Ep. 301 Creatine: The Best Supplement for Better Bones & Brain Health with Darren Candow, PhD, CSEP-CEP

Bio:

Dr. Darren Candow, PhD, CSEP-CEP, is Professor and Director of the Aging Muscle and Bone Health Laboratory in the Faculty of Kinesiology and Health Studies at the University of Regina, Canada. The overall objectives of Dr. Candow’s research program are to develop effective lifestyle interventions involving nutrition (primarily creatine monohydrate) and physical activity (resistance training) which have practical and clinical relevance for improving musculoskeletal aging and reducing the risk of falls and fractures. Dr. Candow has published over 120 peer-refereed journal manuscripts, supervised over 20 MSc and PhD students, and received research funding from the Canadian Institutes of Health Research, Canada Foundation for Innovation, the Saskatchewan Health Research Foundation, the National Institute of Health, and the Nutricia Research Foundation. In addition, Dr. Candow serves on the editorial review boards for the Journal of the International Society of Sports Nutrition, Nutrients, and Frontiers.

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Transcript

Cynthia Thurlow: 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.

Today, I had the honor of connecting with Dr. Darren Candow. He’s a professor, an internationally renowned researcher in creatine monohydrate, the role of nutrition and physical activity. He’s produced 87 peer-reviewed publications and high-quality journals and he’s an absolute delight. Today, we spent an extensive amount of time speaking about the role of creatine monohydrate in bone health, the role of estrogen and anabolic processes, the impact of exercise along with creatine in relevant research, the evolution of sarcopenia, outdated RDA recommendations with regard to protein, the role of creatine utilization in brain health, specifically traumatic brain injuries, sleep deprivation, jet lag, and mood disorders, how to dose creatine properly.

There are some really exciting emerging research in this area, in particular, lots of questions. Thank you so much to listeners. We had several hundred questions submitted and I think I will end up doing an AMA devoted to creatine all in and of itself, very likely with Dr. Candow, who very graciously offered to do that because we had so many questions, and lastly, talking about the role of creatine in not only anaerobic strength training, fat loss, but also the impact of utilizing creatine with cardiovascular and endurance exercise, the role of antiinflammation as well as anti-muscle catabolism. I hope you will enjoy this conversation as much as I did recording it.

As a special for the next week from the date of publication of this podcast, which will be October 4 until October 11, we’re going to be offering a discount code on creatine. So, it’ll be CREATINE15 can be utilized to get 15% off of creatine monohydrate. Go to my website www.cynthiathurlow/creatine to purchase that. Again, this will be a short-term discount of 15% that will be offered from the day of publication of this podcast on October 4 through the 11th utilizing CREATINE15.

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. 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 metabolic health benefits, they understand the improvement in strength and muscle conditioning, but in particular in our conversation 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.

And specific to my listeners, most of whom are middle-aged women that are in perimenopause and menopause, what is some of the new 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 creatine.

Dr. Darren Candow: 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 a female health. I think most people that are familiar with creatine would think of it for athletes getting bigger, stronger, faster. 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. As you point out, the hidden factor or results were around bone health. Creatine was designed for muscle health as we all know. If we can put on muscle mass, we get bigger, stronger, faster and improve a lot of aspects of our life. 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.

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 basically the day you die. And that’s really important because the cessation of estrogen, we decrease that anabolic capability of estrogen. So, we have to come up with lifestyle interventions to replace it. There’s only been a few studies that have actually looked at creatine directly on measures of bone health. The vast majority have focused on postmenopausal females. 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. 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 will be weight training. But we did perform a long-term study with walking. Overall, collectively, creatine seems to preserve some aspects of bone mineral or bone strength around the hip region. It seems to improve lower limb below the knee, bone area. 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. 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: 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. 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. 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.” That’s not what we’re saying. The creatine plus exercise is where you get the conferred benefit.

Dr. Darren Candow: Yeah, it’s so crucial. So, I think a lot of people are always trying to look at a magical pill or powder to save everything about them. 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 the postmenopausal stage. The average age was 59 years of age and they were healthy enough to participate in exercise. We were really fortunate to finally publish a paper that was adequately sample size, 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, a whole-body routine, and then six days of walking. 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 anaerobic type of standpoint per day. And then at least two days of resistance training. So, we 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. 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 the theory here is that as we get older and we’re having natural bone loss, maybe we might need more to overcome or compensate for the natural age-related reduction in bone.

So, typically with muscle, most people hear about 3 to 5 g a day. 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. So, we gave, on average, 11 g a day. 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. 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?” 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 to 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.

For two years, at a really high dose, there was no greater effects than placebo. Most people might be surprised by that. But realistically, when you look at all the evidence-based research, creatine essentially is a nitrogen-containing compound that’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 makes sense that 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? 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 opened the door for a lot of potential research.

