Here’s an in-depth conversation with Ron Rosedale about how bones evolved, and what kind of hormone signaling helps bones stay healthy.
Ron Rosedale, recently, health news has featured many articles that have to do with bone. I’m wondering if you can help me with this. The three questions I have are:
1. Calcium supplements that people take to make their bones strong, have been associated with an increased risk of heart attacks and cardiovascular problems.
2. Drugs designed to strengthen bones are in some cases leading to an increased risk of bone fractures, especially in the thigh bone, rare but documentable.
3. More and more evidence is showing that hormones may influence healthy bones more than taking calcium. And healthy bones may influence hormones, such as insulin and leptin, meaning sick bones may increase the risk of diabetes and messing up the leptin signals can mess up your bones.
Before we get into how you would answer those questions, I’m also thinking of a young man who has a disease where his bones are very thin and very prone to breaking. Maybe in looking at these more newsworthy topics, we’ll figure out something to do for this young man. Let’s start by talking about bones. I brought with me two show-and-tells that are bones. These are soup bones for cooking. They’re the kind of bones that you can give to dogs that they love to chew on. One thing that struck me, if you look at this one that’s cooked, is it mostly bone or mostly hollow?
The one that’s cooked, I’d say about half of each. It’s mostly hollow, if I had to do volume. It’s a trabecular bone, so there would be more air than bone in this piece.
That’s right, we think of bones as these very strong, sturdy things, but even this, which I’m guessing was maybe a cow’s thigh bone—
—and probably would not be considered osteoporotic at all.
It’s got this thick outer bark that’s the bone, but most of what you’d see that you think is solid is actually a hole in the middle. That’s the cooked one, where the hole in the middle has been taken out. But this bone here has not been cooked.
In so-called Paleolithic times, this would be a real gourmet feast.
I’ve heard that in Paleolithic time and in hunter-gatherer cultures, they loved to eat the marrow of a bone.
Yeah. Some of the scientists who study such things have proposed the theory as how brains might have evolved, and one of those is, as brains evolved and became a little bit smarter, and human ancestors were scavengers, smart enough to know not to compete with lions and tigers for a kill, they’d let the lions and tigers kill and have their fill, and then try to eat what was left over, as we became a bit smarter and more adept at the use of tools, we could break open bones, and what was left is the commodity that is revered in animal cultures, and that is fat.
Is fat what’s inside of this bone?
It’s mostly fat. Bone marrow is very high in fats. The Mediterranean diet is bone marrow, it’s mostly mono-unsaturated fat and a lot of other good nutrients. It’s a very nutritious meal, also some protein. So bone marrow is an excellent meal for especially a scavenger, to have something like that left over.
Our ancestors may have become more human-like because they could crack open a bone and eat the inside of it when other creatures couldn’t get to it, because they used tools. I wonder how long ago that could have happened. Could it have been 2 million years ago, 15 million years ago?
Probably longer than 2 million years ago. Probably not as long as 15 million years ago. I think that’s a pretty good range right there, somewhere between 15 and 2 million years ago, as we evolved a bigger brain.
The 15 million years is an interesting moment, because it is a time when primates lost some ability to process uricase, and it’s a possibility that it was just a random mutation that gave them more ability to store fat through fructose. I’ve always wondered, when I’ve heard that, though, whether if there were primates that had gone to Europe and then they got caught in an Ice Age kind of cold, if some of them survived because they ate bone marrow, and if they ate bone marrow and fats, maybe that ability to process some of the byproducts of eating a lot of fruit, because they were fruit-eating primates that went north, maybe they lost that ability to process fruits because they were eating so much bone marrow they didn’t need it any more.
Yeah, bone marrow is a great meal. I think it perhaps initiated a very beneficial cycle where the more bone marrow they were able to acquire, as they got smarter, the smarter they got, because they were able to fuel then the very high-energy needs of a growing brain.
That’s a question that would take some paleoanthropologist to figure out. We’ll just leave that as a question for now. You’re saying that this is actually pretty nourishing stuff here in the middle. But I’ll bet that’s not why this animal made this stuff in the middle of its bone. It didn’t just make it just so we could eat it some day.
I don’t think any animal makes anything so that somebody else can eat it. Well, maybe bees make honey. No, I don’t think they made marrow for us to eat.
Instead of being hard, why do our bones have this stuff in the middle of them?
The typical function of bone marrow is to make red and white blood cells. It has a very good energy store to fuel the constantly replicating cells that are necessary for that animal’s life.
Why did they make it inside of their bones?
Because they can, [laughs] more than anything. It’s a good place for it. I think nature likes to have dual uses. It’s also very well protected, so it’s a very well-protected place to make very, very vital components of our physiology. The immune system is extremely important, making blood, red cells, is extremely important. This is a very safe place to make it that is kind of out of the way.
It’s out of the way, in a safe place that’s avoiding free radicals and all of those insults. Does it make bone any stronger to have it be solid, or is it just fine to have it in the middle of it like that?
One of the major endeavors of any type of architecture is to weigh strength versus weight. It could certainly be solid. You could make bones solid, but they then would be much heavier, which would entail greater musculature to stand upright. It wouldn’t be a very architecturally sound way of making any type of structure. We could make a building, a house, with a solid framework, but instead they have 2×6’s or 2×4’s to hold up a frame that’s hollow in the middle, very much like our bones. So it’s a good balance between strength and weight.
When you said hollow in the middle, it reminded me of this book I have here called Inside the Body. It has beautiful pictures that start out showing things like the skeleton and what different bones look like in the skeleton, and then it gets closer and closer to the actual bone cells. At some point, it actually shows the structure of bone cells. One thing that’s quite amazing to look at with these is that bone cells, side by side, they have all this hard stuff around them, but the bone cells start with a hollow core. Even the cell starts with a hollow core. Aren’t those beautiful?
Yeah, they are beautiful. Nature is incredibly wise. That’s why I think we really have to listen to nature, both in healing and treating people. Listen to what nature does, what nature’s ideas are for healing, for structure, for life, and then don’t fight them, go along with them.
