8. From Discovery to Daily Life: How GMP Transformed Nutrition for PKU With Dr. Denise Ney and David Paolella

Metabolically Speaking
Rare conditions, Real stories.

From Discovery to Daily Life: How GMP Transformed Nutrition for PKU
With Dr. Denise Ney and David Paolella

David and Denise share the story behind GMP and how its discovery transformed
the landscape for people living with PKU. From early research to real-world impact,
they reflect on the importance of involving the PKU community in developing new
medical foods and ensuring they truly meet patients’ needs.

In this episode, we explore how GMP can support quality of life, from making protein intake easier to manage throughout the day, to helping people feel fuller for longer.

We also discuss reported benefits such as improved digestive comfort, reduced
stomach pain and heartburn, and how GMP can better support more active lifestyles compared to traditional formula.

David and Denise also unpack the challenges of bringing medical foods to market,
including the cost, complexity, and need for extensive human trials. At its heart, this is a conversation about partnership and how collaboration across communities, clinicians, and industry has helped create more choice and flexibility for people living with PKU.

Disclaimer: The opinions expressed here are those of the guests/authors and not
necessarily reflective of the views of Ajinomoto Cambrooke Inc. Individual
experiences described herein are unique and not necessarily representative of
typical outcomes.  The content shared today is for educational purposes only.

Show Notes

 Find out more about Cambrooke:
o www.cambrooke.com/about
o www.linkedin.com/company/cambrooke-therapeutics
o www.instagram.com/ajinomoto_cambrooke
o www.facebook.com/AjinomotoCambrooke
 Get in touch with us: MetabolicallySpeaking@cambrooke.com
 Maridith Baker:
o www.instagram.com/phenylketonuriaandme
o www.linkedin.com/in/maridithbaker
o www.facebook.com/maridith.baker
 Resources from David and Denise:
o A Whey Forward: The Civilian - A Whey Forward
o Denise’s LinkedIn: Denise Ney | LinkedIn

Metabolically Speaking
Rare conditions, Real stories.

Transcript

SPEAKER_01 0:04

For decades, the nutritional standard of PKU care remained largely unchanged. Families relied on the same types of medical foods, often with limited choice of flexibility. Then a scientific discovery opened the door to a new way of thinking about protein for people living with PKU. In this episode, we're joined by Dr. Denise Nay and David Pallavella to explore the glycolacride peptides, better known as GMP, which became the first fundamentally new protein source for PKU foods in more than 40 years. Together, they share a story behind its development, what it takes to bring GMP from the lab into everyday life, and what this innovation has meant to patients and families with PKU. Settle in and join us for this thoughtful conversation on metabolically speaking, where science and partnership comes together to support the quality of life of people living with PKU. Welcome to Metabolically Speaking, the podcast that dives into life with inherited metabolic conditions. Proudly brought to you by Cambrook, delivering therapeutic nutrition for more than 25 years and empowering families to live without limits. I'm your host, Meredith Baker. I've lived with PKU my whole life, so I know the ups and downs and all the in-between moments that come with navigating a rare condition. Each month I sit down with experts, advocates, and people with lived experiences for honest conversations about what it really means to live with a metabolic condition. Whether you're newly diagnosed, supporting someone you love, or have been on this journey for a while, this space is for you. So settle in and let's get into it. Joining me today is Dr. Denise Nay and David Palolella, two people who have played a pivotal role in changing how we think about nutrition for PKU. Dr. Denise Nay is a professor of nutritional sciences at the University of Wisconsin-Madison, where she led pioneering research in GMP for PKU. Denise invented a way to use GMP, a whey protein produced during cheese making, to formulate safe low phenylanoline medical foods with improved taste for individuals with PKU. Offering an alternative to traditional amino acid formulas, her work led to licensed GMP medical foods now produced by three companies used worldwide, improving quality to life of people with PKU. She has been recognized as a rare disease hero by the FDA, and we're so excited to have her here. David Palela has spent most of his career working on problems he never planned to tackle. When two of his children were diagnosed with a rare metabolic disorder, he and his wife Lynn founded Cambrook Therapeutics. Now, Cambrook is serving patients in more than 20 countries. David served as president and CEO before joining the board of directors. He is also the founder of Tandem Bio, developing stem cell therapies for liver disorders and managing director of MILKS Technologies, a patent milk concentrate technology. A licensed architect by training, David is driven by the belief that necessity sparks innovation and that with science and persistence, what once seemed impossible can become the new standard of care. Denise and David, we're so glad to have you here with us today.

