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Harvard’s award-winning Dr. Charles Serhan isn’t just an expert on specialized pro-resolving lipid mediators (SPMs), he is the scientist who actually discovered them. His breakthroughs opened up a brand new field of research and clinical application with immense potential. After all, chronic, unresolved inflammation is a contributor or cause of so many conditions.
The growing body of research on the utility of SPMs continues to astound (although when you start to understand the mechanisms, it’s perhaps easy to understand some of the “why”) – pain, rheumatoid, osteo- and Lyme arthritis, macular degeneration, periodontal disease, uveitis, surgical recovery, and repetitive head injury, for instance, have all been shown to be potentially benefited by the ability of SPMs to promote inflammation resolution. Clinically, I consider SPMs in all conditions where unresolved inflammation is a contributing factor. Not only that, but SPMs appear to have some rather surprising additional effects including stem cell regulation, tissue regeneration, and inhibition of amyloid-beta peptide in Alzheimer’s models (even restoring memory loss in mice).
I am honored to host Dr. Serhan here on New Frontiers along with his esteemed colleague, Dr. Megan Sulciner. Dr. Sulciner is a clinician-scientist and resident in the Serhan Lab whose exciting work focuses on advancing postoperative outcomes for surgical patients as well as the role of SPMs in enhancing cancer therapy and preventing cancer metastasis. I’m sure you will love this insightful, tour-de-force conversation! ~DrKF
Specialized Pro-Resolving Mediators: As Close to a Panpharmacon as We Can Get?
Addressing inflammation is rightly a major focus of Functional Medicine, yet it often carries a negative connotation due to misconceptions surrounding its many pathological and physiological roles. But is all inflammation harmful? Or is it the failure to resolve an inflammatory response that is the culprit in a growing number of chronic diseases?
Our guests on today’s episode of New Frontiers, Dr. Charles Serhan and Dr. Megan Sulciner, have spent their careers investigating the impact of specialized pro-resolving mediators (SPMs) on inflammatory diseases. SPMs are bioactive lipids derived from essential omega-3 fatty acids that modulate the immune response and stimulate resolution mechanisms. We discuss how the unexpected discovery of resolvins by Dr. Serhan over 20 years ago paved the way for the application of SPMs in the management of a broad array of inflammatory disorders. We also highlight some of Dr. Sulciner’s ongoing research that aims to use SPMs as an immunonutrition adjuvant therapy to prevent tumor recurrence in cancer.
In this episode of New Frontiers, learn about:
- The history of specialized pro-resolving mediators (SPMs) from one of the world’s pioneering researchers on the topic
- How insights from the lipid composition of laboratory mouse chow led to the discovery of Resolvin-D and Resolvin-E
- Current clinical investigations examining the potential use of SPMs as a disease-modifying treatments for periodontal diseases, cancers, neurological diseases, and many more
- How cells of the immune system convert precursor omega-3s into potent, naturally-derived SPMs that have a variety of roles in disease prevention and resolution
- The manmade deficit in omega-3 fatty acid intake and how this has contributed to a global burden of diseases characterized by a chronic inflammatory state
- The balance between a protective acute inflammatory state and a pathological chronic inflammatory state
- Genetic and environmental factors that are associated with impaired synthesis of resolvins and their link to disease
- Recent evidence supporting the use of SPMs as a prophylactic or adjuvant therapy in the cancer treatment pipeline
- How the work of Artemis Simopoulos on the Mediterranean diet influenced scientific advances in the study of omega-3 fatty acids and SPMs
- Whether taking NSAIDs to manage pain brought on by acute inflammation will compromise endogenous SPM production in the short- and long-term
- How immunonutrition is emerging as an important consideration in the postoperative management of patient recovery
- Detection of bioactive lipids in saliva as an early warning sign for heart failure
Dr. Kara Fitzgerald: Hi everybody. Welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine. And today, of course is no exception. I couldn’t be more excited to have with me here Dr. Charles Serhan out of Harvard. He is of course the scientist who discovered specialized pro-resolving lipid mediators, compounds that we’re using in clinical practice that we’re very, very interested in in the world of functional medicine. And I get to pick his brain today. I have pinged him to podcast for a while, so I’m just super excited. And with him… Actually, let me give you his background and then I’ll introduce you to Dr. Sulciner over here as well. So Dr. Serhan is the Simon Gelman professor of anesthesiology at Harvard. He’s also professor of oral medicine and infection and immunity at Harvard. He’s the director of the Center for Experimental Therapeutics and Reperfusion Injury at Brigham and Women’s Hospital, and past co-director of the Brigham Research Institute.
He is currently program director of the program project entitled Resolution Mechanisms in Acute Inflammation Resolution Pharmacology. He’s received a ton of awards. Just too numerous to mention. You can see on the show notes if you really want to know. And he is just a top, top, top cited researcher. No great surprise there for all the fabulous publications in really building this field.
And then Dr. Sulciner is a MD. She’s a general surgery resident focusing in oncology surgery in Boston. And currently a research fellow at Dr. Serhan’s lab in the Center for Experimental Therapeutics and Reperfusion Injury. Their recent commentary entitled Resolution Medicine in Cancer, Infection, Pain and Inflammation: Are We On Track to Address the Next Pandemic? Was published in Cancer and Metastasis Reviews. Her research focuses on the role of resolution of inflammation and tumor recurrence. I am very honored and excited to have both of you with me today. Welcome to New Frontiers.
Dr. Megan Sulciner: Thank you so much. I’m excited to be here.
Dr. Charles Serhan: Yeah, it’s fun to be here. Thank you for the kind introduction.
Dr. Kara Fitzgerald: Yeah. I’ve been wanting to talk to you for a long time. For our audience, as I mentioned to you before, a lot of these folks are clinicians, we’re using SPMs in practice now. So we’re going to want to get into that, dig in a little bit deeper. But just define them, what they are? And honestly, how did you come to study them? How did you figure this out? I mean this is a huge discovery.
Dr. Charles Serhan: Okay. Like most things, this is truly serendipitous. I’ll give it to you in 30 second snapshot. It’s my personal mission to improve treatments around inflammatory diseases. This is what I think I was meant to do in life. I was doing an experiment asking a very simple, basic, fundamental question about pus in a mouse. Where does it go? How does it resolve? And people thought before that inflammation and the recruitment of leukocytes, because we’re really interested in how leukocytes get to the site of action, how they do their job to protect us from microbes, how do they get out, where do they go? What’s the endogenous mechanism? And I felt that there had to be endogenous mechanisms because each time you got challenged you get a little pimple, think on the back of your hand, it goes away. The little pustule will go away. So there had to be some sort of self-limiting side to that.
Well, the luck part of it, the serendipity is that the experiment was done in mice and the mice were well-fed. I had to backtrack, I got these molecules that had this ability to stop leukocytes from adhering to the vascular endothelium. That was the model that we were using to test different fractions from the pus. And so in backtracking, the precursor, omega-3 – so the mice were eating a diet that the veterinarians had already figured out was beneficial to them.
