In this video, Elliot from EO Nutrition discusses the link between iron overload and low free testosterone in males. He shares his personal experience of dealing with high sex hormone binding globulin (SHBG) levels and how he found a solution by fixing his iron overload. He also references Dr. Paul Saladino, who had a similar problem and benefited from reducing his iron saturation through phlebotomy. They discuss the connection between iron and testosterone production, suggesting that high iron levels may lead the body to reduce free testosterone to prevent complications from increased red blood cell production. Iron saturation testing is recommended to determine if iron overload is a potential cause of low free testosterone.
Key Insights:
- Low free testosterone can lead to symptoms of Androgen deficiency, even if total testosterone levels are normal.
- Elevated sex hormone binding globulin (SHBG) is a common cause of low free testosterone levels.
- Iron overload can contribute to elevated SHBG levels and subsequent low free testosterone.
- Males who eat a diet high in animal-based or organ meat, use cast iron pans, or have genetic variations that increase iron absorption are at a greater risk of iron overload.
- Iron overload can lead to oxidative stress and inflammation, causing damage to the testicles and reducing testosterone production.
- Donating blood through phlebotomy can help reduce iron overload and lower SHBG levels, resulting in increased free testosterone.
- Transferrin saturation is a better marker for iron status than ferritin levels.
- Elevated SHBG may serve as a protective mechanism by reducing free testosterone levels to prevent increased blood cell production in the presence of iron overload.
- Exploring iron overload as a potential cause of chronically high SHBG levels could be beneficial for individuals struggling to find a solution.
Transcript
Guys, if you have low free testosterone, you need to pay attention to this video. So, this is Elliot from EO Nutrition, and today we’re going to focus on one of the most overlooked and hidden causes of low testosterone, usually in males. And the chances are practically no one even knows about it.
I’m speaking from experience in that I had to deal with this problem for years, and I eventually found a solution for it. It also seems as though Dr. Paul Saladino, known as Carnival MD, has also dealt with this similar kind of problem. And based on a comment that I made on one of his YouTube videos a couple of months ago, he seems to have also benefited from the same solution.
So, in this video, we’re going to talk about what that solution actually is. So, although your total testosterone may be normal or may even be high, which is actually quite common, the free portion is the portion which is bioavailable and can act on tissue. So, if you have low free testosterone, you can still develop symptoms of Androgen deficiency despite having normal total levels.
The most common reason for low free testosterone levels is elevated sex hormone binding globulin (SHBG). For those who don’t know, this is a protein which is produced mainly in the liver. It’s pumped into the blood, and then when it’s in the blood, it binds very tightly with testosterone. This renders it not free and reduces its bioavailability.
For what it’s worth, just so that you can see, my SHBG has been elevated for several years now. This was back in 2019, you can see it’s in the red. In 2020, I had it measured again, and we could see that it actually went up. It went up to 83 and it came back down to 58, but that’s still much higher than I would like to see it. And what I can fortunately say now is the last time I had this checked, which was June 2022, you can see it’s come back down. It’s come down to 48, which is the best it’s been in several years. Basically, I found a way to bring down sex hormone binding globulin, and it’s really simple.
There are several potential causes for elevated sex hormone binding globulin. Let’s just say that I had gone through many websites online and looked at many of the risk factors, and I tried as many things as possible. Quite simply, none of it worked. The only way that I could find the solution that worked for me was by going directly to the scientific literature and reading through it.
Turns out that the solution which helped me bring down my levels was fixing iron overload. Iron is one of those dietary minerals with a really high toxic potential if it’s found in too high amounts or if the body can’t process it really well. So, men are at a much greater risk for iron accumulation or iron overload disorders simply because we don’t menstruate and we don’t lose iron.
This is particularly relevant for males who eat animal-based or a diet which is very high in organ meat or red meat, if they eat from cast iron pans, or alternatively if you have any of the genetic variations which might predispose you towards hyperabsorption of iron such as found in hemochromatosis.
It’s well known that iron overload will lead to a progressive decline in testosterone, and this is thought to occur both at the level of the brain and the testes. So, there’s profound oxidative stress and this hyperinflammatory environment where the testicles become damaged, they literally lose the ability to make testosterone. There’s lots of other stuff that goes on, but it’s also known now that iron overload in the liver can also elevate SHBG. It can be one of the things that causes unexplained high sex hormone binding globulin levels.
