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Ep. 433 Creatine Masterclass: Why It’s Essential for Women 40+


Today, we have a mashup episode exploring the benefits of creatine, a supplement gaining more and more recognition for its positive effects on muscle health, brain function, and overall well-being. We feature insights from many experts who clarify how creatine supports metabolic health, enhances exercise performance, and improves cognitive function, particularly for women in perimenopause and beyond. 


Join us as we unpack the science behind creatine and its potential to transform health at every age.


Stacy Sims

[00:59:23] Dr. Stacy Sims highlights creatine as one of the key supplements for women, explaining how creatine supports brain health, muscle performance, and energy metabolism. She advises choosing high-quality creatine like Creapure to avoid bloating. 


Darren Candow

[00:01:40] - [00:03:29] Darren Candow explains the distinct roles creatine and essential amino acids (EAAs) play in the body. EAAs are vital for survival as they support the production of enzymes, hormones, and muscle tissue and are obtained through food or supplements. Creatine, on the other hand, is conditionally essential. Our bodies can produce it from amino acids, primarily in the brain and kidneys. While EAAs are necessary for life and overall health, creatine enhances specific functions like muscle performance and brain energy metabolism but is not essential for survival. So, although both can be beneficial, they work differently in supporting health and performance.

[00:10:32] - [00:15:38] Darren highlights how there is no evidence in humans to support the notion that taking exogenous creatine will halt its natural production. Creatine does not increase fat mass, but some individuals may experience temporary water retention, which they may perceive as extra weight. High doses of caffeine might interfere with the effects of creatine over time, but moderate coffee consumption is unlikely to cause issues. Creatine is versatile and can be taken with water, fruit juice, or other liquids, though avoiding high caffeine intake is recommended for optimal results.

[00:16:16] -  [00:21:14] Creatine supplementation is generally safe and effective. However, there are some considerations around hydration, safety concerns for individuals with health conditions like hypertension, and the long-term impact on younger individuals.

[00:23:55] - [00:27:44] High-glycemic carbs or insulin-stimulating proteins like whey can help creatine enter muscle cells. While carbs work well, protein is often healthier and more versatile.

Foods like salmon provide creatine, making food first the ideal approach for supplementation.

Exercise naturally increases creatine uptake by activating muscle transport mechanisms. Taking creatine before or after workouts can optimize its effectiveness.

For vegans or those avoiding creatine-rich foods, supplementation may be necessary.

[00:39:48] - [00:42:14] Creatine may support bone health by preserving skeletal measures in healthy postmenopausal women. While it could serve as an adjunct to exercise and proper nutrition, it is not a replacement for medications like bisphosphonates.

[00:42:26]- [00:46:14] Younger individuals need less protein to trigger muscle protein synthesis than older adults, who may experience anabolic resistance and require higher protein and creatine doses for similar effects. Research suggests older adults, especially those in their 70s and beyond, may benefit more from creatine supplementation, particularly when combined with exercise, to combat muscle and bone loss. Creatine appears safe for all ages, but individuals with specific health concerns or medications should seek medical advice.


[2:46-12:50]

[15:31-16:53]

[25:58-52:46]

[53:58 - 58:55]

Darren Candow highlights the role creatine monohydrate plays in bone health, particularly in postmenopausal women. It may also support anabolic processes, especially when combined with exercise. Research has shown its connection to brain health, aiding in recovery from traumatic brain injuries, mitigating sleep deprivation and jetlag, and improving mood disorders. Creatine dosing is crucial, with higher doses potentially beneficial for older individuals due to anabolic resistance. It enhances anaerobic strength training, supports fat loss, improves cardiovascular health, and boosts endurance exercise. Creatine may also act as an anti-inflammatory and anti-catabolic agent, protecting against muscle breakdown.


AMA #5 

[00:15:09] - [00:19:51]

Creatine is best taken within a feeding window, particularly for fasting individuals, to ensure sufficient protein intake. While some may experience temporary water weight gain, it is generally safe and offers benefits beyond muscle growth, such as improving sleep quality and supporting brain health. Research shows that creatine, even at higher doses, does not negatively affect kidney or liver function. It is best to avoid adding creatine to hot foods to preserve its effectiveness. 


Louisa Nicola

[57:54] - [1:01:09] Louisa Nicola explains how creatine improves performance.


AMA with Ben Azadi

[1:02:30] - [1:06:20] Ben Azadi clarifies when to take creatine supplement powder for optimal results.


Gabrielle Lyon 

[00:44:24] - [00:48:02] Dr. Gabrielle Lyon discusses the importance of measuring skeletal muscle mass directly using a new method called D3-creatine, which could revolutionize how we assess muscle health. New findings suggest skeletal muscle mass plays a crucial role in aging, insulin resistance, and overall health. Creatine is a well-studied and safe supplement for muscle energy and brain function. It can enhance performance, sleep, and cognition, especially for those who struggle to get sufficient amounts from diet, such as menopausal women. The benefits of creatine extend across all ages, from teens to seniors.


Dr. Amie Hornaman

[1:00:25] - [1:08:33] Dr. Amie Hornaman is a big proponent of creatine, having used it since the late 1990s. She highlights its positive effects, improving strength, muscle growth, and workout performance without side effects. Creatine also boosts testosterone and growth hormone levels, which can help lower Hashimoto antibodies and increase thyroid function. By supporting overall hormone health and reducing inflammation, creatine benefits the thyroid. She encourages its use for day-to-day health and performance, particularly for women seeking strength and wellness improvements.


JJ Virgin

[00:20:58]-  [00:24:25] JJ Virgin believes creatine is essential for menopausal and post-menopausal women. She highlights how women often fear that creatine will make them gain weight, but she explains that any potential weight gain is just water in the muscles, which benefits muscle hydration. JJ compares this to her experience in the 80s, when she reassured women lifting weights would help them build strong and toned bodies.

 

“If I were going to pick one supplement for a menopausal woman peri/post as something that you should be on for the rest of your life, it would be creatine.”


-JJ Virgin

 

Connect with Cynthia Thurlow  


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Connect with Louisa Nicola


Connect with Ben Azadi


Connect With Dr. Gabrielle Lyon


Connect with Dr. Amie Hornaman


Connect with JJ Virgin


Transcript:

Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives. 


[00:00:29] Today is a very special compilation of podcasts that have been creatine monohydrate centric discussions with experts, researchers and clinicians about the benefits and why it is one of the most well researched ergogenic aids/supplement options available. This includes discussions with Dr. Stacy Sims, Dr. Darren Candow, Louisa Nicola, Gabrielle Lyon, Amie Hornaman, and last but not least, JJ Virgin. I know you will enjoy these conversations as much as I did recording them. 


[00:01:12] Yeah, I think people are oftentimes surprised. They forget about some of the plant-based sources of protein that they can use complimentary to buffer their protein intake. Now I'd love to end the conversation talking about supplements. I know that we have some shared supplements that we enjoy. When you're talking to your female subjects or talking on podcasts or publicly, what are some of your favorites that you think for women in perimenopause and menopause can be most beneficial?


Dr. Stacy Sims: [00:01:41] Creatine for one, so good nod to the head there. Yeah, creatine is the good one for all of us. So important because one for women who are eating less and/or following vegetarian vegan-type diet, don't get enough creatine anyway and we also have less stores than men. We also see that creatine is so important for the fast energetics of our body. So, we're talking about gut health, heart health, but in particular brain and brain metabolism. So, we really want to push creatine for health and we also can see a benefit for muscle performance. It's only 3 to 5g, not a lot. And when we start seeing women who start using creatine, not only do they mentally feel better, they're also seeing better muscle performance. 


[00:02:28] It takes about three weeks to fully saturate though, so it's not something that you just take a one off before training, it's something that you actually want to take on a daily basis. The second one that's really important is omega-3 fatty acids, especially in perimenopause for cellular integrity, we’re having more oxidative stress, we need to really protect our cells and so omega-3 fatty acids are super important. And the third one I often talk about is vitamin D because we see such a precedence of low vitamin D intake and low vitamin D levels. We have a lot of the slip, slap, slop in the sun, right? So, we have a hat and sunscreen and a shirt. So, we aren't getting that sun exposure. And we're also looking at a lot of time inside and the ultra-processed foods aren't doing any good. 


[00:03:21] We're looking-- if you need to supplement then a vitamin D3, but also thinking about how mushrooms are your friends because mushrooms are really good sources of vitamin D. So, those are the three big ones that I talk about for the most part. And then there are the individuals, like if you're having sleep issues, you might think about L theanine. If you're having stress issues, you might look at other adaptogens. And if you're having iron issues, then maybe we look at what carbonyl iron and how to use that. But for the most part, most women should really be paying attention to creatine, omega 3s, and vitamin D.


Cynthia Thurlow: [00:03:59] I love that. And for women, if they're listening and say that creatine prompts bloating, it makes them feel like they've retained a great deal of water. I know quality is certainly important. And what do you typically say around those kinds of concerns? 


Dr. Stacy Sims: [00:04:15] So, we want to make sure that you're using Creapure. So, this is a German B2B, a business-to-business company that is all about how pure that creatine is. So, you don't have any acid left over, which is from the cheaper versions that can cause some of the side effects. And start small. Start with 1.5 g and work your way up to 5. Know that there will be some water retention because creatine pulls water into the muscle cell, but it shouldn't be an overt bloat. If it's an overt bloat then look at the type of creatine monohydrate you're having. Again, look for Creapure, start at a lower dose and work your way up. 


[music]


Cynthia Thurlow: [00:04:56] It's great to have you both. I thought this would be fun to do an AMA episode talking about one of my favorite subjects, which is creatine monohydrate. And for listeners, again got hundreds of questions. And from the hundreds of questions, I tried to synthesize themes so that we could stay really nicely organized, curious. How does creatine differ from essential amino acids? Is it necessary to take both? I got this question multiple times. There's a lot of confusion about how they are different mechanistically. Are they both necessary? Do you have any thoughts on this? 


Dr. Darren Candow: [00:05:29] Yeah, there's a big difference. Without essential amino acids, you die. Without creatine, we can still survive because we can make them. So, essential amino acids are found from food products or supplements because we can't produce those and near the quantity that are needed to basically keep our body alive. Enzymes, hormones, bone, muscle, everything we need. So, protein is an essential macronutrient. Some people like to call creatine conditionally essential. But keep in mind, creatine is basically formed from indispensable or essential amino acids and nonessential. So, we're naturally producing it in the body like a lot of our proteins. However, unlike essential amino acids, which are required to keep you alive, essentially. I think the little bit we produce in our brain and kidneys can keep most people very healthy and functionally as well. So that's an excellent question. 


[00:06:18] I'm glad it was essential amino acids versus individual amino acids. There's a huge difference. Essential amino acids are very important. They can improve a lot of beneficial things with muscle growth, whereas the branched chain may be a little limiting, at least with the essential. And I know there's a big EAA-9 new template coming out which is great for individuals to look at food products that have a lot of these essential amino acids. So, there's a huge difference between a creatine and the critically important essential amino acids. 


