I've often wondered about my very high level of vitamin-D boosting my immune system. Blood test when l turned 50 showed very high level (cant remember the figure). I'am a 65 year old male who has worked outside for most of my life, mostly working with animals in dusty and muddy conditions, wearing only shorts and T shirt in summers with no sunscreen. Never been ill..not on any medication. Never had "the flu", Never had a flu shot. No covid vaccine..no covid yet. Had the odd cold but they have always been very mild and never stopped me from working. Only a few vaccines as a child and only one tetanus shot in my mid 30's. I'am also a rarity for someone born here in New Zealand..l did not have the BCG TB shot that was mandatory for 13 year Olds in the 80's and 90's.
High levels of D3 can pose problems. I do know that DCon, a brand of Rat poison, uses it in high amounts to cause the Rats to bleed internally and die.
That is hard to do. Not a concern for most. I've been on D2 50K every 2 weeks and 1K daily for 5 years and not even close to being high in the band of normal range.
If we take it to the extreme, if the only substances in the body were Vitamin D, then we would no longer be a living organism. When it comes to health, there is an appropriate amount, even if there is something that is good for you.
The form of Vitamin D you are taking as a supplement is not the same. The form you and I get takes a very long time to build up in the blood to give you a super-high dangerous amount. There are reliable long-term vitamin D studies done at a residential facility for, I believe developmentally disabled adults, in Ohio. No, I don't remember Every Last Thing I read, but this was indeed a credible and carefully done study. Some of the participants took a year to get their vitamin D levels up to 50 using the form of vitamin D that you and I can legally buy off the shelf, while cattle that are kept for long periods of time in large indoor barns in feedlot situations are allowed to be given a form of vitamin D that brings the levels up to "normal" in just days, if not hours. Here is the link to the blog that shows the changeover to using cholecalciferol form of vitamin D to overdose the rodents. THIS TYPE OF VITAMIN D IS NOT SOLD OVER-THE-COUNTER TO US PEONS. PLEASE NOTICE THE DIFFERENCE!: Cholecalciferol is the new active ingredient in rat poison since apparently, 2018: https://www.petpoisonhelpline.com/veterinarian-tips/breaking-news-d-con-rodenticide-ingredient-changes-to-vitamin-d3/.
Toxicity is a "very high level", which is over 150 ng/ml. Normal range is 30-100 ng/ml. Levels in the upper normal range are probably ideal, but that is difficult to study.
Rat poison companies are using a form that is not available for human consumption. I read about that in an article about a long-term vitamin D study done at an Ohio institution for, I believe, developmentally disabled adults. It took months and months and months for some to get their vitamin D levels up to 50 ng/ml. While cattle kept in indoor compounds are given cholecalciforol to get their levels up in just days...
You have to know where to look for this data. Vitamin D-3 doses of 300,000 IU taken all at once are the equivalent of taking #60 of 5000 IU capsules. Dividing this up over several meals would probably work better. Most people had a normal vitamin-D level in under a week and kept it for a month or so. https://pubmed.ncbi.nlm.nih.gov/24246341/
Nobody I have ever known has routinely done this, but I advised these doses for people acutely ill with COVID in 2020-2022.
(2 of 2) Dear Dr Nass, In your brief video presentation you alluded to how important a good level of 25-hydroxyvitamin D is for the immune system and so for general health, and that this requires a level well above the 20, or 30 ng/mL level many doctors regard as adequate. This is absolutely true. You also stated that the best - or only practical - way of attaining this is with vitamin D3 supplementation. This as also true as I wrote in my first comment and which can be ascertained from the research cited at: https://vitamindstopscovid.info/00-evi/.
You implied that the kidneys as being crucial for immune system health, but this is not the case. This is a common mistake, as is the use of the term "vitamin D" or "vitamin D3" to refer to all the three compounds, which have completely different roles, in the body. These mistakes lead to another one, which is very common, though you did not state this, that "vitamin D" is a hormone.
Reinhold Vieth wrote about this in 2004: "Why 'Vitamin D' is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids": https://sci-hub.se/10.1016/j.jsbmb.2004.03.037. If all vitamin D researchers had taken proper notice of this, then the literature would be much easier to understand and would not lead to fundamental mistakes such as thinking that the immune system can be "boosted", or at least made to work better, by artificially raising the level of circulating 1,25-dihydroxyvitamin D calcitriol.
The immune system does not use hormonal signaling and is not affected by the generally stable, and very low (ca. 0.05 ng/mL) level of circulating calcitriol.
These mistakes remain common in the vitamin D research literature because many researchers, and almost all medical professionals and immunologists, have never heard of 25-hydroxyvitamin D >> calcitriol intracrine and paracrine signaling, which is how many types of immune cell, and other cell types involved in neurodevelopment, use two of the (broadly) "vitamin D" compounds. This is in part due to these signaling systems being only recently discovered - for macrophages and dendritic cells ca. 2010 and for Th1 regulatory lymphocytes, most spectacularly by Chauss et al. https://www.nature.com/articles/s41590-021-01080-3 in 2021. No articles explain these two signaling systems, so even to this day, many vitamin D researchers do not understand, or even know of, them.
The health of all humanity depends on avoiding these mistakes. Here is the briefest possible outline of the functions of the three compounds. My aim is to encourage you and others to read the tutorial https://vitamindstopscovid.info/02-intracrine/ on these intracrine and paracrine signaling systems, on which the immune system depends, rather rely on this necessarily brief account.
Vitamin D3 cholecalciferol can be produced by UV-B light breaking one of the carbon rings in 7-dehydrocholestererol, which is present in the skin since it is the final stage in one of the two parallel long lines of synthesis which produce cholesterol. Since UV-B light in sufficient quantities is not naturally available to most humans all year round, we can only be healthy by ingesting vitamin D3 in supplements, since there is almost none in food.
Vitamin D3's primary or sole role in the body is to be hydroxylated, primarily in the liver, over several days into 25-hydroxyvitamin D3, for brevity "25-hydroxyvitamin D". This is not a vitamin. It is not "vitamin D". It is a separate compound with a different role in the body. It is also known as calcifediol or (confusingly) "calcidiol" which looks and sounds like "calcitriol". Only about 1/4 of ingested or UV-B produced vitamin D3 is hydroxylated into circulating 25-hydroxyvitamin D.
A 24-hydroxylase enzyme is present in some cell types and in the bloodstream. It degrades all three compounds irreversibly. Its activity is broadly proportional to the level of circulating 25-hydroxyvitamin D, so it acts as a self-limiting mechanism by degrading both vitamin D3 and 25-hydroxyvitamin D more rapidly when circulating 25-hydroxyvitamin D levels are high.
