Practitioners, if specialized pro-resolving lipid mediators (SPMs) aren’t already on your radar, you’ll be a convert by the end of this New Frontiers episode.
In functional medicine, we excel at addressing inflammation through nutrition and lifestyle. However, brilliant researchers like Dr. Charles Serhan from Harvard Medical School have shown us that resolving inflammation requires a two-phase approach. We need to shift gears, rally the cleanup crew, start the repair process, and turn down the volume on the immune system. This transition from inflammation to resolution is exactly what our guest, Ashley Koff, RD, will discuss.
We’ll explore why SPMs, discovered by Dr. Serhan, are crucial for healthy inflammation resolution and how Metagenics has developed a product using the patented Serhan method that has numerous clinical applications, from managing inflammation and pain to addressing neurodegenerative conditions, autoimmunity, and even infertility. We’ll also delve into factors that influence our ability to convert omega-3 and -6 fatty acids into these superstar molecules, such as diet, genetics, inflammatory bias, and poor vagal tone.
This conversation is packed with clinical pearls for your practice and personal use. Enjoy.~DrK
In this episode, we delve into the science of resolvins and their pivotal role in the resolution of inflammation. Ashley Koff, RD, joins New Frontiers to dig into the groundbreaking research of Dr. Charles Serhan, the dual nature of inflammation, and the critical importance of properly bringing the inflammatory process to a close. We discuss practical clinical applications of resolvins in conditions like osteoarthritis, traumatic brain injury, and infertility, and touch on their usefulness for pediatric populations. This episode is filled with cutting-edge information that can elevate your practice and offer new strategies that go beyond simply managing chronic inflammation. Join us for an enlightening discussion that bridges the gap between research and clinical application.
In this episode of New Frontiers, learn about:
Dr. Kara Fitzgerald – Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And of course, today is no exception. If you’re here with us on YouTube, you can see I am sitting next to the amazing Ashley Koff. We are going to talk about all things specialized pro-resolving lipid mediators today and we’re going to really dig deeply into the clinical application of these extraordinary molecules. Let me give you her background, I’ll give you an awesome discount code, and then we’re going to dive right in.
Ashley Koff RD, is a 25-plus year, award-winning practitioner developing and providing truly personalized solutions for patients, practitioners, and organizations. Today, she helms a team at the Better Nutrition Program, a company she founded in 2019, and is a fractional Chief Nutrition Officer for entities like Vitaboom. I also want to throw in there that she’s connected with us and our training programs. Ashley, I know our connection goes back years, and it’s always really nice to be with you and mine your brilliance and inspiration. So, welcome to New Frontiers.
Ashley Koff – Thank you. And I’m here today because of New Frontiers, so we’re going to dive back into that. But I’m so pleased to be a part of this conversation on such a cool topic. So let’s go for it. Yeah.
Dr. Kara Fitzgerald – Let’s go for it. And just so I don’t forget, someone just texted me. I want to say that if you listen to this podcast and you’re inspired, which likely you will be, you can get these SPMs at 15% off. Just go over to our show notes page, or if you’re on our newsletter you’ll see it come out in the newsletter as well, there’s a discount code you can use. With that, for anyone who doesn’t know what specialized pro-resolving lipid mediators are, give us a little background on them.
Ashley Koff – Yeah. Well, I say that I’m here literally because of this, because, if we go back to around 2000, I was in this phase, just really fascinated with research, and at the time, some of that was the newer research on fish oil and different fish oil products. For about five years, I was looking at it and you had all these different companies that were launching different products, but there was also this conversation where you would look into the research where you would see fatty fish, yes, check the box always. Things happened differently for people who were eating fish regularly. And then you would see sometimes, as it related to the supplements, but only sometimes, and there were these questions. So it has taken us these two decades, and thank you so much for the podcast with Dr. Charles Serhan. That was when all of these crazy light bulbs went off for me, and I was like, thank you, thank you for this amazing work.
Ashley Koff – Because what we learned are two really important things. First, what you get when you eat a fish is not what’s in most fish oil products. Second, inflammation is not just about turning off inflammation. We have to resolve the inflammation. In terms of being here today and this conversation, these specialized pro-resolving mediators are different than, and what happens to the EPA, the DHA, and the DPA, and interestingly, also the AA (arachidonic acid) — we don’t want to throw out our omega-6s there — when enzymes actually act on them. It’s kind of funny right now because as I’m telling this to you, I feel like I’m defending my thesis to my teacher. Okay, I learned this. Suffice it to say, if anyone wants to dig really deeply into this, Kara’s previous podcast and also the Metagenics Institute, have such fabulous information from the experts who have researched this and gone over that.
Ashley Koff – What I wanted to do today is have a conversation about why we, as practitioners and individuals, have to dive deeper into this. And it’s because we can’t take this previously understood anti-inflammatory approach and just check the box and walk away from a health standpoint. So that’s what I wanted to say about this. Did I miss anything?
Dr. Kara Fitzgerald – I’m just going to circle back and emphasize a couple of points. First of all, Charles Serhan is the guy who actually discovered specialized pro-resolving lipid mediators. These are literally hundreds of molecules coming from omega-6s and omega-3s. These are the derivative molecules that exist system wide. There are compounds specific for the nervous system, specific immune cells, and across the physiology. We’re making these guys all the time if we have that ability. As Ashley alluded to, we can’t get them in most fish oil products. We get them from whole fish, and we can also make them, but there are plenty of times when we’re not, and they’re essential for inflammation resolution. We will put a link to that Charles Serhan podcast in the show notes so you can learn from the guy who discovered them. It was an extraordinary opportunity for me. I had actually been stalking him for some years to get him to come on the podcast, so I was super grateful when he finally joined us.
