Selenium is critically essential to the defense against oxidative stress and to thyroid hormone metabolism. Soil concentrations cause so much variability, however, in the selenium content of foods that any two of us could be eating the same diet and one of us could have too little selenium and the other too much. That makes it essential to understand how to measure and manage our nutritional status. In episode 35, I continue the series on managing nutritional status by teaching you how to do just that.

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This is part of a series on managing nutritional status where all of the episodes are collated on the shownotes page for the introductory post, What Makes a Good Marker of Nutritional Status?

Selenium Status Show Notes

In this episode, you will find all of the following and more:

0:00:34 Introducing the new name, Mastering Nutrition
0:01:00 Cliff Notes
0:10:55 My story with selenium deficiency: white spots in fingernails and frequent colds
0:14:14 Soil variation plays a major role in selenium deficiency and toxicity
0:18:40 Biological roles of selenium
0:29:00 Signs of deficiency
0:39:45 Signs of toxicity
0:43:45 Optimizing between deficiency and toxicity: Hashimoto's thyroiditis and cancer
0:49:00 Different forms of selenium in plant and animal foods
0:49:38 How selenomethionine from plants is metabolized to selenocysteine
0:55:10 How selenocysteine from animal foods enters as selenocysteine
0:55:30 How selenocysteine is converted to selenide for incorporation into selenoproteins
0:56:25 How inorganic selenite and selenate are converted to selenide using glutathione
1:01:46 Markers of nutritional status
1:12:53 Ideal ranges of markers
1:16:42 Dietary requirements and how to meet them with food
1:26:45 Why methyl-selenocysteine is not a substitute for selenocysteine and why selenomethionine is the best currently available option for a supplement
1:28:13 The proper dose of a supplement
1:35:07 Things we will learn in the future: implications of needing methylation to both utilize enough selenium and detoxify excess; interactions with glutathione and antioxidant system; selenoprotein P becoming commercially available to health care practitioners and individuals; the rise of novel markers as we learn more about the poorly understood selenoproteins
1:37:10 Wrapping Up

Measuring and Assessing Selenium Status

I recommend using LabCorp's plasma or serum selenium as the primary test and aiming to keep it between 90 and 140 μg/L, with the possible sweet spot being 120. μg/L and ng/mL are interchangeable, but ppm must be multiplied by 1000 to compare the values.

I recommend augmenting this with glutathione peroxidase activity from the Genova Diagnostics Oxidative Stress 2.0 (blood) panel. Measurements of enzyme activity can be subject to considerable variations between different test kits, and research studies often report them in conflicting units that cannot be standardized, so it would be potentially misleading to to derive normal or optimal ranges from the scientific literature. Therefore, I recommend using Genova's reference range, and using it, when the value appears low, to see if it increases with selenium supplementation. Augmenting plasma selenium with this test is likely more important in premenopausal women than in men or postmenopausal women.

Recommendations: Selenium in Foods and Supplements

Selenium richest in organ meats, seafoods, and Brazil nuts. It is highly variable in all foods, but animal foods are more reliable than plant foods because the degree of variation is much lower in animal foods. Selenium is approximately half as bioavailable from seafood than from other animal foods, and is very poorly bioavailable from mushrooms and cruciferous vegetables. When calculating your selenium intake from a nutritional database, all calculations are likely to be very imprecise, but the precision will greatly increase if your selenium comes mostly from animal products. Therefore, organ meats and seafoods are the most reliable way to improve selenium status with food.

A mixed diet containing some organ meats and seafood is unlikely to require selenium supplementation unless most of the foods in the diet come from selenium-poor environments (which is very possible if you eat only local foods).

Because of the variation in foods, it is more reliable to measure your selenium status and adjust your diet if needed than to try to estimate your selenium from foods and micromanage it.

I do not recommend using methyl selenocysteine supplements because this is a detoxification product of plants and animals and unlikely to have good bioavailability.

I do not recommend using inorganic selenium such as sodium selenite or selenate because, although these are theoretically very bioavailable, their utilization depends on glutathione status and this could be compromised in selenium deficiency.

I do recommend using selenomethionine because this has been shown to be more effective at a lower dose than sodium selenite for the correction of deficiency. I would use 100 μg per day to correct a deficiency within four weeks, and I would use this every other day as a maintenance dose if your local foods are poor in selenium.

Based on cost, convenience, and apparent quality, I recommend this specific seller of Swanson L-selenomethionine on Amazon. It costs $9.99 for 300 capsules as is fulfilled by Amazon and eligible for Prime. It is formulated to last two years from the date of manufacture, so, taken every other day it could last you almost two years and stay fresh provided there is no large gap between manufacture and sale. Or, split among family or friends it could get used even faster and that would guarantee a fresh supply at a very low cost.

Now's selenomethionine is also cost-effective and is a somewhat smaller bottle (250 tablets). It is slightly less expensive on iHerb ($7.86) than Amazon ($8.73) and at the iHerb price is slightly less expensive than the Swanson bottle (3.1 cents per tablet instead of 3.3 cents per capsule).

If you want a smaller bottle to ensure you will use it while it is still fresh, I would recommend Solgar selenomethionine from iHerb, which is $6.72 for 100 tablets each containing 100 μg. However, it is doubtful that this is any more cost-effective even if freshness were a theoretical concern, because it is 6.7 cents per tablet, which costs twice as much as the larger bottles.

Maps of Soil Selenium Content

A simple map

A detailed map

Transcript of Episode 35

I'm Dr. Chris Masterjohn and you're listening to Episode 35 of Mastering Nutrition where we're talking about why you should manage your selenium status and how to do it.

This is Mastering Nutrition with Chris Masterjohn. Take control of your health, master the science and apply it like a pro. Are you ready?

0:00:34 Introducing the new name, Mastering Nutrition

All right, welcome back, everybody. You may have noticed that I changed the name of the show from The Daily Lipid to Mastering Nutrition. It gives a much better instantaneous sense of what the show is about. If you want the full scoop on why I changed it, head to chrismasterjohnphd.com/newname.

0:01:00 Cliff Notes

Today we're talking about selenium, and if you want the Cliff Notes, here they are:

Selenium is super important to protecting against oxidative stress, which is the natural wear and tear on our bodies that underlies all kinds of concerns about just feeling good and looking good as well as protecting against diseases, and it's incredibly important to thyroid health. And yet, it is so easy to have too much or too little selenium because the key driver is not about what we're eating; it's about the soil in which our food was grown, and that is so widely variable. Because of that, it makes it really important to be able to measure and manage our nutritional status. I recommend LabCorp serum or plasma selenium backed up with glutathione peroxidase activity from the Genova Diagnostics Oxidative Stress 2.0 panel. The latter is more important to back up plasma selenium in females than it is in males, but it's probably a good idea for everyone. The best marker selenoprotein P is not yet available. Using this method keeps glutathione peroxidase in the normal range, keep plasma selenium at least above 90 micrograms per liter. You have to multiply that by a thousand if it's reported in ppm and keep it under 140. Maybe the sweet spot is 100 to 120.

The best foods are selenocysteine from animal foods because this is much less variable. Even though the variation is huge, it's much less variable in animal foods. So animal foods rich in selenocysteine, which is probably the more ideal form, are going to be the best sources. Organ meats are better than muscle meats. Seafood is also really great, but the bioavailability is about half of other animal products. In plant products, Brazil nuts are great but incredibly variable. Mushrooms and cruciferous vegetables are not reliable because of low bioavailability. If you eat a mix of a couple Brazil nuts here and there, a lot of unrefined plant foods or some organ meats, some seafood, you probably don't need selenium unless you live in an area where all your food is coming from low selenium soils and low selenium waters. If you do supplement, do not take methylselenocysteine because it is not selenocysteine. Because selenocysteine is not available, I recommend selenomethionine as a maintenance dose 50 micrograms. If you're going to fix a deficiency quickly, 100 to 120 micrograms. Probably as a maintenance dose for someone who has other signs of deficiency across the board, 75 to 100 micrograms is plenty. I would not chronically supplement with more than 100 micrograms.

All right, that's it. Without further ado, here's a word from my sponsors and then the full episode.