Cynthia Thurlow: It’s really exciting because I think for a lot of listeners, I was certainly part of the generation that was prescribed oral contraceptives to fix every menstrual irregularity. So, at the time of my peak bone and muscle mass building years, I was kept in a low estrogen state and not surprisingly, I’m osteopenic. I’m also a thin Caucasian female with a family history, but it makes me think about my nieces and younger women and could this be something people could be incorporating at a younger age to help bolster their bone mass. So, first question was for the menopausal women, were they on HRT I don’t know. Here in the United States, they’re starting to become, we’re getting the second wave of coming off the Women’s Health Initiative, where there was a whole generation of clinicians and patients, frankly, who was terrified about hormones, now starting to get this resurgence and understanding that HRT can be very beneficial. Were any of these study participants also on estrogen or progesterone or testosterone therapy?

Dr. Darren Candow: No, they weren’t. And that’s one of the reasons we went 24 months postmenopausal and then they weren’t allowed to be on any anticatabolic steroids like glucocorticoids or estrogen selective receptor medication or anything that could adversely affect bone biology. So, we are very specific there. We did include females who started with low bone mass, but they were randomized equally across groups. So, no, they had to be very specific because we couldn’t conclude maybe it was the HRT that was influencing the bone. So, we had to be very specific with the selection and inclusion criteria.

Cynthia Thurlow: Yeah, and that certainly makes sense. And then the other question I had was when you were looking at bone strength, were you looking at DEXA scans? Was that the standard that you were using?

Dr. Darren Candow: Yeah, we did DEXA for segments of the whole body and then we had some hip structural analysis we got from John Hopkins University to focus on the bone and actually measure the strength. And something I forgot to mention, we didn’t measure the rate of falls and fractures over the entire study and including one year after. And yes, both groups did experience falls, but there was no difference between conditions.

Cynthia Thurlow: That’s really exciting. For anyone who’s not listening, it’s something that I certainly saw clinically in medicine that you would sometimes get 50, 60-year-old women. We think of it as our grandmothers-

Dr. Darren Candow: Right, right, right.

Cynthia Thurlow: -that’s like women in their 70s, 80s, and 90s. But understanding that if you fall and break a hip at a young age, I mean, it has a tremendous amount of prognostic indication in terms of looking at future fall risk, mobility, etc. So, definitely things that we want to be conscientious about. I know you had mentioned that there were some other smaller bits of research that had 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: 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, [laughs] 1 g and 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 a vitamin pill you would do in the morning and going about your activities of daily living will probably not cause any significant effects. 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 the huge benefits you get from weight training. It 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: I think that’s a really important point. And one other thing that I want to tie up in terms of looking at bone and muscle health is we talk a lot about sarcopenia, how this accelerates after the age of 40. I believe I caught in one of your other interviews you were talking about what is the progression of sarcopenia? Like, do we start with sarcopenia first? What happens first? And I think this is really interesting for people to understand because I know that when I was in the latter stages of perimenopause, the first thing I noticed wasn’t the loss of muscle mass, it was the loss of strength. All of a sudden, I’d be on an airplane with my typically overpacked bag, trying to put it in the overhead, and I would say, “Oh my gosh, it’s the first time in my life,” I’ve noticed this hesitancy about picking that heavy bag up and putting it over my head. So, let’s talk about the progression because I do find this interesting. It may not start with, “Oh, I can’t seem to build muscle.” It actually starts with that strength loss piece.

Dr. Darren Candow: Yeah. So, the evolution of sarcopenia has actually changed quite recently understanding we used to define sarcopenia as the age-related reduction in muscle mass, strength, and functionality. But the problem with that was when we said muscle mass, most research studies would measure lean mass and that includes water and fibrotic tissue and a little bit of lean tissue mass estimation is about 50%. So, recent research groups around the world, leading research groups have now repurposed the definition of sarcopenia in it to talk about first the age-related reduction in strength, as you mentioned then, and or muscle mass and functionality. Theory here is that the reduction in strength highly correlates with a lot of chronic diseases and functionality. There’s some new data suggesting that the lack of strength is one of the main reasons you’re placed in long term care facilities because you can’t live freely independently later on in life.

So, by improving muscle strength, that is crucial that’s called dynapenia. And one of the best ways to improve strength is obviously performing weight training or resistance style of training. So, the reduction in strength and or muscle mass can occur in the fourth decade and that might surprise a lot of people. But around then the biological process of aging starts to occur. And then as we get into the ages of 50, 60, and later on, the reduction in muscle mass seems to occur, but not as fast as the reduction in muscle strength. So, it’s really critical to improve muscle mass and strength and functionality in the early years and hopefully that’ll offset the rate of decline later on. But this is really important. You can have centurions, 100 years of age and older. It’s never too late to start. You will get fast improvements in strength immediately and then eventually muscle mass and functionality.