Yes, so in our very first paper on this topic, which just goes back a ways now, it’s kind of buried into the methods, but 30 to one, 30 times more omega-3 fatty acids present in the chow versus omega-6. And so when I tried to recapitulate that system to figure out how to human cells make… So we used hypoxic chamber, a hypoxic chamber with vascular endothelial cells co-incubated with neutrophils. And so that’s how the E-series resolvins were born. And that’s how the D-series resolvins were born. And then systematically we do the structural elucidation and look for their bio-actions because we have in vivo models. And then to confirm all that total organic synthesis.
And then I was really lucky again to have a program project team, which is a project from NIH where it’s multiple groups working together and I could lead the mission there. And then I got a P50 Center Grant from NIH on resolution of oral inflammation and was able to start working with the periodontist and demonstrate, in animal models all the way up now to humans, that pro-resolving mediators can resolve, can stimulate the resolution of, endogenous mechanisms in humans to resolve inflammation. And we think this is very important. And my colleague Tom Van Dyke periodontist carried out the clinical trial. I just made the mouth rinse carrying the pro-resolving mediator.
It’s impressive and I hope it goes forward. Why? Because in the oral cavity, if you have a little inflammation, it begins to open the barrier. This is a mucosal barrier. And then we get more bacteria circulating. We’re challenging the innate immune system. Those barriers, as you know, are very important. The blood-brain barrier, the oral barrier. And that seems to be one of the functions of the SPMs, to tighten up the barriers.
Dr. Kara Fitzgerald: Oh, isn’t that amazing? Very, very interesting. The blood-brain barrier, the oral barrier, the gastrointestinal, what about the lung barrier? All of them?
Dr. Charles Serhan: Yes, all of them. We’ve done the lung with the new chief of pulmonary here, Dr. Levy. And he studied with me early on and we’ve studied the edema. And starting with very simple models like the mouse ear, just looking at the leak, we could visually see that if we add the SPMs topically, we would get leak that we could measure by fluorescence or trypan blue, its little mouse ears turned blue, very easy signal.
But the important part of the SPMs that you have, and you’re available to, came again by luck.
Dr. Kara Fitzgerald: Since we have like a precursor SPM, the parent SPM, right?
Dr. Charles Serhan: So those precursors are the products that are made by the vascular endothelium in humans and when human leukocytes come by, primarily the neutrophils, they pick them up and they convert them to the very potent SPMs. So I just happened to have a colleague who worked in fish and when we came up… He’s a fish hematopathologist. So when this came up, I sent the people in my lab, “Oh, we better go study the anchovies if this is where omega-3s are isolated for commercial purposes.” And we found that in the anchovies, yeah, they have the 17-HDHA, 18-HEPE. And then I turned to my friend and we looked in the trout and we looked in the trout brain and the trout head kidney gland is really the hematopoietic organ of fish. And they’re the more potent SPMs produced like resolvin D5, resolvin D1.
And what happens, again, just by luck, I… You can hear that I’m from the molecular side of the universe and this was dark matter. This didn’t exist before. So I was very excited about it and my colleagues were excited. So we “Oh, we are going to make a startup” because this is, as you know, most of the non-steroidals and in current treatments, the pharmacopeia for treating inflammation, all antagonists and inhibitors, which have some unwanted side effects. So it’s like, “Oh, this is the way, we’re going to stimulate resolution. We’re going to go out and do it. We’re going to knock’em dead.” Well, it was a lesson for me that even with positive 263, I think, patients treated with a resolvin E1 analog eye drop, positive results, the business guys couldn’t get it together to make it happen to make everybody happy. And I was only caring about the science and improving people. So it was a lesson to me.
However, that molecule, resolvin E1 is advancing the work from Thetis. Thetis emphasizes that they make resolvins druggable and they are doing that in both… For IBD, they’ll be doing a clinical trial in IBD. And in cancer as well. So we wish them luck and hope that it happens because our other mission, which is the overarching mission, and I know that Megan can agree with this, our mission is to save as many people as possible, to help as many people as possible.
And so since the traditional drug route took so long, the next good luck step for me was to run into people who did CO2 purification from marine oils. And that was a group in Spain and we isolated a fraction with them that was very rich in 17-HDHA and 17-HETE. So you’re going a little bit further down the pathway. It’s about a hundred times more potent than just taking DHA or EPA itself. But 17 is very potent in reducing pain. And 18 on its own, subsequent studies from by other investigators, and 18, aside from just being a precursor, also has cardiovascular beneficial effects. Nice papers from groups in Japan.
So I like the SPMs because if you have a little bit of inflammation going on, I want to emphasize this point because this is really key, and we all have a little bit because acute inflammation is protective. So we’re-
Dr. Kara Fitzgerald: Well, the aging journey kicks in inflammation. It’s part of the deterioration as well that we don’t want.
Dr. Charles Serhan: Well, you’re right, but when you have a little bit going on… I’ll give you another point about aging. The leukocytes that are around will convert the SPM precursors to the local molecule that’s bioactive and it’s doing its thing right on site. And that’s why I like it. So you’re right about the aging, you get more debris and you have to clear that debris out of an aging organ. But some of the very cool research now is all directed towards how SPMs are regulating stem cells.
Dr. Kara Fitzgerald: Oh my gosh. Wow.
Dr. Charles Serhan: Muscle stem cells-
Dr. Kara Fitzgerald: Really?
Dr. Charles Serhan: Yeah, it’s nice, nice results.
Dr. Kara Fitzgerald: We’ll link to those studies. My team will harvest them. That’s awesome. We’ll put them on the show notes, folks.
Dr. Charles Serhan: Yeah, nice. It’s a wonderful group in Canada that has discovered that one of our most favorite resolvins, resolvin D2, because it’s so potent, stimulates muscle stem cell. And that could be very useful in Duchenne’s Muscular Dystrophy, other… And the neurodegenerative diseases are all benefiting from… Even the psychiatrist, they say, “Oh, brain on fire.” And that leads to depression. Doing nice studies with EPA and DHA. Our chief here at Mass General Brigham, Maurizio Fava published on EPA reducing depression and leading to a dose dependent increase in E series resolvins.
Dr. Kara Fitzgerald: Oh, is that right? Nice.
Dr. Charles Serhan: Got to love it. Got to love it.
Dr. Kara Fitzgerald: Yeah. It’s incredible.
Dr. Charles Serhan: Moving out in all directions.
Dr. Kara Fitzgerald: Thank God for veterinary designed mouse chow. Geez Louise. Just because that happened to be 30 to one, you discovered-
Dr. Charles Serhan: The agi schools are way ahead of us because they’ve been watching how do we optimize the herd? Not only for their health, but for the economics of it as well. So yes, we were lucky.
Dr. Kara Fitzgerald: Yes, that’s right. It’s incredible. It’s incredible. This is Nobel material. It’s just exquisitely important.
