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The vagus nerve, also known as the Great Nerve, connects the brain to all parts of the body, like an internet (Figure below). Every week we’re learning more about its importance for health and disease. Until recent years the brain and immune system were thought to be in separate “firewalled” compartments. But that turned out to be far from the truth. Dr. Kevin Tracey, who directs the Feinstein Institute at Northwell Health, has been studying the vagus nerve for more than 3 decades. In the early 1990’s he made the seminal observation that stimulating the vagus reduces the inflammatory cytokine known as tumor necrosis factor (TNF), what he described at the time as a “holy s**t” moment. In 2025 he published the book THE GREAT NERVE with many rich patient anecdotes and the history for how this field developed. I wrote about the brain-immune axis previously on Ground Truths, spotlighting the vagus nerve’s role. That included much more on depth of the pathways if you are interested. We discussed the recent FDA July approval for refractory rheumatoid arthritis (RA)(unresponsive to medications or intolerance to medical therapy) based on a sham-controlled randomized trial published in December 2025 in Nature Medicine. It is striking that the benefits were derived from 1 minute of vagal stimulation per day. That stimulation is barely perceived (tingling, many not at all) by device recipients. The surgery takes one hour to implant the tiny stimulator device along side the vagus nerve in the neck. But this is much bigger than a treatment for RA. It is now being tested for lupus, Crohn’s disease, and other autoimmune conditions. That’s beyond the role vagus nerve stimulation (VNS) has played for epilepsy and depression, independent of VNS’s anti-inflammatory impact (Tracey named it “the inflammatory reflex”). We also discussed handheld VNS devices, potential use for Long Covid and POTS, cold plunges, heart rate variability, stress, and other topics related to the vagus nerve and parasympathetic nervous system (the brakes, “rest and digest” as opposed to the sympathetic nervous system (the gas, “fight or flight”). Most people are not aware of this device approved treatment for an autoimmune disease. Our treatments are so drug-centric but they are immunosuppressive, have important side-effects, and are expensive. It’s good to see a non-drug approach get compelling data as an alternative. Moreover, as I recently wrote about, there’s a shift ongoing from treatment to cures vs autoimmune diseases that will be adding to the mix. Here are some very recent papers about the vagus nerve to give you a sense about how its prominence is getting appreciated more all the time Gut-brain-vagus axis for reward circuit and addiction, 30 Jan 2026, Science Advances Randomized trial of VNS for depression , Int J of Neuropsychopharm 2026 The vagus nerve role in heart function after a heart attack, Cell, February 2026 Vagus receptors and hemorrhage, blood volume, Nature, 28 Jan 2026 A Quick Poll Thank you Harshi Peiris, Ph.D., Tay MacIntyre, David Dansereau, MSPT, Max Manwaring-Mueller, RJ, and over 600 others for tuning into my live video with Kevin J. Tracey, MD! Join me for my next live video with Robert Wachter Feb 4th, 12:30 PM PT in the app. ********************************************** Thanks to Ground Truths subscribers (approaching 200,000) from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026. Get full access to Ground Truths at erictopol.substack.com/subscribe

Back in 2005 Dan Buettner patented Blue Zones. He’s written 9 books, of which 5 were NY Times bestsellers, and has another one in the works. His 2023 Netflix documentary series “Live to 100: Secrets of the Blue Zones” won Emmy awards and was widely viewed. Many of the main points that Dan has emphasized over the years—healthy diet (he highlighted whole grains, beans, nuts, greens, and “peasant food” here), physical activity, social engagement, and sense of purpose—are backed up by randomized trials and/or large, prospective studies, as I reviewed in Super Agers. In this interview, I asked Dan about the critique he’s faced, predominantly from Saul Newman, a biologist in the UK, about accuracy of the data for extreme longevity in the blue zones. In December 2025, two of his collaborators published in The Gerontologist a rebuttal response (open-access) entitled “The validity of Blue Zones demography: a response to critiques” on the rigorous demographic work they’ve done. We also discussed the marketing and business operations of Blue Zones LLC, the company he sold to Adventist Health in 2020. His son, Danny, is the EVP of the company and likely successor to Dan’s work in the future. As Dan said, “He’s my genetic upgrade.” I hope you