[Music] hey guys welcome to man medicine what we talk about how men can optimize their health and escape the collapsing US Health Care system today we're going to talk about Testa fening a little bit and I've gotten a few questions uh about this particular drug from you guys and when I did a quick search on YouTube there are all kinds of videos from uh a number of different sources talking about this this drug which is being touted as like the next big weight loss drug it's um it's been drowned out a little bit by The glp1 Agonist for obvious reasons um but it is uh it's it is definitely gaining popularity and I think we need to talk about it a little bit because uh I noticed that a lot of the videos um they they didn't really dive into how this particular drug works and um I think they kind of approached it from a bit of a superficial angle or you know in some cases it was from sources that might be uh might actually be selling it and so you know they're not always as unbiased as they should be so I uh I do not sell this I do not prescribe it um so I'm hoping to give you guys a bit of an unbiased review about this um you know in short there's I have some concerns about this particular drug it uh it certainly sounds very promising um with in terms of the early data certainly the anecdotal stuff that's out there sounds very impressive but um you know I I try not to be swayed by anecdotal stuff I I like studies this is an evidence-based channel so um so we're going to try to stick to that a little bit okay so what the heck is Tess of fencing so Tess of fencing it's it's been around for a while um it's what's called a triple monoamine reup take inhibitor okay now monoamines are a class of uh molecules uh that are neurotransmitters most of them uh so we're talking about serotonin norepinephrine dopamine think epinephrine is technically a monoamine but we're not going to talk about that tesofensine works on all three of these neurotransmitters to inhibit the re-uptake in the um synaptic C and I'm I'm going to show you some detailed uh diagrams and we'll talk about that mechanism a little bit because I think it's it's important to understand that so that you know exactly how this particular drug works and then once you once you understand that you can see where some of the potential dangers with this medication could lie and some of the potential side effects that um we're starting to see with this stuff so um it came out I think it was a Dutch company uh called neuros search uh was I think the first ones that developed it and they they were looking for drugs to treat Parkinson's disease um and and Alzheimer's as well and it was a big flop for that it really didn't work very well but they did notice uh and it was one of the things that they categorized as an adverse effect is that a lot of the test subjects stopped eating and lost a tremendous amount of weight which isn't always the best thing for an elderly person with Advanced Parkinson's and dementia a lot of them are already suffering from sarcopenia so probably a bad idea to give them test of fenine but it's been picked up you know by um by one or more other companies and is going through trials currently um as a weight loss drug trying to get uh approval so this is just a little schematic diagram of the monoamines dopamine norepinephrine serotonin uh it's probably overly simplistic to say that uh how critical these are for for you as a functioning human being um they are critical in uh cellular communication within the central nervous system they control uh almost almost everything related to cognition your mood your level of alertness um your preferences your Cravings uh your ability to uh enjoy pleasure uh they they're involved in depression and sadness and uh a whole host of uh Neuropsychiatric diseases like they are critically critically important so you you have to be you have to respect drugs that manipulate these these particular substances because they they can have some very profound and sometimes unexpected effects and they should not be taken lightly okay here's a diagram just giving you a bird's eye view of how this particular drug and really a lot of other drugs ssris and snris anti-depressants how how they exert their effect so um at the top here we have our presynaptic neurons uh in this particular case there there's three of them so we have a serotonin dopamine and norepinephrine uh pres synaptic neurons and then there's a post synaptic neurons so this is how for you guys that um are not aware this is how neurons um how signals are sent throughout your brain from from one cell uh from one neuron to the other right so they have these little dendrites that go out and they don't actually touch each other there's a there's a microscopic little space in between the two so in order for a signal to get from from one to the other in order to transmit information it has to be Set uh has to be translated into a chemical signal which is one of these neurotransmitters which is ejected out the uh at the end of this PR synaptic neuron it floats across the tiny little space and it's picked up by the post synaptic neuron and then it triggers an action potential and off it goes and you know all of this happens in milliseconds it's obviously incredibly fast otherwise we wouldn't be able to do all the things that we do in terms of you know thinking and and moving quickly and um that sort of thing so let's um I guess we can just pick one here we'll pick the s serotonin one so um serotonin is it's created in the cell and and then it's packaged into these little vesicles which are in a uh they're contained in a um a little bilayer essentially lipid bilayer vesicle and they they float down to the um you know the end of this presynaptic neuron and when the time comes when the signal is given it will merge with the lipid Bayer here and it will discharge its cargo out into the prec aptic space that's these little yellow dots so you can imagine here it's the same thing with dopamine same thing with norpine norepinephrine it it diffuses across this space and then it's picked up by the appropriate receptor on the other side so you can see here there's a 5ht receptor that's serotonin D1 D2 that's dopamine and then we have the norepinephrine receptor here and um they are picked up by that receptor and then that chemical signal is translated into electrical signal uh generating an action potential which takes off and then this process will be repeated thousands or perhaps millions of times uh and uh off you know off a go so it's uh it's very elegant very very simple but but very elegant and very effective so there's a number of different ways to manipulate this process and there are all sorts of drugs that do this um you know all of the anti-depressants work in this system in one way or the other so if we want to increase the intensity of this signal here you know for example if we want to increase the concentration of Serotonin or