Dr. Charles Serhan: I’m going to Stockholm next week for a special symposium and I have to say, not… But my mentor, one of my mentors was a Nobel laureate and I did get a chance to go as a kid and that’s like a fairytale. But Samuelsson, he received his Nobel for the prostaglandin structural elucidation. And that’s how I learned that work. And my other mentor, I got to give a plug to is Gerry Weissmann and he was a guru at NYU of, it was a rheumatology and inflammation.
Dr. Kara Fitzgerald: Fabulous. It’s brilliant. It’s just brilliant. I’m just so, so appreciative. So I want to just sketch a little bit of background and then I just want to jump over to you, Megan, and just talk about your extraordinary work swimming in this pond for the last decade and you’re working cancer. For folks, the specialized pro-resolving lipid mediators, the SPMs are primarily derived from EPA and DHA, our classic omega-3s, the reason that we’re all taking fish oil. I know that arachidonic acid produces lipoxin, which kicks these guys on. So we want a little background.
Dr. Charles Serhan: You got it.
Dr. Kara Fitzgerald: But humans are dwarfed with arachidonic acid. So we don’t need to be supplementing with this. We need to be bumping up our EPA and DHA. And then these resolvins are… I’m sorry, I’m just in the habit of using that colloquialism. These SPMs are… How many have you characterized? Are there hundreds would you say or…
Dr. Charles Serhan: Well, it’s still the tip of the iceberg. Even though we found three different families of molecules, these are the ones that come from lipids. But then we learned that there are gases that are involved in resolution and peptides. And they all interact, like some resolvins turn on local heme oxygenase, makes a little local carbon monoxide, resolves inflammation. It’s a very complex system. This is just the beginning.
Dr. Kara Fitzgerald: We have a global manmade deficiency of these omega-3s. And so we see just incredible inflammation that’s not being resolved. You famously said, “Chronic inflammation is the failure of resolution.” And all of us are operating with a deficit of these. So there’s many of them, it’s the tip of the iceberg. And they’re tissue specific. So there’s the neuroprotectants, there’s the resolvins behaving in different ways in different tissue. And they’re all coming from Omega, EPA and DHA, and so we want to make sure we have enough in our red blood cells, which we can readily measure.
Dr. Charles Serhan: Kara, you make me so happy to hear how much you know. That makes me feel like it’s been worthwhile. Thank you.
Dr. Kara Fitzgerald: You’re appreciated in the functional medicine world. We get it. We get how important this is. One of my questions to you, and then I’m envious that you got to spend a decade studying this, Megan. But I’m also super appreciative of the fact that you’re focusing on cancer because everything is implicated, inflammation is everywhere. But we know that some of us, in fact, painfully those of us who have active inflammation, aggressive inflammation happening may not convert our EPA and DHA. So there’s some sort of disruption in the mechanism that’s not allowing the production of the resolvins to happen.
So there are two things in my mind. A, we obviously have to be using resolvins then. We can use them acutely, I do all the time in practice, but I also think there’s a place for just taking them background along with EPA and DHA, while you’re getting to the bottom of the inflammation issue, getting the patient back to balance. That’s what I think about in my general plans really for almost any kind of condition. Everything’s associated with inflammation. But my question is, what’s the disruption that doesn’t allow people… That inhibits the production of resolvins? And then I want to talk about what you’re seeing in your research.
Dr. Charles Serhan: Actually, that’s at several levels that we can identify. One is, as you point out, where your nutrition is absent of the omega-3. The other is a genetic predisposition of dysfunctional receptors that are the GPCR cell surface receptors that recognize the resolvins. And the third is the loss of specific enzymes that are involved in the biosynthesis. And that’s what we can recognize now that would lead to failed resolution and going on to, let’s say, organ fibrosis. What I can tell you that we are working on right now, it’s a secret because the project we haven’t published on yet. But I’ll tell you that we’re really looking at the impact of environmental agents on resolution now, and they’re all disruptors.
Dr. Kara Fitzgerald: No surprise.
Dr. Charles Serhan: So we need to identify those. You’ll see new things coming from us on that note, hopefully within the next calendar year.
Dr. Kara Fitzgerald: That would be fabulous. Can you mention any of the key disruptors? Can you do that yet?
Dr. Charles Serhan: Not yet, but we’re studying things that are very prevalent in the environment. And I’ve been down to NIEHS, the National Institute of Environmental and Health Sciences. And they’re excited about the work in resolution. And I’m hoping that we can… We’re working with first-class nano-particle groups to help us peel this very complex onion apart because it really gets also to the environment. But let me let Megan tell you about her fantastic…
Dr. Kara Fitzgerald: Ashley, tell me your back… So tell me how you got interested and now you’re focusing in cancer and inflammation resolution using SPMs. Yeah, give me your story.
Dr. Megan Sulciner: Yeah. I was a college student and I was interested in biology. I was interested in cancer biology and a close collaborator of Dr. Serhan’s, Dipak Panigrahy. He had come and presented in our class about his preliminary data actually with Dr. Serhan. He was talking about using SPMs as an adjuvant therapy in addition to chemotherapy and surgery in mouse models. And his data that he had presented just my class was fantastic. It was absolutely amazing. And I thought, “Wow, maybe this is really what I want to do after school.” So I ended up being a research assistant in his lab. And our main project was looking just at that, understanding why is it that tumors come back after patients get chemotherapy or surgery? So understanding those mechanisms, which of course one of the main drivers was inflammation, secondary to chemotherapy or surgery. And then using the SPMs as an adjuvant therapy, which was a really exciting project to work on, especially as someone just out of college.
I actually very vividly remember, I’m sure Dr. Serhan does not remember this, but I remember it was with… I had worked in the lab for about a year and we had come to his lab meeting, which at the time was very big, very formal and academic. And I was presenting my data, which I’m sure for nobody else there, they’re in postdocs, really impressive backgrounds, were really listening. But I remember I gave the presentation and I thought afterwards, “Wow, if I can present in front of Dr. Serhan, I can present in front of everyone.” And even now, now I have presentations. I still actually think back to that moment. But yeah, it was really great.
I worked in lab for a couple years. I went to medical school and I did some dedicated research time where I actually came back to kind of finish up our studies. And then now I’m currently a general surgery resident at Brigham and Women’s Hospital.
Dr. Charles Serhan: Well, in between, there was a big publication with you as first author.
Dr. Megan Sulciner: Yes, there was. Yes, there was a really incredible opportunity to work on that project and certainly has kind of set the foundation for how I now view actually my current surgical training and how I see diseases, I think a little bit through a different lens than we are more traditionally thought of or taught in our textbooks as field of resolution of inflammation is so pertinent, particularly for surgical outcomes. If I think of the main things we’re thinking about all the time about patients coming back after surgery, it is all related to the resolution of inflammation and typically how it’s failed. And now I’m back in the lab and again, very grateful and honored and surrounded by incredibly smart people, in the Serhan lab looking to translate our previous work into patient data. So looking at it.
