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Information about Vitamin-D3 (Cholecalciferol).

When Vitamin-D is mentioned it is going to refer to Vitamin-D3 unless it is clear from context that it is referring to both Vitamin-D2 and Vitamin-D3.

Where ever possible both sets of alternate units to indicate serum concentrations and dose amounts will be used to make the text easier to parse for readers from all regions.

(Cholecalciferol)
This is to be a collection of information relating to Vitamin-D3, this has the chemical name of Cholecalciferol and is considered a sterol pro-hormone. It was categorised as a vitamin initially before the UVB mediated synthesis in skin was established, this designation has firmly persisted and has good and bad implications. A lot of information is available on the web and a good starting place is Wikipedia. This site is intended to provide information that is available somewhere but many or even most people will not know that the information even exists. The goal is to have a answers to questions that you did not know to ask.

The main reason for my interest in Vitamin-D is the huge potential that proper management of population wide supplementation could have on human health and health care costs due to the global Vitamin-D deficiency pandemic. Because there is money involved in health care this issue will be considered here from a few angles, some of the ideas will be controversial but this is because the amount of money involved is so massive.

I make a note here to indicate that this site is still in its infancy and the layout is sure to change and evolve. I will be doing much of the editing myself but will welcome other editors who have similar goals. I hope to leave this in a state that will provide suitable information to assist advocates and activists to promote the rational discussion about Vitamin-D and putting false myths to rest. A lot of medical research will be quoted from and global programs will be mentioned.

Many of these topics will open onto more detailed pages.

Deficiency
Many causes for deficiency

Protective

 * Lighter skin
 * Rare mutations

Aggravating

 * Darker Skin
 * Rare Mutations

Disease
Gall bladder removal
 * Diabetes
 * Kidney disease

Global

 * Solar cycles
 * Air Pollution
 * Urbanisation
 * Polar migration / Latitude

Mean Vitamin D levels in 19 European Countries & COVID-19 Mortality over 10 months

Seasonal
Serum variability as well as serum deficiency may both be risk factors.

https://www.youtube.com/watch?v=MIDWA9-cGdY

Seasonal fluctuation can best be mitigated by regular physiological level supplementation.

Winter

 * UVB inadequacy low sun angle and daylight hours
 * Dressing for cold
 * Less holidays

Summer

 * Avoiding sun
 * Dressing for modesty
 * Mid day siesta
 * Monsoon weather

Work place
Space Arctic Submariner Shift worker , Institutionalised ====

Skin
We synthesize The vitamin in the epidermis from a common precursor 7-Dhydrocholesterol that is used to make all our secosteroidal hormones.

Sun
Tropospheric Emission Monitoring, Internet Service database may provide solar UVB data

Ambient UVB Dose and Sun Enjoyment Are Important Predictors of Vitamin D Status in an Older Population1–3

Fiona OSullivan, Eamon Laird, Dervla Kelly, Jos van Geffen, Michiel van Weele, Helene McNulty, Leane Hoey, Martin Healy, Kevin McCarroll, Conal Cunningham, Miriam Casey, Mary Ward, JJ Strain, Anne M Molloy, and Lina Zgaga

doi:10.3945/jn.116.244079

https://fastrt.nilu.no/VitD.html

UVB therapy
Used already in second world war.

Used by submariners.

Tested by military personel in USA recently.

Heliotherapy
Solariums used to have open sun decks. They were situated in high mountains (like the Alps) to gain altitude and freedom from airborne pollution and be south facing all to maximise the production of Vitamin-D3 (before they knew what it was). Their benefits were reduced when the balconies were enclosed by glass to allow patients to enjoy the sun in colder weather but without the UVB rays so no more Vitamin-D3.

Diet
Mostly from marine oily fish livers and flesh. A report that farmed salmon had lower levels than free range has been made as they are often fed processed food.

Livers of carnivores are said to concentrate and be a rich source they have sometimes been blamed for Vitamin-D3 intoxication but more likely symptoms have been due to high Vitamin-A levels in bear or seal livers.

Some Vitamin-D2 can be had from sun dried mushrooms.

