Table of contents
- Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19
- VitaminDWiki – COVID-19 treated by Vitamin D - studies, reports, videos
- A few publications on 50 ng of Vitamin D to fight COVID
- 40-150 ng of Vitamin D need to treat various health problems
- See also VitaminDWiki
- Nomograms of 50K dosing to get to 50 ng
- Comments by readers on this publication
- VitaminDWiki videos with TRANSCRIPT in title
Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19
Nutrients 2022, 14, 2997. https:// doi.org/10.3390/nu14142997
Sunil J. Wimalawansa Endocrinology & Nutrition, Department of Medicine, Cardiometabolic & Endocrine Institute, North Brunswick, NJ 08873, USA; suniljw at hotmail.com
PDF Table of Contents
Most of the figures and tables
A suitable daily or weekly maintenance dose to be started after completing the loading-dose schedule. The dose should be adjusted for those who are overweight (higher) or underweight (lower). ** To convert ng/mL to nmol/L, multiply the amount in ng by 2.5; One ug = 40 IU. $ Mentioned replacement doses can be taken as single, cumulative doses, two to three times a week spread out over a few weeks. $$ From the day one of week two onwards. # Estimated total vitamin D dose needed to replenish the body stores (i.e., the deficit) is provided in the last column.
Example of a daily or once-a-week dose range for adults with specific body types (based on BMI for white Caucasians and body weight for other ethnic groups). Appropriate dose reductions are necessary for children. #For those with chronic comorbid conditions, such as hypertension, diabetes, asthma, COPD, CKD, depression, and osteoporosis, and to reduce all-cause mortality, higher doses of vitamin D are needed. For them, one can use the doses that are recommended for persons with obesity (BMI, 30-39: the third row). $ Those with multiple sclerosis, cancer, migraine headaches, and psoriasis, and those routinely taking medications such as anti-epileptic and anti-retroviral agents that significantly increase the catabolism of vitamin D should consider taking age- appropriate doses recommended for those with morbid obesity (BMI > 40; the higher end of the daily doses in the fourth row).
Calcifediol [partially activated vitamin D3, 25(OH)D]. ** Use the earliest possible in person with COVID-19, sepsis, Kawasaki disease, multisystem inflammatory syndrome, acute respiratory distress syndrome, burns, and vitamin D deficiency in early pregnancy and other clinical emergencies. # Measurement (or the concentration) of serum 25(OH)D is unnecessary. ## If calcifediol is unavailable, the equivalent dose of vitamin D is administered, as illustrated in Table 2, preferably in divided doses over three to five days. Irrespective of the regimen used, daily or weekly follow-up maintenance vitamin D dose is necessary as described in the text.
Abstract
Vitamin D deficiency is a global public health problem, a pandemic that commonly affects the elderly and those with comorbidities such as obesity, diabetes, hypertension, respiratory disorders, recurrent infections, immune deficiency, and malignancies, as well as ethnic minorities living in temperate countries. The same groups were worst affected by COVID-9. Since vitamin D deficiency weakens the immune system, it increases the risk of infections, complications, and deaths, such as from sepsis and COVID-19. Deficiency can be remedied cost-effectively through targeted food fortification, supplementation, and/or daily safe sun exposure. Its endocrine functions are limited to mineral metabolism, musculoskeletal systems, specific cell membrane interactions, and parathyroid gland functions.
Except for the rapid, endocrine, and cell membrane-based non-genomic functions, all other biological and physiological activities of vitamin D depend on the adequate intracellular synthesis of 1,25(OH)2D (calcitriol) in peripheral target cells via the genome.
Calcitriol mediates autocrine (intracrine) and paracrine signalling in immune cells, which provides broader, protective immune functions crucial to overcoming infections. The synthesis of 1,25(OH)2D (calcitriol) in peripheral target cells is dependent on diffusion and endocytosis of D3 and 25(OH)D from the circulation into them, which requires maintenance of serum 25(OH)D concentration above 50 ng/mL.