find this conversation informative. An AI-generated transcript is available in the tab at top right above. Some biomedical updates from the past week: * A vaccine to prevent colon cancer in carriers of mutations of Lynch Syndrome looks good for strong immune response and safety, ready for Phase 3 clinical trials * A review of the data of Tylenol during pregnancy reaffirms its safety and lack of increased risk for autism, ADHD, and intellectual disability. * Our perspective/review on how AI and large language models can reduce global health inequities * Another big jump vs refractory autoimmune diseases, this time for hemolytic anemia, using engineered T cells. See my recent review of this topic, from treatment to cures. * A pair of new large prospective cohort studies that reinforce the importance of even small increases in physical activity, along with sleep and diet, for reduction all-cause mortality and improvement in healthspan. Thanks to Ground Truths subscribers (nearly 200,000) from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026 Thank you Annie Fenn, MD, Harshi Peiris, Ph.D., Strategy Shots, Rebecca Moore, Lynn L, and many others for tuning into my live video with Dan Buettner! Join me for my next live video in the app. Get full access to Ground Truths at erictopol.substack.com/subscribe

Jonathan Kipnis is a neuroscientist, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology at Washington University, St. Louis, who discovered meningeal lymphatics and has been a prolific researcher in brain drainage and the continuous immune system surveillance of the brain. I made this infographic with the help of Notebook LM to summarize many of the concepts we discussed. (Notebook LM is free and worth trying) We went over his new review with 24 co-author leading experts in the recent issue of Neuron A Clever Cover The drainage system anatomy on influx and efflux (blue arrows) The 3 ways the flow of glymphatics are modulated. I mentioned the recent studies that show atrial fibrillation, via reduced cardiac pulsation, has an effect on reducing glymphatic flow. We also discussed his recent review on the immune surveillance system in Cell: A schematic of key channels for the “faucet” and “drain” and how the system changes from healthy to central nervous system autoimmune diseases (such as multiple sclerosis) and aging with different immune bar codes. The outsized role of astrocytes in the brain, a subject of recent Nature feature, was also mentioned. Our understanding of the brain’s immune system has been completely revamped. Kipnis’s recent review in Nature Immunology highlights the critical role of the outer layers —the skull, dura and meninges—as an immune reservoir that is ready to detect and react abnormalities in the brain with a continuous “intelligence report.” Notably, Kipnis touched on lymphatic-venous anastomosis (LVA) surgery (Figure below) for Alzheimer’s disease which is popular in China, available at 30 centers in multiple cities, and the subject of multiple randomized trials as a treatment for Alzheimer’s. Trials of LVA surgery are also getting started in the United States for treatment of Alzheimer’s and Parkinson’s diseases. Here is a Figure to show the surgical anastomoses (connections) from the deep cervical lymphatics to external jugular and internal jugular veins This podcast was packed with insights relevant to health, spanning sleep quality, sleep medications, autoimmune diseases, and Alzheimer’s disease. I hope you find it as informative and engaging as I did. A Poll ************************************ This is my 4-year anniversary of writing Ground Truths. Post number 250! That’s an average of more than 1 per week, nearly 5 per month. Hard for me to believe. Thanks to Ground Truths subscribers (approaching 200,000) from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026 Thank you EG, Alan, Lynn L, Stacy Mattison, Jackie, and many others for tuning into my live video with Jonathan Kipnis! Join me for my next live video in the app. Get full access to Ground Truths at erictopol.substack.com/subscribe