The half-life of circulating vitamin D3 is days or a week or so. At low, unhealthy, but normal (for most humans) levels such as 20 ng/mL or less, the half-life of circulating 25-hydroxyvitamin D is, very approximately, several weeks to a month for still lower levels. At healthy levels such as 50 ng/mL the half-life is shorter - I don't recall exactly what it is, but at 100 ng/mL, the half life would be in the order of a week or so.
The half-life of circulating (hormonal) calcitriol is measured in hours. In cells where it is generated as an intracrine agent, I guess the half-life would be shorter, with the 24-hydroxylase enzyme mopping up calcitriol rapidly once the intracrine conversion of 25-hydroxyvitamin D to calcitriol is turned off.
Some argue that cholecalciferol is not a vitamin, since we can make it ourselves via UV-B skin exposure, but since this is impossible for most people to attain in sufficient quantities, and since UV-B always damages DNA and so raise the risk of cancer, cholecalciferol is, for all practical purposes, a vitamin - vitamin D3 - since we need to ingest it in order to be healthy.
A hormone is a blood-borne (also in the cerebro-spinal fluid) compound whose level (concentration) is controlled by how much is produced somewhere in the body (in the case of hormonal calcitriol, the kidneys) and how it is degraded. This level controls, or affects, the behaviour of one or more types of cell anywhere in the body. Hormonal (endocrine) signalling is well understood by medical professionals and endocrinologists.
Neither vitamin D3 nor 25-hydroxyvitamin D function as hormones. They are not signaling molecules.
The third of the (broadly) "vitamin D" compounds is 1,25-dihydroxyvitamin D calcitriol. This is sometimes mistakenly referred to as "activated vitamin D". (For simplicity I am ignoring the vitamin D2 versions of these three compounds, since they are unnatural and not as effective as the vitamin D3 versions.)
The kidneys hydroxylate 25-hydroxyvitamin D (actively transported into their cells from circulating 25-hydroxyvitamin D) at the number 1 carbon into this third compound 1,25-dihydroxyvitamin D calcitriol. This goes into circulation a very low level ~~0.05 ng/mL where it functions as a hormone to affect the behaviour of several types of cell which are involved with calcium-phosphate-bone metabolism.
The level of circulating calcitriol depends on the level of circulating 25-hydroxyvitamin D (more means more calcitriol), the level of parathyroid hormone and the level of FGF-23 (fibroblast growth factor) which also acts as a hormone. Osteocytes in the bone produce circulating FGF-23 to signal to the kidneys, as part of regulating calcium-phosphate-bone metabolism.
Calcitriol is a signaling molecule, since it binds strongly to the VDR molecule - the so-called "vitamin D receptor" which is best thought of as the "calcitriol" receptor. Vitamin D3 and 25-hydroxyvitamin D also bind to the VDR molecule, but with much less affinity than calcitriol. The degree to which they bind to the VDR molecule is not significant with healthy vitamin D3 and 25-hydroxyvitamin D levels.
Inside a cell which has VDR molecules in its cytosol, "activated" VDR molecules - bound to (typically) a calcitriol molecule - find their way to the nucleus where they bind to a retinol X molecule. The triple complex exerts powerful influence on which genes are transcribed into mRNAs, so altering protein synthesis and the entire behaviour of the cell. The pattern of up- and down-regulating the transcription of dozens to hundreds of genes is different in each type of cell.
The immune system is not significantly affected by the very low level of circulating (hormonal) calcitriol. Many types of immune cell have an intracrine (inside a single cell) signalling system, in which a particular, cell-type-specific, condition is detected, which results in both the 1-hydroxylase enzyme and VDR being created in the cytosol. Assuming there is enough 25-hydroxyvitamin D in the cytosol (which is *not* the case for most humans today) the intracrine signaling system proceeds to change the cell's behaviour, by the immediate hydroxylation of 25-hydroxyvitamin D to calcitriol, as just described. Once the cell-type-specific condition is no longer detected, the 1-hydroxylase enzyme and VDR production is turned off, these molecules are degraded and the synthesis of calcitriol stops - so the cell's behaviour returns to normal.
Intracrine signaling involves a cell producing signaling molecules which bind to receptors in the same cell's cytosol. It is a common mistake (which I made at first, as did Chauss et al.) to confuse this with autocrine signaling, in which the signaling molecule, produced in response to the cell detecting a particular condition, affects the cell's behaviour, but by it leaving the cell and then binding to receptors on the outside of the cell's plasma membrane.
"Vitamin D" blood tests measure the amount of 25-hydroxyvitamin D in the bloodstream. This is the long term storage which supplies the kidneys, many types of immune cell and other cell types, such as those involved in neurodevelopment.
Because many clinicians don't understand 25-hydroxyvitamin D >> calcitriol intracrine and paracrine signaling, they assume (extrapolating from their understanding of hormonal calcitriol signaling to cells involved in calcium-phosphate-bone metabolism) that the well-known ability of "vitamin D boosts the immune system" works by boosting 25-hydroxyvitamin D levels, which somehow boosts circulating calcitriol levels (this occurs to only a marginal degree). However, this makes no sense since the kidneys closely control the level of circulating calcitriol to whatever level keeps circulating calcium ions within very narrow healthy levels.
You clearly know much more about this subject than I do. Fully Active Vit D is 1,25 dihydroxy Vit D but the blood level that is routinely measured is 25-OH Vit D
Evolution is full of mysteries, but a critical stage of evolution was the appearance of an intracellular protein that became the key to immunity. This protein is what we now call VDR, which stands for Vitamin D Receptor. It was the evolution of VDR 500 million years ago that was probably the initiator of the Cambrian explosion of advanced life-forms. The development of immunity meant that very primitive animal life, for example plankton, could evolve into more complex forms without being at the total mercy of pre-existing bacteria and viruses.
And so it is today. Without immunity we would not survive infancy and we would become extinct. Immunity is vital and we have seen the effects of seriously damaged immunity in the recent AIDS pandemic. We must not forget this. We must respect immunity and the need for its optimisation. We must understand it.
The evolution of VDR was critical, but VDR would have had no function had it not been for Vitamin D which had evolved a billion years earlier.
Plankton at the surface of the oceans were at risk of physical damage by UV from the Sun. They ultimately developed genetically programmed diurnal vertical migration, meaning that they spend the night at the surface and descend deeper in the water during the day.
But they developed another method of protection from UV, a chemical sunscreen. Starting from the long-chain squalene, otherwise known as shark oil, they became capable of synthesising steroid compounds, a process that is blocked by statin drugs (taken only by humankind in recent years). The important sunscreen steroid became the oil 7-dehydrocholesterol, 7-DHC. This will sound familiar to readers of the Blog. UV converts 7-DHC in the skin into cholecalciferol which we know as vitamin D. Within plankton this physico-chemical process absorbs UV energy and thus protects the plankton from damage.
