Thanks Robin! You obviously know a lot about 25-hydroxyvitamin D and nutraceuticals. I personally wouldn't be without my 25-hydroxyvitamin D, vitamin C or Mg. In September of 21, I had Influenza "A" and a week later COVID Omicron and at 74 years I was sick for about 36 hours. When COVID first came out I was still practicing. Since we could be punished severely for original speech or even original thought, we kept our little clinic flying below the radar...one of the advantages of being rural. CMS finds us neither in good times nor bad. We broke all the "rules." We saw people the day they called, and gave them routinely vitamin D, C, Mg, and zithromax. They all got well. Nobody died, and nobody got sick enough to even be hospitalized. We did have three hospital deaths for people who had NOT been seen in the clinic.
As I said in my article, regarding avoidable death, in obstetrics, dying from bleeding or sepsis should both be never events. In residency we get to see what works and what doesn't work and at least when I was there we could learn vicariously. We didn't need to make all the mistakes of others, so I wonder what our residents are being taught and who is doing the teaching.
Sepsis killed about 11 million people, worldwide, in 2017: https://www.thelancet.com/ journals/lancet/article/PIIS0140-6736(19)32989-7/. The toll of suffering and lasting harm goes well beyond this.
Sepsis would be rare if everyone had the the 50 ng/mL (125 nmol/L = 1 part in 20,000,000 by mass) level of circulating 25-hydroxyvitamin D which the immune system needs to function properly. Many doctors are aiming for only 20 ng/mL 50 nmol/L - but this is just what the kidneys need to play their part in regulating calcium-phosphate-bone metabolism.
This is very simple and of immense importance. Many people cannot imagine that such a vast range of problems could be solved or greatly reduced by such a simple nutritional supplement - and they are understandably wary of over-hyped nutrients.
Please see the research cited and discussed regarding the vitamin D compounds and the immune system, at: https:// vitamindstopscovid.info/00-evi/.
This begins with recommendations from New Jersey based Professor of Medicine, Sunil Wimalawansa on the average daily supplemental intake quantities of vitamin D3 which will attain least 50 ng/mL circulating 25-hydroxyvitamin D, over several months, without the need for blood tests or medical monitoring:
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).
For 70 kg (154 lb) body weight without obesity, this is about 0.125 milligrams (125 micrograms 5000 IU) a day. This takes several months to attain the desired > 50 ng/mL circulating 25-hydroxyvitamin D. This is 8 or more times what most governments recommend. "5000 IU" a day sounds like a lot, but it is a gram every 22 years - and pharma-grade vitamin D costs about USD$2.50 a gram ex-factory.
These recommendations are included in a recent article with another professor of medicine Scott T. Weiss and professor of pediatrics Bruce W. Hollis: https:// www.mdpi.com/2072-6643/16/22/3969. All three have been researching vitamin D for decades.
A properly functioning immune system would suppress most of the viral or bacterial infections which lead to sepsis well before they grew so pervasive as to trigger the massive inflammatory (indiscriminate cell destruction) immune response which characterizes sepsis.
Even if so triggered, if the immune system has the 50 ng/mL or more circulating 25-hydroxyvitamin D it needs for its cells to run their intracrine (inside each cell) and paracrine (to nearby cells, often of different types) signaling systems, there would be much less chance of the disastrous, organ destroying, inflammatory response developing.
See Chauss et al.'s 2021 (Nobel Prize worthy, I think) elucidation of 25-hydroxyvitamin D -> calcitriol intracrine signaling in Th1 regulatory lymphocytes. They mistakenly called it "autocrine" signaling, which involves receptors on the cell surface. Lack of 25-hydroxyvitamin D causes these cells to remain stuck in their pro-inflammatory startup program, never transitioning to their anti-inflammatory shutdown program, despite detecting the condition which activates the intracrine signaling process which, with sufficient 25-hydroxyvitamin D, will achieve this. This is a dense cell-biology article https:// www.nature.com/articles/s41590-021-01080-3. It may help to refer to my attempt at summarizing its most important elements: https:// aminotheory.com/cv19/icu/#2021-Chauss.
Neither vitamin D3 cholecalciferol nor 25-hydroxyvitamin D calcifediol, made from vitamin D3, primarily in the liver, are hormones. Approximately 1/4 of ingested or UV-B -> skin produced vitamin D3 is converted into circulating 25-hydroxyvitamin D.
25-hydroxyvitamin D is a different molecule, with a totally different function in the body than vitamin D3. 25-hydroxyvitamin D is tested in "vitamin D" blood tests, since vitamin D3 is hydroxylated, primarily in the liver to form the circulating 25-hydroxyvitamin D on which the kidneys and many types of immune cell (and some other cell types) depend. Without adequate supplies of 25-hydroxyvitamin D the intracrine and paracrine signaling systems cannot work, so individual cells are no longer able to respond rapidly and fully to their changing circumstances.