But again, exercise, it’s never too late to start. I would argue it’s never too early to start. You try to do this on a semiregular basis throughout your whole life. So again, sarcopenia or you’ll hear dynapenia, which is the focus primarily on the lack of muscle strength. They’re hugely important. There is high association from sarcopenia and osteoporosis. So, for example, if you have poor muscle strength and muscle mass, you’ll have less muscle mass pulling on the bone, you’re probably going to be doing reduction in activities of daily living and therefore the bone is not going to be stimulated. So, there is high association between sarcopenia and osteoporosis and it’s formed a new definition called osteosarcopenia. So that’s something that your viewers may have heard of or be aware of and that unfortunately, the third factor with that is obesity. Then you get into something called sarcopenic osteo obesity and it’s a triad of three things that go together.

Cynthia Thurlow: Yeah, it’s really interesting and it’s something that sarcopenia is something we speak about with great frequency on the podcast and really trying to bring greater awareness to the process that by the time it started, you probably aren’t even aware of it. It’s happening very subtly and then all of a sudden, especially for middle-aged women in particular, they’re like, “I’m weight loss resistant, I’m doing all the right things, I’m overdoing orange theory, fitness or CrossFit, I’m not doing enough strength training.” So, it becomes this dual edge understanding that Zone 2 training and the strength training really become critically important.

Dr. Darren Candow: I think it’s interesting that we’ve never looked at the effects of creatine in diagnosed sarcopenic in older adults, that is planned, but individuals who have specific criteria. But the key factor and I think most of your viewers will be well aware of this, is high protein intake is going to be absolutely essential. So, unfortunately, the RDA is so outdated, it’s almost embarrassing. But 0.8 g/kg, if you’re 70 kg, that’s only 56 g of protein a day. And exceptional researchers around the world, including Stu Phillips here in Canada, it’s clearly shown empirically Don Layman in the United States, and Luc van Loon in Europe and Lee Breen[?]. But there’s many researchers clearly showing time after time that about 1.1 to 1.2 g/kg seems to be the minimum. And they can even push that up to a maximal range of around 2.2. But a nice range seems to be about 1.2 to maybe 1.6 even for older adults.

And that’s been shown to hopefully offset the negative effects of sarcopenia. So, resistance training and exercise walking is very beneficial. Please make sure that protein is going to be higher than what the RDA is suggesting and then maybe creatine can be that little icing on the cake to give you a small extra benefit.

Cynthia Thurlow: Yeah, I think it’s really important for people to understand it. 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: [laughs] Exactly.

Cynthia Thurlow: 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. So, thank you again for 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 come back from a trip and dealing with jetlag and I stumbled into some of your work looking at the role of brain stress and creatine, jetlag and creatine. 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. I was doing 10 and 15 g for three days just to help get over that hump of jetlag. It was amazing to see and to experience the lessening of that jetlag. I struggled more going east than I do coming west. 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: Yeah, I echo your statements. I think you were just in Venice, Italy and [unintelligible 00:24:13] same. So, there’s probably been the last decade, if you will, the hottest area to focus on is the neck up. 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 level, so to speak, the brain does it more often than not. Let’s be honest, with today’s society, stress, sleep deprivation, many hours of working, the brain is more metabolically taxed. So, 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 were born with creatine deficiencies, that means they were born with a genetic mutation where they can’t make creatine. We looked 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 common denominator. They had a reduction in brain creatine stores compared to healthy individuals. 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? 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 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. 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’re two things that are going against brain creatine compared to muscle.

One, the blood brain barrier is very selective. It blunts 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. 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 jetlag 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. We’re also seeing some potential in individuals with muscular dystrophy. The other big hot area is depression and anxiety, which is hugely prevalent. 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. In a few studies where individuals were still on their medication, which is really important, creatine seemed 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: 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. 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: Yeah, 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. So, a high dose, again, they’re a lot smaller in size, a creatine or placebo. And then they measured some subjective outcomes for up to about six months. I believe they actually have some data to a year.