Cynthia Thurlow: [00:06:47] Another common question made me laugh. Not because there weren't many people that asked this question, but I was like, it's consistent with other things that we talk about in the body. Since our body naturally makes creatine, will taking exogenous creatine halt my body's own production of it, might seem silly. And this was Tracy's question. 


Dr. Darren Candow: [00:07:04] Oh, certainly not silly. That was the biggest thing when EAS, the pioneering supplement company came out. The theory was that, well, if we naturally produce it, just like take for example insulin. If synthetically inject insulin when your pancreas doesn't need it, there is some theory that it could downregulate that and that was happening in professional bodybuilders. So, the theory was, well, if you're taking a supplement you're naturally producing, maybe the body says, “Whoa, I'm going to rest and take it in.” There was a single study done in mice. It was actually a rodent model and it was shown to downregulate its natural production. But as soon as they stopped taking the super physiological dose, it came back. We're not aware of any good evidence in humans. I guess the theory would be the liver is going to be making it. The brain is going to be making it. Anything addition, which is nice for the human body, will accumulate in the tissues. We now know it's not just muscle and any extra could be dumped down the toilet in the form of creatinine. So, we're not aware of any good data in humans that it does downregulate the natural production. 


Cynthia Thurlow: [00:08:02] It's really interesting because I know even the use of melatonin can be controversial. People say, well you make less of it north of 40, but if you take some of it as you're making less of it, is that problematic? So, I think that's certainly a reasonable question. Does creatine lead to an increase in body fat? This was Kelly's question again, a question that was asked many, many times. 


Dr. Darren Candow: [00:08:23] Yeah. So, we just published the second meta-analysis last week looking at adults 49 and younger. So, if you look at adults 18 to above, when they combine it with resistance training, we saw no increase in body fat across any population. We actually saw a small decrease in percent body fat. It was significant, but it was less than about 1%. So, collectively you should probably conclude that creatine does not increase fat mass. It's probably going to have a minimal trivial effect if you're really going through the weeds. The whole theory here is that if you take creatine where it is osmotic, some individuals experience acute water retention or maybe the number on the scale may go up, probably based on the dose and the length of time you're taking it. 


[00:09:06] And if it is a water fluctuation or distribution, a lot of people feel like, “Hey, I'm a little bit heavier or a little bit more bloated, maybe on the loading phase.” But we're not seeing any evidence that increases fat mass. If anything, it may have a beneficial effect, whole body energy expenditure. 


Cynthia Thurlow: [00:09:23] Yeah, it's interesting. Both my teenagers take creatine and my youngest son, who's put on quite a bit of muscle in the past year. He is so conscientious and he actually listened to the podcast we did together and now his is taking 10 g a day. Because for him, he was like, “I like this brain element. I like knowing that a little more will cross the blood-brain barrier.” And he attends a pretty intense school. So, for him, he's like, “It's helping my brain and my muscles.” And so, for him, that is definitely something that he thinks about quite a bit. I know that we had talked last time that creatine and caffeinated beverages don't meld well together. Is there anything that we should not take creatine with at the same time? I know caffeinated beverages. Is there anything else, any other liquids or foods that you should not take it concurrently with it may impact or lessen its ability to be as efficacious?


Dr. Darren Candow: [00:10:14] Yeah, it's a hot topic. So, let's start with the first one to sort of clarify. I think even for some of your viewers around the caffeine, because a lot of people immediately say coffee, caffeine, it's the same and not really. So, the studies that have looked at the interference with caffeine have typically done pills or powders and some have done solution. However, the dose is usually around at least 250 mL. So, if you think of a normal cup of coffee is about 80, that's about three cups, okay. And that's usually done with a higher dose of creatine. So, there've only been about seven studies and good mechanistic data to suggest that those two metabolites sort of interfere with one another. 


[00:10:52] But if you were to put your creatine acutely in a cup of coffee and drink it really quickly, I highly doubt the acidity of the caffeine is going totally degrade the bioavailability of creatine. But if you do this over time, it could. So, I think, maybe pre-exercise is caffeine. Post exercise or throughout the day is creatine. But temperature will actually improve the solubility of creatine [unintelligible [00:11:14]. If you were to boil it, it would degrade it quicker to creatinine. And I don't think I've heard of anybody actually boiling something and putting the creatine in for a long period of time. A really long answer to a simple question. There's probably really nothing that interferes with creatine. 


[00:11:29] It could be taken in a gel, a lozenge, you can get it through your diet and meat at the end of the day, it might delay the absorption or getting into the bloodstream. Solution is superior to meat, lozenge, candy, whatever that will peak in the blood the quickest. I think that's why a lot of people will just put their creatine in water or fruit juice, whichever. But the only thing we see an interference effect is high-dose caffeine for longer periods of time. 


Cynthia Thurlow: [00:11:54] I was laughing and saying one of the big takeaways from our last conversation was everyone was then paranoid to put the creatine in their coffee. And now reassuringly knowing that one cup of coffee is not going to offset the benefits. But if you're having 20 ounces of coffee at one point, all at once, then that might be the case. Do you feel that there's certain amount of water that needs to be consumed while taking creatine? One listener said, “I heard that it was a gallon or more a day in order to ensure that you stay hydrated while taking creatine.” This was Paige's question. 


Dr. Darren Candow: [00:12:28] Yeah, so theory here is we don't know the exact amount, but it's certainly advantageous to consume more water, ideally to help maintain the plasma or decrease the viscosity of the blood. So, if the blood gets thicker, it has more hematocrit or cells in it, so it could potentially fluctuate blood pressure or heart rate. But I always recommend to drink about two or three more glasses of water a day. That helps maintain the hydration not only of the muscle, but also the plasma or bloodstream. Because hopefully if individuals are taking creatine, they're exercising and therefore sweat rate would go up and you don't want to have metabolic dehydration. So, there's not a fixed number. But in our research studies, we usually recommend to people to drink more water. Now, that could be an increase in fruits and vegetables, whatever vehicle they want to get. But water is just easy. And logically, if you have more water, it could allow a vehicle to get into the muscle cell a little bit quicker. 


Cynthia Thurlow: [00:13:16] Makes a lot of sense. And that was again, one of those questions that I got over and over and over again. Any specific contraindications or safety concerns about creatine? And I got questions about hematologic issues. We just talked about the hydration and viscosity specific to Factor V Leiden. So, people that are prone to clotting, is there anything to support that there's a contraindication to using creatine? 


Dr. Darren Candow: [00:13:41] Yeah, not that I'm aware of. We've looked at blood cell count and function in those long-term studies, especially in postmenopausal study for two years and found no adverse effects. And so, in theory, I guess, if hydration-- if the individual's dehydrated, that could cause some other abnormalities. But there's no mechanistic reason why creatine itself, it's an organic acid, would lead to blood clots. Now, it could influence blood pressure acutely if the individual is consuming too much fluid or not enough where it will take some of the water from the blood into the cell. But all the studies and review papers I read on cardiovascular health and function, there's no adverse effects. If anything, there's potential beneficial effects. So, specifically for blood clotting, thrombosis, there's nothing that I'm aware of. No. 


Cynthia Thurlow: [00:14:27] That's certainly reassuring because that there must have been multiple people who have some hematologic issues who were concerned and wanted to know if there's any research suggestive of that. 


Dr. Darren Candow: [00:14:36] I think though, if they're prone to hypertension, which usually leads to potential risk for stroke and things like that, obviously medical clearance is going to be huge because they could be on a statin or any other type of medication that doesn't normally interfere with bioavailability of creatine or vice versa. But we always like to have medical clearance for sure when they have a preexisting condition. 


Cynthia Thurlow: [00:14:57] No. And what's interesting is you had a really nice segue into a question someone asked, does supplementation with creatine lead to hypertension or lead to high blood pressure? And I think a very reassuring message we want to make sure we send. If you have chronic health conditions, if you have a specific concern, please talk to your healthcare provider, prescribing provider to make sure this is the right decision for you. For most other individuals it sounds like it's very, very safe. I know that we addressed this in our last conversation, but again, lots of questions about safety and efficacy with teenagers. Obviously, my teenagers take it and do really well with it, but any specific research about teenagers, young adults in terms of efficacy? 


Dr. Darren Candow: [00:15:35] Yeah, it seems to be the small body of research. It's very effective for performing agility and performance measures, which we're very accustomed to with creatine. No adverse effects from a subjective standpoint, such as-- doesn't lead to an increase in GI tract irritation, cramping, nausea, things like that. The two good colleagues in the United States I mentioned in last podcast, they are finally looking at blood biomarkers to look at these individuals who are younger in stature and age to see if creatine at recommended dose just have any adverse effects on the development of the kidneys or liver or any other areas that we just don't see in adults or even older adults. My guess is a small dose will certainly be tolerated. Again, it's just three amino acids that our body recognizes. If it doesn't recognize something, we always excrete it.


[00:16:19] And I think it's no different than protein, it’s not going to have any detrimental effects and guess why would creatine. A lot of people think it has steroid like principles because it works. But when you look at the molecular structure, it's identifiable by the body. It's a bunch of carbons and nitrogen and hydrogen and very similar to a protein, is made of three amino acids unlike 20 and comes into our vital organs. And when the renal and hepatic system, liver and kidneys say “Hey I don't need you anymore,” you go to the bathroom and that's kind of what happens. So, I don't expect to see any detrimental effects, but it'll be very interesting to get that data out there. 


Ben Azadi: [00:16:54] Another question I had was, you know, we talked about things that could interfere with creatine effectiveness. Is there anything that can potentiate it? And you know, maybe kind of two questions with that one we talked about like essential amino acids. One of the things that I always wonder is whenever we isolate something comes from a whole food is, are we missing out on any benefit of what would have been being consumed with it in its whole food form. So maybe in the terms of what you could get naturally in a food, is there anything that potentiates it and then aside from that, is there any other ingredients that you could take? Whether it's another something you'd find in a pre-workout or something you could take alongside of it that would potentiate it? 


Dr. Darren Candow: [00:17:28] Yeah, it's an excellent two-part question. Let's start with the individual ingredients because it's pretty clear. So, there's two things that really seem to augment or increase some of the effectiveness of creatine. At least getting into the muscle. Let's focus on muscle. One by far is the insulin or carbohydrate. So, I know that's a faux pas for pretty much anybody on the planet, when you say carbohydrates, we immediately think of sugar. And I say, “Well wait, what about fruits and vegetables and other things that we don't really classify” but high glycemic carbohydrates, simple sugars will spike insulin and that has been shown time after time to increase the amount of creatine getting into the cell. The downfall is a lot of the high glycemic carbohydrates are really unhealthy and/or the amount you would need to consume is considered super physiological.


[00:18:12] So, a lot of people say, “I don't like simple sugars.” We know the toxicity and it's just a bad habit to get into. Is there anything else that you can take. And I say, “Yes, there is. Luckily there is, called protein and primarily whey, which is very insulin genetic and gluconeogenic [unintelligible [00:18:26].” So, if you were to combine creatine with a protein, I would guess casein and other ones like that would do it. That will stimulate insulin and allow maybe creatine to get into the cell as well. And plus, you get the plethora of benefits by taking in protein. So that's what I would recommend from a food ingredient. We'll come back to probably the better one at the very end. It has nothing to do with food, but from a food product. I totally agree. Always emphasize food first. 


