This episode of the Root Cause Medicine Podcast features host Dr. Kate Kresge, ND in conversation with Dr. Jeff Gladd, MD, Chief Medical Officer at Fullscript and an integrative primary care physician. Together, they unpack three timely topics for whole-person clinicians: emerging human data on urolithin A as a mitophagy-activating postbiotic that may support mitochondrial function and immune aging; how to help patients engage with the “fiber maxing” trend in a safe, sustainable way that supports metabolic health, GI function, and diet adherence; and a new industry survey showing that 94% of pharma leaders are running or exploring direct-to-patient (DTP) programs, with implications for GLP-1 therapy access, continuity of care, and the clinician’s central role in guiding treatment decisions. (Nature)
Summary
In this month's CMO Industry Update, Dr. Jeff Gladd, MD joins us to unpack three timely topics for whole-person clinicians:
- Emerging human data on urolithin A as a mitophagy-activating postbiotic that may support mitochondrial function and immune aging
- How to help patients engage with the “fiber maxing” trend in a safe, sustainable way that supports metabolic health, GI function, and diet adherence
- A new industry survey showing that 94% of pharma leaders are running or exploring direct-to-patient (DTP) programs, with implications for medication access, continuity of care, and the clinician’s central role in guiding treatment decisions.
As always, Dr. Gladd gives clinicians practical takeaways and next steps to stay on the leading edge of integrative medicine.
Clinical Takeaways from This Episode
- Urolithin A postbiotic and mitophagy support for immune aging
Urolithin A (UA) is a gut-derived postbiotic produced from ellagic acid–rich foods (e.g., pomegranate, walnuts, raspberries) by specific microbiome profiles. Only a minority of patients appear to generate robust amounts endogenously, making it a candidate for targeted supplementation in select cases (Kuerec, 2024).
- Randomized controlled trial of urolithin A and “younger” immune phenotypes
A 4-week randomized, double-blind, placebo-controlled trial in 50 middle-aged adults (1,000 mg/day UA) found favorable shifts in T-cell subsets (more naïve, fewer exhausted CD8+ cells) and improved mitochondrial activity in immune cells, suggesting UA may help support a more “youthful” immune profile and mitigate aspects of inflammaging (Denk, 2025).
- Mitophagy, mitochondrial fitness, and healthspan-focused care
UA may act as a mitophagy inducer, potentially enhancing removal of dysfunctional mitochondria and supporting mitochondrial biogenesis; this aligns with broader healthspan strategies aimed at maintaining immune competence, muscle function, and cardiorespiratory fitness across the lifespan, without framing UA as a standalone longevity cure (Keurec, 2024).
- Integrating urolithin A within comprehensive mitochondrial and metabolic health plans
Rather than “hero-ing” a single ingredient, Dr. Gladd underscores that any consideration of UA belongs alongside foundational lifestyle medicine: resistance training for muscle preservation, VO₂-max–oriented movement, nutrient-dense diets, sleep, stress regulation, and microbiome-supportive nutrition.
- Evidence-informed high-fiber nutrition to support metabolic and GI health
Only about 5% of the U.S. population meets daily fiber intake recommendations, with average intakes around 17 g/day compared to suggested ranges of roughly 21–25 g for adult women and 30–38 g for adult men (Dahl, 2015). Clinicians can frame fiber not as restriction, but as “nutrition by addition” for metabolic health, GI regularity, cholesterol balance, and satiety.
- Coaching patients through the ‘fiber maxing’ trend safely
Social media trends promoting 30–40+ g/day of fiber can be beneficial in concept but may trigger gas, bloating, or bowel changes if patients increase too quickly or consume large bolus doses; gradual titration across meals, adequate hydration, and movement can improve tolerability and outcomes (McRae, 2020).
- Whole-food fiber strategies pair protein, polyphenols, and GI support
The episode highlights simple upgrades—adding berries, flax, or psyllium to yogurt; spinach and lentils to egg scrambles; swapping regular pasta for lentil pasta; and building soups and stews around beans and lentils—allowing patients to hit fiber goals while supporting blood sugar steadiness, microbiome diversity, and adherence to higher-protein diets.
