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My Top 3 Ingredients for Joint Health, Mobility, and Cartilage Repair

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In this episode we discuss:

  • Why immune function plays a surprising role in osteoarthritis
  • How native type II collagen, NEM, and Boswellia serrata compare to glucosamine and chondroitin
  • The research-backed dosages used in clinical trials
  • Safety considerations and who should consult a healthcare provider
  • Lifestyle habits that maximize joint recovery and resilience

Show notes:

Hey everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. Today, we’re going to talk about joint health, and specifically, why the most popular approach to supporting your joints is probably not working very well for you, and what the science says you should be doing instead.

Joint pain is remarkably common in modern life. Nearly one in five Americans deal with some form of chronic joint pain, and osteoarthritis affects over 32 million people in the United States alone. Yet despite this prevalence, treatment options are surprisingly limited. Most people are told their choices come down to either living with pain, managing it with NSAIDs like ibuprofen and naproxen, or eventually just considering joint replacement surgery. That narrative creates a false dichotomy that misses what the research shows is possible. If you’ve ever dealt with joint pain, stiffness, or that nagging feeling that your body just isn’t recovering the way it used to, you’ve almost certainly been told to take glucosamine and chondroitin. It’s been the default recommendation for over 25 years. Walk in any supplement aisle, talk to your doctor, ask at the gym, and you’ll hear the same thing. But here’s the problem, the evidence behind that approach has always been surprisingly weak, and the major clinical practice guidelines have caught up to this reality. The narrative persisted despite the evidence not backing it. We’ve seen this many times with other issues, and this is a perfect example of something I talk about often: popular doesn’t necessarily mean effective. It often means it was first to market with a simple story.

I have a personal stake in this topic. I’m 51 years old, and I’m extremely active. I ski over 80 days a year. I mountain bike, kayak, hike, do strength training, paddle board, and play pickleball. This isn’t casual activity. I build my entire life around movement and being outdoors. Over the last few years, recovery has become more challenging, which is just the reality of aging, even when you’re doing everything right. I’ve been dealing with a medial meniscus and pes anserine issue in my left knee, an L4-L5 disc issue on the left side, and plantar fasciitis. So I did what I always do when I’m faced with a health challenge. I went deep into the research. I spent months reviewing the clinical trial literature on joint health ingredients, and I landed on three that most people have probably never heard of, each working through a completely different mechanism. I’ve been taking all three consistently, and the difference in my recovery and overall joint function has been substantial.

By the end of this episode, you’ll understand why the old glucosamine and chondroitin approach falls short, what three ingredients the research supports for joint health, how they work through distinct and complementary mechanisms, what the clinical trials show in terms of real outcomes, and how to use them practically. You’ll also understand why these three work together in ways that matter, because that synergy is crucial to getting results. Ready? Let’s dive in.

All right, let’s start with a fundamental question, why doesn’t the glucosamine and chondroitin approach work as well as everyone thinks it does? This is a classic example of a narrative outpacing the evidence. The logic behind glucosamine and chondroitin was simple and intuitive. Cartilage is made of these compounds, so if you give the body more of them, it should rebuild cartilage. It’s the building blocks theory of joint health, and it sounds perfectly reasonable on the surface. The problem is that joint degradation is far more complex than just running low on raw materials. The American College of Rheumatology and Arthritis Foundation issued updated guidelines in 2019 and they conditionally recommend against using glucosamine and chondroitin for knee and hip osteoarthritis. The American Academy of Orthopedic Surgeons has similarly issued limited recommendations. Multiple network meta-analyses have shown that glucosamine and chondroitin frequently fail to meet the minimum clinically important difference for pain reduction. In plain language, they don’t work well enough for most people to notice a meaningful change. In some studies, they perform no better than placebo.

There are practical problems beyond the evidence, too. You need massive doses, typically 1,500 milligrams of glucosamine and 1,200 milligrams of chondroitin, which means swallowing three to four large tablets every single day. Even then, they take weeks to months before any subtle benefit might appear, and most people give up long before that window closes. It’s a compliance nightmare that almost no one maintains.