prolong the amount of Serotonin uh or prolong the amount of time that serotonin spends in this uh space here between these two neurons well we can we can do a number of things we can one we can block its re-uptake so you can see here uh in the pr synaptic neuron there's these little uh um little protein channels that are at at the tip and there's the C the DAT and the net okay and those are the mono monoamine uh reuptake channels or proteins so they suck this stuff back up and then they put it back where it originally came from back inside the cell here in a vesicle and then um you know it may stay there or a lot of times it's broken down by something called monoamine oxidase now uh a lot of people have they confuse uh tesofensine which is a re-uptake inhibitor with uh MAOI inhibitor so uh or monoamine oxidase Inhibitors so these are kind of old school drugs they do not get used very much anymore they were originally used for a number of different things including depression and they still get used a little bit for Parkinson's they are um they're they're potentially dangerous drugs they have a lot of drug drug interactions they um they're not terribly effective uh and they just don't get prescribed very much anymore so um we don't really see those very much but but that's not how tesofensine works so it's not an MAOI um for those of you guys that may be confused on that and and I was originally when I first looked at this so what what Tesla fening does is it blocks the re these little reuptake channels and what's you know relatively unique about it is that it blocks all three of them um there's not very many drugs that do that so it's a triple like a triple inhibitor um you know ssris will block you know the serotonin one and then you'll have U you know snris that can block like the norepinephrine and the serotonin so you get like two maybe two out of the three are blocked but um it's it's not common to have drugs that block all three um but Tesla fening is actually one of them and there is one other one that I'll mention briefly that um was around in the 1960s but had some serious side effects so it was uh it was discontinued okay this is just just one more little little diagram here showing that uh mat protein and again there's a cert SE net NE and dopamine transporter which is dat so you have um the substrate here this this little yellow orange little oval here again we can just pretend that that's we'll say it's dopamine this time so it actually it requires sodium which is usually there's no shortage of sodium but you can imagine that uh in you know situations of like hyponatremia this might be an issue but sodium is required uh in order for this little transporter to work so the substrate uh is out here in the extracellular space it comes down into this binding area this little pocket um and then as long as there's sodium there it induces a confirmational change so it's open it takes a hold of the substrate it closes so you you can see it's encased you know briefly within um within the protein Channel itself and then it under goes another confirmational change and opens up on the bottom side and out it goes it pops out into the intracellular space so kind of a kind of a cool little little diagram that uh that shows how that thing works and again tesofensine messes with this with with this channel so you know as I mentioned there's a ton of drugs and this is like not even close to a comp a comprehensive list ton of drugs that influence these uh these Transporters so I'm not going to go through this whole diagram here because it's it's super busy but at the top here of the Transporters you have dat net insert and we can look down here we'll go down to Inhibitors so cocaine is a very potent inhibitor of of that dopamine uh it actually also inhibits norepinephrine and serotonin also to a certain extent you can see that there as well well buproprion otherwise known as Wellbutrin commonly used um very commonly used anti-depressant uh works on the DAT uh transporter as well methylphenidate otherwise known as rlin uh works on Dat and net so um not so much on on serotonin and then uh you know we can go over to the other side here um the nor net is you know it's for Norine but it actually picks up dopamine a little bit too so um so these the drugs you know just a few of them here uh amphetamines uh MDMA otherwise known as ecstasy does it uh there's does methylphenidate again ryin and then we go over here to C and this is where all your ssris and many of your tricyclic anti depressants like and other things like trazodone uh that affect um the serotonin uh transporter so a lot of different ways to manipulate this this system and again again tesofensine is just one of them but if you look down here there's another little drug called n nomifensine and it's in the involving dat and net um it also affects the C pathway as well they just don't mention it here um but um that that's a cousin of tesofensine that again had some major issues came out as an anti-depressant but was was discontinued so um one of the things that that struck me when I when I when I saw how Tess of fening worked I was like you know that's sounds a lot like cocaine you know and you can see it here cuz cocaine does the same thing it it affects all three of these um these transport proteins so I'm like well so do do people get high off test of fening and you know the answer is no they don't uh it's not psychoactive in that way although it's kind of interesting I came across a number of different videos and maybe you guys have some experience with this drug personally can can chime in on this that um many people feel more activated more alert they have a boost in their mood um they feel more productive um maybe not to the extent that they would on something like Rin or modafanil but there does seem to be you know some people like a bit of a stimulatory effect so certainly like nothing along the lines of cocaine but um there there may be something there I didn't there really wasn't much of that even discussed in any of the actual studies so it all it's all anecdotal but if you again if you guys have experience with that chime in on the comments here because I would love to hear about that a little bit so I don't know if it technically would be classified as a neut Tropic but I think some people think it is uh again I don't have any personal experience with it but uh if you do let me know so yeah it's um it's definitely not not like cocaine uh as it talks about here in this in this article It's Like Cocaine but no fun so what was I put this in here because this was kind of amusing I thought um and uh they it was a study about U that the company neuros search did and they actually gave um Tesla fencing to uh a whole bunch of like very experienced recreational drug users you know men and women who uh used a lot of cocaine in their day among other drugs and um yeah they you know the bottom line is the uh the