Industrial
The production is many stages of extraction and purification of the precursor, followed by a UVB irradiation at a preferred wavelength of ultraviolet light at a preferred temperature for a preferred time, followed by thermal isomerization and then further extraction and purification steps followed by dilution or compounding before shipping to customers either in a pure crystalline form of 40 million International Units per gramme (40MIU/g) or at various dilutions in oil (500kIU/g) or starch bases usually packed under inert gas free of metallic impurities that will degrade the product. Humidity, light and oxygen also degrade the product in shipment or final product storage.

"Vitamin D3 can be produced by irradiating the 7DHC ... with ultraviolet light, such as with a mercury lamp, followed by heating. The heating temperature is preferably 50 to 100° C., most preferably 80° C. to 100° C. The heating time is preferably 5 to 300 minutes, more preferably 10 to 100 minutes. The obtained vitamin D3 may be concentrated by using techniques such as high-performance liquid chromatography, and supercritical chromatography, and collected to obtain highly concentrated purified vitamin D3." - US20170204056A1

Lanolin
This is the most common form available to commerce. Those with a wool or lanolin allergy could avoid this form.

"methods used to extract cholesterol from wool. In particular, a skilled person may refer to the methods described in U.S. Pat. No. 2,688,623, or U.S. Pat. No. 2,650,929, or British Patent No. GB690879, GB646227, or GB613778." - US20170204056A1

Lichen
A vegan alternative. A form of Vitamin-D3 prepared from a few species of Nordic Lichen

Seaweed
A vegan alternative. A form of Vitamin-D3 prepared from a species of Australian sea weed

https://patents.google.com/patent/US20110207952A1/en

Mushrooms
Vitamin-D2: Still found in USA fortified foods and larger supplement doses. Suitable for animal feed, not poultry

Yeast
Vitamin-D2: Still found in USA fortified foods and larger supplement doses. Suitable for animal feed, not poultry

Bacteria
Patent describing how to produce the 7-dehydrocholesterol precursor using a reduced SMT activity Labyrinthulea slime bacteria.

"The method for extracting 7DHC and other sterols from the cells of microorganisms is described in L. Parks et al. [Methods in Enzymology 111 Edited (1985) by L Ming, L. Parks, C. Bottema, R. Rodriguez and Thomas Lewis, p. 333-339]."

"The crude 7DHC thus obtained may be further purified by using a method known to a skilled person, in particular, the method described in Boselli E, Velazco V, Caboni Mf and Lercker G J, Chromatogr A. 2001 May 11;917 (1-2): 239-44." https://patents.google.com/patent/US20170204056A1/en

Patents

 * Preparation of vitamin d3 US2707710A (expired)
 * Process for the production of vitamin d3 US3661939A (expired)
 * Technological method for preparing vitamin D3 CN102276510A (pending)
 * Phototherapeutic apparatus for focused UVB radiation and vitamin D synthesis and associated systems and methods AU2018200369B2 (granted)
 * Photochemical process for the preparation of a previtamin d WO2008128782A2
 * Photolysis of 7-dehydrocholesterol EP0967202A1 (expired) (eximer lamp)
 * Method of production of vitamin-D US4388242A (expired) (laser)
 * Vitamin d3 EP0055999B1 (expired) (poor rats)
 * Photochemical process for the production of previtamin D3 US6180805B1 (expired)
 * Method for improved production of vitamins d2 and d3 JP2021059577A (pending)
 * A kind of vitamin D3Production technology CN106478479B (active)
 * Technology for preparing vitamin D3 CN102850248A (pending)
 * Vitamin D3Purification method of (2) CN110527700B (active) (enzymatic acylation method)
 * Irradiation process of pro vitamin d CA3137162A1 (pending)
 * Method for synthesizing vitamin D3 by segmenting and determining spectral bands CN112110841A (pending)
 * Process for the production of vitamin d3 US3661939A (expired)
 * Method for synthesizing pre-vitamin D3 by using LED ultraviolet lamp CN111960980A (pending)
 * Photochemical process for the preparation of a previtamin d CN101668739A (pending) (LED)
 * Phototherapy unit for creation of focused uv radiation and vitamin d synthesis and corresponding systems and methods RU2644752C2 (granted) (booth)
 * Wearable Ultraviolet Light Phototherapy Device US20190099613A1 (pending) (I also had this idea KMP)
 * Implant modified with non-hydroxylated vitamin D precursors US8821568B2 (active) (coated dental implants)
 * The method for detecting vitamin A and 25-hydroxy-vitamin D in blood simultaneously CN106442761B (active)
 * A cosmetic composition for blocking ultra violet comprising pro vitamin D3 KR101975387B1 (granted)
 * 7-dehydrocholesterol-contained cosmetic composition KR100322208B1 (granted) (stabilised for skin application)
 * Development of healthy and nutritional LED (Light Emitting Diode) light source apparatus CN105276518A (active)
 * Manufacturing method of 7-dehydrocholesterol and vitamin D3 ES2772259T3 (active)

