What’s Inside This Episode?

•  Why creatinine often rises with creatine and why it doesn’t necessarily mean kidney damage
•  The difference between creatinine production and kidney filtration
•  Why lab markers can be misinterpreted when supplements are involved
•  How creatine supports cellular energy and metabolic health
•  The bigger clinical question: how practitioners develop discernment around supplements
•  When creatine may be helpful and when it deserves a closer look

Resources and Links:

• • Download the full transcript here
  • Download our FREE Guide to Customize your Food Plan for Health and Longevity
  • Join the Next-Level Health Practitioner Facebook group here for free resources and community support
  • Visit INEMethod.com for advanced health practitioner training and tools to elevate your clinical skills and grow your practice by getting life-changing results. 
  • Check out other podcast episodes here

Transcript

Dr. Ritamarie Loscalzo 

There's been a lot of talk about creatine lately, a lot. And I decided to record this episode, because I found myself in the middle of it. Not just observing it, not just answering patients' questions about it, but participating in it. I've been taking creatine myself, although sporadically, and I suggested it to my husband recently after I read some studies about it as a possible sleep support strategy for waking up in the middle of the night.

So, when I started to see all these anti-creatine posts surfacing, strong ones, posts claiming kidney damage and synthetic toxicity, and posts claiming long-term harm, I paused. Not because I was convinced that it was bad, but because I believe in questioning everything, including what I personally use, especially what I personally use. 

So this episode isn’t in the defense of creatine. It's a demonstration of discernment, the questions I ask, and the way I make decisions. 

Creatine is one of the most researched supplements in sports medicine and also neurology. It has documented benefits for muscle strength and recovery, and age-related muscle preservation, and brain energy metabolism, and cognitive resilience under stress, and also sleep deprivation tolerance and Certain neurological contexts.

It's been increasingly framed as dangerous. Some of the arguments focus on downregulation of an enzyme called A-G-A-T and kidney function. Others focus on synthetic manufacturing and petrochemical origins. And beneath all of that, there's a deeper question. How do we decide when to supplement at all? 

Endogenous creatine synthesis, that's what's created in the body, occurs through two key enzymes, arginine glycine amido transferase, or AGAT, and guanido acetate methyl transferase, or GAMT. So when you supplement creatine, the body downregulates AGAT. That's called feedback inhibition. It's a common process in the body. It's regulation. It's the way all the hormones and various pathways in the body work, provide the substance, and the body downregulates the production. It just makes sense, right? But this can cause creatinine to rise. 

Creatinine is not the same thing as creatine. Creatine is used inside muscle and brain cells to help regenerate ATP, adenosine triphosphate. That's the energy metabolism in the cell. And every single day, a small percentage of the creatine stored in your muscles naturally breaks down into creatinine. 

Creatine is simply a waste product of normal energy metabolism. Not toxic, it's not dangerous. It's just what creatine turns into after it's been used up. And here's where the kidneys come in. The kidneys filter the blood, obviously, and creatinine circulates in the bloodstream and is removed by the kidneys into the urine. And under normal conditions, the body produces creatinine at a fairly steady rate and the kidneys clear it very efficiently. 

So if kidney filtration declines, creatinine builds up in the blood. That's why doctors use creatinine as one of the markers of kidney function. Higher creatinine can indicate that the kidneys aren't filtering properly. But here's the key nuance. 

Creatinine levels depend on two things. One is how much is being produced, and two is how well is it being cleared? 

So if somebody has more muscle mass, they naturally produce more creatinine. If someone eats a high protein diet, they may produce slightly more creatinine. And if someone supplements with creatine, more creatine is available to convert into creatinine and that can raise blood creatinine levels, even if the kidney function is perfectly normal. 

So sometimes an elevated creatinine doesn't mean kidney damage, it just means increased production. And that distinction really matters. Lab interpretation matters. And these are important things to be looking at to discern how well the body's functioning, and if we're producing too much of a certain chemical. 

So let's stress another concern that's been circulating about creatine. And that has to do with the synthetic argument. Commercial creatine monohydrate, the most common form, is manufactured industrially. It's typically produced from sarcosine and cyanamide. They're two chemical intermediates used in industrial synthesis. Those upstream chemicals may be derived from coal, or coke, or ammonia-based industrial processes. 

That sounds alarming when it's framed this way, right? But the distinction we have to make is there's a difference between the origin of the raw industrial feedstocks and the final purified molecule. Many nutrients we use clinically are synthesized in labs.

Vitamin C is synthesized. Most of the B vitamins are synthesized. P5P, pyridoxal 5-phosphate, a form of B6, is synthesized. Magnesium glycinate is synthesized. The body doesn't evaluate a molecule based on whether it's originated from petroleum, fermentation, or extraction. 

That said, I'm really careful about where things come from. I'm really concerned about byproducts and things that end up in the process when they're synthesized commercially. So I'm really careful about this. In that case, the body is responding to the structure of the final creatine molecule, and it's chemically identical to the endogenous, inside the body produced creatine. This is the same way that vitamin C, ascorbic acid, is synthesized, and it's similar to the vitamin C you find in oranges or food, right?

