Ep 113 Vitamin D: The D stands for drama

family visit. So one friend suggested that maybe I was dehydrated from being on the plane. But it didn't go away no matter how much I drank, and I started keeping track of how much I drank, and for the next little while it was just between one and two gallons of water every day. I just could not get enough water. After a while, I also started craving salt. I wanted chips, pickles, everything salty that I could get, which was a little bit unusual, which was probably due

to all the water I was drinking. So as things went along, things just started adding to that. You know, with all the water drinking, I had some bathroom trips. It was hard to concentrate my head felt really heavy, I was sleepy. My sleep actually was all over the place. Sometimes I had insomnia and sometimes I couldn't get enough sleep, but no matter how much I slept, it didn't help.

Eventually I started developing I think they're called hipnick jerks, which is if you've had this, you'll know right as you're falling asleep, all your muscles just jerk. It kind of feels like you're falling. And that started happening almost every time I went to sleep. I just felt really unwell all the time, and I could not get energy no matter what I did, And eventually it got to the point where it was hard to stand for more than about fifteen minutes. It just felt like my legs

were going to give up. They wouldn't support me anymore. If I didn't sit down right away, I would have staring spells because just my mind couldn't get enough energy to figure out the steps for the tasks. One time, it took me almost half an hour to figure out how to make a salad. And by make a salad, I mean getting a bag of salad out of the fridge and pouring it into a bowl and putting dressing on it. And eating it. Eating was really hard. Sometimes

I didn't feel like it. I had no appetite. Sometimes I forgot Sometimes, like with the salad example, I just couldn't get enough energy. I couldn't figure it out. And then there were other times where I would have bursts of hunger and I just would eat everything I could get to. I had to nap in my car after work after I got home, before I went into the house. Sometimes I had to completely stay home from work and

just rest. Sometimes on the way home from work, I would be in tears just from how tired I was. I think the worst night I remember it was towards the end of January and I was with some friends and getting ready to go home, and I just suddenly lost all my energy. I had to sit down because my legs were giving out. One of my friends helped me walk because I couldn't walk into straight line, and we took an elevator down. Still had to rest, sit down on sidewalk and rest on the way to the

parking lot. And I stayed at their house that night. And that was the first time I had muscle spasms and they were in my chest and.

with both feet like a toddler. I started wondering if I would eventually get to the point where I wasn't able to function at all and had to have full time care or something. And I was starting to wonder about what kind of plans I would have to make, like if I would have to move, who would take care of me, what my life would be like if it changed that drastically. Emotionally, I was a wreck from the fear and not knowing it was just physical and

emotional exhaustion. All in all, I was sick for about three months, but in the beginning of January, probably about a week or two into feeling sick, I had gone to the doctor and they did a basic blood test. It came back and everything was normal except for low vitamin D and low sodium, and because low sodium is life threatening, the doctor rightfully concentrated on that, and I think it was because of all the water had been drinking. I just flushed all the sodium out, so the doctor

put me on a water restriction. I could only drink about I think it was about eighty ounces of water a day, and that added to the emotional toll because I was still very thirsty. But because of the low so sodium, the doctor didn't tell me anything about the vitamin D. Eventually I changed doctors about a month later this so this was about the middle of February. By this point, that doctor didn't have any answers, but did notice the low vitamin D test results from before and

gave me a prescription. That doctor also sent me to a neurologist where I got tested for everything from vitamin B deficiency to multiple sclerosis. Every single test came back normal. But while I was having all this testing, I had started the vitamin D prescription, and within one day I noticed a difference and started feeling better after all of the testing came back normal, but because I was feeling better, they just decided that that must have been the issue.