Therefore, in acute infections such as sepsis and respiratory infections like COVID-19, it is necessary to rapidly provide its precursors, D3 and 25(OH)D, through the circulation to generate adequate intracellular calcitriol. Immune defence is one of the crucial non-hormonal functions of vitamin D.
A single oral (bolus) dose or divided upfront loading doses between 100,000 and 500,000 IU, using 50,000 IU vitamin D3 increase the serum 25(OH)D concentrations to a therapeutic level of above 50 ng/mL that lasts between two to three months.
This takes three to five days to raise serum 25(OH)D. In contrast, a single oral dose of calcifediol (0.014 mg/kg body weight) can generate the needed 25(OH)D concentration within four hours.
Considering both D3 and 25(OH)D enter immune cells for generating calcitriol, using the combination of D3 (medium-term) and calcifediol (immediate) is cost-effective and leads to the best clinical outcome.
To maximise protection against infections, particularly to reduce COVID-19-associated complications and deaths, healthcare workers should advise patients on safe sun exposure, adequate vitamin D supplementation and balanced diets containing zinc, magnesium, and other micronutrients to support the immune system.
Meanwhile, governments, the World Health Organisation, the Centers for Disease Control, and governments should consider similar recommendations to physicians and the public, change the outdated vitamin D and other micronutrient recommendations directed to their population, and organise targetted food fortification programs for the vulnerable groups.
This article discusses a rational approach to maintaining a sustained serum 25(OH)D concentration above 50 ng/mL, necessary to attain a robust immune system for overcoming infections. Such would cost-effectively improve the population's health and reduce healthcare costs. It also describes three cost-effective, straightforward protocols for achieving and sustaining therapeutic serum 25(OH)D concentrations above 50 ng/mL (>125 nmol/L) to keep the population healthy, reduce absenteeism, improve productivity, and lower healthcare costs.
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Conclusions
A robust immune system is essential to overcome infections without complications. It depends on the adequate entry of vitamin D3 and 25(OH)D into immune cells for generating calcitriol. The latter required maintaining a serum 25(OH)D concentration of over 50 ng/mL. Therefore, to successfully manage and overcome an infectious epidemic or a pandemic, it is crucial to maintain the population's serum 25(OH)D concentration above the mentioned therapeutic level.
In acutely ill persons, especially those with vitamin D deficiency having infections, raising serum D3 and 25(OH)D concentrations quickly is paramount and life-saving. In these urgent situations, 0.5 to 1.0 mg of calcifediol can raise serum 25(OH)D concentrations above the minimum therapeutic levels of 50 ng/mL in four hours and boosts the immune system within a day that facilitates to overcome infections.
While calcifediol raises serum 25(OH)D within hours, the oral administration of even high doses of vitamin D takes three to five days to raise serum 25(OH)D concentrations. This delay is due to its less efficient absorption than calcifediol and the need for vitamin D to undergo 25-hydroxylation in the liver, a rate-limiting step. In acutely ill patients, as in those in the ICU, administering even high doses of oral D3 may take a week to increase serum 25(OH)D concentration. Therefore, it is unhelpful in emergencies like SARS-CoV-2 infections.
With a weight-based, single dose of calcifediol, as described in Table 3, circulatory 25(OH)D concentrations are maintained for approximately 8 to 14 days. In contrast, parental high dose vitamin D3, administered as loading or bolus, will maintain serum 25(OH)D concentrations between two to three months. Although the circulatory half-life of D3 is short, due to the larger initial doses, it maintains a higher circulatory concentration of both D3 and 25(OH)D for several weeks—partly because of the release from the storage in fat and muscle tissues.
Therefore, with calcifediol, one should administer a suitable higher dose of vitamin D3. This can be done using 50,000 IU vitamin D capsules in outpatients' setups and emergencies, as illustrated in Table 3. Nevertheless, considering the non-genomic beneficial actions of vitamin D3 and its longer duration of physiological actions described above, the combination of D3 and calcifediol provides better clinical outcomes than either alone. Therefore, administering the proper doses of D3 and calcifediol is recommended for patients with infections as an adjunct therapy at the first outpatient or inpatient encounter.