But the deeper issue is conceptual. Joint degradation isn’t a simple story of mechanical wear and tear. It involves immune responses where your body’s own immune cells attack cartilage fragments. It involves inflammatory cascades driven by specific enzymes and cytokines that actively destroy cartilage matrix. It involves structural breakdown of the tissue itself. You need to address those biological pathways, not just throw building blocks at the problem. This is exactly what the three ingredients I’m going to share with you today are designed to do. They’re not trying to patch a roof. They’re addressing why the roof is leaking in the first place.

Let’s start with native type II collagen, because the mechanism is unlike anything else in the joint health space. This is not the hydrolyzed collagen you see in powders, drinks, and gummies, the stuff people take at 10 to 20 grams a day. Native type II collagen, also called undenatured type II collagen, works at a tiny dose of just 40 milligrams per day, and it operates through a completely different biological mechanism. The key is that collagen’s three-dimensional structure, its triple-helix shape, is preserved. It’s not broken down into amino acids. That intact structure is what makes it work, because the mechanism isn’t structural at all. It’s immunological, which is a fundamentally different approach to joint problems than anything else on the market. When cartilage sustains micro-damage, whether from exercise, aging, or injury, tiny fragments of type II collagen are released into the joint space. In a significant number of people, the immune system mistakenly identifies these fragments as foreign invaders and launches a T-cell-mediated attack. Your own immune cells are accelerating the destruction of your cartilage. It’s almost like a localized autoimmune response, and it creates a vicious cycle. Damage releases fragments, fragments trigger immune attack, immune attack causes more damage, which releases more fragments. The cycle perpetuates itself. This is why some researchers and clinicians have argued that osteoarthritis should be reclassified as an autoimmune disease.

Native type II collagen interrupts the cycle through a well-characterized process called oral tolerance. When you swallow 40 milligrams of intact type II collagen, it survives digestion and reaches the gut-associated lymphoid tissue, specifically structures called Peyer’s patches in the small intestine. This happens because the intact collagen is recognized by the mucosal immune system in a particular way. There, specialized immune cells called dendritic cells, recognize the collagen and present it to T-cells, which then differentiate into regulatory T-cells, also called T-regs. These regulatory T-cells migrate through the bloodstream to your joints, and when they encounter your body’s own collagen fragments, instead of attacking, they release anti-inflammatory signals like TGF-beta and interleukin-10 that tell the immune system to stand down. You’re retraining your immune system to stop attacking your own cartilage. It’s immunological retraining through oral tolerance.

The clinical evidence for this is strong and consistent. In a landmark randomized controlled trial in Nutrition Journal in 2016, about 190 patients with knee osteoarthritis were randomly assigned to receive either 40 milligrams of undenatured type II collagen, a combination of 1,500 milligrams of glucosamine plus 1,200 milligrams of chondroitin, or placebo for 180 days. The results were remarkable. The collagen group showed a 33 percent reduction in overall WOMAC scores, which is the gold standard measure for osteoarthritis symptoms, compared to just 14 percent for the glucosamine and chondroitin group. That’s more than double the improvement. Pain scores dropped by 40 percent in the collagen group versus just 15 percent for glucosamine and chondroitin. The collagen group significantly outperformed both placebo and the glucosamine-chondroitin group on all three WOMAC subscales: pain, stiffness, and physical function. It wasn’t even close.

Whether you’re an athlete, experiencing age-related joint stiffness, recovering from injury, or simply looking to stay active for decades to come, this episode provides an evidence-based roadmap for supporting healthier joints and maintaining mobility. Tune in to learn how a modern, research-driven approach may help you move with less pain and greater confidence. #ChrisKresser #joint health

The cartilage protection data goes even further, because we’re not just talking about people feeling better, though that obviously matters. A six month trial of Collavant n2, a branded native type II collagen, in healthy, active adults with exercise-related joint discomfort found an 18 percent reduction in CTX-II, which is a validated biomarker of cartilage degradation, in the supplement group. The placebo group, meanwhile, saw a 21 percent increase in CTX-II over the same period. That’s nearly a 40 percent differential in cartilage breakdown markers between the two groups. The collagen group also recovered 40 percent faster than placebo by day 180. This is one of the few ingredients where we have actual biomarker evidence that cartilage is being preserved, not just symptom masking. We can see on a molecular level that the tissue is being protected. A women-only randomized controlled trial showed a 45 percent reduction in WOMAC pain scores in just six weeks. One important detail that trips people up: higher doses don’t work better. In fact, animal models of oral tolerance suggest that higher doses can shift the immune response away from tolerance and toward activation, which is the opposite of what you want. Forty milligrams is the sweet spot, and it’s the dose used in virtually every successful clinical trial. There’s no benefit to doubling it.