Some of the improvements that were looked at was an 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 that increases brain creatine content to improve cellular bioenergetics. So, those are the two proposed main family of areas, but that’s all we have. 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 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. Well, 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’re 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: Yeah, it’s interesting. We lived in the Washington DC 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 never needed to use that information. But many, 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: 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. 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, jeez, what if I want to take it for everything?” I personally take about 10 g a day, but if someone says I don’t care about my brain or bone, 3 to 5 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. But one would argue, jeez, 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: Yeah, it’s really exciting. And just to loop in the sleep deprivation/jetlag 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 5 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 that 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: Yeah, that’s a really good strategy. I would even 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 jetlag, 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. I rarely come across someone who say, “Jeez, 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 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: 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 deal with bloating from creatine? So, some people appear to be more water retention sensitive to creatine irrespective of dose. So, how do you encourage people to either work through that? Because I always believe if someone tells me I use creatine and I gained 5 pounds of water weight, especially if this is someone who weighs themselves every single day and is very mentally sensitive to that water weight, what are some of the tips? Or do people have different propensities physiologically? Are certain people more prone to water retention with creatine monohydrate than others?

Dr. Darren Candow: Yeah, it’s probably one of the main reasons people are deterred from taking creatine supplementation. So, our skeletal muscles only have 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 multipoint, 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 or 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 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. What has been shown is 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. 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. A study in 1992 showed that 1 g really had a minimal increase in blood creatine. You 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 your say, what do we do now? We’ve talked about muscle, bone and brain. 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 repeated 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 I work out. 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: Okay. 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: 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: 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? I mean 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 helpful. I’m like, I’m going to ask the expert.

Dr. Darren Candow: So, an increase in temperature will increase some of the solubility. A lot of people say, “Hey, I mix my creatine. It’s 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: That’s really interesting because 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: 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: 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’s 6 ft 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: It’s a hugely popular and very important question a lot of individuals are considering it. So, remember, you can get 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. 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 to protein, seafood or red meat. It comes in, it 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: Yeah. Any research on pregnancy and breastfeeding? Because this always comes up. I think it’s from many years of working in cardiology ER medicine and were always like pregnant and breastfeeding women, we just always say no because we don’t know. But is there any research that shows efficacy or safety in terms of those populations?

Dr. Darren Candow: Yeah, there’s small amounts even less than what’s in children. And Stacey Ellery is the leading researcher out of Australia looking at this, and she’s looked at some really interesting animal data and correlated that to the healthy human female during pregnancy. And there’s potential to improve not only embryonic development, but some health measures in the pregnant female as well. But strongly caution any female out there, please go talk to your medical practitioner to make sure it’s safe and viable for you. We need a lot more research in this area, especially with long-term sample sizes. So, as it stands right now, it appears a viable and a safe intervention, but a lot of caution, and again, you need medical clearance before we move forward with that.

Cynthia Thurlow: Yeah, I think it’s always safe to always say with an abundance of caution when you’re trying to grow a human-

Dr. Darren Candow: Exactly.

Cynthia Thurlow: -for sure. Let’s round things out, talking a bit about fat loss and resistance training and how creatine monohydrate can fit into that picture.

Dr. Darren Candow: 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 sort of thought, “Oh, I increased fat mass.” We published a paper a few years ago looking at the effects of creatine and resistance training on measures of body fat in adults 50 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. 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. 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: 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 or relevant research that you think would be applicable for the everyday wellness community? I tried to be really, 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: I think the other area that gets no press is the aerobically trained or cardiovascular trained individuals, the runners, ironman, triathlon, 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 creatines seem 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 seemed to reduce these things called cytokines or markers of inflammation.

So, we got to give a little bit of love to the aerobically trained individuals out there that I think creatine can have some application 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: 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: That’s a great question. So, from anti-inflammatory perspective, there wasn’t any gender differences across spectrums, however, from an 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 as reducing protein breakdown from a long-term perspective. So, we’ve done a study and a good colleague of mine at McMaster University has 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 pre-menopausal, so maybe estrogen had some effect, but at the end of the day, maybe males have more of anticatabolic effect. 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 are a few studies just to show that muscle protein breakdown was reduced in males compared to females on creatine. But that’s certainly an area for more discovery.

Cynthia Thurlow: Yeah, it’s really exciting. Well, I have so enjoyed this conversation. Please let my listeners know how to connect with you on social media, how to learn more about your research, and if you’re obviously in Canada, if you want to be part of any of the research studies that you’re doing right now.

Dr. Darren Candow: Yeah, I think the easiest on Instagram @drdarrencandow same handle also at Twitter or X, whatever it’s called now. Then my email can be found at the University of Regina website. But I think the easiest is a message on Instagram and hopefully we can do this many times. There’s a lot of new emerging things coming up, so thanks for having me. I really appreciate it.

Cynthia Thurlow: Absolutely. I decided that when I stumbled upon your work because I’m so passionate about creatine, I was like, “Oh, I need researchers to come on and talk about this.” So, it’s not just me echoing, the N of a couple thousands of patients that I’ve worked with. Thank you so much for your time today.

Dr. Darren Candow: Yeah, thank you for having me.

Cynthia Thurlow: If you love this podcast episode, please leave a rating and review, subscribe, and tell a friend.