Looking at these pictures where there’s a hollow center and lots of layers of hardness around them reminds me of a story you told me about how nature doesn’t say, “Some day, we need creatures that have bones in them, so let’s plan to make bones.” You told me that bones started because sea organisms were spitting out a lot of calcium. Sea creatures started out by being soft-bodied animals that had a lot of calcium to spit out. It’s not that they even wanted to make shells, they just wanted to spit out calcium. And in a way, it almost looks like in our bone cells that spitting out of calcium is still going on. There’s a hollow center and then there’s all this hardness around them. Can you tell the story about seashells?
A simplified version evolution, how life came to be as it is. We’re fairly certain that life started with single-celled organisms. We could start even earlier, but that’s close enough. As cells divided, they formed colonies of cells, families of cells that were fairly identical. From a very, very early age, it was critical that once life began, once life evolved, one of the requisites of staying alive was to get rid of calcium. Not to acquire calcium, but actually to get rid of it. Top biologists to this day will know that if cells start accumulating calcium on the inside, if calcium levels start rising on the inside and the intracellular calcium isn’t kept extremely low, cells start dying.
This began almost at the beginning of life. The cell started excreting calcium, and as you had colonies of cells grouping together, and they all were excreting calcium, it would mix with certain elements in the oceans and precipitate from rocks, kidney stones, you might say. These rocks would form adjacent to these columns of cells. Nature is quite smart, all animals are quite smart, and they have to be, or you’re not going to survive in a world that is not easy to survive in, especially back when life was evolving. It was actually much refer than it is now. We have a few tsunamis now, a few hurricanes and volcanoes. Well, life back then was infinitely more treacherous, with much more severe hurricanes and tsunamis. It wasn’t easy. You had to be pretty ingenious to survive, and you didn’t want to waste things.
So these colonies found, quite naturally, that the precipitated calcium that was adjacent to them could be used as protection, as a structure to protect themselves.
So perhaps initially some of them spitting out this calcium, it smothered them, they died in their own calcium, but every now and then one of them survived in that they ended up spitting out the calcium in a way that protected them.
Exactly. This is kind of the leading theory of how shells evolved. The shells didn’t just happen from the ocean, they actually emanated from within, that the colony of cells would excrete the calcium, it would precipitate, form a nice protective shell-like layer that then became part of the organism.
And here in this picture of the bone cell, it has that look of spitting out calcium in a very specialized way. It’s an organized way to spit it out. The center stays hollow. It’s almost like a reminder of that initial creature that wanted to get the calcium out of it in a way that was not going to hurt it and might even help it.
All life is incompatible with high calcium. There are reasons for that.
If calcium is so bad, why does a cell let it into itself in the first place?
It has no choice. [laughs] For that matter, calcium is one of the common elements that surrounds the world, so there will be calcium. But calcium has advantages, too. It isn’t a matter of just getting rid of it and not wanting to ever see it again. It can form a very hard structure, calcium carbonate, and you can use that hardness for protection.
Is that why cells let it in? There’s things where cells say, “I don’t even want this in. I’m going to keep it out.” Why do cells let calcium in? Is it helpful in some way to have it inside the cell?
Calcium is used in many different chemical processes. One of the major chemical processes that calcium is used in is as a signal. It’s kind of an intermediary hormonal signal. When the hormone tells a cell what to do, it doesn’t tell it directly. It usually kind of knocks on the door of the cell and says, “I’m here.” The cell then has to hear the doorbell. And just like somebody coming to the door in your home, it’ll ring the doorbell, and then wires will take it to a bell and allow you to hear it, and you know something’s happening. You have maybe a delivery. Maybe the mailman is here, maybe UPS came to deliver a package that’s quite important, a new hard drive for your computer, and if you don’t pick it up, you’re out of luck in doing your further work. One of calcium’s major uses is as a messenger that when the hormone arrives at your cell, a little trickle of calcium is released, which then sets off a cascade of chemical reactions with calcium being involved in most of those, that then go to the nucleus of the cell and tell certain genes to be read. So the message from a particular hormone can tell a cell what to do. That’s how it works. So it’s important for the proper concentration of calcium to be there so that the message can get across.
I’m imagining it as the sound of the doorbell ringing discreetly to let the whole cell know, “Here comes the message.” And if there’s too much calcium, it would be like a thousand doorbells all ringing at once.
Or like a rock band playing inside the house, and the doorbell rings and it sounds like part of the music, and you have no idea that somebody’s at the door and you don’t answer it.
So all of these are reasons why it’s important to clear the calcium out after it’s done it’s job to get the doorbell rung?
Yeah. And cells have very interact ways to make sure that the calcium remains silent, a very low concentration of calcium, until it’s needed. So the two major mechanisms are, number one, we’re going to extrude calcium from the cell to keep the intracellular calcium really low, and the calcium that remains in the cell gets sequestered in a membrane complex called the endoplasmic reticulum, so that that calcium which isn’t excreted is sequestered so that the space inside the cell, the cytoplasm, has an extremely low calcium concentration. The intra- to extracellular calcium concentration, that gradient, is greater than any other mineral, any other chemical, really, in the body. It takes a lot of energy to maintain that gradient.
So our cells have a whole bunch of sump pumps that keep pumping the calcium out, because the cell says, “We don’t need too much calcium. We need to keep it cleared out of here.”
“We’re going to die if we don’t do that.” Exactly.
Here I see it, in these pictures of these bone cells. It looks like the calcium got spit out in a very organized way, and there’s this hole in the middle each time. We’ve been talking about seashells, but then we go to us, where our shells are not on the outside, they’re on the inside. That’s interesting because I gather that the ability to make bone concedes evolutionarily with the hormone leptin?
It apparently does. You can probably educate me a lot more on that, even, and why that might be so, because I’m not sure. I know that what occurred, and it had to do with fat-burning also, the ability to burn fat, which leptin is critical for, in taking our story a little further about shellfish and shelled organisms, in the ocean, you don’t have to withstand gravity. You’re pretty weightless. You don’t need rigidity. You need protection more than rigidity. The shells weren’t there to be necessarily rigid and to stand up against gravity. The shells there were protection almost entirely, some of them actually were used as weapons, spikes, also sometimes for protection, but also as weapons, to get prey.