Dr. Ritamarie Loscalzo (06:42)

If we're going to be discerning about creatine being dangerous, because it's derived from these chemicals, we really should be questioning all supplementation. And that’s what we're going to be discussing in our next episode. 

So what I'm saying is that it doesn't really mean that we shouldn't care about where things come from. I'm a big fan of getting things from food first, get things from maybe concentrated extracts of food if it's hard to get from the whole food.

I really do care about this, and I care about manufacturing standards. So when I started to really put this in perspective, I started to question my intake of creatine, creatine monohydrate, but then I started questioning, well, my intake of B vitamins and my intake of various mineral sources that are chelated with other chemicals. Purity matters so much, and contamination testing matters.

So testing to see if there is any petrochemical residue left when we're synthesizing these vitamins and creatine. Those are important things. This is why I recommend if you are getting supplements, you get it from reputable sources that care about these things. Heavy metal screening is important, right? The fact that a molecule was synthesized doesn't automatically make it dangerous, right? Philosophically, it is a concern, but physiologically not necessarily.

We have to separate those two and also do due diligence and check the source, check the manufacturing process, check that it's a reputable company and that they do check for residues in their products. 

Layered on top of that, you're going to see some products, some manufacturers, presenting their creatine as superior, as the next level creatine, as geared towards premenopausal and postmenopausal women as if the need for creatine is different. The amount of creatine needed may be different as women age, but not necessarily the kind of creatine, right? But they're putting these out there. 

There's a lot of companies, and it's really hard for our clients to discern what's good and what's bad. What are claims that are based on science, and what are claims that are nice marketing, hype sounding that sounds really good? Let me buy it. And if you're like me, you see people coming in with long lists of supplements that they're taking, because some influencer on social media said they should. Podcasts say that they should, summits that they listen to, and they're on these supplements that they don't even know if they're good for them. They don't know what the interactions are. 

Creatine is not the only supplement that is subject to this right? This is what we're talking about today. 

When you see this, and you see these marketed as superior, you always have to ask why? What's the biochemical reason? How is this put together in such a way that makes it more absorbable or that makes it get into the cells more easily? 

Those are the questions we need to ask, and we need to be able to answer, so we can provide these answers to our clients who are asking us, do I need creatine? Do I need this or that or the other? Should I get this brand or that brand? 

So creatine monohydrate remains the most studied and clinically validated form, no doubt about it. And until there's high quality comparative trials showing meaningful outcomes between different types and different ones with these fancy names, we just need to be discerning, because a lot of those are way more expensive, right? 

So the real question here really isn't whether it's synthetic or whether creatine is good or bad. It's actually who needs it. So let's talk about who needs it. It may be appropriate for people with low dietary creatine intake, those not eating animal products. That is where most of the dietary creatine comes from. People with high cognitive demand, right? Are we already seeing some dysfunction going on? 

Athletes, right? Athletes who are actively engaging in high intensity, they need a lot of support for growing muscles, and they're not necessarily getting anything in their diet, right? These are special cases. These are not like your average person who's just trying to be fit. We're talking about heavy duty athletes, bodybuilders, 

and competitive athletes. 

Aging adults who start to experience muscle decline, right? The muscles are starting to breakdown, and we see that their skeletal body doesn't look all nice and buff, and they're falling apart, right? This is something that can be beneficial. 

And people who have certain mitochondrial inefficiencies, Low energy in their pathways are blocked. We can measure those things in labs, and there are some people who are under a methylation strain. A lot of people have methylation issues genetically, and reducing exogenous creatine synthesis results from those methylation declines. 

So those are things that we can look at and say, okay, these are times when this person might need creatine to be supplemented. 

My personal reason for taking it is I'm starting to do a lot of heavy duty lifting. I want to grow good muscles. I haven't seen that it makes a difference. So I really need to do a trial and be very consistent with taking it for two months, watch my muscles, and then stop it for two months, and see if I notice a decline in strength and in muscle gain. That's really the best way for us to check, is to really look and have a before and after picture, so to speak. 

These are all thoughtful cases, and while I prefer a food first approach, creatine is naturally present in animal foods, no good plant sources. 

For those people who choose to eat higher amounts of animal-based protein, especially red meat or wild game, baseline creatinine intake may already be adequate, and they don't need extra, But for those of us who prefer a more plant-forward approach, dietary creatinine may be much lower, and it might be a good case for supplementation. Neither approach is right or wrong.

Dr. Ritamarie Loscalzo (12:52

Morally, everybody has to make their own decisions and also how it feels in their body, right? There's studies that show less animal products are healthier. There's other studies that can show the opposite. We just have to figure it out for each individual patient and for ourselves, quite frankly. 

Supplementation may make more sense in some dietary contexts than others. But again, it's all about discernment, right? If somebody has great energy and eats adequate protein for their goals, and doesn't have any performance or neurological demand or deficit, and no clinical indication. They have stable kidney labs, you may not need creatine, and that's okay, right? 