And I have just been really careful about my vitamin D levels up things have been okay since then. I should mention your vitamin D should be at about thirty and on that first blood test in January, my levels were eleven. So it took a while to get things up to where they were supposed to be again, but everything just immediately started getting better and things turned round

after that. And so, like I said, I've been really careful to make sure that I take vitamin D and try to get some sunlight because I had never been so miserable before or since, and I am never going to let that happen ever again if I can control anything in my life.

we will get into, I promise. But vitamin D is also a vitamin, which means it's a micronutrient that is essential in our diet because we in general as a rule can't make enough of it, which I find so fun. Right off the bat, there are multiple forms of this vitamin, and all of them have to be activated prior to

being hormonally active. So there's vitamin D two or ergo calciferol, which is found in plants and some fungi, and vitamin D three or cola calcipherol, which is found in animals sources like fish liver oils, for example, and is used for a lot of fortification like in our milk, and is the type of vitamin D that we make in our skin.

converted yet again into the active metabolite, which is one twenty five die hydroxy vitamin D three aka calcid trial

and that is the actual active form. So yes, there are differences between D two and D three, and there's a lot of debate in the literature as to whether, like, is it better to supplement with D two or D three, And there's not a hard and fast rule as of yet, but in general they both have to be converted by a pretty similar, if not exactly the same process, and so really not a huge difference.

this work. Vitamin D calcitrial specifically travels to our guts from our kidneys to our guts, where it promotes the absorption of calcium and phosphorus, both of these are really

important minerals for calcification of our bones. It also works in our kidneys where it's actually made to increase the amount of calcium that gets reabsorbed so that we're not peeing out as much calcium, we lose less in our p And then it does this weird slightly counter into it a thing where it also stimulates our bone cells, specifically osteoclasts, which are responsible for breaking down bone to release calcium, and that seems counterintuitive, but what it ends

up doing is in the long run, resulting in more calcium being available to then be deposited into our bones to build strong bones.

deficiencies of both calcium and phosphorus. So unsurprisingly then one of the biggest concerns when it comes to especially severe vitamin D deficiency is osteomalasia or soft bones, and this can increase the risk of fractures. In children. This results in what is known as rickets. So in kids, their bones are still growing right, so they're not fully mineralized

to begin with. So what happens in a child, infant or a young child who ends up with a vitamin D deficiency is that their bones are never able to mineralize. So what we see in terms of both symptoms as well as signs that we look at like radiographically and on X rays and things, is that their growth plates, like the plates where your long bones and things are still growing, become really widened, and then we see evidence of bones that are not strong, they're not well ossified.

What this results in is slowed growth. So on a growth curve, these kids will be either slowing down in their linear growth like their height growth, or they might fall off of their growth curve that we look at. How they're growing okay. You can also see really commonly a boeing deformity, especially of the legs if the kid is old enough to be walking already, because those long bones like your femur, are so weak that it just can't support the weight of the rest of the body,

so you get this boeing at the knees. You can also see, especially in very young kids, delayed closure of the bones of the skull. Babies are born with skull bones that are not fused, and this fusion can take longer in the case of rickets because because you don't have enough calcium and phosphorus to be able to mineralize that bone. And then what's interesting is that you can see this excessive growth of cartilage in the places where our bones and our cartilage meet, especially in our chest

wall or in the wrists. So this results in these kind of characteristic findings that they're often called like beads on a rosary. It looks like kind of knobby beads along the center of the chest wall. Huh, because the cartilage is like you can almost think of it as like trying to compensate.

result in cardiac failure. Because calcium is also really important in stabilizing the cells of our heart. So when your electrolytes become so out of whack because you're not able to absorb enough calcium and phosphorus, then the electrical system of your heart can start to fail and that's all just under the umbrella of rickets.

half life on the matter of hours. Oh wow, okay, so we have to continually make active vitamin D and what circulates in our body and what we measure to see if somebody is sufficient or deficient in vitamin D. Is that second form the twenty five oh vitamin D that we make in our liver. Okay, So that is kind of an important point, is that you have to first make that liver form, which then we can detect and is kind of floating around in your body in theory or is stored in our fat cells, which is

important and we'll talk more about that later. But then it has to be converted by our kidneys to actually be active, and that active form doesn't last that long. This is all very tightly controlled in conjunction with another hormone called parathyroid hormone and controlled by our calcium levels. So it all works in like very complex hormonal loops that I'm not going to get into. But yeah, So like if you, for example, our milk that we drink in the US, at least milk has very high amounts

of calcium. We fortify milk with vitamin D, but that doesn't mean that the vitamin D that you're drinking in that milk is helping you absorb that calcium in that particular glass of milk.