Testing
Michael Hollick made advances in metabolite testing

VitaminD
Measurement of the primary dietary or synthesised substance Cholecalciferol is rare, partly due to the short half-life. It is also discussed as unbound or free and the bound amount that is associated with the Vitamin-D binding protein that transports it and the other metabolites which compete for the binding protein. The sulphate ion is also supposed to assist with transport and lipids have been proposed as a delivery vehicle and a transport mechanism.

25(OH)D3
Vitamin D 25-oh total (Testing Vitamin D2 & D3) £119.00
 * Mail in tests
 * Thin-film chroma assay, finger tip blood drop Point-of-Care test, puremed is one provider
 * Antibody
 * HPLC-MS/MS
 * UV fluorescence photometry (Zivak)

Some comparative information. August 2018 Product Focus: Vitamin D

1,25(OH)2D3
Rare

Other
Combined, 25(OH)D, 24,25(OH)2D, 1,25(OH)2D measurement technique has been used. [https://www.researchgate.net/publication/16860004_Simultaneous_measurement_of_125-dihydroxy-vitamin_D_2425-dihydroxy-vitamin_D_and_25-hydroxy-vitamin_D_from_a_single_two_milliliters_serum_specimen_Preliminary_clinical_application Simultaneous measurement of 1.25-dihydroxy-vitamin D, 24.25-dihydroxy-vitamin D and 25-hydroxy-vitamin D from a single two milliliters serum specimen. Preliminary clinical application]

Saliva
Mail in tests

Benefits
Please go to Vitamin D Wiki for the research on all the diseases that are better managed with Vitamin-D. This focuses on the regular benefits to health from natural levels with some obvious easy to demonstrate reversible conditions that can be used to advocate.

Congregate Living
[http://militaryhealth.bmj.com/ Does vitamin D supplementation prevent SARS-CoV-2 infection in military personnel? Review of the evidence]

Cancer
Dingli Song 2019 Vitamin D intake, blood vitamin D levels, and the risk of breast cancer: a dose-response meta-analysis of observational studies

Pregnancy
Reduce Preeclampsia

Dental

 * Reduce mouth bacteria
 * Promote implant ossification

Acute toxicity
Cholecalciferol is still used as a rodent poison, the idea is that because it is more toxic to rodents than other beneficial animals it has some value. The doses required to LD50 are so much greater than physiological or therapeutic doses it is not to be compared with supplement dosing dangers.

Bolus
100'000

Metabolites
Faster absorbtion Prompt action Lack of fat buffering

Food
Carnivore livers, excessive fish liver oil.

Sun
Practically not possible, self regulating. Sunburn and skin ageing more of a concern from excessive sun

Journals

 * Ilkka Laaksi 2010 Vitamin D Supplementation for the Prevention of Acute Respiratory Tract Infection: A Randomized, Double-Blinded Trial among Young Finnish Men
 * Sara R Zwart 2011 Response to vitamin D supplementation during Antarctic winter is related to BMI, and supplementation can mitigate Epstein-Barr Virus Reactivation
 * Scott M Smith 2008 Vitamin D supplementation during Antarctic winter

DOI For journal papers

Facebook
[https://www.facebook.com/groups/654795611751847/ Protect with Vitamin D against Covid-19! IMPORTANT!]

Web
Vitamin D Health

Vitamin D Council/

The Vitamin D Society

Vitamin D Wiki

VDMETA: Vitamin D is effective for COVID-19: real-time meta analysis of 71 studies VDMETA: Vitamin-D for CoViD-19

Shotwell: Vitamin D and Covid-19

Larry Brilliant: TED Prize wish: Help stop the next pandemic

Repository
This will be stuff that I have not added here yet.

