Harnessing 6 Years Of Fasting In Clinical Settings

Jeffrey Grimm, NP-C

Thank you. I appreciate it. Thanks for being here, everyone.

Joseph Antoun, MD, PhD, MPP

Yes. Do you mind giving a little bit of background about it?

Jeffrey Grimm, NP-C

Yes. My name is Jeff Grimm. I completed my training at Columbia University. I’m an adult nurse practitioner. I own and operate a clinic in northwest Portland called Biolounge, where we primarily do functional and anti-aging medicine. We have a team of seven medical providers that deliver that to patients, and I got my start around 2010 or so when I completed a fellowship in board certification, anti-aging medicine, and functional medicine. For many years, I’ve been interested in fasting going back to being a teenager. I did my first fast at age 19. I fasted for nine days. It’s been a hot topic since I got more into the science of it as the science evolved. It was an exciting time for those of us who had personally experienced the benefits. Now we had the scientific validation, largely in part due to Dr. Valter Longo’s work, of course, at USC. When these fasting-mimicking diets became available, it coincided with the time when I opened my clinic. Starting in late 2017, we started offering L-Nutra products. The flagship one, of course, was the ProLon five-day fasting-mimicking diet. Since those early days in 17, we have probably used six or 700 at least, maybe even 1000 at this point, of these fasting-mimicking kits with patients. We’ve had feedback from hundreds of people who’ve done this over the last six years in many different contexts, many different ages, and many different situations. I’m very happy to talk about our experience with those products in the context of the other context we’ll talk about today, where we’re thinking about autophagy and fasting as game-changing treatments for our patients.

Joseph Antoun, MD, PhD, MPP

That’s fantastic. Maybe we talk about two topics: a lot of men watching us today thinking about the cardiometabolic transition between age 40 and 65, and a lot of women throughout this age going through menopause as well and having that biological clock ticking and tickling them. I wonder, how do you approach this? These are signs of aging and will impact longevity. How would you describe how in your clinic you’re approaching these profiles, what you do with them, and what fasting and fasting interventions you typically do for these profiles?

Jeffrey Grimm, NP-C

Great. let’s let’s tackle men first.  a lot of guys say 40 to 60 or 50 to 70,  are going to start to develop risk factors for cardiovascular diseases, which is still the number one killer of men. Clinically, what we aim to try to do is find early evidence of that disease process so we can mount some justification for interventions like fasting, among others. what we would do, and we do a lot of now are quarter of calciuGreat. Let’s tackle men first. A lot of guys, say 40 to 60 or 50 to 70, are going to start to develop risk factors for cardiovascular diseases, which are still the number one killer of men. Clinically, what we aim to do is find early evidence of that disease process so we can mount some justification for interventions like fasting, among others. What we would do, and what we do a lot of now, are quarters of calcium scores. We’re looking for arterial plaque in these patients to see if it’s present early and if they’re in a high percentile for their age. For coronary artery disease, we’re doing cardiac ultrasounds in the office once a month. Now we have a tech come out. again, looking for early evidence of vascular aging and endothelial dysfunction, along with the standard blood work, which might highlight insulin resistance or elevated lipids or other risk factors, inflammation, etc., which may take them on an accelerated trajectory toward cardiometabolic disease, heart disease, etc. When we have identified people who are at higher risk or who seem to be catapulting down the heart disease trajectory, we start to stack interventions. One of the things that we’re going to be thinking about is reducing cardiometabolic risk through fasting. 

The other thing we would do is have a body fat scale. We’re going to be looking at their body fat percentage. We’re going to be advocating for things like ProLon to reduce body fat and inflammation. in our patients who we discover have early cardiovascular disease. I had a 47-year-old guy last week who was in the 92nd percentile for an arterial plaque for his age because we cut our calcium score early. So he’s a guy, and one of the interventions we’ll be talking about is a Mediterranean or more plant-centric diet and certain supplements to stabilize endothelial function. Potential drugs to get his LDL to a target of at least 50% below baseline and then fasting. Why do we care about fasting? Well, there’s enough evidence that autophagy is activated by fasting—ProLon fasting. It may have a positive effect on endothelial progenitor cells. So these are the cells that can, in a positive way, remodel your vascular system. All these guys have endothelial dysfunction, which means that in an average healthy person, cholesterol is bouncing around. But if you’ve got dysfunction at the endothelial level and a lot of inflammation and immune activation there, then that cholesterol can form plaque. The disease natus is at the level of the endothelium. We’re thinking that maybe we can get some stability there if we’re activating autophagy, which again, this program does. How often might we do that? It’s a case-by-case thing, but for guys with known cardiovascular disease, the definite plug is two to three times a year. You’re going to be activating autophagy through the fasting-mimicking diet. Along with these other interventions I mentioned, we might also recommend another hot topic these days: frequent sauna bathing, which, along with exercise, could reduce heart disease by another 50%. We would stack the things, and then we would monitor these folks. We would do serial ultrasounds, maybe get a repeat calcium score in five years, and check the inflammatory markers linked to plaque stability. 

