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Kalea Wattles, ND:
Today on Pathways to Well-Being, we welcome IFM Director of Medical Education Dr. Dan Lukaczer and IFM Director of Medical Education Initiatives Dr. Robert Luby. Today we’ll focus our conversation on some of the top functional medicine hot topics of 2020 and what they mean for your practice.

Obviously, the COVID-19 pandemic dominated much of the medical news in 2020, and we will discuss some of the important takeaways for functional medicine practitioners from that research, but there were also several exciting themes in functional medicine that we’ll explore as well. Drs. Lukaczer and Luby, welcome to the podcast.

Dan Lukaczer, ND:
Thank you.

Robert Luby, MD:
Thank you, Dr. Wattles.

Kalea Wattles:
So I’d like to kick off our conversation today with a topic that’s really been at the front of our minds this year. It was highlighted in detail at our Annual International Conference. And that’s fasting and time-restricted eating. We have some data to show that fasting and even eating following circadian rhythm can have a beneficial health impact. Dr. Lukaczer, you and I have talked some about how these health-promoting strategies don’t always need to cost extra money, and fasting is certainly one of those. So I’d love to hear, from your perspective, how can we utilize fasting and therapeutic fasting in a clinical setting?

Dan Lukaczer:
Great question. I think it can be very simple, and it’s a complex topic. And I guess the first thing I’d like to say is the literature often doesn’t differentiate when we’re talking about fasting because, just as you talked about, Kalea, there’s time-restricted eating and how I define that. And I think we should be careful with these definitions because when you look at the literature, they’re talking about different things. So time-restricted eating is basically extending, generally, an overnight fast. So I think there is likely no magic number. It’s probably 14 to 16 hours, but that is my magic number. I try to get people, when I’m talking about time-restricted eating, to a 14-hour fasting window, if you will, and therefore a 10-hour eating window. So that’s time-restricted feeding.

And then there’s fasting. To me, and I think in the literature as well, fasting is 24 hours or longer. And then there’s this thing that we call a fasting-mimicking diet that Valter Longo et al have done a great amount of work [on], which seems to have some similar benefits to a fasting regime. And then there’s these other things that are alternative day fasting, these 5:2 fasts, etc. So the simplest thing to start with, I think, is time-restricted feeding. And so trying to get patients, which can be very simple, of just having them extend their overnight fast, if you will, for 14 to 16 hours. And I think there are very good studies, both in animals and humans, as we had some great presenters at the Annual Conference talk about this, about time-restricted feeding and intermittent fasting and how those can improve obesity and diabetes and cardiovascular disease and even some kinds of cancers.

And the question that I think we should be asking—and there’s more research to be done in these areas, but what are the benefits? Because I think that’s when you get to these different ideas about time restricted-feeding and intermittent fasting and 24-hour fasting, etc. And I think they break down into probably three or four kinds of different benefits. One is we have this metabolic switching in which you’re going from a diesel to a gasoline, as I try to talk to patients about you going from glucose utilization primarily to ketone utilization primarily. And if you do that easier and easier, so you do more of this, I think that metabolic switching happens easier. And we know that there’s a lot of benefits of feeding the body with ketones, and ketones, in fact, are a cellular signal. So that’s an important attribute of these different regimes.

Then particularly in cancer therapy, I think there’s this idea of stress resistance and the idea that cancer cells, which are fast-growing cells, they don’t respond to a fast, whereas other cells do respond to that fast, and so they shut down a bit. And so when you, particularly in chemotherapy—and there’s been some studies done with this—that therefore, you can target, or chemotherapy can better target cancer cells, because they’re not shut down if you’re doing a fast before chemotherapy. There’s good studies on that. The third idea is this word that’s been thrown around a great deal in the past couple of years, is this cellular cleanup or autophagy. And I think that’s a very important aspect. Well, it’s hard to say if it has to do with those other two, but it seems to be a third specific way that fasting works.

And then the fourth is weight loss. There seems to be some good studies that suggest that individuals who are doing some of these fasting, time-restricted feeding approaches do have a pretty significant weight loss if you look at them as a group. And that doesn’t mean that everybody’s going to get weight loss, but in my clinical experience, there is some weight loss just by doing time-restricted feeding. So it’s hard to say whether I’ve answered your question, but I’ve had a lot of fun just going over what we’re talking about. And really, the field has exploded in the past couple of years around these concepts.