SPEAKER_02 3:58

Thanks for inviting us.

SPEAKER_01 4:00

Appreciate the invitation, Merida. Yes. We have a very meaningful conversation plan for today about how scientific discovery became real world innovation. So let's go ahead and dive in. Great. All right. Perfect. So the first question I have here is for Ms. Denise. For decades, the nutritional standard of care for PKU hadn't fundamentally changed. Can you take us back to the discovery of GMP and how it opened the door to a completely new way of thinking about protein for PKU, making it a milestone for our community?

SPEAKER_00 4:36

As we know, PKU requires a lifetime low phenylalanine or low-fee diet to protect the brain. The low-fee diet limits intake of natural foods that contain protein and thus fee, and includes a protein replacement or medical food that is low in fee and supplemented with vitamins and minerals. Since the 1970s, fee-free formulas made with mixtures, mixtures of single amino acids, you know, amino acids are the building blocks of protein that are essential in our diet. These amino acid formulas have been the standard protein replacement for PKU since the 1970s. GMP is a large milk peptide, basically a source of protein from cow's milk that is released into whey during cheesemaking. GMP is unique because it is the only known dietary large peptide that in pure form does not contain phea. Thus, GMP provides, for the first time in 40 years, a new source of dietary protein low in phi for the PKU diet. Because GMP is a large peptide, this means the amino acids are joined together in a chain and not single amino acids as occurs in amino acid formula. Because of this basic structural feature of GMP, it is more physiologic or natural for the body to use for growth and repair. Low-feed GMP medical foods help to normalize the PKU diet and make the diet easier to stick with because these GMP medical foods taste pretty good. Additionally, clinical evidence supports that people taking GMP in comparison to amino acid products have significant improvement in digestive comfort. This includes less stomach pain, heartburn, and reflux.

SPEAKER_01 7:10

Very interesting. And that's great to hear also because GMP has made such a pivotal impact in the community today. So I'm excited for us to get more into this and talk more about the importance of GMP. So with that being said, David, thank you for being here. The next question is for you. And it surprises many people to learn that early PKU formulas weren't fully phenyllenoline-free, that amino acids formulas were also default for so long. When did researchers start to first questioning whether that that was the only answer? And what made GMP so compelling to pursue?

SPEAKER_02 7:49

Boy, that's a that's a great question. And I should probably mention uh to the audience who may not know me that I have two children with PKU, Cameron and Brooke, which really started us on this journey.

SPEAKER_01 8:00

Yes.

