Podcast Bites Ep29 4 of 5 – PD Mangan On Iron Ferritin and Premature Death

Latest Podcast broken into “bites” for those on the run!

Ep29 Segment 4 of 5 here – this episode #29 features PD Mangan who has authored the book “Dumping Iron” and “Stop the Clock” and several others. All contain super insights for resolving health issues and achieving a longer, more productive life. In this episode we focus on the detrimental effects of iron and iron metabolism on the body.

As always, you must know your disease level to know your risk

– please visit and #SHARE the IHDA.ie Website for heart disease awareness and prevention!

INDEX SEGMENT 4 of 5:

00:00:41 High ferritin but not at risk – exceptions to the rule?

00:05:43 “heterochronic parabiosis” – good blood, bad blood getting swapped over

00:08:00 Anti-aging basics – body composition and insulin sensitivity rule

00:11:25 The Diseases of Modernity – “Common Soil” and “One Ring Rules Them All”

FULL PODCAST Ep29 TRANSCRIPT:
Ivor Cummins 00:00:34 I’m here today with Dennis Mangan, more commonly known as P.D. Mangan, on Twitter and everywhere else who’s written a book which I read and I was fascinated by and it’s called “Dumping Iron.” And it’s all about the importance of your iron status in the body. So I had already researched iron because I had a high iron problem many, many years ago when I started researching disease, and then I got Dumping Iron and it gave all the answers. So hey Dennis, first time we’ve talked face to face. Delighted to be here and talk to you.

Dennis Mangan 00:01:07 Thanks, Ivor. I’m delighted to be here too. I’m a big fan of yours. I think the work you’re doing with raising awareness of the real causes of heart disease is incredible. I’m a big fan of that. I love it.

Ivor 00:01:24 Thanks a lot, Dennis. But to be honest, we’ve riffed a lot out on Twitter and elsewhere and had some great fun. I read your book; it was it was just fascinating to me, because just briefly, I had very elevated ferritin around 530 and high gamma-glutamyl transferase (GGT) 6 or 7 years ago. The doctors couldn’t give any guidance. And I started researching and I found out, wow, ferritin and everything to do with iron balance in the body is huge. And then it was afterwards I got your book. It was just unbelievable going through it because I had loads of papers on elevated ferritin and metabolic syndrome, and I thought I had most of them you should have. And then I read your book and I said, “Wow, everything is in here.”

00:02:13 So maybe we’ll start off talking a bit about this for the kind of lay person just going through all the stuff around iron in the body, the measurements of iron, the pathological significance of iron and just go through kind of all of it.

Dennis 00:02:30 Okay. So, iron is a required nutrient. We all need it to live and virtually every living organism needs iron and uses it is as part of the biological system, so we must have it. Historically speaking, or in evolutionary terms, I should say, we’ve lived in an iron scarce environment. So we have, human beings have developed a way to grab as much iron as we can out of the environment, which is our food and to hold on to it. But because of the scarcity of iron in our environment, we have no regulated way of getting rid of iron. So, in theory, we are able to absorb iron from our food and regulate it by increasing or decreasing the absorption of iron. But once you got it in you, it’s very difficult to get rid of. So, women due to the menstrual cycle have much lower iron levels on average than men. So, what happens is that by about the age of 18 to 20, when both sexes have reached the age of maturity, the iron levels in men starts to rise until by middle age, men typically have four to five times the level of iron in their blood as women do. And they also have four to five times the risk of heart attacks, and cardiovascular disease than women do at that age. So this fact, led the late Dr. Jerome Sullivan, to wonder whether, “Gee, you know, iron could be playing a role here.” Until that time, it was thought that the difference in heart disease rates in middle aged men versus women was due to estrogen or other hormones perhaps. And Dr. Sullivan came up with this idea, this hypothesis that it was in reality the higher iron levels of men that was causing the higher heart disease rates. And he worked on this idea for the rest of his life publishing many, many papers.

00:05:16 Iron is measured as the protein ferritin. So, ferritin is a protein that human beings and other organisms have, that controls iron. Because iron is a very reactive metal, so you don’t want it running around loose inside your body because it reacts with all kinds of other molecules that are in the body, oxidizes them, and in general is really bad news.

00:05:48 So you have this protein ferritin that holds iron within its core and keeps the iron safe, so to speak. So ferritin is a measure of stored iron. And if you get a ferritin test, which is a relatively common lab test done in all clinical laboratories, you can tell how much body iron you have.

00:06:15 Now, iron.. I’m not sure which way I should go in this story. So iron is implicated in all kinds of other diseases since it’s been found. For example, brain disorders like Parkinson’s disease and Alzheimer’s disease. Iron is implicated in both of those. It’s been implicated in cancer, in heart disease, like I mentioned, in diabetes. So basically a wide swath of chronic diseases, iron is implicated in all of them. By implicated I mean, it’s strongly suspected that they’re playing a role, how definitive that role is, how strong a role is, this is all continuing to be investigated and researched.