There are a various other genetic or enzyme related disorders that can cause rickets or can cause severe vitamin D deficiency, even apart from like a nutritional deficiency, if that makes sense, but those tend to be more rare. So the most common cause of rickets overall is nutritional deficiency of vitamin D and or calcium calcium because of vitamin D, if that makes sense. Now when it comes to adults, because we can also be deficient in vitamin D severe vitamin

D deficiency results in osteomilasia, which I mentioned already. This is a process of demineralization of the bone. Importantly, this is not the same thing as osteoporosis, which more people

have probably we heard of. Osteoporosis. Now, the risk of osteoporosis may also be increased with vitamin D deficiency, but osteomylasia is a process that's actually interfering with the bone mineralization itself, So that means that in osteomilasia we see a change in the amount of mineralized ossified calcified bone compared to the amount of bone matrix or non calcified bone.

Whereas osteoporosis, which can happen from calcium deficiency that's not related to vitamin D as well as vitamin D deficiency and other things like just aging. Osteoporosis is probably a whole episode in and of itself, but this is a decrease in overall bone mass, but with normal ratios of mineralized to bone matrix bone, that makes sense.

So in terms of symptoms, what we can see with osteomylasia is actually a lot of bone pain. Osteoporosis is a painless process. Osteomylasia can be quite painful, and vitamin D deficiency in osteomolasia can also cause a lot of muscle pain and muscle weakness because our skeletal muscles also have vitamin D receptors, and those two things together can increase the risk of and therefore fractures. Wow, I know.

is an immune modulator. Like the list goes on and on and on, and we are really still learning the extent to which vitamin D has extraskeletal effects. So when it comes to severe, especially severe vitamin D deficiency, rickets and osteomylasia historically have been the two biggest diseases that we see. But when it comes to deficiency or what some people call insufficiency, we actually have a lot of epidemiological evidence that vitamin D deficiency or insufficiency is also associated.

I can see your face and I can't wait to talk about it. But it's also associated with an increased risk of various cancers, potentially with higher overall mortality. It's associated with various autoimmune diseases, including MS type one diabetes.

The risk of cardiovascular disease is increased with vitamin D deficiency, not to mention things like chronic fatigue syndrome and fibermyalgia that we still just don't understand there are a lot of things that epidemiologically are associated with vitamin D deficiency or with having low levels of vitamin D, but that doesn't mean that we have the slightest clue yet if these relationships are causal, or if they might be consequential,

like is vitamin D just a consequence of these various diseases, disorders, conditions, or what any of the mechanisms actually are, or.

the answers to all of the things. And vitamin D is clearly very important, but I feel like we are still so far from understanding not the individual role that it plays in different tissues or in different organs, but how that fits into the bigger picture of health and disease.

and some groups say like sufficient deficient severely deficient. And depending on which paper you read or which consensus statement you read, the laboratory values are going to vary just a little bit, but we at least have some like

generalities here. Many groups define sufficient like you have enough vitamin D. And remember that we are measuring twenty five oh vitamin D, which is the one that is made in our liver, regardless of whether the initial vitamin D came from a plant or your milk or a supplement or your skin that you made. Okay, and it's not the active form that's made in our kidneys, so sufficient most places define it as greater than twenty nanograms per

mili leader or fifty animals per leader. Then they would define insufficient as between twelve and twenty nanograms per mil or thirty to fifty animals per leader. Some places, instead of saying insufficient, say deficient for that category, and then they would say deficiency or severe deficiency as less than twelve nanograms per mil or thirty animals per leader. The lab where I work, and some consensus statements and some societies flag anything less than twenty nanograms per mil as deficient.

So it's like a higher threshold for calling something deficient and anything between twenty one and thirty nanograms per mil insufficient. So basically it's raising it saying that you should have at least thirty nanograms per mil or seventy five animals per leader to act be sufficient in vitamin D. Okay, I know those numbers, like, well, okay, I have.

is a lot of debate still. There's also some societies that say, no, it actually needs to be even higher. Yeah.

that toxicity of vitamin D is exceedingly rare. Interestingly, even though this is a fat soluble vitamin, which means that we can potentially store quite a bit of it in our fat cells, Vitamin D toxicity is generally associated with extremely high supplementation rates, like taking a whole bunch of vitamin D supplements, or, in rare cases, genetic mutations that lead to changes in the metabolism of those various phases of vitamin D. So when you have too much vitamin D,

it can lead to the opposite problem logically, and that is hyper calcemia, too much calcium in your blood, which can then go on to affect primarily the kidney and lead to a lot of kidney problems. Okay, so once we know what our lab values are supposed to look like, the natural next question is like, how do we get enough vitamin D or how do we make enough vitamin D?