recreational drug users they didn't like Tessa fencing they didn't get anything out of it they're like I'm not taking this stuff I'll go back to using cocaine and amphetamines so anyway interesting study but the you know the idea that they put forth is like you know this stuff has it has such a long halflife and you know the one of the reasons that cocaine apparently is so euphoric is obviously it's like extremely potent in manipulating these these neurotransmitters but it comes on very quickly so it's like this you know instant Rush apparently of uh you know Euphoria and energy and you know mood elevation in addition to all the cardiovascular stuff the tapic cardio hypertension Etc you know that come along with it but Tesla fenine is um you know as we'll talk about here shortly is extremely long halflife and it's kind of just slow effect and so it's just not it doesn't give that Rush that um cocaine does and that's they theorize that that's why it just it really doesn't have much in the way of abuse potential um because it's just not that fun to take test of fenine so um so yeah so the halflife I mean if if you took a a a capsule of tesofensine right now it would take 5 to eight hours for you to get uh a peak level with that but the interesting thing is the halflife is really it's like insanely long it's like 220 hours and that's because it has a metabolite that has that has biological activity that's also um you know that has a extremely long halflife it's metabolized through the liver we're going to talk about that at the end uh cuz that you know that that I have some concerns about that um as well but it uh yeah super long halflife 220 hours so you know it raises the possibility this is typically dose daily like all the studies show that it's dose daily but when I see a drug that has such a long halflife like that certainly after you've reached a steady state you've been on it for a while um it sort of makes the case that like maybe you could you could do intermittent dosing on this maybe you could dose this twice a week maybe you could dose it three times a week um and as I'm going to talk about here in a second I there's 's potential to maybe just use this on an as needed basis I don't there's no studies on it but um yeah it makes me wonder like maybe you don't need to take this stuff every every single day when you have such a long halflife um the other thing obviously is if you do take it every day and you know let's say you go on a trip and for a few days and you forget it it's it's not a big deal you know it's going to still be in your system and um you know you're going to still receive the benefits you know from that so um so where we at with Tesla fencing you know in terms of of its approval it's it is still not FDA approved and I'm I'm a little bit you know I'm a little bit surprised by that I mean they they've there's good studies on Tessa feny and going back you know 2005 2006 um that are all positive and so I kind of Wonder like well what is taking so long for this drug to get approved and and I don't know the answer to that uh maybe you guys do um but this is one of the more recent things it's from the company son who I think has picked it up now uh they are also out of Denmark and they published a phase three clinical trial where they had some you know fairly positive effects it was a 24- we trial they had over uh was like 372 obese individuals and um they lost a significant amount of body weight um I think the highest dose um group lost up to like 10% of their body weight so uh with you know a relatively benign side effect profile so so that's a phase three trial without going into too much detail there's uh you know 0 one two three and then finally phase four so you need to have you need to complete a phase three trial that is acceptable preferably more than one to the FDA in order to receive approval and then once it's approved you know then it can be sold on the market and that's where you can do like a phase four trial so with each trial you basically you have a larger and larger and larger group of people um you know to you know and each one has a different goal like you know you want to establish safety okay we not we're not killing people with this drug so this this medication Tes off fening pass that okay um you know is it effective okay seems to be effective um you know how and then you know is it non inferior to um you know the currently available drugs Etc seems to be you know right up there with uh some of the weaker gp1s actually when it comes to weight loss um so so we're still waiting on this and that's why like as a doctor I can't you know write you a prescription and have you go down to Walmart for test off fening so right now to the best of my knowledge this is only available through these quote research chemical sites which you guys know how I feel about those buy or beware um and I believe it can be uh it can be obtained through compounding pharmacies which is probably a safer route um you know with a with a physician's prescription but you know as of as of right now 2023 this is still not FDA approved again if if you guys know what the holdup is let me know um because this drug has been studied for years and years and I have not seen any studies at least any published data showing you know really major adverse effects um anything that would torpedo this drug so we'll have to wait and see um I did a little research you know in terms of like I was wondering well how many drugs that have successful face 3 trials actually make it to the market and it's about 25 to 30% so I mean even even with this phase 3 study it's still not uh certainly not a guarantee at this point but you know I guess I guess time will tell okay let's let's talk about you know how this drug works and some of the studies that are out there so th this is a rat study um but it it's really good it's it it it basically it this translates the the the effects that were seen in the study translate pretty well into humans and it has some Nifty graphs that I wanted to show you which is why I chose it so so this particular article is from neuropharmacology 2010 again this is an old study right 13 years ago this was done uh it's called tesofensine a novel triple monoamine reuptake inhibitor induces appetite suppression by indirect stimulation of alpha 1 adrenoceptor and dopamine D1 receptor Pathways in the diet induced obese r at I don't know where they come up with these names that's a mouthful but um they um they got these you know a whole colony of mice they made them morbidly obese by feeding them a very high fat high calorie diet and then they exposed them to various levels in some cases extremely high levels of um Tesa fenine and you know we look then they looked at the effects and uh they were pretty interesting actually again this is a fairly short they looked at mainly short-term uh data with these with these mice but they you know they did look at some longer term