Kalea Wattles:
Well, I think you certainly answered the question. And I love that you also brought up this concept of metabolic flexibility, which I think is somewhat of a buzz term right now. People want to know how they can become more metabolically flexible. Before we move on from this topic, you mentioned all of the various types of fasting that one can do. And sometimes when I’m talking to patients about fasting and they want to know, ‘Which strategy is right for me?,” I kind of feel like it’s just the one that they’ll do, the one that’s realistic for them and the one that they will actually follow through with. Is that how you approach choosing a strategy as well, or do you have some further insight into how you select the right path?

Dan Lukaczer:
I think that’s a great way to proceed. I almost invariably start with the time-restricted feeding because I think it’s the easiest. And then I do think that actually longer fasting, 24-hour fast, or a three-day fast, if you can get individuals to do that, probably has some other benefits, because when we talk about ketosis, you’re not generally getting into nutritional ketosis if you just do a long, overnight fast. You usually have to go to 24 to 48 hours to actually get into 0.5 to 1.5 millimoles of ketones. So again, directly answering your question, I think that’s a great way to start, Kalea, is, what will they do? And what they will generally do, depending on how you’re framing it, of course, is it’s not that hard to do time-restricted feeding, in my experience. And in fact, it’s not that hard after you’ve done that for a while to actually do a 24-hour fast. If you go from sundown to sundown, that 24 hours. What gets a little more challenging, I think for people, is actually going 36 hours, because then you’re actually going a full day and night, obviously, without eating. And that’s a little bit of a stretch, and you have to work up to that.

Robert Luby:
And before we move away from this, Kalea, too, a few other things to feature here are the time-restricted eating is so amenable to the functional medicine approach, the Go To It. It really fits nicely into the order and prioritize step because you can do it so many different ways that it fits a lot of patient lifestyles and preferences, which we’re trying to take into account in that order and prioritize step. And we alluded to it at the beginning, also, but it’s very affordable. This is something where you don’t need any special classes or anything to do this. In fact, it might even take some change off of your food bill as well.

In addition to that, it’s very much forgiving. When we talk about an elimination diet, it’s 30 days, you really got to stick to it a hundred percent if you want to identify the offending foods, right? And not so with the time-restricted eating. You can do it some days of the week and not others. The more you do of it, probably the better. And even the biological evolutionary experiment of human beings throughout the ages is that they were unpredictably intermittently forced to do time-restricted feeding. And so, in that sense, it’s a very forgiving regimen where patients can get off the wagon, so to speak, but get right back on and not get upset by it.

And it’s also amenable to the collaborative care team approach with coaches and to shared medical appointments. Patients engaging in shared medical appointments can really help each other out with this kind of approach. That’s another advantage for the time-restricted eating. And I think some of the things that will be exciting for the future are things like, well, when’s the optimal timing for an exercise regimen during the time-restricted eating interval in order to get the most metabolic benefit? And are there subtypes of patients who benefit more or who will do better with a longer restriction versus is there some kind of patient cluster who does just as well with a shorter time-restricted feeding? And then with devices, wearable devices and tracking devices. Once we start getting real-time data from time-restricted eating, we might be able to really pinpoint subtypes and individualize just how long an individual needs to be on time-restricted eating based on data from their wearable device. So I think those are things to watch for going into the future.

Dan Lukaczer:
Yeah. I just want to add, Robert, you’re making a great point in two ways. One, it’s such an easy way to start. And doing it five out of seven days, I think, I know you still get benefits from the literature, so that’s a great point. And then the other point that you brought up of using these wearables, I’ve tried to, when I can, encourage people to get a wearable and how that can have your, obviously there’s a biohacking of yourself. And so you’re looking at your sleep and there’s some… like the Oura Ring is a great way to track your sleep and looking at how you’re eating. Obviously, eating later in the day or into the evening can have a significant effect on REM sleep and deep sleep, so it’s very useful to kind of biohack, and putting those things together.

Robert Luby:
And then, of course, the “hanger” that it all induces is a great prompt to get into a good mindfulness practice as well.