- Supplemental fibers: powders, liquids, and gummies in integrative GI care
When diet alone is insufficient, blended soluble/insoluble fiber powders (e.g., psyllium, FOS, apple pectin) and pediatric-friendly liquids or travel-ready gummies can help bridge gaps. The conversation emphasizes quality sourcing, gradual introduction, and pairing supplements with water and movement to reduce GI side effects (McRae, 2020).
- Direct-to-patient pharma programs and the future of GLP-1 therapy access
A recent ixlayer/DHC Group survey found that 94% of pharma leaders are running, planning, or exploring direct-to-patient programs, which may bundle telehealth, diagnostics, and medication fulfillment—including access to GLP-1 therapies for obesity and metabolic disease (Park, 2025). While this may reduce wait times for some medications, it also risks further fragmenting care.
- Preserving the provider–patient relationship in a DTP landscape
Dr. Gladd frames this shift as a “rallying cry” for clinicians and platforms like Fullscript to double down on coordinated, whole-person care—ensuring someone is monitoring polypharmacy, side effects, risks, and lifestyle interventions, rather than allowing care to be driven solely by DTP marketing pipelines.
- Leveraging digital tools to scale integrative, whole-person care
The episode closes with an invitation for clinicians to lean on practice-support tools (e.g., supplement quality curation, lab testing support, interaction checkers, AI-assisted plan-building) so they can stay at the center of patient care while reducing administrative burden and burnout.
Guest Introduction
Jeff Gladd, MD is an integrative and family medicine physician and the Chief Medical Officer at Fullscript, where he guides clinical strategy and product direction with a focus on evidence-informed, whole-person care. He is the founder of GladdMD Integrative Medicine, an Indiana-based clinic that blends conventional primary care with lifestyle medicine, nutrition, and high-access digital tools. Dr. Gladd completed medical training at Indiana University School of Medicine and an integrative medicine fellowship at the University of Arizona under Dr. Andrew Weil. He is a frequent national speaker on physician entrepreneurship, supplement quality, health IT, and the future of integrative primary care. Clinicians can explore more of his work through Fullscript’s practitioner education resources and his GladdMD practice content.
Labs, Nutrition, and Lifestyle Support
- Urolithin A
- Fiber powders
- Fiber liquids
- Fiber gummies
Citations
- Bischof-Ferrari HA, et al. Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial. Nature Aging (2025).https://www.nature.com/articles/s43587-025-00996-x.pdf
- Slavin JL et al. Position of the Academy of Nutrition and Dietetics: Health Implications of Dietary Fiber. J Acad Nutr Diet. 2015;115(11):1861–1870.https://www.jandonline.org/article/S2212-2672(15)01386-6/abstract
- Park, A. DHC Group / ixlayer industry survey reporting that 94% of pharma leaders are currently running, planning, or exploring DTP programs, including telehealth and at-home diagnostics. 2025. https://www.fiercepharma.com/marketing/direct-patient-programs-are-works-94-pharmas-set-become-standard-practice-survey
- Kuerec AH, Lim XK, Khoo AL, Sandalova E, Guan L, Feng L, Maier AB. Targeting aging with urolithin A in humans: A systematic review. Ageing Res Rev. 2024 Sep;100:102406. doi: 10.1016/j.arr.2024.102406. Epub 2024 Jul 11. PMID: 39002645.
- Denk, D., Singh, A., Kasler, H.G. et al. Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial. Nat Aging 5, 2309–2322 (2025). https://doi.org/10.1038/s43587-025-00996-x
- Dahl, Wendy J. et al. Position of the Academy of Nutrition and Dietetics: Health Implications of Dietary Fiber. Journal of the Academy of Nutrition and Dietetics, Volume 115, Issue 11, 1861 - 1870
- McRae MP. Effectiveness of Fiber Supplementation for Constipation, Weight Loss, and Supporting Gastrointestinal Function: A Narrative Review of Meta-Analyses. J Chiropr Med. 2020 Mar;19(1):58-64. doi: 10.1016/j.jcm.2019.10.008. Epub 2020 Aug 29. PMID: 33192192; PMCID: PMC7646157.
