The research around SIBO is evolving, and 2026 has brought more subtypes, testing and treatment options than ever before. Our guest this week, Dr. Allison Siebecker, is an expert in conventional and natural approaches to SIBO, helped to open one of the first integrative SIBO centers in the nation, and frequently teaches physicians about how to effectively treat even the toughest cases of SIBO, ISO, IMO and more. 
Today, we explore how hydrogen, methane (IMO), and hydrogen sulfide–associated (ISO) pattern-typing can help us choose treatment options that help to decrease SIBO symptoms effectively. We discuss how impaired motility - particularly dysfunction of the migrating motor complex - can impact symptom persistence and relapse in addition to microbial type and load, and why we should address it in treatment plans. Dr. Siebecker also reviews the newest advances in SIBO testing, breath test interpretation, and how long to test depending on what you’re looking to discover. 
If SIBO has felt like a guessing game in your practice, or if you’re just looking to stay on the leading edge, this episode offers a clearer, physiology-driven framework grounded in education that will help your clients get and stay well. 
Timestamps

00:00 - Introduction to the episode and guest
03:45 - What SIBO is and how it’s currently defined (including ICD-10 update)
06:50 - Differentiating hydrogen, methane, and hydrogen sulfide subtypes
08:40 - Key symptoms: bloating, IBS symptoms, mood, fatigue
10:54 - Why gas types matter and how they affect motility
15:00 - Primary causes and risk factors: infections, meds, mold, structural changes
18:40 - Mold and mycotoxin impact on gut motility
21:59 - How to test: glucose vs. lactulose, two-hour vs. three-hour tests
24:14 - Choosing a testing method and interpreting flatlines
29:01 - Cost, access, and why testing saves time and money long term
31:03 - Choosing treatment based on gas type and severity
36:32 - Understanding treatment rounds and when to stop or switch protocols
38:59 - Why methane and hydrogen sulfide SIBO are more difficult to treat
43:26 - Nystatin, yeast overgrowth, and when to co-treat for CIFO
47:55 - Rifaximin as a eubiotic and why it’s well tolerated
49:46 - Preview of Part 2: Nutrition, prokinetics, supportive therapies



Clinician Questions & Evidence-Informed Takeaways

• How is SIBO defined and what testing is recommended?
  • SIBO is best understood as a clinical syndrome requiring both characteristic gastrointestinal symptoms and objective evidence of microbial overgrowth in the small intestine. Breath testing may support diagnostic clarity, subtype identification, and treatment planning, particularly in patients with IBS or recurrent digestive disorders (Pimentel, 2020).

• What are the differences between hydrogen-, methane-, and hydrogen sulfide–associated SIBO patterns?
  • Hydrogen-predominant SIBO typically reflects small intestinal fermentation, whereas methane-associated IMO and hydrogen sulfide patterns may involve both the small intestine and colon. Hydrogen predominant types are also usually caused by bacterial overgrowth, while methane and sulfide-predominant types can involve overgrowth of archaea. These distinctions influence motility, symptom expression, and selection of appropriate treatment options (Pimentel, 2020).

• How does impaired gas handling contribute to SIBO and IBS symptoms?
  • Symptom severity may be driven by reduced clearance of gas rather than gas volume alone. Dysfunction of the migrating motor complex and altered neuromuscular signaling can result in significant bloating, distension, and pain even with modest gas elevations. Helping patients restore normal gas-clearing abilities can help to alleviate symptoms, according to Dr. Siebecker (Serra, 2001).

• How does methane slow intestinal transit and result in constipation-predominant presentations?
  • Methane functions as a gasotransmitter that interacts with the enteric nervous system and may slow gut motility. This provides a physiologic explanation for constipation-predominant IBS patterns and the increased treatment complexity seen in methane-associated cases (Park, 2017).

• Which breath test substrate provides the most clinically useful data for SIBO evaluation?
  • There are multiple non-invasive tests available for the detection of SIBO that contain a carbohydrate drink and containers designed to collect breath samples at regular intervals (Losurdo 2020).
  • Lactulose is preferred by Dr. Siebecker in clinical practice because it traverses the full length of the small intestine and into the colon, potentially reducing false-negative results associated with early glucose absorption that can occur in some patients. Dr. Siebecker recommends tests that are at least 3 hours in duration for most patients. (Pimentel, 2020)

• How does breath test duration impact the detection of methane and hydrogen sulfide patterns?
  • Shortened testing protocols may fail to capture later-rising methane or persistently low hydrogen and methane patterns. According to Dr. Siebecker, extended collection windows can improve detection of methane-associated IMO and suspected hydrogen sulfide physiology. It could also help to capture patients with SIBO who also have impaired motility and transit time (Tansel, 2023).

• What is the clinical interpretation of a flatline hydrogen and methane breath test for SIBO?
  • A flatline pattern (i.e. low and relatively stable hydrogen and methane values) could give clues to abnormal function in symptomatic patients. Dr. Siebecker suggests that in appropriate clinical contexts, abnormal patterns like flatline may suggest hydrogen sulfide overproduction or altered microbial metabolism of gases (Lakhoo, 2018).

• How should breath test severity inform SIBO treatment sequencing and prognosis?
  • In Dr. Siebecker’s experience, higher gas levels may justify consideration of strategies with greater average reduction potential, such as elemental diet, while lower or moderate elevations may be approached with pharmaceutical or herbal treatment options. Severity-based planning can improve timelines and patient expectations.

• If patients relapse after SIBO treatment, what does that mean?
  • Symptom recurrence shortly after treatment more often reflects incomplete microbial reduction or the existence of undertreated root causes rather than true relapse. This distinction supports staged treatment approaches with reassessment rather than premature abandonment of therapy. Patients with incomplete resolution can also be evaluated for other disorders like pancreatic exocrine insufficiency, bile acid malabsorption, lactose intolerance, etc. (Rao, 2019).

• Under what circumstances should coexisting fungal overgrowth be considered in SIBO patients?
  • Dr. Siebecker explains that small intestinal fungal overgrowth (SIFO) testing could be considered in patients with prior candidiasis, repeated antibiotic exposure, or persistent symptoms despite improving SIBO markers. Evaluation is typically individualized rather than routine (Soliman, 2025). 

• What is the role of prokinetics in long-term SIBO management?
  • Prokinetics support the migrating motor complex and may help maintain treatment gains following antimicrobial therapy. Addressing motility is central to relapse prevention and sustained gut health (Kim, 2023).

• What factors should be reassessed in patients with recurrent or refractory SIBO?
  • Persistent or relapsing SIBO warrants reassessment of medications (particularly opioids), structural contributors, metabolic and neurologic conditions, immune dysfunction, environmental exposures, and lifestyle factors influencing gut physiology (Rao, 2019 and Pimentel, 2020).

