Inflammation

Dr. M’s Women and Children First Podcast #103: Sam Yanuck, DC – Cogence

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Today on Dr. M’s Women and Children First, we’re joined by Dr. Sam Yanuck, a clinician-educator who has spent more than three decades translating immunology from the bench to the bedside. Dr. Yanuck has been in private practice since 1992 and is the creator of Cogence Immunology, one of the most widely respected functional immunology training programs in the world. Through Cogence, he has trained over 9,900 clinicians internationally to think mechanistically about immune signaling, chronic inflammation, autoimmunity, and the complex, often nonlinear patterns that define chronic disease.

What sets Dr. Yanuck apart is his insistence on precision. His work focuses on understanding the immune system as a dynamic network—one shaped by timing, context, feedback loops, and individual biology—rather than a collection of isolated lab values or diagnoses. In his clinical model, chronic illness is not random; it reflects an identifiable matrix of immune, metabolic, environmental, and regulatory factors that can be mapped, understood, and addressed.

In today’s conversation, we’ll explore how modern immunology reshapes clinical thinking around autoimmunity, chronic inflammatory disease, and long-term health—especially in complex patients where standard frameworks fall short.
This is a deep dive. If you care about mechanism, signal over noise, and treating patients with both scientific rigor and biological humility, this episode is for you.

Today, we’re stepping outside the sterile lab and into the wild world of evolutionary biology — where our immune system didn’t emerge in a vacuum, but in dirt, in danger, and in the delicate dance between microbe and mammal.

Join me and Dr. Sam Yanuck -the clinician, the teacher, and one of the best translators of complex immunology into something both clinically useful and biologically beautiful.

Dr. M

Dr. M’s SPA Newsletter Volume 15 Issue 27 – Immune Aging

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The Evolutionary Tug-of-War – Inflammation’s Double-Edged Sword

“Environmental factors, particularly infections, have fundamentally shaped human evolution by selecting for protective inflammatory response mechanisms that enhance survival. This evolutionary pressure has created a core biological paradox: inflammation is indispensable for host defense, yet its dysregulation significantly heightens disease and mortality risk. This fundamental tension raises three fundamental questions about human aging and immunity: (1) How have selective pressures driven the evolution of mechanisms to balance inflammation’s protective benefits against its harmful consequences? (2) Why does substantial variability in healthspan persist despite historically stable rates of aging? (3) Does evolutionary prioritization of reproductive fitness inherently limit longevity?” (Manoharan et. al. 2025)

Let’s talk about the fire inside us. Inflammation is our body’s 911 system: lightning-fast, life-saving when a bug invades or a thorn rips skin. But leave that alarm blaring 24/7 and the fire torches the house.

Evolution faced this paradox: crank the immune dial high enough to survive infection and childbirth, yet install brakes so we don’t self-destruct by 40. Manoharan’s team just mapped those brakes in 17,500 humans and called it immune resilience (IR) or the ability to fight hard, clean up fast, and stay cool afterward… and linguistic aging associations…

Dr. M

Dr. M’s SPA Newsletter Volume 15 Issue 17

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Inflammaging from a Population View

In a landmark study published in Nature Aging on July 7, 2025, researchers challenge a cornerstone of modern gerontology by showing that inflammaging, chronic, age-associated low-grade inflammation, is not universal across all human populations. The abstract states the following: “Inflammaging, an age-associated increase in chronic inflammation, is considered a hallmark of aging. However, there is no consensus approach to measuring inflammaging based on circulating cytokines. Here we assessed whether an inflammaging axis detected in the Italian InCHIANTI dataset comprising 19 cytokines could be generalized to a different industrialized population (Singapore Longitudinal Aging Study) or to two indigenous, nonindustrialized populations: the Tsimane from the Bolivian Amazon and the Orang Asli from Peninsular Malaysia.

We assessed cytokine axis structure similarity and whether the inflammaging axis replicating the InCHIANTI result increased with age or was associated with health outcomes. The Singapore Longitudinal Aging Study was similar to InCHIANTI except for IL-6 and IL-1RA. The Tsimane and Orang Asli showed markedly different axis structures with little to no association with age and no association with age-related diseases. Inflammaging, as measured in this manner in these cohorts, thus appears to be largely a byproduct of industrialized lifestyles, with major variation across environments and populations.” (Franck et. al. 2025)

The research team analyzed 19 cytokines in over 2,800 individuals from four diverse populations: two industrialized cohorts: Italy’s InCHIANTI and the Singapore Longitudinal Aging Study (SLAS); two non-industrialized, Indigenous groups: the Tsimane of the Bolivian Amazon and the Orang Asli of Peninsular Malaysia.

In Italy and Singapore, the industrialized regions noted classic inflammaging signatures with inflammatory markers like IL‑6, TNF-α, and CRP increased with age, and correlated strongly with age-related chronic diseases such as cardiovascular and kidney disease….. and more on inflammaging…

Dr. M

Dr. M’s Women and Children First Podcast #95 – Sanjay Bhorjaj, MD – Living Longer and Klotho

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Today’s guest is Dr. Sanjay Bhojraj, a powerful voice at the crossroads of advanced interventional cardiology and root-cause wellness. Dr. Bhojraj is board-certified in Cardiovascular Diseases and Interventional Cardiology, and one of only a small number of interventional cardiologists in the United States who is also certified in Functional Medicine through the Institute for Functional Medicine.