Hopefully, we’re showing these patients that things are coming down or stabilizing. It goes underappreciated. But if you’ve stabilized cardiovascular disease, you’ve probably had knock-on positive effects because you’ve stabilized a disease process that goes everywhere in your body. I’ve heard that if the vascular system was flattened out, it would take up five tennis courts. This is a very large surface area organ that you’ve now stabilized and, potentially, improved the function of dramatically. There’s going to be knock-on effects, maybe to your kidneys, your brain, reducing your risk of stroke, dementia—who knows? But it all follows that if you fix that whole organ, you’re going to have a lot of positive downstream effects as well.m scores. we’re looking for arterial plaque in these patients if it’s present early, if they’re in a high percentile for their age, for coronary artery disease, we’re doing cardiac ultrasounds in the office once a month. Now we have a tech come out. again, looking for early evidence of vascular aging and endothelial dysfunction, along with the standard blood work, which might highlight insulin resistance,  elevated lipids or other risk factors, inflammation, etc., which may take them on an accelerated trajectory toward positive metabolic disease, heart disease, etc.. when we have identified people who are at higher risk or they seem to be catapulting down the heart disease trajectory, we start to stack interventions. one of the things that we’re going to be thinking about is reducing cardiometabolic risk with fasting. the other thing we would do is we have a body fat scale. we’re going to be looking at their percent body fat. 

We’re going to be advocating for things like ProLon to reduce body fat, also reduce inflammation. in our patients who we discover have early cardiovascular disease. I had a 47-year-old guy last week who is in the 92nd percentile for arterial plaque for his age because we cut our early with a calcium score. so he’s a guy that one of the interventions we’ll be talking about is a lot of things,  Mediterranean or more plant-centric diet, certain supplements to stabilize endothelial function. Potentially drugs to get his LDL to a target of at least 50% below baseline and then fasting. why do we care about fasting? Well,  there’s enough evidence that autophagy is activated with fasting, obviously ProLon fasting for sure. it may have a positive effect on endothelial progenitor cells.  so these are the cells that can,  remodel positively, your vascular system. All these guys have endothelial dysfunction, which means in an average healthy person, cholesterol is bouncing around. But if you’ve got dysfunction at the endothelial level and a lot of inflammation there and immune activation, then that cholesterol can form plaque. the disease natus is at the level of the endothelium. We’re thinking that maybe we can get some stability there if we’re activating autophagy, which again, this program does. how often might we do that?  it’s a case-by-case thing, but in guys with known cardiovascular disease, the definite plug is two to three times a year. You’re going to be activating autophagy through the fasting-mimicking diet. Along with these other interventions I mentioned, we might also recommend another hot topic these days is frequent sauna bathing, which along with exercise, could reduce heart disease by another 50%. we stack the things and then we would monitor these folks. We would do serial ultrasounds, maybe get a repeat calcium score in five years, and check the inflammatory markers linked to plaque stability. hopefully, we’re showing these patients that things are coming down or stabilizing.    it goes underappreciated at it. But if you’ve stabilized cardiovascular disease, you’ve probably had a knock-on positive effect because you’ve stabilized a disease process that goes everywhere in your body.  the vascular system, I’ve been told if you flattened it out, would occupy five tennis courts. this is a very large surface area organ that you’ve now stabilized and,   potentially improved the function of dramatically. there’s going to be knock-on effects maybe to your kidney, your brain reducing risk of stroke, dementia, who knows? But it all follows that if you fix that whole organ, you’re going to have a lot of positive downstream effects as well.

Joseph Antoun, MD, PhD, MPP

That’s amazing. Do you want to talk about a potential case or two where this intervention and these protocols have shown positive facts and outcomes?