Guest 
Dr. Alison Siebecker, ND is a naturopathic physician, internationally recognized SIBO expert, and educator whose work has shaped how clinicians understand small intestine overgrowth, breath testing, and integrative treatment options. She is known for her clear clinical algorithms, deep expertise in SIBO subtypes, and commitment to practitioner education. Her ongoing collaboration and dialogue with leading researchers—including Dr. Mark Pimentel’s research group—continues to advance the field. You can learn more about her at https://www.siboinfo.com/

SIBO Testing

• Learn more about Optimizing SIBO Diagnosis with Testing 
• Order SIBO testing for patients through Rupa Health and Fullscript with a free account

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 treatment 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

1. Pimentel M, Saad RJ, Long MD, Rao SSC. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. Am J Gastroenterol. 2020;115(2):165-178.
2. Rezaie A, Buresi M, Lembo A, et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am J Gastroenterol. 2017;112(5):775-784. 
3. Serra J, Azpiroz F, Malagelada JR. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Gut. 2001;48(1):14-19. 
4. Park H, Lee K, Park S, et al. The effects and mechanism of action of methane on ileal motor function. Neurogastroenterol Motil. 2017;29(9):e13067. 
5. Losurdo G, Leandro G, Ierardi E, Perri F, Barone M, Di Leo A. Breath Tests for the Non-invasive Diagnosis of Small Intestinal Bacterial Overgrowth: A Systematic Review With Meta-analysis. J Neurogastroenterol Motil. 2020;26(1):16-28.
6. Tansel A, Levinthal DJ. Understanding Our Tests: Hydrogen-Methane Breath Testing to Diagnose Small Intestinal Bacterial Overgrowth. Clin Transl Gastroenterol. 2023;14(4):e00567. Published 2023 Apr 1. doi:10.14309/ctg.0000000000000567
7. Birg A, Hu S, Lin HC, et al. Reevaluating our understanding of lactulose breath tests by incorporating hydrogen sulfide measurements. JGH Open. 2019;3(2):228-233.
8. Lakhoo, Krutika MD1; Liu, Xiaochen MSc1; Lentz, Greg2; Lin, Eugenia BS1; Chang, Bianca W. MD3; Pimentel, Mark MD1; Pichetshote, Nipaporn MD1; Rezaie, Ali MD, MSc1. Phenotype and Antibiotic Response in Patients With Flat Line Breath Test Results: A Large Scale Database Analysis: 448. American Journal of Gastroenterology 113():p S261, October 2018. 
9. Soliman N, Kruithoff C, San Valentin EM, Gamal A, McCormick TS, Ghannoum M. Small Intestinal Bacterial and Fungal Overgrowth: Health Implications and Management Perspectives. Nutrients. 2025;17(8):1365. Published 2025 Apr 17. doi:10.3390/nu17081365 
10. Rao, Satish & Bhagatwala, Jigar. (2019). Small Intestinal Bacterial Overgrowth: Clinical Features and Therapeutic Management. Clinical and Translational Gastroenterology. 10. e00078. 10.14309/ctg.0000000000000078. 
11. Kim YJ, Jo IH, Paik CN, Lee JM. Efficacies of prokinetics and rifaximin on the positivity of a glucose breath test in patients with functional dyspepsia: a randomized trial. Rev Esp Enferm Dig. 2023 Mar;115(3):121-127. doi: 10.17235/reed.2022.8735/2022. PMID: 35748472.

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

1. 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 
2. 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 
3. 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 
4. 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. 
5. 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 
6. 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
7. 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. 

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.

Summary

In this episode of the Root Cause Medicine Podcast, Dr. Kate Kresge is joined by Dr. Eric Viegas, a leader in supplement safety at Fullscript, for a timely and evidence-informed discussion on lead exposure in protein powders and nutritional supplements. Amid rising media attention and consumer concern, the conversation unpacks how and why trace amounts of lead can appear in supplements, how different regulatory thresholds (Prop 65 vs. USP/ICH) should be interpreted clinically, and what toxicologically relevant exposure actually means. Clinicians will gain practical insight into cumulative lead exposure, patient risk stratification, and how Fullscript is advancing supplement quality through enhanced testing, transparency, and practitioner-facing safeguards.


Clinical Takeaways from This Episode

• Lead Detection vs. Clinical Risk Assessment in Supplements
  • Dr. Eric explains that detecting trace lead does not automatically equate to clinical harm; modern analytical testing is extremely sensitive, and risk must be contextualized using toxicology-based thresholds and cumulative exposure.
• Understanding Prop 65 vs. USP/ICH Lead Thresholds
  • California Prop 65 applies large safety buffers designed to trigger warnings, while USP 232 and ICH Q3D limits are toxicologically derived and commonly used in pharmaceutical-grade quality systems.
• Cumulative Lead Exposure and Patient-Specific Risk Factors
  • Total exposure from diet, water, environment, and supplements—especially in pregnancy, pediatrics, kidney disease, or high environmental burden—should guide clinical decision-making (FDA, 2025).
• Why Plant-Based Protein Powders Are More Vulnerable
  • Ingredients such as rice, peas, and hemp may bioaccumulate heavy metals from soil and water, and processing can further concentrate these compounds (Hasan, 2022).
• Beyond Heavy Metals: Broader Protein Powder Quality Metrics
  • Clinicians should also consider microbes, pesticides, residual solvents, phytates, and banned substances when evaluating protein powders.
• Clinical Value of Certificates of Analysis (COAs)
  • Batch-specific COAs provide greater transparency than general certifications and allow clinicians to verify contaminant screening for the exact product lot (CHPA, 2010).
• Role of Enhanced Finished-Product Testing in Integrative Care
  • Platforms like Fullscript are supporting clinicians by conducting independent, third-party testing and surfacing results directly within the clinical workflow.
    
    

Timestamps

00:00 Welcome and episode overview
01:48 Why lead in protein powders is trending now
03:58 Detectable does not always mean dangerous
04:30 How to interpret lead amounts and cumulative exposure
05:58 Other supplement contaminants to consider
07:45 Why plant-based proteins carry higher risk of heavy metal uptake
10:55 What certifications to look for and why they matter
13:10 What Fullscript is doing, enhanced testing, and safeguards
15:10 How to assess lead exposure in clinical practice18:11 What Dr. Viegas wants to change in the supplement industry20:02 How to choose a safer protein powder21:59 Final takeaways and closing


Guest Introduction


Eric Viegas, ND
Dr. Eric Viegas is a leader in supplement safety and quality assurance at Fullscript, where he oversees contaminant screening, regulatory alignment, and enhanced testing initiatives across multiple supplement categories. His work focuses on bridging pharmaceutical-grade toxicology standards with real-world clinical practice to support practitioner confidence and patient safety. Fullscript Quality & Education: https://fullscript.com


Labs, Nutrition, and Lifestyle Support


Lead Exposure Assessment and Monitoring

• Blood lead testing for evaluating current exposure (CDC, 2024)
• Environmental assessment of drinking water and occupational or environmental exposure (PEHSU, 2025)

Protein Powder Selection and Nutrient Quality Considerations

• Preference for brands with third-party cGMP certifications
• Review of batch-specific Certificates of Analysis (COAs) (CHPA, 2010)
• Awareness that organic certification does not eliminate heavy metal risk (Ramakrishnan, 2021)

Citations

• Clean Label Project. Heavy Metals in Protein Powders. Retrieved October 2025 from https://cleanlabelproject.org/protein-study-2-0/ 
• Consumer Reports. Protein Powders and Lead Levels. October 2025. https://www.consumerreports.org/lead/protein-powders-and-shakes-contain-high-levels-of-lead-a4206364640/ 
• United States Food and Drug Administration. FDA Draft Guidance on Lead in Food Intended for Babies, Children, and Adults. Updated January 2025. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-action-levels-lead-processed-food-intended-babies-and-young-children 
• EFSA. EFSA scientific report on dietary exposure to lead in the European population. June 30, 2025. https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9577 
• World Health Organization. Lead Poisoning and Health. September 2024. https://www.who.int/news-room/fact-sheets/detail/lead-poisoning-and-health 
• Centers for Disease Control. CDC Updates Blood Lead Reference Values. April 2024. https://www.cdc.gov/lead-prevention/php/news-features/updates-blood-lead-reference-value.html
• US Pharmacopeia. USP 232 Elemental Impurities - Limits. https://www.usp.org/sites/default/files/usp/document/our-work/chemical-medicines/key-issues/c232-usp-39.pdf 
• International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Harmonised Guideline: Guideline for Elemental Impurities Q3D(R2). 26 Apr. 2022. https://database.ich.org/sites/default/files/Q3D-R2_Guideline_Step4_2022_0308.pdf 
• Consumer Healthcare Products Association. Certificate of Analysis for Dietary Supplement Components. Consumer Healthcare Products Association. Apr. 2010, www.chpa.org/public-policy-regulatory/voluntary-codes-guidelines/certificate-analysis-dietary-supplement 
• Hasan, G. M. M. Anwarul, et al. “Accumulation of Heavy Metals in Rice (Oryza Sativa. L) Grains Cultivated in Three Major Industrial Areas of Bangladesh.” Journal of Environmental and Public Health, vol. 2022, 8 Mar. 2022, p. e1836597, https://doi.org/10.1155/2022/1836597 
• “Chemical Exposure Warnings (Proposition 65 Warnings).” Ca.gov, 2021, www.p65warnings.ca.gov/ 
• Ramakrishnan, Balasubramanian, et al. “Organic Farming: Does It Contribute to Contaminant-Free Produce and Ensure Food Safety?” Science of the Total Environment, vol. 769, 15 May 2021, www.sciencedirect.com/science/article/abs/pii/S0048969721001455 
• “Lead Exposure: Information for Health Professionals.” PEHSU - Pediatric Environmental Health Specialty Units, 7 Nov. 2025, pehsu.net/health-issue/lead-hcp/ Accessed 31 Dec. 2025.