Ashley Koff – Brilliant.
Dr. Kara Fitzgerald – Thanks. So in the show notes we’ll connect over to the Serhan podcast and we’ll connect over to the Metagenics Institute because there is a wealth of information. It’s not a bad idea to have a little bit of a background understanding of where they’re coming from, but to Ashley’s point, where she sits from, her focus is thinking about them in clinical practice. So, with that in mind, take us where you want to go.
Ashley Koff – Yeah. And I will add on to that too. A couple days ago in preparation for this interview, I was listening to even more of the research and it was about how our vagus nerve, when functioning properly, actually also produces these SPMs. So we start to understand as we start to look at how the whole body works together, why this is so important. The question that I’ve been trying to answer from a clinical standpoint is, first and foremost, if I’m putting someone on a fish oil as a supplement, an EPA and a DHA, there have always been conversations about is the supplement just a higher dose? If somebody is not doing well, if somebody has rheumatoid arthritis or if we’re dealing with wound healing, or any of these examples of inflammation, is it just about a higher dose? And I think we got into this place where we were chasing higher doses. And for me, that didn’t make sense, especially as somebody who usually comes from a food first standpoint.
Ashley Koff – We also, of course, find ourselves in the situation today where people are not eating fish or where they’re certainly not able to, from an access standpoint, get the quality of fish that they would need to consume at the frequency. And then I think the additional part of all of this is our genetics. I’ll pause for a second and say that for me, sometimes understanding how something works is to think about how something else might work. So another area, when we look at methylation in the body and we’re trying to understand if somebody should be getting their folate from food. Absolutely. Right? And what happens if somebody goes to folic acid? Well, it would have to go through more processes to actually break it down to be able to be absorbed. Right?
Dr. Kara Fitzgerald – Yeah. That’s a good analogy.
Ashley Koff – Your listeners are totally following that. And so, when we look at fatty acids in the same way, what we’re realizing is that it could seem very easy to get enough EPA, DHA, DPA, which is another omega-3, and make sure you get the right omega-6s in the right amounts. Get all of those in and your body, using enzymes, will staple together and give you these pro resolving mediators. But that isn’t happening for a lot of people. And one of the most exciting discoveries of using these in the supplemental form is seeing solutions for people that prior to that, there wasn’t anything that was getting them over the finish line. We weren’t seeing the impact of resolution.
Ashley Koff – So bringing it back to Charles Serhan, even when you did his podcast it wasn’t like these were super available. Now, thanks to places like Metagenics, we can get these in a supplement form. And what he’s done, even in this short amount of time, there’s been so much more research that’s been done in humans with this application. I think that’s so exciting for us to talk about, because when the body experiences inflammation, if we do not actively work on it, and the body has to have the right equipment to work on the resolution…
Ashley Koff – So, if it doesn’t say to the army, stop, we are done with you. We want to lipid switch now and we don’t want any more attack to happen. We want to come in and clean up the mess and we want to make sure that in cleaning up the mess, we now start the repair work process. That missing link is where we’re seeing people not get better from the inflammation.
Dr. Kara Fitzgerald – So let me underline two things. Hold on to that thought. First of all, folks, we’ll link to that vagus nerve paper that Ashley just mentioned. I want to see it. And I think you’re saying in a variety of ways that many of us don’t effectively make it. So, we may be giving people grams of fish oil per day and not seeing the inflammation turnaround that we’re anticipating. For some reason, people aren’t taking that EPA, DHA substrate and converting or they’re consuming fish and they’re not having the same kind of outcome that we’re anticipating.
Dr. Kara Fitzgerald – Maybe this is the quality of fish. I mean, there could be myriad reasons, but the reality is that some of us, especially those of us with underlying inflammatory bias, don’t effectively convert. There’s evidence in the literature that some of us just don’t effectively make these and I think the inflammatory piece is part of that story. So, we have to kind of jump it, and, and as you pointed out, we can provide the SPMs themselves. And I do want to point out so we don’t forget, the way that Metagenics is producing it is the patented Serhan method. They’re making their SPMs as Serhan is making them in the research setting where he’s using them, which I think is cool. They’ve shown ready absorption. They’ve shown impressive human data on that, as well.
Dr. Kara Fitzgerald – And the other thing that I want to point out on why some of us aren’t making them is that there is potentially a genetic conversion issue and potentially an inflammatory driven inhibition of conversion. But the other thing is — you probably are going to say this so you can repeat it again later — if we’re taking nonsteroidal anti-inflammatories, we’re shutting down that conversion. It’s extraordinary. And this is really game changing, I think, for a lot of us. If our patients are on nonsteroidal anti-inflammatories, even a full dose aspirin — very low-dose aspirin actually, can potentially have a favorable effect on SPMs. But if you’re taking a 300 plus milligram dose of aspirin, you’re shutting down the conversion. You’re shutting down those enzymes, and you can shut down the inhibition. You alluded to earlier that we actually need some arachidonic acid, that classic pro-inflammatory omega-6, you guys, will produce the resolvin/lipoxin, and that starts the party.
