00:00:00.000so today on tpl media we're lucky enough to have dr mark tarnopolsky and thank you doc for being
00:00:12.320with us uh dr mark is that okay if i call you my cousin my problems yeah all right so doctor we've
00:00:21.440we've uh found you or we came across you because char and i both use creatine so we we had this
00:00:28.720conversation about creatine and you know it's interesting because you know my age um it was
00:00:34.800kind of the forbidden fruit when we started using it and we used it um it was a small group of us
00:00:40.400kind of found it at the gym we had this conversation and then we went to our gps uh years
00:00:48.560different times and we were we were given some advice not to use it because our creatine levels
00:00:54.400were off so then we got off creatine and then over time you know friends and that we got uh
00:01:00.160started using creatine again uh became more popular it kind of disappeared for a while out of
00:01:05.600the out of the mainstream um and now it's it's being heralded as kind of the wonder drug of of
00:01:13.440doing a bunch of things that uh quite frankly from sleep to brain to to fitness which was where i
00:01:21.040found it um and shara you know she found it um basically because we got uh on a health kick
00:01:28.400um on a fasting kick yeah and she started to implement it into our coffee routine in the
00:01:33.840morning um so you know for the folks at home doc can you give us a you know creatine a little bit
00:01:41.600of your history with it what you've seen over the years kind of how it kind of came and went
00:01:47.200out of this scene and and where it is today yeah so first of all maybe i'll just explain
00:01:52.800for some folks what creatine is because there's a lot of misunderstanding so creatine is a
00:02:00.400compound it's actually two amino acids which are stuck together and it's made from first they are
00:02:06.560kidneys then a compound called guanadinoacetate goes to the liver liver then sticks this thing
00:02:13.200think of a methyl group on it, and we make creatine. So about a gram or so is made every day
00:02:17.920from all of us just through natural synthesis. That's your endogenous creatine. So then it was
00:02:24.800well known that certain products, things like beef and steak and fish, so the meat of animals
00:02:34.160contains high amounts of creatine. So what happened is in the late 80s and early 90s,
00:02:40.460people were saying, you know, should we take creatine because it's in muscle, so maybe it's
00:02:45.300there for a reason. So in muscle, what happens is creatine gets converted to a high energy thing
00:02:50.240called phosphocreatine, which is really an energy buffer. And so the original rationale behind
00:02:57.180taking it was to say, if we can increase our phosphocreatine, maybe we can increase the energy
00:03:01.540in muscle. So things like doing repetitive sprints, high intensity exercise, when we need that early
00:03:07.440burst of energy folks will do better and that's what the original studies did show that when
00:03:13.520younger people were doing athletic type of activities in the first 10 to you know 20
00:03:18.720seconds of activity they could put out more power because by taking extra creatine in the diet you
00:03:25.040could then increase your muscle creatine levels and then there'd be a little bit more of an energy
00:03:29.440buffer that's really where the research started that roger harris unfortunately he passed away
00:03:34.400recently he's sort of the godfather of the creatine research and did a lot of the stuff
00:03:39.280with muscle biopsy showing how it works in muscle and that was sort of the original concept so lots
00:03:44.480of athletes were using it so in the late 80s pretty much every sprinter in the world and 100
00:03:50.000meters 200 meters was taking creatine to give you that extra energy boost throughout many decades
00:03:56.160of research ourselves included it's pretty clear that it does more than that it shuttles energy
00:04:00.720between the powerhouse of our cell called the mitochondria and what's called the cytosol which is
00:04:05.520sort of the outer part of our cell that contains these high energy compounds it also reduces
00:04:12.000something called oxidative stress which you might be familiar with free radicals or antioxidants
00:04:17.040which some people take creatine actually does have some antioxidant protection and that's perhaps some
00:04:22.240of the long-term benefits that people are seeing in the brain we've actually given creatine to
00:04:27.120folks and shown using these things called gene arrays that it does change a lot inside muscle
00:04:33.120and even decreases the breakdown of protein and muscle so there was a lot of interest as i
00:04:38.640mentioned in the early 90s showing that we could take extra creatine in our diet increase muscle
00:04:45.440creatine phosphocreatine increase exercise performance so where i got interested is i'm a
00:04:52.320genetic specialist in neurologic diseases and we have patients with muscular dystrophy
00:04:57.120So we did muscle biopsies back in 1999 to take a look at creatine.
00:05:01.620And what we found is creatine, phosphocreatine, were very low in these disease states.
00:05:06.420So we published a paper in Boyce with a horrible muscle disease called Duchenne dystrophy,
00:05:11.100showing that we could also increase their strength and their function and even their muscle mass when we gave them creatine.