Yeah, swordfish and things like that, right. Teeth in general, which is kind of an offshoot of bone. But as we went from the oceans to land, as we sought different niches for different organisms and species, the environment changed quite a bit. Certainly one of the big changes as we left the ocean is that we encountered gravity. It’s always been a rule in evolution that bigness afford protection. It’s much easier to get eaten if you’re little than if you’re big. The big eat the little, not the other way around. For animals to grow on land, they had to become more rigid, and that distinction really has to be recognized between rigidity and strength. The two are not the same at all.
Internalizing our external shells, which is a relatively easy thing to do, we already had bone, sort of, and we were using it as shells on the exterior to make bone. We just had to bring it inside. That allowed us greater rigidity, so that we could then grow bigger and stand up and become mobile against gravity.
You’re making me think that perhaps our internal bones have a little different structure than shells, because shells can be just these hard, concrete-y things. But our bones have to be able to move with us. Most shelled creatures stay put, so their bones are dealing with weight and impact, they aren’t dealing with having to flex.
They basically weren’t dealing with having to be strong. They just had to be rigid.
And they didn’t even have to be alive. They were just the walls of the fortress.
Exactly. And that brings us into a philosophical argument or discussion of what life is, because all life, really, is mostly dead. [laughs] You can’t really distinguish between the two.
But our bones inside of us are a little bit more alive than the shells?
They’re definitely more alive than the shells we see in shellfish. The live part confers the strength, and that part doesn’t have to do with calcium.
There are some pictures in this book that show in some of those holes that go through bones, there are things called osteoclasts and osteoblasts, those kind of little scrubber things that are alive that go through and either chew up only bone or get room to make new bone cells they can spit out calcium again. There’s, like, these little Pac-Men going through the bones, scrubbing and cleaning it out. I don’t think that happens in seashells, but it happens in our bones.
You bet. We have living architects in our bones that model and remodel our bones, that make the bones the shape that they’re in so that they can be much more conducive to mobility, to joints and strength. So we have cells that actually eat up bone like a sculpture. You take a big lump of clay and then you take away some of that clay to make a shape. Those are the osteoclasts.
Clasts like “clear away.” C for clear away.
And then we have another type of cell that also make a sculpture, but by adding clay, you might say, in this case not clay, in this case, actually, it’s protein. So we have osteoblasts that make bone, but not by putting down calcium, but by putting down protein.
So osteoblasts B for “build” the bone.
The osteoclasts and the osteoblasts model the bone. They take a piece of clay and they make a sculpture out of it which we know as a femur or a humerus, a particular bone such that it can perform a particular function in the body, be an arm, a leg, have a joint so it can be mobile and convey strength.
What is protein doing in there? Why not just make it be calcium?
That’s a great question, and I think it’s a question that goes to the heart of the fallacy and myth of how we’re treating osteoporosis. One has to distinguish between rigidity and strength. They are not the same thing at all, and they’re mediated by totally different mechanisms. The strength is mediated more by flexibility, and the strength is mediated by the protein content of the bone, just like your muscles are strong. You can get nice strong muscles. Protein is what conveys strength and flexibility. So you have a green stem of a tree that’s bendable, and it’s going to survive a hurricane with a higher probability than an older, rigid oak tree that might be much thicker, and if you took an x-ray of it, you would say, “This is much thicker, that means it must be much stronger,” and the hurricane took it out like it was kindling.
I was hiking recently and saw some people fly-fishing. They do these wonderful bends of their rods. It’s just gorgeous to watch the string and the rod bend and flex. I think those rods are probably hollow, and I think they’re made of something that has some fibers that can bend and flex. I don’t think those rods are made strong because they’re made of thin pieces of stone. I think they wouldn’t work very well then.
No. If they were made rigid, they would crack with any type of pressure. So you’ll see all fishing rods being flexible, the more flexible the better, and that way they’re much stronger and they don’t fracture under pressure.
Fracture under pressure. That’s not what we want to have happen to any bone.
No, that’s not what we want to have happen, but that is what happens. It will happen even more, or to a greater extent, if you have more calcium than the bones should have and less protein. So you can have, for instance, a six-month-old, I remember we did this in medical school, we took a nice little six-month-old infant who at least did say we couldn’t do this, and the medical students were able to bend the forearm of this child, who, by the way, liked the attention, it doesn’t hurt, but you could very visually see that the forearm bent considerably. And it was a very strong bone. That six-month-old has stronger bones than I have, and I think I’ve got pretty strong bones. The reason was because of the flexibility. And yet if you did a test for osteoporosis—
You know, I just recently had one, because I’m at that age where I’m supposed to—
You measure the mineralization of the bone, is what they do. They measure the calcium content, not the protein content. They do not measure the protein content of the bone when you go for a test for osteoporosis and you have a bone scan. Calcium content, however, does not reflect on strength.
After I was done with my bone scan, I’ve got a very light frame, I don’t have very big bones, they said that I wasn’t osteoporotic but I was pretty close. I said, “Hmm, what would that mean? Is it because I have a light bone frame?” I was told, “No, you just don’t have that much calcium in your bones.” Now that I am at the age where I will probably be starting into menopause at some point, they said, “It’s going to get worse.”
And if they compared your bone to that of a six-month-old, they’d find it was much closer than if they compared somebody who had a so-called “good” bone scan study and had less osteoporosis, supposedly, to a six-month-old. Those bones would look much different. In other words, if you did a bone scan on a six-month-old, it would look like the worst case of osteoporosis ever recorded, because their bones haven’t classified very much, which is why they’re flexible and which is why they can actually maintain themselves with all the falling that six-month-olds are doing. They’re flexible. They’re not going to break. They’re much harder to break than somebody who had a perfect bone scan study.
If my bones ever get thin enough and lacking in calcium enough, I’ll be told to take a drug that’s called a bisphosphonate, like Fosamax, which is designed to make sure that my bones will look really good on a calcium bone scan.
Virtually all of the medical treatments right now for osteoporosis do so by inhibiting osteoclasts.
I’m looking at this picture here in this book which shows a very elegant hole in the middle of the bone and a little—it really does look like a little scrubber that you’d use on a pan to get the messy stuff off of a pan when you burn things, and it’s scrubbing away. These drugs take all of those little scrubbers and keep them from scrubbing.