Or who is that risk for not having enough vitamin D for having low levels of vitamin D Vitamin D deficiency And we're going to get into a lot of this in the epidemiology section. It has been on the rise for decades now across the globe. There are a number of different things that can contribute to this risk of deficiency, however specific number you define it. Number one is lack of sun exposure, because we primarily are making

this in our skin from exposure to UVB radiation. So lack of sun exposure can look like a lot of different things. It can look like living at northern latitudes where half the year there is simply not enough sun and specifically not enough UVB radiation to physically make enough vitamin D for like half the year or potentially more. That's one way you cannot get enough sun. It also can mean wearing sunscreen all the time, or covering your body in clothing to protect it from the sun, or

for whatever reason that we wear clothing. And I just want to say that that's important because skin cancer is also very real. Yes, it could also mean more pigmentation in the skin. Melanin is protective to a certain degree against UV rays and so it reduces the amount of UVB that's available to cause the reaction to make vitamin D. So that's another way you can have less vitamin D available.

It also can just be not being outdoors very much at all and being exposed to the sun, even in places that have adequate sunlight for most of the year. But besides sunlight, this is also a micronutrient. It's a vitamin and it turns out that we get very little vitamin D in our diets, especially as we eat not a lot of fish and fatty fish oils, which I don't know, maybe like people used to eat more.

very interesting. So there are a lot of different things that can contribute to the risk of vitamin D deficiency. It's almost never just one thing.

which is just Yeah. Speaking of phytoplankton, we talked about how cod liver oil is a great source of vitamin D well, it's likely that cod liver is packed full of vitamin D because of phytoplankton, which produced tons of vitamin D and then the concentration of it in the food chain and so on.

Some researchers hypothesize that vitamin D two and D three largely served to protect DNA and proteins from damage due to UVB radiation ooh, and that it was only later on, millions of years later on that the endocrine function and immune function of vitamin D evolved. And then about three hundred and eighty five million years ago, water dwelling species began moving on to land, but they encountered a problem that they didn't have to deal with as much in

the water. Gravity gravity. Yes, moving around was a much different ballgame on land than it wasn't water, and some land dwellers underwent changes in their bony skeletons to better support their movement in these new environments, which is where vitamin d's role in calcium absorption came into play.

the history, other mammals, amphibians, reptiles, birds. Vitamin D is fundamental to so much of life on this planet, and it's this vital nature of vitamin D that has led many people to explore its possible role in human evolution, particularly in terms of skin color. Right off the bat, I want to say that I am not familiar enough with the literature of this topic to make any assessments about what is known or commonly accepted about the drivers

of skin pigmentation in humans. But one popular hypothesis that you may have heard of is known as the vitamin D hypothesis or the vitamin D folate hypothesis. This hypothesis states basically that more melanin i e. Darker skin pigmentation was selected for when humans evolved around three hundred thousand years ago in Africa in tropical latitudes, and it evolved

to protect from harmful exposure to UV radiation. Then The hypothesis continues when humans begin to migrate out of Africa around seventy to ninety thousand years ago, those that move to higher latitudes eventually lost melanin to better absorb vitamin

D now that UVB levels were lower. This is a common narrative, a very common hypothesis that I saw repeated in nearly every paper that I read about vitamin D. And again, I haven't read enough of this literature to be able to tell you all the bits of evidence

there are to support or refute this hypothesis. I did read a paper, a recent paper from twenty twenty two, that discussed how people residing in Western Europe had darker skin pigmentation from around forty thousand years ago when they arrived, until around eight thousand years or so ago, and that's when lighter skin became more common. So for that really long chunk of time, about thirty two thousand years, humans

residing in northern and western Europe had darker skin. And the proposed reason for this more recent change in terms of skin pigmentation in that part of the world is that that's around when diet would have shifted to rely more on grain. Basically, the shift from hunting and gathering

to agriculture, so the beginning of the agricultural revolution. But bones from that time and earlier don't, as far as I read, show signs of vitamin D deficiency, which you might expect to see if vitamin D deficiency was such a strong driver. Only after so more recent the past few thousand years, our skeletal remains found that indicate vitamin D deficiency, And of course this could be that we just haven't found many remains from earlier times. I don't know.