( 1 of 2) Hi Meryl, Please see the research cited and discussed at: https://vitamindstopscovid.info/00-evi/. This begins with recommendations from New Jersey based Professor of Medicine Sunil Wimalawansa for how much vitamin D3 to supplement to attain this level safely, without the need for blood tests or medical monitoring. The amount depends on body weight and obesity status. For 70 kg 154lb body weight without obesity, 0.125 milligrams (125 micrograms = 5000 IU) a day is a good amount.
You are absolutely correct about the importance of attaining a higher level (concentration in the bloodstream) of 25-hydroxyvitamin D (calcifediol, the second of the three compounds) than the 20 to 30 nanograms per millilitre (50 to 75 nmol/L) recommended by governments and most doctors.
In 2014, Quraishi et al. (Massachusetts General Hospital) https://jamanetwork.com/journals/jamasurgery/fullarticle/1782085 showed that the risk of post-operative infections - both surgical site infections and hospital-acquired infections - was about 2.5% in 770 morbidly obese patients who underwent bariatric surgery for weight loss, for those with pre-operative 50 ng/mL or more circulating 25-hydroxyvitamin D.
The further the level was below this, the greater the risk of both types of infection. At 18 ng/mL - a level which many people have if they are not supplementing vitamin D3 at all, or perhaps in small quantities such as 0.015 mg (600 IU) a day on average - the risk of each of these two types of primarily bacterial infection rose to 25%. See an annotated diagram at: https://vitamindstopscovid.info/00-evi/#00-50ngmL.
There's no reason to believe that people suffering from obesity need a higher level of circulating 25-hydroxyvitamin D to run their immune systems properly, so this shows beyond question that we all need to attain at least 50 ng/mL to be healthy, no matter what other nutrients we ingest, how much exercise we do etc.
It is a common mistake to refer to all three compounds as "vitamin D" and to assume that the immune system depends on the circulating level of the third compound, 1,25-dihydroxyvitamin D calcitriol, which is produced by the kidneys. This is because very few doctors and immunologists have ever heard of, much less understand, 25-hydroxyvitamin D >> calcitriol intracrine (inside a single cell) and paracrine (to nearby cells, of different types) signaling. These are unrelated to hormonal (endocrine) signaling. There is no tutorial for this so I wrote one in 2020: https://vitamindstopscovid.info/02-intracrine/. Shorter versions are at https://vitamindstopscovid.info/00-evi/#02-compounds and https://brownstone.org/articles/vitamin-d-everything-you-need-to-know/ (with a cheery robotic voice narration).
There's very little vitamin D3 in food or multivitamins - nowhere near enough to attain the 50 ng/mL circulating vitamin D3 required for good health.
Fortunately, vitamin D3 supplementation in sufficient quantities is safe and inexpensive. This takes several months to raise the 25-hydroxyvitamin D level over 50 ng/mL from typical levels in the 10 to 30 ng/mL range. So having a blood test after a month or two will not show the stable level. See Fig 1 of McCullough et al. 2019. For adults in an Ohio psychiatric hospital taking 0.125 mg 5000 IU vitamin D3 a day, it took 5 or 6 months for levels to get close to stabilizing. For 0.25 mg 10,000 IU, about 10 months elapsed before levels got to about 90% of the long-term stable level.
There's no need for blood tests with Prof. Wimalawansa's recommendations for average daily intake of supplemental vitamin D3:
70 to 90 IU / kg body weight for those not suffering from obesity (BMI < 30).
100 to 130 IU / kg body weight for obesity I & II (BMI 30 to 39).
140 to 180 IU / kg body weight for obesity III (BMI > 39).
Vitamin D2 is unnatural and is less effective than vitamin D3. At least 50 ng/mL circulating 25-hydroxyvitamin D is essential for good health. Much lower levels have been a problem for an increasing proportion of humanity since the migration to northern Europe ~60k years ago. Today, with better clothing, housing and glass-windowed vehicles - and, for good reason, sunscreen - most people gain only a very small amount of vitamin D3 via UV-B skin exposure.
Even if such ~293 nanometre UV-B light was available all year round, rather than only in the middle of cloud-free summer days, such as with special lamps, to rely on this to attain 50 ng/mL circulating 25-hydroxyvitamin D would be a bad idea, since all UV-B damages DNA and so raises the risk of skin cancer.
There's very little vitamin D3 in food or multivitamins - nowhere near enough to attain the 50 ng/mL circulating 25-hydroxyvitamin D required for good health. Don't be put off by the very high numbers of IUs in healthy quantities of vitamin D, such as 0.125 milligram 125 microgram 5000 IU. This is a gram every 22 years, and pharma grade vitamin D3 costs about USD$2.50 a gram ex-factory.
I am 68, weight 67 kg (148 lb) and take somewhat more vitamin D3 a day on average that what Prof. Wimalawansa recommends: 0.2 mg 8000 IU. I expected my 25-hydroxyvitamin D level was in the 80 to 110 ng/mL range and never had it tested until recently. It was 96 ng/mL 240 nmol/L. Many doctors regard this as dangerously high, but they are mistaken. 150 ng/mL 375 nmol/L is the level above which toxicity may become a problem for some people. This is very difficult to attain, since there is a self-limiting process which degrades 25-hydroxyvitamin D at a rate which is proportional to its level. See the vitamin D3 (horizontal) and long-term 25-hydroxyvitamin D (vertical) curves in the Heaney et al. 2015: https://www.mdpi.com/2072-6643/7/3/1688 and Ekwaru et al. 2014: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111265https://vitamindstopscovid.info/00-evi/Vitamin-D-levels-Ekwaru-800x792.png
You are a doctor and regard ca. 100 ng/mL as healthy, though it is around twice the average level measured by Luxwolda et al. 2012 https://doi.org/10.1017/S0007114511007161 who found that the mean 25-hydroxyvitamin D level of traditionally living Maasai pastoralists and Hadzabe hunter gatherers was 46 ng/mL 115 nmol/L. I agree, but there's no reason to take notice of my opinion since I am a computer programmer and electronic technician.
Low 25-hydroxyvitamin D such as the 10 to 25 ng/mL (except after lots of high elevation sunlight on ideally white skin), as most people have today, cripples the immune system's responses to cancer cells, bacteria, yeast, fungi and viruses and increases self-destructive inflammation. The problems begin before birth: https://vitamindstopscovid.info/00-evi/#3.2, with preeclampsia, pre-term birth and the later development of autism, ADHD, intellectual disability and schizophrenia. https://vitamindstopscovid.info/00-evi/#3.3 cites and discusses research concerning low 25-hydroxyvitamin D levels, which are common, greatly increasing the risk of neurodegeneration - Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies etc.