Yeah. Gives you a very false sense of security. What you’re doing is, you’re inhibiting a very vital part of bone physiology, which is to get rid of old, damaged, brittle bone and replace it with new, flexible bone. That’s why we have both osteoclasts and osteoblasts that are active throughout our life, not just when the bone is being formed, as we’re a fetus, but after we’re alive up until so-called old age we have very active osteoblasts and very active osteoclasts, and we need both of them for healthy bone. We need the osteoclasts to break down our old bone so that it can be replaced with newer, fresher, stronger, more flexible bone.
And that means bone that isn’t just calcium, it has protein and other minerals in it, it has a live, active process, so it’s bendy.
So it’s bendy, and even the calcium has something to stick to. If you just have calcium, which is basically what they’re causing you to do by taking away osteoclasts and by not paying attention to the processes that allow protein to actually build up in bone, which is a totally separate story on how you get protein into your bone, if you are just concerned about calcium, like the medical profession right now, try taking calcium carbonate or calcium phosphate or any type of calcium you want and making a bone out of it. Take that dust and squeeze it together and make bone out of it. What happens when you let go? Whssst! It’s like sand.
And even if you could squeeze it together, I could just flick it with my finger and it would fracture all over the place. It would be like glass, very much like silica carbonate. X-ray technologists, radiologists will tell you that patients who are on these drugs who fracture their bones have a different structure of that fracture. It’s a much more severe fracture. No longer will you get a so-call “green stick” fracture, which looks just like that. If you take a green stick, the green twig we were talking about before, and you bend it enough that it breaks, it’s that little fine break in the middle, and you really don’t have to do anything to it. It’ll just heal itself. It won’t be in a bunch of pieces.
I have a friend who, her love Weimaraner dog is known with being clumsy. The dog’s name was Grace.
Good name for a clumsy dog. [laughs]
So Grace was following her down the stairs and got clumsy and walked in front of her and she fell down the last stair. Her ankle was shattered like if you dropped a teacup on a marble floor. It took a long time to heal a lot of pieces.
Right. And that’s what happens in the bone that doesn’t have the proper protein function, it doesn’t have proper osteoblastic functions, where you’ve inhibited the osteoblasts to get rid of that brittle bone. In other words, all medical treatment right now for osteoporosis, whether it be taking estrogen or Fosamax or any of the other—the injectable drugs that they’re giving that will last for six months that have all sorts of side effects that you can’t do anything about because it’s going to last in your body for six months once you’ve taken it, it costs $2,000 or some ridiculous amount of money that you’ll be out, they all work the same way, by inhibiting the osteoclastic activity so that you cannot reduce the brittleness of your bone. Your bones become thicker, they look great on an x-ray, but they’re extremely brittle, and if you do fracture them, they fracture like glass.
One thing that happens is that if somebody’s lost calcium in their bones, it is the case that they’re not able to carry as much weight on their bones. Pelvises and spines can start to compress because there isn’t enough stuff to make the bone be able to hold a steady pressure on it. I’ve heard that for somebody who has that kind of weakness, it does help to inject some kind of cement, some calcium in some way.
The cement, actually, is the protein. The calcium would be like the bricks.
That’s right. If you have a whole bunch of just the sandy stuff, it takes the glue to make it be concrete. You’re saying that the protein is kind of like the glue?
The protein actually has the glue. There are certain types of proteins called GLA proteins that essentially glue the calcium to it so the calcium has something to stick to. That’s what, for instance, vitamin K is necessary for, to increase the quantity of GLA proteins that allow calcium and magnesium and other minerals to actually stick to that bone.
But there’s heart disease, and everybody knows that vitamin K is a vitamin that if you’re losing a blood thinner, to have a lot of vitamin K in your blood—
That’s why they say that many heart patients and many people that are taking blood thinner, they’ll go to the extent not only to not take vitamin K, but to not eat green vegetables any more. “Don’t eat green vegetables, because we don’t want you to have vitamin K. That would be horrible.” Because they’ve got heart disease, and a lot of times they’ve got heart disease because they had too much calcium in their arteries, and they have too much calcium in their arteries, not because they’re taking too much calcium, but because the calcium doesn’t know where to go. You’ll find that those people who have lots of calcium in their arteries also have osteoporosis. It’s almost a one-to-one correlation.
So somebody could have calcium blockages in their arteries, they could have arthritis, all things with too much calcium in the wrong place, and they can still have thin bones?
They generally do. And they’ll be told, then, to take more calcium, even though the calcium is going in their arteries and in their gall bladder and in their kidneys and all the wrong places, they’re told to take at least two grams of calcium a day, even though it’s well documented that the calcium physiology is totally messed up, the body has no idea what to do with that calcium any more. More of it is going to go into their arteries, into the kidneys, into the gall bladder. Some of it, almost by default, is going to end up in your bones because that’s where we put excess calcium. That’s one of the reasons we put it there, because we’re trying to get it out of our cells and we have to put it somewhere. It’d be great if it could stick in our bones, because then we could take something that’s harmful, actually, to the cells and give it some use. The use isn’t, however, to make strong bones. That’s a misnomer, a misconception, I should say. The use is to give the bones rigidity. The strength, again, is conferred by the protein.
But if we only had protein, which would essentially be cartilage, if our bones were 100% made of cartilage, if we retained our six-month-old bones into adulthood, for instance, we’d still have really strong bones, maybe stronger than they are now, but we’d be like Gumby dolls. As we tried to grow up and become five feet or six feet tall, we would just bend over. We wouldn’t have enough rigidity to withstand gravity. So we put minerals in our bones to make them more rigid, not to make them more strong, so that they’ll remain straight and allow us to walk upright.
Minerals like calcium, a little big of magnesium?
Boron, silicon. There’s a lot of minerals that go into our bone, not just calcium. But like anything else, health—I think we’ve talked about this in the past numerous times—health is not in the parts. It’s in the instructions given to the parts.
So in us talking here, you’ve answered my first two mysteries, and it sounds like it was no surprise to you that calcium supplements are now being associated with an increased risk of heart attacks. That’s more and more documented, it’s shown as a small risk, but there is a risk there. You’re saying, “Well, of course.”