Dr. Kara Fitzgerald – So from inflammation we want inflammation resolution to occur. So we do need some background there. I’ve yet to see in my practice and when I was in the laboratory, I don’t know that I’ve ever in my entire career seen somebody without arachidonic acid. So we really all have it unless we’re just completely shutting down the pathway and the class switch journey with non-steroidal anti-inflammatories. So for a variety of reasons, we’re not getting it via a number of different mechanisms and that means we’re not cleaning up inflammation. And to your point, there’s a place for these in practice. Okay. Back to you.
Ashley Koff – Yeah. So if we look at the travesty, or the learning experience, unfortunately for some we learn from their health issues, of COX-2 inhibitors, I think that’s so important for us to understand.
Ashley Koff – I remember one time when Andy Weil was launching his book, The Anti-inflammatory Diet, and I walked up to him and said, Andy, you know that it’s not really anti-inflammatory. It’s like the chronic, inappropriate, long, you know, whatever… And he said, “I thought you were in marketing, Koff.” And I said, “Noted”. But we put so much emphasis on this idea of anti-inflammation. I’m so glad that you brought it up because we ditched COX-2 inhibitors for the most part and said, okay, that’s a problem. We don’t want to turn this off. And yet, many patients are coming in, and many practitioners are trying to stop all inflammation across the board, including attacking things like seed oils and saying, have no seed oils, right? Which I think is one of the dumbest blanket statements.
Ashley Koff – If you want to talk about industrial seed oils and get into processing, I’d prefer you actually said just watch out for vegetable oils and look at this. But when we look at this and we say we need to be all this way and not this way, I think that’s so smart. When we, as individuals, are trying to either optimize our health or improve our health to get to the place where we can be in an optimizing state, we have to recognize that part of that is nurturing both of these phases of inflammation. I think for you and me, we could probably give people another way of thinking about it, which is our detoxification system. We talk about it as having two phases, some people talk about a third; it gets too confusing for me. But two phases of detoxification where we need both of those to be working at the same degree of efficiency so that the whole resulting process actually translates into hormones that are used coming through, or toxins that are presented, coming through, getting converted, and then getting eliminated.
Ashley Koff – So if we bring that into what would be the SPMs, I will tell you that SPMs are a foundational part of anybody’s supplemental plan. I actually can find a way, typically, for you to get most nutrients in (through your food), probably not vitamin D and maybe not CoQ10. But I am typically doing SPMs for almost everyone because, number one, I may not have your genetic information and I may not know if there are inefficiencies in, like, ten of these different genes, from the FADS (1&2) genes to the FOX genes, like all of these. Are there inefficiencies? I’m not going to necessarily know that. Are you somebody who trends towards more inflammation? I may not know that. And if I don’t have that information, if I’m coming in with an SPM to make things easier on your system, to turn off inflammation, to do the resolution work, that’s such a win.
Ashley Koff – And yes, we can eat fish, but even in eating fish, I haven’t found anyone where I’m trying to address their resolving and their overall inflammatory condition where I’ve just been able to say, eat fish. When I add in the SPMs, the results go off the charts. Are you seeing the same thing?
Dr. Kara Fitzgerald – That’s interesting. What do I want to say about it? SPMs are a part of my foundational stack. I’m extremely bullish on getting that information. I think of nutrients and food as information, so I want the information of SPMs in my body. I am bullish on them. And I eat fish, and I take fish oil. So the whole complement of the polyunsaturated fatty acid journey, I want in sufficient amounts. And I’ll just throw in the fact that we evolved with about a 1:1 omega-6 to omega-3 intake in our diet. And currently, in some settings, it’s about a 25:1 omega-6 to omega-3.
Dr. Kara Fitzgerald – So this is a really gross modern life experiment of profound deficiency in this information that our bodies evolved with. This is information that we really need. And so for that reason, I take SPMs in my own stack. I prescribe them a lot to my patients. I don’t know that I’m bringing them in as often as you’re articulating, where you’re initiating them as you would vitamin D, although I do use them very, very, very frequently.
Dr. Kara Fitzgerald – One of the things that I would love to see is a lab. I mean, they’re pretty volatile, but could we actually measure and identify who’s making sufficient amounts of SPMs? If you hit the Harris omega-3 index, where eight plus percent of your red blood cell membrane is comprised of omega-3 fatty acids, and you’re healthy, are you taking that information and converting it to resolvins? I mean, I’m looking forward to that granular piece because I don’t know that those of us really focusing on optimal health need to be using SPMs all the time. But underlying inflammation is a thing in this modern world and the little extra insurance of SPMs, for me, has been important. And I know after listening to this podcast, if some of my patients are listening, they’ll ask, why didn’t you start me on SPMs? I started plenty of patients on SPMs.
Ashley Koff – And I think we’re having such a classic doctor-dietitian conversation. Here’s the reason why. Absolutely, I want to continue to get the data. And I think what you’re expressing there makes a ton of sense. Plus, let’s also just have the real conversation about cost, right? So we have to look strategically at what people can afford.
Ashley Koff – The challenge that I have is that neither of us are ever going to prescribe for someone a perfect diet. But even with those better choices, the ability to get in what you need on a daily basis with those better choices… A lot of my clients travel, a lot of them are like, “Oh, I’m driving the kids to four different things, and fast food is happening,” and all of this stuff. So, for me, the reason that it’s become foundational is actually for that reason. Now, what I’ll tell you is, and where we’re a little bit different, I don’t turn to fish oil as often. Fish oil is a significant part of a lot of different recommendations. And a good quality fish oil, game on. I’m a huge, wild Alaskan salmon girl from going up and seeing just what those fish have in them—it’s amazing on that part.