ones as well but it's the short-term ones I want to show you guys that are pretty interesting because this is why I was saying like maybe this could be used on an as needed basis again I take that with a grain of salt what they concluded tesofensine dose dependently induces hypophase so less eating a single dose of tesofensine so they use various doses 0.1 to up to 3 milligrams per kilogram which is a big dose if you translate that into humans that would not be well tolerated um said it robustly and dose dependently inhibited food intake in these rats over a 12-hour period okay so uh they said during the 12-hour observation period so they called the placebo they call it vehicle treated so the they injected the Tes of fencing so you know and it has a carrier I'm not sure what it was uh probably some sort of you know either saline or um you know some sort of carrier oil so they they called the placebo vehicle so they just injected the vehicle whether it was saline or uh a carrier oil with no active ingredients so that's why they called it vehicle just to clear that up because I thought that that was a little strange um so the placebo mice on average would uh consume 54.1 uh kilo calories over this 12h hour period just on average um the ones that got the highest dose of tesofensine their total caloric intake dropped to 12.6 kilocalories which was a they said a 77% reduction in energy energy intake so these high do test of fenine mice they just stopped eating and that's what you can see here with this this graph which really kind of spells it all out so we're looking at time zero here where they're dosed with the test of fenine and then we go out to to a total of 12 hours and as you can see here like the higher the dose the less cumulative food intake that these mice have over that 12 hours let you know and again the the high dose of the 3 milligram per kilogram it just shuts it down completely uh they hardly eat eight at all and um so very profound effect on on feeding behavior in these mice okay this is another graph um also very interesting uh again looking at um you know the first of all 12 hours and then what would happen after that 12 hours without a repeated dose just a single dose and so you can see um you know the white bar is the placebo the black bar is the Tessa fenine and they just looked at 1.5 migs per kig in um in this particular bar graph but the graphs look basically the same with the other doses as well so Before Time Zero you can see they're the White and the black bars are pretty much they're pretty even right they they they match up pretty darn well but in this first 12 hours so 0 to 12 kind of you know agreeing with that previous graph the white bar is right up there still and look at this this black bar is like way down way way down and then once you hit 12 hours there's still a pretty significant difference here but the treated mice they're start the treated mice are starting to eat a little bit more it's starting to come up again right and then once you get into that 24 to 36 hour Mark um they and then beyond obviously they went out to 72 hours they they pretty much go back to eating the same so for that first 12 hours there is a profound effect on these mice with Tesla fencing and then as time goes forward it kind of you know the drug wears off essentially and they start eating normally again and that's why I say you know maybe again there's no studies on this in humans but um you know if if you know you're going to be in a situation where you're going to be tempted to overeat like I did on my recent vacation to Dubai um you know you potentially could strategically dose tesofensine before you get into that situation to perhaps not go completely off the rails like I did with birthday cake that I ate um a few days ago and I'm still feeling the effects of that so again no human studies on that uh but I just bring it up as a possibility if any of you guys use it that way let me know the other interesting thing is um I was wondering you know would you have a rebound effect so you you know you've crushed appetite now for 12 plus hours and then are you going to start eating more to compensate for that and it looks like going out to the 72h hour mark again the bars are roughly the same so you don't have like this rebound hyper phasia where you you overeat to make up for the loss calories that you didn't eat you know in during that treatment window of roughly 12 hours so so that's a good thing um it's very very interesting and then these uh these charts here I want to go over these just just briefly because they they say a lot about the way that this drug affects feeding behavior in mice and it and you know this this is probably you can probably expect similar results in humans so um look at so we'll go we'll just start it like we'll go clockwise I guess so number of meals up here in the left corner a so you know at above once you got above 1 milligram per kilogram so the number of meals that these mice ate started to go down it wasn't doesn't too much different at a lower dose than that so they were still eating the same number of meals for the most part except at the higher dose um but when you go over here to the average meal size it starts immediately going down and just goes down and down and down as the dose goes up so they're going you know they're going to the little food bowl and they're getting their little rat Chow but uh the higher the dose of the Testa fenine they would only eat a little bit and then they would stop okay um average meal duration same thing for the most part uh with escalating doses of Testa fenine um the uh the amount of time that they spent at the feeding Bowl would go down which is what you'd expect and then um the other one that's interesting here is late latency of first meal so that's like they wake up from sleep like how long does it take them to go oh I'm hungry and go to the to the Chow Bowl well you know again at the lower doses here it wasn't terribly different than Placebo but as you got above uh above 1.0 migs per kig it took quite a long time for them to to realize maybe I'm a little bit hungry maybe I should go get a little snack and then go you know run on my little hamster wheel and do whatever it is that rats do um when they're hanging out in their cages uh being subjected to uh research studies so um yeah they they sounds like you know these rats were not terribly hungry when they woke up first thing in the morning and I'll tell you that's an issue for me it may be for you guys too that's I am starving when I wake up in the morning and it's I have a routine to mitigate that so I don't you know go too crazy but um it sounds like tesofensine really had a pretty significant effect in the mice um and again uh you we look at meal size especially that first meal size which you know again that tends to be big for some of us I'm I'm guilty of that again with uh with the exception of the 0.5 mgram dose here which