Dr. Kara Fitzgerald: Awesome. I know that anyone listening to this, again, there’s a lot of clinicians here are wanting to translate it right now. Like “What can we do?” And I think in functional medicine in this integrative model, we’re working with diet and lifestyle and sleep and stress, and we’re making sure people’s nutrients are in adequate supply and… Everybody starts with fish oil really, virtually all of us, unless there would be an allergy or something impeding it. A human has never presented to my practice not in need of fish oil and vitamin D probably. So we’re doing all of that good foundational work. Would you suggest, certainly in your cancer patients… But I’m curious, are SPMs indicated for all of us? Since we can get pretty good quality product now of those potent precursors, are they really indicated for all of us?
Dr. Megan Sulciner: It’s a great question. I think, yes, I can certainly say from our previous studies in our animal models, I would say we used SPMs both as an adjuvant therapy and actually also as a pre-treatment. And in both cases they did prevent tumor recurrence in our mouse models. And it was pretty incredible. I mean, in the space now, there is really limited…. Our therapies for treating tumor recurrence, particularly solid tumors are still limited to the main kind of touchpoints, which are radiation, chemotherapy, and surgery. Of course, there’s some incredible advances made, particularly immunotherapy and targeted therapy. But really the cornerstones are still the same that they were 50 years ago. And so our work-
Dr. Charles Serhan: And transplant, we’re going to do something.
Dr. Megan Sulciner: Yes.
Dr. Charles Serhan: But I just have to jump in and say one thing because this is, I think, really important for every day. The way we want to think about this. Well, the way I think about it, after having spent many sleepless nights thinking about it, is that… And I learned this from the nutritionist, people who’ve studied nutrition for a lifetime, like Artemis Simopoulos, the woman who really validated and brought us the Mediterranean diet. I think of it as resilience, the way that our body pushes back of that little challenge every day. So if you get this little challenge and you have no resilience, no biochemical resilience to make resolvins locally and clear up that little pimple, repeated challenge is going to bring us to the disease states that we’re at. That’s why I’ve become so interested in the environmental impact. So in that you can hear that I think as this is a part of healthy nutrition. We need to do this, we need to do it for kids. Period. And I would like to see those studies as quick as we can.
Dr. Kara Fitzgerald: There’s a scientist who I follow out of University of Kentucky, Bernhard Hennig, who his work is around looking at the influence of nutrients on modulating the impact of toxins. Specifically he’s looked at PCBs and omega-3s, and you can mitigate the damage from PCBs with Omega-3s, which I think is hopeful and important. He was specifically looking at the eicosanoid cascade.
Dr. Charles Serhan: Yes, but you [inaudible 00:29:46] evaluate and there’s a nice paper from the CDC West Virginia group that came to visit us here just before the COVID and shutdown, where they show the resolvins helping to clear these and the impact of nanoparticles on amplifying inflammation.
Dr. Kara Fitzgerald: Awesome. We can’t measure… Well, you just gave me the recommendation, the fact that we can go through Wayne State through a lipidomics panel, and it’s not a horrible price point. We’ll put a link in the show notes, folks, for those of you who want to start looking at resolvins in some of your patients, I think it’s absolutely indicated for some of us. If we’re making adequate resolvins, no need to supplement. In fact-
Dr. Charles Serhan: You’re absolutely right. I wish that we could do like a resolvin dipstick like you do… But I think that will come. People like Bill Harris really advanced the field a great deal with his simple blood-
Dr. Kara Fitzgerald: Yeah, the Omega-3 index. Easy-peasy.
Dr. Charles Serhan: Yeah. And really qualify that so well. The LC-MS-based quantitation is moving very quickly to the clinical sort of utility, but it’s not as turnkey. It’s not as easy as people… It takes an expertise to be able to read it. But my hope is that in the future, cardiologists will be able to look at a LCMS tracing, functional medicine clinician, look at the tracing and say, “Oh yeah,” reading it like an EKG. You can tell what a person needs. But I do want to make one molecular point to you, is that I no longer consider fish oils to be equivalent to EPA and DHA because there’s a lot… And the commercial material that’s available, there’s a lot of other things present. And I’ve done analysis in my lab and I’ve found stuff off the shelf have fish steroids in it and all kinds of stuff. So as we [inaudible 00:32:10] better at purifying at commercial scale, EPA and DHA, that’s what-
Dr. Kara Fitzgerald: That’s where it is. Okay. Okay, very good to know. That’s great. Yes, okay. Perfect. Yeah, quality is definitely an issue. And I think-
Dr. Charles Serhan: You know who can do that really well? And this is – save the planet – is the microalgae, so you want to look for a company in the future that are ramping up the microalgae, and there are. And you’ll see some really cool stuff coming.
Dr. Kara Fitzgerald: So we definitely need to avoid OTC products, go for the high quality ones and microalgae. That’s a hot tip. That’s pretty cool.
Dr. Megan Sulciner: Yeah, the microalgae, DHA, right, Dr. Serhan? That you can get over… There’s one particular one over the counter that’s very good.
Dr. Kara Fitzgerald: Oh, really? What is it? Can you say? We can say on my podcast, if you’re okay with it, I’m super curious. Or tell me later when I hit pause, I’m going to get bugged about it.
Dr. Charles Serhan: No, one I love is Metagenics that’s not a problem. Because we started that with the [inaudible 00:33:20] group, who was their supplier, the group in Spain. And there are many, many copycats. I don’t care about that. All we care about is that it’s getting into the mouths of people and hopefully helping people. And where I see the biggest impact of that is in pain, have a quantifiable reduction in pain.
Dr. Kara Fitzgerald: I used it. I had a patient with uveitis and she would have a very predictable prodrome. It felt like she had dust in her eyes like she dusted the house. She had this predictable prodrome. And I would say, I just told her they’re safe. You can correct me if I’m wrong, but I think that they’re, by and large, we could go pretty aggressively as we could with fish oil. So I would have her just take a couple every two hours for maybe the first day of the prodrome and we would be able to nip that in the bud. She was able to taper off her steroids, but we didn’t mess around. I had her go in there and really use them.
Dr. Charles Serhan: No, you’re on the right track. There are very nice studies from groups in Italy on uveitis and they have used the synthetic resolvins, they’re shown to be very effective.
Dr. Kara Fitzgerald: Drops. Right? Drops.
Dr. Charles Serhan: Yes. And there’s new work on macular degeneration, shows how important the E-series resolvins are. Again from Italy. So yes, you can be very aggressive in the dosing because we can tolerate milligrams to grams, when we eat salmon and so forth. Yes, we have not seen any, what can I say, unwanted side effects in any of the experimental models going all the way up to mini pig.
Dr. Kara Fitzgerald: That’s just so terrific. I mean, I’ve used it in periodontal disease as well. It will be fabulous when we have access to local and the drops. I heard you mention topical, that got my… Because all we have right now are the oral precursor molecules. And I really, really look forward to having access to some of these others. How are you thinking, Megan, about dosing for cancer recurrence or even prevention?
