Aortic valve disease; upcoming weight-loss drugs; helping aging parents: Upstate Medical University's HealthLink on Air for Sunday, March 2, 2025

Host Amber Smith: Coming up next on Upstate's "HealthLink on Air," a chest surgeon goes over options for treating aortic valve disease.

Callistus Ditah, MD: ... A third of the patients who get a mechanical valve will not hear it at all. A third of them will hear the valve clicking, and it wouldn't bother them. A third of them will hear the valve clicking, and it will drive them absolutely nuts. ...

Host Amber Smith: A chemistry professor describes a drug that could promote weight loss without bad side effects.

Robert Doyle, PhD: ... Obviously, the more you take, the greater the effect will be to try to drive that additional weight loss. But the greater the chance, then, that you may have one of these side effects pertaining to stomach emptying, nausea, vomiting and low energy. ...

Host Amber Smith: And a geriatrics expert advises how to tell when aging parents need help. All that, and a visit from The Healing Muse, coming up after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine with the experts from Central New York's only academic medical center. I'm your host, Amber Smith.

On this week's show, a medicinal chemist from Syracuse University talks about weight loss drugs and their unfortunate side effects. Then we'll get some tips on determining when an aging parent needs help. But first, what are your options for treating aortic valve disease?

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." The aortic valve in our heart helps keep the blood flowing in the correct direction through the heart. A damaged or diseased valve can affect blood flow to the rest of the heart and body. Here to discuss aortic valve repair and replacement is Dr. Callistus Ditah, an assistant professor of surgery at Upstate specializing in thoracic, or chest, surgery.

Welcome to "HealthLink on Air," Dr. Ditah.

Callistus Ditah, MD: Thank you. Thanks for having me. It's a pleasure for me to be here today.

Host Amber Smith: Can you please start by telling us about the aortic valve? Where is it in the heart?

The aortic valve is located between the left ventricle, which is really the heart's main pumping chamber, and the aorta. And the aorta is the largest artery in the body. The aortic valve ensures that oxygen-rich blood flows from the heart into the aorta, which is then distributed to the rest of the body.

How big is this valve?

Callistus Ditah, MD: In normal people, it's about 2.5 to 3.5 centimeters in diameter. There's some slight variations that go with that depending on the person's body size. But typically it's about 2.5 to 3.5 centimeters.

Host Amber Smith: And, and what is it made of?

Callistus Ditah, MD: The valve consists of three thin but very strong leaflets, so something that we call cusps. It's made up of connective tissue that's covered by endothelial cells. And in some people, the valve may naturally have two cusps instead of three, which is called a bicuspid aortic valve. And this is thought of to naturally occur at about 1% to 2% of the population.

So if you go to a Syracuse game, you can expect that there are about 1,000 people sitting in the stands with this bicuspid aortic valve.

Host Amber Smith: Interesting. So, does the heartbeat dictate when the valve opens and closes?

Callistus Ditah, MD: Yes, it does. So the heart is normally thought of as beating in two cycles. When the left ventricle contracts, which is what it's normally thought of as systole, the valve opens to allow blood to flow out. When the ventricle relaxes, which is called diastole, it closes tightly, to prevent blood from flowing back into the heart.

So in a sense, it's a one-way valve that allows blood to flow forward to the rest of the body. But then the second function is not to allow blood to flow back into the heart.

Now, how would a person know that something was wrong with their aortic valve?

Oftentimes, there are really no symptoms until late in the disease process. There are some people with certain anatomical features, sort of like the ones we just talked about, like a bicuspid valve, that should have their heart monitored more on a regular basis to catch some of these things early because we know that for people who have this bicuspid aortic valve, the valve deteriorates at a much faster pace. And there can be a host of issues with it. So those people should get their valve monitored over time.

Callistus Ditah, MD: For the rest of the people, common symptoms of aortic valve disease include things like chest pain, shortness of breath, fatigue, fainting, or what we call syncope, if you get heart palpitations. When it gets really severe, you can start having symptoms of heart failure, which will be noted as swelling in your legs.

Host Amber Smith: So what are the main types of aortic valve disease? You mentioned the bicuspid, where there's two leaflets instead of three. Are there others?

Callistus Ditah, MD: Yeah. And just to be clear, bicuspid valve in itself is not a diseased valve. A bicuspid valve, however, changes the flow dynamics across the valve that exposes it to a faster deterioration when compared to people who have a normal three-leaflet, or tricuspid, valve. So just having a bicuspid valve is not an issue that needs to be addressed per se, but then we need to watch you a little bit more closely to make sure that you don't develop issues or to make sure that when you do, we catch them early enough that this can be fixed.