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0:10:55 My story with selenium deficiency: white spots in fingernails and frequent colds

When I was living in Illinois I developed two problems simultaneously. First of all, my fingernails developed white spots. Second of all, I was getting sick all the time. I don't remember exactly how frequently I got colds, but it certainly seems in retrospect from my memory like I was getting sick every few weeks. It was ridiculous. So I thought through the problem, and I thought could there be something associated with moving? Well, I moved, it could be a mold issue, it could be a soil issue especially since I consumed almost the entirety of my food from the local farmers' market and the local food co-op, so all of my food was coming from one place. And if I move from one place to another, then suddenly eating foods that are coming from different soils, and so I thought through what I know about nutrition and what are the things that could relate to me getting sick that could relate to my nail health that could vary from one soil to another, and selenium was one of the minerals that came to mind. So I looked it up, and to the best of my research at that time sure enough, I was living in a low selenium area.

I said okay, let me take a selenium supplement to see if this resolves. I got the quickest selenium supplement I could find. I got it from the local food co-op. It was selenomethionine. I didn't think that was the ideal form at that time. It had alpha-tocopherol in it. I didn't want to take the alpha-tocopherol, but whatever, I bought it anyway and I started taking it as the instructions prescribed. I don't remember exactly how long it took, but relatively quickly, both problems went away. The white spots in my fingernails went away. My frequent colds came to an end.

Now, I did have lingering respiratory problems after that that didn't resolve until I started taking one package of liposomal glutathione and 10 grams of monolaurin per day, but that's another story for another time. Suffice it to say that the basic problem of the frequent colds disappeared with selenium supplementation on its own. Now, I think this is a really powerful indicator of the power that selenium can have in day-to-day life, but it's also very reflective of the fact that we can be eating the same exact good diet and maybe not even in spite of but because we are conscientious about eating local foods, just by virtue of where we happen to live, we can wind up being deficient in selenium.

0:14:14 Soil variation plays a major role in selenium deficiency and toxicity

The selenium story is one that is mostly about the soil. In fact, a lot of what we know about selenium deficiency and toxicity originally comes from China where the variation in soil concentrations of selenium is so vast that people can be eating the same diets and have a 450-fold difference in their selenium intake if they're in one area versus another. And although the variation isn't as great in the United States as it is in China, most soils in the United States have somewhere between 0.1 and 2 parts per million selenium, which is a 20-fold variation, but there are parts that have up to 80 parts per million in the United States which makes at the extremes an 800-fold variation. If you look across the states, what you'll see is that you can look at it at different levels of detail, and I'll post a simple map in and complicated map in the show notes at chrismasterjohnphd.com/35. But basically, if we were to try to summarize it, we could say that across the Northwest, the Northeast, all of the states that border the Great Lakes including most of Illinois across the Atlantic Coast and Florida is low in selenium, and we tend to have adequate selenium throughout the Central and West Central United States and the South.

There are also specific areas where we can have extremely high levels. For example, in South Dakota, Montana, Wyoming, Nebraska, Kansas, Utah, Colorado, New Mexico, we can have 2 to 10 parts per million which is on the high side. In some of those states we can side by side in the same state like in Montana, New Mexico, we can have both very high and deficient levels of selenium.

There's similar variation in Canada. In fact, if you were to look at a simple map, you could basically take the swath of adequate selenium across the Central and West Central United States and just trace it up into Central Canada and you could take the Northwest, the Northeast swaths of deficient selenium and trace those up over Western and Eastern Canada. Again, if you look at Canada in a more detailed level, you'll see much more local variation. Across the globe, Europe and New Zealand are particularly low in selenium. But again, when you're in your locality, there's a lot of variation.

The question then that comes into play is that how are we supposed to manager our selenium status if our conceptions of what a good diet is are all based around eating particular foods, and yet, those foods can be so variable in their selenium content? So what that means is that the only way to attack this is to understand in more detail what we should look out for in terms of the signs that we might be getting too little or too much and then how can we use modern tools like nutritional status testing to assess our status to actually see where we belong? And then how can we use those tools to individualize and approach to managing our nutritional status if those signs and those tests indicate that we should be doing that?

0:18:40 Biological roles of selenium

So let's start this discussion by talking about what does selenium do in the body and why is that so important? Well, selenium is most well-established for its role in protecting against oxidative stress and in thyroid metabolism. Oxidative stress can be thought of as the wear and tear that occurs in our cells and in our tissues with aging and with exposure to stress. If you want a much more detailed explanation of what oxidative stress is and how selenium fits into the broader context of the antioxidant defense system, then I'm currently releasing twice a week a video series that explains this from the ground up at chrismasterjohnphd.com/masterclass. So if you want that better context, then definitely watch those videos from the beginning.

However, we could say for the purposes of this episode, oxidative stress is the natural wear and tear on our bodies that's going to accelerate when we're exposed to toxins, to heavy metals, to metabolic problems, to inflammation and so on, and selenium is necessary as a co-factor for a family of enzymes called glutathione peroxidases. These enzymes are going to allow critical functions of reactive oxygen species such as hydrogen peroxide to play positive roles in addition to simply protecting against the wear and tear on the body, and some of those roles include immune support and thyroid health. For example, in immune cells, just like we may have hydrogen peroxide in our cabinet to pour on a wound and kill a pathogen, our immune cells make large amounts of hydrogen peroxide to do exactly the same thing when we have an infection. But just like that hydrogen peroxide can be toxic to the pathogen, it can also be toxic to the immune cell and to us as an organism. For our immune system to be able to do that properly, to be able to use hydrogen peroxide effectively, it needs to have very powerful antioxidant defense. And although it may sound counterintuitive in the sense that we think of an antioxidant counteracting an oxidant, hydrogen peroxide as an oxidant. But providing better antioxidant support to the immune cell allows that immune cell to produce more hydrogen peroxide to kill more pathogens more effectively because the antioxidant defense is going to protect the immune cell. It's kind of like if you're working in a dangerous job, if you have better protective gear, you're better able to do your job more effectively because you don't need to worry about the dangerous consequences as much.

Very similarly, there is in the thyroid gland an analogous use of hydrogen peroxide, although here it's not for the purposes of destroying anything. It's actually for the purposes of synthesizing thyroid hormone. We cannot properly metabolize iodine for its incorporation into thyroid hormone without hydrogen peroxide. So very much in the same way as for the immune system, the thyroid gland needs incredibly powerful antioxidant support to protect itself against the hydrogen peroxide that it's making in order to produce thyroid hormone. In both of those cases, the selenium is acting as a co-factor for one of the glutathione peroxidase enzymes, which is going to utilize glutathione as well. So what that means is that in order to reap the benefits of selenium in that context, you also need to think about managing your glutathione status, and so that falls back on everything that I talked about in chrismasterjohnphd.com/31, why you should manage your glutathione status and how to do it.

Now, allowing the thyroid gland to utilize hydrogen peroxide safely and effectively is not the only role of selenium in thyroid health. Selenium is also a co-factor for all the thyroid deiodinases, and these are the enzymes that interconvert thyroid hormone between its different forms. To take one of the major examples, the thyroid gland mostly produces T4 which is a precursor to the fully active thyroid hormone, and that needs to get converted to T3. Well, that requires a deiodinases enzyme that is selenium-dependent. Actually, these enzymes function very similarly to the glutathione peroxidase enzymes in that they actually require glutathione as a co-factor as well. So again, this aspect of selenium falls back on the need not only to manage your selenium status but also to manage your glutathione status as well.

Now, the ability to engage in redox reactions, reduction-oxidation reactions, the transfer of electrons, is what allows any metal such as selenium or copper or iron to participate in the antioxidant defense system. Redox reactions not only are a matter for protecting against oxidative stress, but also, there are whole classes of proteins that are under the control of what we call redox switches. What that means is that quite often one of the ways you can turn on a protein or turn off a protein is to oxidize it or reduce it. Generally, the way this is organized is there are hundreds of proteins that are under one particular redox switch, hundreds of proteins that are under another a particular redox switch, and that allows the cell to have a few different systems of regulations that it can turn some of those proteins on, turn others off and so on. One of those master redox switches is called thyroidexin. Selenium is a co-factor for the enzyme thyroidexin reductase, and basically what that means is that it's a raw material to allow that master switch to regulate hundreds of proteins. So there are likely many different health effects that lie downstream from that function of selenium where it's simply acting as — selenium isn't the master switch. It's just allowing the body to be able to control its own master switch. So we can imagine that we could have a whole field of research dedicated to what are the consequences of selenium deficiency in that particular context.