Repository

Other sources
Quick links for the record

Other

Advocates
There are many advocates who promote Vitamin-D, their reasons vary a lot and they may share other goals and beliefs that are opposing or orthogonal to other advocates, this does not detract from the many sound and important reasons for advocating the correct use of Vitamin-D. Here is a list of advocates who hopefully agree to list their names here and some have edited these pages.

It does not take much to be a Vitamin-D advocate, you have six (6) main pathways, you may promote:
 * physiological serum targets,
 * physiological supplement doses,
 * nature identical forms (D3 as opposed to D2),
 * regular daily dosing
 * the need to address co-factors
 * debunk the myths of great harm

If you bring this important information to the notice of others you can call yourself a Vitamin-D advocate, that is all it takes to make the world a better place. You may appreciate all the main reasons or just one, you may have many other issues that are also relevant and you will see many of them described here.

Some of the advocates here will be prepared to respond to reasonable questions and try to assist you with understanding how things work. Some have busy schedules and do not have time to respond personally but you may find they have published relevant information on social media, medical journals, mass media or published books. There are a LOT of other advocates that do not appear here and some other lists will be linked here as they become available.

Each of these advocates will have their own reasons and strengths for advocating, some are from the medical field while others are simple citizen researchers.

Europe

 * Finland This directs to a page with mostly native Finnish advocates who write in Finnish text.
 * Finland, Kalle Pihlajasaari, Facebook, LinkedIn Recomendation, citizen researcher, wiki editor.
 * Greece, Hippocrates of Kos, Whoever wishes to investigate medicine properly should proceed thus: in the first place to consider the seasons of the year., 400B.C.
 * UK, Dr David Grimes, Covid-19 & Vitamin D – Haredi, BAME, Obese, Elderly at risk, Vitamin D and Cholesterol : Book details consultant physician and gastroenterologist

Americas

 * R. Edgar Hope-Simpson, The Transmission of Epidemic Influenza. New York: Plenum Press, 1992
 * John J. Cannell, The difference between a prophet and a madman, founder and  principal  of  the  educational organisation, the Vitamin D Council.
 * John J. Cannell, R. Vieth, J.C. Unhaus, Michael F. Holick, William B. Grant Epidemic influenza and vitamin D Epidemic influenza and vitamin D
 * Dakota Smith, Facebook, Citizen researcher
 * Dr. Alex Vasquez, Telegram Facebook Long term researcher and book publisher on nutrients and Vitmain-D
 * Alan Lewis, Quora Veteran wrote an interesting answer on 2010
 * Henry Lahore, Electronic Engineer, passionate Vitamin-D advocate, founder of Vitamin-D-Wiki
 * Michael F. Holick, Pioneer researcher and widely published. Wisdom we have lost Sunlight and Vitamin D - A global perspective for health, other published works can be searched for using "Holick and vitamin" at PubMed

Other

 * Australia, Robin Whittle, What every MD should know about vitamin D and the immune system

Historical errors
The IoM has a lot to answer for. They proposed reference values for those that fortify food products with Vitamin-D. They made assumptions based on physiological minimum needs that were required to hold off Rickets. Then they were cautious and determined incorrectly the dose that would maintain 95% of the population above this minimum level. These errors have been shown but there has never been a official correction to their papers. These errors were propagated into other heath bodies and used to drive clinical practice and treatment for deficiencies. They linger in all corners of the world still today even though they are based on shown mathematical errors.

Research negligence
Much of the nutrition research is left in the hands of University research centres and small observational trials by interested individuals. Funding is much less than what is received for drug trials in general. There are simple reasons for this that are not really controversial, Private companies have little reason to fund research that will reduce their profits, in simple terms we can say that it would be NEGLIGENT for a drug company COO or CEO or director whoever to authorise research into nutrition or supplements as there is NO resulting income from positive results. They do occasionally seem to be involved in research that has poor results but these studies and papers are often of such a calibre that they should be withdrawn in shame or at least the conclusions should be neutral.