00:05:18.200So we then went on and colleagues of mine like Darren Kandao, who's at the University of Regina,
00:05:23.300said, well, what about more popular things like aging? We know people get skinny muscles,
00:05:29.460their mitochondria don't work properly, and bones get thin. So people started looking at the benefits
00:05:35.000of creatine in older adults. So we did a study in 2003 and again in 2007, showing that older
00:05:42.820adult men and women who exercise for four and six months, depending on which study we were looking
00:05:48.840at. And they gained more muscle mass and better function when they trained with creatine. So those
00:05:55.260are just some of the original studies we were involved in. And like you say, it seemed to
00:06:00.200attenuate a little bit, although certainly in the clinic, it's now standard of care for muscular
00:06:04.960dystrophy. So we've always continued to investigate and be interested. But folks more recently started
00:06:10.740to look at potential brain benefits in people who are sleep deprived. Vegan vegetarians,
00:06:19.840for example, have low muscle creatine. And there have been some benefits from a cognitive
00:06:24.820perspective when they take creatine. So we could go on and on. There's just so many potential
00:06:29.980benefits and studies that have been done that I think we know a lot more about the potential
00:06:34.780benefit now that we did even 20 30 years ago a very quick favor before we continue a large
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00:07:01.540there directly. It takes just five seconds, costs nothing, keeps you informed. So thank you. Now
00:07:08.780back to the show. Dr. Mark, so can you tell us about, compared to men, what are the benefits0.90
00:07:17.700for women? Does it help for menopause, or brain function, and how much they should take it?
00:07:25.160Yeah, it's a great multiple questions there. So certainly we've done studies, and pretty much
00:07:29.840every study we've done, we have equal number of males and females in our study because we have
00:07:36.020seen some sex-based differences. One of the reasons why women tended to shy away from creatine
00:07:43.120is everyone said, oh, I'm going to get bloated. So essentially there is some rationale there.
00:07:48.260When you first start taking creatine as a supplement, it comes into our bloodstream,
00:07:53.080it gets taken out mostly in muscle, about 90 to 95% of all the creatine is in muscle.
00:07:57.760so when it goes into muscle and you increase the concentration water comes along for the rise and
00:08:02.140the muscles do swell a little bit but that's kind of how it works in one sense because that slight
00:08:07.940swelling that you get actually decreases protein degradation and what we found is we looked at
00:08:13.420men and women and we gave them a high dose of loading so in the old days we used to use 20
00:08:19.540grams over a short period of time you know four to seven days that was the loading phase and what
00:08:25.160we found is that the males would gain about 1.5 kilos and the women would gain about 400 to 500
00:08:32.220grams so much less but the problem is if you look on the scale you think you're gaining weight
00:08:37.100but what you're gaining is water in the muscle which is a good thing and so it's not increasing
00:08:43.040fat and I've heard people say oh creatine is going to make me fat I mean there's no calories there
00:08:47.160so that that weight that you see with creatine is actually good weight it's lean body mass weight
00:08:53.300So I think more recently, people have realized that going through menopause, it's absolutely
00:08:58.620certain that there's a decline in bone density.
00:09:02.080And there's more evidence in working studies right now with Alison Shea, who's a world
00:09:06.720expert in menopause, taking a closer look at body composition, which is fat and muscle.
00:09:13.140And how does that change through menopause?
00:09:14.640So certainly the bone benefits for older adult women going through menopause, we have done
00:09:20.700many studies showing benefits to bone, using bone markers and even using petri dish bone cells
00:09:27.020and using some preclinical models where we've damaged the bone with corticosteroids, which is
00:09:33.680a thing called prednisone, and we see benefits. In fact, our boys with Duchenne dystrophy who are
00:09:39.020on prednisone, their bone markers look better when they take creatine. So getting all of that
00:09:44.840research together, I think women are becoming increasingly aware of the potential benefits to
00:09:49.560maintain muscle, maintain bone, especially as we age. Now, a lot of folks think, okay,
00:09:55.580aging begins at 65. No, it doesn't. Even by age 30, we're starting to see early changes. So really,
00:10:03.280it's a lifelong thing that people need to be thinking about exercise and optimal supplementation,
00:10:08.540which I think for most people should include creatine to sort of attenuate that slow decline,
00:10:15.200which we're all experiencing. I just turned 64 this week, and I'm definitely not as strong as
00:10:21.660I was in my 20s and 30s. So I'm doing exercise and taking a number of different supplements,
00:10:26.400including creatine, to try and mitigate those declines. So your second question is, how much?