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.

In this rapid-fire “Health or Hype” installment, Dr. Kate Kresge sits down with performance specialists Dr. Chris Sands, DPT, OCS, and Dr. Gabe Kresge, DPT, to pressure-test the most common running claims through a clinically grounded lens. The conversation moves quickly—but stays evidence-oriented—clarifying where strength training supports running economy, why single-leg capacity matters for load management, how footwear choices should be individualized (especially during transitions), and what the research actually suggests about long-term joint health. They also reframe running assessments as a proactive performance-and-longevity tool, and close with a key injury-prevention principle: for most runners, training load and recovery patterns drive risk more than biomechanics alone.


Clinical Takeaways from This Episode

• Strength Training as a Performance Amplifier (Not a “Bulking” Risk): The guests emphasize that most runners are unlikely to gain meaningful muscle mass that slows them down without a significant caloric surplus and bodybuilding-style programming. In typical runner programming, strength work more often improves running economy, stride efficiency, and neuromuscular coordination (Rønnestad 2014, Llanos-Lagos 2024). 

• Bilateral Strength Helps—But Running is a Single-Limb Sport: Squats can be useful for global strength, but running requires repeated single-leg force absorption and production. Unilateral patterns (split squats, step-downs, single-leg hinge work) better reflect the frontal-plane control, pelvic stability, and side-to-side comparisons that matter for durability and efficiency, particularly over long distances (Li, 2025).

• Minimalist Footwear is a Contextual Tool, Not a Universal Upgrade: Barefoot/minimalist shoes may nudge stride length and foot strike mechanics, but the guests stress that this is only helpful when the runner has adequate calf/soleus capacity and introduces changes gradually. Rapid transitions can increase injury risk (Altman 2015).

• Running and Joint Health: “Cyclic Loading” Can Be Supportive in Moderate Doses: Dr. Chris Sands frames the “running ruins your knees” claim as largely hype for recreational runners, noting that well-programmed, moderate running is not inherently degenerative and may correlate with better long-term joint outcomes compared with sedentary patterns—especially when recovery and cross-training are addressed.

• Running Assessments as Preventive Medicine for the Athlete: A running assessment isn’t positioned solely as an injury service. Instead, Dr. Gabe Kresge describe it as a way to identify subclinical deficits, asymmetries, or capacity gaps before they become pain-limiting—supporting performance, longevity, and more individualized programming.

• Most Injuries Track with Training Errors and Under-Recovery: Biomechanics can contribute, but the episode highlights a consistent theme in the literature: volume spikes, poor programming, and inadequate recovery (sleep quality, nutrition, chronic stress load) are common drivers of injury risk at the population level (Hamstra-Wright, 2021).

Dr. Chris Sands, DPT, OCS, and Dr. Gabe Kresge, DPT, are performance and movement specialists with a clinical background in working with runners across rehab, training, and long-term durability. Their approach emphasizes objective testing, individualized programming, and evidence-based decision-making to support both performance goals and lifelong movement capacity. You can find them at https://kineticptpa.com/

Sponsor: Fullscript – a comprehensive care delivery platform for supplement dispensing, patient education, treatment planning, adherence support, and lab ordering with interpretation. (Visit: fullscript.com)

Clinician FAQ: Running Myths, Load Management, Footwear, and Injury Prevention

• Does strength training usually slow runners down?
  • In this episode, the guests label that claim as hype for most runners and point to evidence that strength work more often improves running economy and efficiency when programmed appropriately.
• Are squats “the best” exercise for runners?
  • The experts say this is partially true: squats can be helpful, but unilateral work more directly matches the single-leg demands of running and helps reveal side-to-side differences.
• Should everyone switch to minimalist shoes?
  • They emphasize a strong “it depends.” Minimalist footwear may change mechanics, but tolerance is highly dependent on calf/soleus strength and a gradual transition plan.
• Is running inherently bad for knees and hips?
  • The experts frame this as largely hype for recreational runners, stressing moderation, recovery, and cross-training as key contextual factors.
• If a runner isn’t injured, is a running assessment still useful?
  • Yes—this episode positions assessments as preventative and performance-oriented, designed to identify capacity and movement risks early.
• Why does poor sleep increase injury risk?
  • The guests distinguish acute tiredness from chronic under-recovery—highlighting that consistently poor sleep quality and insufficient recovery capacity can raise injury susceptibility over time.

Timestamps
00:00 – Welcome to “Health or Hype” + episode setup
00:30 – Sponsor: Fullscript
02:03 – Myth #1: Strength training makes runners bulky/slower
03:23 – Myth #2: Squats are the best exercise for running strength
04:41 – Myth #3: Everyone should run in minimalist/barefoot shoes
06:17 – Cushion vs. stiffness: how distance and running type can matter
07:40 – Myth #4: Running breaks down your joints over time
10:33 – Myth #5: No injury = no need for a running assessment
13:52 – Myth #6: Most injuries are training errors, not biomechanics
15:04 – Why chronic under-recovery (especially sleep quality) raises risk
16:00 – Wrap + listener feedback request + disclaimer

Citations

1. Rønnestad BR, Mujika I. Optimizing strength training for running and cycling endurance performance: A review. Scand J Med Sci Sports. 2014 Aug;24(4):603-12. doi: 10.1111/sms.12104. Epub 2013 Aug 5. PMID: 23914932.
2. Altman AR, Davis IS. Prospective comparison of running injuries between shod and barefoot runners. Br J Sports Med. 2016 Apr;50(8):476-80. doi: 10.1136/bjsports-2014-094482. Epub 2015 Jun 30. PMID: 26130697.
3. Llanos-Lagos C, Ramirez-Campillo R, Moran J, Sáez de Villarreal E. Effect of Strength Training Programs in Middle- and Long-Distance Runners' Economy at Different Running Speeds: A Systematic Review with Meta-analysis. Sports Med. 2024 Apr;54(4):895-932. doi: 10.1007/s40279-023-01978-y. Epub 2024 Jan 2. PMID: 38165636; PMCID: PMC11052887.
4. Prieto-González P, Sedlacek J. Effects of Running-Specific Strength Training, Endurance Training, and Concurrent Training on Recreational Endurance Athletes' Performance and Selected Anthropometric Parameters. Int J Environ Res Public Health. 2022 Aug 29;19(17):10773. doi: 10.3390/ijerph191710773. PMID: 36078489; PMCID: PMC9518107.
5. Huffer D, Hing W, Newton R, Clair M. Strength training for plantar fasciitis and the intrinsic foot musculature: A systematic review. Phys Ther Sport. 2017 Mar;24:44-52. doi: 10.1016/j.ptsp.2016.08.008. Epub 2016 Aug 18. PMID: 27692740.
6. Sun X, Lam WK, Zhang X, Wang J, Fu W. Systematic Review of the Role of Footwear Constructions in Running Biomechanics: Implications for Running-Related Injury and Performance. J Sports Sci Med. 2020 Feb 24;19(1):20-37. PMID: 32132824; PMCID: PMC7039038.
7. Willwacher S, Sanno M, Brüggemann GP. Fatigue matters: An intense 10 km run alters frontal and transverse plane joint kinematics in competitive and recreational adult runners. Gait Posture. 2020 Feb;76:277-283. doi: 10.1016/j.gaitpost.2019.11.016. Epub 2019 Dec 13. PMID: 31884254.
8. Li X, Mao L. Characteristics of Lower Limb Dominant and Nondominant Joint Load Changes After Long-Distance Running in Young Male Runners Under OpenSim Environment. Sensors (Basel). 2025 Oct 11;25(20):6301. doi: 10.3390/s25206301. PMID: 41157355; PMCID: PMC12567293.
9. Hamstra-Wright KL, Huxel Bliven KC, Napier C. Training Load Capacity, Cumulative Risk, and Bone Stress Injuries: A Narrative Review of a Holistic Approach. Front Sports Act Living. 2021 May 28;3:665683. doi: 10.3389/fspor.2021.665683. PMID: 34124660; PMCID: PMC8192811.