[00:18:53] So, let's take for example, I'm going to take whey protein and creatine, great. But I'm like, what if you chose the salmon steak, you got omega 3s, calcium, vitamin D, some minor carbohydrates, you get all the potential vitamins and minerals, really high-quality protein and creatine. And you got to enjoy eating. You got to enjoy it with friends and family and you embrace what humans were kind of meant to do. So, food first, because you're also probably going to have a salad and other things with the meal which could provide that food matrix. Relying always on supplements can be difficult. They're very convenient. But in today's society, it might be a little bit easier to get us through your food. So that's sort of where I look at it, food first. 


[00:19:34] But if you're looking at a quick shake or something after a workout, that's easy to do. And then of course, you can put your creatine and Greek yogurt and you get all benefits. But the other big one that a lot of people don't realize is that exercise will stimulate your muscles to open these doorways to allow creatine in. So, if you were to take creatine postexercise, that's a really viable strategy that can be probably shown to increase creatine uptake into the body. The timing of creatine is probably irrelevant, but it's been shown many times that if you exercise, then take creatine either before or after your workout, those transport kinetics seem to be turned on. So, going back to the creatine-caffeine dilemma, I think most of us take caffeine before we work out to wake up. Well, that's great. 


[00:20:17] Now you can take your creatine later on at supper whenever you want. They don't necessarily have to be taken together if you don't want. So, I think there's some very viable, easy ways to do that. And the other alternative is maybe you don't like taking creatine as a supplement, but you're going to have supper later on, you're going to respond three, four hours later, maybe chicken, seafood, whatever it is. Now, if you're a vegan, it gets a little bit more tricky where you might have to consider a supplement.


Cynthia Thurlow: [00:20:45] Next is focused on my niche, perimenopause and menopause. And so, lots of questions again about bone health. This is from Susan. She said, “I have osteoporosis. I'm doing all the right things, strength training, heavy walking, good nutrition, bioidenticals, calcium. I want to avoid bisphosphates. Can creatine help with bone health?” I think the answer is yes. Has there been any research comparing creatine to some of the pharmaceutical agents or-- 


Dr. Darren Candow: [00:21:10] No, there hasn't. We had some individuals with low bone mass in our long-term study. But to be diagnosed with osteoporosis or God forbid severe osteoporosis and frailty, we did not and that's kind of where we're hoping to go next in some of these institutionalized individuals. It was shown to preserve the skeleton in what we consider healthy postmenopausal females. We don't know the effect it would have on osteoporotic females. Our hope is maybe it would have some, if it does great beneficial effect, it won't compare to a bisphosphonate or any pharmacological intervention. So, although creatine preserves some measures in the skeleton, bisphosphonates are a pharmacological intervention. Please don't stop taking those. They're medically prescribed. Creatine might just be a small adjunct to exercise.


Cynthia Thurlow: [00:21:57] Yeah, the unfortunate thing, and whether or not listeners know that there's some potentially really severe side effects from taking those drugs. They don't actually produce strong bone. And the mandibular necrosis is the thing that, so many of us as clinicians are genuinely concerned about it. But again, don't stop any medications. Talk to your healthcare practitioner about that. 


Dr. Darren Candow: [00:22:17] Certainly not making any suggestions to stop any medication from medical-- Because we don't know what other conditions-- They might have osteosarcopenia, diabetes, high blood pressure. For those watching, if the doctors prescribed you something, please take it. But maybe you might ask them about proper nutrition or exercise or sleep, things like that, that can help. Again, a supplement is designed to usually overcome a deficiency, but there's some compounds that can actually augment some things in the body and creatine is like one of five that seems to be beneficial over time. 


Cynthia Thurlow: [00:22:50] It's interesting because what I'm starting to see, at least clinically, is the women that are on estradiol and testosterone and progesterone are the ones that tend to even if they have some degree of osteopenia and really when you're comparing a 20-year-old’s bone to a 50-year-old’s bone, I mean of course you're going to have less bone mass than a 20-year-old. But for many individuals, being on HRT seems to be one of the biggest predictors of healthier bone mass. Any recommendations? Do you feel like younger women can get away with. I would imagine they eat a lot less protein to trigger muscle protein synthesis versus older women who are going to need more protein for that same threshold. Does the same thing apply to creatine? Are there differences in terms of a younger woman's needs versus an older woman's needs?


Dr. Darren Candow: [00:23:32] Yeah, that's an excellent question. And so, if we start with the protein, there's theory of this anabolic resistance. So, Chris would be the youngest here on the screen, I'm assuming and he's going to need a lot smaller dose of protein compared to me to get the same response. So, he might respond 20, 25 g. I'm 46 years of age I'd probably need about 40 to 45 to get the same relative effect. So, he's high fiving himself. He's like, “Geez, I just don't need as much protein, I don't need to spend as much money.” When it comes to creatine, we have proposed this idea on the last long-term study in postmenopausal women. That's why we gave 0.14 g. We didn't see previously an increase in muscle mass or even an increase in strength. 


[00:24:13] So, logically we thought, “Wow, if there's anabolic resistance to protein, maybe there's anabolic resistance to creatine.” And there's been a few studies to suggest that creatine kinetics in the aging population is impaired primarily in the lower body. So, if creatine kinetics is impaired or the ability to take creatine and sort of utilize it for high energy phosphate kinetics, maybe they need more. And lo and behold, when we gave that higher dose in postmenopausal females, it did improve lean tissue mass. Whereas in our previous study at 0.1 g, it did not. So, indirectly suggesting a little bit more might have been needed. Now, we also did an additional year of weight training.


[00:24:49] So, what has to happen is we now need to compare younger females versus middle age to older individuals, different dosages of creatine, that would probably take about four to six different studies. It's been in the back of my mind for a long period of time. I would speculate if we're anabolic resistant to protein, we're probably anabolic resistant to creatine. And that's maybe why older individuals respond so well when they take a supplement in addition to their diet. They seem to respond favorably. So that's an excellent question, still needs to be done. But my speculation is there's some level of validity to that, yeah. 


Cynthia Thurlow: [00:25:27] Definitely makes sense. And then there were a lot of questions that came about. Is there an age limit to supplementation with creatine? And this is specific to probably parents in my age range, my parents who are in their 70s and 80s I'm assuming if we're dealing with anabolic resistance to creatine, I mean all these things sarcopenia, etc., it's probably safe again in the context of broad generalizations. If you are on medications or you need to check with your doctor or your nurse practitioner, please do. But in terms of age, there are no other any age-related limits that you've discovered or researched?


Dr. Darren Candow: [00:26:03] Yeah, no. We've had people in their 70s and 80s and I guess you could also argue it's probably more important in the seventh, eighth and ninth decade when the muscle is being atrophied, bone is being decreased. This is where creatine can maybe even help even more in combination with exercise. So that's kind of the population we need to look at, those with cachexia or frailty or assisted devices for walking, that's the area we think would be more clinically important. We've done some rehabilitation work with stroke victims, very small sample size, but it did improve their ability to walk compared to placebo. So that has a huge rehabilitation perspective. But I think as we get older, 8th decade, 9th centurions, these are the individuals where we think you might even get any beneficial effect. 


[00:26:44] And again, it's never too late to start exercising, it's never too late to eat properly. And if we can get it through diet, great. But as we get older, impairments in chewing and taste and financially to afford all these expensive foods, there's a lot of issues we have to look at, but there's no reason to suggest someone who's 100 can't take creatine and maybe get a little bit beneficial effect. 


[music]


Cynthia Thurlow: [00:27:06] Good morning, Dr. Candow. It's so nice to have you here. I've been really looking forward to this conversation, largely because I think in many ways creatine is so misunderstood. I know that I probably even had my own misgivings until I really dove into the research. And so, let's start the conversation talking about some of the less known benefits. I think many people think about creatine in the respect that they understand the metabolic health benefits, they understand the improvement in strength and muscle conditioning. But in particular, in our conversations before we started recording, really understanding that there's so much to creatine that I think most people don't understand in terms of conferred benefits.


[00:27:46] And specific to my listeners, most of whom are middle-aged women that are in perimenopause and menopause, what is some of the new kind of relevant research about bone health in particular? Because I think there are so many women that are not appropriate candidates for hormone replacement therapy, maybe they're breast cancer survivors. And understanding that there can be a conferred improvement in bone health and bone quality with the utilization of creativity. 


Dr. Darren Candow: [00:28:14] Yeah, I think you hit the nail on the head. I think that would probably be the number one hidden area that a lot of people didn't expect, especially for female health. I think most people that are familiar with creatine would think of it for athletes getting bigger, stronger, faster. And there's been a lot of emerging research probably in the last two to three decades at most. So, it's not that new, but it is emerging, showing that females across the entire lifespan, so to speak, can get substantial benefits. And as you point out, the hidden factor esults were kind of around bone health. Creatine was designed for muscle health, as we all know. And if we can put on muscle mass, we get bigger, stronger, faster and improve a lot of aspects of our life. 


[00:28:57] But lo and behold, under the muscle there's a really precious tissue that we often don't think of because we can't really see it in the mirror. And that's bone health and bone strength. And as you are alluded to pre-menopause, the menopausal transition, and then we get into the really critical stage of post menopause, the cessation of the last menstrual cycle up until the basically the day you die. And that's really important because the cessation of estrogen decrease that anabolic capability of estrogen. So, we kind of have to come up with lifestyle interventions to replace it. And there's only been a few studies that have actually looked at creating directly on measures of bone health. The vast majority have focused on postmenopausal females. 


[00:29:38] That's probably because they're more susceptible to bone-related diseases such as osteopenia or osteoporosis, and then, God forbid, frailty and fracture later on. And we've done a series of studies and some colleagues in Brazil have done a series of studies as well. And it's very clear with the minimal amount of research, I should preface that. Creatine without exercise probably won't have any beneficial effects on the skeleton. The skeleton really seems to respond just like muscle to mechanical stimuli such as weightlifting or plyometrics or even running. But it seems to have some beneficial effects, primarily in postmenopausal females when combined with exercise, the primary stimulus would be weight training but we did perform a long-term study with walking. And overall, collectively, creatine seems to preserve some aspects of bone mineral or bone strength around the hip region. 


[00:30:33] It seems to improve lower limb below the knee bone area. And those two factors could have huge implications for offsetting the risk of fracture later on in life or withstanding a fall. Most people are living in climates where winter is coming with icy roads. And if you were to fall, most young individuals can bounce back up. They might be embarrassed, but they didn't fracture a bone. Unfortunately, some older individuals suffer hip fracture or ankle fractures, which are very susceptible for osteoporosis. And of course, if you fracture, you are not performing activities of daily living or physical activity and that could lead to a lot of chronic diseases. And so, we can talk about some smaller research or the long-term study, which we did in a large cohort of postmenopausal females. But overall, it seems to have some extra benefit in addition to exercise. 