Now to discuss the other main types of aortic valve diseases, there's something called aortic stenosis, which really just refers to narrowing of the valve, if you remember that diameter that we talked about. This is something that happens over time, and it restricts the amount of blood that can go through this valve.

There's something called aortic regurgitation, or aortic insufficiency. When you heard me talk about the valve preventing blood from flowing back into the heart, a leaky valve is essentially what we call aortic regurgitation, and that in itself is an issue.

Then we talked about the bicuspid aortic valve as well, but there's another thing in this bicuspid aortic valves. Because of the change in the flow dynamics, patients are thought of as being exposed to sometimes developing aneurysms in the ascending aorta because of those changes in how blood flows to a two-leaflet valve as opposed to a three-leaflet valve. And some of those changes makes it so that you may need your ascending aorta replaced. But that is a separate issue from the valve, but it's an issue that the valve can lead to.

Host Amber Smith: Are these aortic valve diseases, are they genetic? Do they run in families?

Callistus Ditah, MD: We, we think so, especially on the bicuspid aortic valve. We do know that they do run in families. Now, there are other issues like the aneurysms that we know for sure run in families.

And things like aortic stenosis, we also see them running in families, but we haven't delineated any genetic factors that we can put our finger on to say that it leads to this.

Host Amber Smith: Now we talked about stenosis and regurgitation. What about connective tissue disease? Does that affect the aortic valve?

Callistus Ditah, MD: It absolutely does, in certain ways. So for patients who have connective tissue diseases like Ehlers Danlos (syndrome), Marfan (syndrome), or Loeys-Dietz (syndrome), those patients basically have what is a weakened aorta, and a lot of them can develop what we call aortic root aneurysms. Now you wonder what's the aortic root. I think for the purposes of this conversation, the aortic root is often thought of as the business end of the aorta where your coronary arteries leave.

It's where the aortic valve lives. It's really that transition from the ventricle to the aorta. So if you have an aneurysm in that area, as you're going to imagine, as the aorta dilates, those leaflets that have to come together to prevent blood from going back into the heart, they can't touch because the aorta, they've been pulled apart by the dilation of the aorta.

So that's what we call aortic regurgitation. So most patients will have connective tissue disorders and have an issue with their aortic valve. It often presents itself in the flavor of aortic regurgitation. And those are the patients where it's absolutely critical for us to do things like the David operation, where I can go in and fix that aneurysm but keep their own valve by taking it and implanting it in some sort of a tube graft and preserving a function in that sense.

Host Amber Smith: I know we'll talk more about that David operation. But first, let me remind listeners, this is Upstate's "HealthLink on Air," with your host, Amber Smith. My guest is chest surgeon Dr. Callistus Ditah, and we're talking about the aortic valve.

So how is valve disease diagnosed? Is there testing that has to be done?

Callistus Ditah, MD: There's a number of tests that we can do to determine whether you have valve disease. The first and the very simplest thing that we use is an echocardiogram, which is essentially an ultrasound of your heart that looks a little bit closely at this valve. That's really the gold standard for evaluating the valve function.

But we can also do a CT scan or an MRI, which is a different kind of imaging to look for calcifications, because this is what leads to aortic stenosis. And we can also look at the valve anatomy and look at the aorta surrounding that.

Then there's something called cardiac catheterization, which is where we inject some dye, either in your coronary arteries, so the arteries that supply blood to the heart, or we can inject this dye directly to the opening of that aortic valve to measure some pressure gradients and see how it's working.

And then lastly, we can also do a stress test, which is really to examine and really interrogate the response of the heart to physical exertion when we test this.

Host Amber Smith: Let's talk about treatment options. Does aortic valve disease always mean surgery?

Callistus Ditah, MD: No, It doesn't always need surgery. There's some surgical and nonsurgical treatments that we target for the aortic valve.

Now, on the non-surgical side, there are medications like diuretics, beta blockers, if you've of these medications. They call them metoprolol or carvedilol. And they often are thought of as some afterload reducers that may manage symptoms, but never really fix the valve. Lifestyle changes can also help in early stages, but severe valve disease typically requires surgical or procedural interventions.

Host Amber Smith: So for those who do end up needing surgery, can you compare the aortic valve repair versus the aortic valve replacement?

Callistus Ditah, MD: It's often taught in our field that any time you can repair the valve that you were born with successfully, that's unanimously the better thing to do. We know that for patients who get their valves replaced, meaning you take a valve off the shelf, and there are two that we can get into later, those patients have, depending on what you use to replace that valve with, some of them may need to be on anticoagulation for the rest of their lives, something called warfarin. Or if you put in what we call a tissue valve, those patients, if they're young enough, they often need to come back and get surgery. So anytime you can repair the patient's own valve, that's what we would like to do.