A recording from my enthralling conversation with Prof Matthew Cobb about the life and science contributions of Francis Crick, regarded as one of the most influential biologists of all times, along with Darwin and Mendel. As you’ll see, there’s so much more to Crick’s story than cracking DNA’s double helix structure in a matter of weeks with James Watson. Matthew Cobb, Emeritus Professor of the University of Manchester, has written several award-winning books on life science, but I think this is his most important one to date, deeply researched and a thrilling account of Crick’s life, clearing up, as best as one can, many questions, and presenting some surprises. The transcript is available (A.I. generated) by clicking at the top right. A few things we discussed —Crick’s reaction to James Watson’s book Crick contrasted his own approach to science writing with Watson’s memoir: “The difference between my lecture and your book is that my lecture had a lot more intellectual content and nothing like so much gossip. (...) Your book on the other hand, is mainly gossip and I think it a pity in this way that there is so much of it that it obscures some of the important conclusions which can be drawn of what we did at the time”. —The Peyote Poem, by Michael McClure (part 1) that had a big influence on Crick —Crick’s 1994 neuroscience book “The Astonishing Hypothesis” “You, your joys and your sorrows, your memories and your ambitions, your sense of personal identity and free Weill, are in fact no more than the behavior of a vast assembly of nerve cells and their associated molecules.”—Crick The book has been reviewed at Science, Nature, The Economist and many other journals. Here is a gift link to The Economist It has deservedly been named a best book of 2025 by The Guardian, The Economist, and many other media. Thank you Bruce Lanphear, Harshi Peiris, Ph.D., Elisabetta Pilotti, Allan Konopka, Stephen B. Thomas, PhD, and over 500 others for tuning into my live video with Matthew Cobb! ********************* Upcoming, this Wednesday 9AM PT, live podcast I will be interviewing Dan Buettner founder of the Blue Zones Join us! ********************** Thanks to US News for recently being named one of the 25 best leaders in the United States https://www.usnews.com/news/leaders/articles/best-leaders-2025-eric-topol ^^^^^^^^^^^^^^^^^^^^^^ Thanks to >190,000 Ground Truths subscribers from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. If you found this interesting PLEASE share it! Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026. Get full access to Ground Truths at erictopol.substack.com/subscribe

A couple of weeks ago, the FDA Commissioner published a WSJ oped “The FDA Liberates Women’s Hormone Replacement Therapy” (←gift link) and, with other FDA colleagues, a JAMA essay entitled “Updated Labeling for Menopausal Hormone Therapy” (open-access). That change, and the data cited, led to a series of articles in the days that followed, such as at STAT News “FDA reverses decades-old warning on hormone therapy products for menopause. Agency says the treatments o!fer heart, brain, and bone health benefits” and at the Washington Post “The FDA finally corrects its error on menopause hormone therapy. Women have been needlessly scared away from effective treatments.” If you read through these links, you’ll be confused. Does MHT have proven cognitive benefits? What about a study from 1991 that showed ~50% reduction of fatal heart events with MHT? Or the 35% decreased risk of Alzheimer’s disease? Or the breast cancer increased risk attributed to medroxyprogesterone acetate? I turned to my go-to gynecologist truth teller, Dr. Jen Gunter, to get her review of the evidence. This is a complex topic, with old data from the 2002 Women’s Heath Initiative (WHI), new reports since, population level analysis, changes in preparations of MHT including local delivery, and much more. Here is our conversation which isn’t just about MHT but includes “Big Wellness” marketing direct to middle aged women, the new FDA approved drug for hot flashes, the $14 million cut of the NIH’s Office of Women’s Health , marked increase in philanthropic support of women’s health research, the Surgeon General nominee, ovarian failure, and a lightning round on proven benefits of MHT. Here’s a brief clip on her views of the women’s health “wellness” predators We also discussed the reasons for Dr. Gunter’s planned move next year back to Canada after practicing gynecology for 3 decades in the United States. I referred to a recent GT I wrote about the WHI and the potential favorable impact of MHT on the immune system, as suggested by new data on organ clocks. That finding, which has been replicated, may be linked to healthy aging, extending healthspan. **************************** Thanks to the >190,000 Ground Truths subscribers from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. If you found this interesting PLEASE share it! Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.Thank you Debbie Weil, Cynthia Brumfield, Sara Garcia, Harshi Peiris, Ph.D., Liane Moccia, and over 1,000 others for tuning into my live video with Dr. Jen Gunter! Join me for my next live video in the app. Get full access to Ground Truths at erictopol.substack.com/subscribe