Dr. Bhojraj earned his medical degree from Indiana University School of Medicine, trained in internal medicine at Northwestern, and completed a cardiology fellowship at the renowned Henry Ford Health System. For over two decades, he practiced in conventional cardiology, saving lives daily with stents, angioplasties, and transcatheter valve replacements.

But along the way, something essential began to stir. He found himself asking bigger questions: Why do people arrive in the cath lab in the first place? Why are we not doing more to prevent the first or second heart event? And what role do nutrition, sleep, stress, and emotional health truly play in long-term cardiovascular outcomes?

These questions led Dr. Bhojraj to Functional Medicine, not as an alternative, but as an evolution, a model that restores agency to patients and equips the body to heal through comprehensive lifestyle optimization. He now leads the Well12 Program, a transformational experience that guides individuals in upgrading the foundational systems of their health from metabolism to mindset, so they can live not just longer, but better.

Today, Dr. Bhojraj and I explore the remarkable protein Klotho and the emerging science linking it to human longevity and health span. This is a conversation you won’t want to miss, a glimpse into what may become a defining frontier in upstream disease prevention.

Enjoy,

Dr. M

Dr. M’s SPA Newsletter Volume 15 Issue 15

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Systemic Maternal Inflammation and Neurodevelopment: The Role of IL-6 and IFN-γ in Autism Spectrum Disorder

I just returned from Estes Park, Colorado where I presented a lecture on the Growing Brain/Mind – a tour through the underpinnings of childhood neurological changes that we call Autism. The timing is perfect for this article to be written.

In an era when chronic disease in children is rising at an unprecedented pace, the search for root causes must include an honest inquiry into the conditions present during fetal development. The review article by Majerczyk and colleagues, Systemic Maternal Inflammation Promotes ASD via IL-6 and IFN-γ, brings forward a critical piece in this puzzle that I began to explore a few years ago when writing a book. It connects the dots between maternal immune dysregulation and long-term neurodevelopmental outcomes, specifically autism spectrum disorder (ASD). Through a synthesis of clinical data and animal research, the authors make a compelling case for the centrality of two inflammatory messengers, interleukin-6 (IL-6) and interferon-gamma (IFN-γ), in shaping fetal brain development during gestational stress. The key words here being GESTATIONAL STRESS, the recurring scientific theme for ASD development, not vaccines… and some literature reviews.

Dr. M

Dr. M’s SPA Newsletter Volume 15 Issue 13

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Literature Review

1) An exciting phase three trial with the CETP inhibitor Obicetrapib has shown serious promise for ASCVD and Alzheimer’s Disease (AD). “In BROADWAY, a pre-specified AD sub-study was designed to assess plasma AD biomarkers in patients enrolled in the BROADWAY trial and evaluated the effects of longer duration of therapy (12 months) with a prespecified population of ApoE3/4 or 4/4 carriers. The sub-study included 1727 patients, including 367 ApoE4 carriers. The primary outcome measure was p-tau217 absolute and percent change over 12 months. Additional outcome measures included neurofilament light chain (“NFL”), glial fibrillary acidic protein (“GFAP”), p-tau181, and Aβ42/40 ratio absolute and percent change over 12 months. NewAmsterdam observed statistically significant lower absolute changes in p-tau217 compared to placebo over 12 months in both the full ITT population (p<0.002) and in ApoE4 carriers (p=0.0215).” (NAMS)

Obicetrapib has shown significant LDL and Lp(a) lowering effects as well in early trials. I will be watching this discovery closely as it may be a game changer for these diseases. “In the BROADWAY trial, more than 2,500 participants with established heart disease or genetic high cholesterol were given either Obicetrapib or a placebo, in addition to their regular cholesterol medications. After 12 weeks, those on Obicetrapib had dropped their LDL cholesterol by 32.6 per cent and Lp(a) by 33.5 per cent on average – many achieved guideline-recommended targets for the first time.” (Sci Tech Daily) The drop in Lp(a) is the profound result as this is a massive risk factor for ASCVD and to date is not moveable by statins and most used meds.

2) GLP1 drugs and risk for macular degeneration?… and more

Dr. M

Dr. M’s SPA Newsletter Volume 15 Issue 8

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Itaconate, what is it and why does it matter?

Science Heavy – skip to the bold for take home if you want to avoid the science.

The biggest takeaway from this complex science is this: High fat, high sugar diets (Ultra Processed Foods) are associated with decreased itaconate activity and increased inflammation. The science further answers the question of whether we should allow ultra processed food in schools.

Ultra Processed Foods likely reduce itaconate production driving inflammation, metabolic dysregulation, and gut dysbiosis, which could worsen active disease. Lower itaconate levels likely impair your body’s ability to resolve inflammation, potentially leading to prolonged issues with healing and repair. To support itaconate’s anti inflammatory activity, shift away from UPFs toward an anti-inflammatory diet (e.g., Mediterranean, rich in vegetables, omega-3s, and fiber) to reduce inflammation, support gut health, and enhance itaconate’s immune-regulating effects.

Science:…..

Enjoy,

Dr. M

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