Now for patients who have aortic stenosis, by definition your valve is bad. It's got calcium on it, and you can't really repair those. But for patients who have a leaky valve, or they have an aneurysm, which is in that area where the valve is, we can often do an operation called a David procedure. For surgeons who are a little bit more sophisticated with the aortic valve, we can do that kind of operation to sort of repair it.

Host Amber Smith: And is that an open surgery or minimally invasive?

Callistus Ditah, MD: All of the options, the surgical options that I've described so far, are open heart surgery, the way that we think about it, where in most cases we kind of split your sternum, get down to the heart, put your heart on what we call a bypass machine, and then arrest it to do all of this work. Then we start it at the end of the work.

Host Amber Smith: So if you're able to do a repair, how long does the repair last?

Callistus Ditah, MD: It really depends. If your valve, if I meet your valve in a pristine condition, this repair can last you your entire lifetime. If I can catch and reverse the condition before it deteriorates, it basically restores your life expectancy to the normal population.

Now if I go in there, and your valve is sort of mediocre to start with, there's nothing I can do to reverse the condition of the valve itself. I can arrest that process of deterioration, but I can't reverse what already happened. And some of those patients may need something done down the road, but having the valve that you were born with for 10 to 15 more years is also better than replacing it at that time.

Host Amber Smith: So if you did have a repair, and it lasted 10 or 15 years, could you potentially get a replacement later if you needed it?

Callistus Ditah, MD: Absolutely. It just means going back to do the operation again, another open heart surgery. If you already have a valve that's in there, the valve that you were born with, we just go back in there, we cut it out and then put in a valve off the shelf. So there are no bridges burned in doing a repair if it -- obviously, there's risk associated with open heart surgery. It's a major operation -- but outside of those you can always go back and replace a valve that we repaired earlier.

Host Amber Smith: Upstate's "HealthLink on Air" has to take a short break, but please stay tuned for more information about the aortic valve.

Welcome back to Upstate's "HealthLink on Air." I'm your host Amber Smith, and my guest is chest surgeon, Dr. Callistus Ditah, and we're talking about the aortic valve.

So let me ask you about valve replacement. What is the valve replaced with?

Callistus Ditah, MD: It's often thought of as using two different kind of valves. There's what we call the biologic or tissue valve, which usually comes from a cow or some sort of a pig skin. And then there's what we call the mechanical valve.

Now, with the biologic valve, we reserve this for patients who are older, that we often think of their life expectancy to be in the order of 10 to 15 years. Because this valve, usually, that's usually the shelf life. Now, the benefit of getting a biological valve is that you don't have to take any kind of medication for the rest of your life. But if you're someone who's younger, let's say you are the age of 50 and you get this valve, you can expect that at about 65 years old, you're going to need to have something done. Either through a TAVR (Transcatheter Aortic Valve Replacement) valve. You can have that done through the groin, or you may need another open heart surgery to go and replace that valve again. But if you get that valve, and your life expectancy is more than 10 to 15 years, be prepared to have something done again, and just think about what that backup option would be.

Now there's the other side of this, which is the mechanical valve. With the mechanical valve, we often think of this as lasting the entire lifetime. The catch with a mechanical valve is that you have to be on a blood-thinning medication that's known as warfarin or Coumadin for the rest of your life. There are obvious implications for being on a medication like that. Your blood oftentimes has to be at least 2.5 times thinner than that of the normal population, which means if you scratch yourself, if you go hiking, if you're someone who likes to go snowboarding, or if you fall and hit your head, that's a big deal. So some patients, for those reasons, will oftentimes shy away from getting the mechanical valve.

So you can, you know, it's pick your own, depending on your lifestyle. If you prefer something that allows you to do all the things that you love, and you are a very active individual, maybe the biological valve works for you. But if you're someone who has a desk job, you don't really enjoy getting out in the woods and things like that, maybe the mechanical valve works for you in that case.

Host Amber Smith: With the mechanical valves, can you hear them clicking as they work?

Callistus Ditah, MD: That's a very good question, and what I usually tell patients is that about a third of the patients who get a mechanical valve will not hear it at all. A third of them will hear the valve clicking, and it wouldn't bother them. A third of them will hear the valve clicking, and it will drive them absolutely nuts. So that's just something that goes with it. And you can think about the rule of thirds as how to deal with this.

Host Amber Smith: So let me ask you about the biological valves then. Do you ever have a patient whose body rejects the the tissue?

Callistus Ditah, MD: That's another good question. The biological valves are what we call decellularized valves. So the human components, or the components that we react to are completely removed, so people don't react to these valves at all. You don't have to take any kind of medication to dumb down your immune system to tolerate this valve because all the elements that are immunologic are removed from these valves.

