1), Article 27. https://link.springer.com/article/10.1007/s10238-024-01294-3O'Neill, L. A. J., Kishton, R. J., & Rathmell, J. (2016). A guide to immunometabolism for immunologists. Nature Reviews Immunology, 16(9), 553–565. https://pubmed.ncbi.nlm.nih.gov/27396447/Zeevi, D., Korem, T., Zmora, N., Israeli, D., Rothschild, D., Weinberger, A., Ben-Yacov, O., Lador, D., Avnit-Sagi, T., Lotan-Pompan, M., Suez, J., Mahdi, J. A., Matot, E., Malka, G., Kosower, N., Rein, M., Zilberman-Schapira, G., Dohnalová, L., Pevsner-Fischer, M., … Segal, E. (2015). Personalized nutrition by prediction of glycemic responses. Cell, 163(5), 1079–1094. https://www.cell.com/cell/fulltext/S0092-8674(15)01481-6

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 patientsEpisode HighlightsWhen the obvious answers have already been exploredRobyn 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 autoimmunityThe 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 findingTesting 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.

What if some of the immune activity we’re looking for isn’t showing up where we expect to find it?In this episode, I sit down with Robyn Puglia of Cyrex Laboratories to explore TG6, lymphocyte patterns, and early autoimmunity—and specialized testing many practitioners may not realize is available through Cyrex Wheat Burden panel, the Lymphocyte Map, and Array 5.We look at neurological manifestations of gluten-related disease, what different immune cell populations may add to the clinical picture, and how autoantibodies can sometimes appear before autoimmune disease is diagnosed.The bigger question: Can seeing more of the immune story help us ask better questions about what may be driving a complex presentation?What You’ll LearnWhy gluten reactivity isn’t always a gut story. TG6 has been studied in gluten-related neurological disorders, particularly gluten ataxia. (Hadjivassiliou 2019) We discuss why neurological symptoms may belong in the gluten conversation and what Cyrex Wheat Burden Panel is designed to investigate beyond conventional celiac markers. (Mearns 2019)What your lymphocyte count may not tell you. T cells, B cells, natural killer cells, and their subsets have different jobs. Robyn explains how the Cyrex Lymphocyte Map looks at these populations and how patterns may help practitioners decide what to investigate next.Why autoimmunity may start before the diagnosis. Disease-associated autoantibodies can precede clinical disease in several autoimmune conditions. (Ma 2017) We explore Cyrex Array 5, tissue-associated autoantibodies, and what these earlier immune signals may—and may not—tell us. (Frazzei 2022)Meet Robyn PugliaRobyn Puglia’s work with celiac disease, neurological symptoms, autoimmunity, and complex chronic illness pushed her to ask what the immune system might be telling us beyond a routine workup. Today, as Vice President of Practitioner Education at Cyrex Laboratories, she teaches practitioners how to think about specialized immune testing without treating an abnormal biomarker as a diagnosis.FAQWhat is TG6, and why does it matter?Most practitioners know tissue transglutaminase 2 (TG2) from celiac testing. Tissue transglutaminase 6 (TG6) has been studied in gluten-related neurological disorders, particularly gluten ataxia. (Hadjivassiliou 2019)TG6 isn’t part of routine guideline-supported celiac screening, but it highlights an important point: gluten-related immune disease can have extraintestinal manifestations, including neurological symptoms. (Mearns 2019) (Rubio-Tapia 2023)What is Cyrex Wheat Burden Panel?The Wheat Burden panel evaluates antibody reactivity to multiple wheat-associated antigens and transglutaminases, including TG6.It provides a broader look at wheat-associated immune reactivity than conventional celiac serology. It shouldn’t replace established evaluation for celiac disease or wheat allergy; the value of additional biomarkers depends on the clinical question and the evidence supporting their intended use. (Rubio-Tapia 2023) (Leonard 2017)What can the Lymphocyte Map show?The Cyrex Lymphocyte Map examines populations and subsets of T cells, B cells, and natural killer cells.Instead of asking whether