seems to be a bit of an outlier as the dose goes up that first you know breakfast meal we'll call it of rat Chow was uh substantially smaller in the in the treated group so you know you eat less often and you eat less you spend less time eating um all of that results in a uh overall a significant decrease in the total amount of calories consumed while the drug is in effect essentially so very interesting stuff um the other thing they mentioned you know that in the title they mention yeah about alpha 1 blockade and I'm not going to get too deep into the you know Alpha and beta receptors but um you know it raises the possibility that you know what if you're on a what if you're on a medication that is an alpha blocker well if if we need to use the alpha1 receptor in order for Tesa fencing to work you know there are a bunch of different drugs that get commonly used uh especially in men that inhibit or block the alpha 1 uh receptor that might interfere with the effects to test of fenine and they actually found that in mice so they use pricin which get doesn't get used very much anymore um you know gets used for um you know it can be for hypertension and prostate issues but um I don't know if I've ever prescribed prisin I mean maybe I did in residency like 20 years ago it's um the brand name is mini press so it's pretty old school I don't think anybody really uses it anymore but if you give these mat these rats mini mini press it blocks the effect of hyren and that's what this chart shows here so um yeah prisin plus place it's the same as uh Placebo prisin plus Tessa fenine also pretty close to Placebo so the prisin blocked the effect of uh of the um of the Tes of fening so why is that relevant well you know you guys you know you may not be on miness or prisin but you might be on Flomax okay for your prostate and you know that that's slightly different it affects the alpha 1A receptor but again I couldn't find any data you know nobody's studying uh tesofensine and Flomax at this point so keep in mind that if you don't get an effect from tesofensine and you just happen to be on Flomax you know you could be these two drugs could be canceling each other out to a certain extent um or at least the flax is canceling out the test of fenine and you're not getting the effect there uh terazosin otherwise known as hyran uh I used to prescribe a lot of that actually for prostate issues BPH specifically uh way back in the day it it still does get prescribed I still see it um every now and then and uh but Flomax you know and some of the other derivatives of of flx some of the newer versions um tend to work a lot better and so you just don't see as much hyron anymore but it's it's totally still out there so if you're on that medication it uh it totally could be an issue okay okay let's look at um another human study here so we talked about the rats um and again there there are tons of studies on on tesofensine they're all small so they're all these like phase one and two and then one case phase three clinical trials they're all small uh and this one is too it's randomized control trial of of tesat for weight loss in hypothalamic obesity so um tesat is a combination they they added mopol into this I'll talk about in a second why they add like why would you add a beta blocker to test off fenine uh I'll talk about that here in a second but that's what they did in this particular uh group of patients so um and this is a particular a unique group of patients with something called hypothalamic obesity which is a very unfortunate condition where you know usually through trauma or you know some secondary or acquired reason uh people have damage to their hypothalamus um and so they lose the ability to control their eating because all those you know those important parts of the brain that regulate satiety food cravings Etc have been now been damaged so a lot of times like you know you'll see this in uh people who've had brain tumors or who have had radiation or some other trauma to the brain perhaps a stroke there are some congenital and genetic uh causes of this as well but it's super difficult to treat like they they don't respond to behavioral and lifestyle stuff they have a structural brain problem um but tesofensine it turns out actually works you know reasonably well for them uh so this this you know maybe it'll get approval for this particular group of people and that will be the way that it gets to the market I don't know but uh anyway in this particular group again a small study 21 adults with hypothalamic obesity and they looked at them for uh a total of uh 24 weeks and the dose uh the test of Fenian dose was 0.5 milligrams which is probably the most common and probably the best dose for this we don't know for sure um some people say that 0.25 works well for them and some people I'll go all the way up to a milligram a day uh you will hear more anecdotal reports of more serious side effects at that 1 milligram dose but you know .5 milligrams or 500 micrograms is uh probably going to be the sweet spot for most people I guess time will tell and then that was combined with uh 50 milligrams of metool uh which is you know fairly solid dose you know mopol is typically started at 25 to 50 mg and um it's typically dosed twice a day so this was not an extended release mopol dose uh but for whatever reason they just they chose 50 milligrams of the the standard mopol and again interesting why they chose this um they they did this because one of the side effects and we'll talk about side effects here shortly is that there there seems to be a um a stat a statistically significant elevation in patients's heart rate um on tesofensine which isn't surprising like if you know if cocaine raises your heart rate so does tesofensine although not as much as cocaine thank god um so the idea is well we can we can combine this with a beta blocker and then you know maybe we can we can blunt some of this tacac cardia that uh patients are experiencing and you know it could be unpleasant for people that you know are prone to you know feeling palpitations and whatnot or maybe who have cardiac d rhythmia uh Etc they probably shouldn't be taking Tes fencing but regardless I think that's um that's the rationale for that it's interesting that they chose mopol um you know beta blockers are not ideal drugs to put on to give to people who are interested in losing weight with a few exceptions um you know moper La in particular some of these older uh generation more cardio selective uh beta blockers they are many cases associated with weight gain there was a Gemini trial which did show metabolic slowdown and some weight gain in patients so it's always a risk benefit analysis um there can be some you know minor perturbations in people's lipids and glucose metabolism which are unfavorable with mopol and and and drugs like that it it would have been a much better choice to use like a third generation beta blocker something like