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D is powerful for sure. Are you familiar with the research on how many forms supplementation can lead to a false signal as D needs to be sulfated by Sunlight?

https://romanshapoval.substack.com/p/why-vitamin-d-supplements-dont-work

It's my understanding that if ingesting D as a supplement, it's absorbed optimally when there is the right balance of A and K2, as in fermented cod liver oil.

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YES! Thank you!

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The diagram depicts, on the lower left, 1,25-dihydroxyvitamin, AKA calcitriol, the molecule which activates the "vitamin D receptor" (VDR) which, when activated causes the cell to change its behaviour via altering the rates of transcription of dozens or hundreds of genes, in a way which varies from one cell type to the next. This is widely referred to as "activated vitamin D". However, it would be better to think of the VDR as the "calcitriol receptor", since its rate of activation by vitamin D3 cholecalciferol and 25-hydroxyvitamin D calcifediol (sometimes also known as calcidiol) is much lower.

Calcitriol is a signaling molecule, while vitamin D3 and 25-hydroxyvitamin D (made primarily in the liver by adding an oxygen-hydrogen group to the 25th carbon) are not. Calcitriol is best known as a hormone, made in the kidneys (as indicated by the diagram) in very limited amounts, to attain a level in the bloodstream around 0.05 to 0.1 ng/mL, with that level being used by the kidneys (as part of a feedback network with the parathyroid gland and osteocyte cells in bone) to regulate calcium-phosphate-bone metabolism.

Hormonal signaling involves some part of the body controlling the level (concentration) of a molecule in the bloodstream and in some cases so the the cerebrospinal fluid (in which the brain and spinal cord are bathed) for the purpose of that level being sensed by one or more cell types, with those cells, anywhere in the body, changing their behaviour according to the level they detect.

All medical professionals understand this. However, what the diagram doesn't show and what most medical professionals don't understand is that the immune system does not work with this calcitriol hormonal signaling system at all. Many types of immune cells - and other cell-types which are not involved in calcium-phosphate-bone metabolism - hydroxylate 25-hydroxyvitamin D, on the number 1 carbon, to become calcitriol, inside the cell, only when a specific, cell-type dependent, condition occurs. That calcitriol functions not as a hormone, but as an intracrine signaling agent (to alter the behaviour of that cell) or as a paracrine signaling agent (by diffusing to nearby cells, probably of different types, and altering their behaviour). This calcitriol is at a much higher level, ca. 1 ng/mL, than the very low level of hormonal calcitriol in the whole body, so these signaling systems are not significantly affected by that hormonal calcitriol.

Without this understanding, many medical professionals assume, wrongly, that the immune system depends on the very low level of circulating, hormonal, calcitriol. This is why Simon and I began our article https://brownstone.org/articles/vitamin-d-everything-you-need-to-know/ with an explanation of 25-hydroxyvitamin D based intracrine and paracrine signaling. Without proper supplies of 25-hydroxyvitamin D, these systems cannot function properly. Most people don't have enough 25-hydroxyvitamin D for their immune systems to work properly.

There is very little vitamin D3 in food. There is enough in food to help towards attaining the 15 to 20 ng/mL circulating 25-hydroxyvitamin D the kidneys need to function properly. The kidney cells bring 25-hydroxyvitamin D across their cell membrane and into their cytosol with an actively powered transporter system which works with the vitamin D binding protein, to which most 25-hydroxyvitamin D molecules in circulation are bound.

Immune cells - and as far as I know, all other cell types which rely use 25-hydroxyvitamin D for intracrine and/or paracrine signaling) have no such active transport. They rely on diffusion across their cell membranes from the small fraction of the circulating 25-hydroxyvitamin D which is not bound strongly to the vitamin D binding protein, or, more weakly to albumin proteins. This means that immune cells can only respond to their changing circumstances rapidly and fully when there is about 50 ng/mL (125 nmol/L = 1 part in 20,000,000 by mass) 25-hydroxyvitamin D in the bloodstream.

There is no way of even approaching this level from the very small amounts of vitamin D3 in food. It is possible to attain 50 ng/mL or somewhat more circulating 25-hydroxyvitamin D from UV-B skin exposure. However, this does not work very well (and so would require massive exposure) on brown or black skin - and all such UV-B exposure causes DNA damage and so raises the risks of skin cancer.

