in these new weight loss medications injections ozempic Manjaro wilgovi they are using a neurotransmitter as a hormone I'm David Brown I'm a bariatric surgeon 98 of what I do is weight loss metabolism bariatric surgery and I've been following this topic for quite a while with great interest I think that there are things people need to understand including Physicians who prescribe these medications I am very focused on human physiology in my practice understanding how the human body really is supposed to work from a cellular biochemical standpoint and I think there are significant parts of this story
that are being missed and I think that people considering these injections need to understand them better and I think that the Physicians who prescribe these medications probably need to understand more about them as well there's a great Paradox in this story of these injections because the people who seem to respond to them most impressively losing the most weight are the people who don't have as much weight to lose the people who are very overweight super obese don't usually have the same response to these medications so what we see is the people who need weight loss
the most don't respond quite as well as people who don't need it as as much and I would argue that the people who respond most impressively in weight loss to these medications are going to suffer the more severe side effects long term so let me explain we do have reports uh pretty widespread of some side effects people are noticing one of them is a significant amount of muscle loss in our Clinic we often see about 40 to 50 percent of the amount of weight that is lost is coming from muscle other clinics are reporting the
same thing and in your bigger studies the public study is in Jama and other medical journals they show this also that of the amount of weight lost on these medications it's about 38 to 40 percent of the weight loss is coming from muscle and if you know anything you know if you study and follow longevity in the science interested in longevity you see this as a very big problem potentially another side effect that is being reported increasingly now is what we call gastroparesis um and this is to some degree paralysis of the stomach people who
are on these medications and stop taking these medications some people are finding persistent nausea vomiting and inability to eat and what they're finding is that this is because their stomach is paralyzed essentially that the motor nerves and the muscles that allow the stomach to contract peristals and empty those are paralyzed these are some Clues as to what is going on with these medications and why they are going to be problematic for some people so what is going on here why do we see these side effects and how do these injections really work the focus here
is physiology and understanding how the medications are changing that physiology that is the only way we can understand really obesity as well as some of these weight loss approaches so these injections they are a synthetic form forms of a naturally occurring peptide a a protein a peptide made of amino acids occurring in the human body it's called glp1 glucagon like peptide one now this really is a neurotransmitter in a healthy human being and with these injections synthetic forms of this are being um injected into a person's body in very high levels and so really what's
happening is a neurotransmitter is flooding the system and being used as a hormone so to understand the way it's supposed to work let's back up a little bit think of the brain as a computer a supercomputer it's more than that but that is where the master controls are for most things many things including weight appetite metabolism Cravings blood glucose hunger pains blood pressure inflammation that's where the controls are now every computer requires input the appropriate input into function properly you think of sitting at a desktop laptop even a cell phone you provide the input on
the keyboard or the screen well this computer the human brain also requires the appropriate input in order to function properly the way that it's supposed to be is that one of the primary most important inputs into the brain comes from the gastrointestinal tract now that GI tract mouth to anus is about 30 feet long and in that 30 feet there's over 400 square feet of surface area which is like a small apartment it's actually our biggest interface with the world around us even though it's inside of us well that 400 square feet of surface area
is packed with specialized cells that are sensors receptors they are gathering information collecting data serving these are called enteroendocrine cells and more recently they're called neuropod cells and increasingly it's becoming recognized that they're a part of the nervous system they are like a neuron or a brain cell now on that surface of the cell which is facing the inside of the intestines um that cell is detecting what's inside the intestines sugar fat proteins many different things and on the other side of the cell so we're talking a very small distance on the other side of
the cell that enteroendocrine cells releasing chemicals molecules neurotransmitters to signal across a very small distance to another cell and that other cell is a nerve cell it's a nerve ending and these enteroendocrine cells they release over 20 different molecules or neurotransmitters to Traverse that tiny distance and signal to the nerve and there are millions of nerve endings throughout the gastrointestinal tract they coalesce into What's called the vagus nerve very important nerve is the primary connection between the brain and the gut and so in this way this huge surface area in the intestines is signaling to