Now, we also know from a process called bioinformatics where we are looking at the DNA sequences of many genes and trying to infer from those sequences what proteins require selenium and what they might do. There are some limitations to this approach in the sense that even if you know very well what the DNA fingerprints of a selenium-dependent protein are, that doesn't mean that in real life that protein does in fact have a selenium-dependent function. However, based on what that information seems to suggest, there are probably at least 25 different selenium-dependent proteins which we call selenoproteins, and some of them probably have a role in folding proteins into their proper three-dimensional structures which is necessary for their function. Some of them are probably additional components of either the antioxidant defense system or the system of redox control of proteins. So there's a whole wide open field of research that we could do into better characterizing what all these different selenoproteins are, how sensitive they are to selenium deficiency, what are the actual health consequences of their malfunctions. Right now we can really only say that the well-established roles of selenium are to protect against oxidative stress, to engage in redox control and to participate in proper thyroid health.

0:29:00 Signs of deficiency

So given those roles, what are the consequences of deficiency? This is important to understand both because it helps us understand why selenium is important, but it's also a tool to look for poor selenium status. One of the interesting things about selenium deficiency is it appears as if it is silent in the absence of additional stressors. Maybe in real life there are always additional stressors, but if we look at the history of laboratory animals that were experimentally subjected to selenium deficiency, we see a very interesting historical arc where in the beginning of the 20th century it was very easy to make an animal deficient in selenium and see disastrous consequences. Now it's very hard to do that. When we first started looking at this in the early 20th century, one of the things that quickly became apparent was selenium deficiency looked a lot like vitamin E deficiency. In fact, they synergized together. When it became clear that vitamin E deficiency was driving all of its consequences through increased lipid perodixation, this allowed us to see that. So did selenium. In fact, lipid perodixation is much worse if you're both deficient in vitamin E and selenium, and that formed part of the basis for understanding selenium's place in the antioxidant defense system.

But as time went on, two things happened to laboratory animals that made selenium deficiency on its own become silent, and that was we started to better understand how to optimize a lab rat's diet. When we first started doing this, what we wanted to do with standardize the diets so we could more easily compare across cancer and toxicological studies. There was so much variation in the “chow diets” of animals that people wanted to look at a cancer study or toxicological study from one lab and another lab and compare the results to try to make inferences from them and they couldn't because who knows how the diet was different. When they first started standardizing the diets, they did it based on what they knew was necessary for the animals and they actually caused a dramatic decline in the animal's health. I wrote about this in a blog post years ago called They Did the Same Thing to the Lab Rats That They Did to Us, and I'll post a link to that post in the show notes. But basically, when they realized that all the animals on the standardized diets had much worse health than the animals on the traditional chow diets, that caused them to start intensively researching how do we fix this? That led to a lot of good research on the nutritional requirements of lab animals in order to make — it took twenty years to do it, but eventually, we got very good at optimizing the diet of a lot of animals and we also threw in extra trace minerals that we didn't know if they were important but maybe they are, so we just threw them in there. So now we have animals that are consistently getting diets that are optimized for their health, whereas in the early 20th century who knows what other nutritional deficiencies the animals had.

Another thing that happened is that animals got fancy. You used to keep an animal in a cage in the same laboratory where you were doing your chemical analysis. Now you pay luxurious rent, like depending on the size of the animal, maybe you're paying at least 30 to 50 cents per day per animal to keep them in very high-quality facilities where there are ventilation systems to protect the animals from pathogens and to protect the lab workers from allergies. There's full-time veterinary staff to check up on the animals, see if they're getting sick, help them if they are. So we now have a situation where all the natural stressors of real life are removed from laboratory animals. In fact, the average human being is probably exposed to far more random stressors than the average laboratory animal. Nowadays, if you make an animal selenium-deficient, at least in the first generation, pretty much nothing happens. You have to introduce vitamin E deficiency or iron overload or a toxin or a virus. And if you do that, suddenly what you realize is that boom! As soon as you purposefully introduce that stressor, suddenly the deficiency manifests. Suddenly you realize that that animal that seemed that it suffered no consequence from the deficiency is now suffering profound consequences because it's far more vulnerable to that stress.

This is probably very true in humans. In fact, if you look at where some of our best knowledge of deficiency comes from, it's from China. In papers that were first published in English in the 1970s, economic conditions in China in the 1970s, I'm sure they were much worse than 2017 mouse in the state-of-the-art laboratory facility. There were likely synergistic nutrient deficiencies alongside this and hygienic issues and the natural stressors that occur in a natural environment of course as well. The traditional deficiency diseases called Keshan disease and what we observed there was liver damage in the form of hepatic cirrhosis changes the fingernails that could range from the whole nail bed turning white to the needles falling out, cardiac insufficiency that would lead to an enlarged heart, and if you looked at the heart in detail you'd see fibrosis, which is the laying down of scar tissue, and necrosis which is an unprogrammed messy form of cell death. There was very strong evidence that selenium deficiency was the underlying problem and that's uncontroversial today, but there were certain aspects that couldn't be explained by selenium deficiency alone. For example, the cardiac effects of Keshan disease varied seasonally, and there was no reason to believe that selenium intakes varied seasonally. One of the hypotheses was that maybe there was a virus that came in waves and there was some synergistic interaction between the virus and the selenium deficiency. In laboratory animals, you can show exactly that, that if you make the animals selenium deficient, you can reproduce what looks like the cardiac effects of Keshan disease if you have the right virus.

One of the fascinating things that's come out of that research is that if you add a virus that is of a nonpathogenic strain, it may become pathogenic in the selenium-deficient animal, and to the extent that you could isolate it from that animal and then cause disease in another animal because that strain became virulent, became pathogenic while it was in the selenium-deficient animal. And there some other evidence that there are similar phenomena with other nutrient deficiencies and with other viruses like flu viruses and some people believe that maybe this is a general feature of viruses that if you have viruses that enter a nutrient-deficient population, that nutrient deficiency compromises the ability of the host to defend against it and allows the virus a competitive advantage that allows it to mutate into a pathogenic virulent form.

So what we can see from this is that whenever you're talking about infection, it is about the infectious organism and it's about the host. In fact, that's not even a true dichotomy in the sense that they each interact with the other. Now, I couldn't find any papers explicitly discussing white spots in the fingernails, but it's actually really hard to find information on this, and it's hard to find color pictures because, first of all, a lot of this information is really old Second of all, a lot of it comes from China and it's not published in English. But I did find information that the nails can become white, and so I suspect maybe in those cases where they observed that, had they observed it earlier, maybe they would have seen white spots and white streaks. I can tell you that in my nails what I saw was white spots and white streaks and they went away with selenium supplementation. So I do believe that that can be an indication of selenium deficiency at least based on my anecdotal experience.

0:39:45 Signs of toxicity

Now, what about the opposite end of the spectrum toxicity? Well, with selenium deficiency, we actually have pretty good ideas about what causes it because we know so much about its biochemistry and its physiology and what it's supposed to do in the body, and we can relate that to what happens when it's not there. The toxicity of selenium is much less well-characterized, and so we don't know what causes it. But the reason that selenium is an important part of the antioxidant defense system is because like iron and like copper it's a redox reactive metal that can easily gain and lose electrons. And if we look at iron and copper, we see that because of that same property, if they accumulate in their free form where they're not properly directed into the proteins that we need, that same property can allow them to act as pro-oxidants. So I suspect that that's what's underlying the mechanism of selenium toxicity as well. And in support of that, although toxicity and deficiency isn't exactly the same thing, there are remarkable similarities in their clinical science. So in toxicity and in deficiency, we see hepatic cirrhosis. In toxicity we see hair loss and loss of the nails, and in toxicity this is where white spots, streaks and brittle nails have been best documented. So maybe the nail changes aren't exactly the same but the fact that cirrhosis and changes to the nails are the key signs of deficiency and toxicity is a pretty remarkable parallel.