Kalea Wattles:
Indeed. Well, thank you both for bringing up the wearables. I asked for a continuous glucose monitor for my birthday this year, so that really just fueled my fire. Before we move on from talking about ketosis, I want to link this to our next topic. Everybody wants to know about COVID—that’s been the theme of 2020. We know that nutritional ketosis, it may be helpful in terms of insulin resistance or metabolic syndrome, these comorbidities that appear to increase severity of COVID-19 infections. So from your perspective, can therapeutic fasting act as a preventative strategy to either prevent viral illness or at least lessen the severity of disease? Do you have any inclinations about that?

Dan Lukaczer:
The old adage of starving a fever I think comes into play. And I think there is something to the immune response and nutritional ketosis. And probably therapeutic fasting as well in terms of a stress response as well. So I do think that there is some research that has come out that has suggested that there are connections there. I can’t say that I have used this specifically for immune support in terms of nutritional ketosis. I’m usually using it around insulin resistance and hyperinsulinemia and blood sugar issues.

Robert Luby:
With time-restricted eating, I think we don’t have great data. I don’t know if there’s any data out there in terms of in the acute phase of COVID infection or even preemptively. But if we look at it from the reverse angle, and we know from animal studies and human studies that overfeeding is certainly proinflammatory. The comorbid conditions of severe infection in COVID are proinflammatory conditions in large part and/or immunosuppressive conditions. So to the extent that overfeeding, we know, is going to have that kind of a detrimental effect on the immune system, one would have to think that time-restricted eating in the preemptive phase of COVID has a good plausibility for being beneficial for reducing or mitigating the chance of severe infection should you become exposed, because you’d naturally not be in a proinflammatory state. So I think that’s one kind of an extrapolation we could safely make. In the acute phase, once you’ve been exposed, I just don’t know that we have any data, and it is much tougher to predict what kind of an effect that would have.

Kalea Wattles:
All right, well, we’ll stay tuned as I’m sure that this is a hot topic and we’ll get some more data about this in the coming year or so, I would suspect. As we’re talking about comorbidities and things that may increase severity of SARS-CoV-2 infection, we saw some evidence this year regarding lifestyle interventions for non-alcoholic fatty liver disease, and this could potentially be one of those comorbidities. Lifestyle treatment, particularly that that results in weight loss, appears to significantly improve fatty liver, liver injury, liver fibrosis. I’m constantly talking to patients about those personalized modifiable lifestyle factors on our functional medicine matrix, the bottom of the matrix, as we say. And it seems that optimizing these factors, especially in terms of nutrition… And Dr. Luby, you talked about overfeeding. This can make a big difference in terms of liver health. And so I’m hoping you can talk about some key takeaways from how we might approach liver health from a functional medicine perspective.

Robert Luby:
Right now, this is—this is a really intriguing question. And there’s two phenomenon that have been observed that are confounding the way I think about this somewhat, is that liver disease is not the most important factor of all the organ-based diseases, as we say, in terms of determining vulnerability to severe COVID infection. Cardiovascular diseases, renal diseases are actually more influential than liver disease. And yet, we know that this non-alcoholic steatohepatitis or NAFLD, non-alcoholic fatty liver disease, as it’s been called, excuse me, they are more associated with visceral adiposity as opposed to BMI per se in terms of their outcomes. And the same, it seems to be true, of COVID, that visceral adiposity—there’s some data now that that is a risk factor. So it strikes me that I think we’re going to see more emerge here in that NASH, NAFLD, and the way that they contribute to visceral adiposity should be more of a risk for severe COVID infection.

I think we’ll see more in 2021 as the data plays out and/or in the chronic COVID syndrome, we might see the case where these chronic liver diseases are more influential and therefore fasting and restricted feeding strategies may be more beneficial. What I think is just so positive in terms of the whole functional medicine approach to chronic diseases in general is that the world is waking up. The medical world, the clinical world, and the world of the public is waking up to the importance of addressing lifestyle factors to mitigate chronic disease before you get exposed to COVID.

The change in nomenclature of NAFLD, this was fatty liver “disease,” and now it’s not a disease anymore, even in terms of the terminology, we’re getting away from that and realizing it’s a metabolic issue, it’s a metabolic issue. So what I love about this is years back before I joined IFM when I was teaching the residents, I would say to them, NAFLD is not a disease, it’s an effect. It’s an effect of other things. It’s not a liver problem. The liver is just the bystander that’s getting affected by the other physiological problems. And they looked at me quizzically then because they didn’t have the background in systems biology until they’ve been with me for a few years. But this is really accelerating the acceptance of systems biology in the conventional medicine world, which is so exciting that we start to see the conventional clinicians starting to talk about metabolic susceptibility. It’s just music to our ears. And I think it’s going to really bode well for collaborations and getting our camps together, so to speak. So I’m really excited about that aspect of it too. Hopefully the pandemic winds down before we’re able to do that, but hopefully the effects linger and the collaboration continues.