Host Amber Smith: How do you tell patients to prepare for aortic valve surgery? It is a major surgery.

Callistus Ditah, MD: It is a big operation. And what I usually tell my patients of things that they can expect, going something like this: I tell them that they're going to come out of the operating room, and in most cases, with a breathing tube in. We usually take that breathing tube out the night after their open heart surgery. They stay in the ICU (intensive care unit) for about a couple of days, and then after that I send them to what we call a step-down unit where they spend another five days there or so. And then they get to go home.

Usually, when I get them home, if it's an operation that I was able to do through the breast bone, I put them six weeks on light duty, just so the breastbone can heal up.

Host Amber Smith: So after those six weeks, can they get back to normal activities, or are there going to be limitations to what they can do, since they've had heart surgery?

Callistus Ditah, MD: Most of my patients actually get back to work in about two to three weeks after open heart surgery. It just needs to be a desk job. You can't be lifting heavy things. And what I usually tell them is you can't lift more than a kettle of water for those six weeks after your operation. Again, it is just time for that breastbone to heal.

After those six weeks, I tell them to get back to the things that they enjoy doing. If it's running, if it's climbing, whatever it is, get back to it. Just pace yourself and ramp it up. But after that time, you are essentially signed off.

Host Amber Smith: Very interesting. Well, Dr. Ditah, thank you so much for making time for this interview.

Callistus Ditah, MD: It's, it's my pleasure. I really enjoyed talking to you this morning. Thanks for giving me the opportunity to discuss a valve I really love.

Host Amber Smith: My guest has been Dr. Callistus Ditah. He's an assistant professor of surgery at Upstate. I'm Amber Smith for Upstate's "HealthLink on Air."

Next on Upstate's "HealthLink on Air," a chemist explains how he's helping to design a weight-loss drug without the bad side effects.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

Medicines that reduce body weight and normalize blood sugar levels are heavily advertised and have become quite popular. A medicinal chemist at Syracuse University and his collaborators think they have better refined the compounds, and he's here to tell us about it. Dr. Robert Doyle is the Jack and Laura H. Milton professor of chemistry at Syracuse University.

Welcome back to "HealthLink on Air," Dr. Doyle.

Robert Doyle, PhD: Thank you for having me.

Host Amber Smith: The medicines I'm referring to are the GLP-1 medications, including Ozempic and Mounjaro and others that are on the market.

Can you explain what these medications do and how they work?

Robert Doyle, PhD: Certainly. They are what are referred to as "glip-1" drugs, essentially GLP-1 drugs. GLP-1 is a peptide that you make naturally and in response to intake of calories. They will respond to those calories, but also the elevated glucose levels in your blood by secreting insulin, but also switching off your appetite.

So they're a natural appetite regulation system.

Host Amber Smith: So they're natural, they're not man-made, chemicals?

Robert Doyle, PhD: The drugs that are out there now are based on these, on your natural GLP-1. So what they do is, they take what is essentially a short-acting, immediate response element in you, naturally, and what they do is, they make it longer-lasting or can be less degraded, will penetrate better into the certain regions of the brain, for example, that you want to exacerbate the effect. And essentially all they do is they take nature's role model, and they just make it work longer, better, faster, stronger.

Host Amber Smith: What are the potential side effects?

Robert Doyle, PhD: Well, the potential side effects are weight loss, which as it turns out, was a side effect of their original use.

Their original use was to treat diabetes. And what they noticed was when treating the glucose dysregulation, patients who were taking these drugs were losing weight. And so it was originally a side effect, and they thought, well, as the side effects go, maybe that's useful. And so these diabetes companies like Novo Nordisk and Eli Lilly, which were companies designing drugs to treat diabetes, became obesity companies because they realized that they could expand on this accidental effect and exploit it.

So now we have these weight-loss drugs, which as you referred to, Ozempic, for example, Zepbound. That's really exciting. But what we also have noted are side effects that include nausea, vomiting, low energy, or what we would call malaise, gastric immobility, so your stomach stops emptying. That's a great effect to make you feel full. After you've just eaten, we all get that, oh, I've had too much Thanksgiving turkey feeling. That's because the food is sitting in your stomach. And of course, instead of moving it out of your stomach to be processed, your stomach stops moving it, and then you feel full, and you stop eating. It's a great mechanical response, but what you don't want to do is drive that response too hard, too far, too long, or any of those responses too far, too hard, too long. And that's why a lot of people ultimately end up feeling pretty bad when they take these medications.

Host Amber Smith: People with diabetes are taking these medications for diabetes, but then people are also taking these for weight loss who don't have diabetes.