00:07:03 Now, getting back to the ferritin tests, there are normal ranges for ferritin just like there are for any laboratory tests. And normal ranges for any laboratory tests are done by finding out in in which range 95% of the normally healthy population falls? So, when you look at ferritin, you find that there’s a range of something like 30 nanograms per deciliter all the way up to depending on which laboratory you asked, 300, 400, even 500 nanograms per deciliter.

00:07:51 So, the problem is that this normally healthy population, this so-called healthy population in reality is subject to lots of chronic disease. They have a high risk of chronic disease. As we know, many, many, many middle-aged people and up have chronic diseases, but by the time people are 70, something like 90% of the population in the United States has some chronic disease or other.

00:08:29 These normal ranges of ferritin are not accurate in the sense that if somebody if somebody had, let’s say, a 250 ferritin level, this shows up as normal on a laboratory tests, and a doctor would very likely say nothing about it. You would think that’s normal. That’s fine. You’re good to go. However, there’s good evidence that a ferritin level anywhere above 100 is associated with health problems.

00:09:12 This work has been done, much of this has been done by Dr. Leo Zacharski, at Dartmouth University, who’s a brilliant researcher and has done a lot of this work on iron. And one of his most recent papers is to the effect that they figured out that a normal range for ferritin shouldn’t be any higher than 100 for optimal health. So, if people have these ferritin levels, let’s say between 100 and 500, at the Mayo Clinic I believe their normal range goes up to 500 ferritin level for men. So, so people have these normal ferritin levels, they may have some kind of problem, health problem that nobody can figure out but nobody’s looking at the iron at the ferritin level because it looks normal.

00:10:10 Now, a ferritin level much higher than 500 may get looked at. You know, I talked to someone just recently who had a ferritin level of 700 I believe it was and he could not get any doctor to take him seriously to do anything about it. They just said, “Don’t worry about it, it’s not a problem.” So, even a level that high which is frankly abnormal, doctors may not care much about… hemochromatosis is a genetic condition that when people have this, they absorb iron much more readily than others and they can get very high ferritin levels into the thousands, doctors will take that seriously. Hemochromatosis is associated with an early death, liver disease, all kinds of other things, this is what the very high iron does. So, the treatment for that, for hemochromatosis, for a very high ferritin level is therapeutic phlebotomy. Therapeutic phlebotomy is essentially the same thing as blood donation, only the blood doesn’t go to a donor; it is discarded. And also in therapeutic phlebotomy, blood can be removed much more often than they are for blood donation. So a healthy blood donor can give blood at a blood bank a maximum of six times a year. And whereas in hemochromatosis depending on the patient, it’s up to the doctor to decide this, but they can have phlebotomy as often as once a week.

00:12:05 So that’s how they get the ferritin levels lower. If somebody has a phlebotomy once a week and they have high iron levels, they will make up those red blood cells very quickly. Iron is a limiting factor there whereas the healthy blood donor may take several weeks to replace the red blood cells that are gone.

00:12:35 Dr. Zacharski had an interesting graph where he plotted average ferritin levels for men and women in the United States. And ferritin levels, average ferritin levels reached a peak at about the age of 65 for men, and then they declined down quite a bit to up to the age of 90. I think the level at the age of 90 was about half, so half of the peak. What is the explanation there? Well, the explanation seems to be that people with high ferritin levels are dying, leaving the lower ferritin level people to make up the average. So that’s the explanation for this declining ferritin level.

00:13:26 The Copenhagen City Heart Study looked at ferritin levels in mortality rates. And they found a very high mortality rate with people that had ferritin levels, I believe it was above 600 and decreasing mortality levels at lower ferritin levels, although they didn’t look at… I think the cut off was less than 200 or more than 200. If they had looked at less than 100, I feel pretty sure they would have found an even lower mortality rate than those at 200. But it was a linear relationship between ferritin levels and mortality rates.
PART 2/5

00:14:18 So, Yeah – what else would you like to know?

Ivor 00:14:20 Well, no. That’s a great summary of the kind of the high-level view of a ferritin. And when I got my 530 reading, I didn’t have a clue what it meant, even though as a biochemical engineer, you know, I’d never got into ferritin in any detail. The doctor was a little concerned because a lot of people in Ireland (relatively) have hemochromatosis. I think we’re like 2% of the population instead of 0.5% in general population.
00:14:49 So I got the genetic test for it first. I also was high in GGT. the liver enzyme, which I later found out was a huge marker for metabolic syndrome and insulin resistance, and then I began to research it and I actually started with ferritin and I could believe in the first two nights. Exactly what you say Dennis, the linkages to mortality made LDL as a risk factor look like a joke. It was stunning! And the same with GGT. But there was a study and you mentioned below 100, and I agree entirely. There was one study that I found that showed carotid atherosclerosis, right, that was examined in men and women, and basically below 50, the rates of carotid atherosclerosis were really low and above 50, just that split, they were way higher, like six, seven times higher. But the interesting thing was that the women who were above 50, like pretty high, they had the same carotid atherosclerosis that middle aged man. In other words, when the ferritin was high, the women no longer had the protective effect. You know? And there are so many other studies that show pretty much exactly what you’re saying.