Dr. Megan Sulciner: That’s a great question. I don’t have a good answer for you on what we’re thinking about dosing, at least in humans. What we’re looking at is similar to what you had alluded to. It was almost like a deficiency. And I actually think, of course, Dr. Serhan’s characterization of having a resilience is a really incredible way to start thinking about it. Because we know in so many other patient studies that there are patients for certain reasons already have baseline higher levels of SPMs and those that don’t. And it’s unclear as to exactly who those patients are.
Dr. Kara Fitzgerald: I’m sure you’re looking at EPA and DHA and making… It’s not just the quantity of EPA and DHA that they’ve got in their lipid membrane, it’s more than that. The folks who are making it.
Dr. Megan Sulciner: Yeah, it’s definitely, certainly also a downstream effect as well. But I think the way I’m starting to think about it more as I’m going along in our translational studies and seeing of course all the really great work by people all over the world is that it falls to me under the same umbrella as immunonutrition, which of course is a really hot topic, particularly when we’re thinking about surgical patients. So that’s how I’ve started to think about it. I think for me is like a next step in terms of what we want to look at in really doing clinical studies.
There was a great group, I believe out of Japan that actually did this study. It was they gave patients SPMs upfront prior to surgery. They underwent a major abdominal surgery, I believe it was hepatobiliary surgery and then measured levels of SPMs in subsequent postoperative-
Dr. Charles Serhan: 80 patients. Right.
Dr. Megan Sulciner: Yeah. And it was amazing. The patients who had higher levels of SPMs each subsequent postoperative day did better than their counterpoints who had lower SPM levels. And again, they had been supplemented preoperatively. It was a really great, I thought exciting study, particularly in surgical patients.
Dr. Kara Fitzgerald: Yeah. Terrific. And we’ve put to bed, I think, in some of these larger clinical trials using omega-3s that there’s any bleed risk.
Dr. Charles Serhan: You’re absolutely right. Phil Calder did an excellent job there because he provided evidence to dispel that old data that “Oh yeah, you’re going to get bleeding from blocking platelet activation and thromboxane production.” And so many surgeons still believe that and ask their patients to prior to surgery, “Don’t take omegas.” But that’s one of Megan’s mission is to teach them that that’s not all the case.
Dr. Kara Fitzgerald: And maybe they’ll let SPMs sneak in because they don’t know what they are. Maybe they’ll just…
Dr. Charles Serhan: The surgeons who have been publishing on SPMs, they know what they are. There’s some really nice papers from academic surgeons. Megan is the future. She’s a surgeon scientist. When she gets out there, it’s going to change.
Dr. Kara Fitzgerald: In real-time still, when you’re co-managing with a surgeon or a cardiologist, there’s anxiety there and they want them to stop. But what you’re saying, Megan, is that we’re actually harming the healing process by keeping-
Dr. Charles Serhan: No, it’s actually the opposite. We have shown very nicely, and now many other groups that the resolvins stimulate tissue regeneration, they expedite wound healing, even topically. And surgical pain, they’re… No, it’s time to clear away those cobwebs and get up with a…
Okay, so there are critics, but that’s because they don’t want to turn the page to the new chapter. What can I say? And there’s already, today there’s 1000, and I’m very proud of this, 1,632 papers in pubmed.gov on all the fantastic things that resolvins and SPMs do in animal models from groups all around the world. Including 38 studies demonstrating, by other groups, taking supplementation and increasing peripheral blood SPMs, and really nice papers from Switzerland where it’s a nice clinical chemistry. Yeah, it’s going to happen.
Dr. Kara Fitzgerald: I would say that it’s like shooting fish in a barrel, no pun intended. Because it’s true, you can go on PubMed for whatever condition you’re interested in and generally find something related to SPMs. Like COVID, you can look at COVID, that’s been studied. You can look at even Lyme-associated arthritis.
Dr. Charles Serhan: Oh, you’re right.
Dr. Kara Fitzgerald: An animal model. I know.
Dr. Charles Serhan: I just heard Charlie Brown give the talk on that.
Dr. Kara Fitzgerald: Yes.
Dr. Charles Serhan: The paper just came out. Wow. I’m impressed.
Dr. Kara Fitzgerald: This is a topic. It’s so fundamentally important-
Dr. Charles Serhan: The resolution of Lyme arthritis. Absolutely.
Dr. Kara Fitzgerald: And endometriosis comes to mind just as I was talking to you offline with the cases that we’ve done in my clinic practice where we really paid attention-
Dr. Charles Serhan: Endometriosis is another potential clinical indication, you’re right. So is vulvodynia and the pain involved vulvodynia. And there are groups working towards trying to make therapeutics there.
Dr. Kara Fitzgerald: So when are we going to… Thank God we know that we can access good quality SPMs, or the precursors. But in the drug development pipeline, when do some of these are going to launch?
Dr. Charles Serhan: I can tell you that in my group and with my colleagues, we’ve made those molecules. The pushback has really been on the cost of goods. This was an education for me. It costs so much to make and because they’re so complicated, the synthetic roots. But groups have already chomped that down. And today if you want to go at it, people like Professor Spur in New Jersey, the people in Thetis. Frank, who’s one of the founders there was a medicinal chemist at Pfizer for his lifetime. He got onto the problem and he made it happen. He made resolvins really druggable by shortening those synthetic roots.
So now we just got to get the money to link up with… In the periodontal disease that was, like I said, safe and effective in the phase I, phase II, phase III, clinical trials on. But it’s still very hard for Dr. Van Dyke to raise the money to get to the next level. Because big clinical trials cost a lot of money. And the big pharma likes to hold tight on the battleships that they have rolling right now. This is a 180 degree turn.
Dr. Kara Fitzgerald: Yeah, it is. It’s revolutionary. It’s going to happen. Its time has to come. But we’ll certainly-
Dr. Charles Serhan: And in France, when I was in France, there were groups there using the apoptotic cell approach and the macrophage secretome. So in the macrophage secretome, they’re throwing out not just the resolvins but the anti-inflammatory cytokines and other factors that we don’t know about yet. And amazing they have approval to use that in patients. That type of cell-based therapy in the states, it wouldn’t happen. It’ll happen it’s just taking more than one scientific lifetime.
Dr. Kara Fitzgerald: What about the aspirin potentiated? Do you recommend a baby aspirin for that reason? In general? For the aspirin potentiated?
Dr. Charles Serhan: Low dose-
Dr. Kara Fitzgerald: resolvins?
Dr. Charles Serhan: Aspirin for the aspiring triggered-
Dr. Kara Fitzgerald: Yeah. The low dose.