Jeffrey Grimm, NP-C

Yes, we believe that that is the best way to show that clinically, and a lot of research has shown that if you can do serial carotid ultrasounds, that’s a noninvasive way to look for improvements in endothelial function. We have cases of plaque in the arterial ball that disappeared on repeat ultrasound. A lot of that has been in patients who go on a pure vegan diet. That’s where we’ve seen the most effectiveness.

Joseph Antoun, MD, PhD, MPP

Jeff, you’re saying fully disappearing.

Jeffrey Grimm, NP-C

Yes. Like, okay, there’s a half-centimeter plaque, and it’s gone a year later.

Joseph Antoun, MD, PhD, MPP

I want to pause for a little bit. I went to medical school and earned an M.D. or Ph.D., and you went into the healthcare trade with me. I went through our training. We were taught about these diseases, whether diabetes, cardiovascular disease, or a progressive disease. You measure, and then you put them on a statin pill, and you put them on a blood thinner pill, and they put them on a blood sugar pill, and they put them on the five or six traditional pills. Then you tell them to eat healthy, and you send them home. these other visits, six months later, a year later, and 90% of the time you’re just waiting for them to add more medication. More medication. They end up with insulin, and they end up with a heart attack. They end up with this notion of reversing. We recently launched the fascinating meeting nutrition protocol for diabetes remission. I see it in the faces of doctors and patients, like, How come you’re going to reverse diabetes? How come you’re doing the reverse? It’s a foodborne disease, and you tell them to fast, then they bring back the disease. It’s shocking how we were a little bit brainwashed to become helpless in regards to disease, and we’re only pill dependent, and even now with it, they’re picking these up like it’s okay, we don’t, we’re not going to change your food. You just inject yourself. Every injection has a lot of good effects, but also a lot of bad side effects. But I just wanted to pause when I heard you say I’m reversing a plaque within the carotid artery.

Jeffrey Grimm, NP-C

Let’s dive into that comment. Nobody thinks twice when they cut their skin and then it bleeds, and then you get a scab. Then, a week later, you have perfectly healthy, normal-looking skin again. Yes. Nobody thinks about that.

Joseph Antoun, MD, PhD, MPP

How come the body self-heal?

Jeffrey Grimm, NP-C

Anybody can do that here again because you’ve got platelets, and the platelets release growth factors, and then you have stem cells, and you have the genesis of new dermal layers. Why can’t the endothelium do that? The assumption was that it’s a chronic, progressive disease process, which unfortunately is true for most people. But if you create the right conditions for healing, stem cell activation, and autophagy, again, autophagy is something interesting in this context because it’s the master regulator of intracellular repair, for sure. Also, with prolonged fasting, we know we get an uptick in circulating stem cells. Some studies have suggested multifold increases. This is how the body heals when the conditions are ripe for healing. You can heal the endothelium just like it can heal your skin. But the conditions cannot be disease-promoting. They have to be healing-promoting. So, Dean Ornish was the first person to show this was possible around 1989. The paradigm started to shift. But yes, we’re still in this disease model. Wait until the disease manifests, then apply the drug to which we’ve all been trained. The pharmaceutical industry has told us which drugs are for what diseases. We plug the patient into the algorithm, and we give them the drugs. 

But, as we all know, and this goes back thousands of years to the Greek doctors, the best medicine is the medicine that treats the disease before it manifests. We’re not there yet, but we’re starting to treat disease much earlier. We’re starting to develop pre-diabetes earlier. We’re starting to treat metabolic syndrome earlier. Maybe in 20 or 30 more years, we’ll be able to predict, maybe with AI or something else, that in ten years somebody will start just to develop the disease, and then we could intervene ten years before the disease is modeled to manifest. Everyone is going to have to shift to medicine. Medicine is reactive in this context. We need to be much more proactive, and we’re going to have the technological tools to be proactive. then hopefully we’re going to have the lifestyle and nutritional and neutral scientific tools to achieve this paradigm shift where, maybe, it happens at birth. We have the epigenetic profile of that baby, and we know immediately what’s going to be their problem when they’re 30, 40, 50, or 60 years old.