Dennis 00:16:08 So yes, that study was great, very striking study, the difference in carotid atherosclerosis between low and high ferritin. There’s a great graph with that study that’s just kind of blows you away when you see it.

Ivor 00:16:24 Yeah, well, I guess, for sure, Dennis. But the other thing is, there are so many studies, many of them similarly striking. Now, a lot of them are associational. They don’t prove direct causality. But I mean, just another one I got in the first week or two was LDL is a risk factor against ferritin and the high LDL versus low LDL people, big differences. But when people were low ferritin, high versus low LDL made no difference. But as the ferritin was higher in the group’s, the higher LDL made more and more difference. And I was already beginning to research cholesterol down and realizing that LDL is not an independent risk factor really, it depends on whether you have inflammation or another problem that’s an arterial installed. So it’s dependent, but this graph showed a beautifully higher and higher ferritin indicating more and more potential inflammation. And the LDL began to be a factor. But there are so many of these studies and yet the world’s interest in ferritin even though it’s a more powerful risk marker than LDL, there is no interest.

Dennis 00:17:34 It’s true there’s no interest. There’s some researchers out there looking at it but it’s very much under the radar. Very little interest. I feel that the emphasis on cholesterol, since, you know going back decades has just put the blinders on people, on the people in this field, the researchers and they’re not seeing this. There’s a very striking trial done by the man I mentioned a while ago Dr. Leo Zacharski. This was a trial of bloodletting, of therapeutic phlebotomy and these were men in the Veterans Affairs, Veterans Administration, right. So they were going to the Veterans Administration for their health care. So these are older men, many of them cigarette smokers, and they all had peripheral arterial disease. So this is what it sounds like. Arterial atherosclerosis but not in the heart, so elsewhere in the body, often in the legs. So they

00:18:59 They did his trial of bloodletting and they randomize these men. They were, I think they were all men, but they might not have been. Anyway, the vast majority were men, at least. And they did a trial of phlebotomy and their results were somewhat underwhelming in the area of heart disease. But when they analyzed the data, they found out that this man that got phlebotomies had lowered their ferritins, had much lower rates of cancer than the man who had not. And even on a further analysis of the data… it’s a very difficult sort of study to carry out because the subjects have to be highly compliant. They have to come in through their phlebotomies and so on and not all of them did that regularly. And they have to calibrate the phlebotomies to figure out, depending on the hematocrit and hemoglobin of the subjects, how much ferritin they’re carrying, and so on so forth, other factors they have to calibrate the phlebotomy. But in any case, they found that in both groups, whether that man have had phlebotomies or not, the ones that had a ferritin level of about 75 had far lower cancer rates. It was cancer mortality, they had far lower cancer mortality than men and either group who had a ferritin of an average of 125.

00:20:41 So yes, very striking. This study, they looked at these men for several years. And this is something that, again, no nobody knows about this. So yes, very striking. This is not a not a randomized controlled trial but an experiment I guess for lack of any other word, of doing phlebotomy on normal people and they find that their endothelial function goes way up when they’ve had phlebotomy, when they lower their ferritin levels. First they found this in blood donors, frequent blood donors who give blood several times a year. They compare them to infrequent blood donors who give blood at most once a year. As I discussed in my book, there’s a problem here in looking at blood donors in regards to health. So many studies have found that blood donors have much better health, lower rates of heart disease, and so on than non blood donors. The problem is is that blood donors are likely to be healthier to begin with, otherwise they would not be giving blood. So, just to analyzing blood donors against the general population may not tell you a whole lot.

00:22:22 A number of other researchers have done is compare frequent blood donors to infrequent blood donors. One study that I know of the frequent donors that given blood several times a year for each of the past three years, I believe it was and then the infrequent donors had only given blood at least once in those three years. And they found out that these, the frequent donors had better endothelial function. So what that means for arterial health, it has a significant meaning for arterial health. It means it that arteries function much better, less likely to get atherosclerosis. And as someone said, you’re only as old as your arteries. So, this is very important.

00:23:18 Other studies have shown that lowering ferritin levels by phlebotomy. So, let me back up a little bit. The study I was just talking about was an associational study. But other studies have shown, when you actually take people and take some blood out of them, do phlebotomy on them, then their endothelial function does increase quite a bit.

Ivor 00:23:45 Right, and that’s direct kind of RCT type or randomized experiment prove the point, prove causality. I did see one and I’ll have to pull it out now for show notes, but a very striking graph and I think it was also peripheral arterial disease. But when they segmented from memory a few years ago, to older people within the group, the younger people not so much signal, which kind of makes sense because younger people that will be harder to see a signal for any deleterious effects, older people see it easier. And they had a graph of events for peripheral arterial disease events. And that was recorded, I think, as any, vascular event or operation or problem arising. And there was a 66% reduction in the people who did [the bloodletting]. I think it was two blood donations or more a year and it was randomized, versus the people who didn’t.