This concept was also demonstrated in another case study of an individual who was presenting with erectile dysfunction but had normal, more actually had high testosterone levels. So, if we go down then we see that this individual also had very high SHBG, which is to be expected, and he had significant markers of iron overload. In fact, if you look at his transferrin saturation, it was absolutely massive, 86%. His ferritin was above 1000, and his gamma GT, which is a marker of liver dysfunction, was 167. So, this guy had progressed pretty far, and we see that there was definitely a correlation between SHBG and this overall tendency of the liver to accumulate iron.
If we look at Paul Saladino’s recent videos, we see that he also seemed to be experiencing something similar to this. Taking a look at his August 2022 blood work update, you see his total testosterone is on the higher side for sure, it’s in the 900s, very close to the reference range. But you see that his free testosterone percentage is pretty low. Let’s see what he had to say about that.
„There is one piece of these hormones that continues to interest me that I’ll talk about. You can see the free testosterone is 14.37 nanograms per deciliter. It’s 1.59 percentage, and I would like that to be a little higher. And I think that is because my SHBG remains a little bit higher than I’d like to see it. You can see here the SHBG on this test was 97.5, so very high SHBG. That would help to explain the low free testosterone.“
But then we look at another part of his test. We see that the iron saturation is up at 42%, which is higher than I would like to see it personally. And then we also go back to a month prior and look at another test that he had done, and you see that the iron saturation was all the way up at 54%. So, this is kind of in the danger zone. It’s a very similar pattern that I saw in myself: high total testosterone, low free testosterone, high SHBG, along with high transferrin or iron saturation.
So, I actually went ahead and dropped a comment on his video and explained my own situation, what I’d seen in my own clients and what I had seen in myself. Fast forward a couple of months, and we see his most recent blood work update in December 2022. Right, so what we can see is a positive trend. We see that the total testosterone comes down, but that’s really quite irrelevant because what we also see is that the free testosterone goes up. The iron saturation coincidentally has gone down. And then if we look at the sex hormone binding globulin, well, that has also gone down significantly. Remember, it was up at 97 and it’s gone down to 69. Let’s listen to what Paul actually did to achieve this.
„For the majority of the time since the last blood draw in August, I’ve actually been doing phlebotomy. So, I’ve been going to a practitioner who will just take my blood and give it to plants or throw it out. So essentially, bleeding out of my vein. I’m doing about 200 cc’s of blood every three to four weeks, or if I can do it more regularly, I would probably aim for 50 to 60 cc’s per week. Now, I don’t have hemochromatosis, but if you look at my blood work and I’ll go back to that in a moment, my ferritin was creeping up, my iron saturation was creeping up, and my transferring saturation was creeping up. And had tipped Elliot Overton who made a comment on one of my YouTube videos and said, ‚You should think about iron overload.‘ This is something where I’ve learned in the past few months, and it’s why I wanted to share this with you guys. I never really thought that a ferritin of 250 or 300 was problematic for most humans, but I’m having to question that in my own mind now. And I think that if I continue doing phlebotomy and my SHBG continues to come down as I get rid of excess iron, then this may lend support for the hypothesis.“
So, this is exactly what happened to me. It’s exactly what I’ve seen on a clinical basis. As I started donating blood and brought down my transferring saturation levels, my sex hormone binding globulin levels followed quite nicely. And it seems to be a very effective way to bring sex hormone binding globulin down if there is evidence of iron overload.
The best way to check for evidence of iron overload, if you suspect that this might be a problem for you, is to look at your transferring saturation. If you’re in the US, you might be doing iron saturation, although transferring saturation is the best marker. Though many doctors will erroneously look at ferritin as the best marker for iron status, ferritin doesn’t become elevated until quite late into the disease. Usually in the early stages, the best way to check is by looking at transferring saturation. It’s the earliest and most accurate marker.
Now, this particular paper is saying if it’s above 40 or 45%, if it’s above 45%, then that’s a very good indication. One might even say that if it’s above 40 or even a little bit higher than that, I personally know that I feel best if I’m sitting between 30 and 35. When I get above 40, that’s when I know that’s when my symptoms kind of start going downhill.