SPEAKER_02 8:01

And, you know, out of uh necessity became invention and connections. So we need to start back in 1951 in Birmingham, England, in a hospital laboratory where a mother named Mary Jones had a two-year-old daughter, Sheila, who couldn't walk, she couldn't talk, and she couldn't even engage with the world. And her doctors told her that nothing could be done. She came back every day anyway, pestering them. And that persistence really changed everything for the history of PKU. And the physician who listened was a gentleman by the name of Dr. Horse Bickle. Those of us in the PKU world know him well. But remember, he didn't have a treatment, but he had a contact. A chemist that he had met in Zurich while he was studying inborn eras of metabolism was now working at the Great Ormond Street Hospital in London. So Bickle got on a train from Birmingham and went to Great Ormond Street. And there he met with Lewis Wolf, again, not a physician, a chemist. And Lewis' own colleagues had told him he was just wasting his time. But Wolf had this idea that was rooted early in his career when he was making proteins for wartime nutrition. He knew that you could filter phenylalanine out of a casein by using activated charcoal, the same charcoal you might use to cook your steak on the weekend. Bickel was taught how to put that in a big column. I'm told it was three feet high, packed it with charcoal, and poured this protein hydrolysate through, and it would take out most of the phenylalanine. So by December of 1951, Sheila Jones, the two-year-old, was on the world's first low phenylalanine diet, and she improved dramatically. Now, here's what most people don't know. That formula was not phenylalanine-free. It never was, because phenylalanine isn't the enemy. It's excess phenolalanine that is. And the goal was never zero. The goal was always precision. So Bickel's team proved this with a striking experiment you couldn't do today. After successfully treating little Sheila with their low-fee formula, they secretly added five grams of pure phenylalanine into Sheila's diet without telling her mom Mary. And within six hours, Mary came back to the hospital in tears. Sheila was banging her head again. The science was confirmed. Now this was uh a different era before internal review boards. And you may find this uh wonderful video on YouTube today where uh Horse Pickle is uh shaking the keys in front of little Sheila. And when she is uh got high fee levels, she's kind of just sitting there not responding. And when she's treated, she's playing with the keys, she's showing you know engagement with the world around her. So that was the proof that he needed. So by 1954, Lewis Wolfe convinced his old employer called Allen and Hanbraze, now absorbed into Glaxo Smith Klein, to make a commercial formula. It was called Simogran in the UK, and it wasn't a complete formula. It was just a cleaned-up hydrolysate base. And the clinical teams and the families had to add vitamins and minerals and milk back to dial in the right amount of phenolalanine for each patient in their kitchens from the different components. In 1958, in the United States, Meade Johnson launched a similar formula called low phenolac. Some of you may have heard about it. And it moved closer to a complete product, but it still had 80 milligrams of phi per 100 grams of powder. So the progress, Meredith, was real, but it was also really slow. And by the 1970s, as you mentioned, you know, we had newborn screening and we had free amino acid formulas that replaced these hydrolyses. They were cleaner, they were more controllable, but they were nearly undrinkable, something I experienced with my children who grew up on them.

SPEAKER_01 12:31

Yeah.

SPEAKER_02 12:32

And that became a problem that nobody solved for 40 years. And full circle to GMP, researchers knew about GMP glycomacropeptide. As Denise describes, a peptide released naturally during cheese making, and in its pure form, it contains no phenolalanine.

SPEAKER_01 12:52

Wow.

SPEAKER_02 12:53

It's the only naturally occurring peptide with that property. Now, researchers in metabolics and nutrition had understood this potential for years. But there were really no commercial suppliers. That was really the obstacle. And in the late 1990s, the purification problem with GMP was finally cracked at the University of Wisconsin, where Denise is, by Dr. Mark Etzel. And a metabolic dietitian, Sally Gleason, learned about Mark's work and teamed up with Denise to prove the clinical case. So my wife Lynn, Sally, and somebody you may know, Virginia Schuart, herself a dietitian, right, trained in Wisconsin. She was also the editor of the PKU News and Low Protein Cookbooks. Well, the three of them began experimenting with small supplies of GMP to make a better low-protein bread. But considering the high cost of the GMP, and it really wasn't even available, but we knew it would be expensive, and seeing the results of Denise's studies that she was conducting with NIH grants, et cetera, we determined that using GMP in a formula made the most sense. So that's a little bit about how it started. But the key message here is I couldn't source any GMP commercially in the U.S. I tried many, many uh dairies and people making cheese and so on. And I finally flew to Denmark to meet with a large dairy. And when I walked into the meeting with the CEO for the first time, he shook my hand and said, I've been waiting 18 years to meet you. And I was taken aback. How's that? Nobody ever said that to me before. And um the fact is that they had known about GMP's potential for nearly two decades. But none of the manufacturers were willing to commit. And the PKU market, as you know, is small.

SPEAKER_01 14:58

Yeah.

SPEAKER_02 14:58

Amino acid formulas were the norm since the 70s.

SPEAKER_01 15:02

Yeah.

SPEAKER_02 15:02

And what broke that log jam in manufacturing was a guarantee. Canberra committed to purchase their entire output, giving them the confidence to build a dedicated GMP production facility. And four years later, glytactin was launched in the U.S. in 2010. The newest formulas today, you should know, contain about one to one and a half milligrams of feed per gram of protein. Low phenolac, that early product, had 5.3, so about five times less is in the new products, but it took 60 years. And even today, infants still need some phenylalanine supplemented because the body and the biology has never changed. What has changed is that for the first time, patients had something that tasted like food.