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.

This episode of the Root Cause Medicine Podcast explores the Modern Running Assessment, an evidence-informed, data-driven framework for evaluating runners’ biomechanics, load tolerance, and performance capacity. Host Dr. Kate Kresge interviews Dr. Chris Sands, DPT, OCS, and Dr. Gabe Kresge, DPT, from Kinetic Physical Therapy to examine how modern tools—dynamometry, force plate testing, slow-motion gait analysis, cadence and vertical oscillation metrics, and single-leg endurance testing—provide objective information that visual observation alone may miss. These measurable insights help clinicians better understand strength-to-body-weight ratios, inter-limb asymmetries, foot-strike loading patterns, and fatigue-related movement changes, offering a clearer picture of the factors that may influence running efficiency, durability, and injury risk.


Clinical Takeaways: Evidence-Informed Running Biomechanics and Performance Metrics

• Dynamometry can quantify strength and help to reveal relevant asymmetries. 
  • Consider dynamometry for hip and knee strength assessment to reveal inter-limb asymmetries that can affect gait and joint load. 
• Limb asymmetries should be interpreted within a broader biomechanical context.
  • Inter-limb differences are common, and evidence for their direct impact is mixed. Reviews indicate that asymmetry effects vary across athletes and may be most useful when tracked over time rather than interpreted as a single cutoff. This conversation focuses on asymmetric joint loading during runs, which can increase with distance and fatigue (Li, 2025).
• Gait analysis is still relevant.
  • High-speed and slow motion video helps clinicians evaluate variables such as vertical oscillation, cadence, pelvic motion, and trunk rotation—mechanics that may support targeted interventions.
• Optimal foot strike patterns can shift depending on a runner’s goals.
  • Reviews show that foot strike patterns redistribute forces differently across joints but do not consistently prevent injury (Altman 2015). Pronation is a normal shock-absorption mechanism, and comfort is a meaningful predictor for footwear selection.
• Progressive strength training supports running economy and performance.
  • Strength programs integrated with endurance training support improvements in running economy (Rønnestad 2014, Llanos-Lagos 2024) and performance (Prieto-Gonzalez, 2022).
• There is no perfect running shoe.
  • Thousands of studies have helped us understand all of the variables that go into shoe choice, from stack height to lace patterns, heel flares and heel-toe drop, bending stiffness, heel cup and more.  The short answer: there’s no perfect shoe. Runners should work with professionals to help them choose the shoes with the right combinations of features for their mileage, pace, goals and physiology. (Sun, 2020) 
• Implement periodic reassessment to refine training and monitor adaptation.
  • Regular reassessment of strength, asymmetry, and gait metrics supports adaptive programming and individualized progression.

Timestamps:

00:00 – Welcome back and introduction to the Modern Running Assessment
03:52 – Setting goals first: performance vs. pain and how that shapes the assessment
05:47 – Dynamometry explained: measuring force, 2–4x bodyweight load, and asymmetry
11:53 – Strength vs. endurance: calf fatigue, single-leg control, and why bilateral lifts don’t always translate
18:13 – Force plate testing, vertical oscillation, and how cadence tweaks can reduce impact
26:58 – Born to Run, barefoot trends, foot strike, and what really changes with minimalist running
30:38 – Shoes, pronation, anti-pronation models, and when added support actually makes sense
34:24 – Trunk and thoracic mobility: how chest position affects breathing, heart rate, and endurance
37:46 – Foundational strength for runners: split squats, single-leg RDLs, lateral work, and deficit calf raises
41:09 – Will strength training make you “too bulky”? What the research says about muscle, speed, and long-term joint health, plus shoe rotation and clinician action steps toward objective running assessments


Guest Introduction: Experts in Running Biomechanics and Strength-Based Performance
Dr. Chris Sands, DPT, OCS: Dr. Chris Sands is a Doctor of Physical Therapy and Board-Certified Orthopedic Clinical Specialist with advanced training in running biomechanics and force-based assessment. At Kinetic Physical Therapy, he co-leads the Modern Running Assessment program, using tools like handheld dynamometry, force plates, and high-speed gait analysis to quantify strength, asymmetry, and load tolerance. His work focuses on helping runners and clinicians connect objective metrics with tailored training plans that support performance, resilience, and long-term joint health.

Dr. Gabe Kresge, DPT: Dr. Gabe Kresge is a Doctor of Physical Therapy and USA Powerlifting coach who specializes in strength and movement optimization for runners and lifters. At Kinetic, he partners with Dr. Sands to deliver data-driven running assessments that merge objective strength profiling, unilateral endurance testing, and individualized programming. His clinical lens emphasizes building durable, strong runners through intelligently progressed strength training, volume programming, and practical education that athletes can apply for life.

Learn more: Kinetic Physical Therapy — Website: https://kineticptpa.com/
Strength, Mobility, and Volume Progression Strategies for Durable, Efficient Runners


Foundational unilateral strength exercises for runners to consider

• Single-leg Bulgarian split squats
• Single-leg Romanian deadlifts
• Single-leg deficit calf raises
• Lateral band walks / hip abduction work

Cadence, gait mechanics, and shoe strategy for optimized load distribution

• Trial modest cadence adjustments and monitor symptoms and perceived effort.
• Teach foot strike as a load-distribution choice dependent on goals and physiology, not as a right-or-wrong pattern.
• Encourage shoe rotation and prioritize comfort and function over marketing claims.

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

1. Rønnestad BR, Mujika I. Optimizing strength training for running and cycling endurance performance: A review. Scand J Med Sci Sports. 2014 Aug;24(4):603-12. doi: 10.1111/sms.12104. Epub 2013 Aug 5. PMID: 23914932.
2. Altman AR, Davis IS. Prospective comparison of running injuries between shod and barefoot runners. Br J Sports Med. 2016 Apr;50(8):476-80. doi: 10.1136/bjsports-2014-094482. Epub 2015 Jun 30. PMID: 26130697.
3. Llanos-Lagos C, Ramirez-Campillo R, Moran J, Sáez de Villarreal E. Effect of Strength Training Programs in Middle- and Long-Distance Runners' Economy at Different Running Speeds: A Systematic Review with Meta-analysis. Sports Med. 2024 Apr;54(4):895-932. doi: 10.1007/s40279-023-01978-y. Epub 2024 Jan 2. PMID: 38165636; PMCID: PMC11052887.
4. Prieto-González P, Sedlacek J. Effects of Running-Specific Strength Training, Endurance Training, and Concurrent Training on Recreational Endurance Athletes' Performance and Selected Anthropometric Parameters. Int J Environ Res Public Health. 2022 Aug 29;19(17):10773. doi: 10.3390/ijerph191710773. PMID: 36078489; PMCID: PMC9518107.
5. Huffer D, Hing W, Newton R, Clair M. Strength training for plantar fasciitis and the intrinsic foot musculature: A systematic review. Phys Ther Sport. 2017 Mar;24:44-52. doi: 10.1016/j.ptsp.2016.08.008. Epub 2016 Aug 18. PMID: 27692740.
6. Sun X, Lam WK, Zhang X, Wang J, Fu W. Systematic Review of the Role of Footwear Constructions in Running Biomechanics: Implications for Running-Related Injury and Performance. J Sports Sci Med. 2020 Feb 24;19(1):20-37. PMID: 32132824; PMCID: PMC7039038.
7. Willwacher S, Sanno M, Brüggemann GP. Fatigue matters: An intense 10 km run alters frontal and transverse plane joint kinematics in competitive and recreational adult runners. Gait Posture. 2020 Feb;76:277-283. doi: 10.1016/j.gaitpost.2019.11.016. Epub 2019 Dec 13. PMID: 31884254.
8. Li X, Mao L. Characteristics of Lower Limb Dominant and Nondominant Joint Load Changes After Long-Distance Running in Young Male Runners Under OpenSim Environment. Sensors (Basel). 2025 Oct 11;25(20):6301. doi: 10.3390/s25206301. PMID: 41157355; PMCID: PMC12567293.