nabol or Carval all which really doesn't have those effects to the same extent and would be a little bit more weight friendly so look for a big Pharma maybe to come out with a carvol or nebivolol and Tesa fening combo uh combo drug at some point maybe when this thing gets finally approved um but anyway I digress that's I think that's the reason why they they they did the mopal LA so um in terms of side effects before we get to the the the the actual data um again pretty well tolerated here there was uh there was a patient that dropped out because it precipitated they they had an anxiety disorder to begin with and apparently made it quite a bit worse and so this particular patient dropped out of the study um the other things were uh they considered them relatively mild so sleep disturbances 50% of them had a sleep disturbance but again it's hard to make you know when you have 20-some patients you know when you say half of them had a sleep disturbance well what would that look like if we had you know 20,000 patients I don't know but uh anyway for what it's worth that sleep disturbances were present in half of them 133% had um in the placebo group had a sleep disturbance dry mouth which isn't too surprising was um dry mouth was 4 3% uh 0% in the placebo group so it's probably a real thing headache 36% in the treatment group 0% in Placebo and in this particular case not surprisingly there was no significant difference in heart rate or blood pressure because of course the moper law probably took care of that the the studies out there by the way I don't mean to skip ahead in terms of side effects but you know some of them do show a some some minor elevations in blood pressure both systolic and diastolic but there's a few others that don't so it's not a consistent finding but um the the elevated heart rate does seem to be a real and consistent uh finding in in most of the studies that I was able to pull okay so these are some charts you know how well did this stuff work in this you know relatively small group of adults with uh hypothalamic obesity turns out it work pretty well so this is uh the first one here that's labeled figure three changes in body weight over time so top one is obviously Placebo and by the way like they all receive received like diet and exercise you know counseling and you know what that entailed who knows but um you know the placebo group did lose a little bit of weight initially but then as often happens you know um they started regaining their weight and at the end of the uh 24 weeks were basically back where they started but not so with the test of fencing group they just continue to lose lose lose lose lose and at 24 weeks they had lost um this is a this is in percent so 6.6% of their original body weight which is pretty impressive um you know the interesting thing is you know at 24 weeks the trajectory still continues down so it would be really interesting to see you know if this goes out 48 weeks you know or longer is that you know when do we hit that Plateau I don't know I don't know that's hopefully we'll get some studies eventually on that but it didn't seem to Plateau very much if at all um over the course of the 24 weeks um so so that was body weight and then here's this next chart here looking at uh satiety scores so they would measure you know how full do you feel at uh with you know after meal Etc and you know surprising not surprisingly the uh these poor people with their damaged hypothalamus they they you know on the placebo group did not feel full at all they were probably hungry all the time but there was a a very significant Improvement in um the the Tesa mat group so the Tesla fencing group um felt uh you know much more satisfied with their meals I I wish they had measured you know how big their meals were and whatnot like like they did with the rats but my feeling is that you know generally if you reach a high level of satiety during a meal what do you do you you stop eating right you push away so you eat less and you probably eat less frequently as well so I think that rat study likely does translate over but just just goes to show you that uh you know we're not just talking about losing weight here but we're um we're addressing like one of the major if not the major issues that causes people to fall off the wagon here which is hunger and in many cases you know Cravings which Tess um tesofensine also helps with food cravings so um it's uh you know in many ways at least on paper this sounds like the ideal drug and you know unfortunately there's no such thing as an ideal drug um but things are looking you know looking fairly promising for this so overall the the placebo group lost 0.4 kg so essentially no weight loss in the placebo group which is exactly what you would expect and the Tesla fenine group they lost 6.9 kilos over uh 24 weeks which again was 6.6% of their um of their starting weight so you know not as high as uh tepati for example but certainly approaching you know glp1 Agonist level of um of uh of efficacy so you know again I I don't know let's assume that this drug comes to Market um I don't know how much it's going to cost it will certainly be expensive at first uh when it comes out as a brand name but um you know I have a feeling it's probably because it's an oral agent you know for no other reason than it's an oral agent will likely be a whole lot less expensive than um mararo AIC you know Etc which you know are extremely expensive um especially since now the FDA is clamping down on compounded versions of it and you know the the only versions available at least in the US to to patients with obesity are going to be the big farm of brand name ones and um as we know insurance companies do not like to pay for stuff like that um so this could potentially be you know a good alternative so okay let's talk about side effects real quick you know I mentioned the heart rate Issue 5 to 10 beats per minute is what most of the studies show that is uh obviously blunted by concominant use of a beta blocker again if you know if at all possible you know you'd probably want to steer towards some of the one of the newer beta blockers Carval all and the bival all would probably be better choice um being that they're a little bit more weight neutral um and if you know especially if you're taking this for uh for weight loss which is obviously what it's intended for the blood pressure studies you know most of them that I saw did have a little bit of a I mean we're talking like less than five points systolic diastolic elevation of blood pressure but a lot of them showed no change in blood pressure and it it may be that you know the Tesla fencing does elevate blood pressure on its own but at the same time you know people are losing tons of body weight which clearly is associated with lowering of blood pressure so it may be that those two effects like offset each other um a little bit so one of the things I'm concerned about with tesofensine