Ashley Koff – So I love that piece. But I also look at blood work and can see where people are making choices where they’re getting in the different fatty acids and may also be doing well in their diet and we’re doing pretty well there. But the SPM for me, that’s why I talk about it like vitamin D. It really is very foundational for me. I was actually just working with a couple on fertility, and I’m not their primary dietitian. I was actually helping to support, and we were going through some things. It’s so hard with the fertility story to be like, and now they’re pregnant! Look, everyone, this has been years in the making. I am very excited that they are pregnant. I also am not going to say that the only thing that switched things on was the SPM. But I do think adding that in there helped someone whose body with the EPA and DHA and some of the other pieces, things were just not resolving.
Ashley Koff – She had a variety of different issues; she had an autoimmune disease, she had other stuff going on. So, to me, it has really become more foundational on that part because I see diets that are “meh”, you know, they are really human on a regular basis. You know what I mean?
Dr. Kara Fitzgerald – Yeah, no, that is fair. And we use SPMs routinely in hormone imbalances. We know that there’s an identified SPM imbalance in endometriosis, for example, one of the classic causes of infertility, among other things. So that’s an awesome indication and an important reason to be prescribing them. So, I agree with you. It’s funny, I don’t exactly want to debate with you, but I do. I agree with you.
Ashley Koff – Why not. Yeah.
Dr. Kara Fitzgerald – I agree with you. That SPM information is essential. However, it’s not going to be populating the lipid membrane as the polyunsaturated substrates, so in my opinion, you need to have both. And again, in active inflammatory conditions, I’m scanning my current patient charts and really, most if not all of them are taking SPMs because they’re in active care with me. But I do absolutely see the lipid membrane. We need to have those. I have to believe that when we get them to the other side of that inflammation-dominant journey, they’re going to be able to make them but we won’t actually have that information until we can measure. And they’re not ready for prime time. I know on my podcast with Serhan, he thought they had them available at Wayne State University, and believe me, we chased it down, but they’re not yet available; they’re only in the research setting.
Dr. Kara Fitzgerald – So I think we’re both right here. Oh, and the other piece I wanted to add regarding fish, even people in my practice who are savvy consumers of fish and making appropriate choices, I’m seeing more and more mercury. It’s anecdotal, this is from my practice, but I’d say out of my last six patients that I can think of– I just presented this in the immune module at IFM because I lecture on fatty acids and cover resolvins there and I just presented this little case series because it’s really alarming to me. It’s very concerning as someone who’s been practicing in this space for many, many, many years. We always look for mercury, but I’m seeing it more frequently in people who know how to select fish, and it’s depressing. So, there’s another reason to think about having clean sources, sure, but also SPMs.
Ashley Koff – Yeah. And I think that’s it. I love quality fish oils as a resource, so there’s no argument in that conversation. I’ve had conversations with vegan clients or I’ll say plant-based, they’re not plant monogamous, and some people say, I just don’t tolerate fish oil. We’ve tried krill oil, whatever, but for some reason, the SPM is totally fine. I had someone on an omega 3, 6, 7, and 9 from plants, and then we’re adding the SPM and that seems to be this really nice collaboration. Now, of course, you have to be able to convert your 3, 6, 7, and 9, and make sure on that…
Dr. Kara Fitzgerald – And you’re not going to be, you’re not going to be converting. The reality is that you’re not going to be converting plant-based. You know, we could explore algae a little bit more, but yeah, if you’re doing plants, you know, and you’re willing to take SPMs, then that’s a–
Ashley Koff – I think that’s the lift. Yeah. I feel like that may be in this space of truly personalized. So look guys, we can do a lot of this from a very data-driven way. We’ve mentioned genetics. I think there’s a lot of value in looking at that. I wouldn’t just look arbitrarily at one essential fatty acid panel, but we could look at a couple and start to see what– You know, I love to use data to judge the ROI of your decisions, but I also think when we look at supplements, it’s rare that I come in and I’m like, oh, definitely on this as a supplement, and I think that is one of the places for this.
Ashley Koff – I love what you said about aspirin, too, because I think that’s actually one that as we look at, not just the tools for reducing inflammation, I mean, I’m seeing people come in on like six different types of anti-inflammatory herbs and all of this other stuff. I think that actually deserves more attention, which is the easy way for you to think about it is if you know that both of these processes need to be happening at an equal or the same degree of efficiency, and you’re investing all of your nutrition and your supplemental nutrition, which is targeted nutrients, hopefully high quality on that part, and you’re doing it on that side and you don’t have the resolving part in there, there’s just this big gap. And I think that, whether it’s as a practitioner or somebody listening, if your practitioner has you following everything from an anti-inflammatory approach and you don’t have the resolving component to it, and especially if you’re somebody who is on that because you’re trying to actively address something that is an inflammatory response, you do want to make sure that you’re doing the resolution phase as well.
Dr. Kara Fitzgerald – I think your detox analogy was nice. So you want phase one and two to kick in and that’s what we’re looking at here. There’s inflammation and there’s anti-inflammation. There’s turning the volume down on the generation of inflammation, so that’s cleaning up the diet, that’s exercising, getting enough sleep, taking care of your gut, using some curcumin, etc. etc. etc. etc.. So that’s the front end of inflammation. The extraordinary thing that Serhan put on the map with specialized pro-resolving lipid mediators, is that white blood cells themselves are pushing out inflammatory compounds during the acute inflammatory response, which kicks into chronic for many, many, many, many, many, many of us. And actually, in the aging phenomena there is inflammaging going on, so arguably it’s a course of aging that we want to really be paying attention to.