SPEAKER_01 15:51

Yeah.

SPEAKER_02 15:51

So 70 years from a charcoal column in Birmingham to cheese whey peptide. The science was never the bottleneck. The supply chain was and the will to build it.

SPEAKER_01 16:04

That's amazing.

SPEAKER_02 16:04

So I've gone on long enough, but that's my story about.

SPEAKER_01 16:07

Yeah, that's amazing. If hearing all of the people that have also been a part of creating this GMP that individuals like myself, I drink glytactin every day, chocolate flavor. But you guys have made such an impact on our daily lives. So I love being able to hear the history of it, and I really appreciate it, of course, as well as a ton of other people in this community. So the next question is for both of you. Before GMP could ever be used in real patients, safety obviously had to come first. What did you need to prove to earn the trust of clinicians and families?

SPEAKER_00 16:43

Yeah, I'll take that. Okay.

SPEAKER_02 16:46

Please.

SPEAKER_00 16:59

We wanted to make sure our efforts were not going to be wasted on uh to make GMP medical foods. And we published an article with in the PKU National News, which Virginia Shuett was running at that time, and basically asked, you know, we've got this idea to make something different than amino acid, you know, formula. Would you like another option? And boy, we got letters from the PKU community. And one I remember very carefully, a mother, and she said, My kids go to bed hungry. I don't have foods that they want to eat. Please work to develop GMP foods, another option for us to follow the PKU diet. Now, David shared with you that the idea that GMP had application to PKU was not new. Okay. But the key thing is from the safety standpoint, while this diet idea was out there, no one had ever fed GMP as the primary source of protein to humans to know that it was safe. And in addition, GMP is not a complete protein, it needs to be supplemented with a limiting amino acid. So when I first started on the research, I started with a study in PKU mice and was able to demonstrate that GMP with supplemental amino acids was nutritionally adequate to support the rapid growth of a weenling mouth. We also noted in this that um the phenylalanine levels in blood were a little bit lower than the mice, the PKU mice and the amino acid diet. And most importantly, and something you can only do in a mouse, we looked at the brains in the PKU mice, and the phenylalanine concentration in the brain of mice and the GMP diet was 20% lower than the concentration of the brains of the mice and the amino acid. So this was very, very encouraging in terms of safety. Um now uh we surmise that this reduction in brain feed with GMP is due to the high concentration of large neutral amino acids that occur naturally in GMP. You know, this is one of the therapies that developed in Denmark on neutral amino acid documentation. Um the these preclinical studies and advice that you're needed in order for you to secure funding for the NIH and the FDA to conduct clinical trials in people with PKU. Such studies are very expensive to do. And in our first study that was funded by NIH, we admitted 11 patients with PKU to a clinical research center at the University of Wisconsin in Madison. They were admitted for eight days, and we controlled everything they ate, and we took daily blood draws, full amino acids, profiles, and other metabolites. This seminal study established the acceptability and the safety of GMP in humans with PKU. GMP did not significantly elevate blood fee levels compared to the usual amino acid diet, despite the small amount of fee in GMP. This study defined the formulation of GMP and limiting amino acids for protein metabolism. We actually had evidence of reduced protein breakdown in this inpatient study, and that the blood urea nitrogen levels were lower with the GMP compared to the amino acid diet. And these findings are all published. Um also people noted that they felt less hungry after a meal with GMP compared to amino acids, and there was some blood work to reinfor uh to um to support that subjective finding of less hunger in the patients, and we kind of coined the phrase feel full longer with GMP because that would describe the experience that our patients were having. And this inpatient study led the way to Cambrook to launch glytactin using our evidence based formulation of GMP and supplemental amino acids. That's amazing. In our next study, we uh conduct. An outpatient clinical trial and 30 adult patients with PKU were recruited from all over the United United States and they were fed glytactin GMP produced by Cameron for three weeks compared to their usual formula. And this this trial sort of sealed the deal in terms of safety because these are patients living in their natural at-home environment using the GMP medical foods. Clearly established the safety of GMP to control blood feed levels in adults and support protein metabolism.