Cynthia Thurlow: [00:31:26] And I think that's really encouraging because you're bringing up a very important distinction. We know that the lack of physical activity is a prognostic indicator, if you will, for metabolic health. And that's certainly a topic that we speak about with great frequency on this podcast. So, understanding that it isn't just enough to take the creatine, you have to take the creatine and move your body. And I think that larger two-year study that I was reading about was speaking about just the process of walking, like ambulation. And how important that can be in getting some of these conferred benefits. And so, let's start there and then we can talk about some of these other smaller studies because I'm sure there are people listening that are thinking, “Oh, this is a great example I can just take the creatine and I don't have to do the exercise.” And that's not what we're saying. The creatine plus exercise is where you get the conferred benefit. 


Dr. Darren Candow: [00:32:17] Yeah, it's so crucial. So, I think a lot of people are always trying to look at a magical pill or powder to sort of save everything about them. And at the end of the day, nothing will replace exercise. I think we can all agree with that. So, exercise is foundational. And then a nutritional supplement such as creatine in this case can provide some small but beneficial effects. So, in summary, the study that you're talking about, we put postmenopausal females, now these were postmenopausal for 24 months. We wanted totally make sure that they were really completely in their postmenopausal stage. The average age was 59 years of age and they were healthy enough to participate in exercise. 


[00:32:59] And we were really fortunate to finally publish a paper that was adequately sample sized. But we were very fortunate. We got funding from the federal government here in Canada to look at the effects of two years of exercise. Now, the exercise protocol was three days of supervised weight training, the whole-body routine, and then six days of walking. And the reason we did that is here in Canada, and I believe the same as in the United States, we're trying to promote physical activity specifically. So, here in Canada, we're advising 150 minutes of physical activity from an aerobic type of standpoint per day and then at least two days of resistance training. So, we sort of adhere to those recommendations with the study. And then we wanted to look at creatine supplementation over time. Now, the dose we gave was a little bit different than what's typically recommended. 


[00:33:50] We've done some preliminary data showing that creatine had some potential and some small favorable effects in postmenopausal females at a higher dose than what's typically given with muscle. But theory here is that as we get older and we're having natural bone loss, maybe we might need more to overcome or sort of compensate for the natural age-related reduction in bone. So, typically with muscle, most people hear about 3 to 5 g a day and I have no issues with that from a muscle perspective. But when you look at the totality of bone research, the lowest dose that seems to be effective for postmenopausal females is at least 8 g. So, we started to see some trends and we thought, why not give a bit more and again, creatine is extremely safe, so giving a bit more should not cause any adverse effects. 


[00:34:41] So, we gave on average 11 g a day-- And this is important, creatine monohydrate, 11 g a day for two straight years. So, it was the longest trial in the world to combine creatine and exercise. And when we did a whole gamut of assessments, we saw that the females on creatine, they had a preservation of bone strength around the area of the hip, and they actually had some indication that the strength of the bone was stronger compared to the females that were on placebo. Now, this is an interesting fact. Even two years of weight training wasn't enough in this large cohort of postmenopausal females. And we actually assessed about 174 to offset the negative effects of exercise. So, some people might say “Why didn't you use a group that did nothing?”


[00:35:31] Well, ethically and morally I would hate to just say, “Hey, volunteer for the study, and we're not going to really do or give you any beneficial effects.” So, exercise was beneficial from performing some activities of daily living, but it wasn't enough or in relation to creatine, have the same effect. So, at the end of the day, we concluded that two years of creatine and resistance training provided small but yet very beneficial effects to the integrity of the skeleton, primarily around the hip region. And that might have huge implications for offsetting fracture later on in life. And just as important, we measured kidney and liver function to measure side effects. And for two years at a really high dose, there was no greater effects than placebo. And most people might be surprised by that. 


[00:36:18] But realistically, when you look at all the evidence-based research, creatine essentially is a nitrogen-containing compound. It's very similar to protein. We naturally produce it in the liver and the brain, and when you consume it in foods such as red meat and seafood, it gets processed very easily. So, it kind of makes sense the body would recognize it and if there was any excess amounts, it would simply be excreted or converted to a byproduct in the urine. So that's probably why we don't see hardly any side effects whatsoever from a liver or kidney aspect even at high dosages. So, it was a foundational study leading into the thought, now what do we do with premenopausal females, females going through the transitional phase. And what about young females? Can we increase or strengthen the bone at the younger age and maybe that'll offset osteoporosis later on in life? So, it's sort of opened the door for a lot of potential research. 


Cynthia Thurlow: [00:37:10] I know you had mentioned that there was some other smaller bits of research that have been done in Brazil. What were some of their findings with regard to the utilization of creatine and bone health as well?


Dr. Darren Candow: [00:37:20] Yeah, my colleagues in Brazil, who I think are probably the best overall group of creatine researchers, they did some really exceptional studies and they looked at a very low dose of creatine. So, this was quite different. They looked at 1 g a day, and then they moved it up to 3 g a day, all the way up to two years. So, the same duration of a study, but they did not include structured exercise. And what they found was basically nothing. [Cynthia laughs] 1 g in 3 g without structured physical activity had no beneficial effect. Of course, it had no detrimental effect, but had no beneficial effect compared to placebo. So, in other words, taking creatine, kind of like a vitamin pill you would do in the morning and going about your activities of day living, will probably not cause any significant effects. 


[00:38:05] We conclude that exercise has to be there. It has to be foundational. And for the young females that are watching that are hesitant to perform resistance training, please understand that huge benefits you get from weight training, it sort of does everything that cardio will do, and then you get the extra benefits from strength and functionality. So again, exercise has to be there and creatine may cause a small beneficial effect. But please just don't take creatine and expect bone benefits. We don't see any evidence to suggest that whatsoever. 


Cynthia Thurlow: [00:38:37] Yeah, I think it's really important for people to understand it. And certainly, a lot of guests have talked about the antiquated RDA here in the United States and that RDA was designed to be the minimal amount so you don't die. 


Dr. Darren Candow: [00:38:50] [laughs] exactly. 


Cynthia Thurlow: [00:38:50] And so, if you think about it from that perspective, I find most, if not all, men and women grossly undereat protein and it contributes to this lack of satiety. It impacts metabolic health. And so, thank you again for kind of weaving that in because that's a very important message. Now, relevant and timely, as I was preparing for this podcast, my husband and I just came back from a trip and we are dealing with jet lag, and I stumbled into some of your work looking at the role of brain stress and creatine, jet lag and creatine. 


[00:39:24] And I'm not exaggerating, from the time that I started down that rabbit hole, I started really increasing the amount of creatine. I normally take anywhere from 3 to 5 g a day. And I was doing 10 and 15 g for three days just to help get over that hump of jet lag. And it was amazing to see and to experience the lessening of that jet lag. And I struggle more going East than I do coming West. And so, let's talk about the impact of creatine in the brain. I think many people may be surprised to know the brain actually makes creatine. It's not something that's just arbitrarily created in other parts of the body. But let's talk about some of the unique properties of our brain, the blood-brain barrier, how creatine can improve brain health, cognition, memory, etc. 


Dr. Darren Candow: [00:40:11] Yeah, I echo your statements. I think you were just in Venice, Italy, and that's the same. So, there's probably been the last decade, if you will, the hottest area to focus on is the neck up. And we put out a seminal paper this year exactly titled that, because it's been emerging that we now know that the liver easily will make creatine or we take it through the diet. But a lot of people didn't realize that the brain is very unique and it also can make its own creatine. The brain, very similar to muscle, uses creatine in a bioenergetic pathway. If the muscle uses creatine to maintain its energy levels, so to speak, the brain does it more often than not. And let's be honest with today's society, stress, sleep deprivation, many hours of working, the brain is more metabolically taxed. 


[00:40:59] And so the theory was, wow, what if creatine could have some impact or potential for improving brain health or function? And when we started to look closely at the data, individuals who are born with creatine deficiencies, that means they were born with a genetic mutation where they can't make creatine. We look at concussion, we looked at individuals with depression and anxiety. And then we looked at some neurological conditions, such as Parkinson's, and they all had a sort of a common denominator. They had a reduction in brain creatine stores compared to healthy individuals. And so, the theory here, just like muscle, well, if they had reduction or reduced phosphocreatine levels, what if we gave a creatine supplement, could that overcome some of the decrements and could it actually increase brain creatine stores? 


[00:41:45] And some exceptional researchers in Norway have a special type of technology and they certainly measured this and again, my colleagues in Brazil, that when you give creatine supplementation, it can increase brain creatine stores. Could that correlate to improvements in memory, cognition, decreasing sleep deprivation? Well, some preliminary data is starting to emerge showing there is some potential. So, let's put it in some categories. Creatine can increase brain creatine levels, but as you mentioned, it's up against sort of a struggle. Unlike muscle, the brain has a barrier called the blood-brain barrier. It's very picky to what it lets in. Now you would argue, well, creatine is good for the body. Why wouldn't it allow all the creatine in? It does let it in a little bit, but not nearly as much as muscle way more than probably a reduction in half.


[00:42:36] And that's probably because the brain makes its own creatine. So, it doesn't want to let a whole bunch of something in to take up a lot of space when it already has enough. So, there's two things that are going against brain creatine compared to muscle. One, the blubbering barrier is very selective. It sort of blunts a creatine uptake from the blood. And of course, if it makes its own creatine, it has its own store. Muscle does not make creatine. So, if we can get it into the brain, and it usually takes higher dosages, even probably higher than bone, to eventually accumulate. So, the first thing is it probably needs higher dosages and longer periods of time to accumulate because 95% of the creatine we ingest goes to our muscles. 


[00:43:17] So, you're only going to have a trickle amount going up and accumulating in the brain. And then secondly, it only seems to work under metabolic or specific examples. So new research is suggesting that if you're a young, healthy individual, you don't have a lot of sleep deprivation, you feel great. Creatine is probably not going to have any cognitive benefits. However, if you take a population in hypoxia, sleep deprivation, I would put jet lag up there for sure. Everybody seems to be so metabolically stressed. I think there's application for creatine to have some cognitive benefits. We see benefits from post-concussion syndrome in children. It seems that creatine can speed up some of the recovery aspects as well. And we're also seeing some potential in individuals with muscular dystrophy. The other big hot area is depression and anxiety, which is hugely prevalent.


[00:44:11] And I haven't seen the latest data from COVID but my guess is COVID has really caused a lot of depressive and anxiety type of symptoms. And in a few studies where individuals were still on their medication, which is really important, creatine seem to decrease some of the depressive symptoms. So, collectively there's a lot of potential, but it seems to be focused on a population base that is very metabolically stressed or what we consider a special population. I think if you're taking creatine and you're healthy and you don't have any depressive symptoms or anxiety and you feel great, it may not have any noticeable effects, it certainly won't have any detrimental effects and that's important. If you're thinking, will creatine hinder? We're not seeing any evidence across any study having any negative effects. So, there's a lot of potential and we can isolate and talk about each one. I know the concussion one is a huge one. 


Cynthia Thurlow: [00:45:06] And it's interesting to me because especially we're out of the crush of the pandemic for the last several years and a lot of my colleagues talking about long haul COVID symptoms and any number of these things are really speaking to mitochondrial dysfunction to some degree or another. And so, it makes sense that if we're taking exogenous creatine, that it could beneficial. So, you mentioned and I know for many listeners, we got hundreds of questions about creatine. So, people were very excited about our conversation. Some of the questions centered around people that have suffered concussions or mild traumatic brain injuries, adults and children. What is the research showing in terms of dosage? And you've already alluded to the fact we need more for these brain benefits. What are the dosages that are being utilized in some of these research studies? 