There’s even a greater risk. It’s been shown, it was shown 15 years ago by Swedish researchers that people who had high normal serum calcium levels had a much higher rate of mortality. So if you really want to use, I think, a better index of health, which is mortality, your mortality goes up if your serum calcium goes up.
So there that is with calcium supplements, high levels of calcium in the blood are maybe not such a great thing. The other question you’ve answered is that drugs designed to strength bones in some cases lead to an increased risk of bone fractures, especially in the pelvis and the long bones of the legs. That would make some sense, because those are areas which need to flex, and if what’s happening is that the supplements are keeping the osteoclasts from clearing out the old bone—
The old dry, brittle bone. The medications being used right now for osteoporosis are inducing in people really dry, brittle bones, very, very susceptible to severe multiple fractures. As you mentioned, like glass or like a teacup breaking, in multiple pieces that are very difficult, certainly almost impossible for the body to heal itself. If it’s going to heal, it’s going to require surgery and multiple pins and most of the time it won’t be able to mend properly because the tools to mend bone and the ability to manufacture protein are being impaired by the treatment. So the treatment, once again, is actually becoming the disease.
let’s go through a quick list of the things that help bones and don’t, and then we’ll get to the cool stuff about how hormones influence the health of bones and how bones influence the health of hormones. The quick list would be, if somebody takes a nonsteroidal anti-inflammatory drug to reduce pain, will that improve bone strength or hurt it?
It’ll hurt it, for sure.
Taking calcium without the proper protein matrix won’t allow the calcium really to incorporate itself into the bone properly. It’s just there, so it looks good in an x-ray, but it really has no positive function as far as even rigidity is concerned. But the detriment is that as we age, cells have a harder and harder time keeping calcium out. As you mentioned, we have calcium sump pumps that constantly have to pump the calcium out. As we age, our ability to do that decreases. But then what they say is to take more calcium, which is like having the sump pump in the basement and making sure that it’s raining all the time. And as the sump pump is getting a bit older, and it’s really not as affective at keeping water or calcium out, and then you’re making sure that it’s raining all the time, you’re saying, “Make sure you take two grams of calcium a day,” which to your cell is like raining calcium, the ability to keep calcium out becomes much more difficult. Intracellular calcium rises, and when that happens, virtually all signaling processes in the cell, of all kinds of cells, not just bone-forming cells, we’re talking about heart cells, nerve cells, kidney cells, every cell that you’re made of this is relevant for. As calcium starts building up in cells and cells start losing signals because there’s too much static inside the cell, they can’t hear the right messages, everything becomes impaired, and you die. Which is why the Swedish study showed that mortality rate increases as serum calcium goes up.
The American Dairy Council is not going to like this interview.
Oh, nobody likes me. I’m not just focusing on them. I focus on everybody.
Although there is some evidence that taking calcium supplements is actually more problematic than eating foods that are higher in calcium. Perhaps that’s because if you take a supplement that has something that your body doesn’t need, it’s harder to get rid of it than when it’s packaged with other nutrients.
And it might not even probably get absorbed as well. There’s no way to get rid of it. It goes in and out.
Walt Willett is with the Harvard School of Nutrition, and he says, “If you really want strong bones, don’t milk your cow, take your cow for a walk.”
RON ROSEDALE[laughs] That sounds good.
Walking and exercise really do help our bones, because it helps them flex, which makes them wake up and say, “Oh, my gosh, it’s time to—”
“We need more strength.”
“And we need to clear out some stuff that’s not flexing well and get those osteoblasts and osteoclasts going.” All of that works as long as you haven’t taken an anti-inflammatory that means that the bones don’t get the signal to be repairing themselves.
That’s exactly right. It’s like, if you want to build your muscle, you exercise your muscle. If you want to build the strength of your arms, you’ll do arm exercises. If you want to build the strength of your bone, you need to do bone exercise your bones.
I’ve got an idea. Since bones have protein in them, how about if people eat more protein?
It boils down to what we just said a little while ago. It’s not so much the parts that even make life, it’s how they’re integrated, it’s the organization of those parts. So if you have hormones that tell your protein what to do, if you have hormones that tell calcium where to go, then you’re going to be healthy. If you don’t, you can take all the calcium you want and there’s not going to be a homing pigeon attached to that calcium that tells it to go to your bone. The calcium has no idea if it’s supposed to go to your bone or your artery or your kidney or your gall bladder. It’s just calcium, it doesn’t have the knowledge. We have to give it the knowledge of what to do. Same with protein. You can’t just take protein and sit on a couch and watch television and expect your muscles to grow. That’s not going to happen. If you don’t have signals to build muscle, you won’t. If you don’t have signals to build the strength of the bone, essentially conferred by the protein content of the bone, then it’s not going to happen. You can take all the protein you want, it’s not going to end up in your bone. You’re going to end up burning it as fuel, and that’s going to be detrimental. Burning protein as a fuel source is highly unhealthy.
All right. That’s a quick primer in some things that can help your bones be stronger and some things that can interfere.
Eat your meat and vegetables and take very vitamin K. Don’t listen to your doctor.
How about the hormones that may influence healthy bones and the healthy bones that can influence hormones, such as insulin and leptin? Gerard Karsenty gave one of the leading lectures at the American Association for Advancement of Science because of his remarkable research where he discovered that serotonin in the brain, the feel-good hormone, if it’s coming from the brain, send signals to strengthen bones. Lepton from the brain sends signals to strengthen bone. Serotonin created inside of our intestines, inside of our duodenum, which is just down below the stomach, if serotonin is being created there, it actually interferes and dampens down how much healthy bone the body will be making. What he has discovered is that these hormones, not only do they make a difference in how the body’s building bone, but it depends on where in the body the hormone comes from. This is very confusing. How would you unconfuse it?
I’m not sure I can, particularly. The body is extremely interact in its information-disseminating orchestration. One of the keys to health is really how signals are orchestrated, not whether you have them or whether you don’t or how much you have or how much you don’t have, but how they’re orchestrated. An example would be antioxidants. Everybody wants to take antioxidants these days. The University of Colorado did a whole institute of antioxidant research. But I think they’re all missing the boat, in that it’s not how much antioxidant capacity you do. They do ORAC studies that measure how powerful the antioxidant capability is of a particular supplement, for instance, and if it has a really high ORAC score, it becomes promoted, pomegranate juice. Acai is really popular because it’s very high in antioxidants. You hear that all over the place.