00:10:33.000The problem is there's a lot of misinformation. So the first studies that came out, a seminal
00:10:38.600study in 1992 it's very clear that if you give 20 grams a day for four to seven days you load muscle
00:10:47.560you can't keep loading so muscle will go up you know 20 to 25 percent and that's about as far as
00:10:53.560it'll ever go brain on contrast when you take creatine goes up about nine percent so it's about
00:11:00.040half the increase that we see in muscle but it follows a similar pattern so studies have shown
00:11:05.400to load brain 20 grams over four to seven days we can increase the concentration in brain
00:11:11.400which is what we've shown in muscle a study everyone seems to forget is that in 1996
00:11:18.840the top researcher eric haltman showed that if you take three grams of creatine
00:11:24.840every day for a month you hit that same level that people were getting on the 20 grams
00:11:29.240so for some reason you forgot to take your creatine you need to load in four to seven
00:11:33.080days yeah sure you might need 20 grams but for most of us that are taking it from a lifelong
00:11:38.200health span perspective you know three to five at most is all you need and it may be we never
00:11:44.680compared three to five and older adults but we gave five grams to older adult men and women
00:11:50.440in 2003 and 2007 and we showed that we maximized their muscle so after four months and six months
00:11:56.920staying on it constantly their muscle is still at the absolute maximum level so clearly showing
00:12:01.960that if you start going above that you're just spending more money uh and just peeing out the
00:12:06.600creatine and you know it's a complete waste of time and the same almost certainly holds true
00:12:12.360for brain there's all this hand waving that you need to take 20 grams a day but one of the top
00:12:17.800colleagues in the world serge ostier showed that people that had chronic fatigue after four months
00:12:24.280taking um four grams of creatine that their brain loaded to a maximal level so again i think if you
00:12:31.800you've forgot your creatine and you need to load in a week, yeah,
00:12:34.860you might need 20 grams, but all of us who are taking it for health,
00:12:38.160then for long-term cognitive benefits, you know,
00:12:40.980I think five grams would be your sort of maximum dose based on.
00:12:46.600Good. I'm taking five grams a day. So I think I'm good.
00:12:50.180Yeah. Well, it's interesting, Dr. Mark, because, you know, you,
00:12:53.980we've listened to other shows and people come on and they've, they've,
00:12:59.220they say you know uh when i'm sleep deprived you know i amp up on my creatine but that's a great
00:13:06.420point they're probably not taking daily creatine or if they're taking daily creatine they actually
00:13:11.700think that they want to increase that increasing it will give them kind of a more uh cognitive
00:13:18.020cognitive um advantage for the day given their sleep deprivation yeah i mean it's a complete
00:13:24.900lack of understanding of biology science and the literature um and you know if you if you want
00:13:31.380influencers to determine what you're going to do versus actually doing the science and understanding
00:13:36.340it it just makes no sense a muscle like brain is it probably more like this that is you know takes
00:13:42.740a while to load once you're there they've done studies in muscle but not yet in brain where if
00:13:47.380you stop it takes about a month for the creatine to go back to baseline from your muscle and it's
00:13:52.500almost certain that brain's the same the only difference between brain and muscle is that you
00:13:56.260get about half the increase in brain but nine to ten percent whereas you get 20 to 25 percent muscle
00:14:02.260but the benefits uh in the brain from that level of increase uh which you know sir jostrick has
00:14:08.180shown for six months uh you still see especially with sleep deprivation some improvement in
00:14:13.700functional complex tasks um certainly vegans who get no creatine from their diet uh seem to derive
00:14:21.140more benefit. There have been innumerable studies in preclinical models, okay, and so again it's hard
00:14:27.940to do these in humans where they induce a stroke or there's head trauma or we genetically manipulate
00:14:34.500to cause Alzheimer's, Parkinson's, Huntington's, Lou Gehrig's disease. Every one of those models
00:14:40.580clearly shows benefits from creatine and the amount that is given to the animals in those studies
00:14:45.940is pretty equivalent to the five to seven grams that a human would take so in physiologically
00:14:51.780reasonable amounts we're likely benefiting from things like you know well cognitive impairment
00:14:58.820if you have diabetes or high blood pressure and you're at risk for stroke and you unfortunately
00:15:02.740have a stroke if you have that creatine on board by taking your you know three to five grams every
00:15:07.540day you are likely to derive some benefit and have less damage so there's many reasons i think to
00:15:13.700take, you know, these optimal lower, you know, three to five grams to keep your muscles and
00:15:19.620your brain at a nice loaded level. But taking extra right before, you know, flying to Europe
00:15:26.240or something is not going to suddenly burst it up. You have a ceiling of about 9% increase in
00:15:31.340weight and 20 to 25%. Right. Hey, question for you. So kidneys, let's say, can we chat about
00:15:39.680this for a minute, you know, is there, and that was always, I think, or one of the things that
00:15:44.440people kind of cautioned people about when they took creatine. And I think you've seen that. Is
00:15:50.260there ever been any studies that have actually talked about negative effects of creatine on the
00:15:54.740kidneys? There's a lot of hand waving, but unfortunately the hand waving ignores the real
00:16:00.400research. So what happened in, when we were doing our studies in the early 2000s, there was a lot of
00:16:07.560negative press that came out of both with, you know, cancer risk and more importantly with the
00:16:11.520kidneys. So big journals love negative press. Drug companies love to bash exercise and nutrition.