More is not always better. We always have to remember that. Just getting more doesn't mean your body's going to work better. We live in a time where influencers push stacks of supplements, fear marketing drives people's purchases and produces great urgency, and people take 15, 20, sometimes even 30 capsules a day, and sometimes even more. And many have never optimized the basics, right? Their food, their sleep, their stress. And that's the real issue, not creatine and whether they need it or not. 

The issue is supplementation without an underlying strategy of improving the things that they can improve. Supplementation without labs, not necessarily a good idea. Supplementation without context is not good, supplementation driven by fear. That's not healthcare, that's consumerism. I paused, because I wanted to make sure I wasn't following a trend in taking creatine. I asked myself, do I need this? Does my husband need this? Are we using it intentionally? And that's the right way to look at it, not panic, not hype, discernment. 

And again, like I said earlier, having a before and after baseline and then looking at it, and looking at the function, and seeing if it's making a difference and looking at the labs, right? Looking at kidney function. Now, if my kidney function looks like it went down after taking creatine, that could be, because I'm just producing more creatinine and creatinine is used in measuring or calculating estimated GFR, estimated glomerular filtration rate.

And quite frankly, I've got to go back and look more carefully, but I have been supplementing creatine recently and my recent labs showed a slight drop in my eGFR. So I'm going to look back and see like, when did I take it? But that wasn't deliberate, right? 

I need to go back and do this deliberately. Look at my function without the creatine, so go six or eight weeks without it and look at my kidney function, because it would go back. If it looks like the creatinine is going up and the EGFR is going down, it will go back in about six to eight weeks. So look at my function without it. And then there's another lab that should be added to the mix, which is cystatin C, and that doesn't rely on creatinine to measure kidney function. 

From my perspective, measure the kidney function, not on creatine. Look at cystatin C, so look at creatinine, BUN, eGFR, and Cystatin-C. Okay, then start the creatine supplementation. Be consistent with it. Go with the daily dose. It's usually around three and a half grams is recommended. Then do it for eight weeks and then go back and recheck. Now, in rechecking, you might see, likely, a decline in EGFR and an increase in creatinine, does that mean your kidneys are not functioning properly? Not necessarily. 

So let's look at this cystatin C at the same time, right? So let's just look, let's just do it deliberately, right? It's very useful to take it. It's a tool and can be very, very helpful and very useful for specific people for specific reasons. And for others, it might be unnecessary.

So I think it requires understanding the pathway, checking the labs, as I talked about, individualization of the dose based on what they're doing and how much muscle build they're doing, and then careful dosing, thoughtful dosing, and quality sourcing. 

Don't just buy it at the local 7-Eleven store. Get a good quality, so you trust that they are testing it for purity. That's what's called mature supplementation. But here's where I want to leave you.

Dr. Ritamarie Loscalzo (17:19)

Creatine is just one example. The bigger conversation is this. When should we supplement? When is food enough? When is isolation appropriate? Specific nutrients, not combinations. Does synthetic automatically mean unsafe? Does natural automatically mean superior? How do we evaluate long-term exposure rationally as practitioners who care about our clients, who care about our patients, who want them to get the best results possible. 

And how many supplements are too many? And I know you've all seen it, right? People coming in with their long, laundry list, and they have no idea why they're taking some of this stuff. And most of them want to get off of stuff. And one of the first things I often do with somebody that comes in, if they're open to it, because some of them aren't, is to say, do you notice a difference with this?

Do you notice a difference with that? Take them off anything that they don't really know why they started and that they don't notice a difference with. And then we really evaluate. We look at their labs. We look at their function. We look at their genetics and determine what exactly they do need. That conversation is way bigger than creatine. And maybe that's the real takeaway, right? 

Creatine is in the headlines, but it isn't the headline. Discernment is the headline. When we slow down enough to ask better questions about supplements, labs, physiology, genetics, and marketing, we practice a different kind of healthcare. One that doesn't react to fear. One that doesn't chase trends. One that respects the intelligence of the body. And that's the direction I believe healthcare must move. 

So we’ve got to go deeper with our thinking. We’ve got to go deeper into context. We have to look for the root cause, because the body isn't fragile. It's adaptive. The body adapts to what's going on out here and what's going on in here. It's intelligent, and it deserves decisions that make sense for the individual. The decisions that are grounded in physiology, not panic, not fear, not click bait on social media. That's the work for us. That's the shift for us as part of the healthcare system that is inherently broken, that we'd like to fix.

That's how we get to reinvent and rethink healthcare, and that's the kind of reasoning you need to strengthen in your own life or practice, so you can be the best practitioner you possibly can. 

So if you want to learn more, go to INEMethod.com and jump in and see how you can become part of our community. 

And next time, we'll expand on this conversation into supplementation itself, when it serves us, when it doesn't, and how to step out of the fear-driven cycle that keeps so many people overwhelmed. 

Together, let's continue to rethink what healthcare can be. And until next time, shine on.