Dr. Darren Candow: [00:45:55] Yes, so ironically, that there's only been a single study in two parts looking at specifically in concussion. Now there is rodent studies that have shown that if you give a rodent creatine before they are surgically induced with concussion, you can have benefits, but obviously to a living human, you can't do that. And unfortunately, the only way we can determine this is, sadly, when someone does suffer TPI or a concussion, then we look at the effects of creatine versus placebo. So, the only study was done in young children when they suffered a traumatic brain injury and/or diagnosed with a concussion. They were immediately randomized to about 0.4 g/kg, well, high dose again, they're a lot smaller in size of creatine or placebo. And then they measure some subjective outcomes for up to about six months. 


[00:46:44] And I believe they actually have some data to a year. And some of the improvements that were looked at was improvement in speech, self-care, reduction in headaches. So overall it was a subjective improvement in their ability to perform activities of daily living. They didn't really look at any brain biology markers. The theory though, from some cellular data is that if creatine does have some potential effects, to your point, it's reducing inflammation and some improvements in the mitochondria to alleviate some of those reactive oxidative species or decrease inflammation. The other theory is maybe it increases brain creatine content to improve cellular bioenergetics. So those are the two proposed main family of areas, but that's all we have.


[00:47:32] The difficulty is randomizing individuals before they suffer a concussion because ethically, you're like, “Oh God, we don't want anybody to suffer any head trauma.” But to really sort of determine this, you would have to take two groups of healthy individuals, randomize them before they get a concussion, and then see the effects. Most people are probably taking concussion. Most people here in the United States, think of football players, while most individuals, if you're already on creatine, there's going to be a washout phase in the brain. It's probably about five weeks, all the way up to 90 days. So, there's a lot of issues and that's probably why we don't really have a lot of data. So, caution is advised, but we're not seeing any reason why an individual who are prone to head trauma would not potentially experience some benefits.


Cynthia Thurlow: [00:48:23] Yeah, it's interesting. We lived in the Washington, D.C. area for a very long time and one of the local hospitals actually offered a pre-concussion evaluation. Like if your child were to get a concussion, we would have an established baseline. And because at that time my kids were playing flag football and lacrosse, we got baseline. Thankfully we never needed to use that information, but many of my friends whose kids were playing soccer and tackle football and lacrosse for that matter, that their kids had multiple concussions before the age of 12. And it's my understanding from my own reading that's a significant metric that if you have multiple concussions before the age of 12, when the brain is still growing, it's much more significant than, God forbid, either you or I or an adult listener falls and has a concussion.


Dr. Darren Candow: [00:49:11] And the other big issue here is the dosage. So, I have a presentation coming up in October trying to look at the three main tissues, muscle, bone and brain. And does each tissue determine a different dosage? Which would be impossible to do from a practicality standpoint. But when you look at the series of studies, the majority have used 20 g a day and that seems to be a dose that has the most validity behind its effectiveness. So, if we backtrack from muscle, maybe 3 to 5 g is a very viable source from a bone directly we're seeing 8 to 11. And now the brain probably requires more. So, people say, “Well geez, what if I want to take it for everything?” I personally take about 10 g a day. 


[00:49:56] But if someone says I don't care about my brain or bone, 3 to 6 g is plenty, that will saturate the muscle but then if you get into someone might wanting a little bit more. So, we need to do a lot more dosing studies, especially in the brain. And then regions of the brain are definitely influenced by different traumatic events. So that's another area. So, I think the brain would probably be the focal point probably for the next few decades trying to pinpoint does creatine work across a variety of populations and if it does, which metabolic conditions does it really work? Which doesn't it? Does exercise need to be involved? We're starting to see the neck up. You can get cognitive benefits in a lot of these studies without exercise. 


[00:50:41] But one would argue, geez, an increase in brain blood flow, exercise, you get all the endorphins, dopamine, can that be a synergistic effect? So, there's a lot more clinical research with large populations is desperately needed. These studies that have looked at brain function have a really, really low sample size. So, we need to have a lot more research with long term studies before we can totally say creatine is going to offset depression and Parkinson's. Again, we need a lot more research. So, a caution is advised. But there's a lot of potential. 


Cynthia Thurlow: [00:51:15] Yeah, it's really exciting and just to kind of loop in the sleep deprivation/jet lag piece because I think for many people listening, we're all human beings. We went to a concert last night. We didn't get home till 2 o'clock in the morning. I'm working on about five hours’ worth of sleep. You better believe I was bumping up my creatine dosing. So, based on your experiences when people are traveling, are you suggesting that they utilize creatine to help with traveling to an alternate destination and traveling home. So, they're using it throughout their vacation or their trip to help bolster some of the net impact of that time change on our circadian biology? 


Dr. Darren Candow: [00:51:52] Yeah, that's a really good strategy and I would even sort of back it up. So, most individuals know, “Hey, I have a very mentally stressful job and that occurs all year round or I'm typically stressed or sleep deprived.” So, since creatine accumulates and again accumulates very slowly, it's unlike caffeine. My suggestion is to do this on a daily basis. That way, even on your non exercise days, please consider taking creatine because that will help accumulate in these demanding tissues. And during times of short-term episodic acute metabolic stress, a jet lag, whatever it is, that's when it can really help. A few of the studies that have looked specifically at sleep deprivation seem to have some of the best results. So that has some promise there as well. But university students, academics, pretty much everybody I talk to are sleep deprived. 


[00:52:44] I rarely come across someone who say, “Geez, I feel great. I always get enough sleep,” you're right. I sleep sometimes three times a night. I'm waking up all the time and preparing for class or whatever it is. You need to have a lot of mental ability. So, I think a safe strategy is to probably take creatine on a daily basis so that it does accumulate and it's already there present when times of metabolic stress. 


Cynthia Thurlow: [00:53:08] Yeah, it's really interesting and inevitably, because we got hundreds of questions. The number one question that we received, which will not be surprising to you, is what do I do with bloating from creatine? So, some people appear to be more water retention sensitive to creatine irrespective of dose. And so how do you encourage people to either work through that? Because I always believe if someone tells me I use creatine and I gain 5 pounds of water weight, especially if this is someone who weighs themself every single day and is very mentally sensitive to that water weight. What are some of the tips or do people have like different propensities physiologically? Are certain people more prone to water retention with creatine monohydrate than others?


Dr. Darren Candow: [00:53:56] Yeah, it's probably one of the main reasons people are deterred from taking creatine supplementation. So, our skeletal muscles only has a small area for creatine uptake and when creatine enters your muscle it's linked with sodium. So, it will drag water in. So, some people say, “Hey, my muscles appear a little bit larger or fuller.” But the vast majority will cause water fluctuations, if you will, to the body. Some people say they feel a net increase in bloating during the initial phases of creatine supplementation. That is very common. It does subside usually after about a week or so. At the end of the day most people say, I didn't really gain much weight if you take creatine for a long period of time. So, the strategy we typically use is multi point.


[00:54:41] One for those who are susceptible to bloating, please do not do the loading phase. So, the loading phase is recommended typically for athletes or for those who really need a quick rapid accumulation. So, the loading phase is 20 g of creatine a day. And that's usually taken in 4, 5 g dosages throughout the day. We're only synthesizing about 2 g of creatine a day and we may only get about 1 to 2 g through our diet. So that's taken in a quite a heavy amount or an extra amount. So, the loading phase is notorious for causing that rapid bloat or water retention during the first week. So, I would eliminate that totally because you don't need it. 


[00:55:23] What has been shown as little as 3 g a day, so that's probably a half a teaspoon taken every day will saturate your muscles in about 30 days and you can take that dose up to about 5 g a day to maintain that thereafter. So, obviously taking a lot smaller dose will result in a lot less bloat and/or water retention. I would even recommend to take that dose mixed with food. That helps with some of the absorption or some of the effects. So that's the first thing I say. Don't do the loading phase, start with a very low dose, and we usually say 3 g a day is probably the lowest amount. You probably could even divide that into two 1.5 g dosages or three 1 g dosages. Now there's a little bit of caution with the 1 g. 


[00:56:08] A study in 1992 showed that 1 g really had a minimal increase in blood creatine. You kind of need a bit more. So, I think if you're okay with that half a teaspoon, mix it in yogurt or cereal or whatever you want. That's probably going to increase its ability to be taken into the body. Don't mix it with a bunch of sugar, you don't need it. And you can drink it with water or with food. And I think that would help alleviate a lot of the symptoms of bloating or net water retention. Now if you want to get up to those greater dosages we've talked about, you say what do we do now? We've talked about muscle, bone and brain. 


[00:56:44] Well, I would suggest to stay with the 3-g dose and maybe take that in three dosages throughout the day or maybe four 2-g dosages, breakfast, lunch, dinner, late in the afternoon, post workout. So, repeat smaller dosages from an absorption and retention perspective seem to be a bit more logical than taking a 20-g dose all at once or a 10-g dose. So, I like to take my 10-g dose in two 5-g dosages and I change that up all the time. I had 5 g this morning. I sometimes like to put 5 g in a water bottle and drink that during my workout. It doesn't matter when you take it, it accumulates. So, unlike caffeine, which is pre-exercise, you can take creatine whenever you want before you work out, during, wake up in the middle of the night, it really doesn't matter. The timing doesn't really seem to be that important. 


Cynthia Thurlow: [00:57:37] Okay. And this ties into another very popular question was when should I take it for it to be most efficacious. And it sounds like the answer is whenever you can remember to take it. It's not that you have to consume it pre workout, intra workout or post workout, it's really when can you remember to take it consistently. 


Dr. Darren Candow: [00:57:55] It's like what's the best exercise to do? The answer is the one you're going to do. And then when is the best time to take creatine? There is no really best time. However, and this is important, a seminal study showed that muscle contractions seem to turn on transport kinetics of creatine into the muscle. So, the theory here is if I take creatine before I exercise or right after, maybe those transport kinetics, or think of this as doorways into the cell are turned on, that could allow creatine into the muscle quicker. So, prior muscle contractions seem to have a stimulating effect on creatine uptake. So, one area, if someone is very focused on this, I think pre or post exercise would be a very logical and viable strategy.


Cynthia Thurlow: [00:58:42] And is there any interrelationship? Does it have to be consumed with cold beverages, hot beverages? Because the question always comes up, does the creatine somehow get denatured if it's exposed to heat? Sometimes I get these questions and I'm like I don't even know how to begin answering this. So having you on board is very high. I'm like I'm going to ask the expert. 


Dr. Darren Candow: [00:59:02] So, an increase in temperature will increase some of the solubility. A lot of people say “Hey, I mix my creatine is kind of gritty at the bottom of the glass.” If you slightly-- not a lot, slightly warm the temperature, that seems to increase the solubility but it doesn't influence the bioavailability or the amount coming in the blood that actually gets to the cell to do something purposeful. So, some people will put creatine in cold water if they don't want to consume it immediately. A decrease in temperature will preserve the integrity of the molecule or they'll slightly increase the temperature. The only thing I would recommend not doing, and this is based on some mechanistic data and some small scale studies, is to mix it directly with caffeine. So, there's some cellular data that suggests that caffeine and creatine oppose one another. So, mixing it directly in coffee may not be advised for the long term. 