Dan Lukaczer:
Side effects, the side effects linger. I would just add that this is to your point, Robert, I think that there were certainly discussions of these two decades ago, because I remember Jeff Bland talking about this and functional medicine updates and lecturing about it. And so this is not a completely new concept, but just in 2020, I know that there are a number of studies, systematic reviews and some larger evaluations, that continue to clarify the relationship between visceral adiposity, insulin resistance, and hyperinsulinemia with the NAL, non-alcoholic fatty liver disease. And so I think that’s gratifying that it’s moving. Something that Jeff Bland was talking about two decades ago is moving in much more into the mainstream. And we all see this all the time of you see slightly elevated LFTs, or it’s easy enough to get an ultrasound.

And it is, of course, rampant. We know all of that. And one very, I think, useful fact, if you will, to clarify with patients is they just need to lose—now it’s the proper kind of weight loss, but a weight loss of 5-10% of body weight. So if you weigh 250 pounds, 20-25 pounds of weight loss, which is not nothing, but we’re not asking somebody to go from necessarily a BMI of 38 to a BMI of 22 before they get results. They can still be overweight but have a significant effect on hyperinsulinemia that then, of course, has a significant effect on triglycerides, which then, of course, has a significant effect on fatty liver.

So it’s not something that you have to say you have to get this huge weight loss, and weight loss is not the be all and the end all of this particular issue, but it’s an important marker that you can point to with a patient, kind of clarifying what is likely to get results in that way.

Kalea Wattles:
All right. Well, speaking of things that are satisfying, it’s so nice, like you said, how we saw what Jeff Bland was proposing 20 years ago becoming more mainstream. And from what I’ve seen in the literature about fatty liver diseases, that the main dietary interventions are reduced saturated fat, reduced refined carbohydrate, increased plant-based foods. And that’s what we want for most people anyway. So that feels really satisfying that that’s becoming more of a mainstream recommendation.

Robert Luby:
And all three of these areas that we spoke of today also put the patient at the center, because the medical magic bullets just aren’t there yet for any of these. And it really does require the patient to make some changes and for the clinician to really facilitate that, bring in the collaborative care team. So these conditions that really emerged in 2020 as newsworthy also put the patient at the center, which is also a place we need to always be in and go to in functional medicine.

Kalea Wattles:
Yeah, that’s the perfect lead in to my next question. Speaking of patients being at the center is the functional medicine matrix, and IFM has done a great job over the last year of really highlighting how specific nodes of the matrix can contribute to COVID infection risk and disease severity, and how we can really do whole person health care to keep people safe. I’m hoping we can talk a little bit about the relationship between lifestyle and chronic disease and the increased risk for severe COVID infection. I’d love to just get your general thoughts on this topic, if you have any insights you wanted to highlight.

Robert Luby:
Well, if we take a tour around the matrix and we make a few stops, certainly in the assimilation node and with gut function and the importance of the microbiome in modulating inflammation and in modulating the function of the immune system, I think we can really infer that the health of the gut, the health of the microbiome, is critical in also mitigating the vulnerability to severe COVID infection.

Studies will probably emerge later, in next year on that, I hope—and we just don’t have that kind of data now, but with this chronic COVID syndrome that we’re now seeing emerge, it’s difficult to imagine that addressing the gut will not be a cornerstone of addressing chronic COVID syndrome. We’re anticipating that with the continuation of our pandemic Resistance, Resilience, and Recovery course, as well with the webinars that we’ll be holding in January through June, if we visit, say, the biotransformation and elimination node, with what we already know of how toxins and the biotransformation of toxins—both endotoxins and exogenous toxins, the effects of those on the immune system. Very plausible that that will have an effect on the probability or the vulnerability of getting severe COVID infection if exposed. And there’s certainly all kinds of emerging lines of evidence that mitochondrial health over there in the bioenergetics node is going to be very important as the effects of COVID-19 on the mitochondria, and how it gets involved in the pathophysiology is going to be very important. And it seems with the fatigue that we’re seeing in the chronic COVID syndrome patients that that is going to be an issue to address in post-COVID survivors. So I’ve touched on some of the nodes of the matrix, so I’ll stop here and see if Dan has some other areas to touch on as well.