and again again it the studies are small and I'm not seeing there's not a huge signal for this but um there's C there's potential just based on its mechanism you know when when you are increasing the levels of these neurotransmitters especially all three of them at the same time you know in susceptible individuals it raises the possibility of like precipitating like some neuros psychiatric issues um agitation panic attacks mood disorders um you know Mania you know I don't know if it would precipitate something as severe as like a schizophrenic or psychotic episode but that certainly is a possibility the the thing that you should be aware of is in these studies I mean they screened out people for the most part with serious mental health disorders in these you know phase one through three trials so we don't really know like if this is released out into the general public which it kind of is already um you know are we going to start seeing you know an uptick in that um so again if any of you out there are using this stuff and you've had issues with uh panic attacks or anxiety or any kind of like neuros psychiatric problems please let me know in the comments cuz I'm I'm super curious about that but you know that that was like one of the first things when I saw how this you know the mechanism of this drug I'm like this could you know in certain susceptible individuals like this could be you know potentially a serious problem and um I guess time will tell so um I mentioned the the cousin of Tessa fenine uh Noma fenine so Noma fenine Works in a very similar fashion it's obviously a slightly different molecule but uh it came out in the 70s as an anti-depressant it didn't really work that well but it was pulled from the market like in the mid 80s because uh it caused homolysis through a mechanism I'm not I don't truly understand uh homolysis is like bursting of your red blood cells so not not a good thing so I don't know if it was an autoimmune thing it was a direct you know Toxic effect of the drug so that thing got yanked um there's been at least in The Limited studies that we have no evidence that tesofensine is associated with homolysis whatsoever uh but again you know we have bigger stud maybe maybe that could be an issue um something to be be uh aware aware of I mentioned the insomnia issue the dry mouth that seems to be a real thing uh a lot of patients experience nausea in these studies the the sleep disturbance makes a lot of sense so I mean it's tough with the the long halflife I mean it's not like you can just take this stuff in the morning and then it's kind of gone in in the evening it's still going to be there in the evening and uh you know could be you know could be a problem if especially if you already have issues with sleep you know as it is so just you know just stuff to be aware of now the other thing that really concerns me that I haven't seen anybody talk about in any of these other um YouTube videos that are out there is is the you know the strong potential for like drug drug interactions and you know a lot of people are on ssris a lot of people are on multiple anti-depressants these days like large percentage of our population which are already affect neurotransmitter levels among other things and so you know there's a potential you're adding in test of fenine in there um you know are we going to start having you know issues with um something like serotonin syndrome which I've seen a lot in the emergency room you know in my career or potentially God forbid something called neuroleptic malignant syndrome which you can look up it's a often fatal condition I've seen it twice and it was super severe uh both patients nearly died um and you know required Innovation and uh you know aggressive cooling measures and and those were precipitated by uh Misadventures I'll call it with anti-depressants so these things are not to be taken lightly um you know I would be extremely cautious if I was on an anti anti-depressant of any kind and with tesofensine I personally my advice would be just to avoid it entirely unless you get a complete green light from your doctor which you know the odds are is your your Prim care doctor even your psychiatrist may never have even heard of test of fenine so I doubt you'll get the green light but I I think the risk would be too high I wouldn't I wouldn't mess with that um so you know the other thing to think about anytime you take a drug you know it has to be metabolized or it has to be excreted and a lot of times that gets done in the liver there's a cytochrome p450 system there um Tesla fenine is metabolized by the CP 3a4 enzyme system which is the most prevalent one um like up to 50% of the drugs that are out there on the market both over the counter and prescription are metabolized in to some extent by this particular enzyme system so it's and and again in and of itself if you don't overload that system it works just fine you can you know you can take drugs that that tax that system to a certain extent but you can run into issues when you start taking multiple drugs that now are both competing for that enzyme and so a lot of times s what will happen is now one of those drugs or both for example are not being broken down as quickly as they should be and you'll get elevated levels and again I see stuff like this in the emergency room all the time where um you know a patient is who is on a on a drug and you know they primary care physician or somebody else uh puts them on another drug uh not knowing that they are also metabolized through the same enzyme process and then now we end up you know with you know serious toxicity from from one from that second drug or maybe the first one so there's a huge long list the the really strong Inhibitors of this uh sip 3a4 so in terms of antibiotics choriyon which doesn't get used that much anymore brand name I believe is biaxin used to be big with sinusitis and otitis and upper restory stuff but a lot of problems with chloris and prolong QT syndrome stuff like that so I don't think I've prescribed that in about 15 years um itraconazol ketoconazol now that does like those are antifungals which have a lot of liver toxicity very hard on the liver and then there's a whole host of like uh HIV drugs so if you have HIV and you're on triple therapy um you probably should avoid tesofensine it's probably a good idea but all kinds of other drugs uh calcium channel blockers uh especially like deltm Verapamil you don't want to get toxic on those trust me uh that that's a serious serious problem uh anti- iic drugs like amone are metabolized there so again adding in tesofensine it just adds more work to that enzyme system and then you can end up with toxicity so um anyway the the list is super long it's just something that you guys should be aware of again I haven't heard anybody talk about it on YouTube so I'm just going to throw it out there and then the other thing to to keep in mind like we're all genetically