Cynthia Thurlow: [01:00:02] That's really interesting because [Cynthia laughs] there's someone in particular who asked the question who likes to put the creatine in their coffee and so they in particular will really appreciate that response. So, when we're looking at, and this is a very specific, you may or may not have any familiarity with hypermobility or EDS, Ehlers-Danlos syndrome, connective tissue disorders. Is there anything suggestive that individuals that are hypermobile that they have differing needs for creatine utilization? My guess is no, but having said that I was like this is such a nuanced question. 


Dr. Darren Candow: [01:00:39] Yeah, we don't have a lot of data, especially around the connective tissue area or collagen. There have been a few studies looking at creatine prior to and post ACL surgery and it didn't really have much benefit. The thought is could you take creatine and collagen together? Could that have some antiresorptive effects to the bone? And that's something we're considering, but to my knowledge I'm not familiar with any of those specificities with specific diseases. 


Cynthia Thurlow: [01:01:07] Unbelievably that question came up again multiple times. I'm just trying to hit the ones that came up with some regularity. How about safety in teens? For full disclosure, my teenagers both take it. They're also one 6’ tall, one's 5’10”, they love taking creatine. But I didn't read anything suggestive that it's harmful. But of course, there were lots of moms asking. My kids are asking if they can take creatine safely. 


Dr. Darren Candow: [01:01:29] It's a hugely popular and very important question. A lot of individuals are considering it. So, remember you can get a about 1 to 2 g of creatine naturally through the day through red meat or seafood. So, if your child is already ingesting that on a daily basis, they're getting some amount of creatine. However, as it stands right now, the subjective safety of creatine from GI tract irritation to headaches to nausea is nonexistent. In other words, if a child is probably taking creatine at recommended lower dosages compared to placebo, creatine is not causing any subjective adverse events. However, two colleagues of mine in the United States, Chad Kerksick and Andrew Jagim, are now looking at some blood biomarkers finally in children to see does this have the same safety profile as we do in adults and older adults? So that data is coming out. 


[01:02:21] So, right now the totality of evidence suggests that creatine at recommended dosages, and I think 3 to 5 g is a great safe way to look at, don't look at the loading phase or even higher amounts. So, a 3 or 5 g dosage is a really easy way to start. You can take higher, but that's an easy way to look at it from a safety profile. As it stands right now, it's completely safe, but we still need that blood biomarker data there. So, a little bit of caution is still advised. But again, it's very similar to consuming protein, seafood or red meat. It comes in, it kind of resembles the same metabolic pathway. So, taking small recommended dosages, in my opinion, and based on what's currently provided from research, is very safe and viable. 


Cynthia Thurlow: [01:03:07] Yeah, I think it's always safe to always say with an abundance of caution when you're trying to grow a human or a human for sure. [Dr. Candow laughs] Let's kind of round things out talking a bit about fat loss and resistance training and how creatine monohydrate can fit into that picture. 


Dr. Darren Candow: [01:03:24] So, a lot of exercising individuals are a little worried about creatine because not only did they think it increased body mass, but they felt bigger. So, they thought, “Oh, I increased fat mass.” And we published a paper a few years ago looking at the effects of creatine and resistance training on measures of body fat in adults 15 and above. And when you combine the two, creatine actually reduced body fat percentage by a very, very small amount. In other words, it did not increase fat mass. And we actually submitted a paper yesterday looking at adults 49 and lower and we saw the exact same results that the combination of creatine and resistance training reduced body fat percentage by a very small amount, about 1%, which is probably clinically or practically insignificant. But the cool thing is we didn't see an increase. 


[01:04:15] So, when people are hesitant, we're not seeing any experimental data showing that creatine increases fat mass. At the best, we say there's no effect or you may experience a very, very small beneficial effect. But overall, it seems to have a positive effect somewhere. We probably think the increase in muscle mass is driving energy expenditure, which might help burn a little bit of calories from fat. 


Cynthia Thurlow: [01:04:40] Yeah. It's really interesting that there are persistent themes in our conversation. A lot of it is strength training is important, protein is important. Making sure you're strategically utilizing ergogenic aids or supplements if you are using them within your continuum. Is there anything that we didn't touch on today with regard to recent irrelevant research that you think would be applicable for the everyday wellness community? I guess, targeted about our conversation to be respectful of your time and I'm not exaggerating. I could probably do two or three AMAs, just about with all the creatine questions that I received, which is a testament to the interest people have in the supplement. 


Dr. Darren Candow: [01:05:20] I think the other area that gets no press is the aerobically trained or cardiovascular trained individuals, the runners, Ironman, triathlons, cyclists. I mean, creatine was designed to improve what they call anaerobic energy. So, really intense weightlifting, multiple sprints. But there's a lot of interesting data coming out now. It has a lot of benefits from recovery and/or some performance benefits for soccer and swimming and sports like that. And the other big thing is they started to look at some proteins that are indications of inflammation. I think a lot of people take Advil or Tylenol for inflammation, but creatine seemed to reduce inflammatory markers post long duration aerobic exercise such as triathlon or Ironman. So, if you're training for a marathon or going, you love long distance aerobic exercise and you typically suffer inflammation or soreness. Taking creatine beforehand seem to reduce these things called cytokines or markers of inflammation. 


[01:06:19] So, we got to give a little bit of love to the aerobically trained individuals out there that I think creatine can have some applications for recovery and maybe the potential for some performance in certain types of sports of intermittent activity. I think soccer and swimming come to mind there. 


Cynthia Thurlow: [01:06:35] Yeah. Did you see more differences between genders? Because I think one of the things I was reading was that it seemed like it was more anti-inflammatory for men versus women, which I know women were a little more complicated with menstrual cycles etc., but anything that you were seeing that was specific, like gender slanted in terms of what the research was showing? 


Dr. Darren Candow: [01:06:54] That's a great question. So, from an anti-inflammatory inflammatory perspective, there wasn't any gender differences across spectrums. However, from anti-muscle catabolic perspective. So, what I mean by this is most people are familiar with protein synthesis, the main pathway that helps get bigger stronger muscles, but just as important is reducing protein breakdown from a long-term perspective. So, we've done a study and a good colleague of mine at McMaster University have done a study looking at indicators of muscle protein breakdown and for some reason males had a reduction in protein breakdown compared to no effect or a slight reduction in females. We have no clue, why that is the only logical theory both population groups were premenopausal, so maybe estrogen had some effect, but at the end of the day maybe males have more of anticatabolic effect. 


[01:07:49] In other words, they might recover from a weight training session a little bit quicker than females. Is the recovery rate that different? I highly doubt it. Males and females respond exceptionally well to creatine and exercise. But there is a few studies to show that muscle protein breakdown was reduced in males compared to females on creatine. But that's certainly an area for more discovery. 


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Cynthia Thurlow: [01:08:14] This is a question from Liz. “I've been taking your brand of creatine for a few weeks now. I'm a recovered vegan, was vegan for 12 years. I strength trained three to four days a week and fast on average 16 to 20 hours a day. I'm 52. When is the best time to take creatine and does it break a fast?” I've done two podcasts on creatine. We will make sure we link the creatine podcast so that you'll have them as a resource with this podcast. Typically, you want to take it in a feeding window. Depending on who you talk to, some people feel like you need to take it immediately after exercise. I think it's just if you're intermittent fasting, the most important thing you can do is make sure you're getting enough protein in a very tight feeding window. 


[01:08:51] If you have a four-hour or six-hour feeding window, I always get concerned that you're not going to be eating enough protein. So, creatine in your feeding window is absolutely fine. “Is it true that it can cause some bloating and weight gain?” I think this is very bio-individual. I'll be honest with you. We occasionally will field questions or concerns from people that'll say, “Oh, I think I'm gaining water weight.” And then when they stop, they lose the water weight. But creatine monohydrate, you hear that word, hydrate, it's hydrating those muscles. So, what it is water weight gain. Some people do need to divide their doses. I think a lot of it really just depends on the individual. 


[01:09:24] But I found for me, it has allowed me to not only lift heavier in the gym, which I think is important, but it has also helped with sleep architecture. On the days that I remember to take creatine, I try every day, but some days I don't, I always sleep better. So, it definitely helps with the sleep architecture. And we know that creatine also has other net impact. There's a podcast with Dr. Darren Candow that'll be out later this week, which again will precede this podcast coming out. And he talks about the research on brain stress, traumatic brain injuries, jet lag, sleep deprivation, bone health. These are other research that's coming out that's showing that creatine is one of the safest, most efficacious supplements that's out there. And I think you don't know until you try the product. 


[01:10:07] So, that would be my best recommendation is just see how you feel with it. For me, my entire family takes creatine, my teenagers, my husband. And what's interesting is Dr. Candow talks about one particular research that was done. It was a randomized controlled trial of menopausal women not on HRT. So, they were within the first two years of menopause without HRT, so that they could have a real sense of like, where their bone health was. And for two years, the control side took creatine every day and exercised. And what's interesting is none of them had-- with 10 g a day of creatine. So, my creatine, the current dose is 3 g. We recommend 5 g for people that are vegetarian, vegan, or men. So, for women, 3 g is the minimum. 


[01:10:47] These women were taking 10 g a day for two years with no issues related to liver or renal function. And so, when people express concerns about hydration with creatine or potentially having health issues, the research doesn't support that. So, please don't let that be a concern. But I would say creatine in the feeding window is always what we're aiming for.


[01:11:08] Next question is from Reena. “Can your creatine denature when added to hot food like soup, stew or curry?” You know, it's interesting. I've asked this question of a couple people now. Darren Candow, who's the researcher, doesn't love creatine in hot food. He does feel like it has the potential to impact the efficacy of the creatine. He said that it's not as if it would blunt all of it, but he prefers that it's in either room temperature or cold water. that's just a thought.


[01:11:37] Other question, “Is creatine beneficial at any time, not just being centered in workouts and strength training?” Yes. And definitely reference that podcast that I did with Dr. Candow, which will be out on October 4, which again will precede this coming out. This will be out in October. Next question is from Karen. “I take your creatine, but many sources seem to caution about hydration when taking it. I work out but not every day. Should this only be taken on workout days?” Karen, as I mentioned, I have just interviewed Darren and based on all the research and this is his area of expertise. There's nothing to suggest that creatine is at all potentially damaging to liver or kidney function at all. I think that taking it daily is probably the best way to take it. 


[01:12:18] Even though sometimes, probably five days out of seven I take it. Lot of it has to do with how busy my morning is just for full transparency. But I do think that there's value in taking it daily. And what's interesting is when I spoke with Darren, he mentioned that if you take creatine and you don't exercise like, let's say you're a couch potato, but you take creatine for the benefits. You don't get the benefits. Like you actually need to be exercising with some consistency to get the most benefits out of creatine. That doesn't mean that if you take a day off that you shouldn't take it. But if you are sedentary for six months, and you think taking creatine is going to offset that, that's not going to actually happen. So just kind of keep that in mind. 