Robert Doyle, PhD: Absolutely. And essentially the same drug is being used for diabetes or for obesity. They just give them different branded names because they've had to go through different FDA (Food and Drug Administration) approval processes. So they're the same drug, of different name. But the big difference is that the obesity treatment is at a much higher dose than the treatment dose for patients with diabetes. And so obviously the more you take, the greater the effect will be to try to drive that additional weight loss. But the greater the chance, then, that you may have one of these side effects pertaining to stomach emptying, nausea, vomiting and low energy.

Host Amber Smith: So what are the two new peptide compound discoveries that you've presented at conferences of the American Chemical Society and the Obesity Society?

Robert Doyle, PhD: Strangely enough, we talk about vomiting a lot in my group, and it won't surprise anybody who listens, who's ever taken a medication and felt ill, that a lot of medications, while making you get better, can make you feel ill in the short term or in the interim. We're all fully aware of chemotherapy-induced nausea and vomiting. Patients who are taking drugs to treat tumors often feel pretty ill. And so it's the same with these types of obesity drugs and some of these diabetes drugs, et cetera. So my group is very interested in creating drugs that will do what the current drugs can do, but do it without the side effects.

So we talk about side effects a lot, and we are very focused and have been for the past decade on drugs that will stop these things. And one, or in this case, two different pathways that we've explored a lot are new drugs to do what these Ozempics can do, but to do it without nausea, vomiting, low energy. It's very hard to do because food intake is often coupled to the emetic response, or the nausea response, and so it's very hard to decouple the two, which is why you see it happen so frequently with Ozempic and Wegovy, et cetera.

That's what we do, and that's what we've been approaching. And thankfully we've, I won't simplify it and say it was easy, but I will say that after a lot of work and a lot of support from the Department of Defense and the National Institutes of Health, we have created two compounds that can do exactly that, and neither of these compounds is what you would call a GLP-1.

It's a completely novel pathway, or pathways, because essentially we recognize that GLP-1's have inherent issues. And so we don't want to just reiterate around those drugs that are already out there. We want to look for new pathways. And so one of them that we described is a drug that goes after a melanocortin pathway.

And people will know melanin from skin pigmentation, but they'll be surprised to hear that there are actually five different types of receptors in this family, and two of them help control your appetite. And so yeah, it's pretty interesting, and so we've been exploring that as a mechanism.

And then we've discovered a pathway that is downstream, is what we would call it, of GLP-1, and so the idea is in this case that instead of waiting to hit GLP-1 and then have all of its signals happen, we will just jump in halfway down the response and completely ignore the GLP-1, and that way we'll still get to the same destination, but we'll start the journey halfway there, and that way we won't have the side effects that triggering these GLP receptors have.

And so two very novel approaches and that are manifesting really nicely to produce significant weight loss and a lot of additional other benefits: lower cholesterol, lower triglycerides, for example, less lean muscle mass loss. Because what we're seeing is glucose uptake into the muscle, so we have a non-insulin-dependent glucoregulation taking place. Our hypothesis is that's what's helping protect the muscle mass, because these drugs we've been talking about also cause lean muscle mass loss. You don't just lose fat, you also lose lean muscle mass. And of course you don't want to do that with an elderly population, for example, or with a young population -- really any population, but some populations more than others.

And so being able to focus on just losing the adipose, or the fat, tissue or mitigating the lean muscle mass loss is obviously much better for long-term use, right? So we're excited about what we are discovering about these drugs, tangential to the main target, right? We're really excited about them.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith. I'm talking with medicinal chemist and professor Robert Doyle of Syracuse University.

So how far along are you in creating a medication that would go on to get FDA approval?

Robert Doyle, PhD: Without giving away the farm, we have two compounds, as we've been mentioning, that have been licensed, and a company has been built around these two assets, and the company has put a board together. There's investment, and we are now moving towards what's called a pre-IND, which is essentially a pre-investigative new drug. And we need that because the FDA would review that package, all that data that we put together, and give us permission to put it into humans in a Phase 1 trial.

And so our aim is to move into Phase 1 human trials in early 2026, which would be highly exciting because a Phase 1 trial is normally just to ensure it's safe in a healthy human population. But because we're aiming to see weight loss without side effects, even in a healthy population, we're tracking them for their health, if we notice they're losing weight, or we notice that they're sick or ill or throwing up. So in a way, even though it's a Phase 1 we'll get a lot of Phase 2 information.

The nice thing about these drugs is that you can move them through pretty quickly, and you can gain a lot of insights very quickly, even at a Phase 1 level. So 2026 is going to be very exciting for these two drugs.

Host Amber Smith: Now, would these be injections or pills that you swallow?

Robert Doyle, PhD: So initially, these are injections. They'll be once a week, akin to what you do now with Wegovy and Ozempic, et cetera. So this would be subcutaneous injector pens, and then you sit back for a week and let them do their thing, hopefully without any side effects.