Measurement variability
The enduring failure in Vitamin-D research is the misguided belief in a inverse "J" or "U" shaped curve in the benefits of dosing and the turning point has been assumed to be at a level much below natural levels which is physiologically unbelievable. This belief is a result of just a few published papers that have since been shown to have errors in data collection due to less than linear measurement systems for determining the 25(OH)D concentrations.

Ergocalciferol / Vitamin-D2
At various points in history the wholesale cost of Ergocalciferol has been below that of Cholecalciferol and it has been proposed and implemented as an alternative, these days the costs are similar. It has very similar chemical structure and also has similar function in humans. However the differences are not insignificant. Firstly the life time of Vitamin-D2 and the metabolites differ from those of Vitamin-D3. The effect is less than the same mass of Vitamin-D3 by a factor of 2 to 3 in various trials. For maternal expression in breast milk it did not provide the function that Vitamin-D3 did for the lactating infant. Some say it is less toxic than Vitamin-D3 but this hardly matters, you need to take more and you should not be near any toxic doses when seeking physiological doses or serum levels. Another added concern is that current measurement techniques do not give accurate results if you have both metabolites in your serum as the sensing peaks overlap. There is one company (Zivak) that makes a dedicated high speed blood analyser that seems to be up to the task but it is a substantial investment if you do not have enough use for it.

It has been promoted as a vegetarian alternative being usually prepared from fungal or yeast sources and is an option though vegan sources of Vitamin-D3(precursors) have been isolated and prepared from lichen and seaweed in recent years.

The Vitamin-D debate seminar came to the conclusion that it should be avoided due to the many negative points and no additional benefits even when the negative points are compensated for.

In spite of this it is in common use in the USA for humans as a supplement and also to be found many of the high potency forms used in treatment and medical trials which can have poor results for this reason as well. "In 2018, it was the 61st most commonly prescribed medication in the United States, with more than 12 million prescriptions."

"in France, China and the USA, where vitamin D2-containing supplements are frequently used"  [LC–MS/MS based 25(OH)D status in a large Southern European outpatient cohort: gender- and age-specific differences]

"Vitamin D2 potency is less than one third that of vitamin D3. Physicians resorting to use of vitamin D2 should be aware of its markedly lower potency and shorter duration of action relative to vitamin D3.", "Another barrier is the lack of a high-potency therapeutic vitamin D3 preparation in the United States. In Europe, several high-potency preparations are available, some used for “stoss” therapy in clinical trials" Vitamin D2 Is Much Less Effective than Vitamin D3 in Humans

It is important to remember that Vitamin-D2 does not work at all in farmed fowls, they develop rickets and fail to thrive if the only source of Vitamin-D is Vitamin-D2 from feed. While Vitamin-D2 has been used for other animal feeds it is not favoured due to the extra management of two supplements and need to ensure that chicken feed does not get the wrong supplement.


 * 10.1093/ajcn/68.4.854
 * 10.1093/ajcn/84.4.694
 * 10.1210/jc.2010-2230
 * 10.1111/nbu.12293
 * 10.4158/EP-2018-0415

A long list starting from here. DOI

Clinical trials
The Vitamin-D Meta collection seems comprehensive.

Europe

 * UK, Scotland, from late 2020 providing a small dose 20ug (800IU) of Vitamin-D to all care home residents and the vulnerable who have been shielding at home.
 * UK, England, from the start of 2021 in a response to the Scotland initiative for an initial 4 months a rollout of providing a small dose 20ug (800IU) of Vitamin-D to all care home residents and the vulnerable who have been shielding at home.
 * UK, Slough - recommendation?
 * Ireland, The Joint Committee on Health puts in place plan to sort out Vitamin-D deficiecny. Report on addressing Vitamin D deficiency as a public health measure in Ireland.
 * Andalusia, after Spanish research published decided to add Vitamin-D to treatment program. Recommendation for institutionalised, calcidiol
 * Italy, Piedmont region, Piedmont introduces Vitamin-D to treat patients at home Document signed by 156 Italian doctors and researchers. Vitamina D nella prevenzione e nel trattamento del COVID-19: nuove evidenze