It’s totally fallacious. It has nothing to do with health. We need oxidation. Breathing is oxidation. You can’t kill cancer without oxidation or viruses or bacteria. It’s not whether you have it or whether you don’t, it’s where, when, and how you have it. It has to be orchestrated. So you want it here and you don’t want it there. You want it now and you don’t want it then. The orchestration is through proper hormones, and those hormones more often than not have to do with nutrient availability and reproduction, because that’s what life is about. For life to perpetuate, you need to know when it’s the proper time to reproduce and what the nutrient availability is, because that’s necessary to reproduce. So the hormones that are essential in indicating nutrient availability and nutrient use and its integration with reproduction then have its fingers in everything else.
Gerard Karsenty I believe would agree with that when it comes to bone. He’s not talking about making lots of baby bone, but I guess in a way he is. We think about reproduction as babies and offspring, and with bone he is saying that it’s an energy-intensive process to make bone, so if the body doesn’t have enough resources, if it’s low on energy, it’s not a time to put into building and refreshing bone. If the energy resources are sending signals that there aren’t enough, then bone will get weaker, is part of what he’s saying, and that has to do with the signals from the brain that there’s enough of resources to make more bone. That’s one thing he’s saying. It’s very energy-intensive to make bone, and that’s one reason he thinks that leptin evolved at the same time as our internal bones did, because it was important to have an overall energy balance resource looking at this to say, when can we build bone?
Yeah. Leptin is really a crucial hormone having to do with virtually all facets of health disease. I’ve maintained for quite a few years that unless leptin is acting properly, if it’s not being signaled correctly, not necessarily high, not necessarily low, but signaled properly when to be high, when to be low, there is no other modality that one can do to be healthy. You have to get leptin right first, and then other things can help. And the only way you can get leptin right is to eat properly. That’s why proper dietary nutrition is so important to me, because it affects the hormones that are instrumental in indicating to the body and brain what the nutrient availability is and therefore, then, what the genetic expression is of maintenance, repair, or reproduction. All of that is extremely critical in all aspects of health.
For instance, if it’s deemed that the body has to live longer to be able to reproduce at a more opportune time, it’s probably going to want stronger bones. If you essentially have been given your opportunity to reproduce, then your body doesn’t care so much whether your bones are stronger and whether you have osteoporosis. Then we have to go essentially to what I would call unnatural modalities, not necessarily following nature, but seeing how nature gave us strong bones to begin with and then maintain it. It’s not that nature wants us to die after the reproductive age, it just doesn’t care whether we do or not. If we do, great. If we don’t, great. But we can use nature’s tricks to be able to live a very long, healthy, happy, post-reproductive lifespan if we follow what nature is telling us to do.
Maybe nature does want us to live a longer time even after reproduction, because we’re not like salmon. We don’t just get to the point where the male and female salmon work hard to swim upstream and they live just long enough to mate and lay the eggs.
There is parenting, so there is a certain post-reproductive span that might be necessary, even for grandparents. But we’re talking about even beyond that. Maybe we can live longer than what nature has thought we were necessary for.
And maybe if we do, maybe that will be an evolutionary advantage because of all of the wisdom that comes from experience if people are healthy. So maybe there’s a real benefit to society. So to get there, when it comes to our bones—
Mobility is certainly one of the sine qua nons of health. Mobility was definitely required for our evolutionary adaptation.
And for mobility, we need good bones. Leptin is an interesting detail, because there is evidence that very overweight people can have very strong bones. People who are very overweight often have very high levels of leptin. On the other hand, there’s also evidence that having very low levels of leptin, if a person’s cells are leptin-sensitive, it’s one of the best possibilities for building and strengthening bones that are too weak. So this is a paradox here?
Not so much a paradox. It’s important not to confuse a hormone level with the strength of the signal. So for instance, we know that in the vast majority of diabetics classified as type 2, they have high insulin, but the activity of insulin is very low. Actually, that’s not exactly correct. It’s low in the so-called blood glucose-controlling aspect of it, high in the ___ aspect. Actually, you lose the orchestration, which is what the problem of debates is. In other words, the high insulin generally means in the liver, the liver is not listening as well. It’s lost its hearing from noise exposure. It’s being exposed to so much noise you can’t hear it any more. The same happens in muscle tissue, the muscles can’t hear insulin properly, so they can’t burn sugar properly, since the liver is not listening to insulin properly, it makes too much sugar, all these contributing to high blood sugar, so a person becomes diabetic.
But the high insulin is not toned down in certain processes that instigate cell division, so the high insulin is then a risk for increased cancer.
So for our cells that multiply a lot, like our gut lining, and in women, breast tissue, linings of things, all of those epithelial cells, they’re more prone to cancer when insulin levels are high—
Prostate, because that has to do with tubes with linings of cells that never become insulin-resistant, so they’re just sittin’ ducks.
They’re sitting ducks. And even in the same cell now, we know that certain processes, like the metabolic processes of insulin, are toned down with insulin resistance, but other processes, the ___ process, which has to do with cell division, are not toned down. So even the same cells in the same organ have different processes. So it’s the orchestration that’s lost, and this is really kind of a sine qua non of ill health, what you’ll see. One must look way beyond just hormone levels. You have to look at the strength of the hormone signal and where. As you were saying, with serotonin, the strength of the hormone signaling in the intestines or the brain? Where is it going to?
If levels are high in people that are obese and their bones may be stronger, it’s hard to tell, because the high signal means that part of their body is leptin-resistant, it’s not understanding, it’s thinking it’s starving. It may be helping the bones, but if a signal of leptin is low and the cells are sensitive to the signal, that can be enough signal to tell the bones there’s enough energy to go ahead and build more bone, without all of the other mess that comes from being leptin-resistant.