David Anderson made a comment that obese people needed to take this “other” form of Vitamin D3 as obesity causes fat storage of the D3 and not available in the blood. Could you please clarify the name of the capsules he held up to the camera? The video conveniently broke up during this portion. Thank you.
Dr. Nass, I have read over the last few months some credible and conflicting reports regarding Vitamin D and it’s relation to Rat Poison and VD being the active ingredient. Is it remotely possible that it worked during “Convid” because it sort of thins the blood and blood clots are an issue in terms of being deprived of oxygen due to environmental effects of 5g etc.? Your input would be greatly appreciated.
This amount is like taking 88 pills of 5000 IU (.125 mg) of vitamin-D3, the largest human pill dose regularly available, too much for a mouse or rat.
[Warning: Do Not Eat A Raw Polar Bear Liver! too Much Vitamin-D.]
"The active ingredient in D-Con bait blocks is cholecalciferol (vitamin D3), which is mixed with flour, fat, and sugar to attract mice. D-Con chose cholecalciferol over other ingredients because it's safer for children and pets. A block of D-Con bait contains about 11 mg of cholecalciferol, which is a toxic dose for most animals under 35 lbs."
The fact that rats are killed by massive intakes of vitamin D3 cholecalciferol is irrelevant to humans' (and all mammals') need for enough vitamin D3, from UV-B exposure of skin or by ingesting it as a supplement (there very little in food, fortified or not) to attain at least 50 ng/mL (125 nanomols/litre = 1 part in 20,000,000 by mass) circulating 25-hydroxyvitamin D, made in the liver over several days by hydroxylating the vitamin D3 on the 25th carbon. If we ingested the same amount of vitamin D3, per kilogram body weight, as rats do, we would die too. Everything, including water and oxygen, is harmful in excessive amounts.
Neither vitamin D3 nor 25-hydroxyvitamin D3 are hormones. They do not "thin the blood". The third compound (they have completely different roles in the body, and it is a mistake to refer to the second and third as "vitamin D") is 1,25-dihydroxyvitamin D. This has the sole hormonal role of the three compounds. All the other functions of calcitriol, such as by the immune system, are not related to hormonal signaling.
Vastly excessive ingestion of vitamin D3, as in the case of the unfortunate rats, leads to the liver converting so much of it into circulating 25-hydroxyvitamin D that the circulating (in the bloodstream) level of 25-hydroxyvitamin D is far, far, beyond what the body needs or evolved to cope with. (Such levels can never occur from UV-B skin exposure, which is self-limiting.) I guess that if an adult human ingested a gram of vitamin D3, this would probably have the same effect as rats ingesting however much rat poison it takes to kill them.
In Australia, the greatest amount of vitamin D3 available, per capsule or tablet, without prescription is 0.025 milligrams 25 micrograms 1000 IU. In the USA, 0.125 mg (5000 IU) capsules are common. This is a good average daily amount to take for 70 kg 154 lb body weight without obesity. The largest capacity capsules generally available are 1.25 mg 50,000 IU.
For 70 kg body weight without obesity, one of these every 10 days is a good healthy intake, though it is is 5 times more than what many doctors mistakenly think is needed.
To ingest a gram of vitamin D3, one would need to take 800 of these 50,000 IU capsules, or 8000 of the once a day 5000 IU capsules which many people take.
The processes of toxicity follow two paths. Firstly, the kidneys convert too much 25-hydroxyvitamin D into circulating calcitriol, despite being instructed via the low level of parathyroid hormone, to convert less. The parathyroid gland senses the level of calcium ions, which needs to be very tightly regulated to maintain a level close to saturation, in order to maintain calcium in the bones. A high calcium ion level causes the parathyroid to lower its production of parathyroid hormone, which the kidneys sense, and which lowers the rate at which the kidneys hydroxylate 25-hydroxyvitamin D to circulating calcitriol. However, the parathyroid hormone level does not drop to zero, and the kidney's do not not completely turn of their 1-hydroxylase enzyme activity.
So even though the kidney's 1-hydroxylase enzyme activity is as low as it can go, there is still enough activity, in the presence of the extremely high level of 25-hydroxyvitamin D, to convert enough of into an abnormally high amount of calcitriol.
This raises circulating calcitriol levels well above the normal, healthy, 0.05 to 0.1 ng/mL range and so perturbs calcium-phosphate-bone metabolism into raising the calcium ion levels into the saturated range. This is due to several types of cell involved in this metabolism having a "vitamin D receptor" molecule (VDR, best thought of as the "calcitriol receptor) which sense the level of calcitriol in the bloodstream.
This raised level of circulating calcitriol causes these cell types to raise calcium ion levels well above the narrow healthy range, to the point where calcified deposits occur in blood vessels and heart valves, which can kill the rat, just as they would kill a human or any other mammal.
A second mechanism (I have a reference somewhere, but not handy) is that the very high level of 25-hydroxyvitamin D directly affects those calcium-phosphate-bone cell types in the same way: to make them raise calcium ion levels well above the healthy range. This is because the VDR molecule - which has a very high affinity for binding to calcitriol (whereupon it binds with retinol X in the nucleus and alters gene transcription into messenger RNA, and so protein synthesis and so cellular behaviour) - has a lower, but non-zero, affinity for binding to 25-hydroxyvitamin D. At these very high 25-hydroxyvitamin D levels, there is a significant activation of (binding to) the VDR molecules in these cells, and this would be the case even if calcitriol levels were normal.
25-hydroxyvitamin D does not function as a hormone at normal, healthy levels. Only at these extreme levels does it activate (bind to) VDR molecules in these cell types to any significant degree.
I gave away over 40,000 doses of 5000 IU of vitamin D3 to patients and coworkers in 2020.
It is probably the single most cost-effective medical intervention in the world.
Vitamin-D is the coin in the jukebox that lets our immune systems work.
;-)
My favorite organic chemist says that D3 is a hormone and shouldn't be called a vitamin at all. I get my D straight from the sun.
Vitamin D: Vitamin or Hormone? https://pubmed.ncbi.nlm.nih.gov/33549285/
Just get it. Some people can only take it as a pill for half of the year where the sun is weaker.
(I get it both ways in Texas.)
https://www.johndayblog.com/2021/12/ancient-vitamin-d-protection.html
I've often wondered about my very high level of vitamin-D boosting my immune system. Blood test when l turned 50 showed very high level (cant remember the figure). I'am a 65 year old male who has worked outside for most of my life, mostly working with animals in dusty and muddy conditions, wearing only shorts and T shirt in summers with no sunscreen. Never been ill..not on any medication. Never had "the flu", Never had a flu shot. No covid vaccine..no covid yet. Had the odd cold but they have always been very mild and never stopped me from working. Only a few vaccines as a child and only one tetanus shot in my mid 30's. I'am also a rarity for someone born here in New Zealand..l did not have the BCG TB shot that was mandatory for 13 year Olds in the 80's and 90's.