the brain really using these neurotransmitters across this tiny little distance well with his injections they are taking one of those 20-some neurotransmitters glp1 and they modify it so that it isn't broken down by the body like normally happens and they're creating very high levels of this in the body now it's important to note that in people who are obese who have diabetes when they're fasting the levels of this glp-1 in their blood are higher than normal people who are lean don't have diabetes they have higher fasting levels of that glp1 and again in people who
are obese who have diabetes when they eat a meal the response to the meal in the level of glp1 is is pretty wimpy it's a small response compared to normal well if you understand type 2 diabetes we see the same thing with insulin in type 2 diabetics that fasting levels of insulin in the blood are higher than normal and their response to a meal the insulin response is wimpy so for the Small Bump and so in diabetes is one of the fundamental problems type 2 diabetes is they have too much insulin and modern medicine often
will approach that problem by giving them more insulin we do that and we say we I don't that is done because it lowers blood glucose and we like that that's it we'd like to see that we think that we're doing good and it is good in part but the bigger picture demonstrates something that's very problematic in type 2 diabetes who are given insulin their mortality rate all-cause mortality goes up pretty dramatically once they start taking uh what we call exogenous insulin insulin shots because fundamentally we're making the fundamental problem worse so what I would suggest
is that is in a significant number of people taking these weight loss injections we're doing the same thing we see a result that we like people lose weight their diabetes gets a little better um but there's a picture that we're not looking at and according to this other picture in a lot of people the fundamental problem is going to get worse with these weight loss injections and that's why when people stop them they gain weight and you know their hemoglobin A1c the other Pro metabolic metrics worsen quite rapidly um another important point is that in
the gastrointestinal tract again this 400 square feet surface area you have all these enteroendocrine cells releasing over 20 different molecules or neurotransmitters peptides to signal to all these nerve endings of the vagus nerve it's incredibly complicated system when people do these injections they have high levels of this glp-1 or synthetic form of the glp-1 in their blood and instead of going through the normal physiologic route through the vagus nerve it bypasses that vagus nerve that connection between the brain and the gut and this molecule in the blood crosses the blood-brain barrier and there are glp-1
receptors in the brain in other words some cells in the brain have the capacity to respond to this molecule or hormone in the blood um people assume that releasing glp-1 in the gut the way it's normally supposed to happen and glp1 and high levels at high levels in the blood crossing the blood-brain barrier and activating centers in the blood that those two things are equivalent it's the same thing it's very much not the same thing there's not a one-to-one relationship between glp-1 receptors in the gut and those in the brain and so although we see
some results that we that we like and that are good um the assumption that we're using the normal system for good results that's a big assumption and I argue it's that's not true in a normal person of all the glp-1 that's generated by the gut um most of us just about all of it is used to signal to the vagus nerve endings and only 10 percent of that glp-1 makes it out of the circulation of the blood beyond the liver and that 10 percent really is broken down in deactivated within a minute so what this
tells you is that in nature in a normal human being this glp1 it's supposed to be working in the gut it's not really being it's not normally a hormone and so increasing levels in people to a very high level it's that's we're not reproducing normal physiology we're perturbing the system in a quite a dramatic way to really understand the background in this um a bit on the nervous system um one branch one part of the nervous system is called the autonomic nervous system you can think of it as the automatic nervous system this is the
branch of the nervous system that really manages and controls most of what is an involuntary things you never think about dilation or constriction of the pupils digestion bladder control all these things you know pulse breathing blood pressure there's a lot and it would be far too much for us to control those things consciously and so this this autonomic nervous system really governs and takes care of that now there are two branches of that autonomic nervous system the sympathetic and the parasympathetic the sympathetic uh it's it's known as the fight or flight branch of the nervous
system you're in the woods you're hiking and you see a grizzly bear you know you think of a shot of adrenaline but there's a lot of things that happen in your body very quickly to help you deal with that scary situation that is the sympathetic branch of the autonomic nervous system it has a counter balancing branch called the parasympathetic and this is often known as the rest and digest branch of that autonomic nervous system digestion healing restoration um recovering ideally in a person with who's healthy has a healthy metabolism those two branches of the autonomic
nervous system are in balance well what we see in obesity in diabetes in heart disease and in Aging in general is a progressive shift of higher than normal sympathetic activity and lower than normal parasympathetic activity and you see this everywhere it affects every organ system in the body in every tissue and this really is a reflection of health of the vagus nerve the parasympathetic nerve really is sort of Center control along with the hypothalamus for the parasympathetic branch of the autonomic nervous system and fundamentally driving obesity diabetes could be argued that a fundamental driver is