There is some evidence showing that variations in particular parts of some genes are associated with vitamin D synthesis, but these variations don't seem to be linked to skin pigmentation variation or skin pigmentation overall mechanistically. And again, there's way more to this field of study if you want to read more. But the reason that I wanted to bring it up was to talk not about variation in vitamin D production and humans, but how we talk about that variation.

If vitamin D was a strong driver, if skin pigmentation over human evolutionary history, that does not necessarily mean that it can explain everything about health today, particularly health disparities.

What do I mean by that? I mean that many medical studies will look at whether a certain outcome like infection with COVID maybe, or cardiovascular disease or cancer or what have you, is associated with vitamin D levels and race presumably, though not necessarily explicitly stated as a proxy for skin pigmentation, which is I think a problem in and of itself.

vitamin D levels. It's like, not not accounting for structural inequalities or even discussing it, not institutionalized racism, nothing, just vitamin D.

the worst, they're not far off from victim blaming. They tell you that you got COVID because your skin color, or because your diet doesn't get you enough vitamin D, or because you don't spend enough time in the sun, or because you have too much body fat. It places the burden solely on the individual rather than on the systems that perpetuate these health disparities in medicine today. This isn't to say that we shouldn't look at vitamin D

in health. We absolutely should, but maybe just take a more thoughtful approach to study design as well as interpretation of results. And this also goes to popular media taking these scientific articles and making a headline that's like, vitamin D will prevent you from dyeing, Like I don't know.

too long a period, it becomes hunchbacked. If moreover, it is too prone to stand up and desirous of walking, the legs may become distorted in the regions of the thighs end.

and we have archaeological evidence backing that up. Skeletal remains have been found from ancient Rome around the fourth century, in France, sixteenth century Italy, and parts of what is now the UK, and these remains show signs of things

like childhood rickets or adult osteomalaysia. I don't know if enough of these remains have been found or analyzed to give any sort of prevalence estimate during this time, but that changes as we head into the seventeenth century, and this is when ricketts really begins to pick up steam

and doesn't slow down until the twentieth century. The word rickets is either said to have an unknown origin, come from the German or Old English word ricken, meaning twisted or to twist, or have its roots in the Greek word racus, meaning spine, which gave rise to the more

medical term rachitis rickittis. Wherever it came from, the word ricketts first appeared in a sixteen thirty two receipt book containing cures for quote rickets and children, and then just a couple of years after, in sixteen thirty four, it makes an appearance on the London Annual Bill of Mortality. That year, fourteen deaths were attributed to rickets out of ten thy nine hundred deaths total for a population of around two hundred thousand.

incidents of the condition in the British Isles. For instance, a sixteen forty publication listing botanical cures includes a reference to what maybe rickets in the thistle section quote Galen saith that the root and leaves hereo are of healing quality and good for such persons that have their bodies drawn together by some spasm or convulsion, or by some

other infirmity, which disease is truly to be called. The rickets, which happening sometimes to children, doeth so buying them in their nerves, ligaments, and whole structure of their body, that it suffereth not to grow or prosper, either in height, strength, or alacrity.

I get to say, uh, do beginneth, suffereth doeth. But most researchers attribute the first clear and controvertible descriptions of Ricketts to either Daniel Whistler, who published a monograph in sixteen forty five while in medical school titled Quote Inaugural Medical Disputation on the Disease of English Children, which is popularly termed Rickets, or Francis Glisten, an English physician who in sixteen fifty published a treat on Ricketts based on

clinical and post mortem experience. Like Whistler, g Listen described the signs and symptoms of the disease pretty well, including the characteristic age of onset, and the suggested treatments that Glisten gave were simple, really, I mean compared to some of the other things that we've talked about on the podcast, incisions to draw bad humors, oh dear, blistring, or tying soft wool around limbs to prevent blood flow.