High levels of D3 can pose problems. I do know that DCon, a brand of Rat poison, uses it in high amounts to cause the Rats to bleed internally and die.
Hmmm.... I thought that was Warfarin, a.k.a. Coumadin when used as a pharmaceutical blood thinner..
See response to this farther down the thread. Ultra-high doses become toxic.
That is hard to do. Not a concern for most. I've been on D2 50K every 2 weeks and 1K daily for 5 years and not even close to being high in the band of normal range.
It turns out that a dose of #100 of 5000 IU vitamin D-3 once is a dose that has been studied in humans.
Don't eat a whole, raw polar bear liver, though...
I just wanted to clarify that I did mean D2 as it is a prescription for the higher dose and the daily is just OTC D3.
If we take it to the extreme, if the only substances in the body were Vitamin D, then we would no longer be a living organism. When it comes to health, there is an appropriate amount, even if there is something that is good for you.
The form of Vitamin D you are taking as a supplement is not the same. The form you and I get takes a very long time to build up in the blood to give you a super-high dangerous amount. There are reliable long-term vitamin D studies done at a residential facility for, I believe developmentally disabled adults, in Ohio. No, I don't remember Every Last Thing I read, but this was indeed a credible and carefully done study. Some of the participants took a year to get their vitamin D levels up to 50 using the form of vitamin D that you and I can legally buy off the shelf, while cattle that are kept for long periods of time in large indoor barns in feedlot situations are allowed to be given a form of vitamin D that brings the levels up to "normal" in just days, if not hours. Here is the link to the blog that shows the changeover to using cholecalciferol form of vitamin D to overdose the rodents. THIS TYPE OF VITAMIN D IS NOT SOLD OVER-THE-COUNTER TO US PEONS. PLEASE NOTICE THE DIFFERENCE!: Cholecalciferol is the new active ingredient in rat poison since apparently, 2018: https://www.petpoisonhelpline.com/veterinarian-tips/breaking-news-d-con-rodenticide-ingredient-changes-to-vitamin-d3/.
Toxicity is a "very high level", which is over 150 ng/ml. Normal range is 30-100 ng/ml. Levels in the upper normal range are probably ideal, but that is difficult to study.
Who would fund that (bad for business) study?
Rat poison companies are using a form that is not available for human consumption. I read about that in an article about a long-term vitamin D study done at an Ohio institution for, I believe, developmentally disabled adults. It took months and months and months for some to get their vitamin D levels up to 50 ng/ml. While cattle kept in indoor compounds are given cholecalciforol to get their levels up in just days...
You have to know where to look for this data. Vitamin D-3 doses of 300,000 IU taken all at once are the equivalent of taking #60 of 5000 IU capsules. Dividing this up over several meals would probably work better. Most people had a normal vitamin-D level in under a week and kept it for a month or so. https://pubmed.ncbi.nlm.nih.gov/24246341/
Nobody I have ever known has routinely done this, but I advised these doses for people acutely ill with COVID in 2020-2022.
Most dont know cervival cancer is a nutritional illness..Women with adequate Vit D levels dont get cervical dysplasia.
Wow. I didn't know that.
Hahaha the more sexual partners the more vitamin D needed I guess 🫣😁
Sounds good!
Reference?
(2 of 2) Dear Dr Nass, In your brief video presentation you alluded to how important a good level of 25-hydroxyvitamin D is for the immune system and so for general health, and that this requires a level well above the 20, or 30 ng/mL level many doctors regard as adequate. This is absolutely true. You also stated that the best - or only practical - way of attaining this is with vitamin D3 supplementation. This as also true as I wrote in my first comment and which can be ascertained from the research cited at: https://vitamindstopscovid.info/00-evi/.
You implied that the kidneys as being crucial for immune system health, but this is not the case. This is a common mistake, as is the use of the term "vitamin D" or "vitamin D3" to refer to all the three compounds, which have completely different roles, in the body. These mistakes lead to another one, which is very common, though you did not state this, that "vitamin D" is a hormone.
Reinhold Vieth wrote about this in 2004: "Why 'Vitamin D' is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids": https://sci-hub.se/10.1016/j.jsbmb.2004.03.037. If all vitamin D researchers had taken proper notice of this, then the literature would be much easier to understand and would not lead to fundamental mistakes such as thinking that the immune system can be "boosted", or at least made to work better, by artificially raising the level of circulating 1,25-dihydroxyvitamin D calcitriol.
The immune system does not use hormonal signaling and is not affected by the generally stable, and very low (ca. 0.05 ng/mL) level of circulating calcitriol.
These mistakes remain common in the vitamin D research literature because many researchers, and almost all medical professionals and immunologists, have never heard of 25-hydroxyvitamin D >> calcitriol intracrine and paracrine signaling, which is how many types of immune cell, and other cell types involved in neurodevelopment, use two of the (broadly) "vitamin D" compounds. This is in part due to these signaling systems being only recently discovered - for macrophages and dendritic cells ca. 2010 and for Th1 regulatory lymphocytes, most spectacularly by Chauss et al. https://www.nature.com/articles/s41590-021-01080-3 in 2021. No articles explain these two signaling systems, so even to this day, many vitamin D researchers do not understand, or even know of, them.
The health of all humanity depends on avoiding these mistakes. Here is the briefest possible outline of the functions of the three compounds. My aim is to encourage you and others to read the tutorial https://vitamindstopscovid.info/02-intracrine/ on these intracrine and paracrine signaling systems, on which the immune system depends, rather rely on this necessarily brief account.
Vitamin D3 cholecalciferol can be produced by UV-B light breaking one of the carbon rings in 7-dehydrocholestererol, which is present in the skin since it is the final stage in one of the two parallel long lines of synthesis which produce cholesterol. Since UV-B light in sufficient quantities is not naturally available to most humans all year round, we can only be healthy by ingesting vitamin D3 in supplements, since there is almost none in food.
Vitamin D3's primary or sole role in the body is to be hydroxylated, primarily in the liver, over several days into 25-hydroxyvitamin D3, for brevity "25-hydroxyvitamin D". This is not a vitamin. It is not "vitamin D". It is a separate compound with a different role in the body. It is also known as calcifediol or (confusingly) "calcidiol" which looks and sounds like "calcitriol". Only about 1/4 of ingested or UV-B produced vitamin D3 is hydroxylated into circulating 25-hydroxyvitamin D.
A 24-hydroxylase enzyme is present in some cell types and in the bloodstream. It degrades all three compounds irreversibly. Its activity is broadly proportional to the level of circulating 25-hydroxyvitamin D, so it acts as a self-limiting mechanism by degrading both vitamin D3 and 25-hydroxyvitamin D more rapidly when circulating 25-hydroxyvitamin D levels are high.