00:24:43 Now, technically it was randomized. You could argue that the people who had the blood taken, well it could have reduced their oxidized lipoproteins, or it could have had some other effect. But to be quite honest, by any reckoning, a couple of pints of blood taken won’t really impact platelets and lipoprotein so much, but it will impact iron quite significantly. And that’s what they were testing. And it’s the only RCT I know that was properly executed. And it’s kind of interesting that as such, it showed a much bigger reduction in events for vascular issues than a lot of the mass market medications. But I guess as we said earlier, there’s not a huge amount of interest because I guess there’s no real profit motive. There’s no real research budget looking for new treatments that’s going to be looking at bloodletting. For God’s sake, it sounds like medieval stuff.

Dennis 00:25:40 It certainly does. Therapeutic phlebotomy, it’s a very inexpensive therapy. I read somewhere where the average doctor bills is $130 for a therapeutic phlebotomy. So as medical care goes, this is dirt cheap.

Ivor 00:26:02 It just occurs to me and I often say it to people that there’s mechanistic science behind this. I mean, we can talk in a minute without going too deep. I went through masses of papers six years ago. There’s fantastic mechanistic evidence for it. There’s really strong associational but we know as you described, it can be confounded. And then there’s so much experimental. So all three pillars of evidence are represented for this. But I always say to people, well, even if it’s not completely a really big beneficial effect if you’re a high ferritin to give blood, giving blood also helps people. So it’s like a win-win.

PART 3/5

So whatever about paying, you can give blood in Ireland three times a year or four times and I think in the States, maybe six, so you can help other people and highly likely improve your own health with the one intervention. I mean, what’s not to like?

Dennis 00:27:06 Absolutely. The thing is is that a large number of people are ineligible to donate blood. I don’t know what the figures are. They say that the Red Cross has a figure like only 5% of people donate blood. I’m not sure if that’s compared to everyone or only 5% of the eligible people. But nevertheless, I believe over half of the adult population is ineligible for one reason or another to give blood, you have to be a healthy person and they have a lot of hurdles to jump.

00:28:33 So therapeutic phlebotomy would be a nice option. And I’ve had a lot of people ask me, “How do I get a therapeutic phlebotomy? I just want to get rid of some blood, you know?” And, “I’m ineligible to donate.” We’re talking about say, you know, a normal age, normal middle-aged man or woman. “I just want to get rid of some blood but I can’t donate.” Or you know people are too busy. They would love to be able to pop into the doctor’s office and get rid of a pint of blood, whereas blood donation processes is a little lengthier. But unfortunately, there are just no good options. A number of doctors who are willing to perform it for an otherwise healthy person with a ferritin level that is not just sky high is very, very few.

Ivor 00:29:28 Yeah, I’d agree. I often made the joke with people about, “Well, Google and find out how to find a vein,” you know? We are not recommending that here. That was a joke. Of course your local drug dealer might be able to help you out with finding one!

00:29:49 Yeah, it’s a pity but in fairness, if it’s not acknowledged in the established medical Canon or medical science, you could understand the reluctance to do, what to a doctor would appear to be quackery having not looked or seen any of the science. So it’s fair enough.

00:30:10 Interestingly on another angle on the iron, when I researched it for a few weeks, like I said, I was quite frankly shocked because I saw the correlations, mortality, cardiovascular disease. I cannot believe how problematic high ferritin was in associational data. And the mechanisms were beautiful. I mean, I just buried myself in them. But I found one night, I predicted, because in engineering you always try and predict, make a hypothesis that can be tested. You know, if you’re a root cause specialist like I was, you always try and make the best hypothesis and you try and test it and when you actually test it, and it works, it’s like, “Whoopee!” But, I was looking for papers on metabolic and insulin resistance syndrome. And I knew for myself research on iron and ferritin, and from my research on hyperinsulinemia and insulin resistance, I knew that iron and ferritin should link to the insulin resistance syndrome. It kind of have to from the way my research was going because I was following certain paths and I could see where they showed intersect. And funnily one night, it was a Tuesday night I remember, my wife was thinking, “Ivor has gone crazy. Like every night he comes home from work, and he’s in there looking at these papers, mountains of papers printed out.” And then I found it. And it was basically a Chinese study, and it said, the title practically said that “Elevated ferritin should be the sixth marker for metabolic syndrome.” And I went running out of the room. Yes, I knew it! The core titles of ferritin against metabolic syndrome components were just stunning.
00:31:56 I guess the point though that then arose was ferritin can be causal in excess through many mechanisms. But also ferritin elevates in inflammatory conditions like metabolic syndrome and even people with lupus or arthritis going to really high ferritin. So this whole iron interaction is so complex and it can be an indicator and a reactant to inflammatory pressure. So it can be both a sign and a driver of problems. So maybe we talk a little about that.