And we know that there is a dichotomy in leptin signaling, just like insulin signaling, where high leptin generally indicates leptin resistance, and much of the end organs for leptin become resistant, and many of these end organs are in the brain. But the synthetic nervous system which is at least partially controlled by leptin doesn’t become resistant. And so the parts of the hypothalamus, for instance, that indicate or that regulate hunger and obesity become resistant to leptin, so you have high leptin, but the ___ nucleus and the hypothalamus is hearing low leptin, which would keep a person hungry and tell a person that they’re too skinny even though they’re fat and make a person make more fat and not burn what they have, which is one of the major causes, if not the major cause of obesity in the world. You have too much leptin, your body’s trying to tell your brain you’ve got too much fat, that you’re going to get eaten by a lion, you’re not going to be an effective hunter, you’re not going to be able to run away from a saber tooth tiger, you’d better lose some of that fat or you’re going to die.
But the brain is hearing a different message. The brain, then, at least that portion of the brain, the ___ nucleus, is hearing that you’re too skinny, you’re not going to be able to survive a famine, you’d better be hungry, you’d better make more fat, and you’d better conserve the fat that you’ve got. So there’s a disconnect.
Those two parts of the brain are sitting pretty much side by side and they’re hearing totally different messages?
And the worst part is, in any type of communication, what’s important is what you hear and not what’s being said. And so that portion of hearing that you have two little leptin, even though you have too much, is going to make you fatter until you make more and more and more leptin, so that it can scream then to the ___ nucleus, which gets the message that you’ve got enough fat. Not too much. You have 200 pounds of extra fat now, and the ___ nucleus is saying you’ve got just enough. But you’re producing massive amounts of leptin, which is telling other areas of your brain, that regulate the sympathetic nervous system, for instance, that your heart’s going to beat too fast, you’re going to have high blood pressure, and that’s going to increase your risk of cancer and diabetes and make you produce a lot more blood sugar through the vagus nerve that goes through the liver so that your liver produces way too much sugar. It then controls insulin in your thyroid and causes all sorts of reproductive problems.
Everything gets more extreme. Some of the feedback loops that rev things up rev up more. Some of the feedback loops that rev down rev things down more. It all gets out of balance.
It gets out of balance, and that out-of-balance-ness is extremely complicated. Medical knowledge is nowhere close to the point where they could regulate all of those imbalances correctly.
Translated, you’re saying you don’t think a drug is going to solve this?
RON ROSEDALE[laughs] Translated correctly. In fact, a drug is going to make it worse, almost for sure.
Serotonin is what most people think of when they think of antidepressants, that if your serotonin levels are low, supposedly, that’s what makes somebody feel depressed, even though there’s some data that says it’s not that they’re low, it’s that if your cells are resistant to the influence of serotonin, you can feel depressed. Whether or not it’s the signal or whether the signal is heard, there’s a debate about that. But most people know serotonin because of drugs that can make you have more serotonin in your body. Serotonin is also known as something that helps during labor for women, because it causes pretty strong muscle contractions. But serotonin causing better bone growth? It turns out that serotonin from the brain improves the likelihood of strong bones, but serotonin in the digestive tract reduces the chance of strong bones.
I don’t know what to say.
This is weird. Here’s some things that Gerard Karsenty I believe is saying, which I’d like to ask him about some day. I’m curious what you think about it. One is that when someone takes an antidepressant, it can actually interfere with bone strength. It’s a slight effect, but it’s there.
And I don’t doubt it. Nature is really thrifty. There are literally thousands of—in fact much more the rule than the exception, where a particular chemical or signal or hormone is used for a wide variety of different functions. It’s much easier to take something that’s already there and give it a new function than create something totally new. So having serotonin from the brain do one thing and serotonin from the intestines do something else would not be surprising in the least. And I think the rules of hormone resistance are universal in most cases. You could probably make a case that any hormone one can develop resistance to if it’s not used properly or if it’s overused, in particular.
So if you have constant high levels of estrogen, you’re going to become estrogen resistant. But that resistance isn’t going to be uniform. Some tissues are going to become more resistant than other tissues, and that’s really why it is impossible to treat medically, because you can’t then just take more estrogen or you can’t just take more insulin, because then you can’t orchestrate it. For instance, one of the problems in type 1 diabetics, they’ll say you can always take the insulin even though your body’s not producing it. Well, not exactly, because when your own body produces insulin, your pancreas will produce it, and there is a direction to where that insulin goes. So there’s a big bolus from the pancreas directly to the liver to shut out glucose production, and then from the liver it goes to the rest of the body. When you take insulin by shot, it’s going right under the skin, and you lose that direction first to the liver, so the liver gets no higher a dose than anywhere else.
The same is true for any type of hormone. It isn’t just how much you have, it’s where you have it. If it’s produced by the brain or if it’s produced by the intestines, there’s going to be a different direction of circulation, a different direction of where it goes and therefore what it does.
Let’s look at the serotonin paradox. I’ve wondered whether if it’s coming from the brain it’s a signal that has to do with telling the whole body to do something, but if it’s coming from the gut, I find myself wondering, why is the gut, why is part of the digestive tract producing serotonin? I’m wondering if it’s a stress signal, if the intestines produce serotonin when for some reason they’re stressed because there is a stress component to serotonin production, and maybe if the digestion is stressed, that’s a signal to the rest of the body, “We need to repair the digestion.” It’s not a time to allocate resources to building bones. That’s a guess.
And it’s a very good best. People have heard the adage, “I’ve got a feeling in my gut.” I think there was a book written a number of years ago that talks about the “gut’s brain,” your gut as having its own brain. So serotonin might be one of the brain neurotransmitters in the gut that allows it to have a gut feeling.
Maybe then that’s a question—if I were to dream of asking Gerard Karsenty some questions about these discoveries of his, maybe that would be one: why does the gut produce serotonin? What is the advantage to it of having this hormone produced? What kind of questions would you want to have him asked?
Why there would be a kind of an opposite action on bone. Why would serotonin from the gut produce a detriment in bone formation as opposed to serotonin from the brain He’s wondering that, too. Having heard a speech that he gave, I believe that he said that to his knowledge, this is the first example of a hormone where its action is different when it’s produced in the brain versus when it’s produced below the brain. Does that mean that as we look, we’ll find no other hormone where this happens? Or does it mean that as people start looking for differences between brain and body hormones, that we will see more and more that have opposite actions?)