Dr. Susan Monarez was the first CDC Director to be confirmed by the Senate and served from July 31, 2025 – August 27, 2025. Because she refused to give approval to new vaccine recommendations without ever seeing them or their evidence and firing scientists without cause, she was fired. In my view, she’s a hero for standing up for science and speaking truth to power. In her first live interview since leaving the CDC, we review her background. That includes growing up in rural Wisconsin and getting her college and PhD education at UW-Madison, the latter in microbiology and immunology. She then went on to 18 years of government service with an extensive portfolio of jobs and management at BARDA, the White House, ARPA-H, and others, before becoming Acting Director of the CDC in early 2025. We discussed the horrific CDC shooting on August 8th, days after she started. Then we reviewed a conversation that we had on August 19th in which she laid out her exciting vision for the future of CDC, emphasizing the goal of prevention (BTW, CDC stands for Centers for Disease Control and Prevention) and asked me to help as an advisor. At the time, she was well aware, with growing tension, that her tenure at CDC might be limited. I asked about her perspective for the jobs of 4,300 people at CDC who have been terminated, which account for more than 1/3rd of the workforce, no less the gutting of the budget. Then we got into what she learned from this ordeal and her plans for the future, which includes a very ambitious initiative: 90/90/2035. As you’ll see from our conversation, Dr. Monarez is exceptionally resilient and an optimist. She’s got lots to do in the years ahead to carry out her mission of promoting human health! Dr. Monarez just started a Substack The Road Best Traveled so you can follow her there. It was a real privilege for me to do this interview with her. In deep admiration of her willingness to not only take on the job of CDC Director in tough circumstances, her professionalism during testimony at the Senate committee hearing, her impressive yet unrealized vision for transforming the CDC, and refusing to cave to immense pressure from the HHS Secretary to move ahead with his agenda. Thank you Julie, Stephen B. Thomas, PhD, David Dansereau, MSPT, Dr. Sara Wolfson, Vau Geha, and >500 others for tuning into my live video with The Road Best Traveled! Thanks for being a Ground Truths subscriber! Please spread the word. Get full access to Ground Truths at erictopol.substack.com/subscribe

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Prof Shana Kelley is the Neena Schwartz Professor of Chemistry and Biomedical Engineering at Northwestern University and President of the CZI Chicago Biohub, which brings together life scientists at Northwestern, University of Chicago, and U. Illinois Urbana Champaign. Her lab’s website provides recent publications in the 3 major areas of biomolecular sensors, rare and single cell analysis, and intracellular molecular delivery. You are undoubtedly familiar with wearable biosensors on the wrist and rings, and continuous glucose monitoring (CGM), all of which can transmit physiologic data in real time to your smartphone. What is different about Prof Kelley’s work is the ingenious way of continuously tracking any proteins in our blood via a sensor that could function just like CGM in the future (hair thin sensor applied just below the skin and data relayed to your smartphone). A proof-of-concept paper in Science showed how exquisitely sensitive such a sensor worked to track inflammation markers [interleukin-6 (IL-6) and tumor necrosis factor (TNF)] in the diabetic rat model. As seen. below, just the injection of insulin evoked inflammation, and introduction of lipopolysaccharide (LPS) did so markedly. This capability opens up the potential for monitoring body-wide inflammation in real time, but also extends to many other conditions such as autoimmune diseases, heart failure (e.g. continuous brain natriuetic peptide monitoring), and neurodegenerative diseases (with specific markers of neuroinflammation). This innovation represents a new dimension in individualized (precision) medicine. In our conversation, Shana takes us through the discovery of these unique bimolecular sensors that have no reagents, and use electricity to shake off the protein from DNA strands. And she maps out the path to clinical trials and commercialization in the next couple of years. Thank you Stephen B. Thomas, PhD, Linda Kemp, Lynn L, Pat Mumby PhD, David Hobson, and many others for tuning into my live video with Shana Kelley! Join me for my next live video in the app, along with posts on biomedical news and analysis. *********************************************************************** Thanks you for your listening, reading and subscribing to Ground Truths. If you found this interesting PLEASE share it! That makes the work involved in putting these together especially worthwhile. All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access. Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don't hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! Get full access to Ground Truths at erictopol.substack.com/subscribe