SPEAKER_01 22:40

So that being said, GMP wasn't about relaxing the standards, but it was about meeting them in another way.

SPEAKER_02 22:46

Yeah, I guess you could say that. More important to me was that we started this journey thinking we had a better tasting food that was low in phenylalanine. But what we learned is from Denise and probably a decade or more of work that it was more, as she would say, physiologic. It was better for the body, is a simple way that I would say. And people felt better. There was, you know, my children really got to try it before it was even launched. And they did not want to go back to their amino acid formula, uh, even though they had this since they were infants. And we're very thankful for that formula. But this was clearly a breakthrough in their mind and made Lynn and I and Canberra commit to supporting the innovation and the invention, quite honestly, that uh Denise was able to uh just create.

SPEAKER_01 23:40

That's amazing. So, Dr. Denise, once safety was established, researchers started noticing other differences. How did GMP behave differently in the body compared to other amino acid formulas? And what did these differences actually mean for patients and their day-to-day lives?

SPEAKER_00 23:59

Yes, um I'd say there are three major areas where uh benefit uh improved quality of life was observed by patients. Um, the first is that um it was much easier to consume GMP in four or more servings per day rather than just chugging your amino acid formula in one, maybe two settings during the day. So this is important because this is consistent with improved protein utilization, and it also decreases the workload of the kidneys to have to get rid of actually all this extra protein when you chug a liter of amino acid formula. Um and actually, in some studies, there is a trend uh towards greater lean body mass with GMP consumption. And there is also a trend in some of the studies in children done in the UK for a trend for greater height in children at GMP amino acid. So taken together, you know, when you you spread the GMP across the day in three, four, five servings, which is easy to do, your body uses that protein better for growth and repair. Um, the second um benefit, which I've already mentioned, is um patients don't have that always hungry feeling, which is common with amino acid formula. Uh and I remember one patient telling me that this feels so different. It feels so good not to be hungry all the time. And in addition, because you're not hungry all the time, it's opened the door for some of the people who are overweight PKU to lose weight working with their dietitian, to lose weight gradually, including GMP in the diet. And lastly, improved digestive health. Patients reported less stomach pain, heartburn, and constipation. And I remember one teenager who was in our clinical study, and this teenager was a very uh strong soccer player, and she had double practice in the morning and in the afternoon. And this is what she told me after she tried the GMP in our study. She said, I can take GMP in the morning before my 7 a.m. soccer practice without feeling stomach pain and heartburn. The energy to practice feels great. That's amazing. Some real, you know, important quality of life feelings consuming the GMP.

SPEAKER_02 26:51

So, Denise, you're reminding me I uh my daughter Brooke would play soccer, and she had difficulty consuming her uh formula. Yeah, and that was one of the things that motivated us at Cambrook to create Restore, which was a hydration beverage with GMP. Uh and you know, it was a sort of thing where you see the life experience and what people need and try to fill that gap. And you know, GMP, because of its versatility, really lent itself well to products like that.

SPEAKER_01 27:24

Absolutely.

SPEAKER_02 27:25

So it it's uh it's something that I could echo as being part of our experience as well with our children.

SPEAKER_01 27:31

It sounds like um we had Stacy and Nora previously on the episode before this, and they were talking about sports and after school activities and how sometimes uh drinking your formula just doesn't feel good on your stomach at all whenever you're being active. So it sounds like the GMP-based formula is also great for people who are very active.

SPEAKER_02 27:53

Yeah, indeed. And you know, anecdotally, I've heard of um many and know many uh maternal PKU moms, too soon-to-be moms, that had difficulty with formula and they switched to GMP because they had less morning sickness and the other symptoms that are fairly common with pregnancy. So, you know, they're different applications, everybody's different. Um certainly um, you know, my children have been on it since about 2009. Okay, and uh they are not children anymore, they're adults. Uh Brooke is uh 28 and Cameron is 33, so that's amazing. They're getting on in age. Um uh my gray hair sort of proves that.