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Louisa Nicola: [01:12:57] So treating your brain as if you're going to war, is a good analogy. So having a high-fat diet, getting a lot of sleep, hydrating with electrolytes as well and water obviously is really important too.


Cynthia Thurlow: [01:13:10] That's super helpful and it's interesting. Although beyond the context of our conversation today, at some point I'd love to hear more about what THC does to the developing brain. So, these young athletes, young adults that are assuming this is this benign entity. But I want to end our conversation talking about a supplement that I know we both embrace and really are huge proponents of. Let's talk about creatine monohydrate, which admittedly I've been using for the last year. And I always say that if as a middle-aged person, if I can be making gains in the gym week to week, that says a lot, a great deal of it is the sleep and the nutrition but I do fervently believe that creatine has really been instrumental. I know you talk about this quite a bit in your research and your newsletters that go out, but when did you start working with creatine or got interested in creatine as an adjunct to brain health?


Louisa Nicola: [01:14:04] This was probably around 18 months ago. Or maybe, yeah, two years to 18 months ago because I wanted to understand how can I help post stroke patients. So, I started to get into creatine monohydrate around 18 months ago, mainly because I was working with a lot of stroke patients and I wanted to understand how can we help speed up the recovery of these stroke patients. And I also had a Parkinson's disease patient and I saw a lot of literature around the benefits of creatine on Parkinson's disease. And I went down this rabbit hole and that's when I was really putting out content, saying that, “Hey guys, creatine isn't just for the neck down, which is the body, and for physical performance, it's also for brain performance.” Because you think about why are we having it. 


[01:14:51] We're having it for increased ATP production, correct? Which helps with the energy that is produced in the cell. So, we can push harder at the gym from a bodybuilding perspective. So, we can push harder and heavier for longer, which means we'll get bigger and grow more muscle. The brain is the same. We need and as we get older, we have a lower affinity to produce ATP. And obviously creatine is obviously naturally occurring already we have it, but it gets decreased as we get older or if we've had a TBI. So, I'm huge in creatine, I'm huge about putting it out there for women because there's this myth around, I'm going to get big and bulky and rightfully, when it pushes more water into the actual cell, you can feel bulkier. Yes, but we can monitor that.


[01:15:42] Maybe have 3 g a day instead of 5. Maybe cycle it. Maybe have 5 g a day for seven days and then come down to 2 g a day. Either way, it's having an effect. And this is having an effect across the lifespan. I've started to give my parents, although at the start they thought I was giving them drugs. But we learned what it was at home. We did some education. So, it helps the brains of elderly individuals, especially post stroke patients. It helps with starving off neurodegenerative diseases. It's been widely implicated in diseases like Parkinson's disease. And I have to tell you, everyone should be taking it. The two best things you can take in my opinion is creatine and omega-3 fatty acids. 


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Cynthia Thurlow: [01:16:30] Well, we have one last question, and this question is from Mary Jo. “I take Cynthia's creatine supplement powder. Can she clarify when is the optimal time of day to take it? Before, during or after working out? Should it be taken on rest days, during the fasting window, etc., Thank you.” 


Ben Azadi: [01:16:47] Yeah. So, that's your question. [laughs] 


Cynthia Thurlow: [01:16:49] Yeah. So, what I would say is I take creatine in my feeding window because it will technically break a clean fast. I do recommend that women supplement every day in particular, because we have less endogenous creatine stores in our bodies. 70 to 80% less. It is absolutely essential that we are taking creatine exogenously outside our body because we can't get enough in our foods. Like, it would be great if I could just eat enough steak and eggs and that would do it for me. 


Ben Azadi: [01:17:17] So, when you say 70, 80%, you mean less than men? Is that what you're saying?


Cynthia Thurlow: [01:17:20] Yep 


Ben Azadi: [01:17:21] Ah, okay, interesting.


Cynthia Thurlow: [01:17:22] Yeah. So, we have less and what's interesting, as you look at the research about women's menstrual cycles, so there's time in our cycles where we need more creatine and there's really good research supporting its use in perimenopause and menopause. So, I always remind women, I think many of us thought of it as a bro supplement. Like it's a gym bro thing.


Ben Azadi: [01:17:38] For sure. Yeah.


Cynthia Thurlow: [01:17:39] And we know based on research, women need 3 g a day, men 5 g. And if you're vegan or vegetarian, you actually need more because you're not eating that animal-based protein. But yeah, it's really easy to take it daily. My product in particular, blends seamlessly into water and anything else. So, it's really nice. But yeah, creatine is my surprise supplement. I think for me personally, I always like to share this, but being a menopausal female and being able to consistently lift more weight week to week, so we're at a metabolic disadvantage in menopause as we've lost testosterone and estrogen unless we're on HRT, it's harder to build and maintain muscle. And so, for me to be able to get in the gym and do that every week really speaks to the fact that it works. 


[01:18:21] And there's a friend of mine who's 70 years old, she's a clinical psychologist, she's 90 pounds and she was showing that she did a 300-pound leg press in the gym. She was like, “If anyone can build muscle, I can.” And so, I love knowing that a lot of people are driving a lot of benefit from it.


Ben Azadi: [01:18:37] That's amazing. So, interesting. Okay, so 3 g for women, 5 g for men, vegans need more, that makes sense. What is it about the creatine? So, you're saying it breaks the fast, you're saying it's best to have it during your eating window. What is it about the creatine that breaks the fast? It activates mTOR, there's a glucose response. What is it about it? 


Cynthia Thurlow: [01:18:53] It upregulates ATP production. So, in a lot of ways, it's like an amino acid. And so, I remind people that-- there are people like, “That's the only time I can take it.” I'm like, “That's fine.” But it's with the understanding that we want to optimize when it's consumed. It doesn't have to be consumed while you're exercising. We just know that we want it to be consumed in your feeding window. And you really just need that one dose a day just really easily can be incorporated into water, beverages or however you prefer to take it.


Ben Azadi: [01:19:22] Awesome. Yeah, that makes sense. Creatine is one of the most researched supplements out there. There's a lot of research on the benefits of it and there's a lot of misconceptions out there. It's not just for bros at the gym, it's for every human being. And I didn't know the 70%, 80% women have 70% to 80% less creatine and they actually need more, which makes a lot of sense. So yeah, I have a bag of your creatine on my counter. I need to be get more consistent with using it. Now you've inspired me. [laughs] 


Cynthia Thurlow: [01:19:46] Yes. So, when people ask, “You know, does it need to be taken in your feeding window or is it only consumed on days you exercise?” I just refer people to the fact that you'll benefit from taking it every day. 


Ben Azadi: [01:19:58] Yeah, makes sense. Awesome.


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Cynthia Thurlow: [01:20:01] What are the best ways to track muscle mass? So, it's interesting. My trainer likes Bod Pod. Are you familiar with Bod Pod? It looks like an egg. 


Dr. Gabrielle Lyon: [01:20:11] Yeah. 


Cynthia Thurlow: [01:20:11] Are you a fan of that? 


Dr. Gabrielle Lyon: [01:20:12] I think they're all okay, but the reality is none of them are directly measuring skeletal muscle mass. How's that to blow your mind? 


Cynthia Thurlow: [01:20:19] Yeah. So, it's indirect measurement. So, when you're working with your patients, do you have other preferred ways. 


Dr. Gabrielle Lyon: [01:20:25] I am hoping will happen is that we will begin to have access to something called a D3 creatine. D3 creatine is the way of the future and it's a way to directly measure skeletal muscle mass. This, my friend, is going to change the way in which we actually think about the importance of skeletal muscle. Here is why, there is this long-standing belief that it is only strength that matters and not the amount of skeletal muscle mass. You'll hear this all the time. It doesn't really matter as long as you are not cachectic or your appendicular lean mass is not two standard deviations below what would be considered average. The reality is we have not been directly measuring skeletal muscle mass. All the information out there is not based on direct measures of skeletal muscle mass. 


[01:20:25] How can we make these statements about skeletal muscle without looking directly at the tissue? This is a problem. This is a problem because we have based decades of research on a modality that is not a direct measurement. Therefore, we've come to largely what I would consider inappropriate conclusions with this idea that it is all about strength because there isn't a correlation between mass. But the reason that there isn't a correlation between mass is because we haven't been directly measuring it. And there is a great paper I recommend you read. I recommend everybody read. And there's a D3 creatine paper. Let me see if I can pull it up, with William Evans, has just really done a fantastic job at distilling down the importance of what has happened and the importance that actual skeletal muscle mass plays and the necessity of directly measuring it.


[01:22:08] And what they're going to find is that skeletal muscle mass is indicative of strength and is indicative of these processes of aging. And we see it indirectly. I'm going to paint the picture in this way. In Galveston, So the Galveston group, formerly Doug Paddon-Jones group, now Emily Lance's group, they show that with the loss of skeletal muscle mass that there is an increase in insulin resistance. They say they see an increase in triglyceride levels, they see an increase in glucose again, and they see an increase in insulin. This is directly related to the loss of skeletal muscle. Yet in the literature, we are still hearing that it's strength that matters, not muscle. But when you account for skeletal muscle mass directly, you see that it is the mass that is important. And the loss of skeletal muscle mass is probably more important than the gain of body fat when it comes to health outcomes. 


Cynthia Thurlow: [01:23:03] That's really interesting. And how far out do you think the D3 creatine is? 


Dr. Gabrielle Lyon: [01:23:08] I don't know. I spoke with him. It's still a couple years out. But it is going to change the face of everything. And it's simply a pill that someone takes. Creatine is tagged, it's a deuterated. Creatine is found in skeletal muscle and then they measure it in urine. 


Cynthia Thurlow: [01:23:20] That's really interesting. Of course, I'm a huge fan of creatine, and we'll definitely touch on that. One of the things that I think is particularly important when we're talking about metabolic health, muscle health, skeletal muscle, is the interrelationship between the loss of skeletal muscle, sarcopenic obesity, and the impact on cognition. I think a lot of people don't understand that the brains that we have in our 60s and 70s are made in our 40s and 50s. Well, I'm so grateful for your work. As I said at the beginning of our conversation, and I say as often as I can, I can't think of a physician that's had a greater impact on my work and my knowledge than you.


[01:24:00] And so, I'd love to end the conversation today talking about a supplement that you and I both embrace and love. Talk about creatine. And obviously you got it on my radar several years ago. But let's talk about how you use creatine in your given patient population. What are the results that you're seeing? Why are you such a fan of it? 


Dr. Gabrielle Lyon: [01:24:25] Well, creatine is interesting. It's probably the most well-studied supplement out there. As you know, creatine has been around for an extremely long time and its very, very, very safe. When you think about creatine, you have to think, where does it come from? Creatine comes from meat. It comes from red meat. In layman's terms, it's this amino acid stored in your muscle, it's in your brain, it's in your gut. Well, it's not actually stored in your gut. It's mostly stored in skeletal muscle. And what has been found is that it's very valuable for not just skeletal muscle, for energy production in skeletal muscle, but it's also very important for brain function. And that is something that I think that we're going to start to see way more of it. 