Dan Lukaczer:
I think you did a great job. I would add just a couple of thoughts. One is directed toward the idea of, “Well, what can you do to prevent COVID-19 in patients that you’re seeing? Or what can you counsel them at?” And certainly, physical distancing, hand washing, all of those things are incredibly important, but as you’re talking about this, Robert, just as important, I think, is increasing the innate immune response and decreasing these comorbidities. And the comorbidities that we know are well related to the severity of COVID-19 are cardiovascular disease, chronic kidney disease, diabetes, hypertension. That’s a lot of people, and that’s a good place to start with talking about, ‘How can you decrease those kinds of things that increase your risk?,’ and I think that’s a hopeful thing to talk to patients about.

And then the somewhat depressing thing is what you talked about, Robert, in these long-haulers. And there’s been studies that suggest that that may be as many as 10% of individuals who get infection. So if you’re looking at the United States right now, long-haulers, there’s somewhere around 15 million people who have developed a COVID-19 infection. So we may be talking about a million or two million people right now that have this quote unquote long-haul syndrome, which is just the chronic manifestations that we don’t completely understand of COVID-19, or what’s left over after the damage from that virus. So there’s a lot of people that, I think, are going to need a functional medicine systems biology approach who have not completely recovered from COVID-19.

Robert Luby:
And I think we have to even multiply… It’s a great point you make, Dan. Multiply the absolute number of those who will develop chronic COVID syndrome by those around them. We are a systems biology­–based approach to the patient, but the patient is in a system, a family system or a community system. And with this number, these millions that Dan talked about, how many caregivers does that affect? How many children does that affect whose parents are not now well? How many incomes are going to suffer? And on and on. So as functional medicine clinicians, we have to address the entire family system as well as the entire physiological system. And to return to the matrix for just a moment, both in preemptive COVID before exposure and in the chronic COVID syndrome, if we visit the base of the matrix, the modifiable lifestyle factors, we know the effect of optimal sleep on the immune system and suboptimal sleep, how detrimental that can be, how positive exercise can be for immune system function when done in moderation.

Nutrition, we’ve already touched on, and of course we know stress and the effects that it has on the immune system, and even all the data on loneliness with the isolation that so many of us are experiencing. So the lifestyle factors at the base of the matrix are so important preemptively before you’re exposed to the virus, and I think they will be just as important, influential in correcting physiology and assisting recovery in the post-COVID syndrome.

Kalea Wattles:
Yeah. And on that note, IFM has curated a really important list of lifestyle practices and nutraceuticals and botanicals that can be used to support patients who have SARS-CoV-2 infection. Can you highlight how our clinicians who are listening might use those tools to support their patients?

Robert Luby:
Yeah. There’s been a published paper come out of that. We’ve developed some wonderful tables and charts with citations and strength of evidence of botanical and nutraceutical agents that can be adjunctive to whatever the guidelines or best practices and recommendations are in conventional medicine. So those are resources that are available. We also have an online course, a six-hour course for which you can register on the website, to be followed up with a six-month course to follow in on the latest emerging evidence in order to address patients with chronic COVID syndrome. So there’s a lot of resources that all of our clinicians can access to help all phases, before you’re exposed to the virus, in the early first week or two of mild-to-moderate symptoms in the hopes of mitigating or preventing the progression, to the severe infection. And then as we learn more and gather the data on the chronic COVID syndrome, we will be adding resources as well to help our clinicians out so that they know how to best address the chronic COVID syndrome survivors.

Kalea Wattles:
Well, I have to say thank you so much to both of you for being here today to discuss really some of the most exciting research that we’ve seen in 2020. And it’s so encouraging that despite a global pandemic, the power of functional medicine continues to emerge in the evidence. So thank you both for being on the show today.

Dan Lukaczer:
Thanks, Kalea

Robert Luby:
Thank you very much.

Kalea Wattles:
To join the conversation on this topic, visit IFM’s pages on Facebook and Instagram. For more information about functional medicine, visit ifm.org.