The main caveat with native type II collagen is patience. It takes four to 12 weeks for the immune modulation to produce noticeable effects, with benefits continuing to build over three to six months. Not a quick fix, but it addresses the root cause of immune-driven cartilage destruction, which is something no amount of glucosamine or chondroitin will ever do, because they don’t address the immune component at all. I treated a patient, a weekend basketball player in his late 40s, who’d been taking glucosamine and chondroitin for years with minimal improvement. His knees ached after every game, and he was starting to dread playing, which is a red flag, because you know something has to change when your recreational activity becomes something you’re dreading. When I suggested switching to native type II collagen at 40 milligrams a day, he was skeptical because the dose seems so small compared to the horse pills he’d been taking. But he stuck with it. By month two, he noticed the post-game stiffness was less intense. By month four, he was playing without dreading the next morning for the first time in years. The gradual improvement is typical, and it reflects the time it takes for the immune modulation to have a full effect. He’s now one of those people who’s convinced the dose being small makes sense because it’s working at the immune level, not trying to build cartilage with raw materials.

Let’s move on to the second ingredient, natural eggshell membrane, usually referred to as NEM. If native type II collagen is the slow and steady immune modulator, NEM is the rapid responder. Eggshell membrane is the thin, protein-rich layer between the eggshell and the egg white, and it contains a dense natural matrix of compounds relevant to joint health: glycosaminoglycans like chondroitin sulfate and dermatan sulfate, hyaluronic acid, type I collagen, and various bioactive peptides. It’s essentially a whole-food joint support complex in a single ingredient. Unlike taking isolated glucosamine or isolated chondroitin or isolated hyaluronic acid separately, NEM provides these in their natural ratios and forms, which appears to matter significantly for clinical efficacy.

NEMs mechanism is multifactorial. It provides structural substrates for synovial fluid viscosity and cartilage matrix maintenance, so you’re getting the building blocks, but in the right context. It suppresses inflammatory cytokines like TNF-alpha and interleukin-1 beta, the key drivers of cartilage destruction. It downregulates NF-kB, which is a master switch controlling the expression of inflammatory genes. It inhibits matrix metalloproteinases, the enzymes that actively destroy  cartilage tissue. And it reduces CTX-II, that same cartilage degradation biomarker I mentioned with native type II collagen. You’re addressing the problem from multiple angles simultaneously. But the standout feature of NEM is speed. This is one of the fastest acting joint ingredients in the published literature.

In the OPTION trial by Ruff and colleagues in Clinical Rheumatology in 2009, 67 patients with knee osteoarthritis received either 500 milligrams of NEM or placebo daily. Pain scores improved by 16 percent and stiffness scores by 13 percent after just 10 days. That’s faster than most people expect from a supplement. By day 60, stiffness had improved by 27 percent compared to placebo. Improvements were statistically significant and rapid, which matters because people start to believe something’s working when they feel it working. An exercise-induced discomfort study in healthy postmenopausal women, also by Ruff and colleagues in Clinical Interventions in Aging in 2018, was even more impressive for speed. Sixty women performed a step exercise protocol while taking either 500 milligrams of NEM or placebo. Recovery stiffness improved significantly by day four. Recovery pain improved by day eight. CTX-II, the cartilage breakdown marker, decreased by 17 percent compared to placebo after just one week. Meaningful changes in a cartilage biomarker in seven days. A 2024 systematic review and meta-analysis by Garcia-Muñoz and colleagues, which pooled data from seven randomized controlled trials, confirmed significant improvements in WOMAC total scores, pain, and physical function with eggshell membrane supplementation.

The 500 milligram dose is key. One study that compared 300 milligrams to 500 milligrams found a clear dose-dependent response, with 500 milligrams significantly superior for pain reduction. The only important contraindication is for people with severe egg allergies, since the membrane is derived from chicken eggs, though the actual protein content is minimal and most people with egg allergies seem to tolerate it fine. But it’s worth checking with your doctor if you do have a severe egg allergy.