The world would have to wait another two hundred and fifty years to learn what ultimately caused rickets, and in the meantime, prevalence of this condition would grow and grow and grow, especially in North America and Northern Europe, particularly Great Britain, to the point where it earned the nickname the English disease. And to what do we owe this

massive increase in vitamin D deficiency the Industrial Revolution? From around the mid eighteenth century to the mid nineteenth century, people in North America, Europe, and Great Britain began moving in large numbers from the rural countryside to cities, often with bad air pollution, where many of them lived in

crowded conditions. The increase in specialized labor and growth of factories meant that people were spending their days indoors working, and that, combined with the change in diet, bread taking the place of the dairy and the reduction in air quality, led to lower calcium intake, lower vitamin D production via both diet, and lower exposure to UVB, and thus higher

cases of rickets and overall vitamin D deficiency. No one during the Industrial Revolution was completely exempt from this drop in vitamin D levels, but rickets did tend to happen more commonly in cities and among those earning lower incomes. Over this period, ricketts cases grew to unimaginable levels. A physician published a report of infants aged eighteen months or less that had died in nineteen oh nine. I don't know how many were in this report, but he reported

that ninety six percent of those infants had rickets at autopsy. Wow. Ninety six percent.

that we ate and how those components sustained life. By the late eighteen hundreds, scientists had started digging into the question of what a diet should contain in order to maintain health, and many experiments were carried out to see what proportion of carbohydrates, fats, proteins, and salts were needed

for animals to survive and thrive. Importantly, but what these scientists were often finding in these experiments using very restricted diets was that even though the caloric needs of these animals were being met, the animals were still dying or failing to thrive. Something was clearly missing, and so researchers set out to find that missing piece of the puzzle, which of course turned out to be not one piece but many. And I feel like I've said that exact

phrase on the podcast before. It is now ringing, like I'm experiencing deja vu.

or cod liver oil. This pattern where certain diseases were cured by certain foods suggested to scientists that these foods contained some sort of micronutrient whose deficiency was behind the signs and symptoms that they observed, and that given the wide array of signs and symptoms, and that different foods cured different diseases, there were likely many micronutrients. I know we've talked about this before on the podcast, but I just think this history of discovery is so fascinating.

first used A and B. Love that love it yep. Anyway, research into vitamin discovery was well underway by the night eighteen tens when Sir Edward Mellonbee decided that he might like to dip his toe into the vitamin waters. In nineteen eighteen, he set out to induce rickets experimentally in his chosen study, animal puppies. He took puppies between the ages of five and eight weeks old and exposed them to one of four limited diets diets like only milk, rice,

oatmeal and salt, or just milk and bread. He reportedly based these diets off of what was commonly consumed by people earning lower income in Great Britain, and these diets were maybe thought to contribute to the high prevalence of rickets. He also crucially kept the puppies indoors the entire time, unsurprisingly I think to us anyway, from this perspective, in the future, the puppies developed rickets, and melon Bee began experimenting with food to see if any particular item could

effectively treat it. Among the foods he tried were cod liver, oil, butter, and whole milk, things that we know today are good sources of vitamin D, but at the time were known to be rich in fat soluble vitamin A, which had

already been found by that point. These foods appeared to relieve the symptoms of rickets, which led Melanbie to conclude that quote it therefore seems probable that the cause of rickets is a diminished intake of an anti rikittic factor, which is either fat soluble A or has a somewhat similar distribution to fat soluble A pretty pretty good conclusion, and this experiment marked a pretty big step forward for ricketts research Number one because it showed that rickets was

likely caused by a dietary deficiency or at least could be treated by diet. And number two, it demonstrated how rickets could be intentionally induced for scientific study purposes. But there were still at least two big things to be figured out, detangling vitamins A and D and understanding the role of ultraviolet light. Before I get into that, though, I want to take a step back in time, because

Melanbee didn't come up with these ideas all on his own. Where, for instance, did he get the idea to treat rickets with cod liver oil? As I mentioned, it had been used successfully to treat xerophthalmia caused by vitamin A deficiency, so maybe he got it from there, Or maybe he got it from d Shoot, who in eighteen twenty four recommended it for treatment of rickets.