[01:25:15] It's not just beneficial for a high intensity interval training, but it is going to be more and more important for cognitive maintenance. And also, I actually was thinking about this. For individuals, it's probably difficult to get a more optimal dose of creatine just from eating red meat or from eating foods. I think that is going to be challenging. And it's challenging especially for women who are going through menopause. The reality is if you are not training like a beast, you will probably have to reduce your calorie intake. It's been shown that women will show an increase in performance when you add creatine simply. It could supplement for 10 weeks and there's evidence to support that it improves performance. There's no downside. There's absolutely no downside. 


Cynthia Thurlow: [01:26:03] Yeah, it's interesting. I've seen improvement in sleep architecture, jet lag, brain cognition. I mean, obviously there's research on traumatic brain injuries, but to me it's one of those supplements that is safe. My teenagers take it. I've got my mother now taking it, who's in her 70s. I think it's one of those supplements the potential of benefits are really endless.


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Cynthia Thurlow: [01:26:31] Well, let's kind of end our conversation talking about one of my favorite supplements, obviously creatine monohydrate, which I know you're a fan of as well. How does creatine impact thyroid function? And how do you utilize this? And with your patients or yourself personally, what have you found to be most effective? 


Dr. Amie Hornaman: [01:26:49] I love creatine. And again, it's kind of funny. We didn't really plan this conversation to continually go back to my bodybuilding days, but it keeps getting pulled in. I remember back in, “Oh gosh, this is the late 90s now.” When there was the EAS body for life contest, which I did, my sister did, my dad did, we all did together as a family. These before and after pictures. And you had to use their products, right. And creatine was one of them. Well, my sister's a physician, so she wanted to do her due diligence and really look into creatine. Is it good for you? Does it have any side effects, anything? And that was the one supplement that had nothing but positive benefits associated with it. There was literally nothing she could find that correlated creatine with anything bad in the body, side effect wise, nothing. Some people back then with the type of creatine we were using would hold a little bit of water, so you get a little bit of water retention. But that's because of the mechanism of action of creatine, literally shuttling nutrients into the muscle cell and providing more energy, providing more hypertrophy of that muscle tissue. 


[01:27:59] So, I've been a fan of it for decades now, literally decades, because I think we can honestly say it really is the one supplement that has been out for decades, that has nothing tied to it in terms of negative effects, negative consequences from use. So, I'm a huge fan, huge fan and I try to get my ladies to understand that. And I think it is being pulled more into the regular market, out of the bodybuilding world, out of the sports supplement world and into the, “Hey, let's use it for day-to-day function, day-to-day benefits in terms of our audience and women are slowly realizing, and especially with your education of creatine, with your audience realizing its importance, realizing the benefits, realizing that this can produce a little bit better workout. 


[01:28:55] Like yeah, those five pushups that you did, that you thought that number five was really hard. Now you just banged out seven and maybe two weeks from now it's going to be 10 and you just went from 5 pounds to 7.5 and then to 10 pounds. So, those little incremental strength changes, that's going to come back and obviously benefit. When we lift heavy, we improve our testosterone and our growth hormone levels naturally. So, the creatine gives us a little bit more strength, we're stronger in the gym because we're lifting heavy. That's going to come back and improve our testosterone levels. That's going to come back and improve our growth hormone levels. Now what do we know about testosterone? It actually has feedback on the thyroid, specifically with Hashimoto's, to lower Hashimoto antibodies.


[01:29:38] So, all this talk about testosterone, I didn't mention that another benefit of it is to lower Hashimoto antibodies. And we see this documented in studies, of course they were done with men, but we see it across the board in women as well. When we optimize a woman's testosterone levels, her antibodies also go down and just that whole inflammatory response of the body goes down. And the thyroid works better. The thyroid is going to work better when all of your other functions in your body are better, when your sex hormones are better. The thyroid is going to work better, when you're not inflamed, when it's not getting beat up by those antibodies on a daily basis, it is going to work better. So yes, we can absolutely say that through that pathway, creatine is beneficial to the thyroid. 


[01:30:24] And then there's just the other benefits of creatine, improving nutrient absorption, like we said earlier, shuttling those nutrients into the muscle cell. You've talked so much about it, I need to go down some more rabbit holes on creatine because I just mainly recommend it. I just tell people, “Start on this, here's the benefits.” But I know that you've even dove into antiaging benefits of creatine, brain benefits of creatine, right? 


Cynthia Thurlow: [01:30:46] Yeah. And even mood and cognition. The thing that's been interesting, I think it's important to get real life testimonials. And the things that I always find amazing is people saying to me, “I've had long-term depression, I'm on medication, within three days of taking creatine, I feel like my mood is lifted.” And I always say, “Don't stop anything you're doing. Talk to your doctor.” Like I'm always like, “Don't change anything.” But I think that's wonderful. And I think it really speaks to mitochondrial health. It really speaks to ATP production. It really speaks to all of these cellular mechanisms that people can tangentially, they're like, “Okay, I lift better, I lift heavier in the gym, I'm sleeping better. It can help with sleep architecture. My mood is better.” And so, people focus in on that. 


[01:31:28] But I always say it always comes down to the same things. Mitochondrial efficiency, ATP production, like getting down to the cellular level. All those things are so important and I think in a sea of the supplement industry that in many ways I think is well intentioned-- Let me just be really clear, well intentioned because I come from a glass half full kind of person. But I think in many ways, like if you really go down those rabbit holes and really spend time like I know you have with your own supplement line, you know that things can be very, very helpful. I'm like, “Let's simplify things, let's not be on 50 supplements, let's be on a curated amount of supplements that we know are very helpful.” 


[01:32:04] My entire family actually takes creatine, which I think is hilarious because people will say, is it safe for teenagers? And I was like, “I have two very athletic teen boys. And you would ask my 15-year-old, he took it with him. He's at a university doing a program right now. And you take it with him.” He's like, “I stick it in my water and I carry around my water bottle and I get to take it.” And so, I love that we both have this shared appreciation for creatine monohydrate. What are you working on now? Anything new? I know you've got these burgeoning like supplement lines which I've loved learning more about. Tell us what you're working on now. 


Dr. Amie Hornaman: [01:32:35] Well, what I'm working on now coming out soon is actually a good tasting beef protein. So that's exciting because sometimes you can really struggle with the taste of protein. And I tell my ladies, please don't go out and just get some plant based, don't get it from Sam's Club, right? Just because it says protein on the label, you don't know what it's going to do inside your body. And personally, anytime that I've tried a beef protein, I've struggled a little bit. It's not something that I look forward to doing every single day and plant-based proteins bloat me. I always get the angry belly with them. So, I have developed and found. I'm super excited. This should be coming out within the next week or two. A beef protein that tastes good.


[01:33:21] I actually look forward to doing it every day. And that you can make it into a mousse, you can make it into an ice cream. So that's pretty cool. So that's next up in the line of the fixer supplements, but really just focusing on edge. I love getting out the message of T2 because I do call it the forgotten thyroid hormone. And just really educating listeners, people everywhere, practitioners even on the benefits of how you can use it. And you don't have to worry about your patient or your client having an elevated heart rate or you yourself having an elevated heart rate. You don't have to worry about their numbers looking all wonky and looking hyper. This is something, this is a tool. You pair a T2 with creatine, my gosh, you're a mitochondrial powerhouse. 


[01:34:08] Now you have that ATP production, you have steady energy through the day. No more crashes, no more looking at the couch at 2 PM going, “Oh man, if I could just lay down and close my eyes.” That's not how were built. We were built to go through the day. We sleep at night when it gets dark, melatonin production, all of that. We weren't designed to be so damn tired at 2 PM that we need a nap. That's not right. So yeah, just continuing to focus on T2 education and getting the word out. 


[music]


Cynthia Thurlow: [01:34:40] Well, it's really interesting because I trained at a time when the Women's Health Initiative came out and so many of my female patients were taken off of their hormone replacement therapy. And so, when I talk to women about the physiologic changes that are happening in our bodies around perimenopause and menopause and as we have less circulating estrogen, so kind of towards the end of perimenopause into menopause and high follicular stimulating hormone, how it creates this catabolism. So, we're breaking down muscle. And a lot of people don't understand, irrespective of whether or not you're using hormone replacement therapy, we are at this incredible disadvantage mechanistically in our bodies. And so, helping women understand that this protein leverage hypothesis. 


[01:35:25] If we don't eat enough protein, our body will figure out a way to get more food in and it's probably going to come from carbs and fat and not from protein. So, really important to understand that we need more protein as we're aging, not less. The amount of protein that my teenagers can eat that stimulates something called muscle-protein synthesis could be 10 to 15 g of protein. It's very little versus as we're getting older, we need 30 g to stimulate that same muscle-protein synthesis so we can make muscle tissue. And so, helping women understand when we talk about more protein, it really is for many reasons. It's the satiety, it's the muscle-protein synthesis. It's for all these things mechanistically that are happening in our bodies. What else do you think is important? 


[01:36:09] When we're thinking about protein and looking at our plates, what are your thoughts on foods that positively impact metabolism? Do you buy into peppers and ginger and things that have some research behind them that can be helpful for improving our metabolism? Do you buy into that or do you think that's sometimes kind of contrived?


JJ Virgin: [01:36:29] I think that I always look for the little hinges that swing the big doors and those are maybe the tiny little nails in the little hinges. 


[laughter]


[01:36:40] If you think adding peppers to your meal is going to have this massive metabolic effect, is it going to help a little bit. Lemon juice or vinegar before a meal? Yes. Good. Could help with some blood sugar control. Although I think we're starting to focus too much on a blood sugar spike rather than the area under the curve. It's like if you say, “Oh, I could eat some vinegar before the meal and eat some crap,” I think you've missed the point completely, right? [laughs] That's not really helpful. So, there are all these things that can be great hacks. Here's my thought on hacks. To me, hacks are like, you're going to get a new car and the first thing you're going to find out, depending on the car you're going to get is what the battery's like or what the engine's like, how safe is it? What's the fuel efficiency, all those things. If you go and you go, you know what I really care about with this car? “The paint job and the interior.”


[01:37:34] Well, those are the nice to have, but they are not the need to have. So, we have to first start with the macro stuff. How much protein do you need? Okay, after protein, what's going to come next? I put non starchy vegetables next and then I look at how much fat I've gotten in between the protein and the non-starchy vegetables, add a little fruit, and then I'm going to see what I need from there, I basically have people dial in their protein, focus about 100 g of carbs as a starting point as close to nature as possible, so that we're getting in at least 30 g of fiber there and then adding in maybe 60 g of fat, and then we start to play with it.


[01:38:12] Some people do better. They've earned more carbs with exercise. They do better higher carbs, some people do better higher fat, lower carb. Everyone's a little different and what they like is a little different. But then you can start to look at, oh, okay, what shall I put in, what herbs and spices and things? I think they're fantastic to do. But if you think cayenne pepper is going to be your secret to burning fat, [Cynthia laughs] I don't think so. I will say one thing that I've seen, and I know you're on this one too. And if I was going to pick one supplement, one extra thing for a menopausal woman, peri/post as something that you should be on for the rest of your life. It would be creatine. 


Cynthia Thurlow: [01:38:53] If you love this podcast episode, please leave a rating in review, subscribe and tell a friend. 



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