Thank you Bruce Lanphear, Clyde Wilson, Tracy Dennis-Tiwary, Diego Pereyra, Dr Mike Hunter, and many others for tuning into my live video with Charlotte Blease! Join me for my next live video in the app. Whether A.I. will transform the practice of medicine in a positive way remains controversial. Health researcher Prof Charlotte Blease, on faculty at Uppsala University in Sweden and researcher at Harvard University, has written a new book —Dr. Bot—that critically assesses the unmet needs in healthcare and whether A.I. can fulfill them. She provides an optimistic viewpoint (see the subtitle), and our conversation probes whether that is justified. She has a substack, too, here Thanks for listening to Ground Truths. Through analytic essays and podcasts, I try to cover the important issues and discoveries in life science and medicine. If you have suggestions for topics I should get into, please pass them along. Get full access to Ground Truths at erictopol.substack.com/subscribe

Thank you Sara Garcia, Andrew O'Malley BSc PhD, Sam Hester, Julie, Stephen B. Thomas, PhD, and so many others for tuning into my live video with Peter Hotez! Join me for my next live video in the app. Peter Hotez and I discuss his new book, co-authored with Michael Mann, SCIENCE UNDER SEIGE, on the anti-science superstorm culminating from the climate crisis, the Covid pandemic, and a vast interconnected network that has waged a direct assault on scientific truth. During our conversation we trace history of priors in civilization, such as Lysenko and Stalinism in the last century. And acknowledge the future role of A.I. for promoting infinite disinformation. Beyond human suffering and direct health outcome consequences (such as Red Covid), the toll this is taking on the career of young scientists, universities, public health agencies, and loss of public trust are reviewed. The interdependent role of the media and the wellness industry is touched on. The book and our conversation puts forth a call to arms, potential solutions, including the need to move away from invisible scientists and political activism. Thanks for listening to Ground Truths podcasts and reading the analytic posts. In case you missed any, these are a few recent and related ones: Podcasts with Michael Osterholm and Sanjay Gupta on their new books—The Big One and It Doesn’t Have to Hurt, respectively. Next up is Charlotte Blease and her new book Dr. Bot on where we are headed with medical A.I. If you found this interesting PLEASE share it! That makes the work involved in putting these together especially worthwhile. All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access. Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don't hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. Get full access to Ground Truths at erictopol.substack.com/subscribe

Thank you Jose Bolanos MD, Dr. Zeest Khan, Lawrence Toole, Julie, Stephen B. Thomas, PhD, and many others for tuning into my live video with Dr. Sanjay Gupta. Join me for my next live video in the app. A Brief Summary of Our Conservation We discussed the new understanding and approach to chronic pain, which affects nearly 1 in 4 adults. Dr. Gupta gets personal telling the story of his wife, Rebecca, who has an autoimmune disease and at one point he had to carry her up stairs. He also tells the story of his mother who had a back injury and didn’t want to live because of the pain. How his family members got relief is illuminating. Our whole understanding and approach to pain has changed, with the acronym change from RICE to MEAT. A newly approved drug Suzetrigine (Journavx) exploits the sodium channel gene mutation initially discovered via a family of fire walkers. It’s the first new pain medicine approved for more than 2 decades. Many other new non-opioid treatments are reviewed, no less lifestyle changes (anti-inflammatory diet and sleep), and acupuncture. Sanjay’s research over the past few years has led to a video special on CNN with the same title as the book, set to air 9 PM EST Sunday. If you know someone suffering chronic pain, please share the post. Get full access to Ground Truths at erictopol.substack.com/subscribe