I think it’ll probably be more the rule than the exception, knowing how the body works. It’s just really interact, which is why it’s much easier to deal with it from it’s root than trying to get all the tentacles correct. That would just be impossible, I would think. That’s why drug therapy for this is really a hopeless cause.
If somebody wants to build bone, you would want them to eat a diet that has their hormone signals nice and clear without getting them resistant in any way, and exercise would be fine. Since serotonin is a stress hormone, maybe finding ways in addition to diet to reduce stress?
Going back to that, it even gets more complicated than we’re making it out. For instance, we know that serotonin and dopamine kind of work together, and that dopamine-to-serotonin ratios are important in the brain and I would assume elsewhere also. If you take so-called SSRI drugs like Prozac that raise serotonin by preventing their breakdown, one of the major problems with it is, number one, you develop resistant to serotonin, which makes it worse than when you started, and number two, you mess up the serotonin-to-dopamine ratios, which then messes up dopamine function, too. Dopamine is extremely important in all sorts of things, the pleasure center, getting enjoyment out of life, addictions. Until we can know what we’re doing with all aspects of the effects of all hormones, know basically how it’s affecting the entire orchestration of the music that our body is playing, we shouldn’t be messing with it, because we’re going to make it worse.
When I think about drugs that change the hormone ratios in the body, it’s interesting to me that our bodies work so hard just to use a little bit of these hormones and then clear them out as quickly as they can. They just send a puff of one of these hormones into the body, and then the body works very hard to clear it out. I don’t know if it’s whether too much is dangerous, or if it’s not good for the body to have stale hormones hanging around. If the hormones are in the bloodstream for very long, they get oxidized, they get dinged up, they may not act as well. So the body’s always working to put them in and then quickly take them out so that their half-lives are just a few minutes, quite often. It’s not like these hormones are there for hours on end. And antidepressants are often selective serotonin reuptake inhibitors, which means that they slow down how long those hormones are in the body. They make them be stale hormones. I don’t know whether that means that their actions can be messed up a bit because they’ve been there too long, or if they’re there very long, there are certain cells that start to burn out on them or get hurt by having too much of it there.
I’m sure that’s all correct, but it has to do, I think, with the language that the body speaks. We’re talking right now. The voice is determined as much by the silent areas as the noisy areas. So if I’m trying to say a wooooooooord [stretches it out] but I don’t shut it off and it just merges right into the next, we’re not going to be able to hear that sentence very well. In any type of language, it’s important to have a noise and then shut it off, have it here and not have it there. That’s what communication is.
You’re a fan of high-fat, low-carb diets. Do you think that kind of way to eat, high fat, low carb, adequate protein, what would that do to bones?
I think it does to bones what it can do everywhere else, and that is make them healthier. The reason for that is, I’ve measured thousands of leptin level and insulin levels and found that that sort of diet maximizes the accuracy of insulin and leptin signaling. Now we know that other signals pertaining to protein, such as ___, are going to be maximized also. And when I say “maximized,” I don’t mean levels. Actually, you’re lowering them. By lowering all three of them, you keep the signal and keep the communication. What that accuracy tells the body is to up-regulate genetic expression of maintenance and repair, which amounts then to longevity. The body will do what it can to live longer because it thinks it’s necessary. It gives the body what it deems to be a purpose to live longer, and strong bones are a part of that.
And that means that those osteoblasts and osteoclasts can get in there and do the job they’re meant to do.
Right. I think there’s very robust science now that shows how relevant leptin is in bone formation and strength. In the Journal of Science maybe eight or nine years ago, they showed that proper leptin signaling in the brain, meaning reduced leptin resistance, the way you reduce leptin resistance, if you have it, as indicated by high leptin, is by lowering the leptin, not by raising it more. As you lower it, you increase the leptin sensitivity of significant areas of the brain, which then through the central mechanism and through nerves, actually, stimulate osteoblastic activity so that bones make more protein, and that gives it more flexibility, which conveys strength and also allows the calcium to accumulate in the bone so that it doesn’t accumulate—and this is kind of a simplistic view—as much in the arteries.
Or in the joints—
—or elsewhere in the body.
Just as a hypothetical, every now and then there’s a child born who does not make bone very well. It’s somewhere of a genetic condition.
It’s called osteogenesis imperfecta, that’s the name of that condition. They get fractures very, very similar to the type of fractures that women are getting on all the osteoporosis drugs. Their bones are like glass.
So we can assume a child like that, they don’t make as good a protein matrix for the bone to build onto?
That’s what it is. It’s a specific genetic defect and an enzyme necessary to manufacture bony protein. Their condition is exactly like you would see in women taking osteoporotic drugs, where it’s great on x-rays, they have the minerals, but they don’t have the protein there to hold those minerals together, so their bones are almost like glass. They fracture their bones very repeatedly, which isn’t the bad part, but the kind of fractures that they get are bad, very difficult to heal, not a single fracture. They’re almost always multiple, compound fractures.
That sounds like one where the ideal solution would be to somehow get that child more of that enzyme?
In that particular case, that would be exactly what one would have to do, a genetic modification, increase the enzyme. But in the average person, it generally isn’t a defect in one’s ability—they didn’t inherit an inability to manufacture the enzyme. That enzyme is not getting the signal to become active.
Could that be also the case in these kids? If they ate differently, is there anything they could do to perhaps give them a little bit more margin for not breaking bones?
I would think that the would be the case, following the diet that you’re familiar with that I’ve recommended to improve leptin signaling. It improves testosterone signaling. Testosterone, by the way, is also very important in bone growth, and that’s one of the reasons why obese women, or men, have stronger bones. It has nothing to do, at least not totally, but also other hormones that leptin very much affects, such as estrogen, and if a person is fact, they make more estrogen, because the fat cells themselves make more estrogen, and that estrogen can turn into testosterone, which is good for the bone, but not so good for everything else. They increase their risk for certain cancers and things like that.
Again, you lose the orchestration, but not everything is bad. As a byproduct of some of the mess-up in hormone signaling, they get stronger bones, almost by luck, actually.
Better yet would be to have better hormone signaling and stronger bones. There may be a pathway for that.
That way you get thinner with stronger bones. You don’t have to be fat and produce all sorts of extraneous exogenous estrogen. That wouldn’t be so great.