We’re launching a new series that brings the insights that Fullscript Chief Medical Officer Dr. Jeff Gladd normally shares only with our internal team—now open to the entire integrative and functional medicine community. 

This month, Dr. Gladd breaks down three emerging clinical priorities with immediate relevance to whole-person care

• Why the American College of Cardiology is now recommending high-sensitivity CRP (hs-CRP) for universal cardiovascular screening
• How grip strength paired with BMI is outperforming traditional biomarkers in predicting metabolic decline and all-cause mortality risk
• What new evidence tells us about saffron as supportive care for patients experiencing SSRI-related sexual side effects.

Clinicians will leave with practical, evidence-informed strategies they can apply right away—from how to add grip strength testing to a routine visit, to how to interpret hs-CRP in the context of inflammation and cardiometabolic disease, to how to navigate sensitive conversations about mood medications and quality of life. If you’ve been looking for research you can trust and tools that simplify decision-making, this episode offers a clear roadmap.


Clinical Takeaways from This Episode

• Grip strength combined with BMI is emerging as a scalable, low-cost predictor of metabolic risk and all-cause mortality
  • Dr. Gladd highlights the UK Biobank’s 90,000-person longitudinal analysis, noting: “Those in the highest grip strength tertile were 20% less likely to develop obesity-related disease,” with reduced all-cause mortality. Grip strength may reflect lean mass, mitochondrial function, and insulin sensitivity better than BMI alone. (Xu, et al 2025)
• Grip strength as a lifestyle, bone health, and functional resilience indicator
  • As Dr. Kresge explains, “having a strong grip can basically imply that you’re likely living a healthier life,” given its links to nutrient-dense dietary patterns, sufficient protein intake, sleep quality, smoking avoidance, and greater sense of purpose. Evidence also shows low grip strength strongly correlates with lower bone mineral density in postmenopausal women. (Gedmantaite, 2020)
• Saffron may improve SSRI-associated sexual side effects
  • RCTs suggest saffron may support sexual function parameters in individuals using SSRIs, with sex-specific benefits observed. As Dr. Gladd notes, “We haven’t had anything, to my knowledge, that really addresses the sexual side effects head-on like this study in saffron.” Findings support integration—not substitution—within existing mental health plans. (Shaifee, 2025)
• Universal hs-CRP screening is now recommended for cardiovascular prevention
  • The American College of Cardiology now recommends hs-CRP as part of routine cardiovascular risk screening—reflecting a shift toward evaluating systemic inflammation. Dr. Gladd emphasizes: “Inflammation is now in traditional healthcare as something that can be measured and understood.” (Mesah, 2025)
• Causes of elevated hs-CRP and how to evaluate them clinically
  • Dr. Kresge outlines the major drivers to consider, including infection, autoimmune activity, periodontal disease, adiposity, insulin resistance, low fitness, smoking, poor sleep, chronic stress, and nutrition patterns. She notes: “It’s no longer enough to run a lipid panel and call it cardiovascular screening.” (Mesah, 2025)
• Dietary patterns, omega-3 fatty acids, and curcumin as inflammation-supportive strategies
  • Inflammation-modulating strategies may include nutrient-dense dietary patterns, omega-3 intake and high-bioavailability curcumin. Dr. Gladd encourages clinicians to verify product quality: “Are you getting enough EPA and DHA?” (Ahmadi, 2025)
• Nutrient monitoring opportunities for patients using SSRIs
  • SSRIs may influence B-vitamin status, and Dr. Gladd notes that clinicians may want to be “proactive in supplementing or monitoring those levels,” when appropriate for patient-centered mental health care. (Mohn, 2018)
• Ensuring AI is used to support—not replace—clinical judgment
  • Dr. Gladd discusses emerging regulations to prevent AI from impersonating clinicians, underscoring Fullscript’s stance: “We’re bringing tooling to support the practitioner, not to replace the practitioner.”
• The persistence of clinician burnout and the need for operational support
  • The 2025 Medscape Well-Being Report highlights burnout as an ongoing challenge. Streamlined clinical tools, thoughtful workflows, and comprehensive care platforms may help reduce administrative load.

Guest Bio: Dr. Jeff Gladd, MD, Chief Medical Officer at Fullscript, is a nationally recognized integrative and lifestyle medicine physician. He founded GladdMD Integrative Medicine and authors Fullscript’s CMO Monthly Dose—a monthly research and industry briefing for keeping Fullscripters up to date. His work focuses on metabolic health, clinical nutrition, and technology that enhances clinical workflow. Learn more at fullscript.com.

Assessments Mentioned in this Episode

• hs-CRP (per ACC universal screening recommendation)
• Lipid panel and triglycerides
• Fasting insulin or HOMA-IR
• CBC, ESR, ANA when clinically indicated
• Oral health evaluation for periodontal inflammation
• Magnesium and B vitamins may warrant assessment in patients on SSRIs
• Handheld dynamometer in-clinic or at-home

Timestamps
00:00 – Introduction to the new CMO Monthly Dose series.
01:53 – Dr. Jeff Gladd joins and shares the origin of the CMO Monthly Dose.
03:40 – Grip strength research overview and why it matters clinically.
05:00 – Using grip strength as a practical tool in metabolic and longevity care.
06:30 – Grip strength as a predictor of bone density and functional health.
07:30 – Lifestyle factors linked to higher grip strength.
09:34 – Emerging evidence for saffron in SSRI-related sexual side effects.
11:10 – Key findings for men and women from saffron trials.
12:30 – Nutrient considerations with SSRI use.
13:44 – ACC announces universal hs-CRP screening recommendation.
15:00 – Nutrition and supplement considerations for supporting healthy inflammation.
16:05 – Clinical causes of elevated hs-CRP and how to evaluate them.
17:20 – Why hs-CRP is essential beyond lipid panels.
18:00 – Physician burnout insights from the 2025 Medscape report.
18:30 – New AI regulations and Fullscript’s commitment to supporting clinicians.
19:12 – Closing remarks and call to share the episode.

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.

In this fast-moving, clinically rich tour through the new frontiers of integrative eye care, Dr. Gioia connects the dots between microbiome-driven inflammation, AI-powered retinal biomarker extraction, and hormonal transitions that reshape ocular physiology—all in a way that feels practical for everyday clinical reasoning. She illustrates how gut permeability markers may parallel ocular surface symptoms, how retinal microvascular mapping can hint at systemic resilience, and why perimenopause and menopause deserve far more attention in the modern eye exam. Throughout the episode, she gives clinicians evidence-informed frameworks for synthesizing gut, hormone, nutrient, and imaging data into a more proactive, prevention-oriented approach to vision health.