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This is a hybrid heart disease risk factor post of a podcast with Prof Bruce Lanphear on lead and a piece I was asked to write for the Washington Post on risk factors for heart disease. First, the podcast. You may have thought the problem with lead exposure was circumscribed to children, but it’s a much bigger issue than that. I’ll concentrate on the exposure risk to adults in this interview, including the lead-estrogen hypothesis. Bruce has been working on the subject of lead exposure for more than 30 years. Let me emphasize that the problem is not going away, as highlighted in a recent New England Journal of Medicine piece on lead contamination in Milwaukee schools, “The Latest Episode in an Ongoing Toxic Pandemic.” Transcript with links to the audio and citations Eric Topol (00:05): Well, hello. This is Eric Topol with Ground Truths, and I'm very delighted to welcome Professor Bruce Lanphear from Simon Fraser University in British Columbia for a very interesting topic, and that's about lead exposure. We tend to think about lead poisoning with the Flint, Michigan, but there's a lot more to this story. So welcome, Bruce. Bruce Lanphear (00:32): Thank you, Eric. It's great to be here. Eric Topol (00:33): Yeah. So you had a New England Journal of Medicine (NEJM) Review in October last year, which was probably a wake up to me, and I'm sure to many others. We'll link to that, where you reviewed the whole topic, the title is called Lead Poisoning. But of course it's not just about a big dose, but rather chronic exposure. So maybe you could give us a bit of an overview of that review that you wrote for NEJM. Bruce Lanphear (01:05): Yeah, so we really focused on the things where we feel like there's a definitive link. Things like lead and diminished IQ in children, lead and coronary heart disease, lead and chronic renal disease. As you mentioned, we've typically thought of lead as sort of the overt lead poisoning where somebody becomes acutely ill. But over the past century what we've learned is that lead is one of those toxic chemicals where it's the chronic wear and tear on our bodies that catches up and it's at the root of many of these chronic diseases that are causing problems today. Eric Topol (01:43): Yeah, it's pretty striking. The one that grabbed me and kind of almost fell out of my chair was that in 2019 when I guess the most recent data there is 5.5 million cardiovascular deaths ascribed to relatively low levels, or I guess there is no safe level of lead exposure, that's really striking. That's a lot of people dying from something that cardiology and medical community is not really aware of. And there's a figure 3 [BELOW] that we will also show in the transcript, where you show the level where you start to see a takeoff. It starts very low and by 50 μg/liter, you're seeing a twofold risk and there's no threshold, it keeps going up. How many of us do you think are exposed to that type of level as adults, Bruce? Bruce Lanphear (02:39): Well, as adults, if we go back in time, all of us. If you go back to the 1970s when lead was still in gasoline, the median blood lead level of Americans was about 13 to 15 µg/dL. So we've all been exposed historically to those levels, and part of the reason we've begun to see a striking decline in coronary heart disease, which peaked in 1968. And by 1978, there was a 20% decline, 190,000 more people were alive than expected. So even in that first decade, there was this striking decline in coronary heart disease. And so, in addition to the prospective studies that have found this link between an increase in lead exposure and death from cardiovascular disease and more specifically coronary heart disease. We can look back in time and see how the decline in leaded gasoline led to a decline in heart disease and hypertension. Eric Topol (03:41): Yeah, but it looks like it's still a problem. And you have a phenomenal graph that's encouraging, where you see this 95% reduction in the lead exposure from the 1970s. And as you said, the factors that can be ascribed to like getting rid of lead from gasoline and others. But what is troubling is that we still have a lot of people that this could be a problem. Now, one of the things that was fascinating is that you get into that herbal supplements could be a risk factor. That we don't do screening, of course, should we do screening? And there's certain people that particularly that you consider at high risk that should get screened. So I wasn't aware, I mean the one type of supplements that you zoomed in on, how do you say it? Ayurvedic? Supplements With Lead Bruce Lanphear (04:39): Oh yeah. So this is Ayurvedic medicine and in fact, I just was on a Zoom call three weeks ago with a husband and wife who live in India. The young woman had taken Ayurvedic medicine and because of that, her blood lead levels increased to 70 µg/dL, and several months later she was pregnant, and she was trying to figure out what to do with this. Ayurvedic medicine is not well regulated. And so, that's one of the most important sources when we think about India, for example. And I think you pointed out a really important thing is