in insufficient amounts. The substances occur in good breast milk also in cod liver oil, but are lacking in sterilized

milk and cereals. Or perhaps melon Bee and probably most of the people I just listed, got the idea because cod liver oil had long been a folk remedy for rickets, like for a very long time, especially for those living along the coast in Great Britain, which I kind of love when like this thing that is like, oh, take cod liver oil, it will cure your whatever, it will cure your you know, and then it's like, oh no, but it does actually does.

post World War One. Vienna. Chick will come back into the story later, but first let's get back into the steps of vitamin D discovery, starting with detangling A and D to test whether rickets was caused by vitamin A

deficiency or something else. In cod liver oil, McCollum, who was the person who first discovered vitamin A, and his colleagues destroyed vitamin A in cod liver oil through like heating or aeration, and then they use the resulting substance to treat rickets, and sure enough it worked, and so they concluded that this was a new vitamin, the fourth to be discovered, hence vitamin D, and that it was

likely involved in bone growth. And around this time other researchers began to shine a light on the roll of light, particularly sunlight I couldn't resist as a treatment for rickets. Harriet Chick noticed that rickets seemed to be seasonal, appearing mostly in the winter, months and wondered if uv irradiation via lamps and sunlight could work as treatment and prevention for rickets. It certainly did, and was as effective as cod liver oil. Ooh, you know, this is actually I'm

thinking of this now. So one of the things that I didn't include in here was the importance of the development of X rays in terms of diagnosing and understanding the extent to which people had vitamin D deficiencies. Some to look at their bones exactly, and that kind of

like really helped understanding the scope of the problem. But as we talked about in our radiation episode, people thought radiation was also this like huge healing thing around that time, and so they were like drink uranium whatever, And so I wonder if uv irradiation and vitamin D like that was that hype around radiation contributed to that in any way.

And I can't help but think of how strange this would have seemed, right like to it blew my mind when I learned, I don't know how when that we make vitamin D from sun.

what sounds like a fairly gruesome experiment. First, they fed rats on a diet that made them develop rickets. Okay. Then they killed those rats, took out their livers, and irradiated them. Still okay. Then they ground up those livers and fed them to other rats with rickets. That seems that's yeah, that's the part yeah, but hey, no more rickets? What uh huh? Okay okay, I know that was exact my reaction, and Steinbach did something similar, minus the forced cannibalism.

So previously, he had worked with goats that showed calcium loss when living indoors in the winter without much sunlight, and so he wondered if that same lack of sunlight could be causing the skeletal changes in rats with rickets via vitamin D deficiency. To test this, he irradiated the rats, their food and the air in their cages to see if there was any improvement. There wasn't with the irradiated air, but definitely there was when the food or the rats

themselves were irradiated. Hesse and Weinstock followed up these experiments by Goldblatt, Somes, and Steambock with yet another grizzly experiment. They induced rickets and rats, irradiated some of their skin but left other parts untouched, and then fed that skin to other rats with rickets. Those that were fed the irradiated skin of their brethren got back better, but those that were fed the non irradiated skin did not.

forest cannibalism part again, but like skin. Once the roll of sunlight and vitamin D production became clear, all that was left to do was characterize the nature of vitamin D, what its chemical structure was, how it functioned, the physiological processes it was involved in, just the simple stuff. And throughout the nineteen thirties and nineteen forties, researchers filled in these knowledge gaps about vitamin D, differentiating D two and

D three describing their chemical structures. Nobel Prize winner Adolph Windhaus played a large role in this, showing that cod liver oil contained D three, that vitamin D was a steroid, and revealing the detailed structure of vitamin D three via X ray crystallography, which was done in nineteen forty eight by doctor Dorothy Crowfoot Hodgkin Nobel Prize winner in chemistry, whom we've mentioned more than months on this podcast. We

love actra crystallography. The rest of the twentieth century was filled with further important developments in our understanding of vitamin D, but for public health officials, the big chunks of knowledge were already there in the early decades of the nineteen hundreds that allowed them to enact measures reducing vitamin D deficiency, namely vitamin D supplementation through food or sunlight to help treat and prevent rickets and the consequences of vitamin D deficiency.