Now, most of what we have about extensive toxicity comes from China. In the United States we do have areas where we have very high selenium levels, but we haven't observed very severe toxicity because we just don't have the same degree of variation in the US as we have in China. For example, in China there are areas where coal pollution has brought soil levels up to 90,000 parts per million. That's a lot higher than that 80 parts per million in the United States. So in the United States, what for spontaneous toxicity we've basically observed is loss of the hair and nails, but the most extensive cases of toxicity in the United States have been acute doses of improperly formulated supplements. In these cases what we see is acute nausea, diarrhea, irritability, fatigue, loss of the hair and nails, and peripheral neuropathy which manifests as tingling in the hands and feet. This has not happened for a long time, decades, but when it did happen, one of the explanations is that someone who was involved in formulating the supplement may have confused micrograms with milligrams. So if you are ever involved in formulating anything, please work on your attention to detail.

0:43:45 Optimizing between deficiency and toxicity: Hashimoto’s thyroiditis and cancer

So somewhere between deficiency and toxicity, there must be some window where we want to optimize, and the problem with trying to find this window is that if we're going to look for evidence of benefits at levels higher than what protects against deficiency, we wind up rubbing up kind of close to the threshold where we start seeing negative effects at levels much lower than what's seen in true toxicity. The areas where this has been studied the most have been more recently in Hashimoto's thyroiditis where there is so some indication that selenium supplementation is probably beneficial to reducing thyroid antibodies and to normalizing thyroid hormone levels. I would say the jury is out on just how effective it is, how important it is, and how universally applicable it is across people with Hashimoto's thyroiditis.

Where it's mostly been investigated is, and in this is older research, but there was a period of time where there was a lot of interest in the ability of selenium supplementation to prevent cancer. Now, one of the things that came out of the cancer trials was that initially it seemed good, but then when we went back to reanalyze the data from one of the major trials, what we saw was that only in people with low baseline selenium status did you see a reduction in cancer; and although there wasn't robust statistical confirmation that you had an increase at higher levels, it did seem like the people who had good selenium status at the beginning, even just taking as much as 200 micrograms of selenium was increasing their cancer risk. And then after that, there was a population level study that found that people who had higher levels of plasma selenium had increased risk of diabetes. So although the risk of diabetes and cancer at higher selenium levels is nowhere near conclusive, it still should provide caution in the sense that if we don't have strong evidence that we're going to get a benefit from pushing up our levels that much, then why would we err on the side of flirting with the line of increased risk of cancer and diabetes? It just doesn't make any sense.

Now, I suspect that the lesson from the cancer research could be applied to Hashimoto's in the sense that if we were to identify the people who needed the selenium, then target the selenium supplementation to the dose that those people need. I think that individualized approach would probably have very robust benefit. But it's not just about finding the right people. It's also about finding what are the other interactions that are necessary? So as I mentioned before, every single benefit of selenium to thyroid health requires glutathione, and as I covered in chrismasterjohnphd.com/31, why and how to manage your glutathione status, there are a lot of components — a lot of components, not all of which are interchangeable, that go into managing glutathione status. That's just one layer of the onion. If you peel back the next layer you'll find other interactions and then you'll find more and then you'll find more and then you'll find more. So I really suspect in these trials that there are factors that would allow selenium to become safer and more effective.

So the issue is number one, how do we find the people who are in most need of the selenium supplementation and figure out how much they need? And then number two, how do we optimize the milieu into which we're putting that selenium so that it is more effective and safer than it is if we're putting it into an unoptimized milieu? To really grasp with either of these questions, we really need to discuss how selenium is metabolized because it's different depending on the form of selenium that comes in different foods and supplements, and that can impact markers of nutritional status differently. But also understanding its metabolism will help us better understand what do you need to do to optimize that milieu to be able to take advantage of selenium.

0:49:00 Different forms of selenium in plant and animal foods

If you look at animal foods and plant foods, plant foods mostly contain selenomethionine; animal foods mostly contain selenocysteine. This distinction is critically important. So first of all, methionine and cysteine are the two amino acids known as the sulfur amino acids because they contain sulfur. But in methionine the sulfur plays a structural role, and in cysteine the sulfur engages in physiologically important chemical reactions.

0:49:38 How selenomethionine from plants is metabolized to selenocysteine

In selenomethionine, the selenium replaces the sulfur in methionine and replaces its structural role. There's basically no difference between the physiological and structural benefits of methionine where selenium is playing that structural role instead of sulfur. But in cysteine, there's a fundamental critical, absolutely essential difference between sulfur being the thing that's engaging in chemical reactions and selenium being the thing that engages in chemical reactions, such that in, for example, the fundamental molecule, the sulfur of the cysteine is what allows glutathione to perform all its physiological functions, and in any of the selenoproteins, the selenium of the selenocysteine is what allows it to engage in its physiological functions. The fact that these are so clearly different can be seen by something like glutathione peroxidase where selenium is part of the enzyme, selenium does one thing, then glutathione comes and recycles the selenium. They're in no way whatsoever interchangeable. They're critically interdependent.

This is really important to understand because that means that the selenium in selenomethionine is not fulfilling any particular physiological role. It's just randomly replacing sulfur. So in plants and fungi, the fact that they mostly accumulate selenomethionine reflects the fact that there is no physiological function of selenium in those plants or in fungi. What happens is in proportion to the amount of selenium in the soil, there will be random incorporation of selenium into the selenomethionine. If selenium gets incorporated into cysteine molecules, those plants will detoxify it by methylating it and so you get minor proportions of methylated selenocysteine in plants, and in certain plants you'll see more of those methylated forms like cruciferous vegetables and certain mushrooms and so on.

Neither plants nor animals have a need for selenomethionine, and in animals the whole goal of selenium in the diet is to get selenocysteine incorporated into selenoproteins. Selenomethionine is perfectly capable of making its way into selenocysteine, but it takes a rather torturous path to get there. Selenomethionine will come in through the diet, and then it will be randomly equilibrated into the methionine pool. If you're going to build a protein, let's say you're going to build a contractile protein in your muscles so you can get swole, whatever proportion of selenocysteine in your diet, that will just randomly insert selenomethionine in place of regular methionine in those proteins.

In the process of methylation, where methylation is used as the universal methyl donor for the synthesis of compounds, for the regulation of compounds, methionine donates a methyl group and becomes homocysteine. Selenomethionine can donate a methyl group and become selenohomocysteine. And just like we use vitamin B6 to convert homocysteine to cysteine to use it for all its purposes, through the exact same pathway, we can take selenohomocysteine or homoselenocysteine — I'm not sure what you call it — and convert it to selenocysteine, and then we have that entering the selenocysteine pool. So if you supplement with selenomethionine or you eat selenomethionine in plant foods, some of it will go right into the methylation pathway and wind up as selenocysteine, but much of it will be incorporated into all your other proteins wherever methionine would, then you have to wait for those proteins to be catabolized. Once they're broken down, that selenomethionine will now become available to enter the methylation pathway and then it will become available to be converted into selenocysteine. The conversion of homocysteine to cysteine, that's called the transsulfuration pathway, it's analog with the selenated forms of these amino acids, is the transselenation pathway, but it's the same enzymes working on these molecules.

0:55:10 How selenocysteine from animal foods enters as selenocysteine

So if we look now at having finally derived selenocysteine from plants, then this is the entry point of selenocysteine from animal foods. So eating animal foods provides a much simpler and quicker path to derive selenocysteine from. Now, it may seem that you could just take that selenocysteine and put it into your selenoproteins; you can't.

0:55:30 How selenocysteine is converted to selenide for incorporation into selenoproteins

What you need to do with it is you break it down using a vitamin B6-dependent pathway to get selenide, and selenide is the universal form of selenium from which all other forms of selenium must enter in order to get incorporated as selenocysteine into our proteins. In fact, there is a fascinating and rather seemingly bizarre process by which we put selenocysteine into proteins, and it doesn't even start with cysteine. It starts with serine and selenide, and we construct the selenocysteine molecule de novo in the process of building that protein itself.

0:56:25 How inorganic selenite and selenate are converted to selenide using glutathione

Now, there are other ways to get selenide. For example, if we take a supplement with inorganic forms of selenium such as selenite or selenate, it can be reduced directly to selenide in a glutathione-dependent manner. What that means is that it can be equally bioavailable, but your ability to use it may be limited by your glutathione status. So it may be more difficult to correct a deficiency because if you're selenium-deficient, you probably shouldn't count on having good glutathione status. So using selenite may not be the most effective way to correct a deficiency. In fact, we do have very good evidence that selenomethionine is superior to sodium selenite in humans for correcting a deficiency.