There are multiple healthy aspects of being outdoors, and being exposed to the Sun. However, to try to attain 50 ng/mL or more circulating 25-hydroxyvitamin D via limited vitamin D3 in food, with the need for high levels of UV-B exposure all year round, would be impractical for most people living far from the equator (and impossible during monsoon season) and unhealthy due to the increased risk of skin cancer.

The only practical and safe way of attaining 25-hydroxyvitamin D levels of 50 ng/mL or more is vitamin D3 supplementation. Fortunately, the quantities involved a minuscule - such as, for 70 kg body weight without obesity, 1 gram every 22 years. This is 1/8000th of a gram per day, on average. Unfortunately, this is also known by the scarily high number of "5000 International Units", which tends to put people off - especially if they believe, wrongly, that "vitamin D is a hormone".

Our article gives some body-weight ratio based guidance on how much vitamin D3 to take for most people to attain at least 50 ng/mL circulating 25-hydroxyvitamin D, without the need for blood tests and medical monitoring.

The magnesium article: Cazzola et al. 2020 "Going to the roots of reduced magnesium dietary intake: A tradeoff between climate changes and sources" https://www.cell.com/heliyon/fulltext/S2405-8440(20)32233-7 looks interesting.

Is it really necessary to have 100 mg magnesium per 0.025 mg (1000 IU) of vitamin D3?

Here are three articles on vitamin K2: https://doi.org/10.1155/2017/6254836 , https://doi.org/10.1155/2018/4629383 and https://doi.org/10.3390/ijms20040896 - I have only read the first one so far.

Zinc and omega 3 fatty acids are also very important.

My website https://5nn.info links to other sites on which I have nutrition information. This is easy to remember - and it stands for "5 neglected nutrients". These are vitamin D3, magnesium, boron, omega 3 fatty acids and zinc.

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What are your thoughts on boron? Lots of talk about VitD, K2, and Mg...but I rarely hear anyone mention boron in the mix.

https://open.substack.com/pub/conspiracysarah/p/boron-the-little-trace-mineral-that?r=thuli&utm_medium=ios&utm_campaign=post

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Hi Sarah, I haven't yet read your article on boron. Here are some links to research in this seriously neglected nutrient - the essential nutrient almost no-one gets enough of, in part because most people do not regard it as a nutrient: https://aminotheory.com/cv19/#08-boron . I have not yet read or added this apparently very comprehensive review article: Khaliq et al 2019: "The physiological role of boron" https://link.springer.com/article/10.1007/s12011-018-1284-3 . There is only small amount of research on boron nutrition. Its mechanisms in the body are unknown. It does not seem to form lasting compounds - if it did, I guess these would have been detected. I understand that boron, as the borate ion, washes in and out of the body by the day, so it is best to take it at least once a day. We generally get 1mg or so - more with lots of fruit and vegetables. I take around 9 mg a day, as borax in water, in several drinks a day, but for most people 3 mg tablets are probably more convenient.

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Robin, thank you so much for the information! I look forward to reading the articles you included.

Regarding dose...I read that 6mg was the minimum to reap Boron's benefits. I found it interesting that all of the multivitamins and supplements I have looked at only have 3mg. I alternate between a boron capsule and Borax in my water.

Anecdotal story...I have a 75 year old client that had osteoporosis. She has been on Fosomax for a while with no change in T or Z Score. I suggested that she ask her doc if it would be ok to add boron. He wasn't familiar with it at all, but told her that she would be fine to add it. She's been taking it for probably 18 months now. At her last osteo visit, her bone density showed improvement and she now is considered osteopenia (which I remind her wasn't "a thing" until there was a drug for it). Of course, correlation doesn't equal causation, yada yada....but she's not stopping the boron anytime soon, as that's the only thing she says that she has changed.

Two weeks ago she tripped on a cord in her needlepoint room and fell face first (literally) onto the coffee table. Right on the bridge of her nose. There was a lot of blood and it was scary. She was VERY bruised, but x-rays showed no broken anything...which felt like a real win.

Anyway...I appreciate your sharing all of this information and look forward to reading all of it. Thank you!

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Dr. Göddeck, can you please share the best forms of magnesium and zinc to take? There are so many of each and it gets confusing…

Thank you in advance for your reply. God bless!

Barbara

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October 12, 2023
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Exactly! Stop with the pills and chemicals people! Sunshine and food is medicine ! Concentrate on finding organic & pasture-reared food and getting outside daily and you will get and be able to optimally absorb all the vitamins in the quantities and combinations you need.

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