one value is simply high or low, Robyn looks at the pattern and asks what might explain it. Infection? Medication effects? Immune dysfunction? Another clinical process?The pattern isn’t the diagnosis. It helps sharpen the investigation.Can autoimmunity start before the diagnosis?Yes. In several autoimmune diseases, researchers have detected disease-associated autoantibodies before patients meet formal diagnostic criteria—sometimes years earlier. (Ma 2017)Cyrex Array 5 evaluates multiple tissue-associated autoantibodies that Robyn discusses in this context. But an autoantibody isn’t a crystal ball. Its significance depends on the specific marker, the patient, and the evidence supporting its clinical use. (Ma 2017)Does Cyrex offer all of these tests?Yes. Cyrex offers the specialized tests discussed in this episode, including Wheat Burden Panel, the Lymphocyte Map, and Array 5, along with additional testing related to mucosal immunity and barrier function.The important question isn’t, “How much can I test?”It’s “What am I trying to understand, and will this result change what I do next?”Timestamps02:42 — The patients who pulled Robyn deeper into immunologyHow celiac disease and unexplained illness changed her approach to complex patients.11:41 — TG6: When gluten becomes a brain conversationWhy gluten-related immune activity isn’t necessarily confined to the gut.13:49 — Are we asking enough questions about wheat?The thinking behind Cyrex Wheat Burden Panel and its broader look at wheat-associated antigens and transglutaminases.28:29 — What if autoimmunity starts before the diagnosis?Tissue-associated autoantibodies, Array 5, and preclinical autoimmunity.33:49 — Your lymphocyte count isn’t the whole storyT cells, B cells, natural killer cells, and the Cyrex Lymphocyte Map.39:25 — The abnormal result is where the investigation startsHow immune patterns can generate better clinical questions.44:20 — Stop looking for one perfect root causeRobyn’s “aggregate gains” approach to complex illness.50:49 — What else can we see in the immune system?Tissue autoantibodies, mucosal immunity, and barrier biomarkers.57:42 — When neurological symptoms change the workupWhy brain symptoms may require a broader metabolic, vascular, and immune picture.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.CitationsFrazzei, G., van Vollenhoven, R. F., de Jong, B. A., Siegelaar, S. E., & van Schaardenburg, D. (2022). Preclinical autoimmune disease: A comparison of rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and type 1 diabetes. Frontiers in Immunology, 13, 899372. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281565/Hadjivassiliou, M., Croall, I. D., Zis, P., Sarrigiannis, P. G., Sanders, D. S., Aeschlimann, P., Grünewald, R. A., Armitage, P. A., Connolly, D., Aeschlimann, D., & Hoggard, N. (2019). Neurologic deficits in patients with newly diagnosed celiac disease are frequent and linked with autoimmunity to transglutaminase 6. Clinical Gastroenterology and Hepatology, 17(13), 2678–2686. https://www.cghjournal.org/article/S1542-3565(19)30278-2/fulltextLeonard, M. M., Sapone, A., Catassi, C., & Fasano, A. (2017). Celiac disease and nonceliac gluten sensitivity: A review. JAMA, 318(7), 647–656. https://jamanetwork.com/journals/jama/article-abstract/2648637Ma, W. T., Chang, C., Gershwin, M. E., & Lian, Z. X. (2017). Development of autoantibodies precedes clinical manifestations of autoimmune diseases: A comprehensive review. Journal of Autoimmunity, 83, 95–112. https://www.sciencedirect.com/science/article/abs/pii/S0896841117303542Mearns, E. S., Taylor, A., Thomas Craig, K. J., Puglielli, S., Cichewicz, A. B., Leffler, D. A., Sanders, D. S., Lebwohl, B., & Hadjivassiliou, M. (2019). Neurological manifestations of neuropathy and ataxia in celiac disease: A systematic review. Nutrients, 11(2), 380. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412791/Rubio-Tapia, A., Hill, I. D., Semrad, C., Kelly, C. P., Greer, K. B., Limketkai, B. N., & Lebwohl, B. (2023). American College of Gastroenterology guidelines update: Diagnosis and management of celiac disease. The American Journal of Gastroenterology, 118(1), 59–76. https://pubmed.ncbi.nlm.nih.gov/36602836/