Dennis: 00:32:32 Yes, absolutely. There’s sort of a, when you’re talking about elevated ferritin and things like metabolic syndrome or diabetes, there is a chicken or egg problem here. Which came first, what’s causing what? On the one hand, what appears to be happening is that when someone has metabolic syndrome a lot of the system is screwed up, right? So the system that regulates iron absorption is screwed up and they could absorb more iron.

00:33:16 Another thing going on is then when you have this ferritin… so you’ve read my book and you know, I use this metaphor in my book about ferritin. It’s like “stored dynamite.” So, if you have a bunch of dynamite in a crate, it’s supposed to be safe. But you don’t really want to have a crate of dynamite in your house. Accidents happen. So with ferritin, what happens… the ferritin itself, that’s the safe form of iron but the iron gets out of it. And then when the iron gets out of it, the atomic iron in it reacts with all these other molecules in the body, causes oxidative stress, it oxidizes the LDL, it oxidizes the cellular proteins and cellular membranes.

00:34:16 That’s what exactly what you don’t want to have happen. In Alzheimer’s disease for example, there appears to be it’s not ferritin as such, it’s causing the problem but it’s free iron in the brain that so for some reason, the body and the brain are unable to keep that iron safely locked away in ferritin and it goes out into the brain and causes all these problems. As you know, Alzheimer’s disease is often referred to as Type 3 Diabetes. So there you have a connection, where you’ve got this insulin resistance syndrome in the brain and then you’ve got this free iron causing problems.

00:34:59 Which came first? Well, that’s hard to say. But what appears to happen in metabolic syndrome and diabetes is that the high blood sugar as you know, causes glucose linking to proteins and other molecules in the body and renders them dysfunctional or non-functional. And what appears to be happening is that ferritin itself is subject to this attack by glucose and blood glucose goes very high. So somebody who has a high blood glucose is more likely to have this glycosylated ferritin. Their ferritin is then no longer able to hold the iron within it and it gets out and causing these oxidation reactions.

00:35:49 So, as you say, it is very complex. There are several things going on here, many things going on here. It does appear by my reading that elevated ferritin alone can cause these problems. But then on the other hand, metabolic syndrome can lead to elevated ferritin with lots of free iron in the system causing all these problems.

Ivor 00:36:16 Yeah. So essentially in a way it may be slightly like insulin itself and hyperinsulinemia and insulin resistance. It’s got insulin resistance, the state has causal pathways, myriad causal pathways to actually damage the body. But insulin resistance and hyperinsulinemia also act as a really good gauge of another damaging process that it reacts and rises in response to, like infections smoking, your insulin resistance rises in response to many insults that in turn cause damage to your vasculature. So similarly, the raised ferritin may, being high may be bad for many different reasons.

00:36:58 Mine actually, I projected that when I switch to a low carb, healthy fats diet, that my metrics would get better. And I expected because of the metabolic syndrome that the ferritin would too and certainty the GGT. What happened in seven or eight weeks was the ferritin went from 532, I think to 20, the GGT went from 115 down to, in eight weeks or nine weeks, the high 20’s. And my cholesterol ratios all dramatically got better. So it’s very pleasing to see that every marker I researched, went exactly where it ought to go based on switching the diet and fixing the root causes. But there seems to be people with high ferritin who do not have much disease. So I wonder, and I’ve wondered this for a couple of years and recently we did calcification scans on 45 sportsmen, and we had all their bloods and all their scan results, and there were zero up to 3,200. These were famous sporting players from the 1990’s. And I noticed the ferritin didn’t correlate very well. And there were zero calcification with high ferritins. It was kind of more randomized. The triglyceride to HDL and the ratios correlated well with the calcification as expected. And the HbA1c was pretty good. But I’ve wondered from small pieces of data over the years, can certain people have a high ferritin and yet it really is sequestered safely and are managing it without any deleterious effects?

PART 4/5

Dennis 00:38:40 I think in theory, that could be absolutely correct. However, I’ll just bring up… well, I want to speak to one thing you said where you had a stack of papers and going through this stuff. I had exactly the same experience. I mean, it was amazing. You look at this stuff and you think, “My God, this is just… what is going on here? And nobody knows this.” What happened to me was I started looking into this and thinking, you know, “This is just incredible.” And I wrote several articles on my website for it and then at some point I said, “Well, you know, I have to write a book about this because this is just too important, just to have a few articles on my website.” So I did, obviously.

00:39:41 But back to your question about high ferritin levels and whether or not somebody could have a high ferritin and be healthy otherwise. There was a recent study that looked at people with the genes for hemochromatosis. People with the genes for hemochromatosis can have a wide range of ferritin levels. So not all of them get super high, right? So somebody with hemochromatosis that has obvious health problems may have a ferritin levels over 1,000, over 2,000, even higher. But other people for various reasons, may not develop ferritin levels that high, even with the gene because there’s so many factors that go into iron levels. Just to name a couple. Alcohol consumption. Alcohol increases the rate of iron absorption. Vitamin C, you know, from orange juice, increases the rate of iron absorption. Things like that. So, depends on what people eat and genetic makeup and other factors.