Joseph Antoun, MD, PhD, MPP

I remember when Dean Ornish published in The Lancet. This is an intervention for those who are not familiar with Dean Ornish; he has this lifestyle intervention to reverse coronary artery disease. It was a major visual reversal of the plague. Even though you can see it in the cath lab, it took him 15 to 20 years to get insurance to reimburse it and more doctors to change his lifestyle. Still today, she goes to mainstream cardiologists; they’re going to get that recommendation or that protocol, but I’m reinforcing these points for all the doctors that are going to watch the summit and for all the patients: there’s a role for allopathic medicine, which is critical. I come from that field, and there’s also a very important role that has to grow even further for lifestyle medicine in terms of medicine and functional medicine, whereby we’re saying 80% of the disease we’re suffering from is lifestyle-driven. We’ve been taught about genetics; we’ve been taught about predisposition and the environment that plays a factor. But even if you have the API gene, you’re not going to have Alzheimer’s at age 20. It’s about aging, and it’s about how you age—about how you stress, how you sleep, how you eat, how you exercise, and the happiness and social capital that you embrace your life with. Maybe, with this, we can wrap up the cardiovascular protocols that you have and that you follow in your clinics, and I’m very interested in talking about the interventions you do for perimenopausal women or have been a menopausal woman before that. We talk a little bit about some of the recent drug use and how you combine nutrition and drugs.

Jeffrey Grimm, NP-C

That’s a great segue. Just to preface that, the bulk of my clinical practice is focused on things that happen to women during and after menopause. A large component of that is the appropriate type of hormone replacement to help these women. But the context is often this: I’d say you have your average 47- to 52-year-old woman who has gained 10 to 30 pounds around menopause, mostly in the midriff area, who is having problems sleeping, who is overstressed. That’s a time in life when you now maybe have teenage kids, maybe you’ve been through a divorce, maybe you’re overworked, or maybe you’re drinking alcohol excessively and not eating particularly well. Then you’re confronted with this massive endocrine shift, which we call menopause, which goes underappreciated. We can remember how dramatic puberty was and the few years that it took to go through puberty. Well, not so dissimilar. A major shift happens to women around menopause, where they’re you. The hormones are changing dramatically. Estradiol levels are going way down, FSA (follicle-stimulating hormone) levels are going way up, and cortisol levels are going way up. You have this shift in these endocrine hormones that directly cause metabolic problems, the most obvious one being awakened. But there are many others as well. We get a big shift. The average woman experiences the most dramatic change in her bone density within five years of menopause. They are shunted very strongly, catabolically. They’re gaining weight. They also become very insulin-resistant at this age. One thing we notice is that if these women are wearing glucose monitors or they’re self-reporting how they feel, we’re intuiting a lot that, at this age bracket, their ability to deal with refined carbohydrates and alcohol is compromised. It’s much different than it would have been at age 30 or so. They have to be very attentive to the glycemic load of their diet. 

They need to avoid alcohol. They need to take care to manage their stress and sleep seven to nine hours a night. Even if we do all those things, we still have to appreciate that the average woman in this culture has estrogen levels that drop so abruptly that they get catapulted catabolically. In anti-aging, this is a disaster because what happens when you’re catabolic is that you’re going to have accelerated destruction, perhaps of the endothelium of your bone density. bone mineral density potentially goes way down. You may develop some sarcopenia or lose muscle mass as you’re getting fat, which is not what you want. So, in this field of anti-aging, one of the tendencies to try to keep this anabolic catabolic balance so that we don’t deteriorate is that you need the right balance of buildup, which is anabolic buildup and repair versus breakdown. We don’t want to be too anabolic. We don’t want to be too catabolic. We have to appreciate menopause as a major catabolic event for women. So, having painted the picture now, what do we do about it? We have anabolic hormones like testosterone, DHT, estradiol, and progesterone, which, in combination, appear to be safe, according to the aggregate of data. There’s a bit of a sea change happening in the philosophy in that respect. We can support women that way; we can test women’s bone mineral density, percent muscle mass, and body fat at this age too, to track those measures. 

But we can be thinking about cracking the code on insulin resistance and also making sure these women have adequate capacity for growth, repair, and healing. That’s where fasting comes in. When I inherit these women in this age bracket who are complaining of their muffin tops and who’re overweight and overstressed, we’re advocating for ProLon, for sure. A similar recommendation to men is that if I get a new patient, just trust me to do this five-day diet. It’s going to immediately knock off the pounds, and you’re going to feel better; you’ll be less inflamed, and that will prime a lot of the other interventions that will start later on for these women. But we know some things and many of these probably, but Joseph could speak more to this probably. But what the science shows us with a ProLon fasting state or fasting-mimicking diet is incredibly relevant for these women. We get preferential fat loss, check. We see improvements in glucose and insulin resistance. That’s exactly what we get. Improvements are probably in stem cells. We get improvements in bone mineral density, as evidenced by the highly relevant clinical endpoints for this population in this context. Why wouldn’t we use this tool when women have a greater appreciation for how this tool is contextualized to their benefit? They’re on board, and we’ve had a lot of women. I can give ProLon.