These are unrelated to hormonal (endocrine) signaling. Since, as far as I know, there are no tutorial explanations of 25-hydroxyvitamin D -> calcitriol (1,25-dihydroxyvitamin D) intracrine and paracrine signaling, I wrote a non peer reviewed tutorial in late 2020: https://vitamindstopscovid.info/02-intracrine/.
A less detailed tutorial is at the start of: https://vitamindstopscovid.info/00-evi/. Every doctor, nurse, immunologist, vaccinologist, virologist etc. needs to understand these signaling systems - but most have never heard of them. Most people who write vitamin D research articles have either never heard of these signaling systems or have only a vague understanding of them. They should read Chauss et al. and the earlier work of Prof. Martin Hewison and colleagues in the late 2000s, who originally discovered these signaling systems. I think these two bodies of work are Nobel Prize worthy.
Other than maintaining breathing and proper blood pressure, the most urgently needed intervention for someone suffering from sepsis is to boost their circulating 25-hydroxyvitamin D level safely over 50 ng/mL. Many people have half to one tenth of this. Severe illnesses can somewhat deplete the level.
Ordinary healthy daily intakes of vitamin D3, such as 0.125 mg 5000 IU, are not much use since this takes a few months to raise 25-hydroxyvitamin D levels from typical 10 to 25 ng/mL baseline levels to 50 ng/mL or more.
To boost circulating 25-hydroxyvitamin D in clinical emergencies, a loading (bolus = single, large) dose of 10 mg (400,000 IU) for average weight adults will raise the level safely over 50 ng/mL in several days, since it takes time for it to be hydroxylated in the liver. The best approach, as recommended by Prof. Wimalawansa, is a single oral dose of about 1 mg of calcifediol (for 70 kg body weight), which *is* 25-hydroxyvitamin D. This is easily absorbed and goes straight into circulation in the bloodstream. This will raise the 25(OH)D level safely over 50 ng/mL in about 4 hours. https://vitamindstopscovid.info/00-evi/#4.7.
The annual toll of suffering, harm and death from sepsis rivals that of COVID-19 at its peak.
It took decades for the benefits of hand-washing to be recognised, and centuries for vitamin C to be fully recognised as essential for preventing scurvy - this was discovered and forgotten many times.
History will record these decades as being blighted by ignorance of the research which shows clearly that the immune system only works well with more 25-hydroxyvitamin D than most people have today.
Thanks Robin! You obviously know a lot about 25-hydroxyvitamin D and nutraceuticals. I personally wouldn't be without my 25-hydroxyvitamin D, vitamin C or Mg. In September of 21, I had Influenza "A" and a week later COVID Omicron and at 74 years I was sick for about 36 hours. When COVID first came out I was still practicing. Since we could be punished severely for original speech or even original thought, we kept our little clinic flying below the radar...one of the advantages of being rural. CMS finds us neither in good times nor bad. We broke all the "rules." We saw people the day they called, and gave them routinely vitamin D, C, Mg, and zithromax. They all got well. Nobody died, and nobody got sick enough to even be hospitalized. We did have three hospital deaths for people who had NOT been seen in the clinic.
As I said in my article, regarding avoidable death, in obstetrics, dying from bleeding or sepsis should both be never events. In residency we get to see what works and what doesn't work and at least when I was there we could learn vicariously. We didn't need to make all the mistakes of others, so I wonder what our residents are being taught and who is doing the teaching.
Sepsis killed about 11 million people, worldwide, in 2017: https://www.thelancet.com/ journals/lancet/article/PIIS0140-6736(19)32989-7/. The toll of suffering and lasting harm goes well beyond this.
Sepsis would be rare if everyone had the the 50 ng/mL (125 nmol/L = 1 part in 20,000,000 by mass) level of circulating 25-hydroxyvitamin D which the immune system needs to function properly. Many doctors are aiming for only 20 ng/mL 50 nmol/L - but this is just what the kidneys need to play their part in regulating calcium-phosphate-bone metabolism.
This is very simple and of immense importance. Many people cannot imagine that such a vast range of problems could be solved or greatly reduced by such a simple nutritional supplement - and they are understandably wary of over-hyped nutrients.
Please see the research cited and discussed regarding the vitamin D compounds and the immune system, at: https:// vitamindstopscovid.info/00-evi/.
This begins with recommendations from New Jersey based Professor of Medicine, Sunil Wimalawansa on the average daily supplemental intake quantities of vitamin D3 which will attain least 50 ng/mL circulating 25-hydroxyvitamin D, over several months, without the need for blood tests or medical monitoring:
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).
For 70 kg (154 lb) body weight without obesity, this is about 0.125 milligrams (125 micrograms 5000 IU) a day. This takes several months to attain the desired > 50 ng/mL circulating 25-hydroxyvitamin D. This is 8 or more times what most governments recommend. "5000 IU" a day sounds like a lot, but it is a gram every 22 years - and pharma-grade vitamin D costs about USD$2.50 a gram ex-factory.