Many programs supplementing children's diets with vitamin D had been underway since the late nineteen tens, and the widespread fortification of food with vitamin D, especially in milk and infant formula, led to ricketts nearly being eliminated in many places. But nearly is not the same thing as completely, and rickets is just one aspect of vitamin D deficiency. And I think that, as you mentioned erin, we are kind of

increasingly becoming more vitamin D deficient. And so I'll turn it over to you now to tell me a little bit more about that.

UK currently. It's a whole other thing. And human breast milk is also very low in vitamin D. It has very poor transfer into breast milk in human breast milk, and so breastfed babies are actually at high risk in vitamin D deficiency, which I didn't mention when I was mentioning all the other ways that you can become vitamin D deficient.

estimate I saw. Another one is that exposure to where your skin gets just a little bit red not recommended skin cancer, et cetera, while wearing only a bathing suit is the equivalent of ingesting about twenty thousand international units of vitamin D. WHOA, I know, isn't that interesting?

numbers for you. Looking at deficiency as defined as less than twenty nanograms per mill or fifty animals per leader, which is kind of the most common definition. Rates of vitamin D deficiency are as high as twenty four percent in the US, thirty seven percent in Canada, and forty percent in Europe, depending on what paper you look at. Some studies even say that up to one hundred percent

of elderly adults might be deficient. That seems excessive. WHOA if we look at severe deficiency or what in some cases is just defined as deficiency. If the other version is just insufficiency, and that is less than twelve nanograms per mill or thirty animals per leader, that's estimated to be at around six percent in the US, seven point

four percent in Canada, and thirteen percent in Europe. And now these are all very big places, and these are all very big populations, and that's not even including so much of the rest of the world. I do have numbers as well for India, Tunisia, Afghanistan. These just happen to be some places that have data in the papers that I read there, those estimates tend to be around twenty percent or more of the population that may be deficient,

and I don't have numbers for severely deficient globally. What this adds up to is that it's estimated that one billion people worldwide have vitamin D deficiency or insufficiency, that less than twenty number, and of course this is going to be higher in certain subpopulations as well, like kidney failure or with severe liver disease. When it comes to looking at the diseases that we know are caused by vitamin D deficiency, specifically rickets, the numbers are thankfully much

less dire than they once were. In a twenty seventeen review looking at rickets, the case rates were estimated at between three and twenty seven cases per one hundred thousand individuals in the US and in Europe.

well as supplementation. The recommendation for supplementation in like breast fed infants and things like that. So we know that those kind of programs can improve this risk of severe vitamin D deficiency can reduce the prevalence of things like rickets osteomolasia in adults. I had a really hard time finding data on probably because it's just widely underrecognized in general. Despite all of that, like good news, we still know that those numbers of overall deficiency are pretty high.

across the board. They were also like, hey, we also need a lot of better research to figure out do we need supplementation widespread or are we doing okay with

just our diets and the fortification programs that exist. So a lot of studies have come out since that twenty eleven paper that have tried to look at this, specifically looking at widespread supplementation with vitamin D supplements at various levels one thousand a day, two thousand a day, four hundred a day, whatever, without checking first if someone is deficient or not for them to be in the study. Okay, let's take a group. Yeah, let's take a group of people.

Let's give them vitamin D and see what happens. And most all of that data, whether in individual studies or in meta analyzes, does not improve outcomes. So there is data to suggest that this widespread supplementation without checking if people are deficient before they're in the study, does not reduce the risk of fractures, does not reduce the risk of low bone mass or osteoporosis. Those are just the

skeletal things. It also doesn't have any evidence for prevention of cardiovascular disease, prevention of falls, improvement in cognitive function, prevention of stroke, prevention of all cause mortality, or cardiovascular mortality. And this is all super fascinating to me.

on everybody. That happens in a lot of places as a matter of routine, and there's not a lot of data to suggest that it's beneficial, especially when you look at what the supplementation studies also show that, like widespread supplementation also isn't helpful. And yet at the same time we know that deficiency is probably underestimated. So it's just it's really interesting.

We wouldn't expect it, so are they. A consequence is vitamin D deficiency some kind of early or easily identified consequence of various diseases, disorders, conditions.

those are coming from the Vital Study VIL. We will post the list of all of our sources from this episode and every one of our episodes on our website. This podcast will kill you dot com.