Joseph Antoun, MD, PhD, MPP

Jeff, we grew a lot during the five days of fasting nutrition and just finished a randomized clinical trial on skin. I don’t know if you had the chance to see that.

Jeffrey Grimm, NP-C

I haven’t seen that. Tell me.

Joseph Antoun, MD, PhD, MPP

It was a fully randomized clinical trial, and we divided women into eating normally and doing their ProLon fasting nutrition because that comes with the menopause profile and the aging rate. We were betting on no creams, nothing, no touch, no external touch on the skin. We were betting on showing the rejuvenation just at the skin interface. These results were very successful. We had a significant increase, and we did the Arisa as well to see the cells and to see the detox. had a better glow and better hydration, and a lot of the Arisa metrics and objective metrics on the skin were all statistically deficient. But as importantly, before we did this trial, we went. I asked one of the chief marketing officers about one of the big anti-aging creams, and I asked him, “What do you sell?” I wanted to know why they were so successful. Although he puts a cream on the skin, it helps a little bit, but it does not bring you cells. ProLon, through nutrition and fasting, is rejuvenating those cells. But I just wanted to see from afar how women look at their skin and what they want. He said it’s confidence and happiness. We did ask the women in the trial, and again, this is a third-party, dermatology clinic-run trial, and one of the most statistically significant increases was in happiness and confidence. You’re talking about autophagy and cell rejuvenation. 

We wanted to show it even on the outside. We’ve been around that age, and it was very statistically positive. I just want to add one more thing, which is that we talk about autophagy, and for those listening, it’s a phenomenon that happens mostly on day three of fasting after day two of fasting. So the cells get so stressed from the fact that they rejuvenate to survive. It’s like, when you’re driving, you’re in a Formula One race car, and then the engine is heated, and you’re concerned about the cars, and you go for a pit stop, and the mechanics come in, screen, and fix it the same way. Doing ProLon is like rejuvenating the body in that sense. But a lot of my studies on stem cells, autophagy, and rejuvenation in humans were difficult. ProLon has done some stem cell detection in humans. That autophagy was difficult to measure. In mentioning that the national health department has now deployed new machines to measure autophagy in humans, one of them is, I believe, the University of San Antonio here in Texas. The first product that was tested was ProLon. It’s showing a huge spike in autophagy after day three, and we stayed to day seven and beyond. For the first time in humans, major autophagy signs are being shown within health machines to prove the point that you’re making about the rejuvenation and self-healing that are within the body.

Jeffrey Grimm, NP-C

And just to add to that, we’ve all been waiting for that moment because what we need to do is do a lot of things, but we also need to look at different so-called health interventions and see how they stack up in terms of the degree of autophagy upregulation, and then see if those different degrees of upregulation lead to clinically significant endpoints. Then you can characterize what a good level of autophagy is for the employee studying. What a lot of us suspect is that a lot of the things people think are healthy. We’re going to find out why you shouldn’t activate this pathway.

Joseph Antoun, MD, PhD, MPP

Yes.

Jeffrey Grimm, NP-C

That’s going to be an interesting moment because that will evolve the public narrative in the social media sphere as it relates to pontificating health interventions.

Joseph Antoun, MD, PhD, MPP

If you remember, we’re saying that intermittent fasting isn’t going to take you to autophagy because the stress is so mild, and it did show no autophagy on day one, which is equal to controlling no autophagy on day two. Will autophagy start after the third and/or fourth?

Jeffrey Grimm, NP-C

A 16-hour fast is not going to do anything, but yes, you need three days.

Joseph Antoun, MD, PhD, MPP

It may help with weight loss if you do it right. If you’re front-ended, they will help with some metabolic markers. But cellular rejuvenation. There’s not enough crisis. A lot of us skip a meal by default at breakfast. The body still has a lot of fat, a lot of glycogen, and a lot of the liver can help.

Jeffrey Grimm, NP-C

it’s no gain rate.

Joseph Antoun, MD, PhD, MPP

You’ve got it if you’re going to stress it.