The half-life of circulating vitamin D3 is days or a week or so. At low, unhealthy, but normal (for most humans) levels such as 20 ng/mL or less, the half-life of circulating 25-hydroxyvitamin D is, very approximately, several weeks to a month for still lower levels. At healthy levels such as 50 ng/mL the half-life is shorter - I don't recall exactly what it is, but at 100 ng/mL, the half life would be in the order of a week or so.
The half-life of circulating (hormonal) calcitriol is measured in hours. In cells where it is generated as an intracrine agent, I guess the half-life would be shorter, with the 24-hydroxylase enzyme mopping up calcitriol rapidly once the intracrine conversion of 25-hydroxyvitamin D to calcitriol is turned off.
Some argue that cholecalciferol is not a vitamin, since we can make it ourselves via UV-B skin exposure, but since this is impossible for most people to attain in sufficient quantities, and since UV-B always damages DNA and so raise the risk of cancer, cholecalciferol is, for all practical purposes, a vitamin - vitamin D3 - since we need to ingest it in order to be healthy.
A hormone is a blood-borne (also in the cerebro-spinal fluid) compound whose level (concentration) is controlled by how much is produced somewhere in the body (in the case of hormonal calcitriol, the kidneys) and how it is degraded. This level controls, or affects, the behaviour of one or more types of cell anywhere in the body. Hormonal (endocrine) signalling is well understood by medical professionals and endocrinologists.
Neither vitamin D3 nor 25-hydroxyvitamin D function as hormones. They are not signaling molecules.
The third of the (broadly) "vitamin D" compounds is 1,25-dihydroxyvitamin D calcitriol. This is sometimes mistakenly referred to as "activated vitamin D". (For simplicity I am ignoring the vitamin D2 versions of these three compounds, since they are unnatural and not as effective as the vitamin D3 versions.)
The kidneys hydroxylate 25-hydroxyvitamin D (actively transported into their cells from circulating 25-hydroxyvitamin D) at the number 1 carbon into this third compound 1,25-dihydroxyvitamin D calcitriol. This goes into circulation a very low level ~~0.05 ng/mL where it functions as a hormone to affect the behaviour of several types of cell which are involved with calcium-phosphate-bone metabolism.
The level of circulating calcitriol depends on the level of circulating 25-hydroxyvitamin D (more means more calcitriol), the level of parathyroid hormone and the level of FGF-23 (fibroblast growth factor) which also acts as a hormone. Osteocytes in the bone produce circulating FGF-23 to signal to the kidneys, as part of regulating calcium-phosphate-bone metabolism.
Calcitriol is a signaling molecule, since it binds strongly to the VDR molecule - the so-called "vitamin D receptor" which is best thought of as the "calcitriol" receptor. Vitamin D3 and 25-hydroxyvitamin D also bind to the VDR molecule, but with much less affinity than calcitriol. The degree to which they bind to the VDR molecule is not significant with healthy vitamin D3 and 25-hydroxyvitamin D levels.
Inside a cell which has VDR molecules in its cytosol, "activated" VDR molecules - bound to (typically) a calcitriol molecule - find their way to the nucleus where they bind to a retinol X molecule. The triple complex exerts powerful influence on which genes are transcribed into mRNAs, so altering protein synthesis and the entire behaviour of the cell. The pattern of up- and down-regulating the transcription of dozens to hundreds of genes is different in each type of cell.
The immune system is not significantly affected by the very low level of circulating (hormonal) calcitriol. Many types of immune cell have an intracrine (inside a single cell) signalling system, in which a particular, cell-type-specific, condition is detected, which results in both the 1-hydroxylase enzyme and VDR being created in the cytosol. Assuming there is enough 25-hydroxyvitamin D in the cytosol (which is *not* the case for most humans today) the intracrine signaling system proceeds to change the cell's behaviour, by the immediate hydroxylation of 25-hydroxyvitamin D to calcitriol, as just described. Once the cell-type-specific condition is no longer detected, the 1-hydroxylase enzyme and VDR production is turned off, these molecules are degraded and the synthesis of calcitriol stops - so the cell's behaviour returns to normal.
Intracrine signaling involves a cell producing signaling molecules which bind to receptors in the same cell's cytosol. It is a common mistake (which I made at first, as did Chauss et al.) to confuse this with autocrine signaling, in which the signaling molecule, produced in response to the cell detecting a particular condition, affects the cell's behaviour, but by it leaving the cell and then binding to receptors on the outside of the cell's plasma membrane.
"Vitamin D" blood tests measure the amount of 25-hydroxyvitamin D in the bloodstream. This is the long term storage which supplies the kidneys, many types of immune cell and other cell types, such as those involved in neurodevelopment.
Because many clinicians don't understand 25-hydroxyvitamin D >> calcitriol intracrine and paracrine signaling, they assume (extrapolating from their understanding of hormonal calcitriol signaling to cells involved in calcium-phosphate-bone metabolism) that the well-known ability of "vitamin D boosts the immune system" works by boosting 25-hydroxyvitamin D levels, which somehow boosts circulating calcitriol levels (this occurs to only a marginal degree). However, this makes no sense since the kidneys closely control the level of circulating calcitriol to whatever level keeps circulating calcium ions within very narrow healthy levels.
You clearly know much more about this subject than I do. Fully Active Vit D is 1,25 dihydroxy Vit D but the blood level that is routinely measured is 25-OH Vit D
In December 2021 I devoted a blog post to the Vitamin-D research of David Grimes MD, in the UK, perhaps the best medical authority on vitamin-D:
Ancient Vitamin-D Protection https://www.johndayblog.com/2021/12/ancient-vitamin-d-protection.html
It began like this:
Evolution is full of mysteries, but a critical stage of evolution was the appearance of an intracellular protein that became the key to immunity. This protein is what we now call VDR, which stands for Vitamin D Receptor. It was the evolution of VDR 500 million years ago that was probably the initiator of the Cambrian explosion of advanced life-forms. The development of immunity meant that very primitive animal life, for example plankton, could evolve into more complex forms without being at the total mercy of pre-existing bacteria and viruses.
And so it is today. Without immunity we would not survive infancy and we would become extinct. Immunity is vital and we have seen the effects of seriously damaged immunity in the recent AIDS pandemic. We must not forget this. We must respect immunity and the need for its optimisation. We must understand it.
The evolution of VDR was critical, but VDR would have had no function had it not been for Vitamin D which had evolved a billion years earlier.
Plankton at the surface of the oceans were at risk of physical damage by UV from the Sun. They ultimately developed genetically programmed diurnal vertical migration, meaning that they spend the night at the surface and descend deeper in the water during the day.