Multiple observational and RCTs have demonstrated that serum 25(OH)D concentrations (pre-infection or on admission) inversely correlated with the incidence, severity, and rates of death from COVID-19 [45,55,56,153. Meanwhile, vitamin D supplementation significantly reduces complications and deaths [33,44,45,150,154]. Irrespective of the regimen, initial bolus or loading doses of vitamin D and/or calcifediol should follow a daily or weekly, longer-term maintenance regimen [11,118,155].
The described schedules in the three tables are highly cost-effective ways to raise serum 25(OH)D concentrations and maintain it to keep the immune system on high alert. Consequently, it prevents and/or reduces infections and complications from COVID-19 and other infections. For non-obese 70 kg adults, the recommended longer-term vitamin D3 maintenance dose is 5000 IU/(0.125 gg) day or 50,000 IU (1.25 mg)/week (or every ten days). Nevertheless, this regimen takes a few months to reach the desired serum 25(OH)D concentration above 50 ng/mL. It can be expedited by ingesting vitamin D, 10,000 IU/day (250 gg/day) for 8 to 10 weeks and reverting to the daily dose of 5000 IU.
Rectifying vitamin D deficiency costs less than 0.1% of the costs related to evaluating and treating comorbidities and complications associated with vitamin D deficiency [156]. For example, in western countries, vitamin D supplementation to maintain serum 25(OH)D costs approximately $8 per person/year, versus an average cost of $5000 to $15,000/year per person to manage vitamin D deficiency-associated diseases and related complications [156]. Despite a favourable cost-benefit ratio, availability as a non-prescription over-the-counter nutrient, and exemplary safety profile, millions of people become ill due to vitamin D deficiency requiring medical attention, markedly increasing the cost of healthcare. Vitamin D deficiency increases healthcare costs, absenteeism and opportunity costs and reduces productivity.
Considering the described significant benefits associated with disease prevention, reduced illness severity, reduced absenteeism, complications and deaths, improved wellbeing and higher productivity, the calculated overall cost-benefit ratio for administered vitamin D3 supplements exceeds 1 in 20,000. Despite these data, no country is yet to recommend vitamin D (or has published proper guidelines with the right doses) for disease prevention or recommended it as an adjunct therapy to prevent complications and deaths from infections or other diseases. This report provides rationale, justifications, straightforward guidance, and practical tables that provide regimens for use in clinical practice for achieving and maintaining the serum 25(OH)D concentrations needed to ensure a robust immune system that helps to overcome infections, including SARS-CoV-2.
VitaminDWiki – COVID-19 treated by Vitamin D - studies, reports, videos
As of March 31, 2024, the VitaminDWiki COVID page had: trial results, meta-analyses and reviews, Mortality studies see related: Governments, HealthProblems, Hospitals, Dark Skins, All 26 COVID risk factors are associated with low Vit D, Fight COVID-19 with 50K Vit D weekly Vaccines Take lots of Vitamin D at first signs of COVID 166 COVID Clinical Trials using Vitamin D (Aug 2023) Prevent a COVID death: 9 dollars of Vitamin D or 900,000 dollars of vaccine - Aug 2023
5 most-recently changed Virus entries
A few publications on 50 ng of Vitamin D to fight COVID
- Is 50 ng of Vitamin D enough to fight COVID - TrialSiteNews - Jan 2024
- COVID etc. prevented and treated with 50,000 IU Vitamin D capsules - July 2022
- Discussion of COVID and 50 ng of Vitamin D (video and transcript)– Dr. Campbell Nov 17, 2021
- COVID probably fought by Vitamin D, might need 50 ng - Dr. Patrick Nov 8, 2021
- COVID-19 mortality extrapolates to zero at 50 ng of vitamin D – 18th Meta-analysis Sept 2021
- Vitamin D and COVID, review of evidence, loading dose if less than 50 ng - Masterjohn Sept 2021
- T-cells need at least 40-50 ng of Vitamin D to fight COVID-19 - June 2021
- COVID-19 prognostic indicators in plasma extrapolate to zero if Vitamin D is 40 to 80 ng – March 2021