Jeffrey Grimm, NP-C

To get to autophagy.

Joseph Antoun, MD, PhD, MPP

I use the example of if you have your own company and you say you need $1,000,000 per month to operate it. If I come and say, Oh, you need a million, I’ll give you the million tomorrow. If you wait for tomorrow, your bank account will drop a little bit. This is weight loss, and then it’s good to drop the weight because it’s getting you some metabolic changes, but you’re not going to go and restructure the company and change. If I come to you and say sorry this month, there will be no revenue. It’s a crisis. Now you’re going to go, and you’re going to try to restructure the company, cut costs, and do the right thing in every department. That’s how autophagy is going to stress the body so that the cells rejuvenate and self-heal.

Jeffrey Grimm, NP-C

I wonder if Matt Chamberlain alone can get access to this machine at the University of Washington with rapamycin that upregulates autophagy.

Joseph Antoun, MD, PhD, MPP

Yes.

Jeffrey Grimm, NP-C

Okay cool.

Joseph Antoun, MD, PhD, MPP

Yes, I didn’t mean to interrupt, and the middle part. What if I come to you today and I’m a 50-year-old woman? I’m gaining weight? It’s resistant to fat for a while. On probably my last visit to my family practitioner, he said, “Hey, your cholesterol starts to increase a little bit. I’m worried about your bone density starting to decrease a little bit, and your blood sugar is white. Right there in your HB, you have that metabolic syndrome of pre-diabetes.” What would you do for such a woman? You love testing. You’re going to put in a lot of testing. But on average, what is something you expect that you would do from an aging and function medicine perspective that typically maybe the general practitioner might do or might not do depends, and I would adhere to discrediting any of that. We come from that field, and we’re highly supportive, but the goal of the summit here is to also help add additional thoughts and additional ways to add to the therapy.

Jeffrey Grimm, NP-C

So, yes, the first is diagnostic. You have to paint the picture on an individual level. We might call that precision medicine. We’re going to look at the unique patient, their health history, their family history, and how they present. then going to look at diagnostics. The thing I have done most consistently over the last 15 years is do serial bone densities. These women need DEXA scans every 1 to 2 years to make sure that they’re not falling off a catabolic cliff. Because if they get a fracture at age 80, it’s game over. After that, nobody does well after a hip fracture, especially in that age bracket. We’re thinking about 30 years in the future. In the bloodwork, we’re going to corroborate pre-diabetes and hyperlipidemia. We’re going to look at some inflammatory markers and then hormones. Practically speaking, if the woman is symptomatic hormonally and they’re losing bone mass, we’re going to get them on. We’re going to get them on estradiol, testosterone, DHEA, and progesterone, probably some combination of those products. We’re going to advocate for some derivative of fasting, whatever is practical. If ProLond is practical, which it is for many people, we’re going to advocate for that. We might also advocate, as we often do, for some derivative of intermittent fasting, as you mentioned, to help the cardio-metabolic picture. That’s where we start in our clinic. We also have two nutritionists who have our master’s level of training in functional medicine. We may shunt the patients to those folks to work on their diet. We’re advocating for a plant-centric Mediterranean-type diet for as many of these patients as is feasible. We might be a little more attentive to the protein level in this age group in women because they’re going to get this catabolic shift quicker than men. In men, I’m thinking more about their protein intake. Maybe after age 60 or 70, if they’re showing clinical signs that they’re catabolic, like sarcopenia, for example. But for women, we have to appreciate that they may need to mind their protein intake at this age because there are a lot of catabolic things potentially occurring. In an ideal universe, we wouldn’t have to be as attentive to this or hormones. 

But what we see on the street is that lots of women have serious hormone dysfunction at menopause, and they have all of the clinical signs to show that there are, again, shunted catabolic leads rather abruptly. For weight loss, we have other tools; we have drugs that we can use, like these new GLP-1 agonists like semaglutide and tirzepatide, which is mounjaro. Because they’re wildly popular now and they have good safety data, that’s an adjunct for a percentage of our patients. It’s also like a ProLon, relevant intervention because what we’re dealing with often is pre-diabetes or pre-diabetes with insulin resistance. If you can delay gastric emptying with the GLP one-1 agonist, which delays gastric emptying and improves satiety, you also get attenuation of what would be a much bigger spike of glucose and insulin postprandial later after eating. Again, this is relevant because these women are often more insulin-resistant at this age. They’re gaining weight in all the wrong places, and they’re often overeating or overdrinking. Frankly, these GLP-1 agonists interrupt all those things. That’s a nice adjunct to all these other tools we have. As I mentioned with men, our approach practically involves stacking tools. You’ve got good tools that seem to offer a much greater benefit than harm; you’re stacking tools from lifestyle to diagnostics to potentially pharmaceutical interventions, and you have access to all these tools as medically trained professionals. 