These recommendations are included in a recent article with another professor of medicine Scott T. Weiss and professor of pediatrics Bruce W. Hollis: https:// www.mdpi.com/2072-6643/16/22/3969. All three have been researching vitamin D for decades.
A properly functioning immune system would suppress most of the viral or bacterial infections which lead to sepsis well before they grew so pervasive as to trigger the massive inflammatory (indiscriminate cell destruction) immune response which characterizes sepsis.
Even if so triggered, if the immune system has the 50 ng/mL or more circulating 25-hydroxyvitamin D it needs for its cells to run their intracrine (inside each cell) and paracrine (to nearby cells, often of different types) signaling systems, there would be much less chance of the disastrous, organ destroying, inflammatory response developing.
See Chauss et al.'s 2021 (Nobel Prize worthy, I think) elucidation of 25-hydroxyvitamin D -> calcitriol intracrine signaling in Th1 regulatory lymphocytes. They mistakenly called it "autocrine" signaling, which involves receptors on the cell surface. Lack of 25-hydroxyvitamin D causes these cells to remain stuck in their pro-inflammatory startup program, never transitioning to their anti-inflammatory shutdown program, despite detecting the condition which activates the intracrine signaling process which, with sufficient 25-hydroxyvitamin D, will achieve this. This is a dense cell-biology article https:// www.nature.com/articles/s41590-021-01080-3. It may help to refer to my attempt at summarizing its most important elements: https:// aminotheory.com/cv19/icu/#2021-Chauss.
Neither vitamin D3 cholecalciferol nor 25-hydroxyvitamin D calcifediol, made from vitamin D3, primarily in the liver, are hormones. Approximately 1/4 of ingested or UV-B -> skin produced vitamin D3 is converted into circulating 25-hydroxyvitamin D.
25-hydroxyvitamin D is a different molecule, with a totally different function in the body than vitamin D3. 25-hydroxyvitamin D is tested in "vitamin D" blood tests, since vitamin D3 is hydroxylated, primarily in the liver to form the circulating 25-hydroxyvitamin D on which the kidneys and many types of immune cell (and some other cell types) depend. Without adequate supplies of 25-hydroxyvitamin D the intracrine and paracrine signaling systems cannot work, so individual cells are no longer able to respond rapidly and fully to their changing circumstances.
These are unrelated to hormonal (endocrine) signaling. Since, as far as I know, there are no tutorial explanations of 25-hydroxyvitamin D -> calcitriol (1,25-dihydroxyvitamin D) intracrine and paracrine signaling, I wrote a non peer reviewed tutorial in late 2020: https://vitamindstopscovid.info/02-intracrine/.
A less detailed tutorial is at the start of: https://vitamindstopscovid.info/00-evi/. Every doctor, nurse, immunologist, vaccinologist, virologist etc. needs to understand these signaling systems - but most have never heard of them. Most people who write vitamin D research articles have either never heard of these signaling systems or have only a vague understanding of them. They should read Chauss et al. and the earlier work of Prof. Martin Hewison and colleagues in the late 2000s, who originally discovered these signaling systems. I think these two bodies of work are Nobel Prize worthy.
Other than maintaining breathing and proper blood pressure, the most urgently needed intervention for someone suffering from sepsis is to boost their circulating 25-hydroxyvitamin D level safely over 50 ng/mL. Many people have half to one tenth of this. Severe illnesses can somewhat deplete the level.
Ordinary healthy daily intakes of vitamin D3, such as 0.125 mg 5000 IU, are not much use since this takes a few months to raise 25-hydroxyvitamin D levels from typical 10 to 25 ng/mL baseline levels to 50 ng/mL or more.
To boost circulating 25-hydroxyvitamin D in clinical emergencies, a loading (bolus = single, large) dose of 10 mg (400,000 IU) for average weight adults will raise the level safely over 50 ng/mL in several days, since it takes time for it to be hydroxylated in the liver. The best approach, as recommended by Prof. Wimalawansa, is a single oral dose of about 1 mg of calcifediol (for 70 kg body weight), which *is* 25-hydroxyvitamin D. This is easily absorbed and goes straight into circulation in the bloodstream. This will raise the 25(OH)D level safely over 50 ng/mL in about 4 hours. https://vitamindstopscovid.info/00-evi/#4.7.
The annual toll of suffering, harm and death from sepsis rivals that of COVID-19 at its peak.
It took decades for the benefits of hand-washing to be recognised, and centuries for vitamin C to be fully recognised as essential for preventing scurvy - this was discovered and forgotten many times.
History will record these decades as being blighted by ignorance of the research which shows clearly that the immune system only works well with more 25-hydroxyvitamin D than most people have today.