But they developed another method of protection from UV, a chemical sunscreen. Starting from the long-chain squalene, otherwise known as shark oil, they became capable of synthesising steroid compounds, a process that is blocked by statin drugs (taken only by humankind in recent years). The important sunscreen steroid became the oil 7-dehydrocholesterol, 7-DHC. This will sound familiar to readers of the Blog. UV converts 7-DHC in the skin into cholecalciferol which we know as vitamin D. Within plankton this physico-chemical process absorbs UV energy and thus protects the plankton from damage.
( 1 of 2) Hi Meryl, Please see the research cited and discussed at: https://vitamindstopscovid.info/00-evi/. This begins with recommendations from New Jersey based Professor of Medicine Sunil Wimalawansa for how much vitamin D3 to supplement to attain this level safely, without the need for blood tests or medical monitoring. The amount depends on body weight and obesity status. For 70 kg 154lb body weight without obesity, 0.125 milligrams (125 micrograms = 5000 IU) a day is a good amount.
You are absolutely correct about the importance of attaining a higher level (concentration in the bloodstream) of 25-hydroxyvitamin D (calcifediol, the second of the three compounds) than the 20 to 30 nanograms per millilitre (50 to 75 nmol/L) recommended by governments and most doctors.
In 2014, Quraishi et al. (Massachusetts General Hospital) https://jamanetwork.com/journals/jamasurgery/fullarticle/1782085 showed that the risk of post-operative infections - both surgical site infections and hospital-acquired infections - was about 2.5% in 770 morbidly obese patients who underwent bariatric surgery for weight loss, for those with pre-operative 50 ng/mL or more circulating 25-hydroxyvitamin D.
The further the level was below this, the greater the risk of both types of infection. At 18 ng/mL - a level which many people have if they are not supplementing vitamin D3 at all, or perhaps in small quantities such as 0.015 mg (600 IU) a day on average - the risk of each of these two types of primarily bacterial infection rose to 25%. See an annotated diagram at: https://vitamindstopscovid.info/00-evi/#00-50ngmL.
There's no reason to believe that people suffering from obesity need a higher level of circulating 25-hydroxyvitamin D to run their immune systems properly, so this shows beyond question that we all need to attain at least 50 ng/mL to be healthy, no matter what other nutrients we ingest, how much exercise we do etc.
In 2008 leading researchers called for 40 to 60 ng/mL (100 to 150 nmol/L) to be the target for general health: https://www.grassrootshealth.net/project/our-scientists/. In 2024 this campaign is being renewed, for the same levels: https://www.grassrootshealth.net/scientists-call-daction-public-health-2024/.
It is a common mistake to refer to all three compounds as "vitamin D" and to assume that the immune system depends on the circulating level of the third compound, 1,25-dihydroxyvitamin D calcitriol, which is produced by the kidneys. This is because very few doctors and immunologists have ever heard of, much less understand, 25-hydroxyvitamin D >> calcitriol intracrine (inside a single cell) and paracrine (to nearby cells, of different types) signaling. These are unrelated to hormonal (endocrine) signaling. There is no tutorial for this so I wrote one in 2020: https://vitamindstopscovid.info/02-intracrine/. Shorter versions are at https://vitamindstopscovid.info/00-evi/#02-compounds and https://brownstone.org/articles/vitamin-d-everything-you-need-to-know/ (with a cheery robotic voice narration).
There's very little vitamin D3 in food or multivitamins - nowhere near enough to attain the 50 ng/mL circulating vitamin D3 required for good health.
Fortunately, vitamin D3 supplementation in sufficient quantities is safe and inexpensive. This takes several months to raise the 25-hydroxyvitamin D level over 50 ng/mL from typical levels in the 10 to 30 ng/mL range. So having a blood test after a month or two will not show the stable level. See Fig 1 of McCullough et al. 2019. For adults in an Ohio psychiatric hospital taking 0.125 mg 5000 IU vitamin D3 a day, it took 5 or 6 months for levels to get close to stabilizing. For 0.25 mg 10,000 IU, about 10 months elapsed before levels got to about 90% of the long-term stable level.
There's no need for blood tests with Prof. Wimalawansa's recommendations for average daily intake of supplemental vitamin D3:
70 to 90 IU / kg body weight for those not suffering from obesity (BMI < 30).
100 to 130 IU / kg body weight for obesity I & II (BMI 30 to 39).
140 to 180 IU / kg body weight for obesity III (BMI > 39).
Vitamin D2 is unnatural and is less effective than vitamin D3. At least 50 ng/mL circulating 25-hydroxyvitamin D is essential for good health. Much lower levels have been a problem for an increasing proportion of humanity since the migration to northern Europe ~60k years ago. Today, with better clothing, housing and glass-windowed vehicles - and, for good reason, sunscreen - most people gain only a very small amount of vitamin D3 via UV-B skin exposure.
Even if such ~293 nanometre UV-B light was available all year round, rather than only in the middle of cloud-free summer days, such as with special lamps, to rely on this to attain 50 ng/mL circulating 25-hydroxyvitamin D would be a bad idea, since all UV-B damages DNA and so raises the risk of skin cancer.
There's very little vitamin D3 in food or multivitamins - nowhere near enough to attain the 50 ng/mL circulating 25-hydroxyvitamin D required for good health. Don't be put off by the very high numbers of IUs in healthy quantities of vitamin D, such as 0.125 milligram 125 microgram 5000 IU. This is a gram every 22 years, and pharma grade vitamin D3 costs about USD$2.50 a gram ex-factory.
I am 68, weight 67 kg (148 lb) and take somewhat more vitamin D3 a day on average that what Prof. Wimalawansa recommends: 0.2 mg 8000 IU. I expected my 25-hydroxyvitamin D level was in the 80 to 110 ng/mL range and never had it tested until recently. It was 96 ng/mL 240 nmol/L. Many doctors regard this as dangerously high, but they are mistaken. 150 ng/mL 375 nmol/L is the level above which toxicity may become a problem for some people. This is very difficult to attain, since there is a self-limiting process which degrades 25-hydroxyvitamin D at a rate which is proportional to its level. See the vitamin D3 (horizontal) and long-term 25-hydroxyvitamin D (vertical) curves in the Heaney et al. 2015: https://www.mdpi.com/2072-6643/7/3/1688 and Ekwaru et al. 2014: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111265 https://vitamindstopscovid.info/00-evi/Vitamin-D-levels-Ekwaru-800x792.png
You are a doctor and regard ca. 100 ng/mL as healthy, though it is around twice the average level measured by Luxwolda et al. 2012 https://doi.org/10.1017/S0007114511007161 who found that the mean 25-hydroxyvitamin D level of traditionally living Maasai pastoralists and Hadzabe hunter gatherers was 46 ng/mL 115 nmol/L. I agree, but there's no reason to take notice of my opinion since I am a computer programmer and electronic technician.