Host Amber Smith: Now, if everything goes well with the Phase 1, 2 and then 3, trials, realistically, we're looking at a few years, though, before this would be available.

Robert Doyle, PhD: Yeah, and essentially, if we look in the three- to five-year space, I mean, that's where we always look. So these drugs that are currently on the market are going to be replaced in the next two to three years, and then those drugs will see competition come in the three to five years from now after that. And so I think ultimately what's going to happen is it's going to be very exciting space for the next five to 10 years, and then the space will settle into those optimum 10 to 12 drugs that have ticked all of the metrics of success that we would like to see: weight loss, no lean muscle mass (loss), no side effects in terms of nausea, malaise, gastrointestinal distress, et cetera, lower cholesterol, triglycerides, and, ultimately, watch this space for the next 10 years.

Host Amber Smith: Do you have a name for the medications that you're working on creating?

Robert Doyle, PhD: So the two that we're, focused on primarily right now are DG-260 and KCEM-1. They are just generic internal names that we have. Obviously, as they move towards human use next year they'll be given some snazzy title, some name usually with a Z and a couple of X's in there, or something along those lines. But that would be marketing, and that is over my pay grade.

Host Amber Smith: Would these new medications that you're working on work on someone who eats a lot of high-fat food and who doesn't do any exercise?

Robert Doyle, PhD: Ultimately, we're going to take away your desire to do what you just said you want to do. You won't want to do what you just said. What we're really dealing with here is switching off hedonism (pleasure-seeking), the hedonistic part of your brain. GLP-1's, the current medications, also switch off hedonism or desire to do what you would call sort of dopamine-driven or hedonistic things. And so what's happening with these drugs right now is that they're being used to investigate addiction. What they're finding is that people who take GLP-1's suddenly don't want to smoke. They suddenly don't want to drink alcohol. They're less likely to go and shoot up. It's extending the satiety period, delaying relapse, or in some cases, just making people who smoke their whole life suddenly be like, "I don't want a cigarette." They've lost the desire to smoke. You're not going to just be able to counteract what it is you're doing. You won't do it.

Host Amber Smith: If you did try it, would it make you feel sick?

Robert Doyle, PhD: No, you wouldn't. You would be perfectly fine. But the thing is, what would happen is, you would either not do it at all or do it so much less that you would generally be better off, healthier, right? And even if you did do it, because it offsets your cholesterol levels, your triglyceride levels, your ability to store fat, it would also counteract it anyway.

If I could predict 20, 30 years into the future, this is the kind of thing they would have everybody taking as if they were taking vitamins off of a shelf. This would be over the counter. You should take this with your gummies. Because it would mitigate all of these nasty habits of yours, but also counteract the ones that you still haven't got rid of.

And so why not just take it? Because, well, the other thing that you're going to see is they increase vasculature (blood vessels), which is another side effect they've noted. And so, they're now currently looking at it for Alzheimer's, because what we really realize is that Alzheimer's is being caused by decreased blood flow or vasculature in the brain and damage to the brain over time.

And so if these drugs increase vasculature and increased blood flow in the brain, they'll almost certainly offset cognitive decline. And so what they'll probably tell people is, as soon as you're 40, start taking it and then take it for the rest of your life. Of course that makes Pharma (drug manufacturers) very happy, but If you think about it, if it's going to stave off heart attacks, and it will, and stave off fatty liver disease, and it will, and stave off Alzheimer's, and it will, and it's going to help you maintain a healthy and active lifestyle, and it's going to stop you from pursuing bad habits, then everybody's going to say to take it.

Then the other argument is, well, are you not just generating a set of boring old humans? Yeah, maybe, and maybe you don't want to take it, but I think eventually that's going to be on offer.

I think it's going to be like taking a vitamin.

If you think about it, before Linus Pauling (scientist who advocated taking vitamin C) in the 1960s, nobody took vitamins or minerals. The idea of taking vitamin C didn't exist until the mid- to late 1960s. And now it's who doesn't take a vitamin is more the question than who does, right? You probably took vitamins this morning, or multivitamins or multi-gummies or whatever, right? That didn't happen 50 years ago; nobody did that. Everybody thought you were crazy. Physicians thought it was crazy. Now it's as common as fluoridated water. Nobody thinks about it. But I think you're going to see something along the lines with this too.

Host Amber Smith: How long would a person have to keep taking these vitaminlike drugs?

Robert Doyle, PhD: Oh, you stop the drug, it stops working. Compensation is pretty quick.