Clinical Takeaways from This Episode

• Gut-Eye Axis and Systemic Inflammation Pathways: Dysbiosis may influence cytokine activity, intestinal permeability, and endotoxin load—factors that can contribute to ocular discomfort or inflammatory pathways affecting the uveal tract, conjunctiva, and retina. Clinicians may consider gut-driven contributors when chronic ocular symptoms persist despite standard care.
• AI-Driven Oculomics for Early Risk Detection: Retinal photography and OCT/OCT-A imaging combined with AI allow analysis of microvascular integrity, tortuosity ratios, nerve fiber patterns, and biological age metrics—supporting prevention-focused evaluation of cardiovascular, neurologic, metabolic, and longevity-related risk patterns.
• Hormone-Responsive Ocular Tissues and Midlife Vision Changes: Sex-hormone receptors in the lacrimal and meibomian glands, cornea, and retina help explain perimenopause- and menopause-related symptoms such as dry eye, fluctuating vision, and ocular-surface sensitivity. Hormonal transitions may influence lipid secretion, tear stability, and DHA metabolism.
• Preventive Vision Care as a Whole-Systems Touchpoint: Regular retinal imaging, nutrient status assessments, and symptom scoring may help clinicians identify early ocular patterns associated with metabolic or inflammatory changes. Annual eye exams remain essential—even when vision clarity appears stable.
• Nutrient Density and Ocular Resilience Across the Lifespan: Nutrients such as DHA, lutein, and zeaxanthin play supportive roles in retinal structure, macular function, and tear-film stability. Identifying nutrient insufficiencies or imbalances—especially in zinc and copper ratios—may help clinicians guide personalized nutrition strategies.
• Integrative Data Linking: Gut, Hormones, Labs, and Retinal Biomarkers: Combining stool markers (e.g., zonulin, calprotectin, SCFAs), hormone trends, nutrient analysis, and ocular imaging may offer a more complete preventive picture for chronic eye symptoms and systemic health mapping.

Guest Introduction
Dr. Neda (Nehda) Gioia, OD, CNS®, IFMCP, FOWNS, is the founder of Integrative Vision, where she merges optometry, functional medicine, and clinical nutrition into a prevention-first model of eye care. Drawing on her advanced training—including certification from the Institute for Functional Medicine and credentials in clinical nutrition—she educates clinicians on ocular nutrition, gut–eye interactions, and modern imaging applications. She consults nationally, offers virtual ocular nutrition services, and publishes on integrative optometry.

• Website: integrativevision.com
• Professional site: https://www.drnedagioia.com/

Labs, Nutrition, and Lifestyle Support

• Gut-Eye Axis & Microbiome Assessment
  • Stool Markers to Consider: zonulin for permeability; calprotectin for gut-immune activity; SCFAs for microbial metabolite status.
• Hormone-Aware Eye Health
  • Labs: DHEA-S, estradiol, SHBG for midlife symptom mapping; consider androgen patterns when evaluating dry eye.
  • Key Insight: Meibomian gland lipid secretion is influenced by androgen receptor activity and local conversion of testosterone to DHT.
• AI-Enhanced Oculomics
  • Tools: OCT / OCT-A, retinal photography, and AI-driven vascular analytics that assess capillary density, tortuosity, and nerve fiber patterns.
  • Use Case: May support early identification of cardiovascular, neurologic, metabolic, or other trends.
• Nutrient Support for Retinal and Tear-Film Health
  • Core Nutrients: DHA-rich marine sources; lutein and zeaxanthin; balanced zinc-to-copper intake.
  • Evidence Note: AREDS2 highlights the role of targeted nutrient formulas in reducing progression risk for specific macular conditions.
• Lifestyle Strategies for Preventive Eye Care
  • Dietary Pattern: Mediterranean-style eating pattern for broad ocular-supportive nutrient density.
  • Visit Frequency: Annual eye exams beginning in midlife, or more often with ocular or systemic risk factors, even if vision is normal. 

Clinician FAQ: Gut-Eye Axis, Oculomics, Hormones, and Preventive Eye Care

1. How strong is the evidence linking dysbiosis to ocular inflammation? Emerging research shows meaningful associations between gut dysbiosis and ocular inflammatory pathways, including effects on cytokines, permeability, SCFA signaling, and retinal immune activation. Mechanistic animal and human data continue to expand, though large interventional trials remain limited. Citation: Rowan S, et al. Front Cell Neurosci. 2024. Available at: https://www.frontiersin.org/articles/10.3389/fncel.2024.1468187/full
2. Which stool markers may be relevant when patients present with chronic ocular symptoms? Markers such as zonulin, calprotectin, and SCFAs may help clinicians understand permeability, gut-mediated immune activity, and microbial metabolite patterns that could interact with ocular-surface or retinal inflammatory pathways.
    Citation: Rowan S, et al. Front Cell Neurosci. 2024. Available at: https://www.frontiersin.org/articles/10.3389/fncel.2024.1468187/full
3. How does AI-enhanced oculomics fit into preventive medicine? AI-driven retinal imaging can identify subtle microvascular changes, nerve-fiber patterns, and tissue integrity metrics that may correlate with cardiovascular, neurologic, metabolic, and longevity-related risk. These tools expand prevention by extracting systemic biomarkers from retinal data. Citation: Keane P, et al. Theranostics. 2024. Available at: https://www.thno.org/v15p3223.pdf
4. Which hormonal shifts are most relevant to midlife changes in ocular comfort? Perimenopause- and menopause-associated fluctuations in estrogen and declines in androgen activity may impact meibomian gland lipid output, tear film stability, ocular surface sensitivity, and inflammatory thresholds.Citation: Jin, Xiuming, et al. “Hormone Replacement Therapy Benefits Meibomian Gland Dysfunction in Perimenopausal Women.” Medicine, vol. 95, no. 31, Aug. 2016, p. e4268, https://doi.org/10.1097/md.0000000000004268
5. Should clinicians routinely evaluate eye symptoms when initiating hormone therapy? Changes in ocular comfort—including dryness, irritation, or fluctuating vision—may accompany hormone transitions or therapy adjustments. Incorporating eye-symptom questions may help clinicians detect hormone-related effects on the ocular surface. Citation: Abelson MB, Lines L. Review of Ophthalmology. 2006. Available at: https://www.reviewofophthalmology.com/article/hormones-in-dry-eye-a-delicate-balance
6. Which nutrients are most essential for long-term ocular support? DHA, lutein, and zeaxanthin are well-studied nutrients supporting retinal function and macular pigment density. Balanced zinc and copper intake is also important for ocular and neural physiology. Citation: Age-Related Eye Disease Studies (AREDS/AREDS2): major findings https://www.nei.nih.gov/research/clinical-trials/age-related-eye-disease-studies-aredsareds2/about-areds-and-areds2 
7. How often should adults receive a comprehensive eye exam? Dr. Gioia explains that many adults benefit from annual examinations starting around age 40—earlier or more frequently for those with ocular symptoms or systemic risk factors—because asymptomatic conditions such as early glaucoma or macular changes may be detectable only through imaging. 
8. What’s the clinical advantage of combining gut, hormone, and retinal imaging data? According to Dr. Gioia, integrating these data streams can help clinicians observe multi-system patterns earlier—linking inflammatory load, hormonal fluctuations, nutrient availability, and microvascular integrity into a unified preventive strategy. 

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.

This conversation reframes joy as a physiological state with measurable clinical impact, not just an emotion. Dr. Libert blends neuroscience, functional medicine, and spiritual reflection to show how cultivating joy and gratitude can help to restore parasympathetic balance, support healthy immune function, and enhance cognitive flexibility. The episode offers an accessible, hopeful model for physicians—one that unites emotional health, brain resilience, and integrative lifestyle care.