Low 25-hydroxyvitamin D such as the 10 to 25 ng/mL (except after lots of high elevation sunlight on ideally white skin), as most people have today, cripples the immune system's responses to cancer cells, bacteria, yeast, fungi and viruses and increases self-destructive inflammation. The problems begin before birth: https://vitamindstopscovid.info/00-evi/#3.2, with preeclampsia, pre-term birth and the later development of autism, ADHD, intellectual disability and schizophrenia. https://vitamindstopscovid.info/00-evi/#3.3 cites and discusses research concerning low 25-hydroxyvitamin D levels, which are common, greatly increasing the risk of neurodegeneration - Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies etc.
You do need a blood level--I am a prime example--because multiple brands did not raise my level. Allergy Research Group's oily brand did raise it.
David Anderson made a comment that obese people needed to take this “other” form of Vitamin D3 as obesity causes fat storage of the D3 and not available in the blood. Could you please clarify the name of the capsules he held up to the camera? The video conveniently broke up during this portion. Thank you.
Dr. Nass, I have read over the last few months some credible and conflicting reports regarding Vitamin D and it’s relation to Rat Poison and VD being the active ingredient. Is it remotely possible that it worked during “Convid” because it sort of thins the blood and blood clots are an issue in terms of being deprived of oxygen due to environmental effects of 5g etc.? Your input would be greatly appreciated.
no, this is incorrect and it does not thin blood.
But the main active ingredient in DCon, which is a product to kill Rats, is D3…….. In high amounts it causes the Rats to bleed internally and die.
This amount is like taking 88 pills of 5000 IU (.125 mg) of vitamin-D3, the largest human pill dose regularly available, too much for a mouse or rat.
[Warning: Do Not Eat A Raw Polar Bear Liver! too Much Vitamin-D.]
"The active ingredient in D-Con bait blocks is cholecalciferol (vitamin D3), which is mixed with flour, fat, and sugar to attract mice. D-Con chose cholecalciferol over other ingredients because it's safer for children and pets. A block of D-Con bait contains about 11 mg of cholecalciferol, which is a toxic dose for most animals under 35 lbs."
Please see the research cited and discussed at: https://vitamindstopscovid.info/00-evi/.
The fact that rats are killed by massive intakes of vitamin D3 cholecalciferol is irrelevant to humans' (and all mammals') need for enough vitamin D3, from UV-B exposure of skin or by ingesting it as a supplement (there very little in food, fortified or not) to attain at least 50 ng/mL (125 nanomols/litre = 1 part in 20,000,000 by mass) circulating 25-hydroxyvitamin D, made in the liver over several days by hydroxylating the vitamin D3 on the 25th carbon. If we ingested the same amount of vitamin D3, per kilogram body weight, as rats do, we would die too. Everything, including water and oxygen, is harmful in excessive amounts.
Neither vitamin D3 nor 25-hydroxyvitamin D3 are hormones. They do not "thin the blood". The third compound (they have completely different roles in the body, and it is a mistake to refer to the second and third as "vitamin D") is 1,25-dihydroxyvitamin D. This has the sole hormonal role of the three compounds. All the other functions of calcitriol, such as by the immune system, are not related to hormonal signaling.
Vastly excessive ingestion of vitamin D3, as in the case of the unfortunate rats, leads to the liver converting so much of it into circulating 25-hydroxyvitamin D that the circulating (in the bloodstream) level of 25-hydroxyvitamin D is far, far, beyond what the body needs or evolved to cope with. (Such levels can never occur from UV-B skin exposure, which is self-limiting.) I guess that if an adult human ingested a gram of vitamin D3, this would probably have the same effect as rats ingesting however much rat poison it takes to kill them.
In Australia, the greatest amount of vitamin D3 available, per capsule or tablet, without prescription is 0.025 milligrams 25 micrograms 1000 IU. In the USA, 0.125 mg (5000 IU) capsules are common. This is a good average daily amount to take for 70 kg 154 lb body weight without obesity. The largest capacity capsules generally available are 1.25 mg 50,000 IU.
For 70 kg body weight without obesity, one of these every 10 days is a good healthy intake, though it is is 5 times more than what many doctors mistakenly think is needed.
To ingest a gram of vitamin D3, one would need to take 800 of these 50,000 IU capsules, or 8000 of the once a day 5000 IU capsules which many people take.
The processes of toxicity follow two paths. Firstly, the kidneys convert too much 25-hydroxyvitamin D into circulating calcitriol, despite being instructed via the low level of parathyroid hormone, to convert less. The parathyroid gland senses the level of calcium ions, which needs to be very tightly regulated to maintain a level close to saturation, in order to maintain calcium in the bones. A high calcium ion level causes the parathyroid to lower its production of parathyroid hormone, which the kidneys sense, and which lowers the rate at which the kidneys hydroxylate 25-hydroxyvitamin D to circulating calcitriol. However, the parathyroid hormone level does not drop to zero, and the kidney's do not not completely turn of their 1-hydroxylase enzyme activity.
So even though the kidney's 1-hydroxylase enzyme activity is as low as it can go, there is still enough activity, in the presence of the extremely high level of 25-hydroxyvitamin D, to convert enough of into an abnormally high amount of calcitriol.
This raises circulating calcitriol levels well above the normal, healthy, 0.05 to 0.1 ng/mL range and so perturbs calcium-phosphate-bone metabolism into raising the calcium ion levels into the saturated range. This is due to several types of cell involved in this metabolism having a "vitamin D receptor" molecule (VDR, best thought of as the "calcitriol receptor) which sense the level of calcitriol in the bloodstream.
This raised level of circulating calcitriol causes these cell types to raise calcium ion levels well above the narrow healthy range, to the point where calcified deposits occur in blood vessels and heart valves, which can kill the rat, just as they would kill a human or any other mammal.
A second mechanism (I have a reference somewhere, but not handy) is that the very high level of 25-hydroxyvitamin D directly affects those calcium-phosphate-bone cell types in the same way: to make them raise calcium ion levels well above the healthy range. This is because the VDR molecule - which has a very high affinity for binding to calcitriol (whereupon it binds with retinol X in the nucleus and alters gene transcription into messenger RNA, and so protein synthesis and so cellular behaviour) - has a lower, but non-zero, affinity for binding to 25-hydroxyvitamin D. At these very high 25-hydroxyvitamin D levels, there is a significant activation of (binding to) the VDR molecules in these cells, and this would be the case even if calcitriol levels were normal.
25-hydroxyvitamin D does not function as a hormone at normal, healthy levels. Only at these extreme levels does it activate (bind to) VDR molecules in these cell types to any significant degree.
You can get more vit D in the US, and D2 (ergocalciferol) comes in 50,000 I units per capsule.