00:40:56 Anyway, there are people with the hemochromatosis genes that have a wide range of ferritin levels, not all of them necessarily super high. A lot of people, they had these hemochromatosis genes but were not necessarily diagnosed with hemochromatosis and they found that these people had much higher risk of various health problems, liver disease, heart disease and so on, than others in the population.

00:41:26 What does that show? That seems to show that high ferritin levels even when not as high as to cause hemochromatosis are damaging, generally speaking. Whether one individual necessarily has health problems if they have a relatively high ferritin, maybe, maybe not. But in general, higher ferritin levels are associated with health problems in this population.

Ivor 00:42:00 Yeah, for sure. And the data is very compelling that in general, it’s a really bad sign. I mean, even the studies we referred to and I referred to earlier and I was just piqued, or my curiosity was piqued, are there exceptions that prove the rule a bit like… I mean, you can take familial hypercholesterolemia. People who have familial hypercholesterolemia have a genetic susceptibility to damage from the modern environment. That’s the way I view it, like ApoE4 people. Some of them who have very high particle numbers go to long, healthy lives with no problem with atherosclerosis, and some burn up really young. Now, I think the environmental influence is huge – that interacts with the high particle account.

00:42:47 But again, you know, there may be a pocket of high ferritin people where their physiology is running a high ferritin but manages to keep it safe like you say in the ferritin macromolecule, it’s just kept physiologic and it’s okay. But to be honest, we’re not going to get the data for that. The message today for people is ferritin is a really powerful risk factor with many, many mechanisms. And I just mentioned actually years ago, I came across a Chris Kresser video called “Iron Behaving Badly.” It was quite a good summary, and Chris is really a smart guy, but it was essentially the same as what we’re talking about broadly speaking? You know, it is something to really watch and watch carefully. And the dimwits who are just looking at their cholesterol and not looking at ferritin and GGT and other key markers, you know, you’re kind of missing wood for trees in many cases.

Dennis 00:43:43 Absolutely. There is another, I’m just remembering here, just something I saw a couple of days ago, a study about heterochronic parabiosis which is of great interest to those of us who are interested in the anti-aging field and aging research. So, heterochronic parabiosis involves exchanging the circulations of two lab animals, usually mice. This is a so called, probably most people have heard of this, “Young Blood Rejuvenating idea.”

00:44:22 In this particular experiment what they found was this was highly related to iron, that the old animals had higher levels of tissue iron and that being exposed to the young blood from from the younger animals lowered their levels of tissue iron. And these particular researchers concluded that iron was a huge factor in this phenomenon of heterochronic parabiosis. This is something you know, all modesty aside that I’ve been saying for a while.

00:44:56 Here’s another interesting factor about this in heterochronic parabiosis is that old blood appears to be worse for a young animal than the young blood is good for the old animal. So, you think, “Oh, well what’s going on here? Maybe it’s iron.” You know, that’s the obvious thing that occurs to me, and animals do accumulate iron as they age. There was a good study about that, how it’s related to sarcopenia, and that the known anti-aging treatments that we know work for instance in lab animals, calorie restriction, giving them much less food. It also means they accumulate much less iron as they age.

00:45:48 There’s an iron angle here in everything. I’m not saying that that’s the whole story by any means. It’s just an overlooked factor here in not only in disease but in aging in general.

Ivor 00:46:00 Yeah, for sure. And actually you wrote, I’m so busy the past couple of years I can’t keep up with anyone’s books, but you’ve also written a book on anti-aging. So if we twisted away from iron for a moment, any thoughts you have in anti-aging in general? I mean I have thoughts and that myself and Dr. Gerber wrote essentially a longevity book, “Eat Rich, Live Long.” But it’s all the usual things like the critical vitamins, minerals, the lower carb, no vegetable oils, you know, resistance training, fasting, everything is in there including a bit on iron. But your book in longevity, yeah, would you want to pull out some of your top things that you’re excited about?

Dennis 00:46:45 You know, it’s like you just said that most of the things that conduce to good health are also anti-aging. So for example, we know that in lab animals restricting their food makes them live longer. So for human beings, fasting is an obvious anti-aging intervention. What’s interesting is the parallels between aging and obesity. So, when human beings age, their insulin resistance increases, they tend to get more body fat and lose muscle, and they accumulate iron obviously. But so many of these, there’s so many parallels between obesity and aging.

00:47:44 When we age, we’re not able to regulate metabolism as well. Those are the facts. What’s causing that how much of that is due to aging and how much of that is due to the modern environment, modern lifestyle?
00:48:05 That’s a good question. These are actually kind of deep questions because even when you study laboratory animals, you get into… I’ve discussed this on my site quite a bit. Well, you know, if you’re feeding them garbage and keeping them in cages, is that really a study of aging? If you feed them less garbage and they live longer, that makes sense. But is it really anti-aging or just feeding them less garbage? In any case, what we can do for anti-aging, the most important things are those things that are the opposite of obesity and insulin resistance. So have a low level of body fat, a high level of muscle, have a high level of insulin sensitivity. In my view, that calls for eating whole minimally processed foods, preferably lower in carb but certainly not including refined grains, sugar and vegetable oils. Those are out. In a nutshell, that’s what I think that people should do for anti-aging is body composition and insulin sensitivity are very important.