Dr. Charles Serhan: Yeah. So we found some years ago that low-dose aspirin acetylated one of the enzymes that changes the chirality and makes the resolvins longer acting. And yes, I think that that… If you can get a good high or pure source of EPA, DHA and your doc says it’s okay to take a baby 81 milligram dose every other day, if that’s indicated for you, then sure, why not to crank up your aspirin? Because they’re longer acting and that makes them more potent. So they’re longer acting. Because like most potent signals, even in the brain, once they communicate with their neighboring cell, they have to get inactivated. And that’s what happens to the resolvins, they get locally inactivated so that we’re not in an off mode, that we’re in the on mode for the next challenge. But the aspirin triggered ones, they stay around longer.
Dr. Kara Fitzgerald: That’s very interesting. That to me strikes me as the likely mechanism of action of the low-dose aspirin benefit.
Dr. Charles Serhan: Well, that’s a… 360 is what people prescribe for RA. And usually two aspirins, like 180. But in the state’s, low-dose is like 81.
Dr. Kara Fitzgerald: But I just want to be clear, since I have you here, non-steroidal anti-inflammatories, ibuprofen, naproxen, et cetera, are you going to actually inhibit inflammation resolution?
Dr. Charles Serhan: Well, you certainly lower the amplitude of the acute inflammatory response. That’s why you take… The swelling, you feel better, you block prostaglandins. But those prostaglandins are needed to turn on the resolution phase and those non-steroidals have been shown to be disruptors of resolution in animal models and lead you into fibrosis.
Now, that’s where we really lock horns with some of our pharmacology friends. Because everybody wants to think they’re the drug of choice. I don’t want to mention product names, but you can imagine what we’re talking about. Sometimes I get bruised.
Dr. Kara Fitzgerald: And it’s not to say don’t take an acute couple of ibuprofens, but I would imagine it’s the chronic use.
Dr. Charles Serhan: That’s right. It’s the prolonged use. Okay, so I have to say this from where I live, from my heart, I have two children that are active military. They take bruises all the time. No, don’t take that non-steroidal. Sports, I think the kids go out sometimes ahead of time thinking if they load up on non-steroidal, they’re not going to get banged up so much. No, are you kidding? You are going to actually make it worse. Then there was a… Then a guy named Markworth went after it and did a nice study with strenuous exercise in, I think it was 60 adults in New Zealand. He published… James Markworth, that’s right. He published this in physiology journals, showed that non-steroidals uncoupled what was called lipid mediator class switching and news. And really laid it up.
Dr. Kara Fitzgerald: They just shut it down.
Dr. Charles Serhan: Now he’s moved to the US and he got a faculty position at Purdue and he is putting out some very nice work on how resolvins are regulating muscle tone and yeah.
Dr. Kara Fitzgerald: Fascinating. Cool. So really you’re saying if you can avoid the ibuprofen even acutely, do it. I mean, you could… We’ve prescribed resolvins.
Dr. Charles Serhan: There are cases when you need to have it. There’s no question about it.
Dr. Kara Fitzgerald: But just limit it?
Dr. Charles Serhan: When there’s an enormous pain. So acutely fine, but prolonged-
Dr. Kara Fitzgerald: Or prophylactically.
Dr. Charles Serhan: There are people who have RA that want to… They’re in pain every day, rheumatoid arthritis, and they want to take non-steroidals every day for the pain. And in some cases, some of those do really effectively reduce pain. But in the long run, you’re throwing a risk against cardiovascular disease and the resolvins. And the resolvins themselves are very potent. Our pain colleagues have shown they’re log orders more potent than morphine. So wouldn’t you want to have a resolvin?
Dr. Kara Fitzgerald: That’s awesome. That is really awesome. There’s a study that I cite showing that fish oil, this was fish oil, I’ll have to get your whole resolvin library, but was effective as Humira for pain relief in RA. But you needed to be taking an adequate dose for a long enough duration.
Dr. Charles Serhan: That’s absolutely right and there are nice studies in animal models of RA and from Canada in OA, osteoarthritis with resolvins. And it’s the question of trying to get pharma to put up the dollars to help do the human trials. And then it’s a head to head. And then the business guys go, “What’s in it for us?” A head to head. Ok, if you lose… We wish the whole world revolved around scientific evidence and molecular mechanisms and increasing wellness through improved nutrition. It makes sense for a bacteria to be in a good environment, a nutritious environment, right?. That’s a simple experiment. They gave a Nobel Prize to that for Jacob and Monod, I think, a long time ago. So is it so hard for us to think that we have to be well-nourished? And probably what we don’t understand is that there are different compartments in the human body that require different types of nutrients constantly.
So I don’t know. If you ask me “Do I need a circulating level of resolvin D2?” I don’t know. I want to know. It’s hard for us to get the answer, but I would think based on my own blood, yeah. Maybe yes.
Dr. Kara Fitzgerald: And going back to, you were talking about Artemis, I always feel like-
Dr. Charles Serhan: Yeah, Simopoulos.
Dr. Kara Fitzgerald: Simopoulos’ work-
Dr. Charles Serhan: She’s a pediatrician who was at NIH her entire career and she understands the genetics really well.
Dr. Kara Fitzgerald: I think it was her, she was certainly one of the people who talked about us evolving with a 25 to one, up to a 25 to one omega-3 to omega-6 ratio.
Dr. Charles Serhan: You’re right.
Dr. Kara Fitzgerald: Which is like your mouse chow. And if we were still consuming anywhere in that neighborhood, we’d be bathed in resolvins all the time.
Dr. Charles Serhan: That’s true.
Dr. Kara Fitzgerald: All of our tissues, right? We probably evolved to have them in a pretty ample supply.
Dr. Charles Serhan: You’re absolutely right. She has a table that I showed from one of her publications where she has the ratios calculated from early evolution when we have evolved from the marine or living close to the shore and then continually going down and how that’s different or in different parts of the world. And I guess that was part of the argument about the Mediterranean diet.
Dr. Kara Fitzgerald: Yeah, its benefit. I’ve got two more questions I want to ask you about neurodegenerative conditions and resolvins. Oh, and I have a little story that I want to share, a paper that I want to share. And then Megan, I want to circle back to you for our future, where we’re going with this. And it’s like some of the science that you’re excited about.
One of that I present when I talk about EPA and DHA and resolvins and so forth, is that there’s some interesting cases. They’re case reports in the literature like severe traumatic brain injury with massive amounts of EPA and DHA given. I expect what I say is they’re probably converting to neuroprotectins and that’s exerting the influence. So that’s one, I want to hear your thoughts on that. But then I also, I’m just curious about using resolvins in neurodegenerative conditions, dementia, Alzheimer, Parkinson, et cetera.
Dr. Charles Serhan: Okay. So you hit two things I really love. So I got an invitation to Kentucky, and there’s a traumatic brain institute there. And they have published beautiful work showing in animal models repetitive injury, TBI, traumatic brain injury from repetitive injury, that resolvin D1, resolvin E1 are all protective. And I think that that’s really important. And it puts us right ins to our… Those that help, our first responders and are defenders of our nation, our military. We want them to have nutritional armor. Okay, think about it. And so yes, massive… The studies, I’ve seen those. And yes, the brain produces resolvins. No question about that. They produce NPD1.