Now, one of the key differences between consuming selenomethionine in plant foods or in supplements and consuming selenocysteine from animal foods is that selenocysteine only serves the purpose of forming selenide or getting detoxified if there's too much of it. By contrast, selenomethionine isn't recognized as excess selenium. It is recognized as methionine. So the body is not going to detoxify it according to its needs for selenium. It's going to treat it according to its needs for methionine. So let's keep that in mind as we think about how would we expect different markers of selenium status to change with depletion and repletion.

Well, one of the things that happens is that your ability to make important selenoproteins declines in selenium deficiency. If we look in the blood, most of the selenium in the blood is going to be in glutathione peroxidase which in this particular case this is the form of glutathione peroxidase that serves a critical function in blood and the extracellular fluids to protect against oxidative stress and in selenoprotein P. Selenoprotein P is a transporter of selenium that allows it to more effectively reach the brain, and in males it also plays a role in transporting selenium to the testes. The other thing that you could measure in blood would be selenomethionine, and remember, selenomethionine is not the fulfilling a specific selenium-related function in the body. So what you see over the course of deficiency and repletion and excess is that glutathione peroxidase and selenoprotein P increase with progressive repletion of deficiency until they reach the point at which you don't need any more of them and they plateau. If you add selenocysteine over and above what you need or you add sodium selenite or you add selenate over and above what you need, you're probably going to see the same plateau in plasma selenium levels because all of the plasma selenium is overwhelmingly glutathione peroxidase and selenoprotein P. So if they plateau, plasma selenium plateaus with them because plasma selenium is essential to some of them. By contrast, if you are eating mostly selenomethionine from plant foods or supplementing with selenomethionine, plasma selenium will linearly increase with no end in sight across levels of exposure because the more and more selenomethionine you get, the more you just progressively enrich your circulating methionine pool with that selenomethionine. So when you measure plasma selenium, what you will see is that it will rise until glutathione peroxidase and selenoprotein P plateau, and at that point, most of the selenium in your blood reflects those two proteins, but then it just keeps going and going like the energizer bunny. At that point now, all of the additional plasma selenium is additional selenomethionine.

1:01:46 Markers of nutritional status

So considering this, what can we say is a good marker of nutritional status? Keep in mind that this is part of a series on managing nutritional status. The first one was called What Makes a Good Marker of Nutritional Status? That can be found at chrismasterjohnphd.com/marker, and that's also where the other episodes in the series are collected. In that first foundation episode, what we said was we want to understand the biochemistry and physiology of the marker. That's what we've been doing this whole episode so far. We want to see it validated against changes in nutritional status. We actually have really good data for a lot of the forms of selenium, so we'll talk about that momentarily. We want to look at that data and we want to see what's more sensitive, what's more specific, and we want to integrate it into the big picture of how we're looking at this person's health.

Well, based on what we've said so far, we already have a very good idea about specificity. In someone who is consuming mostly inorganic selenium or selenocysteine from animal products, then body tissue levels of selenium will mostly reflect selenium nutritional status in a functional way in the sense that the reason the selenium is in the body tissue is because it's been purposefully incorporated into selenoproteins. If you're looking in the blood or you're looking in some fraction of the blood, you're going to mostly see glutathione peroxidase and selenoprotein P representing that selenium pool. In general, across the board, we could say that toenail selenium and hair selenium, platelet, red blood cell, plasma, serum, whole blood, whatever body tissue it is, that body tissue's physiological needs are going to rise and then plateau once nutritional status is met for its physiological needs if the form is not selenomethionine. If the form is selenomethionine, then body tissues, whether it's hair or nails or blood or some fraction of blood, are going to rise linearly with exposure not according to the physiological need for nutritional status, but simply according to whatever was in the diet. And the reason is that if you look, for example, at progressive increase in hair selenium content with increasing selenomethionine intakes, eventually what you're seeing is just the random incorporation of selenomethionine into the methionine pool that would be in those proteins otherwise. So selenium levels and tissues aren't in and of themselves markers of nutritional status unless we can show that one or more of them strongly correlate as a reliable proxy for a physiologically important functional marker like a glutathione peroxidase or selenoprotein P. So let's talk about the sensitivity and specificity of those and then look at whether there's even a need to look at tissue levels of selenium as such a proxy.

What we find is that the production of selenoproteins is under triage control in that when we're in a deficient state we conserve selenium in our brain, we conserve selenium in our thyroid gland, we conserve selenium in our reproductive organs to some extent, and the liver is pretty low on the totem pole and the liver is what's making our selenoprotein P. Selenoprotein P's physiological function is to transport selenium. So we would expect it to be very specific and because it's made in the liver and because the liver does not conserve selenium very well in deficiency, it's a very good candidate for something that would be sensitive. We could say very similar things about glutathione peroxidase. However, glutathione peroxidase is critical to defense against cellular damage. Selenoprotein P is transporting extra selenium. You always need to protect yourself against oxidative damage. You don't need to transport extra selenium when you don't have any extra selenium to get anywhere. So we wouldn't expect glutathione peroxidase to be as sensitive. Also, it's not going to be as specific because your need for glutathione peroxidase depends on the oxidative stress in your body. So if you're suffering from oxidative stress, you're going to make more of it. Nevertheless, you can't make functional glutathione peroxidase without selenium. So there's got to be some point of selenium deficiency in which your glutathione peroxidase activity is compromised.

What we see in a very rigorous study that I'll post in the show notes of looking at the time course of repleting a true selenium deficiency in China over the course of 40 weeks with six different doses of selenium, what we see from that is that you need almost twice as much selenium to optimize selenoprotein P status as you do glutathione peroxidase showing that it is much more sensitive than glutathione peroxidase activity is. So then selenoprotein P should be the sensitive marker, the specific marker, the one that's well characterized to respond to depletion and repletion. The marker that we really understand its functioning can fit it into the big picture.

The problem with selenoprotein P, however, is twofold. Number one, across research studies, selenoprotein P assays are not equally reliable. Just in the last year, a group produced a standardized kit for measuring selenoprotein P to meet this need, and they pointed out in their paper that there were studies that had selenoprotein P values that were orders of magnitude too high or too low to be considered physiologically plausible, and so they're publishing papers saying selenoprotein P is associated with diabetes risk or something like that when their selenoprotein P values couldn't possibly be true based on what we know is actual selenoprotein P values.

Now, the second problem is that no one offers it as a clinical test. If you're a healthcare practitioner, you can order it for your patients. If you go to Direct Labs or HealthCheckUSA or you want to or your own lab test in any of these venues that offer independent testing, you're not going to find it. So then the question becomes can we use something that is available as a proxy for selenoprotein P status? And we can. In fact, if we look at depletion-repletion studies or if we look at this new paper on the standardized selenoprotein P testing kit, what we see is that there is a very clear correlation with plasma selenium levels where we can use them as a proxy for selenoprotein P.

Now, there are some caveats to this and that is that in men, the correlation is very strong between selenoprotein P and plasma selenium across the lifetime. In women, it's very strong for elderly women ages 60 to 80, and it's three times weaker in women ages 20 to 35. I don't know about the ages in between. They didn't test them in the study that I'm referring to. But we're talking explaining 90% of the variation between one and the other versus 30%. So for young women, plasma selenium is yes, it correlates with selenoprotein P but much more weakly. Part of the issue here may be that glutathione peroxidase activity, this is the other major plasma selenium source and it's higher in women than men, and it's regulated by estrogen. Oddly enough, the correlation between plasma selenium and selenoprotein P doesn't seem to be affected by birth control. So there are a lot of questions about exactly what is impacting this relationship, and I think we're going to need a lot more research to clarify that. But in the meantime, we can say that it's probably valuable for a man or an elderly woman to use plasma selenium as a proxy for selenoprotein P. But for a young woman, the options are more limited and the best approach is going to be to look at plasma selenium and to supplement it with glutathione peroxidase activity which is probably relatively more important in young women and maybe it's even the best marker. I think ultimately, what we're going to want is to look at the sex and age differences in selenoprotein P and glutathione peroxidase and use those as the major markers of glutathione status. We can't do that yet because they're just not available.