SPEAKER_01 28:36

Well, that's amazing, and I can agree I'm also an adult. I'm 25 on a GMP glytoctin. So totally agree with the formula changing our day-to-day lives. But with that, PKU care has always focused on type phenylanoline, also known as fee control. But life doesn't happen in a lab. How do clinicians use GMP to help balance metabolic control with quality of life for patients and families?

SPEAKER_02 29:04

So that's a great question. I'm happy to jump in. Um, so in a healthy person, we know that there's an enzyme, phenylalanine hydroxylase, and it acts somewhat like a pressure relief valve. So whenever phenolalanine isn't immediately captured by the cells for making proteins, building muscles, it travels to the liver where this PAH quietly converts phenylalanine into tyrosine. It runs continuously. You never have to think about it. That conversion is the automatic safety valve. And here's what Denise helped me truly understand: that your cells are using phenolalanine around the clock. They're building protein, maintaining tissue, keeping you alive. And your body is breaking protein down just as continuously, releasing phenolalanine back into circulation. This isn't a mealtime event. It never stops. And in PKU, this automatic valve is missing, and nothing really replaces it except the diet. Your diet becomes the safety valve. Every formula dose, every measured meal, that's the valve doing manually what the enzyme would have done automatically, which means any deviation has outsized consequences for the patient. A missed formula dose isn't just a missed meal, it's a valve that didn't open. Partly due to its more food-like taste, GMP patients can take their formula more often. We talked about this earlier at playing soccer and elsewhere. It keeps that valve working all the time. And I know that, Denise, you've spent your career understanding exactly how that valve works. Can you talk a little bit about what GMP changes about that equation in the body?

SPEAKER_00 30:58

Sure. So when you consume your GMP medical food, that reduces protein breakdown in the body. And so it reduces more fee coming into the blood. And the key thing is to take the GNP medical food four times a day is optimal, but three is okay too, because then you have the ability to quiet the body's protein breakdown and instead use the nutrients in the formula for protein synthesis, which is going on continually in the body. And in fact, that is the biggest challenge to following the PKU diet, taking sufficient amounts of medical food distributed across the day. And GMP medical foods clearly make that a lot easier and helped to control blood feed levels.

SPEAKER_01 32:04

That makes a lot of sense. And I think you comparing the valve also makes sense with how everything's working in an individual's body with PKU. So thank you for explaining that. Nutrition innovation hasn't always moved as quickly as pharmaceuticals. What makes nutrition research and bringing new medical foods to patients especially challenging compared to drug development?

SPEAKER_00 32:32

It's very expensive to conduct human feeding studies with such as I did. And it would not have been possible to do that research without money from NIH and FDA. There's over a million dollars into conducting the human feeding studies that I conducted. And you know, that money really needs to come from the federal government to support the health of our population. Drug companies, there's not enough profit in medical foods for them to put that kind of money into it. And the the beauty of the of the GMP medical foods story is that is this wonderful partnership that I had as a as a professor at a major research university. You know, I could do the research, but I shouldn't should certainly could not bring a product to market. And it would not have happened without Cambrook and the supply chain. So the beauty of what we did is this partnership between a major research university who supported the initial studies that my university paid for the mouse studies, and that led the way to being able to secure the federal funding. Um and my ability to work with Cambrook to bring this to market and to educate the community about the advantages.

SPEAKER_02 34:12

And you can't think about cost without thinking about the reimbursement landscape and the ability for families ultimately to either pay out of pocket for some very expensive food that they need for their children or have their insurance company pay. And I could go on for an hour about the insurance landscape here in Europe and other places, but it's uh it's always a challenge because cost is a factor. And that and the ability, as you mentioned, um, you know, is it protectable? Is there a patent or some way that if a company were to invest lots of money in research and product development, would they be able to have market exclusivity like they have with drugs? And in general, it's really not available in nutrition. So you know, those two things, reimbursement and uh patentability exclusivity, which come with breakthrough drug development, et cetera, are not really available in the nutrition space. So this partnership that um Cambrook and uh Denise's lab and the university uh undertook was really essential, I think, to make it happen. And now, as we've mentioned, there are other companies that have benefited from uh the hard work, initial work that uh Denise was able to do, and Cambrook was able to um encourage the manufacturer to make this raw material.