In Alzheimer’s disease, I worked with the group of neuroscientists at the Karolinska Institute some years ago, and we found that resolvins stimulated the clearance of A[Amyloid]-beta peptide.
Dr. Kara Fitzgerald: Fascinating. Wow.
Dr. Charles Serhan: So Marianne Schultzberg has continued that line of research. We put this idea that it was failed resolution and it… But then they publish something really fantastic, which is in that Alzheimer’s mouse, they lose memory because they have this plaque and disruption of their neuro circuits. They gave a nasal dose… A nasal dose of resolvins, and the mice got their memory back. I can’t believe it. It’s so cool. Yeah, so Marianne Schultzberg’s paper you need to take a look at. And there is a company that got started from one of the early Resolvix guys that focused solely on neurodegenerative diseases. And I do think there is an opportunity there because you know that just the drainage system of the brain was only discovered, the lymphatic system, a few years ago.
Dr. Kara Fitzgerald: I know.
Dr. Charles Serhan: Can you believe that?
Dr. Kara Fitzgerald: I know. It’s amazing.
Dr. Charles Serhan: And now the neuroscience is saying, “Oh yeah, you need to sleep so that you can flush what you’ve accumulated during the day.” Okay, good. Well, that’s what the resolvins do in resolving inflammation. Okay. And there’s very nice papers again from Japan. Why Japan? Japan, they have a very high omega baseline in their diet. They’re really interested in this. They have very good neuropharmacology. They have presented data suggesting that the resolvins E-series and D-series are endogenous neurotransmitters, they’re endogenous antidepressants.
Dr. Kara Fitzgerald: Oh, incredible. Very interesting. So this could be the mechanism of why we’ve seen fish oil effective.
Dr. Charles Serhan: Absolutely. Don’t you feel down when you feel lousy? It’s part of our IL-1, PG2 circuit.
Dr. Kara Fitzgerald: Yeah, it’s part of-
Dr. Charles Serhan: It’s general malaise. We’re supposed to do that so that we don’t exert ourselves and at a time when our body needs energy supposedly to heal. It’s a divert. At least that’s what I was taught. But that’s all… You can hear I’m old school.
Dr. Kara Fitzgerald: And we know that DHA and EPA both crossed the blood-brain barrier in our… We’re packed with DHA. Do you know do resolvins cross the blood-brain barrier as well?
Dr. Charles Serhan: They heal the blood-brain barrier. I do know that. And they regulate the TNF. We’ve done that in my line. We’ve published it on that. We’ve published on Parkinson’s. But I don’t know. But they’re present in cerebral spinal.
Dr. Kara Fitzgerald: Yes. They are.
Dr. Megan Sulciner: I was just going to say that, yeah. That was a great study.
Dr. Kara Fitzgerald: Are we producing them locally? Obviously, I’m sure we are, but maybe they’re also-
Dr. Charles Serhan: Well, we did publish with some neuroscientists that came to work with us from the Netherlands, that the choroid cells that make cerebrospinal fluid make SPMs. And I’ve seen other groups publish on cerebrospinal fluid. So I would tend to believe it that is part of the normal. But the coolest thing that I’ve seen, let’s talk about measurements. You want the future?
Dr. Kara Fitzgerald: Yeah.
Dr. Charles Serhan: Okay. But we need the rest of the evidence. So a group from France and Italy just published that you could measure bioactive lipids in saliva and that the saliva can dictate cardiovascular events. I was like, “Wow.” Wouldn’t that be better than drawing blood on your patients…
Dr. Kara Fitzgerald: Yeah. Hundred percent.
Dr. Charles Serhan: or getting a finger prick? Just for your audience, just to differentiate from sputum. Sputum is different. Saliva, this is a secretory gland, and it doesn’t take much. You can milk it. I learned this from the oral medicine people. And there are some very nice papers by a woman named Olga Baker, who’s been studying resolvins on the salivary gland. So the group is Thierry Durand’s group in France, Montpellier working together with an Italian group. Please take a look at the paper. It’s the first of its kind.
Dr. Kara Fitzgerald: That’s amazing. And again, folks, we’ll build as big a library on the show notes as we can. You can see there are many, many papers.
What are your thoughts, Megan, for the future and what you’re interested in going where, what you see?
Dr. Megan Sulciner: Yeah, I definitely think it’s a really exciting time to be in the field of resolution of inflammation. It is truly so applicable to the diseases we see every day coming into the emergency department. And of course, I can speak particularly to the surgical patients. I think where I see the future going is, one, having more of the medical community, in particularly the surgical community, really understanding the resolution of inflammation. I think we take a stance a lot of the time of just addressing the sequelae of inflammation or anticipating postoperative outcomes that are related to inflammation. But if we start to take more proactive stance, thinking about it, I really think in the field of immunonutrition, it’s going to be a big place where resolvins and SPMs can really participate in how we’re thinking about improving postoperative outcomes, surgical patient outcomes.
There’s so much to do. Every day in the lab I’m thinking of other applications that it’s just really incredible. That’s where I’m thinking. It really is so broad and wide-
Dr. Charles Serhan: In the ICU. In the critical care medicine.
Dr. Megan Sulciner: Yeah. Especially when we were writing our recent commentary too. It was just every day we were coming with this other way, we’re like, “Wow, it’s so incredibly important for this disease, for this disease, for this disease.” It really is a kind of overarching theme that I think has been really overlooked of how we’re still practicing medicine in a much more of a defensive posture instead of being really proactive, as you’re saying. It’s been a really exciting place to be, particularly during my research times.
Dr. Charles Serhan: You would think that everyone that sees the data would feel the same way. But obviously the big pharma doesn’t feel like that. And it’s not all about doing the right thing for humanity. And it’s all about making money. And I was talking to a colleague at the Weizmann in Israel, and he is saying, “Charlie, they’re smart. Don’t think that they’re not smart.” He says “They’re just greedy.”
Dr. Kara Fitzgerald: Yeah, I know.
Dr. Charles Serhan: But I was telling Megan today how acutely… What position we’re in, it’s nice to be on the cutting edge, but “Megan, can’t you get a grateful patient to make a donation. We need a donation so we can push the ball over.” Because that’s what it’s going to take. It’s going to take these Bill Gates guys to open up and say, “Hey, we’ll help you and move the peg forward.” Because… Why do I say Bill? Because one of the unexpected findings, and you know what I’m going to say, Megan, is that the SPMs not just regulate the acute inflammatory response, but they help the acute inflammatory response clear bacteria and viruses, clear bacteria. That was totally unanticipated, it’s like, “Wow.” Anti-inflammatory treatments do what? They immune suppress. So sure, Humira is a great drug, if you don’t mind the risk of TB. Anti-TNF therapy, okay, fine.
We didn’t get enough money out of it for RA, so let’s try it for IBD. TNF, TNF is such an important molecule for host defense. I don’t want to sound too critical, but people are critical of me, I’m going to be a critical back.