So later on in that podcast, Paul discusses some of his genetics, and he shows that he doesn’t have any of the classical risk factors or the genetic predispositions for hemochromatosis, at least the ones that are commonly known about. Interestingly, if you look at my 23andMe data, you see I’ve only got one variant. I’m heterozygous on the c282y. If you look at the research, this isn’t technically or classically associated with iron overload or hemochromatosis, but we know that I actually do now.
Paul doesn’t have any of these variants. However, Chris Masterjohn makes an excellent point. There are lots of steps along the way that there can be potential problems with iron homeostasis. So, there could be several different genes and several different variants which have simply not been identified. The best way to really check is to look at your own blood work in real-time.
Just on this topic, I mean, what we do see is that people who shouldn’t technically have iron overload with a similar genetic profile to me, so heterozygous c282y, they did develop. There are two cases of this. There’s this one paper and then there’s another paper which is saying that there are kind of novel or rare HFE variants which have not been studied and which scientists really don’t know to look out for.
Indeed, another thing which is super interesting is that c282y heterozygotes, so people with only one variant and who shouldn’t technically have hemochromatosis, there was a study which essentially showed that the c282y polymorphism was associated with higher levels of sex hormone binding globulin in men who didn’t even have iron overload. Now, I’d be interested to see how they were measuring that, like whether they were looking at transferring saturation or whether they were looking at any other different markers, but that is very interesting.
I assume that because iron overload is associated with inflammation, because it’s associated with oxidative stress, then that must be the thing that’s increasing the production of this protein in the liver. That is something that I’d read online somewhere, and that kind of made some sense to me. But when I looked into it, it doesn’t seem as though that is really that could be explained by the evidence whatsoever because it turns out that sex hormone binding globulin tends to be reduced under conditions of oxidative stress and inflammation.
If we look, for instance, at obesity, metabolic syndrome, PCOS, and other inflammatory conditions of the liver, these kind of systemic inflammatory conditions are usually associated with lower sex hormone binding globulin. In fact, sex hormone binding globulin is associated with insulin sensitivity. As someone regains insulin sensitivity, sex hormone binding globulin improves. It increases. So, it makes me wonder, given that the body is innately intelligent, like why would it want to increase sex hormone binding globulin levels in the context of iron overload? Surely it must be beneficial in some way. Like what purpose does it serve?
And when I think about it, it’s really quite obvious. This particular case study was looking at a case of hemochromatosis which was unmasked by testosterone replacement therapy. He presented with erectile dysfunction, so they gave him testosterone. And what they found was that his red blood cells increased. He developed erythrocytosis.
It’s well known that people who take testosterone replacement or anabolic steroids can develop high hematocrit, basically a thickness or higher viscosity of the blood. And in some cases, this can be very, very dangerous. And so, this is one of the reasons why people who do take anabolic steroids or do take testosterone generally need to measure their blood parameters because they can develop too many red blood cells. The blood can get too thick.
Well, the same thing can happen with hemochromatosis. In fact, elevated hemoglobin, elevated hematocrit is quite common when it comes to people who have hemochromatosis. You see if you have too much iron, then that can be a signal for erythropoiesis, which is basically the development and maturation of red blood cells. Testosterone can do the same thing. So when you add up the effect of high testosterone along with high iron, that is potentially going to lead to a situation where you’re producing too many red blood cells, hematocrit gets too high, your blood gets too thick, and you develop circulatory failure.
So might it make sense, at least if the body senses that there is some degree or the initial steps of iron overload, then it might adapt to that in a way is to reduce free testosterone levels so that you don’t get the additional or the added effect of both extra iron and high testosterone on blood cell production? I don’t know. That is something that immediately comes to mind, and it seems as though high sex hormone binding globulin may actually be somewhat protective. Although we know that low testosterone or low-free testosterone is not protective for males, it might be the case that the body has to choose between the two and says, „Okay, as long as I’ve got high iron, as long as I can’t do anything with it, then I’m going to need to downregulate testosterone production or testosterone free testosterone bioavailability so that I can do what I can with the best that I can.“
Again, I think it’s probably quite common in males, especially if people have the early stages of iron overload and they don’t know that they’ve got it. So, it’s definitely only something to work to look into, and it might be the solution for someone who does have chronically high levels of SHBG like I did but can’t find a solution for that.
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