Dr. Kara Fitzgerald – So inflammation is happening. We can attack it at the front end, we’re very good at that in functional medicine. What we’re starting to get better at, but I think it’s not fully appreciated, is this inflammation resolution, the phase two detox if you will. So that is within those very same white blood cells, lipoxin is released from arachidonic acid — this is the resolvin coming from arachidonic acid, and that lipoxin initiates a class-switch of the behavior of the cell to start pumping out resolvins. And these guys go in and literally start dumping out molecules and attracting the cleanup crew, you know, the macrophages to start eating the debris up, etc., etc. And there’s this whole incredible class switch journey to clean up and to repair and to turn the volume down, and it’s extraordinary–
Ashley Koff – And to have a different type of macrophage. Right? What is that expression, for every action there’s an equal and opposite—We just can’t say that, hey, we want to just push on one level. So glad you brought up sleep, because one of the other areas that I was looking at, I think this is more new science — so stay tuned and let’s dive into the research and keep looking at it — but they’re actually looking at a circadian rhythm production component to your resolvins. So what Kara was just–
Dr. Kara Fitzgerald – It makes total sense.
Ashley Koff – Yeah. And it was basically saying in people with heart disease, which impacts millions and millions of people, there is a lesser production. And then if you look at, okay, so if I’m on a statin drug and what is the statin medication… There are so many pieces to this for us to look at, where to me, what has felt like a very simple starting point, is to make sure that I’m getting in at least a couple times a week, if I’m in good health and looking to stay that way, I’m nurturing the resolvin phase. So, nurturing that, we’ll call it phase two now of that resolvin phase. And if I’m somebody who is more of an active patient, if I’m trying to actually help my system, especially in autoimmune, turnaround and not attack itself, you need to arm the resolvins so that the messages can go in and say– I was describing it to somebody the other day saying, imagine if tomorrow (one can hope), the war in the Ukraine is over. But if nobody actually told the people fighting there that the war was over and nobody got the message, and we’re all celebrating that the war is over, people would still be fighting and there would still be death and also nobody would be rebuilding, and all of the damage. Right? And so we need all of that to come in. And I think that’s such a key place.
Ashley Koff – The other place that I’m really excited about is in performance athletes, where we can think about the amount of stress that we are intentionally incurring. I’m a huge NBA fan and I’ve had two sleepless nights. Last night’s games were blowouts, but the night before, my Cavs and the Magic were down to the minute with a single shot. So I think my stress needed it, imagine what the actual players, you know, what their bodies… And so when we look at this and we say hey, how do we make sure that your body can interpret the messaging of, I am going to go in and do all of this intense stress work for you in this time period, and then how am I going to turn the stress off? Of course, we look at things like magnesium and we look at the benefits of cold and hot and all of these other things. Well now throw in an injury. Right?
Ashley Koff – If we don’t have the ability for a resolution to occur, or just a slight injury- What we can see a lot of times with athletes is that an injury just sticks around. It’s literally not getting better. To me that’s been just such an exciting area. I’ve talked to a number of different sports performance dieticians and also the physicians, and just saying, hey, look at your protocol differently, especially in season for someone in terms of what they’re getting in.
Dr. Kara Fitzgerald – Yes, and another arm we could go down in that direction is athletics at the pro level or at the competitive level. I frequently bring up myself as a former low-level competitive cyclist and I would get sinusitis at the end of every season. I was pushing and pushing and pushing and pushing and moving into a chronically inflamed place.
Dr. Kara Fitzgerald – So SPMs would have been entirely appropriate, but that was before they were available. What’s interesting is that these are about inflammation resolution, but they’re not immune suppressive. This is not an NSAID, this is not a biologic, this is not shutting down the immune system. It’s balancing it and it’s supporting it. So even in an appropriate immune activation case you can still use these. They are not contraindicated. If anything, some of our go to medications, again thinking about NSAIDs etc., etc., will shut down the inflammation resolution journey. Will shut down that balancing phenomenon. So, I do think athletics is a great place to be considering them. In fact, I presented a case series. We use them in practice all the time, but we did a very intentional data dive into our cases in 2019 and 2020, and then I presented those data in Australia, actually. It was really quite fun.
Dr. Kara Fitzgerald – One of the anecdotal cases was from a team member who was skiing and using SPMs acutely. So this is another… Listen, put a pin in it. After I make this statement I want you to circle back and start talking about how you’re using them and how you’re dosing them beyond just part of your foundational stack. Let’s talk about indications. Let’s talk about dosing, both chronic and acute. One of the really amazing things is that you can’t take two fish oil capsules and say, you know, call me in the morning. You will not get acute relief for fish oil. So fish oil you’re changing the guards in the lipid membrane and that’s going to take, what? Three months or more, just thinking about the lifespan of a red blood cell, so it’s not something you can use acutely, but you can absolutely use SPMs acutely. And that’s one of the really exciting things that we’ve seen.
Dr. Kara Fitzgerald – And the evidence corroborates that they’re absorbed and they can identify them in circulation, I think within 15 minutes. It’s awesome. So we can absolutely use these acutely. She was using them acutely post-skiing instead of popping a couple of Advil. She was able to pop a couple of SPMs. Let’s talk about how you’re using them, what indications beyond the healthy stack, and how you’re dosing them in a variety of indications.