1:12:53 Ideal ranges of markers

So here's what I recommend. Selenium concentrations can be measured in any blood fraction and they probably all are good. However, I recommend using plasma or serum for a couple of reasons. One is that we just have much more robust data about how plasma and serum selenium respond, and also we have a lot more research that uses plasma and selenium that correlates it with disease risk. So if you're looking at a paper on diabetes risk or cancer risk and it says “At plasma or selenium values of this or that, this is where risk changes,” it's a lot easier to translate that to plasma or serum and a lot harder to translate it to platelets or red blood cells or something like that. So I would recommend LabCorp's plasma or serum selenium, and based on the study of optimizing selenoprotein P you want to maintain that above 90 micrograms per liter. Micrograms per liter is the same as nanograms per milliliter, and it's the same as parts per billion. I would watch out for the fact that Genova Diagnostics includes a red blood cell selenium where they report it as parts per million, and you have to multiply it by a thousand to look at these values. Their normal range, I would not trust. It is high. In fact, the low end of their normal range is what is very close to being associated with diabetes and it's considerably above what's associated with normalizing selenoprotein P. So I wouldn't use their normal ranges. I think they're actually too high and I think that reflects the fact that in the United States we have a number of areas where selenium is downright deficient, but we also have a number of areas where people are pushing their have blood selenium levels up to eight times what's needed because of the local selenium in the area and we also have people who are health conscious who are getting these reports who tend to be taking supplements.

Now, the cancer studies suggested that the ideal blood levels of selenium for cancer prevention may be around 120 micrograms per liter, and the diabetes research suggested that 140 may increase the risk of diabetes. I think it's probably safe and maybe beneficial to push those levels up to 120 micrograms per milliliter, but I think pushing it any higher than that is really flirting with the line of increasing the risk of cancer and diabetes, and I think on all of these things, the evidence is very mediocre, whether it's going to do anything one way or the other. So I don't think that you should be paranoid about a value that's 120 or 140 micrograms per liter. I just don't think anyone should purposefully push it that high, and if it gets that high and you're taking a supplement, I think you can certainly eliminate the supplement.

1:16:42 Dietary requirements and how to meet them with food

So how do we get our status into that range? Well, the first and most basic defense is to eat a collection of selenium-rich foods. The soil variation please a huge role in the variation of selenium contents of foods, but there are still a handful of principles that we can say about what makes a good form of selenium. First of all, we have this dichotomy between the forms in plant foods and animal foods. In plant foods we have selenomethionine; in animal foods we have selenocysteine. There's no studies directly comparing them, but based on the biochemistry, I think it's almost certain that to maintain good selenium status there won't be much of a difference. But to fix a deficiency, selenocysteine is going to work much more rapidly than selenomethionine. And we don't really know much about the toxicity in terms of its mechanism, and we really don't know anything about whether selenium levels above 140 are truly causing an increased risk of diabetes and cancer, and if so, what the mechanism is.

But it's notable that selenocysteine from animal foods probably isn't going to push your blood levels of selenium up as high as selenomethionine will simply because the selenocysteine is going to be directed either into selenoprotein synthesis or detoxification, whereas the selenomethionine is going to increase linearly with exposure. So now this is a bit speculative. I suspect selenocysteine is safer, but until we really know what the mechanisms are, it's very well may be the case that selenomethionine isn't toxic at all and it's all about the free selenium and then we really need to study how plant foods versus animal foods affects that.

Apart from the forms, however, plant food selenium is much more variable than animal food selenium based on the soil. One study that looked in the United States at variations in the animal feed, the feed used to feed farm animals, found that in animal products, you generally had a two- to five-fold variation in selenium, whereas in plant products, you could generally get a hundred-fold variation in selenium. So between plants and animal foods, because animals physiologically regulate their selenium status and plants don't, then animal foods are going to tend to protect you against high and low extremes of soil selenium. But two- to five-fold variation is no small variation, and by all means animal foods vary a lot. It's just the variation is so narrow compared to the variation in plant foods.

If we look at plant foods as well as mushrooms, one of the things that we find is that the methylated detoxification products of selenocysteine are more predominant in cruciferous vegetables and mushrooms. So the selenium in those foods probably has lower bioavailability. In particular, mushrooms have been found to be almost meaningless as a source of selenium in rodent studies because the bioavailability of the selenium is only 5% versus 50% to 100% in most other foods, and part of that is because the selenium is methylated metabolites and part of it is also because some of the selenium is bound to polysaccharides in the cell walls that are very difficult to digest and so it doesn't get released in the digestive system. If you look at something like Brazil nuts, you have a very high amount of selenium. You have it in the form of selenomethionine and very bioavailable, but you also have massive variation. You may have one Brazil nut that has almost 100 micrograms or in some cases 180 micrograms, 219, 220 micrograms in a Brazil nut; in other cases 15 micrograms, 11 micrograms, 8 micrograms per Brazil nut.

So I think I keep Brazil nuts in my cabinet and I eat a couple every day but I don't think it's very wise to eat huge amounts of Brazil nuts because you may wind up getting huge overloads of selenium from them. I also don't think it's very sensible or wise to rely exclusively on Brazil nuts because you may not be getting very much at all. So unless you know, even if it's listed on the package, I would call the company and find out if they independently verified that that's what's actually in their Brazil nuts, because if they're just taking it from a database, then who knows what's actually in those Brazil nuts. Hopefully it's at least estimated based on the location.

Now, if you look at animal foods, then there's a couple things you could say. First of all, it's going to be primarily selenocysteine in most animal foods, and organs are consistently higher than muscles. If you're looking at liver and kidney versus muscle meat, you're talking five to ten times more selenium on average, and seafood is extremely high in selenium, but here the bioavailability of the selenium is roughly cut in half. That's because one of the roles of selenium in fish is to protect the fish from mercury by binding to the mercury, and so selenium bioaccumulates up the food chain in proportion to the mercury bioaccumulating up the food chain in fish. On the one hand, that means that if we look at the mercury content of the fish, it's not as harmful as it seems because the selenium will protect us from the mercury. But the selenium isn't as high as it seems because the mercury will cause us to not absorb the selenium. In addition, at least in tuna, selenium has been found to be present as a modified form of the amino acid histidine rather than as selenocysteine, and I don't know if that applies to all fish, but least in fish there's mercury and the possibility of other amino acids that are modified that have lower bioavailability. So if you're looking at a database, you kind of have to take it with a grain of salt because of the variation between different foods. But I would say estimate that you're actually getting half of what it says you're getting from the seafoods versus all of what you're getting from the organs and the muscles with the caveat that there's always going to be a very large range of variation in these foods.

So because of the variation, I think that it's actually counterproductive to get granular about how you would design your diet. I think that if you're going to decide how much liver to eat, it should be based on once a week it's going to provide you the vitamin A that you need for example or it's going to provide you the copper that you need for example, although copper also varies a lot. But I think that you shouldn't be micromanaging your foods based on the selenium just because you can so easily get misled by the values in nutritional databases. So what I would do is manage it more on the macro. Look at the big picture. If you're including several servings of organ meats in a week and that's a diversity of liver and kidney and heart and you're eating some muscle meat and you're eating several servings of seafood and you're eating a diversity of plant foods, providing that you're not eating all of these foods grown in one location where the selenium levels in the soil are deficient or in the waters, then I think that it's very unlikely that you need to supplement with selenium. And I think that if you're not eating organ meats and you're not eating seafood and you're eating a lot of refined foods and junk foods, then I think it is very likely that you may need to supplement. However, the first line of defense should simply be to increase the organ meats and the seafood in your diet and to a couple of Brazil nuts each day in that case rather than supplementing with selenium.

1:26:45 Why methyl-selenocysteine is not a substitute for selenocysteine and why selenomethionine is the best currently available option for a supplement

If you do you choose to supplement, I believe it should be because you have shown that your selenium status is low. In that case, what form should you take and how much? Well, there is no selenocysteine supplement. There's a methylselenocysteine supplement offered by Life Extension and I believe some other companies are making it now. Methylselenocysteine is not selenocysteine. It is a detoxification product of selenocysteine. There is a salvage pathway by which we could use it, but it's an intermediate in our own detoxification pathway. So I can't imagine that it has good bioavailability. I'm sure it has some. So I would not use methylselenocysteine. I think that in someone with glutathione status, selenite is probably fine, but what we've seen is that when you're fixing a deficiency, sodium selenite is probably half as good as selenomethionine. So because the availability of the supplements does not include selenocysteine, I would opt for selenomethionine.