I treated a patient, an active woman in her early 50s and an avid hiker who’d been struggling with morning stiffness and post-hike knee pain for over a year. She described that frustrating warming up period every morning where it took 15 to 20 minutes before her knees felt functional enough to really move. She was using ibuprofen to manage it, but she didn’t want to become dependent on daily NSAIDs. After starting NEM at 500 milligrams a day, she noticed within the first week that she’d get out of bed and move without that prolonged warm up. By two weeks, her post-hike recovery was dramatically faster. She told me it felt like someone had oiled her joints. And that image stuck with me, because that’s exactly what’s happening mechanistically. The glycosaminoglycans and hyaluronic acid are improving synovial fluid viscosity. The speed of improvement with NEM is one of the things that makes it so valuable, because people can feel the difference quickly enough to stay motivated and committed to consistency.

The third ingredient is Boswellia serrata, specifically a highly bioavailable form called AprèsFlex, also known as Aflapin in the clinical literature. Boswellia is Indian frankincense, and it has a long history in Ayurvedic medicine for treating inflammatory conditions. But not all Boswellia is created equal, and this is crucial to understand, because generic Boswellia extracts at standard doses don’t come close to matching what the clinical trials show for this specific form. This is where people often make mistakes with supplementation– they assume all forms of an ingredient are similar, and they’re not. AprèsFlex is standardized to contain at least 20 percent AKBA, which stands for 3-O-acetyl-11-keto-beta-boswellic acid, the most potent anti-inflammatory compound in Boswellia resin. It’s also formulated with non-volatile Boswellia oils that enhance AKBA bioavailability by roughly 52 percent compared to the standard extracts. This enhanced absorption is what allows AprèsFlex to work at just 100 milligrams per day, while generic Boswellia products would need 1000 to 3600 milligrams to approach similar AKBA delivery. You literally can’t get the dose of active compound from generic products that you get from 100 milligrams of AprèsFlex. This is important to understand when you’re looking at supplements, because bioavailability and standardization matter enormously.

The mechanism is targeted and potent. AKBA is a selective inhibitor of 5-lipoxygenase, or 5-LOX, the enzyme that converts arachidonic acid into pro-inflammatory leukotrienes. This is mechanistically distinct from NSAIDs like ibuprofen, which primarily target the COX pathway and inhibit prostaglandins. Boswellia targets the leukotriene pathway that NSAIDs miss entirely. You’re inhibiting a completely different inflammatory cascade. AprèsFlex also inhibits NF-kB, reduces MMP-3, a cartilage destroying enzyme, and lowers TNF-alpha and hsCRP. Think of it as a multi-target anti-inflammatory agent that works through pathways conventional pain relievers don’t touch, but without the gastrointestinal, cardiovascular, and kidney risks of chronic NSAID use. This is why people who switch from NSAIDs to Boswellia often notice not just joint improvement, but also improvement in their digestion and overall health. Imagine that, positive side effects.

The clinical evidence is compelling. In a 30-day double-blind, randomized, placebo-controlled trial by Vishal and colleagues in the International Journal of Medical Sciences in 2011, 60 patients with knee osteoarthritis received either 100 milligrams of Aflapin (or AprèsFlex) or a placebo daily. Significant pain reduction appeared by day five. By day 30, stiffness scores had dropped by 66 percent. That’s a two-thirds improvement in stiffness in 30 days. A separate 90-day comparative trial by Sengupta and colleagues in the same journal in 2010 showed that Aflapin at 100 milligrams outperformed both placebo and another Boswellia extract across all outcomes. But the study that really sets AprèsFlex apart is a six month randomized, placebo-controlled trial of 80 subjects with mild to moderate knee osteoarthritis. Participants received either 100 milligrams of AprèsFlex or placebo daily for six months, and the researchers didn’t just measure symptoms and biomarkers. They used MRI to physically image cartilage thickness and joint space width before and after the trial. They could see the cartilage. The AprèsFlex group showed significant improvements in cartilage volume, thickness, and joint space width compared to placebo.  Meanwhile, the placebo group continued to experience cartilage thinning and joint space narrowing over the same period, which is the normal progression of osteoarthritis. Pain scores dropped by 70 percent, stiffness by 72 percent, and walking speed improved by 27 percent. Biomarkers of cartilage destruction, including hsCRP, MMP-3, and CTX-II, all decreased significantly. We can see on imaging that the cartilage is actually being preserved. This is the strongest structural evidence for any botanical joint ingredient I’m aware of. We’re not just talking about people feeling better, though they clearly did. We can see on MRI that the cartilage is being protected and maintained. For a 100 milligram per day botanical, that level of structural evidence is rare. Most supplements can’t come close.