Ashley Koff – Yeah. And part of this is also whether it’s my patient or it’s in collaboration with a practitioner who’s sending a patient over and talking to them about their stacks and what they’re doing with different patients. And we’d have to be living under a rock right now to not be thinking about Ozempic, so let’s just start right there.
Ashley Koff – When we look at your incretin hormones, of course, we’re having a conversation about the lining of your digestive tract around the mucosal layers. There are so many factors that impact inflammation and so many ways that inflammation can go awry in the mucosal layer. That is personal to me. That started me on my journey and that certainly has been the bulk of my work and perhaps that’s actually part of the reason that it’s more foundational for me. It could be that conversation, because I do believe that part of our foundational work right now has to be to do everything that we can to support that healthy mucosal layer, right? To have the inflammation response occur appropriately there. So why did I go immediately to Ozempic? Well, one of the things that we’re seeing with individuals is, first of all, just a decrease in intake and in some instances a significant and very marked reduction in intake.
Ashley Koff – That concerns me a lot about their inflammatory status. I do use Metagenics SPM Active and it’s actually small. It’s not one of those huge capsules. I do have some people put a pin in it and they actually squeeze it into their beverage or just directly into their mouth if they just don’t want to swallow the capsule. But I find that size works very well.
Dr. Kara Fitzgerald – And there’s no fish burps or fish stomach ache.
Ashley Koff – Yeah. So, whether it’s the burping or just the size of something, one of the things that I want for anyone who is deciding to go on that journey and to use Ozempic as a tool to help with, whether it’s food noise, guilt, or whether it’s to stimulate incretin hormone for metabolic health or whether it’s the whole picture, we know that the two actual approved indications for the medication are obesity and diabetes.
Ashley Koff – And in both of those places, we need to make sure that we’re addressing the root cause of inflammation. And so that’s actually been a really useful spot for me. One of the things that we’ve had people talk about is including SPMs, as you mentioned, with your skier, that it has this side benefit, because there is a potentially an anti-inflammatory component to the GLP-1 agonist, to semaglutide and tirzepatide, but now adding the resolvins, to me, has been a really nice, collaboration.
Dr. Kara Fitzgerald – And there’s evidence out there showing that those on the metabolic continuum, specifically they looked at metabolic syndrome, were not making sufficient SPMs, so your suspicion, your hunch is correct in that. Yeah.
Ashley Koff – And we are already addressing so many factors there with digestion and with your stomach acid and so many other pieces.
Ashley Koff – So when we asked about different places, for me, that is typically I’m trying to get them to get two capsules in a day. If I can get one in, I’m actually happy. If somebody has an active autoimmune disease, and we’re trying to reduce symptoms, if they’re symptomatic and we’re working on that process, then I’m typically recommending two, twice a day. I go to a higher amount. That also depends on what else they’re able to get in. I may just be keeping them at 1 or 2 because I don’t want to overwhelm a system and just start to see at an individual level, how does our whole approach, whether I’ve removed gluten, whether I’ve got you on gut healing stuff, we’re doing all this other stuff, how responsive are you? But a lot of times we’ll actually start off at that higher amount of the two and two. Is that where you’ve been tracking with things like rheumatoid arthritis and psoriatic arthritis and….
Dr. Kara Fitzgerald – I think two and two is entirely reasonable. And the toxicity studies – they’re just really safe, they’re well tolerated, you’re not going to be limited by stomachaches, etc., so I will go higher, especially for acute indications. A really interesting case was an HLA b27 uveitis patient that I worked with, and she had a prodrome experience, where it would feel like she had dust in her eyes. And actually, here’s another amazing indication, she would have post-steroid, rebound flares [in skin, etc.] as we see all the time. And so I would have her at the first sign dose a couple of SPMs, like every 2 to 3 hours at that prodrome and we effectively shut it off.
Dr. Kara Fitzgerald – We shut that prodrome off and she didn’t move into it. I’ve used it in a few different cases for steroid rebound effect. It’s not a cheap product. That’s a potential rate limiter, but if people can invest maybe a bottle or so, maybe two bottles and use it acutely, we can really shut things down. And then I would say that two, twice a day or two, once a day, So two, twice a day in early treatment and then maybe just BID (one, twice a day) after that long term, would be my approach in autoimmunity and again, in certain instances just turning the volume up for that first sign. There’s another patient I’m thinking of right now and we’ve shut down chronic sinusitis in her many, many years and SPMs has been a piece of that journey along with some other–
Ashley Koff – And I know we love Himalayan Tartary buckwheat, so part of it is the polyphenol, like the other conversation. One of the things I think we’re always evaluating with our patient care is we’re looking at their total nutrition. And so of course, here when we’re talking about the dosage, we’re talking about it just as it relates to the SPM, but part of that’s going to be impacted. If I can get somebody on something like Microbiome Rejuvenate, a product I love with Himalayan Tartary buckwheat in it, and the SPM for some of these patients, I’m going to be in a better spot for them overall. But if I can’t, that might be where I’m at. And so it just kind of depends on what we can do in that space.
Ashley Koff – I did mention fertility. I really like it.
Dr. Kara Fitzgerald – And how do you dose it?