Why not use them? Use all the tools; cultivate a team of people who can deliver all the other tools. If you’re not adept with, say, nutrition, for example, so that you can stack evidence things on to your patients for the best outcome, we have a lot of women in my practice, and let’s say there are around five or six who would have been 200 pounds for 20 years, and they need to be 150 pounds to be cardiometabolic. Luckily, they’re stable, and nothing they’ve tried helps. Then we stack all these tools, and I have numerous patients that now walk into the clinic, and they are 150 or 160 pounds, and they look completely different. I have women again who were 200 pounds for ten years and are now walking in the clinic at 150. If you stack these things and they feel great, they’re super confident. Everybody’s remarking on how good they look, their joint pain and all these problems that have plagued them seem to disappear. They don’t all disappear, but you get huge reductions and a lot of the gripes of aging. If you can make people more cardio-metabolically fit, we advocate exercise as well. We don’t have an exercise partner or facility in our office. But obviously, we want people to engage in things like resistance training and cardiovascular exercise. The data there is unequivocal. So, that’s what we do. We try to espouse that ourselves. The people who work at our clinic are into health to a large degree. Creating an environment where you talk the talk is important, too. As a personal side note, I’ve done ProLon 15 times at this point, so I can tell my patients about the experience. I can relay anecdotes to patients. My wife and I do it together. A lot of this work is the opposite of what you get in some branches of medicine. You might meet with a doctor to talk about your heart and then lament later that the doctor you talked to was 100 pounds overweight. How could they possibly help you reverse heart disease? But when you’re on the health journey yourself and you’re also able to leverage these tools, then the universe supports alignment. If people are aligned with this lifestyle, things will flow. Patients feel that they’re in a great place for health interventions. I would just leave folks with that thought: as you stack things in your favor health-wise, your patients feel that, and they want that. They want to interface with health-minded healthcare providers.

Joseph Antoun, MD, PhD, MPP

Yes.

Jeffrey Grimm, NP-C

So, yes, the first is diagnostic. You have to paint the picture on an individual level. We might call that precision medicine. We’re going to look at the unique patient, their health history, their family history, and how they present. then going to look at diagnostics. The thing I have done most consistently over the last 15 years is do serial bone densities. These women need DEXA scans every 1 to 2 years to make sure that they’re not falling off a catabolic cliff. Because if they get a fracture at age 80, it’s game over. After that, nobody does well after a hip fracture, especially in that age bracket. We’re thinking about 30 years in the future. In the bloodwork, we’re going to corroborate pre-diabetes and hyperlipidemia. We’re going to look at some inflammatory markers and then hormones. Practically speaking, if the woman is symptomatic hormonally and they’re losing bone mass, we’re going to get them on. We’re going to get them on estradiol, testosterone, DHEA, and progesterone, probably some combination of those products. We’re going to advocate for some derivative of fasting, whatever is practical. If ProLond is practical, which it is for many people, we’re going to advocate for that. We might also advocate, as we often do, for some derivative of intermittent fasting, as you mentioned, to help the cardio-metabolic picture. 

That’s where we start in our clinic. We also have two nutritionists who have our master’s level of training in functional medicine. We may shunt the patients to those folks to work on their diet. We’re advocating for a plant-centric Mediterranean-type diet for as many of these patients as is feasible. We might be a little more attentive to the protein level in this age group in women because they’re going to get this catabolic shift quicker than men. In men, I’m thinking more about their protein intake. Maybe after age 60 or 70, if they’re showing clinical signs that they’re catabolic, like sarcopenia, for example. But for women, we have to appreciate that they may need to mind their protein intake at this age because there are a lot of catabolic things potentially occurring. In an ideal universe, we wouldn’t have to be as attentive to this or hormones. But what we see on the street is that lots of women have serious hormone dysfunction at menopause, and they have all of the clinical signs to show that there are, again, shunted catabolic leads rather abruptly. For weight loss, we have other tools; we have drugs that we can use, like these new GLP-1 agonists like semaglutide and tirzepatide, which is mounjaro. Because they’re wildly popular now and they have good safety data, that’s an adjunct for a percentage of our patients. It’s also like a ProLon, relevant intervention because what we’re dealing with often is pre-diabetes or pre-diabetes with insulin resistance. If you can delay gastric emptying with the GLP one-1 agonist, which delays gastric emptying and improves satiety, you also get attenuation of what would be a much bigger spike of glucose and insulin postprandial later after eating. Again, this is relevant because these women are often more insulin-resistant at this age. They’re gaining weight in all the wrong places, and they’re often overeating or overdrinking. 