- To protect against COVID-19, how much vitamin D – 20 to 50 ng – March 19, 2021
40-150 ng of Vitamin D need to treat various health problems
Vitamin D | Treats |
150 ng | Multiple Sclerosis * |
80 ng | Cluster Headache * Reduced office visits by 4X * |
70 ng | Sleep * |
60 ng | Breast Cancer death reduced 60% Preeclampsia RCT |
50 ng | COVID-19 T1 Diabetes Fertility Psoriasis Infections Review Infection after surgery |
40 ng | Breast Cancer 65% lower risk Depression ACL recovery Hypertension Asthma? |
30 ng | Rickets |
* Evolution of experiments with patients, often also need co-factors
See also VitaminDWiki
- Sepsis is both prevented and treated by Vitamin D - many studies
- Vitamin D helps both the innate and adaptive immune systems fight COVID-19 – Jan 2022
- Is 50 ng of vitamin D too high, just right, or not enough
- Take lots of Vitamin D at first signs of COVID
- Can get 50,000 IU Vitamin D anywhere on the globe
Wimalawansa
- COVID-19 Vitamin D Overview - Sunil video and transcript - Dec 8, 2020
- Boosting Immunity with Vitamin D to reduce COVID-19 risks - Aug 2021
- FLCCC COVID guidelines now include vitamin D loading doses - Jan 2022
Nomograms of 50K dosing to get to 50 ng
Suggested dosing to get 50 ng of Vitamin D (if healthy) - July 2022 - based on Wimalawansa
Horizonal axes: body weight Black = kilograms, Red = pounds
Vertical dose axis: Black = milligrams or IU
Vertical dose axis: Blue= IU per week;
Vertical dose axis:Purple = days between 50,000 IU capsules
Comments by readers on this publication
Thanks Henry - this is one of the best, accurate papers I've read. I believe differently concerning the calcifediol than the authors - of course, giving 25-OH D (calcifediol) is going to have a higher measured 25-OH D level - but that does not necessarily mean that the amount of fully activated D (1,25) is any less than required by the body. I believe that since D can be fully activated ih the periphery, as well as deactivated, that this is a push-through phenomenon. Provided that enough D3 is given such that the liver capacity to 25-OHylate is saturated (about 15-20,000 IU/day D3) that the body will push-through activate what is needed, where it is needed, in the amount needed and deactivated when no longer needed. This is likened to the function of the common light switch on the wall.
If you look at this site listed below - you'll see why I don't want to implant the idea that docs should be instructing patients to take or hospitals to have calcifediol on the formulary. Dave M
https://clincalc.com/DrugStats/Drugs/Calcifediol
Thank you Sunil,
This is most comprehensive. I think it helps that it is very repetitive on certain points. There's nothing like repetition to make sure a point is made! The 50 ng/mL minimal ideal level may have been mentioned 50 times and the importance of the half-iife almost as often, but this is the point of the article, to not allow anyone to be able to ignore these finding. I like the allowance for, and even recommendation for bolus dosing, but with guidelines on maximum days between doses.
I also appreciate the particulars, early in the document, on some of the exact ways immune system integrity is maintained:
"As described in the next section, 25(OH)D and 1,25(OH)2D also mediate rapid non-genomic actions that are vital for some physiological actions, including endocytotic cellular entry of precursors, the integrity of tight junctions in epithelial and endothelial cells, and immune responses."
It seems endothelial cell boundaries in both vascular and intestinal tissue will be compromised significantly without significant levels of vitamin D:
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803557/
- https://pubmed.ncbi.nlm.nih.gov/17962355/
- https://pubmed.ncbi.nlm.nih.gov/21115878/
I'm guessing Henry has references to these vitamin D insufficiency situations, but I did not bother to search his site. I'm just happy to see some specifics on some of the immune system impairments possible if one is low in 25(OH)D.
Glenn Atkisson, Saint Clouid, FL, USA
VitaminDWiki videos with TRANSCRIPT in title
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