Americas

 * USA, Roma, Starr Country, Texas - good serum level goals of 100-250nmol/l (40-100ng/ml)
 * USA, Nebraska - good dose recommendations 125-150ug/day (5000-6000IU/day)
 * USA, Central NY, New York State - 250ug (10'000IU) to those at food bank
 * Brazil, Figueirão, Mato Grosso do Sul (MS) - Dose 250ug/day (10'000IU/day) with co-factors
 * Brazil, Cristal, Rio Grande do Sul (RS) - Dose 250ug/day (10'000IU/day)
 * Brazil, Porto Seguro, Bahia (BA) - Dose 250ug/day (10'000IU/day)
 * Brazil, Juiz de Fora, Minas Gerais (MG) - supplement symptomatic and healthcare workers
 * Brazil, Nova Petrópolis, Rio Grande do Sul (RS) - Not sure only saw passing mention
 * Brazil, São Paulo, São Paulo (SP) ? - Not sure if this city should be on the list, I only saw a vague mention
 * Real-World Evidence: The Case of Peru

Some resources for Brazil. Mapa do coronavírus por cidades no Brasil, ESPECIAL COVID-19 - Dados por Município

Other

 * Iraq eye hospital, give Vitamin-D on admission to all CoVID-19 patients.
 * University of Health Sciences (UHS), Lahore, Pakistan Established a Vitamin-D academy in Lahore and plans to extend the program to all provinces.
 * Russia, supplement (even) after vaccine, recommendation
 * Israel, recommendation from early on, vaccine side effects may be less
 * Ivermectin crushes Delhi cases
 * 1 in 4 COVID patients hospitalized while vitamin D deficient die – Israeli study

Vitamin-D for All
Over 200 Scientists & Doctors Call For Increased Vitamin D Use To Combat COVID-19

France doctors and learned bodies
73 experts and 6 learned societies call for population wide supplementation. Covid-19 : 73 experts lancent un appel pour qu'on donne de la vitamine D à la population française

Treatment regimes
The Functional Medicine Approach to COVID-19: Virus-Specific Nutraceutical and Botanical Agents

Unit conversions
Doses of Vitamin-D3
 * 1ug of Cholecalciferol = 40 International Units (IU) of Anti-Rachitic effect
 * 100ug = 4000IU
 * 125ug = 5000IU
 * 250ug = 10'000IU
 * 375ug = 15'000IU safe limit for adults long term
 * 500ug = 20'000IU
 * 750ug = 30'000IU

Serum levels 25(OH)D
 * 1ng/ml = 2.5nmol/l
 * 10ng/ml = 25nmol/l
 * 20ng/ml = 50nmol/l
 * 30ng/ml = 75nmol/l
 * 40ng/ml = 100nmol/l
 * 50ng/ml = 125nmol/l Target level
 * 60ng/ml = 150nmol/l
 * 70ng/ml = 175nmol/l
 * 100ng/ml = 250nmol/l
 * 150ng/ml = 375nmol/l no harm detected

Glossary
25(OH)D : 25 Hydroxy Vitamin-D 25(OH)D2 : 25 Hydroxy Vitamin-D2, 25-hydroxyergocalciferol 25(OH)D3 : 25 Hydroxy Vitamin-D3, calcifediol, 25-hydroxycholecalciferol 1,25(OH)2D3 : 1,25 Dihydroxy Vitamin-D3, calcitriol, 1,25-dihydroxycholecalciferol ug : μg, mcg, microgram mg : milligram IU : International Units nmol/l : nano-mole per litre ng/ml : nanogram per millilitre

Endocrine Society
USA, Sets guidelines for targets and supplementation for good health and clinical treatment.

IoM
America, Institute of Medicine, sets guidelines for conservative daily allowances to guide food fortification.

THL
Finland, Department of Health and Welfare (THL, Terveyden ja Hyvinvoinnin laitos), sets guidelines for daily vitamin and mineral allowances and safe limits. Is subservient to Food Agency (Ruokavirasto). Which is subservient to the State Nutrition Advisory Board (VRN, Valtion Ravitsemusneuvottelukunta)

The current serious controversy in Finland on the prohibition on publishing medical research Elintarvikkeiden markkinoiminen koronaviruksen ehkäisyyn tai hoitoon tulee lopettaa välittömästi, Ruokavirasto kieltää yrityksiltä vitamiinitutkimuksien jakamisen kuluttajille ja ammattilaisille

The benefits of Vitamin-D for bone muscle and immune function are accepted in Finland and Europe.