dysfunction of that vagus nerve dysfunction of the parasympathetic nervous system and you get this imbalance too much sympathetic not enough parasympathetic activity and that system the autonomic nervous system it is a part of governing every tissue in the body from cognition to digestion to the cardiovascular system skeletal muscle a lot of people don't know this but that autonomic nervous system has a very important role in regulating and managing the the muscles skeletal muscles and so when I hear that people are losing a significant amount of muscle on these injections that back up and why is
this happening it's happening because with these injections this glp1 or the synthetic forms of it they're bypassing the vagus nerve they're not using the vagus nerve as is normal they're bypassing it crossing the blood brain barrier and activating some places in the brain but in doing that they're bypassing the vagus nerve and there is this important principle in nature use it or lose it you think of a muscle if you don't use a muscle it's going to get smaller and fundamentally what's happening is by bypassing that vagus nerve with these injections that nerve is not
used as much and it becomes even more dysfunctional so it increases dysfunction of the autonomic nervous system and that is why people are losing muscle that is why the stomach paralysis issue is Raising its ugly head and there's a lot of other things that we are seeing so one measure of the autonomic nervous system in the balance in it is called HRV heart rate variability and it's fairly easy to measure and calculate it can become very complicated but in general it is a measure of balance in that autonomic nervous system specifically how well the parasympathetic
nervous system is functioning and what we see in people who are who are metabolically healthy that when they use these injections HRV goes down meaning you have decreased function of the parasite sympathetic nervous system there's higher than normal sympathetic activity at the site of nerves joining muscles and so a good argument could be made that these injections in many people are accelerating the aging process um an important point is that if somebody already has erect vagus nerve you know they're diabetic they're obese they have high blood pressure they have heart disease they sort of have
end-stage autonomic neuropathy yeah these injections are not going to do as much damage to those people and it could be argued it makes sense to use them in those folks if someone is younger and they're not as metabolically ill these injections are going to damage their vagus nerve because again it's bypassing the nerve the nerve is not going to be used and it's going to become more dysfunctional so in my opinion it is a huge problem that the studies that have been done on these injections have been done on people with significant metabolic disease initially
in diabetes heart disease most of the studies are done in people who have diabetes and heart disease and so you can assume their vagus nerve is already fairly dysfunctional and what was noted is that when on these injections yeah a lot of people seem to lose weight it's a huge jump to take the injections from that group of people and use it in people who just want to lose weight just need to lose weight the assumption that it's doing the same thing or the side effect profile is going to be the same that it's a
faulty assumption in my opinion so the people that are the healthiest seem to be the ones that respond the best to these injections it's because they don't have glp-1 resistance and it's in those people that their vagus nerve is going to be most impacted negatively and they're going to suffer the worst side effects long term this is that great Paradox or the unfortunate Paradox the people in whom these injections don't result in as much weight loss in part it's because they do have glp-1 resistance and their vagus nerve is already dysfunctional so it's incredibly important
for doctors who prescribe these medications to understand this physiology and patients I mean quite frankly people are ordering these things online and bypassing the medical community um you really have to understand what's happening long term with these injections I think that there it's reasonable to think and this is speculation upon withdrawal of these injections um there's a chance there will be cognitive results negative results in other words like decline in cognitive function as well in if someone's been using these injections and they have a healthy metabolism and they're using them just to lose weight if
withdrawing those injections you know reveals a more dysfunctional vagus nerve I would expect that those people are going to be insulin resistant to some degree they're going to struggle with high blood pressure and they're going to be metabolically in a much worse place after using the injections than before you might say hey you're a bariatric surgeon you're biased in this yeah everybody has bias I'm biased I'm sure but I've been thinking about this for a long time many years and as a bariatric surgeon I'm quite obsessed with understanding what causes obesity as well as why
bariatric surgery works um in the way that it does we see much better results with bariatric surgery and the reason for that is that bariatric surgery actually does the opposite by stapling the stomach and the intestines it's restoring the vagus nerve activity so it is restoring normal physiology whereas these injections they're bypassing it to sort of taking a shortcut and I think in a lot of people it's going to be a an end negative for them hate to be a downer but this is these are things that I don't hear anywhere and I think it's
very important in this craze of this social craze with these injections somebody's got to speak up and explain what the risks really are thanks for listening if you're interested in more content visit our YouTube page Idaho BMI I'm David Brown of Idaho BMI [Music] thank you