different right so um you know one to 2% of the world's population and it does vary by ethnic group will have some sort of a loss of function mutation in this ZIP 3a4 U enzyme system where you know you have it there it works it just doesn't work that well or doesn't work as well as the quote wild type so if you're unfortunate to have one of those then you know you have to be extra careful with what you put in your body in terms of prescription drugs of course it's not even it's not just prescription drugs though it's supplements too so um you know I would be very cautious about like St John's wart um oh what's the other one so uh uh Rod ola which you know is popular in the naturopathic world is an MAOI inhib it's an MAOI I always say MAOI inhibitor but the I means inhibitor so um you know that could be seriously problematic you start taking a lot of riola with your Tesla fenine and now now you've got toxicity from that so uh I just would be extremely cautious with this particular drug and um and just in general like poly Pharmacy is generally a bad idea you know there there are times when poly Pharmacy is indicated but you know needs to be done under the supervision of a of a competent physician who understands pharmacology and who's intimately familiar with all of the drugs that you're taking how they work their mechanisms Etc you know and unfortunately with test of fening because you know I think I'm going to guess that 99% of you have gotten this drug um probably off of uh research chemical sites and are or are basically just managing it on your own you know no offense but you probably don't have that that kind of a pharmacology background to do this in a safe manner so again if if you're going to use test of fenine I think um it needs to be done under a physician's a competent Physician's uh supervision so you don't get yourself in trouble okay so um other precautions um and we'll just we'll end with that um again you know most of the Tesla fencing that's out on the market my impression is that it comes from these research chemical sit so and I've mentioned this multiple times in other talks you know when I've mentioned sarms and peptides and things like that is you know it's buyer beware right like you have no idea what's in that bottle the the quality control is uh is highly suspect in my opinion and I know that a lot of them you know they say that they provide a you know an independent third-party testing sheet that shows the Purity okay great you know maybe that's true but you know I could Photoshop one of those in in about five minutes and I'm not very good with Photoshop okay um so just consider the source be careful guys um you know hate to see anything bad happen to you uh again I mentioned this before but if you're on any other if you're on an an anti-depressant of any kind if you're on a mood stabilizer of any kind um especially you know if you have bipolar that'd be concerned about you know precipitating a manic episode if uh you know if you took too much uh or even any Tesla fencing um you know anything that messes with dop mean serotonin norepinephrine and this includes some of these uh over-the-counter neutop supplements I think you just need to be very very cautious you need to work with a doctor who understands this stuff um uh or you know ask questions of a you know pharmacists are pretty well versed in this stuff as well uh many of them are so you might be able to if your doctor doesn't know you can potentially get a hold of a pharmacist and ask them and then finally you know just like with any drug if you are going to use this uh I would use the lowest effective dose uh um and I would use it for the shortest duration of time like to achieve a certain goal it's probably not a good idea to be on test of fencing for years and years and years we just don't know we don't have any data you know there's no safety data going out past a year that I'm aware of so just you know again just be cautious and then the final the final recommendation I'll have with this is the same recommendation I give to people who use these glp1 agonists you know both of these drugs uh drug you know drug classes they they work by causing you to eat less you know the mechanisms are different but at the end of the day you're eating less so yeah you're losing weight but again you want to make sure that you're not losing precious muscle tissue so you you need to not you need to have a plan you need to have a plan so you need to make sure that you're eating an adequate amount of protein which at a minimum is going to be 2.2 gram per kilo and if you're in a serious calorie deficit which you probably will be on this drug it's probably going to be more than that at least based on the current literature you AB absolutely need to be incorporating resistance training that's the one of the best things you can do to hold on to muscle tissue eating adequate amounts of protein is is nice but if you're not also engaged in resistance training you are going to lose more muscle muscle tissue so just make sure that you do that don't just take this stuff and go about your business and you know every day when you step on the scale get get happy because what's again at the end of the day maybe you lose 30 lbs well if 10 of that is muscle tissue now you've you've wrecked your metabolic rate and guess what that weight's coming back that's coming back and then you're going to be like H I got to get back on TES fenine or gop1 Agonist of your choice whatever the case is and it's just becomes this roller coaster and you know that's obviously not not healthy it's not good for you long term so um make sure you you have a plan if um and if you need help with that reach out to a physician or a nutritionist or somebody uh or even a trainer who's well versed in this sort of stuff and can help you do this uh in a safe manner so that's all I got on Tesla fening guys super interesting compound um I I'm expecting this to get FDA approval I don't know what's taken so long I guess we'll see um I would love to hear you guys stories I have no personal experience with tesiny and I have no reason to take test of fenine I'm not terribly interested in it um but you know as a doctor that treats obesity I I want as many arrows in my quiver as I can and so if this ends up being a viable drug that I can use in addition to what else is out there then I would love to have it but clearly I want it to be safe um and I think that we need a lot more studies to to help iron that out a little bit so all right guys take care I will catch you next time all man medicine video and audio has been created and shared online for informational purposes only this podcast does not constitute the practice of medicine or professional Healthcare Services of any kind including the giving of medical advice I am not your doctor no doctor patient relationship has been established this content 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