Clinical Takeaways from This Episode

• Joy as a Measurable Biological State: Joy, positive affect and gratitude practices appear to increase activity in the ventral striatum and prefrontal cortex (Rueschkamp, 2019), and have some evidence for improving neuroplasticity, vagal tone, and immune resilience while reducing inflammatory cytokines like IL-6 (Dutcher, 2021).
• Gratitude Practices and Neurochemistry: Regular gratitude journaling boosts dopamine and serotonin, rewiring the reward pathways that reinforce positive affect and motivation. It may even help people to exercise more often over time (Emmons, 2003).
• Positive Affect and Cognitive Performance: Studies show that positive affect can enhance cognitive flexibility and attention-switching—even brief exposure to positive emotion improves executive function (Wang, 2017).
• Micro “Joy Prescriptions” for Busy Clinicians: Dr. Libert recommends short “Vitamin G” (gratitude) walks, deep-breathing practices, or quick notes of appreciation to activate joy and resilience in under 10 minutes per day.
• Integrative Cognitive Health Framework: Joy supports foundational systems—sleep, movement, nutrition, and connection—that underlie cognitive longevity, aligning with the Bredesen Protocol and functional medicine principles.

Guest Introduction

Cynthia Libert, M.D. is a board-certified family physician, educator, and founder of the Caring for the Body Functional Medicine Center in Asheville, NC. With over 20 years of experience, she specializes in cognitive health, longevity, and burnout prevention. She is the creator of ReThink Aging and The Joy Prescription, a podcast and clinical framework helping patients and practitioners reconnect with purpose and vitality. caringforthebody.org | thejoyprescription.com


Labs, Nutrition, and Lifestyle Support

Functional Labs for Brain and Mood Health

• High-sensitivity CRP, IL-6, and HbA1c for inflammatory and metabolic insight
• B12, vitamin D, magnesium, and thyroid panels for cognitive optimization
• Sex hormones, insulin resistance, and micronutrient status for personalized longevity mapping

Nutrition and Supplement Considerations

• Anti-inflammatory protocols rich in omega-3s, polyphenols, and curcumin
• Supportive nutrients for neurotransmitter balance: B-complex, magnesium glycinate, phosphatidylcholine
• Gut–brain support through probiotics, fiber diversity, and fermented foods

Lifestyle and Behavioral Strategies

• Daily gratitude or journaling rituals shown to reduce anxiety and depression by ~7 % (Diniz, 2023)
• Movement and strength training for muscle preservation and insulin sensitivity
• Structured rest—weekly breaks, retreats, or community connection for burnout prevention
• Group programs like Dr. Libert’s SoulCare circles to rebuild belonging and resilience

Timestamps

00:00 - Introduction and episode overview
02:50 - Why joy is crucial in clinical care & science behind it
05:28 - Dr. Libert’s personal story with burnout and rediscovery of joy
07:29 - Practical ways to prevent burnout and cultivate joy
11:33 - The science of joy, neuroplasticity, and brain connectivity
12:35 - Joy’s effects on the stress response and inflammation
18:37 - Observed patient changes with joy and lifestyle interventions
24:41 - Neuroanatomy: prefrontal cortex & limbic system role in emotional regulation
26:12 - Impact of brain connectivity in ADHD & emotional control
31:38 - Practical strategies for reconnecting patients with joy and purpose
36:20 - Research on gratitude and mental health improvements
38:24 - Dr. Libert’s movement and exercise routine
41:10 - Adjusting fitness goals according to life seasons
46:05 - Final thoughts on addressing neurodegeneration and root causes
48:00 - Closing remarks 

Citations

1. Emmons RA, Sefick, WJ, Froh, JJ. Counting blessings versus burdens: An experimental investigation of gratitude and subjective well-being. J Pers Soc Psychol. 2003.
2. Van der Stigchel S et al. Positive emotion and cognitive flexibility. Front Psychol. 2017.
3. Ochsner KN et al. Cognitive regulation of emotion: functional networks and mechanisms. Soc Cogn Affect Neurosci. 2012.
4. Cole SW et al. Eudaimonic well-being and gene expression: CTRA down-regulation. Proc Natl Acad Sci USA. 2013.
5. UC Braid Clinical Trials Registry: Ventral striatum activity correlated with decreases in IL-6 and CRP.
6. Diniz, et al. The effects of gratitude interventions: a systematic review and meta-analysis. PMC 2023.
7. Rueschkamp, Johanna M Grosse. “Neural Correlates of Up-Regulating Positive Emotions in FMRI and Their Link to Affect in Daily Life.” Social Cognitive and Affective Neuroscience, vol. 14, 2019

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.

In this episode, Dr. Chris Magryta and Dr. Erik Lundquist to discuss their new course, Advanced Blood Labs 201—a masterclass in interpreting metabolic and immune biomarkers for proactive, data-informed clinical care. They explore how early identification of metabolic dysfunction and immune dysregulation can improve long-term health outcomes through advanced yet accessible diagnostics. The discussion covers biomarkers such as C-peptide, adiponectin, leptin, fructosamine, LDH, GGT, and glutathione, along with emerging immune markers like SII and SIRI. Listeners will learn how to integrate these insights into practice for earlier, more precise intervention in both children and adults.


You’ll Learn

• Why early biomarker detection matters for identifying metabolic and immune imbalances before symptoms develop
• How to interpret C-peptide, adiponectin, leptin, fructosamine, LDH, and GGT for a clearer picture of metabolic and oxidative stress
• What advanced immune markers—cytokines, NK cells, T-cells, SII, and SIRI—reveal about inflammation and immune activation
• How to use affordable tests like a CBC to gain immunometabolic insights
• Why trend tracking and pattern recognition offer more clinical value than single lab snapshots
• How oxidative stress and mitochondrial biomarkers can guide chronic disease prevention and management

About the Guests

• Dr. Chris Magryta is a pediatrician at Salisbury Pediatrics and host of Women and Children First. His work centers on identifying the root causes of pediatric chronic illness through biomarker analysis, nutrition, and early intervention.
• Dr. Erik Lundquist is the founder of Temecula Center for Integrative Medicine and host of The Root Cause Business of Medicine Podcast. He specializes in integrative and functional medicine, teaching clinicians to bridge evidence-based practice with systems biology.
• Together, they lead the Blood Labs 101 and Advanced Blood Labs 201 courses—comprehensive programs helping practitioners translate complex biomarker data into actionable insights.

Labs Mentioned

• C-peptide
• Fructosamine
• Adiponectin
• Leptin
• LDH (Lactate Dehydrogenase)
• GGT (Gamma-Glutamyl Transpeptidase)
• 8-Hydroxy-D-Guanine
• MPO (Myeloperoxidase)
• CBC (Complete Blood Count)

Supplements Mentioned

• Glutathione (discussed for educational purposes only; not intended as a treatment recommendation)

Courses Mentioned

• Advanced Blood Labs 201 November 2025

Timestamps

• 00:00 – Introduction and course overview
• 02:03 – Early biomarker detection and childhood metabolic health
• 04:07 – Evolution from Blood Labs 101 to 201
• 08:27 – Understanding C-peptide and insulin activity
• 11:08 – Fructosamine and short-term glucose trends
• 13:24 – Adiponectin and leptin in inflammation and metabolism
• 15:20 – Oxidative stress, LDH, glutathione, and DNA damage
• 17:20 – GGT and antioxidant balance
• 20:54 – Cytokines, NK cells, and the SIRI index
• 26:07 – Monocytes and immune pattern recognition
• 32:41 – Why each clinician chose medicine
• 50:52 – Personal growth and lessons beyond the clinic
• 54:00 – Final reflections

Learn More

• Dr. Chris Magryta’s Podcast: Women and Children First
• Dr. Erik Lundquist’s Podcast: The Root Cause Business of Medicine
• Course Information: Advanced Blood Labs 201 at rupahealth.com
• Sponsor: Fullscript – Free platform for whole person care, lab ordering, and supplement management

Frequently Asked Questions About Pediatric and Adult Biomarkers


What is C-peptide and why might it be important to measure in both children and adults?