I treated a former competitive tennis player in his early 50s who’d been forced to largely stop playing due to persistent knee pain. He was in a difficult position. His pain was significant. He was taking ibuprofen daily to manage it, but the ibuprofen led to GI problems and reflux, and his doctor told him he needed to stop the NSAIDs or risk serious harm to his stomach and cardiovascular health. That’s what brought him to my office, and it’s a common situation I ran into in practice. We started him on Boswellia, the AprèsFlex form, at 100 milligrams a day. Within the first week, his pain had noticeably decreased. By three months, he was playing tennis regularly again, performing at a level he hadn’t reached in years, and his recovery time between sessions had shortened dramatically. His GI issues not only resolved, but his digestion improved to a point that was better than he had experienced in years. The key was that we addressed the inflammatory pathway driving his pain without the side effects that had made his previous approach unsustainable. He could do the activities he loved again.

A word on safety: AprèsFlex is generally well tolerated at 100 milligrams. However, it has some mild anti-platelet activity and may interact with medications metabolized by the CYP pathways. So if you’re on blood thinners like warfarin or other medications, talk to your doctor before starting it. It’s not a contraindication necessarily, but it’s worth discussing, especially if you are on blood thinners.

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Okay, so now we’ve covered each ingredient individually. I want to talk about why these three make sense together, because this is where the picture really comes into focus and the benefits become more substantial. Joint degradation isn’t a single problem. It’s at least three simultaneous biological problems happening at once: an immune response where your body attacks its own cartilage fragments, an inflammatory cascade driven by enzymes and cytokines that destroy the cartilage matrix, and a structural breakdown of the tissue itself. Each of these three ingredients targets a different axis of that problem, and they do it through mechanisms that don’t overlap. Native type II collagen addresses the immune axis. Through oral tolerance it generates regulatory T-cells that shut down the autoimmune-like attack on your cartilage. This is something no other ingredient in this combination does. NEM addresses the structural and broad anti-inflammatory axis. It provides the glycosaminoglycans and hyaluronic acid your joints need, while simultaneously suppressing the enzymes that tear them apart. And AprèsFlex addresses the targeted anti-inflammatory axis, blocking the leukotriene pathway that conventional pain relievers miss entirely, while also protecting cartilage at a structural level as shown on MRI. There’s virtually no mechanistic overlap at the primary level. They don’t compete for the same receptors. They don’t redundantly inhibit the same enzymes. They don’t interfere with each other. They’re complementary by design, not by marketing, which is an important distinction.

The timeline synergy is important too, and it solves what I call the valley of disappointment problem with joint health supplements. Most people give up on supplements before they’ve had enough time to work because they’re not feeling improvement, and then they assume the supplement doesn’t work. With this combination, AprèsFlex and NEM provide noticeable relief within days to two weeks, which keeps you motivated and engaged. You’re getting tangible evidence that something is happening. Meanwhile, native type II collagen’s immune modulation is building in the background over weeks to months, providing the deep, lasting structural benefits that address the root cause of the problem. By the time you’re a few months in, all three are contributing fully, and the benefits are compounding. Your knee isn’t just feeling better, it’s being preserved at a structural level. All three ingredients show reductions in CTX-II, the cartilage breakdown biomarker in human studies, but through entirely different mechanisms. That convergence of evidence from independent pathways is compelling because it suggests the effect is real and robust, not a one-off finding.

When I’m skiing or mountain biking, I notice these effects in practical ways. My knee recovers faster after demanding activity. The morning stiffness that was becoming routine is minimal. I can push hard on the ski run without the nagging fear that I’m compromising my joints long-term. This matters because I’m not just talking about pain relief, I’m talking about preservation and recovery, which are what matter to someone who wants to stay active. From a practical standpoint, the total daily dose across all three ingredients is just 640 milligrams: 40 milligrams of native type II collagen, 500 milligrams of NEM, and 100 milligrams of AprèsFlex. That easily fits into one or two capsules. Compare that to the 2,700-plus milligrams needed for a standard glucosamine-chondroitin regimen, which requires a handful of large tablets that people have to take with food multiple times a day. The practical burden is completely different.