Frankly, these GLP-1 agonists interrupt all those things. That’s a nice adjunct to all these other tools we have. As I mentioned with men, our approach practically involves stacking tools. You’ve got good tools that seem to offer a much greater benefit than harm; you’re stacking tools from lifestyle to diagnostics to potentially pharmaceutical interventions, and you have access to all these tools as medically trained professionals. Why not use them? Use all the tools; cultivate a team of people who can deliver all the other tools. If you’re not adept with, say, nutrition, for example, so that you can stack evidence things on to your patients for the best outcome, we have a lot of women in my practice, and let’s say there are around five or six who would have been 200 pounds for 20 years, and they need to be 150 pounds to be cardiometabolic. Luckily, they’re stable, and nothing they’ve tried helps. Then we stack all these tools, and I have numerous patients that now walk into the clinic, and they are 150 or 160 pounds, and they look completely different. I have women again who were 200 pounds for ten years and are now walking in the clinic at 150. If you stack these things and they feel great, they’re super confident. Everybody’s remarking on how good they look, their joint pain and all these problems that have plagued them seem to disappear. 

They don’t all disappear, but you get huge reductions and a lot of the gripes of aging. If you can make people more cardio-metabolically fit, we advocate exercise as well. We don’t have an exercise partner or facility in our office. But obviously, we want people to engage in things like resistance training and cardiovascular exercise. The data there is unequivocal. So, that’s what we do. We try to espouse that ourselves. The people who work at our clinic are into health to a large degree. Creating an environment where you talk the talk is important, too. As a personal side note, I’ve done ProLon 15 times at this point, so I can tell my patients about the experience. I can relay anecdotes to patients. My wife and I do it together. A lot of this work is the opposite of what you get in some branches of medicine. You might meet with a doctor to talk about your heart and then lament later that the doctor you talked to was 100 pounds overweight. How could they possibly help you reverse heart disease? But when you’re on the health journey yourself and you’re also able to leverage these tools, then the universe supports alignment. If people are aligned with this lifestyle, things will flow. Patients feel that they’re in a great place for health interventions. I would just leave folks with that thought: as you stack things in your favor health-wise, your patients feel that, and they want that. They want to interface with health-minded healthcare providers.

Joseph Antoun, MD, PhD, MPP

That’s fantastic. and we’re hitting. We’re hitting in a little bit of time. If I want to ask you two questions, number one is, if you were to leave the folks who are listening to us today with one or two messages or things that have helped you change your life or change your patients’ lives, what would those be?

Jeffrey Grimm, NP-C

Just reflecting on what I said, if the things you’re doing are bringing you great joy and personal satisfaction, you’re on the right path in life. If it’s great to get up in the morning and you don’t enjoy what you’re doing, you won’t get longevity. If you look at blue zones, a piece of the pie is a healthy, plant-centric diet. A piece of the pie is drinking water, avoiding drugs and alcohol, and sleeping adequately. But a big chunk of this is personal fulfillment because the positive radiation that comes from that cannot be underestimated. So, fasting, a healthy diet, good sleep, managing your stress, hanging out with people you love, don’t do things you hate doing for too long and making sure that there’s alignment with what you do in life so that you’re excited to get up and do the work you do every day.

Joseph Antoun, MD, PhD, MPP

That’s fantastic. I want to thank you very much today. Dr. Grimm, you’ve been an avid speed and longevity expert for years. I’ve encouraged people to reach out, even directly, to you if they live around your area in Oregon and the clinic. I’ve seen amazing results and patient stories coming out of your clinic, so I appreciate you for that. I appreciate your time today and thank you very much.

Jeffrey Grimm, NP-C

Thank you so much. Take care of everyone. It was my great pleasure to be here and have a great day. Have a good day, everyone.