00:16:19.240So what happened is in two prestigious journals, they published garbage stuff, which could never
00:16:24.900pass peer review with anything else other than trying to bash a supplement. And what they found
00:16:30.800is one individual who took 20 grams a day, which I would never condone, who had pre-existing kidney
00:16:37.180issues is creatinine went up so the issue here is lack of understanding from most doctors of biology
00:16:44.620and that is that creatine when it goes into muscle gets non-enzymatically converted to creatinine
00:16:51.340creatinine then is excreted in the urine so what happens is that if we are on a constant dose of
00:16:58.380creatine in our diet then we hit an equilibrium and our creatinine in the blood will reflect
00:17:04.940what's going on with our kidneys if our kidneys stop working then the amount of creatinine coming
00:17:11.340into the system is constant then it'll start building up your creatinine right because you're
00:17:16.700not getting rid of it so people have conveniently used creatinine as a marker of kidney function
00:17:23.020and unfortunately the creatine came along for the ride in a negative connotation and that is that
00:17:28.620when you start taking more creatine your creatinine will drift up a little bit if your kidney function
00:17:34.700is constant. So then people interpreted that, that it was kidney damage, but it's not. It's
00:17:39.200an increased what we call rate of appearance of creatinine into the system. And so the second
00:17:44.380publication was published in the New England Journal, where an athlete was taking 20 grams.
00:17:50.960Again, not recommended, there's no logic behind it, but even if it was low dose, and they had
00:17:56.800what's called interstitial nephritis. What they didn't report is the most common cause of
00:18:01.620interstitial nephritis from a drug is taking anti-inflammatories.
00:18:04.700And as a former, you know, top sport, you know, athlete for many decades, I can tell you, many of us take anti-inflammatories, but they didn't report on that. So they just immediately assumed it was the kidney team. So essentially, yes, creatinine will creep up a little bit, not because your kidneys are damaged, but because there's more coming into the system.
00:18:23.820So when we measure creatinine excretion, which is the true measure of your kidney function by collecting 24-hour urines, in older adults who already have partially compromised kidneys, we found that the creatine did not affect that proper measure of creatinine excretion through the kidneys, and if anything, it was slightly better.
00:18:43.160there's other independent measures of kidney function and many studies have shown that when
00:18:48.180you take creatine those measures which are independent of using creatinine as your marker
00:18:52.940show that there was no damage to kidneys so that's a huge myth which unfortunately does persist
00:18:58.800and even doctors you know they just sometimes don't even know the difference between creatine
00:19:04.020and creatinine which is really a shame yeah no no and i've had that unfortunately i've had that
00:19:09.760incident happened to me um creatine monohydrate so uh the differences and there's different
00:19:17.680what i understand and you help me with this a little different types of creatine so and
00:19:24.060the most common one is the monohydrate from what i remember is there is there is there better uh
00:19:32.980or is it when you you know what do you yourself you say you take uh creatine do you take monohydrate
00:19:38.940do you is there a yeah so there's uh and you know i've been involved i've published about 30 papers
00:19:46.620in the area so we're pretty familiar with this and we've seen things come and go so the first thing
00:19:51.740is creatine is bound to something so it's sort of like um you know sodium in salt it's sodium
00:19:58.780chloride so it's creatine and something else so creatine and monohydrate means that there's water
00:20:05.340but you can also have creatine citrate creatine hydrochloride there's a whole bunch of other
00:20:09.980salts that you can combine it with and i remember very early on there were patents on i won't say
00:20:16.140what it was but it was creatine in another salt and someone challenged the patent saying this is
00:20:21.500garbage because at the end of the day and once it comes into your body the creatine comes off
00:20:25.260and it's the creatine that goes into your muscle so it doesn't matter what the salt is but they're0.92
00:20:29.180trying to claim that you get better absorption and your muscle levels go higher i know from
00:20:34.300roger's work you know you have this limit you can't go any higher once you're at you know 150
00:20:38.620millimoles kilogram in your muscle you can't go higher than that so we were commissioned to do
00:20:43.900some research and to look at this so blindly we gave people creatine and this other salt creatine
00:20:49.020monohydrate or placebo and what we found is creatine and the other salt loaded muscle the same as