If you're on it, you're on it. It's like someone with schizophrenia, they're on it, they feel great, they decide not to take it because they feel great -- (but then) the effects come back. You have to stay on it: minimal, clinically relevant dose for you, and then you would just stay at that maintenance dose for life, or as long as you wanted to be on it.

Host Amber Smith: Would these become made in pill form at some point?

Robert Doyle, PhD: Yeah. I mean, ultimately, these are peptides, though, so oral absorption of peptides is inherently challenging, so that's why they are injectables. And because some of these drugs target multiple targets, there's no way to make a small molecule that you could take as an oral medication.

But if you have completely new pathways, and you can have a single target, then turning that into a small molecule is feasible and ultimately would happen. But weirdly enough, there is an oral form of a GLP-1 inhibitor right now, Rybelsus. And it's less than 5% of the market.

Physicians haven't been able to get people to take it. It's just as effective, but it has had a really hard time penetrating into the market. And Ozempic still rules, and Zepbound will now outpace Ozempic, and even though there's an oral Ozempic, and it's called Rybelsus, I think it's 5% of the market.

Peptide drugs were considered persona non grata by the pharma industry forever because they were injectable, and they said that people won't take them. And it actually took vanity, in the form of obesity, then people would inject. And it turns out, if motivated enough, people will inject.

Host Amber Smith: So this could destroy the alcohol and junk food industry?

Robert Doyle, PhD: Never say never. First of all, junk food industry and alcohol industry is already declining, right? I mean, people are already drinking nonalcoholic beverages; that part of the market has exploded, and it's getting bigger, and even fast food companies offer healthier alternatives and stuff.

The mindset is already changing, but all these drugs would do is sort of parlay into that and maybe drive it forward a bit more, but ultimately, a lot of people won't take them, will never be convinced to take them. You can't convince some people to take a vaccine, right? You're not going to convince them to take a drug that somebody online is going to say turns them into a zombie who doesn't think for themselves anymore or whatever it is that it would be spun as. But at the end of the day, it's not meant for people to live forever. And it's not meant for overweight people. It's meant to help people who have a high risk of Alzheimer's and dying a horrible Alzheimer's-related death, or people who are morbidly obese and are going to die at 32 years of age. Now, for people who have real addictions to opioids and alcohol, and it's life destroying, it's for those people. It's not for those of us who are an average human doing average human stuff, and who's going to be in and above the average human life.

Now, if you think taking it is going to give you another three years, or four years, or five years, and it's going to make you ripped, so you can go to the beach in Puerto Rico, it's not for you, right? That doesn't mean there's not a population of people who will take it for that reason, but it's not for you.

And the FDA is currently refining obesity and then refining the recommendations for physicians to be allowed to prescribe it.

So what you're going to see now is, it's going to be morbidly obese, then there's going to be obese, and then there's going to be overweight. And they're going to say, obese and overweight shouldn't be prescribed these drugs, and they're going to redefine morbidly obese as "here." And unless you're here, you shouldn't be prescribed these drugs.

And that isn't just because, there's side effects to them, and it's not good to be just giving them everybody, but also people who do need them can't get them because they can't make them fast enough. And so there's that side of it too, right? So there's the bioethics of it, and then the FDA has to catch up, because the field is always ahead and then you have to play catch up.

Host Amber Smith: Good luck to you in your research. I appreciate you making time to tell us about it.

Robert Doyle, PhD: Thank you for having me.

Host Amber Smith: My guest has been Dr. Robert Doyle, a medicinal chemist and professor of chemistry at Syracuse University.

I'm Amber Smith for Upstate's "HealthLink on Air."

Here's some expert advice from geriatrics chief Dr. Sharon Brangman. How do adult children know when their parents need help?

Sharon Brangman, MD: Well, it's a very individual thing, and actually the holiday season is a time when we often get the most calls. And that's because that's when families come into town, and they may get a totally different impression as to what's going on compared to what they got while they were talking on the telephone or FaceTiming with their parents. They can see up close and personal what's actually going on in the home. And so many adult children, especially if they don't live in the area, call us during the holidays wanting to get things organized.

And so the first thing they often notice is that the house is not really being kept up well, and maybe their parent is just having more and more trouble with repairs and managing the mail, keeping the refrigerator stocked, getting rid of clutter and those sorts of things. And that is often the first sign that something may be amiss. Sometimes they will notice the car has a lot of unexplained dents on it or things that look like little fender benders, and usually the parent will minimize it and try to say that the son or the daughter is making a big deal about nothing, or something like that. But those are usually the early telltale signs.

And then when they're spending more time with their parents, they may notice that the day just doesn't go in an organized way. There may be long periods of sleeping or not getting dressed and ready for the day, or difficulty organizing meals. I had one family, for example, who came for Thanksgiving, and usually the mother would prepare this enormous meal for everyone. And when they got there, things were in disarray. The food was not prepared. And when you think about making a big meal like for Thanksgiving, that involves many, many little decisions in order to get the food on the table and cooked and ready to go at the right time. And some people, as we get older, start to have trouble keeping track of all those little details.