Ashley Koff – I’ve just had one [case]. So, infertility has a different story. That’s a conversation about what’s the root cause of the infertility, what are we looking at, you know, etc., on that part. but in collaboration with a prenatal, I love it. And I think we do have to be careful about the buyer beware. I love that you have the intricacy, and we’re able to communicate about the fact that the way Metagenics is making their product is the way that Serhan has established. With the popularity of SPMs, which sometimes you’ll just see PRM on there, we’re kind of seeing it pop up on a lot of fish oil products, and that’s a little bit concerning to me too. Is it something that somebody added back in? Did they add a little back in? Are you going to get the efficacy? So, buyer beware and look at the product. But I think just one that is really good quality, in collaboration with your fish oil, or for women who don’t want fish oil but will take SPMs. So I don’t know on that part.
Dr. Kara Fitzgerald – EPA and DHA are in the SPMs, just at lower quantities.
Ashley Koff – At a lower quantity, on that part. To me, I think that piece is significant. The other one that I think is totally worth the conversation. Well, I think the heart health side, and then I think we really have to talk about this perimenopause, menopause piece in there. I think on heart health, for me, there are two things. If I have genetics and I’m able to see, especially with somebody’s ApoE status, that’s going to help me really figure out if I want to hit it a little bit harder or sort of what we’re looking at and then also their LP little a (lipoprotein A), etc. So I think there’s definitely an indication there. And then–
Dr. Kara Fitzgerald – ApoE4.
Ashley Koff – Yeah. And just to make sure that we’re getting that genetic part, we’re not missing something. Perimenopause, I’m fascinated, I’m in it. So there’s that conversation, and so I have been adding it to most of my perimenopausal women’s stack. I also really love to hit gamma linolenic fatty acid at a good amount and have been adding that in, again, typically it’s 1 to 2 a day. So, if I can get somebody to have two a day, especially if they’re having hot flashes, if they’re having skin issues, if they’re having dryness, especially the dry eye. There’s also some really good research on SPMs around glaucoma and other things. So, especially if you’re worried about that piece, it’s an area to look at. But I would say that’s another one that I’m really focused on too.
Dr. Kara Fitzgerald – That’s awesome. That’s awesome. That’s really interesting. Gamma linolenic acid, that is in omega-6, you guys, that converts to dihom*o-γ-linolenic acid and it is converted to DGLA. It has a handful of really beautiful anti-inflammatory eicosanoids it’s converted to. I actually am pretty bullish on the idea that GLA to DGLA. DGLA probably has a host of resolvins yet to be discovered, and I was talking to Serhan about that. You know, if I had a different career, I would probably want to be a lipidologist, at least in part. I mean, I’d probably want to do epigenetics as well, but it’s funny. I’m pretty sure those have yet to be discovered. And he said that he thought so as well. Just structurally with DGLA, it makes sense that it would be able to and the fact that it’s already known to be able to make anti-inflammatory eicosanoids. And so that’s why we’re using the GLA from evening primrose or from borage oil, you guys
Ashley Koff – Or I use hemp seed and hemp seed oil, just depending on the quality and what you’re able to get in. But I call it the glamor fatty acid. We just gotta get enough of that in, you know? And yeah, I’m with you on the DGLA.
Dr. Kara Fitzgerald – And we’ll see deficiency. A lot of people don’t have enough. Always take that with some EPA and DHA, and probably the SPM, the EPA, DHA. It doesn’t take a lot, even the EPA and DHA in an SPM is sufficient. Otherwise, it can be converted to arachidonic acid. So yeah, thanks for bringing GLA into the picture. It’s a molecule that has yet to have its moment in the sun, but it’s got a nice long traditional use history, especially in naturopathic medicine, and there are important reasons to believe in it. Those are awesome indications.
Dr. Kara Fitzgerald – So for me, we’re using SPMs. We had a fun case using it acutely in a thumb tendonitis case, and this woman found it to be as effective as ibuprofen when she had flares. I’ve used it in neurodegenerative conditions. I think your ApoE4 point is brilliant. I’ve used it in Parkinson’s disease, again, uveitis and other eye conditions. I’ve used it in allergic diseases. There’s some nice evidence in animal models around having a balancing and inhibitory effect on IgE. A chronic urticaria case comes to mind. Certainly, autoimmunity across the board, pain of any flavor. We’ve used it in headaches. I will say that we used it aggressively in a plantar fasciitis case, which didn’t have a big impact. However, she was able to do the fabulous Graston Technique.
Dr. Kara Fitzgerald – She went to a chiropractor, and I refer for that routinely for plantar fasciitis and you can just kind of kick it out. You can just resolve it. So yeah, what else would I say? I think, you know–
Ashley Koff – What about, you’ve mentioned a couple of the bacteria and virus. I actually haven’t seen that many long Covid patients, but part of that is this long Covid bucket of definition. So, we’ll talk about it and say this is probably long Covid, but that’s not specific to the work that we’re doing. And yet I’ve had repeated conversations about, and actually with somebody with EBV (Epstein-Barr virus) where it was like, here’s what I would recommend, and I’ve had people go off and talk about it and perhaps pursue that with their practitioner. Is that something that you have any more experience with, either with patients or what you’re seeing?