Ivor 00:49:25 Yeah, couldn’t agree more. And I love as well, I mean for the general person who’s not going to get into all of the different factors here and the myriad factors, you know, sugar, refined carbs, veg oil elimination, and the processed foods that carry those constituents. Because ultra-processed food is full of vegetable oils and refined carb, take all that out and just eat real food. Most people if they start young enough wouldn’t even have to worry too much about counting macros to the last degree. You know, that’s the reality.

00:49:57 I always love Dr. Ron Rosedale’s phrase and maybe he took it from somewhere. He said, “Diabetes is essentially a model of accelerated aging.”

Dennis 00:50:09 Yes, very good. Yes, I agree with that.

Ivor 00:50:11 And it’s so perfect because all the diseases of modernity, all the chronic diseases that have come in the last century, diabetes accelerates them all. There was a lovely study by Professor Gerald Reaven, the kind of Master of Insulin Resistance research. And it only had a few hundred middle aged people but they were randomly picked and he split them into third tiles, thirds of insulin sensitivity with a really accurate steady state plasma glucose insulin test. So a proper test, not just a fasting insulin. And basically the bottom third who were insulin sensitive over seven years had zero disease, death or any problem. The middle third had 12 cases of disease and death out of that whatever, 80 number. And the top third of insulin resistance had 28, and it was cancers, diabetes, all the hypertension, all the usual stuff. And he basically, they said essentially insulin resistance or sensitivity kind of sits at the center of diseases of aging. But still though, I know I met many doctors six years ago when I started my research. Good guys. I mean good guys. And they actually were not really familiar with metabolic syndrome or insulin resistance syndrome. And only when they googled it after I told them, they came back to me and said, “Oh my God,” – and they were quite frankly shocked.

PART 5/5

I told them just go and Google insulin resistance and any disease that you’re seeing in your population in the last 30 years. And they did and within minutes, their jaws dropped. They had no idea that the literature is absolutely crammed with hundreds of thousands of papers linking insulin sensitivity to all the diseases they’re trying to deal with. Mad.

Dennis 00:52:09 It is mad. This study that you mentioned by Gerald Reaven and colleagues, one of whom (I got to throw this in) was… one of his colleagues that worked on that was Dr. Francesco Zucchini who wrote blurb for my book, Dumping Iron. He’s done a lot of iron research. But in any case, the study by Reaven and colleagues, yes, it’s incredible. When you see that graph of the people grouped by insulin sensitivity, third tiles of insulin sensitivity and the diseases, it’s one of the most striking things that you can ever see related to health. Insulin sensitivity is just critical for health.

00:52:58 I would have to assume that your experience with the doctor is not knowing this is typical. It’s sad.

Ivor 00:53:07 It’s very sad because I mean, in say engineering or high-tech industry, that could never happen because businesses can only survive by knowing the real causes and addressing them. Otherwise their competitors would kill them. But in medicine though, there isn’t that selection pressure and you can easily go ahead without knowing root causes and it technically won’t affect your business. I think it’s not a conspiracy. It’s just no one’s interested if there’s no drug for it, I guess.

00:53:41 But yeah, the other paper from Reaven, it actually springs to mind as we speak, Reaven had one and I nearly can remember the title; it’s years ago. He said, “All of these people are not created equal – insulin resistance is the determinant of cardiovascular risk in the obese.” And I mean he just split them out again large numbers by insulin sensitivity and all the cardio metabolic risk factors dramatically went from high down to low as they got more insulin sensitive and they were all the same big BMI. And you’re right, no one knows this, even many doctors.

Dennis 00:54:25 Right. I I like your analogy there with business that this couldn’t happen in business because it’s like you say your competitors would get you. But yeah, the same selection pressures are not in medicine apparently because it just keeps going on. I think that yes, this problem of them generally not knowing and wanting to prescribe drugs, there’s another chicken or egg problem there too. As I’m sure you know, pharmaceutical companies are very involved in influencing medical research and influencing medical practice and influencing the standard of care. But there’s also the case where patients are often reluctant to do anything much about changing. Also, the fact that most doctors really wouldn’t know what to tell them to change, rather than prescribing a drug. So there’s lots of levels here, where people are not getting the help they need, in my view.

Ivor 00:55:46 Yeah, and that’s true. And hopefully things are changing though. I was chatting earlier, I did a podcast with Dr. Andy Phung, and he’s new to this. But he was 8 years a doctor, he’s in New York. He went through college residency and seven or eight years of practice. And then he became prediabetic himself. He’s Asian extraction, obviously. And he spent a whole year exercising an hour a day on an elliptical machine, didn’t lose any weight, did improve his blood glucose level. And then he discovered, I think it was Dr. Jason Fung, and it blew him away. But long story short, he’s now for the last year massively helping his patients rather than just giving them pills. And he admitted and acknowledged in fairness, and so what I what you said, he still has a lot of patients who won’t do it even when he explains it but a large proportion are doing it and he’s got guys lost nearly a 100 pounds insulin down from 25 down to like five, like massive VLDL and triglyceride levels collapsed and he is a huge proportion of his patients who are just absolutely ecstatic. Because someone actually has told them what they need to do. And they won’t all do it. But a huge amount will.