SPEAKER_01 35:40

Absolutely, absolutely. I think there's always the conversation of cost and insurance with everything PKU related and not PK related, but that is a big aspect to this. So thank you for sharing that information. Looking back now, what do you think GMP has changed most about PKU care, not just clinically, but how people experience everyday life with PKU? And how do you see GMP fitting into modern PKU care alongside the newer therapies that are becoming available?

SPEAKER_00 36:13

I would say uh I'll jump in now that um in terms of you know what's different about GMP, and and I believe that people with PKU using GMP medical foods have a more normal relationship with diet and their the foods they eat. And what do I mean by that? Um they don't feel hungry all the time and they don't have heartburn and stomach upsets. Can you imagine if you don't have PKU? You know, you take for granted that when you eat, you feel full afterwards, and you know, you have your gut feels good, and if it if it doesn't, then you probably make some adjustments in your diet. But prior to GMP, the normal for people with PKU was this feeling always hungry feeling, and having you know some GI discomfort throughout the day. So I think those are the um the major long-term effects of GMP that people with with um using GMP medications with experience. And in terms of modern therapies, the drugs that are coming out in the small molecules, the cofactors oraline hydroxylase, um a lot of them have side effects that are important, and good nutrition does not have side effects, and it it's tailored to enhance drug therapies for each individual. So the good nutrition with appropriate medical foods is a vital part of the therapies working as they should. Um unless remember, everybody needs to eat. Absolutely.

SPEAKER_02 38:10

So my thought, just if I might, uh briefly, um my two children are classical PKU. And so they have a pretty severe dietary restriction. Yeah. And they've tried all the medications that are approved on the market. And unfortunately, in the case of uh, say BH4, they are really not responsive uh in terms of controlling that safety valve. So their serum phenolalanine levels stay high. Even though with my daughter, she actually feels better taking it.

SPEAKER_01 38:43

Okay. Okay.

SPEAKER_02 38:44

So that's a plus. But the cornerstone of her treatment of her safety valve is still that diet, having you know, three, four servings a day, which honestly sometimes she doesn't. She'll take two because that's just how her day went. And I think you know, people need to get comfortable with the fact that they're in control of their safety valve, and whether that is going to be supported a bit by some medications, which are wonderful uh when they work. Um and you know, if they don't work, then they always have a diet, as Denise points out, is uh is very safe. So um it's given the more choices, ultimately. There are more PKU formulas now than there were when my son Cameron was born in '92 and when Brooke was born in '97. So it's a tremendous advance. Um and I'm sure, well, I hope, I guess, maybe, that um anyone born with PKU today can find a formula they enjoy.

SPEAKER_01 39:43

Absolutely, for sure. With this all being said, if listeners walk away today remembering one thing about GMP and PKU nutrition, what do you hope it is today, David?

SPEAKER_02 39:55

Hmm, one thing. Well, for people with PKU, the diet is your safety valve.

SPEAKER_00 40:01

Yeah.

SPEAKER_02 40:01

Whatever low phenolalanine formula you can tolerate, taken on schedule every day, that's precision management of phenolalanine in your body. You do it manually, you do it continuously, and it replaces the enzyme that you really were weren't born with. Yeah. And it's worth repeating. A missed formula dose isn't just a missed meal, it's a valve that didn't open. And as Denise mentioned, good nutrition has no side effects. So, you know, keep using the formula, whichever one, and um you'll stay healthy.

SPEAKER_01 40:36

Absolutely. And thank you for sharing all of this information today. I would definitely say for people wanting to learn more about GMP formulas, to ask your clinic. And if you're not sure if you're on a GMP formula or not, also ask your clinic. And there are ways to get samples through Cambrook as well and through your clinics. All right, perfect. Well, thank you so much for joining us today, Denise and David, and for sharing your story about GMP from scientific discovery to real world impact. It's been inspiring to hear about the very beginning of the journey, the challenges that you've overcome, and what its innovation has meant to people living with PKU today. Your insights are a powerful and reminder that with research, industry, and patient community come together, change is possible. Now it's time for our community conversation. So in this segment, we'll ask questions you've submitted, giving us a chance to explore our guests' stories and new personal perspectives. One of our listeners sent us a question today. So that is here for David and Denise. So the question is: I would like to see if there can be advice about nutrition for someone in the 50 age group. What foods and how much formula should we have for this age group? And what do you think we should be consuming in foods?