I mentioned earlier that I’ve been taking all three of these ingredients consistently, and I want to give you an honest account of my experience. I’m not going to tell you that they’re a miracle cure, because they’re not. And I always recommend that people connect with a skilled physical therapist or someone who can help them with biomechanics, because that is very important when you’re looking at a root-cause approach to these issues. However, supplements can make an enormous difference when you choose the right ones. At 51, skiing 80-plus days a year, mountain biking, paddleboarding, kayaking, doing strength training, and playing pickleball, I’m going to have some wear and tear. That’s just the deal when you’re active. But the difference has been meaningful and consistent. My knee recovers faster after demanding activities. The morning stiffness I was dealing with, like I said, has been improved substantially. The L4-L5 disc issue and plantar fasciitis aren’t completely gone, but I rarely notice them, and they don’t really limit my activities at this point. I can maintain my activity level without the constant worry that I’m paying too much for it the next day or that I’m accelerating joint damage. For someone like me who builds my entire life around movement, that’s enormous. It’s the difference between a life I want to live and a life of limitation.

Let’s wrap up now with some practical guidance on how to use these if you want to try them. For native type II collagen, look for native or undenatured type II collagen, not hydrolyzed collagen peptides. The dose is 40 milligrams per day. Branded forms like Collavant n2 or UC-II have the most clinical data behind them. Some research suggests taking it on an empty stomach to improve the oral tolerance response, though this isn’t absolutely critical. Give it at least two to three months before judging the effects, with full benefits typically emerging over three to six months. Patience is key here, because you’re retraining your immune system and that takes time.

For NEM, the dose is 500 milligrams per day, not 300. The dose-response data clearly supports 500 milligrams for optimal pain reduction. Look for a branded, clinically studied eggshell membrane product. You can take it with or without food, and effects are often noticeable within one or two weeks. Avoid it or speak to your doctor if you have a severe egg allergy. Though, as I mentioned, the actual egg protein content is very small and many people with mild allergies can tolerate it well.

For Boswellia or AprèsFlex, this one is especially important to get right because standardization and bioavailability matter. You want 100 milligrams per day of a standardized extract with at least 20 percent AKBA and enhanced bioavailability, like AprèsFlex or Aflapin. Generic Boswellia at 100 milligrams will not produce the same results because the AKBA delivery is too low. You need the bioavailability enhancement. Effects are often noticeable within the first week. Check with your doctor if you’re on blood thinners or medications metabolized by CYP enzymes.

You can find these ingredients separately, but as of today, it’s not possible to buy them in a single product. Spoiler alert: that may change in the next couple of weeks! Either way, check the doses carefully. Some multi-ingredient products skimp on amounts to fit everything on one label while using sub-therapeutic doses that won’t match the clinical trial results. If you’re going to invest in these, get real therapeutic doses. These supplements work best alongside foundational strategies: an anti-inflammatory diet, regular movement that includes both strength training and mobility work, working with a physical therapist who can assess your biomechanics, maintaining a healthy weight, and getting adequate sleep for recovery. These aren’t substitutes for those fundamentals. They work with them. Consistency is key. The benefits compound over time, especially the cartilage-protective effects. So give it a full three to six months to experience a complete range of benefits before deciding it’s not working.

The bigger lesson here is one I come back to again and again. The most popular approach isn’t always the most effective one. Glucosamine and chondroitin became the default not because the evidence was overwhelming, but because they were the first to market and the narrative was simple and intuitive. A good story beats good evidence, unfortunately, and that’s usually how these things work. But the science has moved well beyond that now. We understand that joint health requires addressing the immune, inflammatory, and structural dimensions simultaneously, and the ingredients that do this are available today, backed by rigorous clinical trials, and far more practical to take daily. Your joints don’t have to be the thing that slows you down.

Thanks for listening, everyone. You can find show notes and links to all the studies I mentioned at ChrisKresser.com. If you have questions about this episode or suggestions for future topics, head over to ChrisKresser.com/podcastquestion and leave me a message. I read all of them and your questions help shape the content I create. I’ll talk to you next time.



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