Dr. Kara Fitzgerald – So just to bring back to my earlier point, we don’t want to be afraid of SPMs when we’re looking at some sort of an immune-driven problem. There’s a cool Lyme arthritis paper, again, it’s in an animal model, but it’s still really compelling. They published using SPMs in Covid. Certainly, I’ve used SPMs routinely in my patients where I suspect EBV or some other sort of occult chronic infection is a piece of the puzzle. So, yeah, without question, I think it has a role and we don’t want to mistakenly look at inflammation resolution as immune inhibition, in a way that would allow the condition to flourish. In cancer, it’s not contraindicated for me in cancer, and I’ll just pin it to the show notes again along with the Serhan podcast. Actually-
Ashley Koff – Well, in the Serhan podcast–
Dr. Kara Fitzgerald – We discussed using it in cancer. Yeah.
Ashley Koff – Yes. Is it his student or his colleague who, like…
Dr. Kara Fitzgerald – Yes. That’s right.
Ashley Koff – I mean, that’s like, that stuff is blowing me away. When you look at the ability with breast cancer cells… I’ll tell you what else is in that podcast. I think I’ve listened to that like six times. So, let’s talk for a second also about kids, because I think that’s an interesting area where, when we talk about giving the analogy of phase one, phase two, I end up typically seeing children, either for what one might say, “weird allergies or intolerances” or where somebody has limitations to their diet based on diagnosis or other pieces on that. And one of the things that I find that I very much appreciate, and I’ve been really comfortable with using it in children, is that the idea of I’m trying to do as much as possible to support a system working the way that it’s supposed to work as easily as possible from the early days.
Ashley Koff – So I’m using it in children and in pediatric care. I had a kid who, oh my gosh, the histamine response was just off the charts and I felt so bad they were on a low histamine diet for like three years. It was just so much food avoidance. And then it was just, let’s keep taking away more and more foods, and they were on antihistamines. Just going about it, in my opinion, really the wrong way. We’ve been able to really improve the diversity of the diet and as a result, what they’re able to tolerate. So I’m a really big fan there. I would not say it’s foundational there. I just want to be clear. I’m not coming in saying every child needs to be on this, but I do think that we can look at the benefits there, especially for children where it may be that the system is showing that one side is over-operating, the other is less efficient. Yeah.
Dr. Kara Fitzgerald – There’s really cool data going back to fish oil as having an immune balancing and immune maturation effect in kids. And it doesn’t take a lot. The immune system is really being developed, obviously, especially in infancy, and a piece of that is allowing the Th1 arm — I know this is an oversimplification — but the Th1 arm to be developed and then it can turn the volume down on Th2, which is the classic allergy arm. And there are some data really showing that happening with fish oil. I wouldn’t be surprised if we saw the same thing, obviously with SPMs, or that maybe some of the mechanism has to do with the SPM production. So for sure there’s a piece. And the other obvious piece is that it can be difficult getting fish into our kids. My daughter takes an EPA/DHA supplement when I can get it in her. Probably they’re deficient, at least a lot of them, because it can be challenging to get in.
Dr. Kara Fitzgerald – And again, it can be challenging to find really good quality sources of fish. And the other piece Ashley, is we’re seeing plenty of kids these days marching towards the chronic diseases of adulthood way earlier. We’re seeing metabolic disease. Those conditions that seem to have built into them an inability to make the resolvins, those are happening in our children at younger and younger ages. There’s a handful of reasons to use them and I certainly don’t shy away from using them in my pedes population.
Ashley Koff – Yeah, I think it’s so key. You, much more so than I, are much more evidence-based and I’m extremely practice-based, and then I look at the individual and in terms of using this, and again, it really is the supplement. I’m saying, hey, I’m going to see what I can do for you right now by adding this in, and as we said, increasing the dose. But it will be really fascinating to just keep following the research. And now that the SPMs are available, see if does it help women who struggle with breastfeeding? Does it improve early gut development? I mean, there are just so many pieces.
Dr. Kara Fitzgerald – Yes, yes, yes,
Ashley Koff – Concussions. Somebody was asking me about concussions. I mean it’s just fascinating to me.
Dr. Kara Fitzgerald – Well, listen, let me go back to concussion. We’re at time but let me just go back to that because there are reports in the literature of using massive amounts of EPA and DHA. We know DHA is the main omega-3 in the lipid membrane in the central nervous system and then we retro convert it to EPA and then we go on to make resolvins. But what about those cases when we’re not? Anyway, using these mega amounts of fish oil in traumatic brain injury, it has to be that the mechanism is that you’re pushing the neuroprotectins, that you’re pushing that class of resolvins that specifically exist in the brain that are produced from DHA. That just has to be, in my mind, what’s happening here and Serhan could speak to that, and maybe there is evidence in a mouse model or something. But no doubt we want to be thinking about these plus high-dose fish oil in brain injury for sure.
Ashley Koff – Yeah, and especially, that’s a population that’s very likely going to be taking those anti-inflammatories at high, high doses.
Dr. Kara Fitzgerald – Yeah. That’s right.
Ashley Koff – I could talk to you about it forever. I love it.
Dr. Kara Fitzgerald – You guys, I want to hear from you on this one. I don’t usually put that out there, but I would be really curious to hear from the clinicians. You can post your comments on iTunes or you can just email us. I think you can make a comment on the transcript page if you go over to our show notes. We’ll populate our show notes with as much as we can because there’s so, so, so much out there. Go to the Serhan podcast if you haven’t had a listen. It’s one of my all-time favorite podcasts ever. Thank you, Dr. Serhan, for joining me. And yeah, we’ll circle back maybe in a year or so, Ashley, and continue the conversation. Thanks for joining me.
Ashley Koff (00:58:17) – Thanks for having me.