SPEAKER_00 42:00

For those people over 50 years of age, protein needs and phenylalamine tolerance do not decrease. You still need um adequate medical food in your diet. And that's usually two to four cups a day of medical food, depending on your phenylaline tolerance and your ability to eat other fruits and vegetables. So the diet continues. You need to support your protein even as you as you as you age. And the vitamins and minerals provided by the formula are also especially important as we age, particularly as antioxidants. Vitamin D and calcium are especially important for bone health. Dark green and colored vegetables such as tomatoes, carrots, and lettuce are excellent sources of vitamin A, antioxidants, and also fiber. Important to include these every day. And the last point I would make is that we know that many people with PKU, especially women, gain weight and become overweight as they grow older. And so it's important to monitor your weight and watch it and to remain active. Okay. And the GMP formula again makes it maybe easier because to not eat too much because you're not hungry all the time, basically. And it's you can work with your dietitian if you need to lose weight and incorporate GMP medical foods into a program for gradual weight loss. I'd also try if I was trying to uh lose weight or watch my weight in PKU, I'd be careful with sugar sweetened beverages, you know, Cokes and sodas. I know. They're free, but they also have a lot of calories without vitamins and minerals. And drink at least eight glasses of water a day to support your kidney with health as you grow older.

SPEAKER_01 44:14

That's awesome. Thank you so much for answering that. And David, did you have something you wanted to add?

SPEAKER_02 44:19

Yeah, I'll uh briefly just say that I've met many uh PKU patients that are uh close to my age, uh over 50, let's just say. And and to that extent, um many of them have been off diet at some point.

SPEAKER_01 44:34

Yeah.

SPEAKER_02 44:35

So um, you know, notwithstanding all the advice that Denise gave, they need to figure out what medical food they can use. And in my experience, um there are, you know, as I mentioned before, many more formulas to choose from, and they can get their protein in any number of ways. GMP has played a role for many returning to diet.

SPEAKER_01 44:56

Yeah.

SPEAKER_02 44:56

The other thing I'd say is that the challenge often is that the clinics in this country are in children's hospitals. And so a 50-year-old going to a children's hospital is uh a bit of a barrier. And any of the companies that manufacture uh these medical foods, I'm sure would be delighted to try to help them get them samples, and just know that you're not alone. So, you know, whether you go to your children's hospital where you went um, you know, 50 years ago, or you join uh the National PKU Association or a regional support group in your part of the country, uh I highly recommend getting some support. So uh that's kind of a couple of thoughts I had.

SPEAKER_01 45:39

I think that's great. And the power of connection really ends up bringing us all together at the end of the day and figuring out which what what works best for you and for a lot of people we've been able to experience GMP supporting that. So definitely there's many outlets, and it would be just reaching out and figuring out what works best for your body. With that being said, yeah, that's it for the community conversation today. If you want to include a question in the future episodes, keep an eye out on my social podcast platforms such as Instagram, Facebook, and more, as I'll regularly ask for input on our community questions. As we wrap up today's show, remember that you can find helpful resources as well as more information from David and Denise in the show notes. Thank you for listening, and we'll see you all next time.

SPEAKER_02 46:30

Thanks, Meredith. Thanks, Denise. Great to see you.

SPEAKER_01 46:33

Thank you, Denise and David. Take care now. Bye-bye. That is it for today's episode of Metabolically Speaking. Rare conditions, real stories, and a reminder that life with a metabolic condition is about living, not limits. If today's episode resonated with you, share it with someone who might need to hear it. And if you have a moment, leave us a review. It helps others find their way here too. We'd love to hear from you. If you have feedback, a story to share, or a question, send us an email. You'll find the email address in the show notes below. Make sure to subscribe to Metabolically Speaking on your favorite podcast platform and tune in each month to join your tribe, breaking barriers and living without limits. Thanks for being here, and we'll see you next time.