Dr. Kara Fitzgerald: But it’s absolutely true. They’re not long-term solutions. They’re not. This is why our mortality numbers are getting worse and worse and worse, in this country and around the world. We have to, as Megan says, start to engage in prevention, start to… The whole medical model absolutely has to undergo a paradigm shift. Peter Attia just wrote an awesome book that I’m tucked into, and he talks about Medicine 2.0, which is what we’re existing in, the paradigm we’re existing in, and needing to move to Medicine 3.0, which has active patient involvement where prevention is paramount before there’s any evidence of disease, or the evidence is strictly at the molecular level.
Dr. Charles Serhan: Absolutely. Where it’s undetectable. People are talking about biomarkers. Okay, well, something’s already going on. Why don’t we be figuring out what’s the best for normal health? We don’t know that what the metabolism picture should look like. We only have some ranges. Artemis’ book just came out.
Dr. Kara Fitzgerald: Oh, good. All right. I’ll have to get it.
Dr. Charles Serhan: On the ideal diet for… And she explains it very nicely.
Dr. Kara Fitzgerald: Good. Yeah, I’m sure she does. Yeah, she’s brilliant. I just have a question I know I’m going to get from listeners, so I want to just ask it of you. It’s a little bit of a left turn, but some of these larger EPA, DHA studies have shown in a vulnerable sort of older polypharmacy population, the risk of AFib. I don’t think that you’ve seen AFib with SPMs, but just any thoughts on that?
Dr. Charles Serhan: I don’t have any thoughts on that. There’s Alex Leaf who has passed now. That was how he focused the use. He was the chair of medicine at Mass General and was an early advocate for increasing EPA and DHA and getting the American Heart Association to change their recommendations because he was a strong believer… And I had a chance to meet Alex on a number of occasions. And he was around even to see the early works on the resolvins. And I know he thought it was cool, but he and his group over the years published that EPA and DHA are actually ion channel regulators. So I think in his frame of mind that they would diminish the risk of atrial fibrillation. But I really don’t know.
Dr. Kara Fitzgerald: I think that that’s right. But they have shown in a very small, a minority, subgroup, polypharmacy older individuals that there was at least trends and some significant, they did hit some significance, but still very low, very low risk in an isolated population. Anyway, for the folks who are going to ping me and ask me about it.
Dr. Charles Serhan: I can tell you one thing we found with the group that’s now in Florida, just quickly, but again, it’s an animal model, but still, it was ahead of its time. Ganesh [Halade] is a cardiovascular researcher and physiologist and found in his heart models, ischemic injury models that the spleen sends out white blood cells. So why the spleen? Okay, spleen is a lymphoid organ in the mouse, but in humans, it’s the lymphoid organs. Send out monocytes that carry… reparative monocytes that carry resolvins up to the heart and starts repair and restoration. I think we’re going to see a little bit more of that in the future.
Dr. Kara Fitzgerald: The whole muscle regeneration, the stem cell support, all of that. Maybe you’ll get your dollars from Jeff Bezos and his new Altos Labs where they’re all about… Well, actually, you’re at Harvard, so you know David Sinclair and his-
Dr. Charles Serhan: Resveratrol.
Dr. Kara Fitzgerald: Yes. I’m telling you, SPM’s been in there somewhere.
Dr. Charles Serhan: Well, there are papers that say that they interact with each other.
Dr. Kara Fitzgerald: Yeah, no doubt. No doubt about it.
Dr. Charles Serhan: Yeah.
Dr. Kara Fitzgerald: Well, both of you, it was just a pleasure. Thank you for-
Dr. Charles Serhan: Hey, it was my pleasure to hear how knowledgeable you are on the field. It’s really great. I know that you’re delivering the best information.
Dr. Kara Fitzgerald: Thank you.
Dr. Charles Serhan: Wow. Thanks for-
Dr. Kara Fitzgerald: That’s an honor. That’s a real honor. Yeah, it’s important information. I am a dedicated and committed mouthpiece for the work that you’re both doing, so thank you.
Dr. Megan Sulciner: That’s amazing.
Dr. Charles Serhan: Good luck.
Dr. Megan Sulciner: Thank you so much.
Dr. Kara Fitzgerald: As always, thank you for listening to New Frontiers in Functional Medicine, where our sponsors help bring the very best minds in functional medicine, and today is no exception. Not everyone can be a sponsor on my platform, and I so appreciate the good work, relentless research, and generous support from my friends at Rupa Health, Biotics and Integrative Therapeutics. These are brands I know and trust in my own clinic and can confidently recommend to you. Visit them at RupaHealth.com, BioticsResearch.com and IntregrativePro.com, and please, tell them you learned about them on New Frontiers.
If it’s not too much to ask, I would appreciate a thumbs up and a kind review wherever you listen to New Frontiers. Thanks.
Charles is the Simon Gelman Professor of Anaesthesia (Biochemistry and Molecular Pharmacology) at Harvard Medical School and also Professor of Oral Medicine, Infection and Immunity at Harvard School of Dental Medicine;
He is Director of the Center for Experimental Therapeutics and Reperfusion Injury at Brigham and Women’s Hospital and past Co-Director of the Brigham Research Institute. Charles received a BS in biochemistry from Stony Brook University followed by a Doctorate in experimental pathology and medical sciences from New York University School of Medicine. He was a visiting scientist and post-doctoral fellow at the Karolinska Institutet, Stockholm with Professor Bengt Samuelsson (Nobel Laurate Medicine 82). In 1987, he joined the faculty at Harvard Medical School and in 1996 received the honorary degree from Harvard University.
Megan Sulciner, MD is a General Surgery Resident in Boston and a current Research Fellow in Professor Charles N. Serhan’s laboratory in the Center for Experimental Therapeutics and Reperfusion Injury. Their recent commentary entitled, Resolution medicine in cancer, infection, pain and inflammation: are we on track to address the next Pandemic?” was published in Cancer and Metastasis Reviews. Her research focuses on the role of resolution of inflammation and tumor recurrence.
Wayne State Lipidomics Analytics
Paper: Resolvin-D2 targets myogenic cells and improves muscle regeneration in Duchenne muscular dystrophy
Bengt I. Samuelsson Nobel Prize in Medicine 1982
Charles Serhan: A tribute to Gerald Weissmann (1930-2019)
Paper: Resolvins suppress tumor growth and enhance cancer therapy
Paper: Fish oil and rheumatoid arthritis: past, present and future
Paper: The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis
Jacob & Monod Nobel Prize in Physiology or Medicine 1965
Paper: Cerebrospinal Fluid Profile of Lipid Mediators in Alzheimer’s Disease
Paper: Salivary lipid mediators: Key indexes of inflammation regulation in heart failure disease
Paper: Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases
Outlive – The Science & Art of Longevity by Peter Attia
The Healthiest Diet for You: Scientific Aspects by Artemis P Simopoulos
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Which specific algal oil is recommened by Metagenics? Are the SPM’s typically listed on label? 17 or 18? thank you! This is such fabulous information!