number one, we don't know that there's any safe level even though blood lead levels in the United States and Europe, for example, have come down by over 95%. The levels that we're exposed to and especially the levels in our bones are 10 to 100 times higher than our pre-industrial ancestors. Bruce Lanphear (05:36): So we haven't yet reached those levels that our ancestors were exposed to. Are there effects at even lower and lower levels? Everything would suggest, we should assume that there is, but we don't know down below, let's say one microgram per deciliter or that's the equivalent of 10 parts per billion of lead and blood. What we also know though is when leaded gasoline was restricted in the United States and Canada and elsewhere, the companies turned to the industrializing countries and started to market it there. And so, we saw first the epidemic of coronary heart disease in the United States, Canada, Europe. Then that's come down over the past 50 years. At the same time, it was rising in low to middle income countries. So today over 95% of the burden of disease from lead including heart disease is found in industrializing countries. Eric Topol (06:34): Right. Now, it's pretty striking, of course. Is it true that airlines fuel is still with lead today? Bruce Lanphear (06:45): Well, not commercial airlines. It's going to be a small single piston aircraft. So for example, when we did a study down around the Santa Clara County Airport, Reid-Hillview, and we can see that the children who live within a half mile of the airport had blood lead levels about 10% higher than children that live further away. And the children who live downwind, 25% higher still. Now, nobody's mapped out the health effects, but one of the things that's particularly troubling about emissions from small aircraft is that the particle size of lead is extraordinarily small, and we know how nanoparticles because they have larger surface area can be more problematic. They also can probably go straight up into the brain or across the pulmonary tissues, and so those small particles we should be particularly worried about. But it's been such a long journey to try to figure out how to get that out of aircraft. It's a problem. The EPA recognized it. They said it's an endangerment, but the industry is still pushing back. Eric Topol (07:55): Yeah, I mean, it's interesting that we still have these problems, and I am going to in a minute ask you what we can do to just eradicate lead as much as possible, but we're not there yet. But one study that seemed to be hard to believe that you cited in the review. A year after a ban leaded fuel in NASCAR races, mortality from coronary heart disease declined significantly in communities near racetracks. Can you talk about that one because it's a little bit like the one you just mentioned with the airports? Bruce Lanphear (08:30): Yeah. Now that study particularly, this was by Alex Hollingsworth, was particularly looking at people over 65. And we're working on a follow-up study that will look at people below 65, but it was quite striking. When NASCAR took lead out of their fuel, he compared the rates of coronary heart disease of people that live nearby compared to a control group populations that live further away. And he did see a pretty striking reduction. One of the things we also want to look at in our follow-up is how quickly does that risk begin to taper off? That's going to be really important in terms of trying to develop a strategy around preventing lead poisoning. How quickly do we expect to see it fall? I think it's probably going to be within 12 to 24 months that we'll see benefits. Eric Topol (09:20): That's interesting because as you show in a really nice graphic in adults, which are the people who would be listening to this podcast. Of course, they ought to be concerned too about children and all and reproductive health. But the point about the skeleton, 95% of the lead is there and the main organs, which we haven't mentioned the kidney and the kidney injury that occurs no less the cardiovascular, the blood pressure elevation. So these are really, and you mentioned not necessarily highlighted in that graphic, but potential cognitive hit as well. You also wrote about how people who have symptoms of abdominal pain, memory impairment, and high blood pressure that's unexplained, maybe they should get a blood level screening. I assume those are easy to get, right? Bruce Lanphear (10:17): Oh yeah, absolutely. You can get those in any hospital, any clinic across the country. We're still struggling with having those available where it's most needed in the industrializing countries, but certainly available here. Now, we don't expect that for most people who have those symptoms, lead poisoning is going to be the ca