Dennis 00:57:10 Yes. I’m sure that many people if they hear from their doctor, you know, doctor’s orders and all that, they’ll do it. But obviously, right now, not very many people are getting those doctor’s orders.

Ivor 00:57:26 Yeah. Well, I think, to be quite honest, the power of the internet six or seven years ago with PubMed, Researchgate and other published science databases, and all the data and published papers, allowed me to find out the same thing allowed you and there’s a growing army of citizen scientists and the beauty is doctors are too busy. The guys I mentioned are great guys. They said like there’s no way they’re going to go home at night and start looking up stuff. They’ve got their CME’s, they’ve got their education, continued medical education. And that’s mostly kind of pharmaceutical based, and there’s no way they have time. But by feeding back to the doctors, and all these podcasts and all of this worldwide, the conferences on low carb, this massive groundswell, I think it’s going to get back in the next few years to more and more doctors, particularly young ones. And I’m expecting a kind of a revolution. Am I too positive about it?

Dennis 00:58:25 No, I don’t think so. I see a lot of the same things that you are. I’ve seen on Twitter, I’ve seen doctors actually changing their minds. I’m sure you know, Dr. Tro Kalayjian I think is his last name. And he was obese himself and now he’s very much not obese. He changed his mind. He got on Twitter and he was talking to people and he decided that he was going to give this low carb a try. And now he’s an event. He’s lost a lot of weight, like 150 pounds or something along those lines and he’s become an evangelist for it. I think that’s great.

00:59:18 I just saw another one just the other day. A doctor who I couldn’t tell you her name at the moment, and I had not heard of her before, but she was basically figuratively slapping herself in the forehead saying, “I can’t believe medicine as a profession is overlooking all this. It’s got to change.”

Ivor 00:59:42 Yeah, man. You’re absolutely right, Dennis. Tro is fantastic. I had a massive Twitter fight with Tro a few years ago about LDL. And he was just coming into the low carb thing, I think but he was still a big LDL believer. We’re great friends now but Tro is not just converted. He’s not just been able to change his mind about everything and lose an enormous amount of weight. He’s become a trailblazer and actually it’s himself and Brian Lenzkes, I think I met in San Diego, another doc, those two guys now are doing the Low Carb MD podcast.

01:00:24 But you know something, know we both got time our heart stops here it’s late in the evening here in Ireland and you’ve got a busy day. But that’s a quite a positive note to kind of begin to wrap up on. What do you think?

Dennis 01:00:37 Yes. We can only hope. I’m out trying to spread the word myself. We didn’t talk too much until the end here about low carb but I’m very much in favor of it. And especially getting rid of all the ultra-processed foods, eating whole minimally processed food. Unfortunately, the vast majority of the food that people eat is ultra-processed food. I think that’s pretty much the root cause of our problems, our modern health problems right there.

01:01:12 Yes. So hopefully people are becoming more aware of that and the doctors will become more aware of that too.

Ivor 01:01:22 Yeah. I just thought of another positive note to end on the calcification scan and I work on behalf of Irish Heart Disease Awareness charity to get out information about a life-saving scan CAC score. It basically tells you if you’ve got big disease and huge risk and allows you to take action, even if your bloods don’t really say much. But in the 2018 guidelines, delighted last year, they’ve now come out with CAC level II-A evidence to use it for middle risk people, a paradigm shift to actually use a scan that sees the heart disease directly rather than blood tests in medication decisions. So there may very well be people now finding out their true level of heart disease, maybe not needing medications rather needlessly getting medications for life, and then finding people who are a huge risk who can get medications in every other intervention. So that’s another shot in the arm for me this year.

Dennis 01:02:22 That’s fantastic, Ivor.

Ivor 01:02:24 Oh, yeah. Good to go! So we got to keep getting the message out. Listen Dennis, it was a pleasure to talk to you. And you know what, we’re going to be back talking again and we got to pick a few more topics to kill.

Dennis 01:02:35 That’s great, Ivor. It was totally a pleasure talking to you. I’m a big admirer of yours. I think the work you’re doing is fantastic. And I hope you keep on going with it. It was really great talking to you.

Ivor 01:02:49 And yourself too Dennis. Hugely enjoyed your book and I need to get to your others. And you’re a big force on Twitter too. And I think I agree, Twitter is where a lot of this is going to really get out.
Dennis 01:03:00 Yes, absolutely. Yes.

Ivor 01:03:02 Thanks a lot, Dennis. Goodluck!

Dennis 01:03:04 Thanks. Thanks, Ivor. Talk to you later.

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