The Root Cause Medicine Podcast

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 Takeaways
Ferroptosis 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 discussed
Pentadecanoic acid (C15:0)
Heptadecanoic acid (C17:0)
Odd-chain saturated fatty acids
Saturated fatty acids
Polyunsaturated fatty acids
Linoleic acid
Alpha-linolenic acid
EPA
DHA
Cell-membrane lipids
Lipid peroxidation
Ferroptosis
Reactive oxygen species
Mitochondrial function
Iron metabolism
Ferritin

Clinical markers and conditions discussed
Ferritin
Transferrin saturation
Hemoglobin
Red blood cell distribution width (RDW)
ALT
AST
GGT
Lipid peroxidation
LDL cholesterol
Glucose
Insulin
Metabolic hyperferritinemia
Insulin resistance
Type 2 diabetes
Metabolic syndrome
MASLD
MASH
Iron overload
Cognitive 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.

References
Chooi, 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.0268778
Venn-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/2218-1989/14/7/355
Weitkunat, 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/

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 Takeaways
Food 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.

References
Maker-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).

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, PhD
Ellie 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 FAQ

1. 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 Moments
00:00:36 Why familiar botanical names do not make products equivalent
00:01:27 Understanding Boswellia and boswellic acid standardization
00:02:05 Total boswellic acids and individual compounds
00:03:47 Why the boswellic acid profile matters
00:05:40 Matching botanical extracts to the supporting evidence
00:06:09 Curcumin delivery methods and formulation differences
00:07:12 Phospholipid-based curcumin formulations
00:08:29 How piperine is used with curcumin
00:10:43 Finished-product testing and label claims
00:13:43 Heavy metals and synthetic curcumin concerns
00:14:09 Understanding California Proposition 65
00:16:40 Curcuminoid complexes and certificates of analysis
00:18:18 How supply-chain controls affect botanical composition
00:20:07 Why standardization matters from batch to batch
00:21:05 What practitioners can look for when reviewing products
00:22:40 Fullscript's approach to supplier and product quality review

Botanicals and Compounds Discussed
Boswellia
Boswellia extracts
Boswellic acids
AKBA (3-O-acetyl-11-keto-β-boswellic acid)
Beta-boswellic acid
Turmeric
Curcumin
Curcuminoids
Piperine
Phospholipids

Quality Methods and Documents Discussed
Botanical standardization
Finished-product testing
Ingredient identity verification
Potency testing
Heavy-metal testing
Adulteration screening
Synthetic curcumin testing
Certificates of analysis
Branded ingredient documentation
Raw-material sourcing
Supply-chain controls
Extraction methods
Stability data
Batch-to-batch consistency
Supplier and brand vetting

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 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.

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. Dietary supplements may cause side effects or interact with medications. Patients should consult a qualified healthcare professional before changing their healthcare routine.

References
Ammon, 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 curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomedicine & Pharmacotherapy, 85, 102–112. https://pubmed.ncbi.nlm.nih.gov/27930973/
Ribnicky, D. M., et al. (2008). Evaluation of botanicals for improving human health. The American Journal of Clinical Nutrition, 87(2), 472S–475S. https://pubmed.ncbi.nlm.nih.gov/18258640/
Sarma, N., Upton, R., Rose, U., Guo, D.-A., Marles, R., Khan, I., & Giancaspro, G. (2021). Pharmacopeial standards for the quality control of botanical dietary supplements in the United States. Journal of Dietary Supplements, 20(3), 485–504. https://pubmed.ncbi.nlm.nih.gov/34699287/
van Breemen, R. B., Fong, H. H. S., & Farnsworth, N. R. (2008). Ensuring the safety of botanical dietary supplements. The American Journal of Clinical Nutrition, 87(2), 509S–513S. https://pubmed.ncbi.nlm.nih.gov/18258648/
You, H., Gershon, H., Goren, F., Xue, F., Kantowski, T., & Monheit, L. (2022). Analytical strategies to determine the labelling accuracy and economically-motivated adulteration of “natural” dietary supplements in the marketplace: Turmeric case study. Food Chemistry, 370, 131007. https://pubmed.ncbi.nlm.nih.gov/34507212/

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 Episode
Immunometabolism 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.com

Guest Introduction

Dr. 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.

FAQ

What 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.

Timestamps

02:22 — What immunometabolism means
Why immune function and metabolism can no longer be viewed as separate biological systems.
06:15 — From “angry fat” to systems biology
How communication between immune cells and adipose tissue helped shape modern thinking about immunometabolism.
09:31 — Immunometabolism and root-cause thinking
Looking upstream from organ dysfunction toward the processes that may be influencing it.
17:23 — Metabolism is more than weight
Cellular energy production, mitochondria, inflammation, and why metabolic function affects the entire body.
22:01 — What a routine CBC may reveal
Moving beyond gross abnormalities to explore patterns within the CBC with differential.
23:20 — Introducing SII and SIRI
How researchers combine neutrophils, lymphocytes, platelets, and monocytes into inflammatory indices.
34:06 — Translating biomarkers into whole-person care
Nutrition, polyphenols, movement, sleep, and stress management enter the conversation.
39:27 — Why food complexity matters
Dr. Bland uses buckwheat to illustrate the diversity of plant polyphenols.
46:38 — Big data and personalized medicine
How large health datasets may help researchers identify more individualized biological patterns.
54:43 — Owning your health
Dr. 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.

Citations
Burak, 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/S0002916524004556
Islam, 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=S0034-83762024000200001
Koelman, 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/s10238-024-01294-3
O'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 Takeaways
How Robyn approaches highly complex patients who have already addressed many common contributors
Why gut health should not automatically be assumed to be the primary driver of every autoimmune presentation
How testing identified a respiratory microbial pattern that had not been clinically obvious
Why laboratory findings are most useful when interpreted alongside symptoms, history, prior testing, and the overall clinical picture
How unexpected findings can change clinical decision-making in complex cases
Why 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 Takeaway
When 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.

Disclaimer
The 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.