C-peptide is released with insulin from pancreatic β-cells and reflects endogenous insulin production and β-cell function. Elevated C-peptide may indicate insulin resistance, while low levels can signify β-cell exhaustion. It can be a key tool for identifying early metabolic dysfunction in both pediatric and adult patients early in disease progression (American Diabetes Association, Diabetes Care, 2025).


How does adiponectin relate to inflammation and metabolism across ages?

Adiponectin regulates glucose and lipid metabolism and has anti-inflammatory properties. Low adiponectin levels are linked to insulin resistance and chronic inflammation in children and adults (Nature Reviews Immunology, 2024) and respond positively to healthy lifestyle interventions (The Journal of Clinical Endocrinology & Metabolism, 2008).


What does leptin resistance imply in pediatric and adult patients?

Leptin helps to regulate appetite and energy balance. When cells become resistant to leptin, metabolism and inflammatory control are impaired. Elevated leptin with low adiponectin can correlate with metabolic syndrome and obesity risk across age groups (Nature Reviews Immunology, 2024).


How do SII and SIRI biomarkers relate to immune dysregulation?

The Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI) use platelet, neutrophil, lymphocyte, and monocyte counts from a CBC to reflect immune activation and inflammation balance. Elevated SII or SIRI can indicate systemic inflammation or immune imbalance. Recent pediatric studies found these indices correlate with insulin resistance and metabolic status in adolescents (Frontiers in Endocrinology, 2024).


Can oxidative stress markers like LDH and GGT help to assess long-term health?

These markers can reflect the body’s oxidative stress burden and antioxidant capacity. Elevated LDH or GGT may suggest increased oxidative load and reduced resilience, potentially influencing mitochondrial and metabolic health (Artery Research, 2024).


What is the role of fructosamine in blood sugar evaluation for children and adults?

Fructosamine can provide a two- to three-week snapshot of blood glucose control, offering faster feedback than HbA1c. It’s useful in both adults and children for monitoring short-term glycemic changes (BMJ Open, 2015) and for pediatric patients with variable glucose control (Diabetes Care, 1991).


Are these biomarkers clinically useful in pediatrics, or only in adults?
The guests describe that these biomarkers can be relevant across ages. Early metabolic and immune imbalances often begin in childhood, and monitoring markers like C-peptide, adiponectin, leptin, and SII/SIRI can help identify at-risk children (Frontiers in Endocrinology, 2024).

References

1. Connecting the Spots: Serial Home C-Peptide Measurements for Assessing β-Cell Function. Diabetes Care, American Diabetes Association, 2025. https://diabetesjournals.org/care/article/48/9/1472/163233/Connecting-the-Spots-Serial-Home-C-peptide
2. Adiponectin as a Key Regulator of Inflammation and Metabolism. Nature Reviews Immunology, 2024.  https://www.nature.com/articles/s41577-024-01103-8
3. Changes in Adiponectin and the Leptin/Adiponectin Ratio During Lifestyle Intervention and Association With Metabolic Improvement in Obese Children. The Journal of Clinical Endocrinology & Metabolism, Vol. 93, Issue 8, 2008. https://pubmed.ncbi.nlm.nih.gov/18492759/
4. Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI) as Markers of Metabolic Risk in Adolescents. Frontiers in Endocrinology, 2024. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1426404/full
5. Oxidative Stress Biomarkers and Mitochondrial Dysfunction in Cardiometabolic Health. Artery Research, 2024. https://arteryresearch.biomedcentral.com/articles/10.1007/s44200-024-00062-8
6. Evaluation of Fructosamine as a Short-Term Glycemic Marker in Diabetes. BMJ Open, 2015. https://bmjopen.bmj.com/content/5/5/e007689
7. Use of Fructosamine Test in Diabetic Children. Diabetes Care, Vol. 14, Issue 7, 1991. https://diabetesjournals.org/care/article/14/7/578/17573/Use-of-Fructosamine-Test-in-Diabetic-Children
   
   

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.

Is lithium the missing link in brain health and dementia prevention?

In this episode of The Root Cause Medicine Podcast, Dr. Kate Kresge sits down with Dr. James Greenblatt, a renowned integrative psychiatrist and expert in nutritional psychiatry, to explore the latest research on lithium’s role in brain health. From the groundbreaking 2025 Harvard study to practical clinical applications, they discuss how low-dose lithium - particularly in the form of lithium orotate - may offer a safe, natural approach to preventing and reversing cognitive decline, including Alzheimer’s disease. The conversation covers the science, safety considerations, and how clinicians can thoughtfully integrate lithium into their practice to support neurological resilience and mental well-being.

If you’re ready to expand your understanding of mineral neuroscience and explore innovative strategies to support cognitive health, this episode provides the science, clinical insights, and practical tools you won’t want to miss.

Clinical Takeaways from This Episode

• The Latest Harvard Research & Its Implications: The recent study showing that lithium naturally exists in the brain and diminishes early in Alzheimer’s, with animal models demonstrating that lithium orotate can reverse memory deficits.
• Mechanisms of Lithium in Brain Health: Its anti-inflammatory, neuroprotective, and neuroregenerative actions, including inhibition of GSK3, enhancement of neurotrophic factors, and support of myelin integrity.
• Differences Between Lithium Forms: Lithium carbonate (medication) vs. nutritional lithium orotate; why the latter is safer at microdose levels and less sequestered by amyloid plaques.
• Safety and Monitoring: Practical considerations for dosing, laboratory testing (such as hair mineral analysis), and monitoring thyroid and kidney function over time.
• Environmental and Dietary Lithium: The influence of water sources, diet, and geographic variations on lithium status, and implications for mental health and neuroprotection.
• Impulsivity, Mood, and Behavioral Regulation: How low-dose lithium may support impulse control, reduce irritability, and improve emotional stability across various psychiatric and neurological conditions.
• Future Therapeutic Directions: The potential for broader use of low-dose lithium as a public health intervention to reduce rates of suicide, neurodegenerative diseases, and mental health disorders.

Guest Bio:

Dr. James Greenblatt, MD — An integrative psychiatrist and pioneer in nutritional psychiatry, Dr. Greenblatt has over 40 years’ experience in the field. He is the author of The Cinderella Story of Nutritional Lithium and offers extensive training programs for clinicians on natural interventions for mental health and cognitive decline.

Labs Mentioned (Monitoring & Context)

• Hair mineral analysis (lithium marker)
• Thyroid function tests
• Kidney function tests

Ingredients & Therapeutic Nutrition Mentioned

• Lithium orotate 
• Magnesium supplements
• Dietary sources of lithium (e.g., drinking water, herbs like thyme)

Resources Mention

• Nutritional Lithium: A Cinderella Story 
• Lithium deficiency and the onset of Alzheimer’s disease 2025 paper

Timestamps

• 00:00 Introduction & episode overview
• 02:04 Harvard’s groundbreaking research on lithium and cognition
• 05:36 Historical context: lithium in psychiatry and nutrition
• 07:43 Lithium’s neuroprotective mechanisms: inflammation, neurogenesis, GSK3 inhibition
• 11:54 Differences between lithium carbonate and lithium orotate—clinical implications
• 13:35 Lithium sequestration by amyloid plaques and the unique properties of orotate
• 15:28 How lithium supports neurotransmitter balance and mood stability
• 19:21 Safety strategies: dosing, lab monitoring, and real-world practice
• 23:35 Assessing lithium levels: hair analysis and environmental factors
• 26:54 Geographic influences on natural lithium exposure and implications for mental health
• 29:03 Lithium’s role in impulsivity regulation and behavioral health
• 35:16 Clinical case examples: children to adults, mood stabilization, addiction, and cognitive decline
• 37:15 Treatment timelines and patient outcomes with low-dose lithium
• 42:50 Long-term management considerations and lab monitoring protocols
• 46:12 The preventive potential of low-dose lithium for Alzheimer’s disease and dementia
• 49:18 Industry influence, patent issues, and future directions in natural lithium therapies
• 55:05 Resources for clinicians and closing remarks

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.