So there can be any number of little hints, and adult children start to recognize this when they spend time with their parents.

If there is signs of that house not being kept up, and it may just be too much, too much house. You know, after children are gone, and there's no need for three or four bedrooms and a lawn to mow and a driveway to shovel and a house that needs painting or some sort of repairs. You know, a house constantly needs repairs, and that can just become overwhelming.

So it's time to have a frank conversation. And it's usually not settled in one discussion. And it has to be approached with respect and consideration. Now, if the parent does not have dementia or any kind of cognitive impairment, they really have the ability and the right to live the way they want to live. So we cannot impose what we think is appropriate, even though it may be safer and it may make sense. You can't make someone do anything. And you know it, it just doesn't work that way.

So this can be a challenge for adult children, particularly those who do not live near their parents. So, you know, we have a very mobile society, and many of us do not live close to our parents or where we grew up. Or our parents may still live in our hometown, and we adult children have moved elsewhere. So the ability to kind of reach back across the miles can be very challenging. Now, there are a lot of resources for people who recognize a problem and want to seek help, but it can take a while for some parents to have that level of insight to get there.

It could be that the parent has too many things to keep track of, and it may be time to simplify their routine or downsize, or get help taking care of some of the details in life. It doesn't always correlate with an illness, but sometimes it can be the first signs of a memory problem, or someone who's just becoming what we call physically frail. That is someone who may not have that robust vitality that they used to have, maybe to mow the lawn or to clear the driveway of snow. And they may not have dementia or any specific medical problem, but just physically it's harder to keep up their previous routines.

The challenge is, often the parents don't see the same problems or have the same level of concern. So this is often a challenging discussion. There are very few older adults who have that same level of alarm, for example, that an adult child might have. They also are not comfortable with that role reversal with a child, telling them what should be done.

You know, we spend our whole lives looking for autonomy and independence and doing things the way we want, and it's inevitable at some point that we are all going to need some help when we get older. There are very few people that have the insight to recognize when they need that help. And so that's a bit of a challenge for adult children and for parents. And it can be a source of friction if it isn't approached properly.

Host Amber Smith: You've been listening to Dr. Sharon Brangman, from Upstate Medical University.

And now, Deirdre Neilen, editor of Upstate Medical University's literary and visual arts journal, The Healing Muse, with this week's selection.

Deirdre Neilen, PhD: Is there anything better than a love poem? Especially in these times? Vincent Casaregola, who teaches at St. Louis University, sent us a gorgeous and yet bittersweet testament of a love now gone. Here is "This Poem Is Just About You":

This poem is just about you, not you,

not some substitute to hold you

out of time's reach and cost --

this poem cannot touch you, cannot

feel the softness of your skin beneath

a fleeting brush of fingers,

cannot reclaim the sight of you

reclining on a chaise or standing

in the window's morning light,

cannot be the light reflected

in your glance across the table

or be the gentle tilt of your head

when listening, or speak your thoughts

with your voice, tender or alarmed,

angry or soft, as moods propel.

No, this is a thing of words, poor

currency that barely pays the price

of simple goods on ordinary days,

passing words, mortal and fleeting,

with no eternity in store, no marble

meaning etched in history.

And when your rebel cells collude

again, rise in secret, then strike,

bringing insurrection to the lung

or brain, these words, bring no relief

from any throbbing pain, no salve

for the sting of doubt and fear

as you, sleepless, outstare

the darkened midnight ceiling, nor

can they ease the ache that grows

stronger with each morning, or feel

the tangled tightness in your grip

as you reach for help to cross a room.

These words bring me no comfort,

not even cold comfort, but lie

dry as old paper in the musty attic,

less comfort, even, than a cold,

post-mortem final kiss that seals

the moment in the dim, grey room.

These words themselves have little or no

life, no breath for me to hear as from you

when you'd lain asleep beside me,

and they will fade, as ink on paper fades

in heat and angry sun, or as screens will

fade when the grid itself will die --

carve them on our stones, if you will,

the stones themselves erode to dust,

and even while they last, the sharp carving

smooths with age, making words clefts

for blown sand, for spores of lower plants,

for fibers of what, once, had flowered.

Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York.

If you missed any of today's show, or for more information on a variety of health, science and medical topics, visit our website at healthlinkonair.org.

Upstate's "HealthLink on Air" is produced by Jim Howe, with sound engineering by Bill Broeckel and graphic design by Dan Cameron.

This is your host, Amber Smith, thanking you for listening.