1:28:13 The proper dose of a supplement

Now how much should you take? Well, if we look at recommendations across the board, we find World Health Organization has a relatively low recommendation of 44 micrograms per day for men and 30 for women, and that's based very much on the old idea of how do you protect yourself from severe deficiency. So the World Health Organization said let's look at the amount needed to get two-thirds maximal status of glutathione peroxidase activity because we only need two-thirds in order to stop red blood cells from falling apart. The United States RDA is set at 55 micrograms. The United States said we don't want to stop red blood cells from falling apart. We want to get maximal glutathione peroxidase activity. So the United States RDA is much more based around optimizing and the World Health Organization is much more based on preventing overt deficiency. However, we now have better data and if what we really want is to optimize, the US RDA is out of date. So if we look at the very rigorous study in China showing that you could over the course of 40 weeks reverse fully optimized selenoprotein P status with an intake of 63 micrograms per day, if we were to apply an uncertainty factor to try to cover variations and requirements and adjust for average body mass going from the typical Chinese person to the typical American person, we would wind up saying that an American likely needs 75 micrograms per day to optimize selenoprotein P status.

The perspective of the United States was that women are more vulnerable to Keshan disease than men are, so let's not correct for the lower body weight of women and the US RDA doesn't differ between men and women. There's also no good data for how it varies across the lifespan. So with infants, they just took what's the normal amount found in breast milk, and for children they just wound back 55 micrograms for body weight. So taking that principle, we could say if you have if you take a healthy adult at 75 to 80 kilograms or multiply that by 2.2 to get pounds, if you're trying to deal with children, I would just adjust that amount by body weight.

Now, if you're looking at the studies that advocated a higher level of selenium to protect against cancer, what they concluded was 96 micrograms for women, 120 micrograms for men to maintain blood levels that were associated with cancer protection. If you were to try to get that extra amount, you could take the principle of the RDA that women might have higher needs and just say 120 micrograms across the board. Children aren't vulnerable to cancer. So I don't even know if it makes sense to back-calculate that. But if you wanted to have a less conservative view about how much selenium you need, you could take 120 micrograms and adjust it for body weight to adjust down to whatever. If you have children, compare your healthy adult body weight to theirs and adjust it.

Now, all this probably sounds conservative because selenomethionine supplements out there are 200 micrograms. I would take no more than a hundred micrograms supplement because almost certainly you're getting 20 micrograms in your diet. The supplement alone at a hundred micrograms per day would more than normalize your selenoprotein P status and it would probably push you into the range that we can suspect maybe maximize protection against cancer. So I really don't think anyone should be taking 200 micrograms per day of selenomethionine. All of this subject of course to the caveat that if you have some kind of unusual persistently low blood level of selenium, then maybe in your individualized case you may need a higher dose. But off the top of my head and from what I've read, I actually don't really see any reason to know of the specific situation that would call for that.

If you look at the Chinese study of normalizing selenoprotein P status, they found that you could use 100 to 125 micrograms to optimize selenoprotein P status in as little as four weeks. But this more conservative number of 63 micrograms would get you the same level of optimization over the long term. So if you're thinking about a maintenance dose, then certainly you want to think about that dose that would correct a deficiency over 40 weeks, not the dose that would correct the deficiency over four weeks, because if you're not even deficient, why would you need to supplement with 100 or 125 micrograms.

1:34:07 Things we will learn in the future: implications of needing methylation to both utilize enough selenium and detoxify excess; interactions with glutathione and antioxidant system; selenoprotein P becoming commercially available to health care practitioners and individuals; the rise of novel markers as we learn more about the poorly understood selenoproteins

There are some things that I think we'll be discovering in the future that are important to keep in mind. First of all, I suspect that one of the key modifiers of the ability to safely and effectively utilize selenium is methylation. Methylation is the system that we use to control what selenoproteins we make when we have adequate selenium status. Selenoprotein P, for example, we turn that switch on with methylation when we have enough selenium to make it. At the same time, methylation is one of the primary routes of disposal of excess selenium. When we have too much selenium, we start spilling it out into the urine. If it gets really bad, we start exhaling it in our breath. In the urine we're mostly finding selenosugars and both in the urine and the breath we find a lot of methylated selenium metabolites.

So if methylation is needed to effectively utilize selenium and methylation is needed to get rid of excess selenium, then I suspect that in someone who has compromised regulation of the methylation pathway, whether it's because of genetics or other nutritional deficiencies, they're going to be more vulnerable to selenium deficiency and less able to utilize selenium safely, so vulnerable to both deficiency and toxicity with a more difficult time fixing either of them. That's me speculating based on the biochemistry of selenium. There is little research on it, so I think in the future that may be one area where we have very rich promise for discovery.

Another area is all these selenoproteins that we don't know what they do. We know there's at least 25. We're pretty sure that we have a good idea what half of them do, half of them we don't even know. Many of these might be good markers of selenium deficiency.

Number three, we want to see selenoprotein P make it to primetime. It's definitely the best marker, but we can't use it because no one offers it. So we want to see this test standardized, tested and distributed for healthcare practitioners and people who want to order tests independently to be able to get it.

There are lots of other things here like selenium is its key roles depend so much on glutathione and the rest of the antioxidant system. I won't go into any of that detail here. Check out chrismasterjohnphd.com/masterclass to get a full appreciation of what that means and why that means that properly utilizing selenium is about many other macronutrients and micronutrients. I think we have a lot to learn about what that means for finding the people who need more selenium or less selenium and managing that properly.

1:37:10 Wrapping Up

So to sum up, selenium is super important to thyroid health and to antioxidant protection. Those two things make it really important to energy and really important to preventing the wear and tear on the body that comes with oxidative stress and to boosting thyroid health and immune health because of their need for really high levels of oxidants. So selenium is super important across the board for many aspects of health. Maybe it has special roles in dealing with Hashimoto's and preventing cancer.

The critical variation in selenium is less about what we eat and more about where that food was grown and the soil selenium. In the show notes I'll post maps and more to read about how you can figure out whether your location is low in selenium, but it's very hard to deal with due to that variation between the different foods. So measuring our status can be really important Selenoprotein P is not available. So I recommend plasma or serum selenium from LabCorp backed up with glutathione peroxidase activity which can be found in the Genova Diagnostics Oxidative Stress 2.0 panel. I think backing plasma selenium up with glutathione peroxidase activity is more important for women than men. I think glutathione peroxidase activity, you want to maintain in the normal range, and I think that plasma selenium you want to maintain around 90 or 100 micrograms per milliliter, maybe as high as 120. Don't forget to multiply by a thousand if you have that reported in ppm.

The way that you get selenium to boost your status is to eat more organ meats and to eat more seafood, remembering to assume that the seafood is probably half bioavailable. And Brazil nuts can be very useful with keeping in mind that because they're a plant food the variation is enormous. If you're going to supplement your selenomethionine, probably 50 micrograms is plenty for a maintenance dose with no signs of deficiency. If you have rational reasons use it, I would use 100 micrograms, maybe even a little bit less, definitely not more of that in the long term. If you're going to use it for a few weeks, I think it's safe to use 100 or 200 micrograms.

All right, that's it. I hope you found this useful. Remember this is part of a series on measuring nutritional status. You can find the first episode in the series as well as links to all of the episodes in the series at chrismasterjohnphd.com/marker. And remember that selenium is an important part of the antioxidant defense system. You can learn all about the antioxidant defense system at chrismasterjohnphd.com/masterclass. This particular episode is Episode 35, so it's found at chrismasterjohnphd.com/35. I hope you enjoyed this and found it useful. Signing off, this is Chris Masterjohn of chrismasterjohnphd.com, and I will see you in the next episode of Mastering Nutrition.

This episode is brought to you by Kettle and Fire bone broth.

This episode is brought to you by US Wellness Meats.

I discovered this company at Paleofx this spring and I fell in love with them as soon as I tried their liverwurst.

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14 Comments

Lindsay says:

Posted on February 1, 2019 at 10:33 am

Hi Chris,
I asked for and confirmed with the phlebotomist that I was getting plasma selenium and yesterday got my results for RBC. So frustrating. 220 mcg/L on a range of 120-300 (Quest). I’m a 29 yo woman. Can I be relatively confident of sufficiency? If so, frankly I’m bummed, as I was hoping this might be behind my long-standing thyroid symptoms and low T3 with normal T4 and TSH, not to mention frequent colds and nail spots and ridges. Oh well, no easy answers.
Thanks for all your info; I really enjoy your podcasts!

Reply
1. Chris Masterjohn, PhD says:
  
  Posted on February 5, 2019 at 6:13 pm
  
  You have too much. I would stop supplementing if you are.
  
  Reply
  1. Lindsay says:
    
    Posted on February 7, 2019 at 10:58 am
    
    Oh, interesting, thank you. I don’t supplement but was considering it because, in addition to what’s mentioned above, I’ve read it’s protective to the thyroid when taking iodine, which i am taking for fibrocystic breasts.
    
    Reply
Stuart says:

Posted on August 4, 2018 at 12:53 am

Chris, thank you for this very informative post and especially for providing a transcript. Life’s too short to listen to podcasts!

I wonder whether the high rates of low thyroid function and Hashimoto’s are mainly a result of selenium and/or iodine deficiency. If so surely the first step should be testing for those minerals and correcting any deficiencies found. Instead the knee-jerk reaction of most doctors seems to be to prescribe Synthroid.

Also what do you think about a possible link between Se deficiency and heart disease? Ancel Keys was criticised for selectively using data from Eastern Finland in his Seven Countries Study because heart disease rates there were much greater than in Western Finland despite a similar dietary intake of saturated fats. It so happens that the soils in the east have 1/3 of the selenium of the (already low Se) western areas. . In the 1930s-50s the majority of Finns were small farmers who ate a lot of their home-grown produce and even the urban population would have sourced much of their food from the local area. The one big exception to this was wheat and other grains since local production was insufficient. Given that pre-war Western Europe was overall a grain importer, this was likely to be high-Se North American grain and thus the main Se source in the food supply. From 1941-45 Finland was cut off from those imports and probably also couldn’t afford to import much in the late 40s-early 50s when it was paying crippling reparations for its “aggression” against the USSR (ie fighting back when attacked by the Red Army). I would therefore hypothesise that the population of Finland generally had been Se-deficient for about 15 years from 1941-55 and those in E Finland especially so. Consequently the high rate of heart disease may have been due to Se deficiency not saturated fat.

Of course since the 1950s grain imports resumed and presumably the Se intake increased. Also since the 1980s the Finnish govt required that all fertilisers be supplemented with Se. So maybe the reduction in heart disease in Finland that gets trumpeted as a success for saturated fat reduction is in fact the result of correcting Se deficiency.

On another issue you recommend that we should avoid seleno-methyl-cysteine (SMC) and take solely seleno-methionine (SM) . In this study
https://www.sciencedaily.com/releases/2011/03/110316113049.htm
they found that SMC was far more toxic to cancer cells than SM. I also read elsewhere that one of the advantages of SMC is that it does not get diverted down the selenoprotein pathway and so is available to combat cancer whereas it’s only when the selenoprotein requirement is satisfied that excess SM is available for anti-cancer purposes. The Cochrane meta-analysis seems to dismiss the anti-cancer effects of Se largely on the failure of the SELECT trial, where they used 100% SM and did not select participants who were Se-deficient. Whereas Clark in his original study specifically focussed on Se-deficient patients and treated them with Se-yeast that was 80% SM and 20% other Se forms including SMC. I would have thought that in order to prove or disprove a finding you would strive to replicate it as closely as possible but apparently not.

Reply
Michelle says:

Posted on June 29, 2018 at 6:44 pm

Thanks for such an informative podcast on selenium. After buying Ben Lynch’s book “Dirty Genes” and following his recommendations, I decided to evaluate my supplements, stop taking so many and as Dr. Lynch put it, “save some money and go on vacation”! My heart fell when I saw the amount of combined selenium in my multi (150 mcg) and in a selenium supplement (100 mcg), used along with 3 mg. molecular iodine. I take the iodine on M-W-F, but the selenium EVERY day…250 mcg for about 18 to 24 months. The selenium is in the form of SelenoExcell (natural food form of selenium yeast). I don’t recall you mentioning this form. What has this amount of selenium supplementation done to my glutathione? My 23andMe is v.5, and StateGene report lists GPX1 as NA. I also take Vitamin E and C. By the way, I feel great – sleep good, think good, digest good – just darn fibrocystic breasts. I’ve stoped the 100 mcg selenium supplement, but there’s still 150 mcg in the multi.

Reply
Aleš Svoboda says:

Posted on February 20, 2018 at 1:56 am

Hi Chris,
what’s your opinion on selenium supplement derived from selenium yeast (saccharomyces cerevisiae), available in “Zinc plus Selenium” made by Dr. Mercola?

Thank you
Aleš

Reply
Joe says:

Posted on September 24, 2017 at 1:02 pm

Chris, when I take a capsule of selenomethionine (now brand 200mcg) my hair sheds really badly for about 24 hours.

The weird thing is I feel great in every other way, I feel more positive and more energetic and I know my thyroid is benefiting because I feel nice and warm like I do from T3 thyroid.

Any idea why it causes hair loss. I can’t imagine it’s because of toxicity

Reply
David Clark says:

Posted on June 8, 2017 at 3:03 pm

It seems that not too long ago the high range for selenium intake was 1000 mcg/day. Now all you hear people saying is not to take more than 200 mcg, and in a lot of cases, as in yours, to only take below 100 mcg/day. What science caused this new paradigm of selenium supplementation? With cancer rates on the increase, people being more toxic and needing more glutathione, etc., etc., you would expect the opposite recommendations. How did people all of the suddent become selenium toxic to the point of reducing supplementation and high selenium foods?

Reply
Adriane says:

Posted on April 30, 2017 at 2:58 am

Great information Chris, thank you! One thought I have is for people with mercury amalgams who use up their selenium regularly detoxifying mercury via glutathione, wouldn’t they be a case for a higher need of selenium? Maybe for them 100 to 200mcg would be a maintenance dose?

Reply
1. Chris Masterjohn, PhD says:
  
  Posted on May 9, 2017 at 9:27 pm
  
  Adriane, they should measure their plasma levels and adjust accordingly.
  
  Reply
Dylan says:

Posted on March 5, 2017 at 3:49 pm

Chris,

Any thoughts on the additives to the supplements you recommended (dicalcium phosphate in Swanson’s and magnesium stearate in Now’s)?

Reply
1. Chris Masterjohn, PhD says:
  
  Posted on April 7, 2017 at 5:16 pm
  
  Dylan, at the moment I do not have much to say about them. However, if you’re concerned about that I’m sure you can find supplements without these additives.
  
  Reply
ben says:

Posted on February 19, 2017 at 11:18 pm

Is there a particularly special connection between selenium and hair?

For example, not enough leads to hair loss, but an excess seems to also cause hair loss:
https://www.ncbi.nlm.nih.gov/pubmed/8592839

Maybe it’s the same mechanism, but what is selenium doing topically in many dandruff shampoos (ex. Selsun Blue)?

Also I’ve seen many selenium products sold in ‘colloidal’ form. They usually seem to target cancer prevention, but wondering if you had any thoughts on this ‘colloidal’ form in terms of absorbability and/or toxicity.

Reply
1. chrismasterjohn@gmail.com says:
  
  Posted on February 21, 2017 at 9:48 pm
  
  Hi Ben,
  
  I’m not sure why selenium is in shampoo, but that’s an argument against using hair selenium as a marker of nutritional status.
  
  I don’t think the colloidal stuff has been studied well and I wouldn’t bother with it.
  
  I don’t know the exact mechanism of hair loss. My guess is it relates to oxidative stress but again, I don’t know the exact mechanism.
  
  Chris
  
  Reply

Why You Should Manage Your Selenium Status and How to Do It

Selenium Status Show Notes

Measuring and Assessing Selenium Status

Recommendations: Selenium in Foods and Supplements

Maps of Soil Selenium Content

Further Reading: Selenium Links and Research

Related Posts

Transcript of Episode 35

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